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Xueya Chen,1,&ast; Zhiling Yan,2,&ast; Weipeng Liu,1 Lili Guo,1 Jinmei Xu,2 Li Shi,3 Yufeng Yao1 1Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China; 2Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Shi, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email shili.imb@gmail.com Yufeng Yao, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email leoyyf@gmail.com; yufeng_yao@imbcams.com.cnPurpose: Cervical cancer (CC) poses a significant threat to women’s health worldwide, and multiple signaling pathways have been confirmed to be involved in its development. The AMPK signaling pathway plays a central role in maintaining energy homeostasis, and its dysregulation is closely associated with the occurrence of CC. Changes in microRNA (miRNA) expression levels might be related to the AMPK signaling pathway. Single nucleotide polymorphisms (SNPs) can affect the function of miRNA and result in the development of CC. To investigate the association between the SNPs of AMPK pathway-associated miRNAs and CC in a Han Chinese population, we selected eight miRNA genes located in the AMPK pathway and analyzed nine SNP loci within these genes to explore whether they are associated with genetic susceptibility to cervical intraepithelial neoplasia (CIN) and CC.Methods: A total of 2,220 subjects were included in this study, including 928 healthy controls, 421 CIN patients, and 871 CC patients. Nine candidate SNPs (rs895819 in miR-27a, rs10061133 in miR-449b, rs41291179 in miR-216a, rs76481776 in miR-182, rs10406069 in miR-5196, rs12803915 and rs550894 in miR-612, rs66683138 in miR-3622b, and rs2620381 in miR-627) were genotyped using the TaqMan method.Results: The results showed significant differences in the allele distribution of rs41291179 and rs12803915 between the control group and the CIN group, as well as between the control group and the CC group (all P values < 0.005). The A allele of rs41291179 and the G allele of rs12803915 were associated with decreased risk of CIN (OR = 0.05, 95% CI: 0.01– 0.39; OR = 0.61, 95% CI: 0.49– 0.76) and CC (OR = 0.08, 95% CI: 0.01– 0.66; OR = 0.71, 95% CI: 0.59– 0.86), respectively.Conclusion: Our results suggest that polymorphisms in miRNA genes of the AMPK signaling pathway are associated with the development of CC.Keywords: genotyping, SNP, gene enrichment, genetic susceptibility

Xiaolong Wang,1,2,&ast; Guanyi Wang,2,&ast; Peibin Cen,1,&ast; Hongyu Lan,1 Linfa Guo,2 Zuhaer Yisha,2 Aodun Gu,2 Guiyong Liu,3 Zijian Wang,2 Tongzu Liu,2,4– 8 Qingfeng Yu1,9– 11 1Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Urology, Qianjiang Central Hospital of Hubei Province, Qianjiang, People’s Republic of China; 4Hubei Key Laboratory of Urological Diseases, Wuhan University, Wuhan, People’s Republic of China; 5Hubei Clinical Research Center for Laparoscopic/Endoscopic Urologic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 6Institute of Urology, Wuhan University, Wuhan, People’s Republic of China; 7Hubei Medical Quality Control Center for Laparoscopic/Endoscopic Urologic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 8Wuhan Clinical Research Center for Urogenital Tumors, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 9Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, People’s Republic of China; 10Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou Medical University, Guangzhou, People’s Republic of China; 11Guangzhou Institute of Urology, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongzu Liu, Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email liutongzu@163.com Qingfeng Yu, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Email sunriseyu@yeah.netIntroduction: Overactive bladder (OAB) is a highly prevalent condition with limited treatment options due to poor efficacy, side effects, and patient compliance. Novel drug delivery systems that can target the bladder wall may improve OAB therapy.Methods: We explored a polydopamine (PDA)-coated lactobacillus platform as a potential carrier for localized OAB treatment. Urinary microbiome profiling was performed to identify the presence of lactobacillus in healthy and OAB groups. Lactobacillus-PDA nanoparticles were synthesized and characterized by electron microscopy and spectrophotometry. A rat bladder perfusion model and human bladder smooth muscle cell spheroids were used to assess the distribution and penetration of the nanoparticles. The efficacy of the Lactobacillus-PDA system (LPS) for delivering the antimuscarinic drug solifenacin was evaluated in an OAB rat model.Results: Urinary microbiome profiling revealed lactobacillus as a dominant genus in both healthy and OAB groups. The synthesized Lactobacillus-PDA nanoparticles exhibited uniform size and optical properties. In the rat bladder perfusion model, the nanoparticles distributed throughout the bladder wall and smooth muscle without toxicity. The nanoparticles also penetrated human bladder smooth muscle cell spheroids. In the OAB rat model, LPS facilitated the delivery of solifenacin and improved treatment efficacy.Discussion: The results highlight LPS as a promising drug carrier for targeted OAB therapy via penetration into bladder tissues. This bacteriotherapy approach may overcome limitations of current systemic OAB medications. Lactobacillus, a probiotic bacterium present in the urinary tract microbiome, was hypothesized to adhere to and penetrate the bladder wall when coated with PDA nanoparticles, making it a suitable candidate for localized drug delivery. Keywords: polydopamine, lactobacillus, nano material, drug delivery, overactive bladder

Linghong Guo,1,2 Xu Liu,1,2 Qingfeng Liu,1,2 Xiaoqin Xie,1,2 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-028-85423315, Fax +86-028-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comObjective: This randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy of tranexamic acid essence combined with iontophoresis in treating melasma.Methods: Thirty participants were recruited and randomly assigned to the experimental (Group A) or control group (Group B). Group A received tranexamic acid essence iontophoresis treatment twice weekly for three months, while Group B received placebo treatment. Melasma Area and Severity Index (MASI) scores and skin luminance (L) values were assessed at baseline and weeks 4, 8, and 12.Results: No significant differences in baseline characteristics were observed between the groups. The mean MASI score reduction rate was significantly higher in Group A (− 0.10± 0.12%) compared to Group B (− 0.02± 0.09%) (p< 0.05). Skin L values significantly increased in Group A from 61.32± 3.53 to 63.32± 1.78, while slightly decreasing in Group B (p=0.037).Conclusion: Tranexamic acid essence combined with iontophoresis significantly improved MASI scores and skin luminance compared to placebo, demonstrating its effectiveness in treating melasma. Further research with larger sample sizes and longer follow-up is warranted to validate long-term effects and recurrence rates.Keywords: tranexamic acid, iontophoresis, melasma, clinical trial

Xiuqi Qiao,1,2 Xiaoxia Wang,1 Lixin Guo,1,2 Qi Pan1,2 1Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of ChinaCorrespondence: Lixin Guo; Qi Pan, Email glx1218@163.com; panqi621@126.comBackground: Prior research based on observations has furnished evidence that supports a connection between daytime napping and the prevalence of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the question of whether this correlation is indicative of a causal link has not been definitively answered.Methods: We used meta-analysis and Mendelian randomization (MR) to synthesize genetic and observational data. A two-sample MR analysis was conducted, leveraging 105 single-nucleotide polymorphisms (SNPs) known to be associated with daytime napping patterns. Additionally, summary-level data pertaining to NAFLD outcomes were acquired from the comprehensive UK Biobank study. Network meta-analyses were employed to investigate the relationship between excessive daytime napping and NAFLD, while subgroup was also performed.Results: Significant associations were observed between daytime napping and NAFLD. The systematic review/meta-analysis uncovered a heightened risk of NAFLD development among individuals who engaged in daytime naps exceeding 30 minutes, when compared to those who did not nap(odds ratio [OR] = 1.32, 95% confidence interval [CI]: 1.05 to 1.66). Furthermore, MR analysis indicated that a genetic propensity towards longer daytime napping was significantly linked to an increased likelihood of NAFLD (OR = 2.26, 95% CI: 1.38 to 3.73).Conclusion: Daytime napping has been found to be causally related to a higher risk of NAFLD. Furthermore, across all participants, napping for an average duration over 30 minutes was linked to an elevated likelihood of NAFLD.Keywords: daytime napping, non-alcoholic fatty liver disease, genetic variants, Mendelian randomization, network meta-analysis

Boye Zhang,1,2 Jianliang Man,3,4 Lingyun Guo,1 Xiaoxia Ru,1 Chengwu Zhang,1,2 Wen Liu,1,2,5 Lihong Li,1,2,5 Sufang Ma,1,2 Lixia Guo,2,4 Haojiang Wang,1,2 Bin Wang,1,2 Haipeng Diao,1,5 Renchao Che,6,7 Lili Yan1,2,5 1School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Shanxi Province Brain Degenerative Diseases Precision Diagnosis and Treatment Engineering Research Center, Shanxi Medical University, Jinzhong, 030606, People’s Republic of China; 3Academy of Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4College of Pharmacy, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 5Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 6Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Academy for Engineering &Technology, Fudan University, Shanghai, 200438, People’s Republic of China; 7Zhejiang Laboratory, Hangzhou, 311100, People’s Republic of ChinaCorrespondence: Lili Yan; Renchao Che, Email yanlili@sxmu.edu.cn; rcche@fudan.edu.cnBackground: Challenges such as poor drug selectivity, non-target reactivity, and the development of drug resistance continue to pose significant obstacles in the clinical application of cancer therapeutic drugs. To overcome the limitations of drug resistance in chemotherapy, a viable treatment strategy involves designing multifunctional nano-platforms that exploit the unique physicochemical properties of tumor microenvironment (TME).Methods: Herein, layer-by-layer nanoparticles with polyporous CuS as delivery vehicles, loaded with a sonosensitizer (tetra-(4-aminophenyl) porphyrin, TAPP) and sequentially functionalized with pH‐responsive CaCO3, targeting group hyaluronic acid (HA) were designed and synthesized for synergistic treatment involving chemodynamic therapy (CDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and calcium overload. Upon cleavage in an acidic environment, CaCO3 nanoparticles released TAPP and Ca2+, with TAPP generating 1O2 under ultrasound trigger. Exposed CuS produced highly cytotoxic ·OH in response to H2O2 and also exhibited a strong PTT effect.Results: CuS@TAPP-CaCO3/HA (CTCH) delivered an enhanced ability to release more Ca2+ under acidic conditions with a pH value of 6.5, which in situ causes damage to HeLa mitochondria. In vitro and in vivo experiments both demonstrated that mitochondrial dysfunction greatly amplified the damage caused by reactive oxygen species (ROS) to tumor, which strongly confirms the synergistic effect between calcium overload and reactive oxygen therapy.Conclusion: Collectively, the development of CTCH presents a novel therapeutic strategy for tumor treatment by effectively responding to the acidic TME, thus holding significant clinical implications.Keywords: mitochondria damage, calcium overload, reactive oxygen oncotherapy, pH-responsive, synergistic treatment

Yi Chen,1,&ast; Xiangsheng Xiong,2,&ast; Rui Qin,1 Lei Guo,1 Yongqiang Shi,1 Xinli Ni1 1Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Anesthesiology, the Fifth People’s Hospital of Huaian, Huaian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Ni, Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China, Email xinlini6@nyfy.com.cnBackground: Fluid loading improves hemodynamic stability and reduces the incidence rate of post-spinal anesthesia hypotension when prophylactic vasopressors are administered. We investigated the impact of different crystalloid coload volumes on the 90% effective dose (ED) of prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension in non-hypertensive patients undergoing cesarean section.Methods: Patients were randomly allocated to receive one of the different crystalloid coload volumes (0mL/kg [0mL/kg Group], 5mL kg [5mL/kg Group], and 10mL kg [10mL/kg Group]) in combination with prophylactic norepinephrine infusion immediately after the induction of spinal anesthesia. The prophylactic norepinephrine infusion doses were determined using the up-and-down sequential allocation methodology, with an initial dose of 0.025 μg/kg/min and a gradient of 0.005 μg/kg/min. The primary endpoint was the effective dose at which 90% (ED 90) of patients responded to prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension.Results: The estimated effective dose of norepinephrine infusion, at which 90% (ED 90) of patients responded, was found to be 0.084 (95% CI, 0.070 to 0.86), 0.074 (95% CI, 0.059 to 0.077), and 0.063 (95% CI, 0.053 to 0.064) μg/kg/min in the three groups, respectively.Conclusion: A crystalloid coload of 5 mL/kg or 10 mL/kg, as opposed to the groups receiving 0 mL/kg crystalloid coloads, resulted in a reduction of approximately 11.9% and 25.0%, respectively, in the ED90 of prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension during cesarean section.Keywords: crystalloid, coload, norepinephrine, postspinal anesthesia hypotension, cesarean section

Wenjie Liu, Li Guo, Lizhen Feng, Jie Wang, Miao Zhang, Xiaobin Fan Department of Obstetrics and Gynecology, Xi’an No.3 Hospital, The Affiliated Hospital of Northwest University, Xi’an, 710018, People’s Republic of ChinaCorrespondence: Xiaobin Fan, Email liuwj0709@163.comObjective: To evaluate factors predictive of the success of a slow-release dinoprostone vaginal insert for cervical ripening.Methods: This retrospective study included 187 women who received dinoprostone vaginal inserts for cervical ripening. The participants were divided into two groups: the transvaginal delivery group (n = 87) and cesarean section termination group (n = 100). The correlation between the parameters present before cervical ripening with dinoprostone slow release and its success, as well as complications and adverse outcomes, was analyzed. Cesarean section predictors and area under the curve (AUC) were compared between the two Groups.Results: There were statistical differences between the two groups in body mass index (BMI), height, cervical Bishop score, cephalic position, time of medication use, and fetal head position at the time of medication use (P< 0.05). The optimal thresholds for identifying cesarean section in dinoprostone vaginal insert for cervical ripening were 162.5 for height (AUC = 0.61), 10.65 cm for amniotic fluid index (AUC = 0.6), S-2.5 for cephalic position (AUC = 0.61), 5.5 for bishop score of cervix (AUC = 0.65). The height, amniotic fluid index, cephalic position, and Bishop score of the cervix were included in the same model. The AUC value of the combined model was higher than the AUC value of the single factor.Conclusion: The combined model was a better predictor of cesarean section in dinoprostone vaginal inserts for cervical ripening and labor induction. The success of cervical ripening with a dinoprostone slow-release vaginal insert can be predicted by the factors that can be recognized at admission.Keywords: dinoprostone, cervical ripening, labor induction, predictive model

Jianbao Zheng,1,2,&ast; Zepeng Dong,1,&ast; Xianzhen Jin,1 Jing Li,2 Yuanwu Zou,2 Guanghong Bai,2 Qianhong Wu,2 Shenghang Xu,3 Zifeng Wang,3 Xuejun Sun,1 Dingxin Liu,3 Li Guo3 1Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Tuberculosis Prevention and Treatment Hospital in Shaanxi Province, Xi’an, 710100, People’s Republic of China; 3Center for Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianhong Wu; Li Guo, Email 15902969531@126.com; guoli35@mail.xjtu.edu.cnPurpose: This study aimed to investigate the antibacterial effects of plasma-activated saline (PAS) on My-cobacterium tuberculosis (Mtb).Methods: We conducted a growth assay on 3 strains of Mtb and an antibiotic sensitivity test on 4 strains of Mtb. Both tests included groups treated with normal saline (NS), PAS, and hydrochloric acid (HCl). The test of antibiotic sensitivity consisted of parallel tests with two concentrations of bacteria suspension: 10− 2 and 10− 4. The selected antibiotics were rifampicin (RIF), isoniazid (INH), ethambutol (EMB), and streptomycin (SM). The number of bacteria was determined after one month of culture under different conditions. The Kruskal–Wallis test was used to analyze the differences in grouping factors at representative time points.Results: The growth assay indicated that PAS significantly inhibited the growth of 3 strains of Mtb compared with NS and HCl treatment groups. Furthermore, except for the initial observation time point, the remaining three observation time points consistently demonstrate no significant differences between the NS group and the HCl group. The antibiotic sensitivity test of INH, SM, and RIF indicated that PAS could inhibit the growth of antibiotic-resistant Mtb, and the antibiotic sensitivity test of INH and SM with bacterial suspension concentration of 10− 2 and SM with bacterial suspension concentration of 10− 4 showed statistically different results. The antibiotic sensitivity test of EMB indicated that the growth of Mtb in PAS was slower than that in NS and HCl in both antibiotic-resistant and sensitive Mtb, but there was no statistical difference.Conclusion: The study indicates that PAS contains a significant amount of active substances and exhibits high oxidizability and an acidic pH state. The unique physicochemical properties of PAS significantly delayed the growth of Mtb, compared to the NS and the HCl. PAS not only inhibited the growth of drug-sensitive strains but also significantly enhanced the sensitivity of drug-resistant strains to anti-tuberculosis drugs, which may provide a new therapeutic strategy for the treatment of tuberculosis.Keywords: plasma-activated saline, mycobacterium tuberculosis, antibacterial effect, antibiotic sensitivity

Li Guo,1,&ast; Shi-Cui Hong,1,2,&ast; Xuan Wang,1,3,&ast; Sheng-Qi Wang,1,4 Neng Wang,4,5 Xiao-Qing Wei,1 Hong-Lin Situ,1,3,4 Zhi-Yu Wang1– 5 1Breast Disease Specialist Hospital of Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 2The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 4Guangdong-Hong Kong-Macau Joint Laboratory on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 5The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Yu Wang, Breast Disease Specialist Hospital of Guangdong Provincial Hospital of Chinese Medicine, No. 55, Inner Road West, Higher Education Mega Center(Hospital Branch Address), Guangzhou, 510120, Guangdong, People’s Republic of China, Tel +86-18819480766, Email wangzhiyu@gzucm.edu.cnBackground: Triple-negative breast cancer (TNBC) is the most aggressive malignancy. Psychological distress and elevated CXCL1 level have been reported to be closely associated with the poor prognosis and quality of life of patients with TNBC. In preclinical studies using xenograft mouse models, XIAOPI formula, a nationally approved drug prescribed to patients at high risk for breast cancer, inhibited CXCL1 expression and improved survival. Traditional Chinese medicine has unique advantages in improving patients’ emotional disorders and quality of life. However, the impact of XIAOPI formula on the serum level of CXCL1, psychological distress, and quality of life among patients with TNBC is currently unknown.Methods: In this study, we designed a randomized, double-blind, placebo-controlled trial. Patients with TNBC were randomly assigned to receive either the XIAOPI formula or a placebo for three months. The primary outcomes include serum CXCL1 expression, Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy-Breast (FACT-B).Results: A total of 60 patients with TNBC were enrolled in the investigation. The results showed that the XIAOPI formula significantly decreased CXCL1 expression compared with the control group. Moreover, in comparison to the placebo, the XIAOPI formula increased FACT-B scores while decreasing SDS, SAS, and PSQI scores.Conclusion: In patients with TNBC, XIAOPI formula may be effective in reducing CXCL1 levels, enhancing psychological well-being, and quality of life. While our research offers a natural alternative therapy that may enhance the prognosis of TNBC, future validation of its therapeutic effects will require large-scale, long-term clinical trials.Clinical Registration Number: Registration website: www.chictr.org.cn, Registration date: 2018-1-19, Registration number: ChiCTR1800014535.Keywords: anxiety, CXCL1, depression, quality of life, sleep quality, triple-negative breast cancer, XIAOPI formula

Xu Liu,1,&ast; Qingfeng Liu,1,&ast; Linghong Guo,1 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85423315, Fax +86-28-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comAbstract: The increasing popularity of tattoo art, including facial cosmetic tattoos, has led to a growing societal acceptance of tattoos. However, complications such as lip inflammation following cosmetic lip tattoos remain a concern. This article presents the case of a 47-year-old Asian woman who experienced recurrent lip swelling, purulent discharge, and scarring after receiving lip tattoos. Despite previous treatment with corticosteroid injections yielding unsatisfactory results, the patient showed significant improvement with topical application of 2% Crisaborole, a phosphodiesterase-4 inhibitor. Crisaborole modulates intracellular cyclic adenosine monophosphate levels, thereby reducing tissue inflammation and swelling associated with chronic cheilitis. Additionally, pulse laser therapy was effective in addressing residual tattoo pigment and scar tissue. This case highlights the therapeutic challenges of managing chronic inflammatory diseases of the lips secondary to cosmetic tattoos and introduces Crisaborole as a promising treatment option, offering insights for managing similar conditions in the future.Keywords: lip tattoo, chronic cheilitis, Crisaborole, phosphodiesterase-4 inhibitor, laser therapy

Tongchao Jiang,1,&ast; Haishuang Sun,2,&ast; Tiankai Xu,1 Shuyu Xue,1 Wen Xia,2 Xiang Xiao,1 Ying Wang,1 Ling Guo,3 Huanxin Lin1 1Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huanxin Lin, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email linhx@sysucc.org.cn Ling Guo, Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email guoling@sysucc.org.cnBackground: The C-reactive protein-albumin-lymphocyte (CALLY) score is a novel indicator associated with inflammation, immunity, and nutrition, utilized for cancer prognostic stratification. This study aimed to evaluate the integrated prognostic significance of the pre-treatment CALLY score and Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) patients and to develop prognostic models.Patients and Methods: A total of 1707 NPC patients from September 2015 to December 2017 were retrospectively enrolled. The cut-off point for the CALLY score, determined by maximum selected rank statistics, integrates with the published cut-off point for pre-EBV DNA to develop a comprehensive index. Subsequently, patients were randomly allocated in a 1:1 ratio into training and validation cohorts. Survival analysis was conducted using the Kaplan-Meier method with Log rank tests, and the Cox proportional hazards model was applied to identify independent prognostic factors for constructing predictive nomograms. The predictive ability of the nomograms were assessed through the concordance index (C-index), calibration curves, and decision curve analysis.Results: By integrating CALLY scores and EBV-DNA levels, patients were categorized into three risk clusters. Kaplan-Meier curves reveal significant differences in overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) outcomes among different risk groups (all P values < 0.05). Multivariate analysis revealed that CALLY-EBV DNA index serves as an independent prognostic factor for the OS, DMFS, and LRRFS. The prognostic nomograms based on the CALLY-EBV DNA index provided accurate predictions for 1-year, 3-year, and 5-year OS, DMFS, and LRRFS. Additionally, compared to the traditional TNM staging system, the nomograms exhibited enhanced discriminatory power, calibration capability, and clinical applicability. All results were in agreement with the validation cohort.Conclusion: The CALLY-EBV DNA index is an independent prognostic biomarker. The nomogram prediction models, constructed based on the CALLY-EBV DNA index, demonstrates superior predictive performance compared to the traditional TNM staging.Keywords: CALLY score, EBV DNA, nasopharyngeal carcinoma, biomarker, prognostic model

Enhao Huang,1,2,&ast; Huadao Li,2,3,&ast; Hanghang Han,1,2,&ast; Lianshan Guo,4 Yubing Liang,3 Zijin Huang,1 Ke Qin,5 Xueke Du1 1Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 2Key Laboratory for Basic Science and Prevention of Perioperative Organ Dysfunction, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 3Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 4Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 5Guilin People’s Hospital, Guilin, Guangxi Zhuang Autonomous Region, 541100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Qin; Xueke Du, Email qinke303@163.com; duxueke@gxmu.edu.cnPurpose: The primary objective of this study was to develop an innovative nanomedicine-based therapeutic strategy to alleviate Postoperative Neurocognitive Disorder (PND) in patients undergoing surgery.Patients and Methods: To achieve this goal, polydopamine-coated Kaempferol-loaded Metal-Organic Framework nanoparticles (pDA/KAE@ZIF-8) were synthesized and evaluated. The study involved encapsulating Kaempferol (KAE) within ZIF-8 nanoparticles, followed by coating with polydopamine (PDA) to enhance biocompatibility and targeted delivery. The characterization of these nanoparticles (NPs) was conducted using various techniques including Scanning Electron Microscopy, Fourier-Transform Infrared Spectroscopy, X-ray Diffraction, and Ultraviolet-Visible spectroscopy. The efficacy of pDA/KAE@ZIF-8 NPs was tested in both in vitro and in vivo models, specifically focusing on their ability to penetrate the blood-brain barrier and protect neuronal cells against oxidative stress.Results: The study found that pDA/KAE@ZIF-8 NPs efficiently penetrated the blood-brain barrier and were significantly taken up by neuronal cells. These nanoparticles demonstrated remarkable Reactive Oxygen Species (ROS) scavenging capabilities and stability under physiological conditions. In vitro studies showed that pDA/KAE@ZIF-8 NPs provided protection to HT-22 neuronal cells against H2O2-induced oxidative stress, reduced the levels of pro-inflammatory cytokines, and decreased apoptosis rates. In a PND mouse model, the treatment with pDA/KAE@ZIF-8 NPs significantly improved cognitive functions, surpassing the effects of KAE alone. This improvement was substantiated through behavioral tests and a noted reduction in hippocampal inflammation.Conclusion: The findings from this study underscore the potential of pDA/KAE@ZIF-8 NPs as an effective nanotherapeutic agent for PND. This approach offers a novel direction in the postoperative care of elderly patients, with the potential to transform the therapeutic landscape for neurocognitive disorders following surgery. The application of nanotechnology in this context opens new avenues for more effective and targeted treatments, thereby improving the quality of life for patients suffering from PND.Keywords: nanomedicine, reactive oxygen species, blood-brain barrier

Caizhi Sun,1,2,&ast; Yongpeng Xie,1,&ast; Chenchen Zhu,2 Lei Guo,2 Jingjing Wei,2 Bowen Xu,2 Yang Song,2 Haidong Qin,2 Xiaomin Li1 1Department of Emergency Medicine, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang City, Lianyungang, Jiangsu, 222000, People’s Republic of China; 2Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, 210006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaomin Li, Department of Emergency Medicine, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang City, 182 Tongguan North Road, Haizhou District, Lianyungang City, Jiangsu Province, People’s Republic of China, Email lyglxmsj@163.com Haidong Qin, Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing City, Jiangsu Province, People’s Republic of China, Tel/Fax +8602552271264, Email icuqhd@163.comBackground: To date, there are no studies regarding the Mrp 8/14 in predicting the occurrence of acute respiratory distress syndrome (ARDS) induced by sepsis. Thus, the objective of this study was to investigate the expression of Myeloid-related proteins 8 and 14 (Mrp 8/14) and its role in ARDS induced by sepsis.Methods: A total of 168 septic patients were enrolled in the observational study. The baseline information and clinical outcomes were obtained retrospectively. Serum Mrp 8/14 level was determined by enzyme linked immunosorbent assay (ELISA). The patients were categorized into sepsis and ARDS group based on whether they developed ARDS during the intensive care unit (ICU) hospitalization.Results: There was significant difference in the level of Mrp 8/14 between the sepsis group and ARDS groups (P < 0.05). Mrp 8/14 correlated positively with procalcitonin (PCT), interleukin-6 (IL-6), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score on day 1, mechanical ventilation time, length of ICU stay and hospitalization expenses in ICU (all P < 0.05). Logistic regression analysis showed Mrp 8/14 was the independent factor for forecasting the occurrence of sepsis- induced ARDS (P < 0.05). The areas under receiver operating characteristic curves for Mrp 8/14 were higher than that of PCT, APACHE II score and SOFA score on day 1 (P < 0.05).Conclusion: The serum Mrp 8/14 level at admission may be a potential marker for predicting the occurrence of ARDS induced by sepsis. Early detection of serum Mrp 8/14 could help clinicians to identify and evaluate the severity of ARDS induced by sepsis.Keywords: sepsis, acute respiratory distress syndrome, Mrp 8/14, inflammation, intensive care unit

Jingmei Huang,1,&ast; Lianshan Guo,1,&ast; Xiaoxiao Huang,1 Xiaoping Yu,2 Liqiao Lin,1 Xinlin Jiang,3 Zhihao Bai,4 Zhengzhao Li1 1Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China; 2Department of Radiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China; 3Department of General Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China; 4College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengzhao Li, Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China, Email lizhengzhao7680@163.com Zhihao Bai, College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, People’s Republic of China, Email zhihao_bai@163.comPurpose: The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2).Methods: Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD’s active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells.Results: Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity.Conclusion: The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.Keywords: metal-organic frameworks, cytotoxins, photodynamic therapy, liver cancer

Kang Yang,1,&ast; Chengye Liu,1,&ast; Jun Shao,2 Lingxiang Guo,2 Qing Wang,3 Zhaoxiang Meng,1,&ast; Xing Jin,1,&ast; Xianghe Chen4,&ast; 1Rehabilitation Medicine Department, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou city, Jiangsu Province, People’s Republic of China; 2Cardiovascular Disease Center, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou city, Jiangsu Province, People’s Republic of China; 3Respiratory Department, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou city, Jiangsu Province, People’s Republic of China; 4College of Physical Education, Yangzhou University, Yangzhou city, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xianghe Chen, College of Physical Education, Yangzhou University, Huayang West Road 196, Yangzhou city, Jiangsu Province, People’s Republic of China, Email huashixh@163.com Xing Jin, Rehabilitation Medicine Department, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Nantong West Road 98, Yangzhou city, Jiangsu Province, People’s Republic of China, Email yzjinxing@qq.comBackground: Swimming and intermittent fasting can both improve obesity-induced NAFLD, but which of the two is more effective and whether the combination of the two has a superimposed effect is inconclusive.Methods: The model of NAFLD in obese rats was established by a high-fat diet and performed swimming, intermittent fasting, and a combination of both interventions for 8 weeks. Serum lipids and enzyme activity were measured by an automatic biochemical analyzer. Liver morphostructural analysis was observed by transmission electron microscopy, and morphology was observed by HE staining. RT‒PCR was used to detect the mRNA level.Results: Morphology and microstructure of the liver of model rats were impaired, with the upregulation of miR-122-5p, SREBP-1c, FASN and ACC1. Eight weeks of swimming exercise, intermittent fasting and the combination of both attenuate these effects, manifested by the downregulation of miR-122-5p and upregulation of CPT1A mRNA levels. There was no significant stacking effect of the combination of the swimming and intermittent fasting interventions.Conclusion: NAFLD leads to pathology in model rats. Eight weeks of swimming exercise, intermittent fasting and the combination of both can inhibit miR-122-5p and improve hepatic lipid metabolism, while no significant additive effects of combining the interventions were found.Keywords: obesity, NAFLD, swimming, intermittent fasting, miR-122-5p

Lina Guo,1 Jaclene A Zauszniewski,2 Gege Zhang,1 Xiaoyu Lei,1 Mengyu Zhang,1 Miao Wei,1 Keke Ma,1 Caixia Yang,1 Yanjin Liu,3 Yuanli Guo1 1Department of Neurology, National Advanced Stroke Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 3Department of Nursing, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Yuanli Guo, Email gylzd@163.comObjective: To explore distinct longitudinal trajectories of resourcefulness among initial ischemic stroke patients from diagnosis to 12 months, and to identify whether sociodemographic factors, disease-related factors, self-efficacy, family function, and social support can predict patterns in the trajectories of resourcefulness.Methods: A prospective longitudinal study was conducted. Initial ischemic stroke patients who met inclusion and exclusion criteria were followed up when still in hospital (Preparing for discharge, Baseline, T1), at 1 month (T2), at 3 months (T3), at 6 months (T4), at 9 months (T5) and 12 months (T6) (± 1 week) after discharge. General information, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), General Self-Efficacy Scale (GSES), General Family Functioning Subscale (FAD-GF), and Social Support Rate Scale (SSRS) were used in T1. The Resourcefulness Scale© was evaluated at 6 time points. Growth mixture modeling was used to identify trajectory patterns of resourcefulness. Logistic regression was used to identify predictors of resourcefulness trajectories.Results: Three longitudinal trajectories of resourcefulness were identified and named as the high-stable class (38.9%, n=71), fluctuation class (41.2%, n=75), and low-stable class (19.9%, n=36), respectively. Dwelling areas (x2= 6.805, P= 0.009), education (x2= 44.865, P= 0.000), monthly income (x2= 13.063, P= 0.001), NIHSS scores (x2= 44.730, P= 0.000), mRS scores (x2= 51.788, P= 0.000), Hcy (x2= 9.345, P= 0.002), GSES (x2= 56.933, P= 0.000), FAD-GF (x2= 41.305, P= 0.000) and SSRS (x2=52.373, P= 0.000) were found to be statistically significant for distinguishing between different resourcefulness trajectory patterns. Lower education (OR=0.404), higher NIHSS(OR=6.672) scores, and higher mRS(OR=21.418) scores were found to be risk factors for lower resourcefulness, whereas higher education(OR=0.404), GSES(OR=0.276), FAD-GF(OR=0.344), and SSRS(OR=0.358) scores were identified as protective factors enhancing resourcefulness.Conclusion: This study obtained three patterns of trajectories and identified their predictive factors in initial ischemic stroke. The findings will assist health care professionals in identifying subgroups of patients and when they may be at risk of low resourcefulness and provide timely targeted intervention to promote resourcefulness.Keywords: initial ischemic stroke, resourcefulness, longitudinal study, social ecology theory, predictive factors, nursing care

Li Guo,1 Li-Qin Zhao,2 Jin-Yu Chen,2 Ming Li2 1Third Department of General Surgery (Breast Armor Surgery), Ezhou Central Hospital, Ezhou City, 436000, People’s Republic of China; 2Department of Oncology, Ezhou Central Hospital, Ezhou City, 436000, People’s Republic of ChinaCorrespondence: Ming Li, Department of Oncology, Ezhou Central Hospital, No. 9 Wenxing Road, Echeng District, Ezhou City, Hubei Province, 436000, People’s Republic of China, Tel + 86-15969693217, Email yeaher9986@163.comObjective: This study investigates the impact of nursing interventions on treatment outcomes and adverse reaction rates in renal cell carcinoma (RCC) patients treated postoperatively with Interleukin-2 and recombinant human Interferon.Methods: In a retrospective analysis of 90 RCC patients, 43 received standard care (control group), while 47 received additional nursing interventions (intervention group), including psychological care, vital signs monitoring, dietary care, adverse reaction management, and post-discharge care. Patients with concurrent major diseases or other malignancies were excluded. Key assessments included clinical symptom improvement, treatment efficacy, and postoperative adverse reactions.Results: Among the 90 participants, no significant demographic differences were found between the two groups. The intervention group showed significant improvements in fever resolution, leukocyte normalization, and shorter hospital stays. The overall treatment effectiveness was similar in both groups (90.7% in the intervention group vs 91.5% in the control group). However, the intervention group experienced significantly fewer postoperative adverse reactions, including fever, gastrointestinal symptoms, bone marrow suppression, and neurological abnormalities (6.3% vs 23.2%).Conclusion: The study suggests that nursing interventions can improve treatment outcomes by reducing postoperative adverse reactions in RCC patients receiving postoperative Interleukin-2 and recombinant human Interferon. The overall effectiveness of treatment and care was comparable between the groups. Further extensive studies are needed to confirm these findings and fully understand the impact of nursing interventions on RCC patient outcomes.Keywords: renal cell carcinoma, interleukin-2, recombinant human interferon, nursing interventions, treatment outcomes, adverse reactions

Ting Li,1,&ast; Lianshan Guo,2,&ast; Jiaxu Li,3,&ast; Xingyu Mu,4 Lijuan Liu,1 Shulin Song,1 Ningbin Luo,1 Qi Zhang,5 Bin Zheng,1 Guanqiao Jin1 1Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 3Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, College of Chemistry and Materials, Graduate School, Nanning Normal University, Nanning, 530001, People’s Republic of China; 4Department of Nuclear Medicine, Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China; 5Laboratory Animal Center, Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanqiao Jin, Email jinguanqiao77@gxmu.edu.cnBackground: The anti-Programmed Death-Ligand 1 (termed aPD-L1) immune checkpoint blockade therapy has emerged as a promising treatment approach for various advanced solid tumors. However, the effect of aPD-L1 inhibitors limited by the tumor microenvironment makes most patients exhibit immunotherapy resistance.Methods: We conjugated the Sialyl Lewis X with a polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO-PEG) to form UPS nanoparticles (USPIO-PEG-SLex, termed UPS). The physicochemical properties of UPS were tested and characterized. Transmission electron microscopy and ICP-OES were used to observe the cellular uptake and targeting ability of UPS. Flow cytometry, mitochondrial membrane potential staining, live-dead staining and scratch assay were used to verify the in vitro photothermal effect of UPS, and the stimulation of UPS on immune-related pathways at the gene level was analyzed by sequencing. Biological safety analysis and pharmacokinetic analysis of UPS were performed. Finally, the amplification effect of UPS-mediated photothermal therapy on aPD-L1-mediated immunotherapy and the corresponding mechanism were studied.Results: In vitro experiments showed that UPS had strong photothermal therapy ability and was able to stimulate 5 immune-related pathways. In vivo, when the PTT assisted aPD-L1 treatment, it exhibited a significant increase in CD4+ T cell infiltration by 14.46-fold and CD8+ T cell infiltration by 14.79-fold, along with elevated secretion of tumor necrosis factor-alpha and interferon-gamma, comparing with alone aPD-L1. This PTT assisted aPD-L1 therapy achieved a significant inhibition of both primary tumors and distant tumors compared to the alone aPD-L1, demonstrating a significant difference.Conclusion: The nanotheranostic agent UPS has been introduced into immunotherapy, which has effectively broadened its application in biomedicine. This photothermal therapeutic approach of the UPS nanotheranostic agent enhancing the efficacy of aPD-L1 immune checkpoint blockade therapy, can be instructive to address the challenges associated with immunotherapy resistance, thereby offering potential for clinical translation.Keywords: immunotherapy resistance, immune checkpoint blockade, nanotheranostic agent, photothermal therapy, enhancing efficacy

Luyang Pi,1 Yu Wang,1 Lirong Zou,1 Xinxin Mo,2 Leilei Guo3 1College of Humanities and Law, Guangdong University of Petrochemical Technology, Maoming, People’s Republic of China; 2School of Education Science, Guangdong Preschool Normal College in Maoming, Maoming, People’s Republic of China; 3School of Marxism, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Leilei Guo, Email guollei3@mail.sysu.edu.cnPurpose: To explore the potential classification of Problematic Mobile Social Media Usage (PMSMU) in Chinese college students, analyze whether there is group heterogeneity in PMSMU, and discuss the differences in the latent profile of PMSMU in fear of missing out, online positive feedback, and boredom proneness.Methods: A total of 2591 Chinese college students were investigated using the Problematic Mobile Social Media Usage Questionnaire, Fear of Missing Out (FOMO) Scale, Online Positive Feedback Scale and Short-form Boredom Proneness Scale, and heterogeneity was tested by latent profile analysis.Results: The PMSMU of college students can be divided into three latent profiles: no-problem use group (26.44%), mild problem use group (56.66%), and severe problem use group (16.91%). Male students, as compared to female students, showed a significantly lower likelihood of being classified as mild problematic users (OR=0.50, p< 0.001) and severe problematic users (OR=0.29, p< 0.001). Additionally, students with higher levels of FOMO, a stronger craving for online positive feedback, and increased boredom proneness are more likely to belong to the severe problematic use group (OR=2.91, p< 0.001; OR=1.42, p< 0.01; OR=8.72, p< 0.001).Conclusion: The results of this study highlight the factors influencing the heterogeneity of individual PMSMU. Specifically, female college students and those with a higher fear of missing out, greater susceptibility to boredom, and a stronger craving for positive online feedback are more likely to exhibit severe PMSMU. These findings provide valuable empirical evidence for developing preventive strategies to address PMSMU among college students.Keywords: problematic mobile social media usage, latent profile analysis, fear of missing out, online positive feedback, boredom proneness

Feiyang Liu,1 Huicun Duan,2 Yongqing Hou,3 Bohua Zhang,3 Jinlong Wu,1 Liya Guo1 1School of Physical Education, Southwest University, Chongqing, People’s Republic of China; 2Research Center of Psychology and Social Development, Southwest University, Chongqing, People’s Republic of China; 3Faculty of Psychology, Southwest University, Chongqing, People’s Republic of ChinaCorrespondence: Liya Guo, School of Physical Education, Southwest University, Tiansheng Road, Beibei District, Chongqing, People’s Republic of China, Email 974634029@qq.comPurpose: The deleterious impact of aggressive behavior on college students necessitates urgent mitigation. To explore the influencing factors and underlying mechanisms of aggressive behaviors among college students, this study aims to validate the mediating roles of life satisfaction, meaning in life, and depression by examining the relationship between physical exercise and aggressive behaviors among college students.Methods: The Physical Activity Rating Scale-3 (PARS-3), Satisfaction with Life Scale, Meaning in Life Questionnaire, Chinese Version DASS-21 and 12-item Perception of Aggression Scale (POAS) were tested on 1596 college students from three universities in western China, and SPSS 26.0 and Mplus 8.3 were used for analysis.Results: Physical exercise exhibited a significant negative correlation with both aggressive behaviors and depression among college students (r = – 0.57, P < 0.001; r = – 0.36, P < 0.001), as well as a significant positive correlation with life satisfaction and meaning in life (r = 0.45, P < 0.001; r = 0.27, P < 0.001). Regarding the impact of physical exercise on aggressive behaviors among college students, the mediating effects of life satisfaction, meaning in life, and depression were significant. The respective effect sizes were − 0.11, − 0.08, and − 0.03. The chain mediation effect of life satisfaction through depression was also found to be significant, with an effect size of − 0.02.Conclusion: This study elucidates the mechanistic pathways through which physical exercise influences aggressive behavior among college students. The relationship between physical exercise and aggressive behavior is influenced by the individual mediating effects of life satisfaction, meaning in life, and depression, as well as the chain mediation effect of life satisfaction through depression. These findings provide a novel perspective on the prevention and intervention of aggressive behaviors among college students in China and potentially worldwide. This suggests that more attention should be paid to the organic combination of students’ physical activity and mental health education.Keywords: physical exercise, life satisfaction, meaning in life, depression, aggressive behavior

Yuguo Liu,1 Bo Zhang,1 Haichen Lv,1 Yifan Zhu,2 Xuchen Zhou,1 Hao Zhu,1 Lei Guo1 1Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Lei Guo; Hao Zhu, Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian City, 116011, People’s Republic of China, Tel +86 411-83635963 ; +86 411-83635963, Email leiguo@dmu.edu.cn; drhaozhudmu@163.comObjective: To investigate the precise changes in the lumen and lesions, and clinical outcomes after DCB treatment for de-novo coronary lesions exceeding 2.5 mm in diameter through a detailed analysis of OCT.Methods: This is a prospective study including 53 consecutive patients with 55 de-novo coronary lesions, who underwent DCB angioplasty-only between January 2021 and April 2022. Quantitative coronary angiography (QCA) and OCT were performed before percutaneous coronary interventions (PCI), immediately after PCI, and at 6– 9 months follow-up after PCI. Target lesion failure (TLF) was the primary endpoint of the present study. Multivariate logistic regression analysis was performed to identify the predictors or risks for late lumen enlargement (LLE).Results: A total of 52 patients were successfully treated with DCB. The median follow-up was 7 months, and the incidence of TLF was 7.5%. After the DCB procedure, 43 patients had their scheduled angiographic and OCT examination. QCA demonstrated that the late lumen loss was − 0.79 ± 0.28 mm. OCT demonstrated LLE in 79.1% and dissection healing in 65.1% of lesions. After multivariable logistic analysis, type B dissection (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.34– 7.41, p = 0.037) was found to be a predictor of LLE, but lipid plaque (OR 0.09, 95% CI 0.01– 0.63, p = 0.015) was a risk of LLE.Conclusion: This is the first and largest prospective study to assess the outcomes of DCB treatment for de-novo coronary lesions exceeding 2.5 mm in diameter and the detection of significant vessel enlargement and dissection healing guide by OCT. DCB could be a novel, safe and effective treatment for de-novo coronary lesions exceeding 2.5 mm in diameter through a detailed analysis of OCT.Keywords: drug-coated balloon, optical coherence tomography, late lumen enlargement, de novo, coronary artery disease

Xinsheng Li,1,&ast; Zhongzhen Wang,1,&ast; Yifan Zhu,2 Haichen Lv,1 Xuchen Zhou,1 Hao Zhu,1 Jinqiu Liu,1 Lei Guo1 1Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, Dalian City, People’s Republic of China; 2Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Guo; Jinqiu Liu, Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian City, 116011, People’s Republic of China, Tel +86 411-83635963, Email leiguo@dmu.edu.cn; 18098875755@163.comObjective: To investigate the prognostic value of fibrinogen-to-albumin ratio (FAR) in the adverse outcomes of patients with coronary three-vessel disease (TVD).Methods: A total of 4061 patients with TVD between 2013 and 2018 were analyzed in this retrospective cohort study. The best cut‑off value of the FAR determined by receiver operating characteristic (ROC) curve analysis was 0.084. 2782 (68.5%) patients were in the low FAR group (FAR

Xiaolong Wang,1 Linfa Guo,1 Guiyong Liu,2 Tongzu Liu1,3,4 1Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Qianjiang Central Hospital of Hubei Province, Qianjiang, People’s Republic of China; 3Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Wuhan, People’s Republic of China; 4Hubei Province Key Laboratory of Urinary System Diseases, Wuhan, People’s Republic of ChinaCorrespondence: Tongzu Liu; Guiyong Liu, Department of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Hubei Province Key Laboratory of Urinary System Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China, Email liutongzu@163.com; nogardmd@whu.edu.cnIntroduction: Leptin is a metabolic peptide hormone produced by adipocytes, with proven roles in proliferation of prostate cancer cells and of prostate cells in animal models of benign prostatic hyperplasia (BPH). Thus, the role of leptin as a molecular link connecting BPH and lower urinary tract symptoms (LUTS) suggestive of BPH with metabolic symptoms appears feasible but is still unknown. In fact, a connection between metabolic syndrome and BPH is becoming increasingly evident from epidemiologic studies. Key factors of Lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH/LUTS) are increased prostate smooth muscle tone, and prostate enlargement. Here, we examined the effects of leptin on contraction of human prostate smooth muscle and on growth of stromal cells.Methods: We performed microarray analysis to identify genes (fold change ≥ 1.5) associated with BPH/LUTS progression, such as those involved in proliferation, apoptosis, and mitochondrial metabolism, in rat prostate tissue (data from GSE129561). We then used electric field stimulation (EFS) to induce frequency-dependent, neurogenic contractions of human prostate strips, which were enhanced by leptin. We also examined the effect of leptin on human prostate stromal cells (WPMY-1) and found increased cell proliferation and viability upon exposure. To explore the underlying mechanism, we conducted mitochondrial stress assay using near-infrared (NIR) fluorescent dye and flow cytometry (FACS) analysis and observed reduced cellular apoptosis and preserved mitochondrial membrane potential (∆ψM) after leptin treatment.Results: Microarray analysis reveals that leptin regulates prostate smooth muscle contraction and stromal cell proliferation, shedding new light on its involvement in BPH/LUTS pathogenesis and mitochondrial function. We found that leptin enhanced the proliferation rate of prostate stromal cells relative to the control group (0.67 ± 0.05 vs 0.54 ± 0.08, p-value= 0.024). Moreover, leptin (100 ng/mL) potentiated the frequency-dependent, neurogenic contractions of prostate strips elicited by EFS (p= 0.047 between leptin and control group). We also show that leptin treatment increased the mitochondrial membrane potential of prostate stromal cells and inhibited mitochondrial apoptosis.&#x00A0Discussion: Our results indicate that leptin stimulates the contractility and proliferation of smooth muscle and stromal cells in the human prostate, implying a potential role for leptin in exacerbating BPH/LUTS in obese men. Leptin modulation may be a beneficial therapeutic strategy for patients with metabolic syndrome and BPH/LUTS. Further studies are warranted to elucidate the mechanisms and implications of the leptin system in BPH/LUTS.Keywords: metabolic syndrome, leptin, prostate, contraction, mitochondrial

Shuo Tian,1,2 Lin Guo,3 Yagang Song,1,2 Huiyan Yang,1 Jia Wang,3 Jingyi Qiao,1,2 Xiangxiang Wu,1,2 Ming Bai,1,2 Mingsan Miao1,2 1Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 2Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 3Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of ChinaCorrespondence: Mingsan Miao, Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China, Tel/Fax +86 371 65962546, Email miaomingsan@hactcm.edu.cnPurpose: Radix Salvia miltiorrhiza (RSM), a commonly used medicinal plant, has been reported to have anti-inflammatory effects, but relevant studies on burn injuries are lacking. We investigated the anti-inflammation and wound healing (WH) effects of an aqueous extract of RSM on a burn model in rats.Methods: The effects of RSM were studied by heat-induced burns in rats, treatment with vehicle, Jinwanhong ointment, and RSM (1.5 or 0.75 g/mL). Indicators of burn tissue (BT) were photographed by digital machines and analyzed. The microcirculation in BT was detected by scattered full-frame real-time imaging. Levels of inflammatory mediators and growth factors were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Local pathologic changes in BT were observed by hematoxylin-and-eosin (HE) staining. Ultrahigh pressure liquid chromatography–linear ion trap–Orbitrap mass spectrometry (UHPLC–LTQ–Orbitrap-MS) was used to explore the absorption of RSM in local skin, subcutaneous tissue, muscle tissue, serum, liver tissue, and kidney tissue.Results: RSM treatment could reduce the wound area, increase percent WH, increase blood perfusion in BT, reduce serum levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF-α), increase levels of epidermal growth factor (EGF), transforming growth factor (TGF)-β, and hydroxyproline (Hyp) in serum, and increase protein expression of basic fibroblast growth factor (bFGF), TGF-β 1, EGF, and insulin-like growth factor-1 (IGF)-1 in skin tissues. RSM treatment led to micro-absorption in the skin, subcutaneous tissues, and muscle, but not in the blood, liver, or kidney.Conclusion: RSM may promote WH by exerting anti-inflammatory effects, improving local-wound microcirculation, and accelerating the metabolism at the wound surface.Keywords: Radix Salvia miltiorrhiza, burns, anti-inflammatory, wound healing

Zitian Liang,1,&ast; Ding Chen,2,&ast; Ye Jiang,1 Zhikang Su,2 Yixing Pi,2 Tao Luo,2 Qianzhou Jiang,1 Li Yang,1 Lvhua Guo2 1Department of Endodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, 510182, People’s Republic of China; 2Department of Prosthodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, 510182, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Lvhua Guo, Affiliated Stomatology Hospital of Guangzhou Medical University, No. 195 West Dongfeng Road, Guangzhou, 510182, People’s Republic of China, Tel +86-020-81299942, Email 2019686001@gzhmu.edu.cn; 2010686002@gzhmu.edu.cnIntroduction: Effective infection control without irritating the pulp tissue is the key to successful vital pulp therapy. Developing a novel antibacterial biomaterial that promotes dentin regeneration for pulp capping is thus a promising strategy for enhancing vital pulp therapy.Methods: Lithium-doped mesoporous nanoparticles (Li-MNPs) were synthesized using an alkali-catalyzed sol-gel method. The particle size, elemental distribution, surface morphology, pore structure, and ion release from Li-MNPs were measured. Human dental pulp stem cells (hDPSCs) and Streptococcus mutans (S. mutans) were used to evaluate the biological effects of Li-MNPs. In addition, a dental pulp exposure mouse model was used to evaluate the regenerative effects of Li-MNPs.Results: Li-MNPs had a larger surface area (221.18 m2/g), a larger pore volume (0.25 cm3/g), and a smaller particle size (520.92 ± 35.21 nm) than MNPs. The in vitro investigation demonstrated that Li-MNPs greatly enhanced the biomineralization and odontogenic differentiation of hDPSCs through the Wnt/β-catenin signaling pathway. Li-MNPs showed a strong antibacterial effect on S. mutans. As expected, Li-MNPs significantly promoted dentin regeneration in situ and in vivo.Conclusion: Li-MNPs promoted dentin regeneration and inhibited S. mutans growth, implying a possible application as a pulp capping agent in vital pulp therapy.Graphical Abstract: Keywords: lithium, mesoporous nanoparticles, dental pulp stem cells, dentin regeneration, Wnt/β-catenin signaling pathway, antibacterial properties

Mingzhen Li,1 Bing Zhang,2 Lichuan Guo,2 Yuan Zhang,2 Xiaoyan Du,3 Bingyi Wang,3 Zheng Xu,4 Ning Sun,4 Ruibin Chen,4 Wanwen Han,4 Liming Chen,1 Zhenqiang Song1 1Department of Endocrinology, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Information Management, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Medical, Happy Life Technology Co Ltd, Beijing, People’s Republic of China; 4Department of Yutang, Andon Health Co., Ltd, Tianjin, People’s Republic of ChinaCorrespondence: Zhenqiang Song, Department of Endocrinology, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, No. 6 North Huanrui Road, Beichen District, Tianjin, People’s Republic of China, Tel +86-18602276218, Fax +86-022-59562017, Email zsong@tmu.edu.cnBackground: Our previous study demonstrated that digital diabetes care model (DDCM) created by multidisciplinary care team (MDCT) can improve glycemic control for patients with diabetes than usual care. Therefore, we aimed to explore long-term glycemic control with DDCM and influencing factors in type 2 diabetic cohort, in order to make a portrait for diabetes with goal-achieved HbA1c in clinics.Methods: A total of 1198 outpatients with type 2 diabetes using DDCM for at least 12 months were recruited as a cohort. Medical records and specific DDCM indexes were collected. The influencing factors for glycemic control were explored by multivariate logistic regression analysis, followed by an internal and external validation.Results: A total of 887 patients were finally included. HbA1c target-achieving rate was increased from 39.83% at baseline to 71.79% after 3-month follow-up. A shorter duration of diabetes, more frequent self-monitoring of blood glucose, lower HbA1c level at baseline, and less frequent emergency out-of-hospital follow-ups were influencing factors for HbA1c < 7% at 12-month follow-up. AUC of the prediction model was 0.790, with a sensitivity of 69.7% and specificity of 76.1%. Internal and external validation in patients using the DDCM monitored by MDCT indicated that the DDCM was robust (AUC =0.783 and 0.723, respectively).Conclusion: Our findings made a portrait for T2DM with goal-achieved HbA1c in our DDCM. It is important to recognize associated factors for health providers to make personalized intervention in clinical practice.Keywords: digital diabetes care model, glycemic control, type 2 diabetes management

Hongchuan Liu,1 Huaihuai Dong,2 Liangjun Guo,3 Yongsheng Jin,2 Lihong Liu1 1Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2School of Pharmacy, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Department of Drug and Equipment, The 72st Group Army Hospital of PLA, Huzhou, 313000, People’s Republic of ChinaCorrespondence: Yongsheng Jin, School of Pharmacy, Naval Medical University, No. 325 of Guohe Street, Yangpu District, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 21 8187 1227, Email ysjinsmmu@163.com Lihong Liu, Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, No. 8 of Gongti South Street, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel/Fax +86 10 85231786, Email hongllh@126.comBackground: The synergistic effect of dihydromyricetin (DHM) and fluconazole (FLC) can improve the killing effect of FLC-resistant Candida albicans in vitro and in vivo. However, it is not clear whether DHM affects the pharmacokinetic characteristics of FLC.Methods: In this study, 12 Sprague–Dawley (SD) rats were randomly divided into two groups as follows: (1) an FLC group in which rats were administered FLC only (42 mg/kg orally); (2) an FLC with the combined administration of DHM group, in which rats received an equivalent FLC dose immediately following the administration of DHM (100 mg/kg). Blood samples were collected from the ocular choroid vein of rats and converted into plasma. The concentrations of FLC in the rat plasma were then determined by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS), and the related pharmacokinetic parameters were analysed. The initial mobile phase included 0.1% acetonitrile and water with gradient elution. Multiple reaction monitoring modes of m/z 307.2→ 220.1 for FLC, and m/z 237.1→ 194.2 for carbamazepine, were utilised to conduct quantitative analysis.Results: The calibration curve of FLC in rat plasma demonstrated good linearity in the range of 0.1– 30 μg/mL (r > 0.99), and the lower limit of quantification was 0.1 μg/mL. Moreover, the intra- and inter-day precision relative standard deviation of FLC was less than 9.09% and 6.51%, respectively. There were no significant differences in the pharmacokinetic parameters between the two groups.Conclusion: The results showed that DHM administration did not significantly alter FLC pharmacokinetics in SD rat plasma.Keywords: HPLC-MS/MS, dihydromyricetin, fluconazole, pharmacokinetic

Jiaojiao Xue,1 Ziwei Zhang,1 Yuting Sun,2 Di Jin,3 Liming Guo,1 Xiangyan Li,4 Daqing Zhao,4 Xiaochun Feng,5 Wenxiu Qi,4 Haoyu Zhu5 1College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Department of Nephrology, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 4Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Biomacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 5Department of Nephropathy and Rheumatology in Children, Children’s Medical Center, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of ChinaCorrespondence: Wenxiu Qi, Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Biomacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel +86-431-860177630, Email qiwenxiu0517@163.com Haoyu Zhu, Department of Nephropathy and Rheumatology in Children, Children’s Medical Center, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, 130021, People’s Republic of China, Tel +86-431-81953813, Email doctorzhuhaoyu163@163.comAbstract: Endothelial cells (ECs) are widely distributed inside the vascular network, forming a vital barrier between the bloodstream and the walls of blood vessels. These versatile cells serve myriad functions, including the regulation of vascular tension and the management of hemostasis and thrombosis. Inflammation constitutes a cascade of biological responses incited by biological, chemical, or physical stimuli. While inflammation is inherently a protective mechanism, dysregulated inflammation can precipitate a host of vascular pathologies. ECs play a critical role in the genesis and progression of vascular inflammation, which has been implicated in the etiology of numerous vascular disorders, such as atherosclerosis, cardiovascular diseases, respiratory diseases, diabetes mellitus, and sepsis. Upon activation, ECs secrete potent inflammatory mediators that elicit both innate and adaptive immune reactions, culminating in inflammation. To date, no comprehensive and nuanced account of the research progress concerning ECs and inflammation in vascular-related maladies exists. Consequently, this review endeavors to synthesize the contributions of ECs to inflammatory processes, delineate the molecular signaling pathways involved in regulation, and categorize and consolidate the various models and treatment strategies for vascular-related diseases. It is our aspiration that this review furnishes cogent experimental evidence supporting the established link between endothelial inflammation and vascular-related pathologies, offers a theoretical foundation for clinical investigations, and imparts valuable insights for the development of therapeutic agents targeting these diseases.Keywords: endothelial cells, endothelial inflammation, vascular-related diseases, atherosclerosis, diabetes mellitus, cardiovascular diseases

Yonghua Ye,1 Yuping Yang,1 Li Yan,1 Li Zhou,2 Shihui Yu,1 Quan Du,3 Xiaoqiao Dong,3 Qiang Yuan,1 Letian Shan,2,4 Le Guo1 1College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Neurosurgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, People’s Republic of ChinaCorrespondence: Letian Shan, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Tel +15355015568, Email letian.shan@zcmu.edu.cn Le Guo, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Tel +18986648306, Email le.guo@zcmu.edu.cnPurpose: To explore the pharmacological effects and mechanisms of Qinghao Biejia decoction (QBD) against non-small-cell lung cancer (NSCLC) based on network pharmacology and to verify the anticancer effect of artemisinin B (ART B), the active ingredient of QBD, on H1299 cells.Methods: Ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied to explore the chemoprofile of QBD. A zebrafish xenograft model was used to determine the anti-cancer efficacy of QBD. Cell counting kit-8 assay, terminal deoxyribonucleotide transferase-mediated-dUTP nick-end labeling assay; immunofluorescence, and flow cytometry were used to evaluate the in vitro anti-proliferative and pro-apoptotic effects of QBD and ART B on H1299 cells. Subsequently, the related targets and action mechanisms of both QBD and ART B predicted by network pharmacological analyses were experimentally validated by real-time PCR and Western blot assays on H1299 cells.Results: UPLC-QTOF-MS/MS identified a total of 69 compounds (such as ART B, mangiferin, and artemisinic acid) in QBD. The in vivo data showed that QBD significantly inhibited the growth of H1299 cells in xenograft larval zebrafish from 125 to 500 μg/mL. The in vitro data showed that QBD induced apoptosis of H1299 cells, accompanied by down-regulating the expression of BCL-2 and up-regulating the expression of BIM, PUMA, BAX, c-PARP, γ-H2A.X, c-CASP3, and c-CASP8. Alike QBD, ART B exerted similar anti-proliferative and pro-apoptotic effects on H1299 cells. Moreover, ART B inhibited expressions of BCL2L1, AKT1, AKT2, MMP-2, and EGFR, and up-regulated ALB expression. Mechanistically, ART B promoted apoptosis of H1299 cells by inhibiting PI3K/Akt signaling pathway.Conclusion: This study revealed the anti-NSCLC efficacy of QBD. ART B, the effective component of QBD, plays an anti-NSCLC role by down-regulating the PI3K-Akt signaling pathway. It suggests that QBD and ART B are promising drug candidates for NSCLC treatment.Graphical Abstract: Keywords: Qinghao Biejia decoction, non-small-cell lung cancer, larval zebrafish, network pharmacology, artemisinin B

Han Li,1,&ast; Ke Su,1,&ast; Lu Guo,2,&ast; Yi Jiang,1 Ke Xu,1 Tao Gu,1 Jiali Chen,1 Zhenying Wu,1 Pan Wang,3 Xi Zhang,4 Yushan Yan,1 Siyuan Li,1 Xue Wu,1 Lei Han,5 Kun He,6 Lianbin Wen,7 Bo Li,4 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 6Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 7Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han; Bo Li, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598 ; +86-830-3165613, Email lanpaoxiansheng@126.com; liboer2002@126.comBackground: At present, it is not known whether targeting plus immunotherapy combined with transarterial chemoembolization (TACE) can improve the efficacy of hepatocellular carcinoma (HCC). The aim of this retrospective experiment was to explore the difference in clinical efficacy between antiangiogenic drugs plus PD-1 inhibitors combined with and without TACE.Methods: Clinical data of 145 patients with HCC who received anti-angiogenesis therapy plus PD-1 inhibitor combined with TACE (TACE-P-T) (n = 62) or anti-angiogenesis therapy combined with PD-1 inhibitor (P-T) (n = 83) in China from October 2018 to December 2022 were collected and reviewed. We used propensity matching (PSM) to create two groups with comparable baseline scores, compared their median survival time (mOS) and median progression-free survival time (mPFS), and performed subgroup analysis.Results: Before PSM, the mOS and mPFS of patients were 20.3 and 5.0 months in the triple therapy group and 13.6 and 7.4 months in the control group, respectively. After PSM, the mOS and mPFS of patients were 19.7 and 6.6 months in the triple treatment group and 10.5 and 3.7 months in the control group, respectively. Therefore, the TACE-P-T group showed better survival outcomes than P-T. In the subgroup analysis, compared with the control group, the mOS was 10.7 vs 20.3 months in the alpha fetoprotein (AFP) (≥ 400ng/mL/< 400ng/mL) group, 29.3 vs 7.4 months in the alkaline phosphatase (ALP) (≥ 125u/L/< 125u/L) group and 10.5 vs 20.0 months in the Portal vein invasion (PVTT) group.Conclusion: Antiangiogenic therapy combined with PD-1 inhibitors combined with TACE has significant survival benefits for HCC patients.Keywords: HCC, PD-1 inhibitors, antiangiogenic therapy, TACE

Susu Feng,1 Lin Guo,1 Sijing Wang,1 Lijuan Chen,1 Hang Chang,2 Bo Hang,2,3 Jianhua Mao,2 Antoine M Snijders,2 Yibing Lu,1 Dafa Ding1 1Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; 3Department of Biomaterials, Berkeley-Nanjing Research Center, Nanjing, People’s Republic of ChinaCorrespondence: Dafa Ding, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, People’s Republic of China, Tel +86 15850514014, Email dingdafa@njmu.edu.cnAim: We aimed to identify the ability of serum bile acids (BAs) and unsaturated fatty acids (UFAs) profiles to predict the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) patients.Methods: We first used univariate and multivariate analysis to compare 15 serum BA and 11 UFA levels in healthy control (HC) group (n = 82), T2DM patients with DR (n = 58) and T2DM patients without DR (n = 60). Forty T2DM patients were considered for validation. Then, the receiver operating characteristic curve (ROC) and decision curve analysis were used to assess the diagnostic value and clinical benefit of serum biomarkers alone, clinical variables alone or in combination, and the area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to further assess whether the addition of biomarkers significantly improved the predictive ability of the model.Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) of serum BAs and UFAs separated the three cohorts including HC, T2DM patients with or without DR. The difference in serum BA and UFA profiles of T2DM patients with or without DR was mainly manifested in the three metabolites of taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA) and arachidonic acid (AA). Together, they had an AUC of 0.785 (0.918 for validation cohort) for predicting DR in T2DM patients. After adjusting for numerous confounding factors, TLCA, TUDCA, and AA were independent predictors that differentiated T2DM with or without DR. The results of AUC, IDI, and NRI demonstrated that adding these three biomarkers to a model with clinical variables statistically increased their predictive value and were replicated in our independent validation cohort.Conclusion: These findings highlight the association of three metabolites, TLCA, TUDCA and AA, with DR and may indicate their potential value in the pathogenesis of DR.Keywords: type 2 diabetes mellitus, diabetic retinopathy, serum bile acid, unsaturated fatty acid

Zhengzhao Li,1,&ast; Lianshan Guo,1,&ast; Liqiao Lin,1 Tongting Wang,1 Yanqiu Jiang,1 Jin Song,1 Jihua Feng,1 Jianfeng Huang,2 Haoyu Li,2 Zhihao Bai,3 Wenqi Liu,4 Jianfeng Zhang1 1Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China; 2Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China; 3College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, China; 4Department of Radiation Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China&ast;These authors contributed equally to this workCorrespondence: Zhihao Bai, College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, China, Tel/Fax +86 771-3237584, Email zhihao_bai@163.com Jianfeng Zhang, Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China, Tel +86 771- 3277068, Fax +86 771- 3277277, Email zhangjianfeng@gxmu.edu.cnPurpose: Although the combined photo-thermal (PTT) and photodynamic therapy (PDT) of tumors have demonstrated promise as effective cancer therapy, the hypoxic and insufficient H2O2 supply of tumors seriously limits the efficacy of PDT, and the acidic environment reduces the catalytic activity of nanomaterial in the tumor microenvironment. To develop a platform for efficiently addressing these challenges, we constructed a nanomaterial of Aptamer@dox/GOD-MnO2-SiO2@HGNs-Fc@Ce6 (AMS) for combination tumor therapy. The treatment effects of AMS were evaluated both in vitro and in vivo.Methods: In this work, Ce6 and hemin were loaded on graphene (GO) through π-π conjugation, and Fc was connected to GO via amide bond. The HGNs-Fc@Ce6 was loaded into SiO2, and coated with dopamine. Then, MnO2 was modified on the SiO2. Finally, AS1411-aptamer@dox and GOD were fixed to gain AMS. We characterized the morphology, size, and zeta potential of AMS. The oxygen and reactive oxygen species (ROS) production properties of AMS were analyzed. The cytotoxicity of AMS was detected by MTT and calcein-AM/PI assays. The apoptosis of AMS to a tumor cell was estimated with a JC-1 probe, and the ROS level was detected with a 2’,7’-Dichlorodihydrofluorescein diacetate (DCFH-DA) probe. The anticancer efficacy in vivo was analyzed by the changes in the tumor size in different treatment groups.Results: AMS was targeted to the tumor cell and released doxorubicin. It decomposed glucose to produce H2O2 in the GOD-mediated reaction. The generated sufficient H2O2 was catalyzed by MnO2 and HGNs-Fc@Ce6 to produce O2 and free radicals (•OH), respectively. The increased oxygen content improved the hypoxic environment of the tumor and effectively reduced the resistance to PDT. The generated •OH enhanced the ROS treatment. Moreover, AMS depicted a good photo-thermal effect.Conclusion: The results revealed that AMS had an excellent enhanced therapy effect by combining synergistic PTT and PDT.Keywords: nanomaterial, photo-thermal therapy, photodynamic therapy, hypoxia

Han Li,1,&ast; Lu Guo,2,&ast; Ke Su,1,&ast; Changlun Li,3 Yi Jiang,1 Pan Wang,4 Jiali Chen,1 Zhenying Wu,1 Ke Xu,5 Tao Gu,1 Hao Zeng,1 Kun He,6 Hao Chi,1 Wenxi Zhao,7 Lei Han,3 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 4Clinical Skills Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Oncology, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China; 6Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 7Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598, Email Lanpaoxiansheng@126.com Lei Han, Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China, Email hanleixxf@126.comBackground: TACE and TACE with or without targeted immunotherapy are crucial comprehensive therapies for middle and advanced HCC. However, a reasonable and concise score is needed to evaluate TACE and TACE combined with systemic therapy in HCC treatment.Methods: The HCC patients were grouped into two groups: training group (n = 778) (treated with TACE) and verification group (n = 333). The predictive value of baseline variables on overall survival was analyzed using COX model, and easy-to-use ALR (AST and Lym-R) scores. The best cut-off value of AST and Lym-R were determined using X-Tile software based on total survival time (OS) and further verified via a restricted three-spline method. Meanwhile, the score was further verified using two independent valid sets: TACE combined with targeted therapy and TACE with targeted combined immunotherapy.Results: In multivariate analysis, baseline serum AST> 57.1 (p < 0.001) and Lym-R≤ 21.7 (p < 0.001) were identified as independent prognostic factors. The OS of patients in the TACE pooled cohort with 0, 1, and 2 scores were 28.1 (95% CI 24– 33.8) months, 15 (95% CI 12.4– 18.6) months, and 7.4 (95% CI 5.7– 9.1) months, respectively. The time-varying ROC curve based on ALR showed that the AUC values for predicting 1, -2-and 3-year OS were 0.698, 0.718, and 0.636, respectively. These results are confirmed in two independent valid sets of TACE combined with targeted therapy and TACE with targeted combined immunotherapy. And we established a nomogram after COX regression to predict the 1 -, 2- and 3-year survival time.Conclusion: Our study confirmed that ALR score can predict the prognosis of HCC treated with TACE or TACE combined with systemic therapy.Keywords: TACE, immunotherapy, targeted therapy, nomogram

Le Guo,1,&ast; Xijun Li,2,&ast; Chao Zhang,3,&ast; Yang Xu,4 Lujun Han,5 Ling Zhang1 1Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan, Hunan Province, People’s Republic of China; 3Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 4Department of Interventional, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhang, Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Tel +86-2062786561, Email zhangling_smu@163.com Lujun Han, Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China, Tel +86-2087342125, Email hanlj@sysucc.org.cnPurpose: To explore whether texture features based on magnetic resonance can distinguish diseases combined hepatocellular-cholangiocarcinoma (cHCC-CC) from hepatocellular carcinoma (HCC) before operation.Methods: The clinical baseline data and MRI information of 342 patients with pathologically diagnosed cHCC-CC and HCC in two medical centers were collected. The data were divided into the training set and the test set at a ratio of 7:3. MRI images of tumors were segmented with ITK-SNAP software, and python open-source platform was used for texture analysis. Logistic regression as the base model, mutual information (MI) and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to select the most favorable features. The clinical, radiomics, and clinic-radiomics model were constructed based on logistic regression. The model’s effectiveness was comprehensively evaluated by the receiver operating characteristic (ROC) curve, area under the curve (AUC), sensitivity, specificity, and Youden index which is the main, and the model results were exported by SHapley Additive exPlanations (SHAP).Results: A total of 23 features were included. Among all models, the arterial phase-based clinic-radiomics model showed the best performance in differentiating cHCC-CC from HCC before an operation, with the AUC of the test set being 0.863 (95% CI: 0.782 to 0.923), the specificity and sensitivity being 0.918 (95% CI: 0.819 to 0.973) and 0.738 (95% CI: 0.580 to 0.861), respectively. SHAP value results showed that the RMS was the most important feature affecting the model.Conclusion: Clinic-radiomics model based on DCE-MRI may be useful to distinguish cHCC-CC from HCC in a preoperative setting, especially in the arterial phase, and RMS has the greatest impact.Keywords: magnetic resonance, radiomics, machine learning, primary liver cancer, differential diagnosis

Xiaoling Zhang, Xuting Jin, Jiajia Ren, Jueheng Liu, Haichang Ma, Xiaoming Fang, Huifan Zhang, Yujie Zhao, Yanli Hou, Yanni Luo, Lei Guo, Qi Ma, Ya Gao, Jingjing Zhang, Jiamei Li, Xiaochuang Wang, Gang Wang Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Xiaochuang Wang; Gang Wang, Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xi 5 Lu, Xi’an, Shaanxi, 710004, People’s Republic of China, Tel +86-029-8767-9630 ; +86-029-8767-9633, Email dr_xc_wang@163.com; gang_wang@xjtu.edu.cnPurpose: In patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infection, the impact of appropriate empirical antibiotic treatment (AEAT) initialized before culture results were available remains controversial. We aimed to investigate the effect of AEAT on the prognosis of critically ill patients with hospital-acquired pneumonia (HAP) caused by CRGNB.Patients and Methods: Patients with CRGNB-infected HAP and received empirical antibiotic treatment (EAT) for at least 3 days in the intensive care unit (ICU) of a tertiary teaching hospital in China from February 2017 to September 2021 were included in the retrospective cohort study. Patients were categorized into AEAT and inappropriate empirical antibiotic treatment (IEAT) groups based on whether they received EAT covering CRGNB. The associations of AEAT with ICU and 28-day mortality were assessed using multivariable logistic regression model.Results: A total of 94 patients were enrolled, including 29 patients in AEAT group and 65 patients in IEAT group. Patients in AEAT group had a higher Sequential Organ Failure Assessment (SOFA) score (P = 0.003), levels of procalcitonin (PCT) (P = 0.001), and lactic acid (LAC) (P = 0.026); while patients in the IEAT group had a higher platelet count (PLT) (P = 0.001). There was no significant difference in the length of ICU stay between the two groups (P = 0.051). Compared with IEAT, AEAT was associated with an increased risk of 28-day mortality in the univariable logistic regression model (OR: 2.618, 95% CI: 1.063– 6.448). However, after adjusted for SOFA score, PLT, PCT, and LAC level, the association between AEAT and 28-day mortality diminished (OR: 1.028, 95% CI: 0.353– 2.996). AEAT showed no significant association with ICU mortality in neither univariable (OR: 1.167, 95% CI: 0.433– 3.142) nor multivariable (OR: 0.357, 95% CI: 0.097– 1.320) models.Conclusion: AEAT showed no significant influence on ICU or 28-day mortality in critically ill patients with HAP caused by CRGNB infection.Keywords: appropriate empirical antibiotics, hospital-acquired pneumonia, carbapenem-resistant, gram-negative bacteria, ICU mortality

Lei Guo,1,&ast; Xiangzhao Xu,2,&ast; Rui Qin,1 Yongqiang Shi,1 Wei Xue,3 Ling He,3 Shuqin Ma,3 Yi Chen1 1Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Anesthesiology, The People’s Hospital of Nanchuan, Chongqing, People’s Republic of China; 3Department of Obstetrics, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Chen, Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, 804S Shengli Street, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel +86-951-6743252, Email czzyxgp@163.comBackground: Norepinephrine and phenylephrine are widely used for obstetric anesthesia. Our central objective was to determine the ED (effective dose) 90 and potency ratio of prophylactic norepinephrine and phenylephrine boluses for preventing postspinal anesthesia hypotension during cesarean section.Methods: Patients scheduled for elective cesarean section (n = 80) were randomly allocated to receive prophylactic norepinephrine (NE) or phenylephrine (PE) boluses immediately after induction of spinal anesthesia. An initial dose of NE (3 μg) and PE (37.5 μg) was given to the first patient, and an up-and-down sequential allocation method was used to determine the next dose level according to the responses (the effectiveness for preventing postspinal anesthesia hypotension [defined as SBP < 80% of baseline value]). Primary outcomes were ED90 and the potency ratio of prophylactic norepinephrine and phenylephrine boluses. Secondary outcomes were the incidence of postspinal anesthesia hypotension, severe postspinal anesthesia hypotension, nausea, vomiting, bradycardia, hypertension, umbilical artery blood gas values, and Apgar scores.Results: The ED90 values for prophylactic norepinephrine and phenylephrine boluses were 8.0 μg (95% CI 7.1– 11.0 μg) and 90.9 μg (95% CI 82.0– 123.9 μg), respectively. The estimated relative potency ratio was 11.4:1. The incidence of bradycardia was lower in the NE group (2.5% vs 20%, P = 0.034). Other outcomes were comparable between the two groups.Conclusion: An 8-μg prophylactic bolus of norepinephrine and a 90-μg prophylactic bolus of phenylephrine can effectively prevent postspinal anesthesia hypotension in patients during cesarean section.Keywords: cesarean section, norepinephrine, phenylephrine, postspinal anesthesia hypotension

Tianshui Niu,1,2,&ast; Lihua Guo,2,&ast; Xiaoyang Kong,2,&ast; Fei He,1 Chuhui Ru,1 Yonghong Xiao2 1Department of Respiratory and Critical Care Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Xiao, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel/Fax +86 571 87236421, Email xiaoyonghong@zju.edu.cnBackground: Different sequence types of Acinetobacter baumannii (AB) have their own epidemiological characteristics, drug resistance, and toxicity.Methods: AB bloodstream infection (BSI) in the First Affiliated Hospital of Medical College of Zhejiang University from January 2012 to December 2017 were classified by multilocus sequence typing. Clinical data of patients were retrospectively analyzed, drug resistance and toxicity were respectively studied by drug sensitivity and complement killing tests.Results: 247 unduplicated AB strains were collected, and ST191/195/208, the main epidemic dominant strain, accounted for 70.9%. Patients with ST191/195/208 on infection had higher white blood cell (10.8 vs 8.9, p = 0.004), neutrophil% (89.5 vs 86.9, p = 0.005), neutrophil count (9.5 vs 7.1, p = 0.021), D-dimer (6.7 vs 3.8, p = 0.000), total bilirubin (27.0 vs 21.5, p = 0.038), pronatriuretic peptide (324 vs 164, p = 0.042), C-reactive protein (82.5 vs 56.3, p = 0.048), clinical pulmonary infection score (CPIS; 7.33 ± 2.30 vs 6.50 ± 2.72, p = 0.045), and acute physiology and chronic health evaluation-II (APACHE-II; 19.620 ± 5.1850 vs 17.648 ± 6.1251, p = 0.011). Patients with ST191/195/208 had more complications, including pulmonary infection (p = 0.041), septic shock (p = 0.009), and multiple organ failure (p = 0.019). Patients with ST191/195/208 had higher 3 day mortality (24.6% vs 13.9%, p = 0.043), 14 day mortality (46.8% vs 26.8%, p = 0.003), and 28 day mortality (55.0% vs 32.4%, p = 0.001). ST191/195/208 strains had higher drug resistance to most antibiotics, and higher survival rate at 90% normal serum concentration (p < 0.001).Conclusion: ST191/195/208 strains predominate in the hospital and prevails in patients with severe infections with increased multidrug antimicrobial resistance and excessive mortality compared to any other AB stains.Keywords: Acinetobacter baumannii, bloodstream infection, MLST, mortality, toxicity

Litao Guo,1 Yu Liu,1 Lei Zhang,1 Qing Li,2 Haibo Qiu,2 Yaling Guo,3 Qindong Shi1 1Department of Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Infectious Diseases, Xi’an Eighth Hospital, Xi’an, People’s Republic of ChinaCorrespondence: Qindong Shi, Department of Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Road Yanta West, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel +86 029 85323186, Email shiqindong@163.comBackground: Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been widely used in treating patients with coronavirus disease 2019 (COVID-19) with severe respiratory failure. However, there are few reports of the successful treatment of patients with massive airway hemorrhage in severe COVID-19 during VV-ECMO treatment.Methods: We analyzed the treatment process of a patient with a massive airway hemorrhage in severe COVID-19, who underwent prolonged VV-ECMO treatment.Results: A 59-year-old female patient was admitted to the intensive care unit after being confirmed to have severe acute respiratory syndrome coronavirus 2 infection with severe acute respiratory distress syndrome. VV-ECMO, mechanical ventilation, and prone ventilation were administered. Major airway hemorrhage occurred on day 14 of ECMO treatment; conventional management was ineffective. We provided complete VV-ECMO support, discontinued anticoagulation, disconnected the ventilator, clipped the tracheal intubation, and intervened to embolize the descending bronchial arteries. After the airway hemorrhage stopped, we administered cryotherapy under bronchoscopy, low-dose urokinase locally, and bronchoalveolar lavage in the airway to clear the blood clots. The patient’s condition gradually improved; she underwent ECMO weaning and decannulation after 88 days of VV-ECMO treatment, and the membrane oxygenator was changed out four times. She was successfully discharged after 182 days in hospital.Conclusion: Massive airway hemorrhage in patients with severe COVID-19 and treated with ECMO is catastrophic. It is feasible to clamp the tracheal tube with the full support of ECMO. Notably, bronchoscopy with cryotherapy is effective for removing blood clots.Keywords: coronavirus disease 2019, acute respiratory distress syndrome, mechanical ventilation, cryotherapy, airway hemorrhage, extracorporeal membrane oxygenation

Rui Liu, Dandan Shi, Lu Guo, Shan Xiao, Mengmeng Shang, Xiao Sun, Dong Meng, Yading Zhao, Xiaoxuan Wang, Jie Li Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Jie Li, Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Email jieli@email.sdu.edu.cnIntroduction: Triple-negative breast cancer (TNBC) is known to be the most aggressive form of breast cancer. Due to its high recurrence and mortality rates, the treatment of TNBC is a significant challenge for the medical community. Besides, ferroptosis is an emerging regulatory cell death that may provide new insights into the treatment of TNBC. As a central inhibitor of the ferroptosis process, the selenoenzyme glutathione peroxidase 4 (GPX4) is its classical therapeutic target. However, inhibition of GPX4 expression is quite detrimental to normal tissues. Ultrasound contrast agents, as an emerging visualization precision treatment, may provide a solution to the existing problem.Methods: In this study, nanodroplets (NDs) carrying simvastatin (SIM) were constructed using the homogeneous/emulsification method. Then, the characterization of SIM-NDs was systematically evaluated. Meanwhile, in this study, the ability of SIM-NDs combined with ultrasound-targeted microbubble disruption (UTMD) to initiate ferroptosis and its respective mechanisms of ferroptosis induction were verified. Finally, the antitumor activity of SIM-NDs was investigated in vitro and in vivo using MDA-MB-231 cells and TNBC animal models.Results: SIM-NDs exhibited excellent pH- and ultrasound-responsive drug release and noticeable ultrasonographic imaging ability, also showing good biocompatibility and biosafety. UTMD could promote increased intracellular reactive oxygen species and consume intracellular glutathione. However, SIM-NDs were efficiently internalized into cells under ultrasound irradiation, followed by the rapid release of SIM, which inhibited intracellular mevalonate production, and synergistically downregulated GPX4 expression, thereby promoting ferroptosis. Moreover, this combined treatment demonstrated strong antitumor ability in vitro and in vivo.Conclusion: The combination of UTMD and SIM-NDs presents a promising avenue for harnessing ferroptosis in the treatment of malignant tumors.Graphical Abstract: Keywords: ultrasound-targeted microbubble disruption, nanodroplets, ferroptosis, glutathione peroxidase 4, theranostics, lipid peroxidation

Peng Huang,&ast; Xinyu Zhu,&ast; Li Guo Department of Radiology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Guo, Email guolidoc@163.comAbstract: In this study, we report a case of idiopathic cutaneous calcium deposits in the scrotum diagnosed by imaging and pathology. A 31-year-old male presented 4 years ago with multiple nodules on the scrotal skin that had increased significantly in the past 2 years. MR showed mainly low signal nodular shadowing and diagnosed idiopathic cutaneous calcium deposits in the scrotum. To our knowledge, this is one of the rare diagnoses of the disease by imaging presentation.idiopathic scrotal calcinosis, scrotum, MRI

Recent years have witnessed a rapid development in the field of structural coloration, colors generated from the interaction of nanostructures with light. Compared to conventional color generation based on pigments and dyes, structural color generation exhibits unique advantages in terms of spatial resolution, operational stability, environmental friendliness, and multiple functionality. Here, we discuss recent development in structural coloration based on layered thin films and optical metasurfaces. This review first presents fundamentals of color science and introduces a few popular color spaces used for color evaluation. Then, it elaborates on representative physical mechanisms for structural color generation, including Fabry–Pérot resonance, photonic crystal resonance, guided mode resonance, plasmon resonance, and Mie resonance. Optimization methods for efficient structure parameter searching, fabrication techniques for large-scale and low-cost manufacturing, as well as device designs for dynamic displaying are discussed subsequently. In the end, the review surveys diverse applications of structural colors in various areas such as printing, sensing, and advanced photovoltaics.

Ke Su,1,&ast; Weihong Huang,2,&ast; Xueting Li,3,&ast; Ke Xu,4,&ast; Tao Gu,1 Yanlin Liu,1 Juan Song,2 Keyi Qian,5 Yaoyang Xu,2 Hao Zeng,1 Yipei Yang,6 Lu Guo,7 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Oncology, 363 Hospital, Chengdu, 610041, People’s Republic of China; 4Department of Oncology, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China; 5Department of Nursing, Sichuan University, Chengdu, 610065, People’s Republic of China; 6Department of Orthopedic Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, 518000, People’s Republic of China; 7Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han; Lu Guo, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598 ; +86-830-3165613, Email hanyunwei@swmu.edu.cn; guolu68@163.comBackground: Tumor proliferation is frequently accompanied by aberrant enzyme production. We aim to investigate the potential predictive value of both plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in patients with HCC and to develop a nomogram to assess the prognosis of HCC.Methods: The trial involved 2327 patients between May 2015 and March 2022. Within 7 days of enrollment, the levels of ALP and LDH were measured, and their association with survival was assessed. And we had developed and validated a new nomogram based on ALD and ALP.Results: Using X-tile software, the optimal cut-off values were determined to be ALP = 172 U/L and LDH = 241 U/L. The high ALP (≥ 172), LDH (≥ 241), and ALP/LDH (≥ 0.91) groups had lower median overall survival (mOS) than low ALP (< 172), LDH (< 241), and ALP/LDH (< 0.91) groups (all p < 0.001). In addition, elevated ALP and LDH levels are independent negative prognostic indicators. Moreover, we established that the area under the curve (AUC) values of the predicted 1-, 2-, and 3-year survival rates of receiver operating characteristic curve (ROC) based on the nomogram were 0.79, 0.77, and 0.74, respectively. In addition, the calibration curves and decision curve analyses (DCA) demonstrated that this model possessed strong predictive capability.Conclusion: ALP, LDH and ALP/LDH can be employed as biomarkers for predicting the prognosis of HCC. Furthermore, the nomograph based on ALH and ALP demonstrates good HCC prediction performance. For HCC patients with high ALH or ALP or ALP/LDH, close surveillance program and adjuvant therapy should be considered.Keywords: lactate dehydrogenase, alkaline phosphatase, hepatocellular carcinoma, overall survival, nomogram

Litao Guo,1,* Jingjing Zhang,2,* Jin’e Lei,3 Gang Wang2 1Department of Critical Care Medicine, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Clinical Laboratory, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin’e Lei, Department of Clinical Laboratory, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email 871884191@qq.com Gang Wang, Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email gang_wang@xjtu.edu.cnAbstract: Mucormycosis (MCR) is a rare but aggressive fungal disease. Rhino-orbito-cerebral mucormycosis is the most common clinical form of MCR infection, and sinonasal inoculation is the primary site of infection. The morbidity and mortality rates associated with MCR remain high. In this case report, we describe the successful use of amphotericin B in a 40-year-old male with hemorrhagic fever with renal syndrome (HFRS) complicated by rhinomucormycosis. This case report provides evidence for the successful treatment of HFRS.Keywords: hemorrhagic fever with renal syndrome, mucormycosis, pulmonary aspergillosis, sepsis, COVID-19, acute kidney injury

Aqian Hu,1,&ast; Faping Li,2,&ast; Lei Guo,1 Xiaoxi Zhao,1 Xiaojun Xiang1 1Department of Psychiatry and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China; 2Department of Psychiatry, The Second People’s Hospital of Guizhou Province, Guiyang, 550004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojun Xiang, Department of Psychiatry and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China, Tel +86-731-85295814, Email xiangxiaojun@csu.edu.cnObjective: Accumulating evidence has demonstrated that schizophrenia is associated with mitochondrial and immune abnormalities. In this pilot case–control study, we investigated the level of mitochondrial impairment in lymphocytes in patients with acute relapse of schizophrenia and explored the correlation between the level of mitochondrial damage and symptoms or treatment response.Methods: Lymphocytic mitochondrial damage was detected using mitochondrial fluorescence staining and flow cytometry in 37 patients (at admission and discharge) and 24 controls. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale (CGI-S).Results: The levels of mitochondrial damage in CD3+ T, CD4+ T, and CD8+ T lymphocytes of the patients with schizophrenia at admission were significantly higher than those of the controls (p< 0.05) and did not return to normal at discharge (p> 0.05). The mitochondrial damage of T cells significantly improved at discharge for responsive patients only, as compared with that at admission (P< 0.05). However, no significant difference was found in mitochondrial damage in CD19+ B cells between patients and healthy controls, or between admission and discharge (p> 0.05). Furthermore, the reduction in mitochondrial damage of CD3, CD4, and CD8 lymphocytes was positively correlated with the reduction of the score of the PANSS positive scale at discharge (p< 0.05), while no significant correlation was found between the level of mitochondrial damage in lymphocytes and the scores of PANSS and CGI-S.Conclusion: Acute relapse of schizophrenia might be associated with higher levels of mitochondrial damage in peripheral blood T lymphocytes. The degree of recovery of mitochondrial impairment in the T cells may be used as a predictor of treatment response in schizophrenia. As this is a pilot study, the conclusion still needs further verification in large-scale studies.Keywords: immune metabolism, mitochondrial impairment, lymphocyte, schizophrenia, biological marker

Jiayi Li,1,2,&ast; Qiao Chen,1,3,&ast; Lei Guo,4,&ast; Ji Li,5 Bao Jin,1 Xiangan Wu,1 Yue Shi,1 Haifeng Xu,1 Yongchang Zheng,1 Yingyi Wang,6 Shunda Du,1 Zhili Li,4 Xin Lu,1 Xinting Sang,1 Yilei Mao1 1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 4Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, People’s Republic of China; 5Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 6Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunda Du; Zhili Li, Email dushd@pumch.cn; lizhili@ibms.pumc.edu.cnPurpose: To quantitatively analyze lipid molecules in tumors and adjacent tissues of intrahepatic cholangiocarcinoma (ICC), to establish diagnostic model and to examine lipid changes with clinical classification.Patients and Methods: We measured the quantity of 202 lipid molecules in 100 tumor observation points and 100 adjacent observation points of patients who were diagnosed with ICC. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were handles, along with Student’s t-test to identify specific metabolites. Prediction accuracy was validated in the validation set. Another logistic regression model was also established on the training set and validated on the validation set.Results: Distinct separation was obtained from PCA and OPLS-DA model. Ten differentiating metabolites were identified using PCA, OPLA-DA and Lasso regression: [m/z 722.5130], [m/z 863.5655], [m/z 436.2834], [m/z 474.2626], [m/z 661.4813], [m/z 750.5443], [m/z 571.2889], [m/z 836.5420], [m/z 772.5862] and [m/z 478.2939]. Using logical regression, a diagnostic equation: y = 3.4&ast;[m/z 436.2834] - 3.773&ast;[m/z 474.2626] + 3.82&ast;[m/z 661.4813] - 4.394&ast;[m/z 863.5655] + 10.165 based on four metabolites successfully differentiated cancerous areas from adjacent normal areas. The AUROC of the model reached 0.993 (95% CI: 0.985– 0.999) in the validation group. Compared with the adjacent non-tumor area, three characteristic metabolites FA (22:4), PA (P-18:0/0:0) and Glucosylceramide (d18:1/12:0) showed an increasing trend from stage I to stage II, while seven other metabolites LPA(16:0), PE(34:2), PE(36:4), PE(38:3), PE(40:6), PE(40:5) and LPE(16:0) showed a decreasing trend from stage I to stage II.Conclusion: We successfully identified lipid molecules in differentiating tumor tissue and adjacent tissue of ICC, established a discrimination logistic model which could be used as a classifier to classify tumor and non-tumor regions based on analysis in tumor margins and provided information for biomarker changes in ICC, and proposed to related lipid changes with clinical classification.Keywords: intrahepatic cholangiocarcinoma, in situ lipids profiles, metabolomics, mass spectrometry, classification and diagnostic model

Tingting Ye, Liujin Lu, Liuqing Guo, Min Liang Department of Geriatric Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Min Liang, Department of Geriatric Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Tel +86 13878838907, Email liangm@gxmu.edu.cnPurpose: To explore the relationship between hemoglobin levels and osteoporosis and the risk factors for osteoporosis in patients with type 2 diabetes mellitus (T2DM).Patients and methods: A cross-sectional study was conducted in 495 T2DM adults. Medical data were collected from electronic medical records.Results: T2DM patients with osteoporosis had significant lower hemoglobin levels (P < 0.001). Spearman correlation analysis and logistic regression analysis showed that age, female, body mass index (BMI), smoking, drinking and hemoglobin levels were significantly associated with osteoporosis in T2DM patients (all P < 0.05). After adjustment for BMI, diabetic duration, estimated glomerular filtration rate (eGFR), smoking and drinking, a significant association between hemoglobin levels and osteoporosis was observed in T2DM males aged 50 years and older (odds ratio [OR] = 0.978, 95% confidence interval [CI]: 0.958– 0.998, P = 0.030). Compared to Q3 groups with normal hemoglobin levels, Q1 groups with anemia had an odd of osteoporosis increased 2.9-fold in T2DM men after adjustment for age, BMI, diabetic duration, eGFR, smoking and drinking (P = 0.032).Conclusion: Hemoglobin levels were associated with the presence of osteoporosis in T2DM men, especially in those aged 50 years and older.Keywords: type 2 diabetes mellitus, osteoporosis, hemoglobin, bone mineral density

Ji Zhao, Haichen Lv, Da Yin, Xuchen Zhou, Hao Zhu, Lei Guo, Junjie Wang Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, Dalian City, People’s Republic of ChinaCorrespondence: Lei Guo; Junjie Wang, Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian City, 116011, People’s Republic of China, Tel +86 411-83635963, Email leiguo@dmu.edu.cn; junjiewdmu@163.comObjective: This study aimed to investigate the prognostic value of systemic immune inflammation index (SII) concerning long-term outcomes in patients with the three-vessel disease (TVD) after revascularization in a large cohort.Methods: In total, 3561 TVD patients who had undergone revascularization between 2013 and 2018 were included in the study. Patients were divided into the low SII (< 694.3 × 109/L) (n = 2556, 71.8%) and the high SII (≥ 694.3 × 109/L) group (n = 1005, 28.2%). The C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess whether the addition of SII to a baseline model with traditional risk factors improved the accuracy of cardiac event prediction. The primary outcome was the frequency of major adverse and cerebrovascular events (MACCE). The secondary outcome was the incidence of all-cause death.Results: After 2.4 years of follow-up, the Cox proportional hazard regression model analysis displayed that high SII was independently associated with an increased risk of developing future MACCE (hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.23– 2.21, p = 0.001) and all-cause death (HR: 2.96; 95% CI: 1.19– 7.32, p = 0.019). The addition of SII significantly improved the reclassification beyond the baseline model with traditional risk factors (MACCE: NRI, 0.115; p = 0.0001; all-cause death: NRI, 0.369; p = 0.0001). Reclassification with the addition of SII also demonstrated an IDI of 0.0022 (p = 0.006) in MACCE and 0.0033 (p = 0.014) in all-cause death.Conclusion: In TVD patients after revascularization, increased SII is an independent prognostic factor for long-term outcomes of MACCE and death. Compared to traditional risk factors, SII improved the risk prediction of major cardiovascular events in TVD patients who underwent revascularization.Keywords: three-vessel disease, revascularization, systemic immune inflammation index, outcomes, coronary artery disease

Qian Liu, Ran Wei, Jian Lu, Hongke Ding, Hui Yi, Li Guo, Jing Wu Department of Medical Genetics Center, Guangdong Women and Children Hospital, Guangzhou City, Guangdong Province, People’s Republic of ChinaCorrespondence: Jing Wu, Department of Medical Genetics Center, Guangdong Women and Children Hospital, NO. 521 Xingnan Road, Panyu District, Guangzhou city, Guangdong Province, People’s Republic of China, Tel +86 20-39151548, Email wujing020@126.comObjective: To analyse the risk of clinical chromosomal abnormalities in foetuses with umbilical cord cysts.Methods: Data from all genetic assays that were performed as part of invasive prenatal diagnoses of umbilical cord cysts between October 2014 and June 2021 were retrospectively collected from Guangdong Women and Children Hospital. We compared the differences in genetic assay findings in isolated and nonisolated umbilical cord cyst cohorts.Results: A total of 49 singleton pregnancies and 2 foetuses that were one of the cotwins in monochorionic twin pregnancies were enrolled in the cohort; 20 isolated and 31 nonisolated umbilical cord cysts were identified in the cohort. One foetus (5%, 1/20) in the isolated umbilical cord cyst group showed chromosomal abnormalities and 17p12 microduplication. Twelve cases (38.7%, 12/31) of chromosomal abnormalities, including seven cases of trisomy 18, two cases of trisomy 13 and three cases of microdeletion, were identified in the nonisolated umbilical cord cyst group. The incidences of chromosomal abnormalities between the two groups were significantly different (1/20, 5% vs 13/31, 38.7%, p=0.003). There was no relative pathological medical exome sequencing finding in the three foetuses suffering from nonisolated umbilical cord cysts whose parents chose to undergo chromosomal microarray analysis (CMA) and medical exome sequencing.Conclusion: This retrospective cohort study evaluated the value of CMA in foetuses with umbilical cord cysts and suggested that copy number variants (CNVs) may be the basic genetic aetiological factors that should be considered for diagnostic evaluation. We recommended CMA as a basic genetic evaluation in cases of umbilical cord cysts, especially in nonisolated cases.Graphical Abstract: Keywords: chromosomal microarray analyses, CMA, umbilical cord cyst, G banding karyotype

Jianhua Liu,1,&ast; Liantao Guo,1,&ast; Yan Rao,2 Weijie Zheng,1 Dongcheng Gao,1 Jing Zhang,2 Lan Luo,1 Xinwen Kuang,1 Saraswati Sukumar,3 Yi Tu,1 Chuang Chen,1 Shengrong Sun1 1Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Animal Biosafety Level III Laboratory at the Center for Animal Experiment, Wuhan University School of Medicine, Wuhan, People’s Republic of China; 3Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA&ast;These authors contributed equally to this workCorrespondence: Shengrong Sun; Chuang Chen, Tel +86-13707198696 ; +86-1476064785, Email sun137@sina.com; chenc2469@163.comPurpose: Triple-negative breast cancer (TNBC) is challenging to treat with traditional “standard of care” therapy due to the lack of targetable biomarkers and rapid progression to distant metastasis.Methods: We synthesized a novel combination regimen that included chemotherapy and photothermal therapy (PTT) to address this problem. Here, we tested a magnetic nanosystem (MNs-PEG/IR780-DOX micelles) loaded with the near-infrared (NIR) photothermal agent IR780 and doxorubicin (DOX) to achieve chemo-photothermal and boost antitumor immunity. Intraductal (i.duc) administration of MNs-PEG/IR780-DOX could increase the concentration of the drug in the tumor while reducing systemic side effects.Results: We showed more uptake of MNs-PEG/IR780-DOX by 4T1-luc cells and higher penetration in the tumor. MNs-PEG/IR780-DOX exhibited excellent photothermal conversion in vivo and in vitro. The release of DOX from MNs-PEG/IR780-DOX is pH- and temperature-sensitive. Facilitated by i.duc administration, MNs-PEG/IR780-DOX displayed antitumor effects and prevented distant organs metastasis under NIR laser (L) irradiation and magnetic field (MF)while avoiding DOX-induced toxicity. More importantly, MNs-PEG/IR780-DOX alleviated tumor immunosuppressive microenvironment by increasing tumor CD8+ T cells infiltration and reducing the proportion of myeloid-derived suppressor cells (MDSCs) and Tregs.Conclusion: Intraductal administration of pH- and temperature-sensitive MNs-PEG/IR780-DOX with L and MF had the potential for achieving minimally invasive, targeted, and accurate treatment of TNBC.Keywords: triple-negative breast cancer, photothermal therapy, near-infrared image, intraductal administration, tumor immunosuppressive microenvironment

Lijing Guo,1,2,&ast; Shihua Chen,1,2,&ast; Liping Ou,1,2,&ast; Shangmei Li,1 Zhen-Nan Ye,1,2 Hua-Feng Liu1,2 1Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China; 2Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen-Nan Ye; Hua-Feng Liu, Email yezhennan12@mails.ucas.ac.cn; hf-liu@263.netAbstract: Alpha-ketoglutarate (AKG) is a key intermediate of various metabolic pathways including tricarboxylic acid (TCA) cycle, anabolic and catabolic reactions of amino acids, and collagen biosynthesis. Meanwhile, AKG also participates in multiple signaling pathways related to cellular redox regulation, epigenetic processes, and inflammation response. Emerging evidence has shown that kidney diseases like diabetic nephropathy and renal ischemia/reperfusion injury are associated with metabolic disorders. In consistence with metabolic role of AKG, further metabolomics study demonstrated a dysregulated AKG level in kidney diseases. Intriguingly, earlier studies during the years of 1980s and 1990s indicated that AKG may benefit wound healing and surgery recovery. Recently, interests on AKG are arising again due to its protective roles on healthy ageing, which may shed light on developing novel therapeutic strategies against age-related diseases including renal diseases. This review will summarize the physiological and pathological properties of AKG, as well as the underlying molecular mechanisms, with a special emphasis on kidney diseases.Keywords: alpha-ketoglutarate, kidney diseases, metabolism, diabetic nephropathy, acute kidney injury