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Shengfeng Liu,1,2 Jian Liu,1,2 Xueni Cheng,1 Dahai Fang,1 Xiaolu Chen,1 Xiang Ding,1 Xianheng Zhang,1 Yiming Chen1 1Department of Rheumatology, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, People’s Republic of China; 2Anhui Key Laboratory of Application and Development of Internal Medicine of Modern Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Rheumatology, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, People’s Republic of China, Tel +86 13955109537, Email liujianahzy@126.comAbstract: Rheumatoid arthritis (RA) is a chronically progressive autoimmune disease with increasing age-standardized prevalence and incidence of RA worldwide. Its pathological features are persistent synovitis of the joint, accompanied by the release of a large number of inflammatory cytokines and cartilage and bone destruction. RA can lead to progressive joint damage, stiffness and swelling, vascular and bone-related complications, and irreversible disability, which seriously affects patients’ life treatment. Early diagnosis and treatment can enhance the quality of life of RA patients. Platelet-to-lymphocyte ratio (PLR), as a common indicator in routine blood tests, has been proposed as an indicator of systemic inflammation in recent years. Its clinical detection is less invasive, economical, rapid and simple, and has been applied to the clinical evaluation of a variety of diseases. Of note, this indicator is important in assessing disease activity in RA, co-diagnosing RA, detecting subclinical complications, and monitoring responses to anti-inflammatory therapy. Therefore, this review summarizes the relationship between PLR and RA and the relevant mechanisms, further advancing the understanding of the clinical value of PLR.Keywords: platelet-to-lymphocyte ratio, rheumatoid arthritis, inflammatory, blood platelets, lymphocytes

Shengyang Liu,1 Hui Zhao,2 Li Shi,1 Hongzhi Ji1 1Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Radiology, Shandong Second Provincial General Hospital, Jinan, People’s Republic of ChinaCorrespondence: Hongzhi Ji, Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, 4 Duanxing West Road, Jinan, 250000, People’s Republic of China, Email jhz_jx163@163.comAbstract: In this case report, we describe a 21-year-old man with recurrent hemangiomas in his left eye socket and nasal cavity. Traditional surgeries were unsuccessful, so we used Bevacizumab, a drug that inhibits blood vessel growth. This approach significantly reduced the tumor size and stopped frequent nosebleeds. Over two years, the tumor remained controlled without major side effects, suggesting Bevacizumab as a promising non-surgical treatment for recurrent hemangiomas.Keywords: Bevacizumab, orbital hemangioma, vascular endothelial growth factor, treatment efficacy

Chunlei Tan,1 Jinling Xu,2 Shiyuan Zhang,1 Shuqiang Liu,1 Xiaotian Yang,1 Danping Wu,1 Boqian Yu,1 Yuanxi Huang1 1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Endoscope Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of ChinaCorrespondence: Yuanxi Huang, Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China, Tel/Fax +86-0451-86298053, Email rxwk@163.comPurpose: The current investigation is to assess FOXP3 expression in breast cancer patients and evaluate the predictive significance of FOXP3.Patients and Methods: A cohort of 313 cases between January 2015 and November 2015 were enrolled this research. Immunohistochemistry (IHC) assay was utilized to detect the expression levels of FOXP3 in primary breast carcinoma specimens. These patients were separated into two groups by semiquantitative scoring approach. Chi-square test and Fisher’s exact test were conducted to investigate the correlations between FOXP3 expression in tumors and clinicopathological variables. Kaplan–Meier method and Log rank test were utilized to generate survival curves for disease-free survival (DFS) and overall survival (OS). The independent factors were examined using Cox regression analysis. Nomogram models were created for assessing DFS and OS rates.Results: Depending on the levels of FOXP3 expression in tumors, these patients were categorized into two groups: low FOXP3 expression (174 cases) and high FOXP3 expression (139 cases). The patients exhibiting low levels of FOXP3 expression in tumors demonstrated a longer survival duration contrasted with those with high expression (DFS: 88.75 vs 65.87 months, χ2=36.1100, P< 0.0001; OS: 89.70 vs 78.37 months, χ2=32.4900, P< 0.0001). Multivariate analysis revealed that FOXP3 was a significant prognostic factor [DFS: hazard ratio (HR): 2.822, 95% CI: 1.595– 4.992, P< 0.0001; OS: HR: 3.232, 95% CI: 1.812– 5.763, P< 0.0001]. The good predictive clinical utility of FOXP3-based nomograms within the threshold probability range for different survival rates was demonstrated by calibration curve and decision curve analyses.Conclusion: FOXP3 expression serves as a crucial prognostic indicator in breast cancer patients, and may aid preoperative evaluation in clinical practice.Keywords: breast cancer, FOXP3, chemotherapy, radiotherapy, survival

Shen Liu, Bijia Song, Liang Zhang, Xiuliang Li, Lingli Cui Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of ChinaCorrespondence: Lingli Cui, Email clinly@126.comIntroduction: Liver transplantation is considered an effective treatment for end-stage liver disease. Laparoscopic donor hepatectomy (LDH) has become a new standard procedure. And it is important to minimize the pain of the donor. Good postoperative analgesia can reduce the occurrence of postoperative complications and promote the early recovery of the donor. Ultrasound-guided transversus abdominis plane (TAP) block can provide effective analgesia for liver donors and reduce postoperative opioid consumption. This study aims to use ultrasound-guided TAP block for LDH to improve postoperative analgesia for donors while reducing opioid consumption and improving patient rehabilitation quality.Methods/Analysis: This study is a prospective blinded, randomized, controlled clinical trial with a concealed allocation of patients (living liver donors) scheduled to receive laparoscopic partial hepatectomy 1:1 to receive local infiltration anesthesia or TAP block. This study will recruit a total of 80 patients. The primary outcome is the dosage of opioids within 24 hours after surgery.Ethics and Dissemination: This trial has been approved by the Institutional Review Board of Beijing Friendship Hospital of China Capital University. This trial study protocol was approved on 8 May 2023. The trial will start recruiting patients after being registered on the Chinese Clinical Trial Registry.Trial Registration Number: ChiCTR2300071694.Keywords: liver transplantation, liver donor, laparoscopic hepatectomy, TAP block, postoperative analgesia

Xiao Shen,1 Jin-Xing Zhang,1 Jin Liu,2 Sheng Liu,1 Hai-Bin Shi,1 Yuan Cheng,3 Qing-Qiao Zhang,4 Guo-Wen Yin,5 Qing-Quan Zu1 1Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Clinical Medicine Research Institution, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 3Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, People’s Republic of China; 4Department of Interventional Radiology and Vascular Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China; 5Department of Interventional Radiology, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Qing-Quan Zu, Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-13913807470, Fax +86-25-83724440, Email zuqingquan@njmu.edu.cnPurpose: Transarterial chemoembolization (TACE), when used in combination with immunotherapy and antiangiogenic therapy, has been shown to have synergistic anticancer effects. The aim of this study was to further assess the efficacy and safety of TACE combined with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC) in the real world.Methods: Between August 2021 and September 2023, clinical information was collected from consecutive HCC patients who received treatment via TACE-Atezo/Bev at four tertiary institutions. This study evaluated the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) as outcomes. Predictors for OS and PFS were also analyzed. Treatment-related adverse events (TRAEs) were recorded and assessed.Results: Ninety-two patients were enrolled in this study, with a median follow-up duration of 14.1 months. The ORRs based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST 1.1 criteria were 54.3% and 41.3%, respectively. The median OS and PFS of the patients were 15.9 months [95% confidence interval (CI), 14.5– 17.2 months] and 9.1 months (95% CI, 7.4– 10.8 months), respectively. Multivariate analyses revealed that the Eastern Cooperative Oncology Group score and neutrophil‒lymphocyte ratio were independent risk factors for OS, whereas tumor size and extrahepatic metastasis were independent risk factors for PFS. Grade 3/4 TRAEs occurred in 16.3% (15/92) of the patients and were controlled conservatively.Conclusion: The combination of Atezo/Bev with TACE demonstrated acceptable synergistic therapeutic effects and manageable safety profiles in patients with unresectable HCC.Keywords: atezolizumab, bevacizumab, efficacy, hepatocellular carcinoma, transarterial chemoembolization

Shang-Yu Lu,1,&ast; Han-Yao Sun,1,&ast; Yan Zhou,2 Xi Luo,3 Sheng Liu,1 Wei-Zhong Zhou,1 Hai-Bin Shi,1 Wei Yang,1 Wei Tian1 1Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Yang; Wei Tian, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-18705164897 ; +86-13770615508, Email youngwei1988@163.com; tianwei@jsph.org.cnPurpose: Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE).Patients and Methods: This was a retrospective study that included 295 HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification.Results: The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set.Conclusion: For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE.Keywords: hepatocellular carcinoma, transarterial chemoembolization, prognostic model, risk assessment, AD score

Ping Wang,&ast; Shuli Liu,&ast; Ling Min Kong, Nannan Qi Department of Pediatrics, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nannan Qi, Department of Pediatrics, The Second Affiliated Hospital of Shandong First Medical University, No. 366, Taishan Street, Taian, Shandong, 271000, People’s Republic of China, Email 13953851791@163.comBackground: Childhood obesity has become a global pandemic, leading to a range of diseases. Childhood obesity appears to be associated with an increased prevalence of sleep apnea syndrome. Sleep apnea is an inestimable risk factor for thrombosis, hypertension, cardiomyopathy and many other diseases. Therefore, exploring the relationship between childhood obesity and sleep apnea syndrome will help to understand the potential link between the two and provide research directions for future disease prevention and treatment. However, no studies have confirmed whether there is a causal relationship between childhood obesity and sleep apnea syndrome.Methods: The IEU OpenGWAS project provided the GWAS-aggregated data for childhood obesity and sleep apnea syndrome. Inverse-variance weighted (IVW) was used as the main method to evaluate the causal relationship between childhood obesity and sleep apnea syndrome. Single nucleotide polymorphisms (SNPs) were regarded as instrumental variables, and the screening threshold was P < 5.0× 10− 6. Leave-one-out method was performed to confirm the robustness of the results.Results: IVW analysis confirmed a causal relationship between genetic susceptibility to childhood obesity and an increased risk of sleep apnea syndrome [odds ratio (OR)=1.12, 95% confidence interval (CI): 1.02– 1.23, P=0.016]. However, two-sample MR results also showed no causal relationship between genetic susceptibility to sleep apnea syndrome and an increased risk of childhood obesity (OR=1.50, 95% CI: 0.95– 2.38, P=0.083). The intercept of MR-Egger regression was close to 0, which implies that there are no confounding factors in the analysis to affect the results of two-sample MR analysis. The leave-one-out results show that the bidirectional two-sample MR analysis results were robust.Conclusion: There is a causal relationship between genetic susceptibility to childhood obesity and increased risk of sleep apnea syndrome. People with a history of childhood obesity should pay more attention to physical examination to early prevention and management of sleep apnea syndrome.Keywords: bidirectional two-sample Mendelian randomization, childhood obesity, sleep apnea syndrome, causal relationship, single nucleotide polymorphisms

Weiqian Zhang,1,&ast; Shuiying Chen,1,&ast; Zhongyu Bai,1 Menglai Gan,2 Mingwei Chen,2 Ying Zhang,1 Sai Liu,2 Dongjuan Liu1 1Department of Emergency and Oral Medicine, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, People’s Republic of China; 2Department of Dental Materials, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongjuan Liu, Department of Emergency and Oral Medicine, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People’s Republic of China, Email dongjuanliu@cmu.edu.cn Sai Liu, Department of Dental Materials, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People’s Republic of China, Email liusai@cmu.edu.cnAbstract: Oral squamous cell carcinoma (OSCC) is the most prevalent and deadly malignancy of the head and neck. The standard treatments for OSCC are surgery, radiotherapy, and chemoradiotherapy, which can cause severe cosmetic and functional damage to the oral cavity and impair the patients’ quality of life. Photodynamic therapy (PDT) is a promising alternative that uses light-activated photosensitizers to induce selective phototoxicity and necrosis in the target tissues. PDT has several advantages over conventional treatments, such as minimal invasion, low side effects, high selectivity and preservation of the oral function and appearance. This review explores the principles, mechanisms, and current applications of PDT for OSCC. We address the challenges, such as the depth of light penetration and tissue hypoxia, and underscore the progressive innovations in photosensitizer enhancement, nanotechnological integration, and precision therapy. The exploration of biomarkers for refining patient selection and tailoring individualized treatment regimens is also undertaken. PDT holds promise as a secure and efficacious modality for OSCC management. Nonetheless, additional investigation is imperative to refine treatment protocols and validate sustained therapeutic success. Keywords: oral squamous cell carcinoma, photodynamic therapy, photosensitizers, nanotechnology, biomarkers

QianYang Chen,1,&ast; Shuo Liu,1,&ast; Yuhan Wang,1,&ast; MeiChen Tong,2 HaiBo Sun,2 Ming Dong,1 Yun Lu,1 WeiDong Niu,1 LiNa Wang1 1Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China; 2Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: WeiDong Niu; LiNa Wang, Email 13840886663@139.com; wanglina@dmu.edu.cnIntroduction: Chronic apical periodontitis is a typical inflammatory disease of the oral cavity, the pathology is characterized by an inflammatory reaction with bone defects in the periapical area. Chinese medicine is our traditional medicine, Carbon Dots (CDs) are a new type of nanomaterials. The purpose of this study was to prepare Yam Carbon Dots (YAM-CDs) to investigate the mechanism of action of YAM-CDs on bone differentiation in vivo and in vitro.Methods: We characterized YAM-CDs using transmission electron microscopy (TEM), Fourier Transform Infrared Spectrometer (FTIR), X-Ray Diffraction (XRD) and photoluminescence (PL). CCK-8 assay, Real-time qPCR, and Western Blot were conducted using bone marrow mesenchymal stem cells (BMSCs) to verify that YAM-CDs promote osteoblast differentiation. In addition, we investigated the role of YAM-CDs in promoting bone formation in an inflammatory setting in an in vivo mouse model of cranial defects.Results: The results of TEM and PL showed that the YAM-CDs mostly consisted of the components C1s, O1s, and N1s. Additionally the average sizes of YAM-CDs were 2– 6 nm. The quantum yield was 4.44%, with good fluorescence stability and biosafety. Real-time qPCR and Western blot analysis showed that YAM-CDs promoted osteoblast differentiation under an inflammatory environment by regulating expression of histone demethylase 4B (KDM4B). In vivo, results showed that YAM-CDs effectively repaired cranial bone defects in a mouse model and reduced the expression of inflammatory factors under the action of lipopolysaccharides (LPS).Conclusion: YAM-CDs promoted the proliferation and differentiation of osteoblasts by regulating the expression of KDM4B to repair cranial bone defects in mice under an LPS-induced inflammatory milieu, which will provide a new idea for the treatment of clinical periapical inflammation and other bone defect diseases.Keywords: traditional Chinese medicine, carbon dots, YAM, bone defect, KDM4B

Ciyi Hua,1 Feifei Li,1 Youyang Shi,2 Yuan Xu,1 Mengdie Zhu,1 Yang Wang,1 Xiqiu Zhou,2 Sheng Liu1,3 1Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Breast Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Sheng Liu, Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China, Tel +86 18917763005, Fax +86-64385700, Email shengliu@shutcm.edu.cnBackground: Patients with clinically cured granulomatous lobular mastitis (GLM) still face a high probability of recurrence and new occurrence.Purpose: To evaluate the long-term efficacy of traditional Chinese medicine (TCM) in treating GLM and to hypothesize potential risk factors for recurrence or new occurrence.Patients and Methods: A retrospective analysis was conducted on GLM patients treated with TCM at Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine from January 2016 to July 2021. We analyzed general data, two-year recurrence and new occurrence rates, and 12 risk factors associated with recurrence or new occurrence.Results: This cross-sectional study included 261 GLM patients with an average age at onset of 31.95 years (primarily aged 31– 40). The two-year recurrence rate for GLM was 1.53%, and the new occurrence rate was 4.21%. Univariate and multivariate conditional logistic regression analyses revealed that a history of inverted nipples was associated with the risk of both recurrence and new occurrence of GLM (HR = 8.672, 5.375, P < 0.05), and menstrual irregularity was related to a higher risk of recurrence (HR = 13.172, P < 0.001).Conclusion: A history of inverted nipples is identified as a potential risk factor associated with the long-term recurrence and new occurrence of GLM, while menstrual irregularity is associated with recurrence. Despite this, patients with GLM undergoing TCM demonstrate low rates of long-term recurrence and new occurrence after achieving clinical cure, underscoring the effectiveness of TCM. This study lays the groundwork for a long-term effectiveness strategy to guide future GLM treatments.Keywords: granulomatous lobular mastitis, GLM, recurrence, new occurrence, risk factor

Zhongbao Zuo,1,&ast; Jing Wu,1,&ast; Miaochan Wang,1 Rui Wu,2 Xiaojing Zhang,2 Lanlan Hu,1 Huaizhong Cui,1 Ting Feng,3 Aifang Xu,1 Shourong Liu2 1Department of Clinical Laboratory, Hangzhou Xixi Hospital, Zhejiang, 310023, People’s Republic of China; 2Department of Hepatology, Hangzhou Xixi Hospital, Zhejiang, 310023, People’s Republic of China; 3Ultrasound Department, Hangzhou Xixi Hospital, Zhejiang, 310023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aifang Xu; Shourong Liu, Email 13616500869@163.com; lsr85463990@126.comIntroduction: This study aimed to explore serum HBV pre-genomic RNA (pgRNA) levels and its associated factors among HBV-infected patients in the real world.Methods: This retrospective cohort study was conducted from May 10, 2023, to January 15, 2024. Univariate logistic analysis for positive serum HBV pgRNA was performed first, and variables with statistical significance were included in a multivariate logistic model. A decreasing trend of serum HBV pgRNA and HBV DNA levels was also detected first by univariate logistic regression and then by multivariate logistic regression.Results: 482 patients were included in our analysis at baseline, and 191 patients were followed up. Multivariate logistic regression revealed that positive HBV DNA (AOR: 2.63, 95% CI: 1.46– 4.75, P=0.001), ≥ 1000 hBsAg (AOR: 2.29, 95% CI: 1.08– 4.89, P=0.03), positive HBeAg (AOR: 28.26, 95% CI: 15.2– 52.55, P< 0.001), and ALP (AOR: 1.01, 95% CI: 1.001– 1.02, P=0.03) were positively correlated with positive HBV pgRNA at baseline. Two independent multivariate logistic regression models were constructed for the decreasing trend of serum HBV pgRNA and HBV DNA for the 191 follow-up patients. Results showed that the decreasing trend of HBV pgRNA was positively correlated with positive baseline HBV DNA (AOR: 4.60, 95% CI: 1.84– 11.51, P=0.001), baseline HBsAg ≥ 1000 IU/mL (AOR: 8.74, 95% CI: 1.09– 70.10, P=0.04), and HDL (AOR: 5.01, 95% CI: 1.28– 19.66, P=0.02). The decreasing trend of HBV DNA was positively correlated with positive baseline HBV pgRNA (AOR: 3.80, 95% CI: 2.00– 8.83, P< 0.001) and AST (AOR: 1.06, 95% CI: 1.03– 1.08, P< 0.001).Conclusion: Our study revealed that HBV DNA, HBsAg, HBeAg, and ALP were significantly correlated with positive HBV pgRNA at baseline. The baseline HBV DNA, HBsAg, and HDL were significantly correlated with decreasing levels of HBV pgRNA. A decreasing trend of HBV DNA significantly correlated with patients’ baseline HBV pgRNA and AST.Keywords: chronic hepatitis B, HBsAg, HBV pgRNA, HBV DNA

Siqi Liu, Xin Sun, Na Liu, Fangcai Lin Department of Breast Surgery, Beijing Electric Power Hospital, Beijing, 100071, People’s Republic of ChinaCorrespondence: Fangcai Lin, Beijing Electric Power Hospital, Beijing, 100071, People’s Republic of China, Email bjdltgyx@163.comBackground: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an RNA-binding protein with N6-methyladenosine (m6A) reader function, is associated with the poor prognosis of various tumors, including triple-negative breast cancer (TNBC). Small nuclear ribonucleoprotein D1 polypeptide (SNRPD1), a spliceosome member, exerts diagnostic and therapeutic functions in breast cancer by regulating the cell cycle and is a potential therapeutic target. However, the interaction between IGF2BP2 and SNRPD1 in the progression of TNBC remain unclear.Objective: This study aimed to investigate the interaction between IGF2BP2 and SNRPD1 in TNBC and elucidate the underlying mechanisms.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression levels of SNRPD1 and IGF2BP2 in human normal breast cells (MCF10A) and TNBC cells (MDA-MB-231). MDA-MB-231 cells were transfected with SNRPD1 interference or overexpression vectors, or co-transfected with SNRPD1 interference and IGF2BP2 overexpression vectors simultaneously. Cell viability, apoptosis, and invasion were assessed using MTT, flow cytometry, and Transwell assays. RNA stability, m6A levels, and the interaction between SNRPD1 and IGF2BP2 were evaluated using qRT-PCR, methylated RNA immunoprecipitation, and RIP assays.Results: SNRPD1 was significantly up-regulated in TNBC cells, promoting cell viability and invasion while inhibiting apoptosis. IGF2BP2 was also up-regulated in TNBC cells and enhanced SNRPD1 mRNA stability via m6A modification. Furthermore, IGF2BP2 overexpression reversed the anti-tumor effect of SNRPD1 knockdown.Conclusion: IGF2BP2 and SNRPD1 were significantly highly expressed in TNBC cells. IGF2BP2 might enhance the stability and protein expression of SNRPD1 through m6A-dependent mechanisms, potentially contributing to the progression of TNBC.Keywords: triple-negative breast cancer, IGF2BP2, SNRPD1, m6A-dependent

Sandip Patil, Xinye Li, Huirong Mai, Ying Wang, Xue Tang, Sixi Liu, Feiqiu Wen Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Sixi Liu; Feiqiu Wen, Email tigar467@126.com; fwen62@163.comBackground: This case report underscores the intricate challenges in managing paediatric patients with acute myeloid leukaemia (AML) undergoing intensive chemotherapy, particularly when complicated by the emergence of multidrug-resistant pathogens such as Carbapenem-Resistant Pseudomonas aeruginosa (CRPA).Case Presentation: An 11-year-old male with AML presented with skin purpura and persistent cough. Clinical and laboratory assessments revealed a high-risk AML profile with genetic mutations, leading to the initiation of intensive chemotherapy per the C-HUANA-AML-2015 protocol. Despite successful disease remission after initial chemotherapy courses, the patient experienced unexpected complications. Notably, septic shock, bone marrow failure, and the emergence of CRPA were encountered during the clinical course. Septic shock occurred following Course B3 chemotherapy, marked by a fever unresponsive to initial antibiotic therapy. Despite negative blood cultures, meropenem and vancomycin were initiated, successfully normalizing temperature. Subsequent challenges included persistent bone marrow suppression, perianal dermatitis, and the identification of CRPA in stool cultures, leading to altered antibiotic therapy guided by minimum inhibitory concentration (MIC) considerations. Whole-genome sequencing (WGS) of the CRPA strain revealed a highly virulent clone (ST-970) with numerous resistance and virulence genes.Conclusion: This case report offers new insights into the complexities of pediatric AML management, with a focus on the emergence of CRPA. The discovery of a high-risk CRPA clone with detailed genomic data underscores the growing challenge of antimicrobial resistance in pediatric oncology. The persistent presence of CRPA and ongoing bone marrow failure highlight the difficulties in managing these complications. This case calls for a reassessment of treatment strategies and encourages further research to improve outcomes in pediatric AML, emphasizing the need for a multidisciplinary approach to address infectious complications and antimicrobial resistance.Keywords: acute myeloid leukaemia, carbapenem-resistant Pseudomonas aeruginosa, paediatric oncology, antimicrobial resistance, superbugs

Man Huang,1,2,&ast; Yudi Jin,3,&ast; Mengyuan Wang,2 Qiang Song,4 Yanjia Fan,1 Yu Zhang,1 Cheng Tian,1 Chi Zhang,1 Shengchun Liu1 1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Breast Center, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Central Laboratory, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengchun Liu, Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email liushengchun1968@163.comBackground: HER2-low breast cancer represents a distinct subgroup with unique clinical characteristics and treatment challenges. Nevertheless, it remains uncertain whether there exists a distinction in δKi67 between patients with HER2-low and HER2-zero statuses, and whether the prognosis varies among patients with differing HER2 statuses and δKi67.Methods: We conducted a multi-center retrospective study to investigate the correlation between alterations in Ki67 index following NAC and the prognosis among patients with HER2-low or HER2-zero breast cancer. 3 distinct cohorts comprising patients with HER2-negative breast cancer who underwent NAC were included. Comprehensive clinicopathological data were documented, with particular emphasis on evaluating changes in Ki67 index from baseline to post-NAC. These changes were then correlated with disease-free survival (DFS) through rigorous analysis.Results: Three cohorts, comprising 403, 315, and 72 patients respectively, were finally included. The study found that δKi67 did not show significant associations with other variables and were not identified as independent risk factors for survival. Nevertheless, across the three cohorts, following NAC, HER2-low breast cancer patients with δKi67 below the cut-off value demonstrated a better prognosis compared to those with δKi67 above the cut-off value. Additionally, their prognosis was also superior to that of HER2-zero breast cancer patients with δKi67 below the cut-off value.Conclusion: Our study demonstrates that HER2-low breast cancer patients with δKi67 values below the cut-off point after NAC are associated with improved prognosis. Monitoring δKi67 index and HER2 status may help identify patients who are likely to benefit from NAC and guide personalized treatment strategies.Keywords: HER2-low breast cancer, neoadjuvant chemotherapy, Ki67 index, prognosis, survival

Shanshan Liu, Ju Li, Zhongyuan Zhang, Deqian Meng, Kai Wang Department of Rheumatology and Immunology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, 223001, People’s Republic of ChinaCorrespondence: Kai Wang, Department of Rheumatology and Immunology, The affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, 223001, People’s Republic of China, Tel/Fax +86-17551710317, Email morrosun@hotmail.comObjective: To evaluate belimumabf’s efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response.Methods: In this single-arm retrospective study, we assessed clinical responses in LN patients at baseline and six months after initiating belimumab. Serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified using multiplex magnetic bead flow immunoassay before and after treatment.Results: Fourteen patients with various subtypes of refractory LN participated in the study: seven with class III and V LN, three with type V alone, two with class III, and two with class IV+V and V LN. Post six months of belimumab therapy, all participants exhibited a reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores from their respective baseline values. Notably, most patients showed a decrease in the dosage of prednisone, levels of 24-hour urinary protein, immunoglobulins, erythrocyte sedimentation rate (ESR), and anti-double-stranded DNA antibody IgM, along with serum levels of IL-4, IL-6, IL-10, and IFN-γ. Meanwhile, levels of C3, C4, IL-2, and TNF-α were observed to increase. Of the participants, nine (64.29%) achieved a complete renal response, one (7.14%) showed a partial response, and four (28.57%) exhibited no response. Significantly, higher baseline serum IFN-γ levels were found in patients who did not achieve complete renal response (CR) compared to those who did (p = 0.009). Receiver operating characteristic (ROC) curve analysis demonstrated that baseline IFN-γ levels had an area under curve (AUC) of 0.96 (0.70– 1.00), with a sensitivity of 0.89 and a specificity of 1.00 (p < 0.001).Conclusion: Belimumab shows potential efficacy in treating refractory LN. Baseline serum IFN-γ levels may predict response to belimumab therapy, potentially enabling more targeted treatment approaches for this challenging condition.Keywords: refractory lupus nephritis, belimumab, treatment, biomarker, IFN-&#x03B3

Qingyang Yu,1,2 Yuanyuan Cui,1 Shuwen Dong,1 Yanqing Ma,1 Yi Xiao,1 Li Fan,1 Shiyuan Liu1 1Department of Radiology, Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Neurosurgery, Changhai Hospital, Navy Military Medical University, Shanghai, 200433, People’s Republic of ChinaCorrespondence: Shiyuan Liu, Department of Radiology, Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Fax +86 2181886012, Email radiology_cz@163.comObjective: Hemifacial spasm (HFS) is a clinical neurosurgical disease, which brain structural alterations caused by HFS remain a topic of debate. We evaluated changes in brain microstructure associated with HFS and observed their relevance to clinical characteristics.Methods: We enrolled 72 participants. T1-weighted structural and diffusion tensor images were collected from all participants using 3.0T magnetic resonance equipment. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to identify changes in gray matter volume (GMV) and disruptions in white matter (WM) integrity. The severity of the spasms was graded using the Cohn scale.Results: VBM analysis revealed that the GMV was significantly reduced in the left Thalamus and increased GMV in the right Cerebellum IV-V of the HFS group. TBSS analysis showed that FA in the left superior longitudinal fasciculus (SLF) of the HFS group was significantly increased. GMV in the thalamus showed a negative correlation with disease duration and Cohn grade, while FA in the left SLF had a positive correlation with both the disease duration and Cohn grade.Conclusion: We identified regions with altered GMV in HFS patients. Additionally, we determined that FA in the left SLF might serve as a significant neural indicator of HFS.Keywords: hemifacial spasm, voxel-based morphometry, diffusion tensor imaging, tract-based spatial statistics, Cohn grading

Anbang Zhao,1,2,&ast; Bin Hao,1,2,&ast; Simin Liu,3,&ast; Xiaoyu Qiu,1,2,&ast; Xiaoping Ming,1,2 Xiuping Yang,1,2 Jie Cai,1,2 Zhen Li,4,5 Xiong Chen1,2 1Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Neurosurgery, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 5Bariatric and Metabolic Disease Surgery Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Chen, Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email zn_chenxiong@whu.edu.com Zhen Li, Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email kamel_li@163.comPurpose: The diagnosis of severe OSA still relies on polysomnography, which causes a strong sense of restraint in patients with obesity. However, better prediction tools for severe OSA applicable to patients with obesity have not been developed.Patients and Methods: Relevant clinical data of 1008 patients with OSA who underwent bariatric surgery in our hospital were collected retrospectively. Patients were divided into training and test cohorts by machine learning. Univariate and multivariate logistic regression analysis was used to screen associations, including liver stiff measurement (LSM) and abdominal visceral tissue (aVAT), and to construct a severe OSA risk prediction nomogram. Then, we evaluated the effectiveness of our model and compared our model with the traditional Epworth Sleepiness Scale (ESS) model. Finally, our associations were used to explore the correlation with other indicators of OSA severity.Results: Our study revealed that age, biological sex, BMI, LSM, aVAT, and LDL were independent risk factors for severe OSA in patients with obesity. A severe OSA risk prediction nomogram constructed by six indicators possessed high AUC (0.845), accuracy (77.6%), and relatively balanced specificity and sensitivity (72.4%, 82.8%). The Hosmer-Lemeshow test (P=0.296, 0.785), calibration curves, and DCA of the training and test cohorts suggested better calibration and more net clinical benefit. Compared with the traditional ESS model, our model had higher AUC (0.829 vs 0.545), sensitivity (78.9% vs 12.2%), PPV (77.9% vs 53.3%), and accuracy (75.4% vs 55.2%). In addition, the associations in our model were independently correlated with other indicators reflecting OSA severity.Conclusion: We provided a simple, cheap, and non-invasive nomogram of severe OSA risk prediction for patients with obesity, which would be helpful for preventing further complications associated with severe OSA.Plain Language Summary: Question: Can we predict severe OSA in patients with obesity by their metabolic complications through some non-invasive examinations?Findings: Compared with traditional questionnaires, we developed and validated a new prediction model, including liver stiffness measurement and abdominal visceral adipose tissue, to screen severe OSA in bariatric surgery candidates through non-invasive examinations, which may contribute to perioperative safety and ultimate weight loss outcomes.Meaning: For patients with obesity who are in hospital because of metabolic disorders, it is necessary for them to be screened for possible severe OSA according to our new prediction nomogram, which is helpful for preventing further complications and perioperative risk associated with severe OSA.Keywords: obstructive sleep apnea, obesity, liver stiffness measurement, visceral adipose tissue, nomogram

Linan Ren,1,2 Feng Ju,3 Siyuan Liu,1,2 Yunjia Cai,1,2 Xiaokun Gang,1 Guixia Wang1 1Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 3Department of Orthopedics, Yuci District People’s Hospital, Yuci, Shanxi, 030600, People’s Republic of ChinaCorrespondence: Xiaokun Gang; Guixia Wang, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email gangxk@jlu.edu.cn; gwang168@jlu.edu.cnAbstract: Obesity represents a substantial risk factor for a multitude of metabolic disorders, which seriously threatens human life and health. As the global obesity epidemic intensifies, obesity-related nephropathy (ORN) has attracted great attention. ORN arises from both physical/mechanical and non-physical insults to the glomerular and tubular structures precipitated by obesity, culminating in structural impairments and functional aberrations within the kidneys. Physical injury factors include changes in renal hemodynamics, renal compression, and mechanical stretching of podocytes. Non-physical injury factors include overactivation of the RAAS system, insulin resistance, lipotoxicity, inflammation, and dysregulation of bile acid metabolism. Exploring molecules that target modulation of physical or nonphysical injury factors is a potential approach to ORN treatment. ORN is characterized clinically by microproteinuria and pathologically by glomerulomegaly, which is atypical and makes early diagnosis difficult. Investigating early diagnostic markers for ORN thus emerges as a critical direction for future research. Additionally, there is no specific drug for ORN in clinical treatment, which mainly focuses on weight reduction, mitigating proteinuria, and preserving renal function. In our review, we delineate a progressive therapeutic approach involving enhancements in lifestyle, pharmacotherapy, and bariatric surgery. Our emphasis underscores glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as poised to emerge as pivotal therapeutic modalities for ORN in forthcoming clinical avenues. Keywords: Obesity-related nephropathy, pathophysiology, diagnostics, therapeutics

Mengyi Shen,1,&ast; Leyu Zhou,1,&ast; Xiaoli Fan,1 Ruiqi Wu,1 Shuyun Liu,2 Qiaoyu Deng,1 Yanyi Zheng,1 Jingping Liu,2 Li Yang1 1Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2NHC Key Laboratory of Transplant Engineering 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: Li Yang; Jingping Liu, Email yangli_hx@scu.edu.cn; liujingping@scu.edu.cnBackground: Autoimmune hepatitis (AIH) is a serious liver disease characterized by immune disorders, particularly effector T-cell overactivation. This study aimed to explore the therapeutic effect and underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment on CD4+ T-cell overactivation and liver injury in AIH.Methods: The metabolic changes of CD4+ T cells were assayed in human AIH and mouse hepatitis models. The liver protective effect of MSC-EVs was evaluated by transaminase levels, liver histopathology and inflammation. The effect of MSC-EVs on the metabolic state of CD4+ T cells was also explored.Results: Enhanced glycolysis (eg, ~1.5-fold increase in hexokinase 2 levels) was detected in the CD4+ T cells of AIH patient samples and mouse hepatitis models, whereas the inhibition of glycolysis decreased CD4+ T-cell activation (~1.8-fold decrease in CD69 levels) and AIH liver injury (~6-fold decrease in aminotransferase levels). MSC-EV treatment reduced CD4+ T-cell activation (~1.5-fold decrease in CD69 levels) and cytokine release (~5-fold decrease in IFN-γ levels) by reducing glycolysis (~3-fold decrease) while enhancing mitochondrial oxidative phosphorylation (~2-fold increase in maximal respiration) in such cells. The degree of liver damage in AIH mice was ameliorated after MSC-EV treatment (~5-fold decrease in aminotransferase levels). MSC-EVs carried abundant mitochondrial proteins and might transfer them to metabolically reprogram CD4+ T cells, whereas disrupting mitochondrial transfer impaired the therapeutic potency of MSC-EVs in activated CD4+ T cells.Conclusion: Disordered glucose metabolism promotes CD4+ T-cell activation and associated inflammatory liver injury in AIH models, which can be reversed by MSC-EV therapy, and this effect is at least partially dependent on EV-mediated mitochondrial protein transfer between cells. This study highlights that MSC-EV therapy may represent a new avenue for treating autoimmune diseases such as AIH.Keywords: autoimmune hepatitis, extracellular vesicles, metabolic reprogramming, mitochondria, inflammation

Guomiao Su,&ast; Zifan Xu,&ast; Shiyue Liu,&ast; Dou Hao, Yanxi Li, Guoqing Pan Department of Pathology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoqing Pan, Department of Pathology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email guoqing_pan@163.comPurpose: Semaphorin 5A (SEMA5A) and autophagy-related genes (ARGs) are pivotal in the pathogenesis of gastric cancer (GC). However, the potential regulatory role of SEMA5A in autophagy via its associated ARGs and the underlying molecular mechanisms remain unresolved.Patients and Methods: GC-related datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes (DEGs) between GC and control samples. The intersection of DEGs with ARGs produced candidate genes, which were further analyzed using Spearman correlation with SEMA5A to identify signature genes. Stratification of GC samples based on signature gene expression, followed by Kaplan-Meier survival analysis, identified key genes. Subsequent analyses, including gene set enrichment analysis (GSEA), immune infiltration, and immune checkpoint evaluation, were conducted on the key genes and SEMA5A. The mRNA expression level was quantified using real-time quantitative polymerase chain reaction (RT-qPCR).Results: Ninety candidate genes were identified for Spearman correlation with SEMA5A, revealing TNFSF11, BMP6, ITPR1, and DLC1 with correlation coefficients exceeding 0.3. Survival analysis underscored DLC1 and BMP6 as key genes due to significant prognostic differences. GSEA implicated SEMA5A, BMP6, and DLC1 in the ECM receptor interaction pathway. Immune infiltration analysis indicated a negative correlation of SEMA5A and BMP6 with M1 macrophages, while DLC1 exhibited the strongest association with the immune checkpoint PDCD1LG2 (p < 0.05, cor = 0.43). The mRNA expression level of SEMA5A was significantly upregulated in AGS parental cells compared to GES-1 cells (p < 0.01), whereas DLC1 and BMP6 mRNA levels were markedly downregulated in AGS parental cells relative to GES-1 (p < 0.0001).Conclusion: ARGs BMP6 and DLC1, associated with SEMA5A, were identified, and their prognostic significance in GC was demonstrated. Additionally, their regulatory mechanisms were further elucidated through immune infiltration analysis and molecular network construction, providing a theoretical foundation for future research on the molecular mechanisms in patients with GC.Keywords: GC, SEMA5A, autophagy, ARGs, bioinformatics analysis

Qingbao Guo,1,2,&ast; Manli Xie,3,&ast; Qian-Nan Wang,4,&ast; Jingjie Li,1,2 Simeng Liu,1,2 Xiaopeng Wang,1,2 Dan Yu,5 Zhengxing Zou,5 Gan Gao,1,2 Qian Zhang,5 Fangbin Hao,1,2 Jie Feng,5 Rimiao Yang,5 Minjie Wang,1,2 Heguan Fu,5 Xiangyang Bao,5 Lian Duan2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Neurosurgery, First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Occupational Diseases, Xi’an Central Hospital, Xi’an, Shanxi, People’s Republic of China; 4Department of Neurosurgery, Eighth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Department of Neurosurgery, Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Bao; Lian Duan, Email bzy123@163.com; duanlian307@sina.comBackground: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD.Methods: Twelve MMD patients—six children and six adults—along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis.Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD.Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms. Keywords: proteomics, metabolomics, pediatric patients, moyamoya disease, integration analysis

Yi Wang,1,2 Wenhui Zhang,1,3 Shourong Liu,1 Fei Wang,1 Qian Huang,1 Er Li,3 Mingli Zhu,4 Jianhua Yu,1,&ast; Jinchuan Shi1,&ast; 1Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China; 2Institute of Hepatology and Epidemiology, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China; 3Department of Nursing, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China; 4Medical Laboratory, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianhua Yu; Jinchuan Shi, Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China, Email yujhmc@126.com; shijinchuan2008@126.comObjective: Precise prediction of the occurrence of complicated perianal abscesses (PAs) in monkeypox (mpox)-infected patients is important for therapeutic optimization. This study sought to identify risk factors of complicated PA.Methods: A total of 48 patients with mpox infection (PA group, n = 10; non-PA (NPA) group, n = 38) were enrolled in our study, who were hospitalized in Hangzhou Xixi Hospital, China from 29 June to 3 September 2023. The data of demographic characteristics, and clinical symptoms, serum SAA, PCT, CRP, and IL-6 levels were collected by the Electronic Medical Record. The diagnostic values of these biomarkers were assessed using multivariate logistic regression and ROC curve analyses.Results: A decrease in serum IL-6, SAA, and CRP levels (all p-value < 0.05), but not PCT, was observed in all mpox-infected patients. A significant positive correlation was also noted between IL-6, SAA, CRP, and PCT levels (all p-value < 0.05). There was a significant increase in IL-6 and SAA levels and the SAA/CRP ratio in serum samples from patients in the PA group. Multivariate logistic regression and ROC curve analyses identified that the combined use of perianal symptoms and SAA was more sensitive than perianal symptoms or SAA alone as predictors of complicated PA. This combination had the highest predictive value for disease progression, with an AUC of 0.920 (p-value < 0.001).Conclusion: The combination of perianal symptoms and SAA levels was strongly linked to the occurrence of complicated PA in mpox-infected patients. These findings may inform the early diagnosis of this patient population.Keywords: serum amyloid A, perianal symptoms, perianal abscess, mpox-infected patients

Jingying Xu, Yuan Chen, Jianhua Yu, Shourong Liu, Ying Meng, Chaodan Li, Qian Huang, Yunlei Xiao Department of Infectious Diseases, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Qian Huang; Yunlei Xiao, Department of Infectious Diseases, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, No. 2, Hengbu Street, Liu Xia Town, Xihu District, Hangzhou, 310023, Zhejiang, People’s Republic of China, Tel +8613575746522 ; +8615258639960, Email tcm99hq@163.com; 15258639960@163.comPurpose: Developing countries, invasive Salmonella infections can cause considerable morbidity and mortality. There is a relative lack of data on coinfection with Salmonella in HIV-infected patients in Hangzhou, China.Patients and Methods: In this study, we manually collected case data of patients aged > 18 years with HIV combined with invasive Salmonella infections admitted to Xixi Hospital in Hangzhou from January 2012 to August 2023 by logging into the Hospital Information System, and identified 26 strains of invasive Salmonella using a fully automated microbiological identification system and mass spectrometer. Serotypes were determined using Salmonella diagnostic sera based on the White-Kauffmann-Le Minor scheme. Drug sensitivity tests were performed using the automated instrumental method of the MIC method.Results: A total of 26 HIV-infected patients with invasive Salmonella coinfections were identified over 11 years; Twenty-five of the 26 patients (96.2%) were males, with a mean age of 33.5 years (26.75, 46.75). The most common type of infection was bloodstream infection (92.3%). One patient also had concomitant meningitis and osteoarthritis, followed by pneumonia (7.7%). The presence of multiple bacterial infections or even multiple opportunistic pathogens was clearly established in 7 (26.9%) patients. Three (11.6%) patients were automatically discharged from the hospital with deterioration of their condition, and one (3.8%) patient died. Salmonella enteritidis was the most common serotype in 6 patients (23.2%), and Salmonella Dublin was the most common serotype in 6 patients (23.2%). Drug sensitivity results revealed multidrug resistance in a total of 8 (30.8%) patients.Conclusion: The clinical presentation of invasive Salmonella infection in HIV patients is nonspecific and easily masked by other mixed infections. A CD4+ count < 100 cells/μL and comorbid intestinal lesions may be important susceptibility factors. Salmonella has a high rate of resistance to common antibiotics, and the risk of multidrug resistance should not be ignored.Keywords: Salmonella, invasiveness, HIV, serotype, antibiotic resistance

Yang Gou,1,2 Ping Wang,1,2 Wucheng Yang,1,2 Yimei Feng,1,2 Xiangui Peng,1,2 Hong Liu,1,2 Shuiqing Liu,1,2 Xi Zhang1,2 1Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 2Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Hong Liu; Shuiqing Liu, Email 1241580141@qq.com; liushuiqing062@tmmu.edu.cnAbstract: Hereditary spherocytosis (HS) is the most common hereditary hemolytic disease with defects in red blood cells (RBC) membrane proteins caused by mutations in membrane protein genes, like SPTB, SPTA1 and ANK1. Gilbert syndrome (GS) is a disease characterized by a mild deficiency of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) enzyme activity and unconjugated hyperbilirubinemia, largely caused by UGT1A1 mutations. The two inherited diseases HS and GS are rarely occurred in the same patient and are easy to be misdiagnosed, resulting in excessive diagnosis and treatment. Here, we report a rare case of HS combined with GS due to mutations in the SPTB and UGT1A1 genes. A 50-year-old man who had an over 40-year history of jaundice was admitted to our hospital owing to fatigue and fever. His blood analysis showed low hemoglobin (74 g/L), high reticulocyte (23.5%) and high serum bilirubin (65 μmol/L); abdominal ultrasound revealed calculous cholecystitis and splenomegaly. Considering a possible diagnosis of hemolytic anemia, further examinations showed 42% spherocytes in blood smears and high erythroid lineage hyperplasia in bone marrow. Subsequently, 151 jaundice-related genes panel sequencing was done and results showed SPTB p.N1260fs and UGT1A1 p.G71R mutations. Then the patient was diagnosed with HS complicated with GS. Anti-infection and supportive treatments were providing to the patient, while infection removed, the hemoglobin recovered to normal, and no additional treatment was given. These findings of this report indicate that patients who are considered hemolytic anemia presenting with jaundice and anemia, genetic testing is a crucial method for the final diagnosis and bilirubin metabolic disease should also be concerned.Keywords: hereditary spherocytosis, Gilbert syndrome, SPTB, UGT1A1

Fuming Li,1,2 Shimeng Liu,1,2 Yuanyuan Gu,3 Shunping Li,4 Ying Tao,1,2 Yan Wei,1,2 Yingyao Chen1,2 1School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2National Health Commission Key Laboratory of Health Technology Assessment (Fudan University), Shanghai, People’s Republic of China; 3Macquarie University Centre for the Health Economy, Macquarie Business School & Australian Institute of Health Innovation, Macquarie University, Macquarie Park, Macquarie Park, New South Wales, Australia; 4Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shimeng Liu; Yingyao Chen, School of Public Health, Fudan University, 130 Dongan Road, Xuhui, Shanghai, 200032, People’s Republic of China, Tel +86 198 2182 4471 ; +86 135 6450 8981, Email smliu19@fudan.edu.cn; yychen@shmu.edu.cnPurpose: Discrete choice experiment (DCE) and profile case (case 2) best-worst scaling (BWS) present uncertainties regarding the acceptability of quantifying individual healthcare preferences, which may adversely affect the validity of responses and impede the reflection of true healthcare preferences. This study aimed to assess the acceptability of these two methods from the perspective of patients with type 2 diabetes mellitus (T2DM) and examine their association with specific characteristics of the target population.Patients and Methods: This cross-sectional study was based on a nationally representative survey; data were collected using a multistage stratified cluster-sampling procedure between September 2021 and January 2022. Eligible adults with confirmed T2DM voluntarily participated in this study. Participants completed both the DCE and case 2 BWS (BWS-2) choice tasks in random order and provided self-reported assessments of acceptability, including task completion difficulty, comprehension of task complexity, and response preference. Logistic regression and random forest models were used to identify variables associated with acceptability.Results: In total, 3286 patients with T2DM were included in the study. Respondents indicated there was no statistically significant difference in completion difficulty between the DCE and BWS-2, although the DCE scores were slightly higher (3.07 ± 0.68 vs 3.03 ± 0.67, P = 0.06). However, 1979 (60.2%) respondents found the DCE easier to comprehend. No significant preferences were observed between the two methods (1638 (49.8%) vs 1648 (50.2%)). Sociodemographic factors, such as residence, monthly out-of-pocket costs, and illness duration were significantly associated with comprehension complexity and response preference.Conclusion: This study yielded contrasting results to most of previous studies, suggesting that DCE may be less cognitively demanding and more suitable for patients with T2DM from the perspective of self-reported acceptability of DCE and BWS. This study promotes a focus on patient acceptability in quantifying individual healthcare preferences to inform tailored optimal stated-preference method for a target population.Plain Language Summary: Stated preference methodologies such as the discrete choice experiment (DCE) and case 2 best-worst scaling (BWS-2) are gaining popularity as methods for quantifying individual preferences in healthcare. However, the acceptability of the two methods to participants must be considered in practice to reduce cognitive burden and ensure the validity of preference elicitation.DCE was perceived to be less cognitively burdensome than BWS-2. In contrast to patients who thought that DCE was more acceptable, BWS-2 was more accepted by rural patients, patients who lived with the disease for a longer period, and those who had lower monthly out-of-pocket costs.These findings demonstrate potential differences in the acceptability of DCE and BWS-2 for patients with type 2 diabetes mellitus. To improve efficiency, it would be useful for researchers to consider the optimal stated preference method for identifying target populations according to sociodemographic and disease-related characteristics.Keywords: patient-reported outcomes, acceptability, discrete choice experiment, best-worst scaling, preference, type 2 diabetes

Yue He,1,&ast; Qianhan Liu,1,&ast; Yurong Zheng,1 Shengdan Liu,1 Mingling Yu,1 Changhe Ren,2 Guangxiang Chen1 1Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Pain, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changhe Ren, Department of Pain, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982784626, Email riverrch@163.com Guangxiang Chen, Department of Radiology, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982409881, Email cgx23ly2002@163.comPurpose: Zoster-associated pain (ZAP) is frequently concomitant with psychiatric comorbidities. However, the underlying neuropathological mechanisms of ZAP with psychiatric comorbidities remain poorly understood.Patients and Methods: Rest-stating functional MRI (rs-fMRI) data from 41 ZAP patients without anxiety or depression (noA/D-ZAP), 11 ZAP patients with anxiety or depression (A/D-ZAP) and 29 healthy controls (HCs) were acquired. Degree centrality (DC) based on rs-fMRI was used to explore the node changes in the brain functional network in these subjects. Moreover, correlations and receiver operating characteristic curve analysis were performed.Results: One-way analysis of variance revealed abnormal DC values in the right middle frontal gyrus (MFG) and bilateral precuneus among the three groups. Compared with HCs, A/D-ZAP showed increased DC values in the bilateral pons, while noA/D-ZAP showed increased DC values in the right pons, left brainstem and rectal gyrus and decreased DC values in the right cingulate gyrus and bilateral precuneus. A/D-ZAP showed increased DC values in the left MFG and precentral gyrus (PG) compared with noA/D-ZAP. The DC value of the left pons in A/D-ZAP was positively correlated with the self-rating anxiety scale score. Areas under the curve of DC values in the left PG and MFG for distinguishing A/D-ZAP from the noA/D-ZAP group were 0.907 and 1.000, respectively.Conclusion: This study revealed the node differences in the brain functional network of ZAP patients with or without psychiatric comorbidities. In particular, abnormal DC values of the left MFG and PG may play an important role in the neuropathologic mechanism of the disease.Keywords: functional MRI, degree centrality, zoster-associated pain, anxiety, depression

Yan-Jun Xiong,&ast; Yu Xiao,&ast; Lei Xie, Lei Gao, Yi Han, Peng-Fei Huang, Shuang Liu, Ya-Xue Liang, Hua Wang Department of Tuberculosis, Anhui Provincial Chest Hospital (Anhui Institute of Tuberculosis Control), Hefei, Anhui, 230022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Wang, Department of Tuberculosis, Anhui Provincial Chest Hospital (Anhui Institute of Tuberculosis Control), No. 392, Jixi Road, Hefei, Anhui, People’s Republic of China, Tel +86 13395694530, Email 1726553540@qq.comBackground: Linezolid (LZD) is a cornerstone medication in the treatment of drug-resistant tuberculosis (DR-TB). However, it frequently triggers adverse effects such as bone marrow suppression, optic neuropathy, and peripheral neuropathy, all of which can impact treatment outcomes and prognosis. Contezolid (CZD), a novel oxazolidinone antibiotic, exhibits comparable antimicrobial efficacy against Mycobacterium tuberculosis as LZD, but with potentially enhanced safety profiles.Case Presentation: This report presents five cases (Cases 1– 5) of LZD intolerance, wherein CZD served as an effective alternative treatment. In Cases 1– 3, LZD administration resulted in bone marrow suppression, primarily manifested as anemia. Transitioning to CZD therapy led to a rise and stabilization of hemoglobin (HGB) levels in Cases 1– 2, and a return to baseline values in Case 3. In Case 4, CZD treatment alleviated symptoms of LZD-induced peripheral neuritis, although complete resolution was not achieved, hinting at potential irreversibility of this type of peripheral neuropathy. In Case 5, direct CZD anti-TB therapy was initiated for recurrent leukopenia and neutropenia, resulting in no further severe myelosuppression and successful recovery.Conclusion: These case studies suggest that CZD could represent an effective and safe option for anti-TB therapy, especially for patients intolerant to LZD.Keywords: contezolid, linezolid, drug-resistant tuberculosis, myelosuppression, peripheral neuropathy

Liming Qin,1,2,&ast; Moqin Qiu,3,&ast; Jingmei Tang,2 Shuyan Liu,4 Qiuling Lin,5 Qiongguang Huang,2 Xiaoxia Wei,5 Qiuping Wen,1 Peiqin Chen,6 Zihan Zhou,7 Ji Cao,7 Xiumei Liang,8 Qian Guo,9 Cunli Nong,9 Yizhen Gong,5 Yuying Wei,1 Yanji Jiang,10 Hongping Yu,1,2,11– 13 Yingchun Liu1 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Biological Molecular Medicine Research, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 6Editorial Department of Chinese Journal of Oncology Prevention and Treatment, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 7Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 8Department of Disease Process Management, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 9Liuzhou Worker’s Hospital, Liuzhou, People’s Republic of China; 10Department of Scientific Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 11Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Medical University, Nanning, People’s Republic of China; 12Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China; 13Key Cultivated Laboratory of Cancer Molecular Medicine of Guangxi Health Commission, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingchun Liu; Hongping Yu, Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71&num; Hedi Road, Qingxiu District, Nanning, People’s Republic of China, Tel +86-15877191237 ; +86-771-5330850, Fax +86-771-5312000, Email liuyingchun@stu.gxmu.edu.cn; yuhongping@stu.gxmu.edu.cnPurpose: P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC.Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal.Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10– 1.48) and 0.77 (0.66– 0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (Ptrend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells.Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.Keywords: hepatocellular carcinoma, hepatitis B virus, p53 signaling pathway, genetic variants, survival

Fujie Jiang,1,&ast; Shuling Liu,1,&ast; Lu Wang,1 Huifang Chen,1 Yao Huang,2 Ying Cao,2 Xiaoxia Wang,1 Meng Lin,1 Jiuquan Zhang1 1Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing, 400030, People’s Republic of China; 2School of Medicine, Chongqing University, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiuquan Zhang; Meng Lin, Department of Radiology Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel/Fax +86-23-65079339, Email zhangjq_radiol@foxmail.com; 15823113338@139.comPurpose: Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging.Methods: Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe3O4) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3O4/ PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied.Results: The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging.Conclusion: MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options.Keywords: targeted drug delivery, photodynamic therapy, ROS-responsive chemotherapy, bimodal imaging

Chao Meng,1 Ping Yang,2 Yanan Wang,3 Siyan Liu,3 Xueyan Wu,3 Shaolian Wang3 1Department of General Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Integrated Chinese and Western Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Shaolian Wang, Email 15318816221@sina.cnBackground: To investigate the prevalence of thyroid nodules among medical staff and health check-up population in a Level-A hospital (Primary-level hospital) in Jinan City and analyze its influencing factors.Methods: A total of 5812 cases from the two groups were screened. t-test and χ2 tests were used to analyze the differences in the prevalence of thyroid nodules. Multivariate Logistic regression analysis was used to explore the influencing factors.Results: The average age of medical staff was (36.20± 9.11) years old, and the total prevalence was 48.5%. The average age of the healthcare population was (57.89± 12.51) years old, and the total prevalence rate was 63.9%, with statistical significance between the two groups (P

Licai Miao,1,&ast; Zihao Xu,1,&ast; Junhao Sui,1,&ast; Xiangyu Meng,1,&ast; Shicheng Huo,2 Shu Liu,1 Mengchen Chen,1 Zhong Zheng,1 Xiaobin Cai,3 Hao Zhang1 1Department of Orthopedics, Changhai Hospital Affiliated to the Navy Military Medical University, Shanghai, 200433, People’s Republic of China; 2Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Navy Medical University, Shanghai, 200003, People’s Republic of China; 3Department of Orthopedics Shanghai Tenth People’s Hospital Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobin Cai, Department of Orthopedics Shanghai Tenth People’s Hospital Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Tel +8613122575295, Email caixbjn@163.com Hao Zhang Department of Orthopedics, Changhai Hospital Affiliated to the Navy Military Medical University, Tel +8613917856377, Email zhanghsmmu@126.comPurpose: Skin injury, often caused by physical or medical mishaps, presents a significant challenge as wound healing is critical to restore skin integrity and tissue function. However, external factors such as infection and inflammation can hinder wound healing, highlighting the importance of developing biomaterials with antibiotic and wound healing properties to treat infections and inflammation. In this study, a novel photothermal nanomaterial (MMPI) was synthesized for infected wound healing by loading indocyanine green (ICG) on magnesium-incorporated mesoporous bioactive glass (Mg-MBG) and coating its surface with polydopamine (PDA).Results: In this study, Mg-MBG and MMPI was synthesized via the sol-gel method and characterized it using various techniques such as scanning electron microscopy (SEM), the energy dispersive X-ray spectrometry (EDS) system and X-ray diffraction (XRD). The cytocompatibility of MMPI was evaluated by confocal laser scanning microscopy (CLSM), CCK8 assay, live/dead staining and F-actin staining of the cytoskeleton. The antibacterial efficiency was assessed using bacterial dead-acting staining, spread plate method (SPM) and TEM. The impact of MMPI on macrophage polarization was initially evaluated through flow cytometry, qPCR and ELISA. Additionally, an in vivo experiment was performed on a mouse model with skin excision infected. Histological analysis and RNA-seq analysis were utilized to analyze the in vivo wound healing and immunomodulation effect.Conclusion: Collectively, the new photothermal and photodynamic nanomaterial (MMPI) can achieve low-temperature antibacterial activity while accelerating wound healing, holds broad application prospects.Keywords: infection-related wounds, magnesium-doped bioactive glass, photothermal therapy, photodynamic therapy, immunomodulation

Simin Liu,1,&ast; Zhiyuan Tian,2 Taiming Zhang,3 Jirong Zhang,3 Yanlei Huo,1,&ast; Chao Ma1 1Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nuclear Medicine, Zibo Ninth People’s Hospital, Zibo, Shandong, People’s Republic of China; 3Department of Medical Imaging, People’s Hospital of Shuangjiang Autonomous Country, Lincang, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Ma, Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University, Yanchangzhong Road 301, Shanghai, 200072, People’s Republic of China, Tel +86 21-66302075, Email mc_7419@hotmail.comObjective: To explore analgesic effect and bone repair mechanism of non-radioactive technetium-99 conjugated with methylene diphosphonate (99Tc-MDP, brand name, Yunke) on bone metastases (BM).Procedures: In vivo experiment, mouse BM models of prostate cancer RM-1 cell were constructed and divided into Control, Yunke, 99Tc+SnCl2 and MDP groups based on medicine composition. Tumor specimens were inspected for size, X-ray, microCT and histopathology. In vitro experiment, with Cell Counting Kit-8 (CCK8), scratch, clone, apoptosis, Polymerase Chain Reaction (PCR) and Western Blot experiments, effects of Yunke on RM-1 cells and osteoclast-related cells were observed.Results: In vivo experiment, there was no difference in tumor size between Yunke and control group. Contrasted with control group, in Yunke group, trabecular spacing (Tb.Sp) of tumor bone was lower, bone volume/total volume (BV/TV) on marrow cavity and bone cortex were higher. Tunnel staining showed that positive rate of apoptosis in Yunke group was higher than that in control group. Ki67 staining showed that Yunke could not inhibit proliferation of tumor cells. In vitro experiment, CCK8 and scratch experiments showed that Yunke neither can inhibit proliferation nor can inhibit migration of RM-1 cells. High concentration of Yunke promoted late apoptosis of RM-1 cells. Yunke could inhibit BMM cell proliferation, differentiation of osteoclasts, and osteoclast-related transcription factors. Yunke displayed different degrees of inhibitory effects on MAPKs signaling pathway during osteoclast differentiation. It had obvious inhibitory effects on osteoclast-related transcription factors, such as cFOS, NFATC1, ACP-5, CTSK, D2 and MMP-9, the strongest inhibitory effects were observed with ACP-5, CTSK and D2. Yunke also displayed different degrees of inhibitory effects on protein activities of JNK, pERK, ERK and pP38.Conclusion: Yunke cannot inhibit the proliferation and migration of RM-1 cells, so we think it is not recommended for the treatment of primary tumors and prevention of occurrence of tumors metastatic to bones. The mechanism of therapeutic effect of Yunke on BM by inhibiting proliferation of BMM, inhibiting MAPKs signal transduction and activation of transcription factors during differentiation process of BMM-derived osteoclasts, inhibiting number and size of osteoclasts, inhibiting bone resorption and protecting bone destruction through enhancing bone hardness and bone mass. Thereby, we believe that Yunke is more suitable for promoting the repair induced by BMs, delaying its progression and reducing the occurrence of SREs.Keywords: 99Tc-MDP, bone metastases, molecular mechanisms, RM-1, prostate cancer

Lei Liu,1,&ast; Shanshan Liu,2,&ast; Fuyan Bai,1 Yangxin Deng,1 Xinhuan Zhang,1 Li Wang3 1Department of Endocrinology, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China; 2General Gynecology, the Tai ‘an Central Hospital, Taian, Shandong, People’s Republic of China; 3Department of Pharmacy, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinhuan Zhang; Li Wang, Email zhangxh22009@126.com; suxinlan1027@126.comBackground: An important factor in the pathogenesis of polycystic ovary syndrome (PCOS) is chronic low-grade inflammation. However, the exact pathophysiology of PCOS is currently unknown, which makes clinical diagnosis and the development of effective treatments more difficult. We aimed to investigate the role of the inflammatory response in initiating and progressing PCOS.Methods: 13 control granulosa cell samples and 15 granulosa cell samples from patients with PCOS were obtained from the GSE102293, GSE34526, and GSE5850 datasets. The gene set variation analysis (GSVA) method was used to calculate the inflammatory response score. Subsequently, the genes associated with inflammation in the hub were identified using differential expression analysis and weighted gene co-expression network analysis (WGCNA). The findings were confirmed by analysis of independent datasets and examination of clinical samples by qRT-PCR analysis. A consensus cluster analysis was conducted to categorize the PCOS samples into subtypes related to inflammation. Functional enrichment and analysis of immune cell infiltration were conducted to explore the potential mechanisms involved. Additionally, the CMap database was utilized to predict potential drugs, and the results were confirmed through molecular docking.Results: During the training cohort analysis, we identified five distinct genes (TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2) that could serve as potential diagnostic markers for PCOS. The expression levels of these genes were confirmed through validation in both the test set and clinical samples. In training cohort, two distinct inflammatory patterns (C1 and C2) were identified, and the C2 subtype exhibited activated immune- and inflammation-related pathways. Esmolol was shown to have potential as a drug to treat PCOS and it showed good results for molecular binding at TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2 proteins.Conclusion: Five diagnostic biomarkers and two inflammation-related molecular types associated with PCOS were identified, and esmolol was a potential drug for PCOS treatment. Our findings provided new diagnostic markers and potential small-molecule drugs for PCOS diagnosis and prevention.Keywords: polycystic ovary syndrome, inflammatory response, diagnostic biomarkers, molecular subtypes, esmolol

Bin Hu,1 Jingchun Pei,1 Cheng Wan,1,2 Shuangshuang Liu,1 Zhe Xu,3,4 Yongwei Zou,1 Zhigao Li,1 Zhiwei Tang1 1Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Medical Imaging, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, People’s Republic of China; 4School of Basic Medical Sciences, Qujing Medical College, Qujing, People’s Republic of ChinaCorrespondence: Zhiwei Tang, Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, People’s Republic of China, Email tangzhiwei7755@hotmail.comAbstract: Ischemic stroke constitutes a significant global health care challenge, and a comprehensive understanding of its recovery mechanisms is imperative for the development of innovative therapeutic strategies. Angiogenesis, a pivotal element of ischemic tissue repair, facilitates the restoration of blood flow to damaged regions, thereby promoting neuronal regeneration and functional recovery. Nevertheless, the mechanisms underlying postischemic stroke angiogenesis remain incompletely elucidated. This review meticulously examines the constituents of the neurovascular unit, ion channels, molecular mediators, and signaling pathways implicated in angiogenesis following stroke. Furthermore, it delves into prospective therapeutic strategies informed by these factors. Our objective is to provide detailed and exhaustive information on the intricate mechanisms governing postischemic stroke angiogenesis, thus providing a robust scientific foundation for the advancement of novel neurorepair therapies.Keywords: ischemic stroke, angiogenesis, signaling pathways

Wenze Han,1,2 Ran Zhang,1,2 Shuzhi Liu,1,2 Tong Zhang,1,2 Xuemin Yao,1,2 Yuxin Cao,1,2 Jiadi Li,1,2 Xiaoming Liu,1,2 Bing Li1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Xiaoming Liu; Bing Li, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China, Email lxming0912@163.com; libing1975vip@163.comAbstract: Whiskers are nanoscale, high-strength fibrous crystals with a wide range of potential applications in dentistry owing to their unique mechanical, thermal, electrical, and biological properties. They possess high strength, a high modulus of elasticity and good biocompatibility. Hence, adding these crystals to dental composites as reinforcement can considerably improve the mechanical properties and durability of restorations. Additionally, whiskers are involved in inducing the value-added differentiation of osteoblasts, odontogenic osteocytes, and pulp stem cells, and promoting the regeneration of alveolar bone, periodontal tissue, and pulp tissue. They can also enhance the mucosal barrier function, inhibit the proliferation of tumor cells, control inflammation, and aid in cancer prevention. This review comprehensively summarizes the classification, properties, growth mechanisms and preparation methods of whiskers and focuses on their application in dentistry. Due to their unique physicochemical properties, excellent biological properties, and nanoscale characteristics, whiskers show great potential for application in bone, periodontal, and pulp tissue regeneration. Additionally, they can be used to prevent and treat oral cancer and improve medical devices, thus making them a promising new material in dentistry.Keywords: whiskers, dentistry, growth mechanism, biomaterials

Sijia Liu,1,2,&ast; Ting Yang,1,2,&ast; Qingsong Jiang,1,2 Liang Zhang,1,2 Xinhui Shi,1,2 Xin Liu,3 Xiaoli Li1,2 1Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People’s Republic of China; 3Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoli Li; Xin Liu, Email lixiaoli@cqmu.edu.cn; liux0704@tmmu.edu.cnAbstract: Sepsis is a disorder of the immune response to infection or infectious factors with high morbidity and mortality in clinical settings. The lactylation of lysine residues, fueled by lactate, plays a pivotal role in its pathophysiology. In conducting a literature review on sepsis-related research, we employed a systematic approach to ensure comprehensiveness and accuracy. Initially, we conducted an extensive literature search through the PubMed database, utilizing a range of keywords including “sepsis”, “lactate”, “lactylation”, and “epigenetic modification”. The aim was to capture the most recent research related to the pathophysiological mechanisms of sepsis, metabolic disorders, and the role of lactylation. The results of the literature review revealed a close link between sepsis and metabolic dysfunction, particularly the pivotal role of lactylation in regulating immune responses and inflammatory processes. Lactate, not only an energy metabolic byproduct produced during glycolysis, affects the activity of various proteins, including those involved in immune regulation and cell signaling, through lactylation. In the context of sepsis, changes in the levels of lactylation may be closely associated with the severity and prognosis of the disease. In summary, lactylation, as an emerging type of epigenetic modification, provides a new perspective for the diagnosis and treatment of sepsis. Future research needs to further elucidate the exact mechanisms of lactylation in sepsis and explore its potential as a therapeutic target.Plain Language Summary: The annual incidence and mortality rates associated with sepsis are on the rise, and to date, no medications or therapies have been proven effective in clinical practice. Glycolysis plays a pivotal role in regulating lactylation, a process derived from lactate generated by cellular glucose metabolism. In the context of sepsis, elevated lactate levels are indicative of a poor prognosis. It is imperative to delve into the mechanisms underlying lactylation alterations during sepsis to enhance our comprehension of its complex pathophysiology and to pinpoint innovative therapeutic targets for the condition. Keywords: sepsis, lactate, lactylation, epigenetic modification

Yuwei Jiang,1,2,&ast; Wenjun Dang,3,&ast; Lirong Sui,1 Tianci Gao,1 Xiangying Kong,1 Jin Guo,1 Shuang Liu,1 Hong Nie,3 Zhimei Jiang1,2 1College of Rehabilitation Medicine, Jiamusi University, Jiamusi City, Hei longJiang Province, People’s Republic of China; 2Pediatric Cerebral Palsy Prevention and Treatment Center of Heilongjiang Province, Jiamusi City, Hei longJiang Province, People’s Republic of China; 3College of Jiamusi, HeiLongJiang University of Chinese Medicine, Jiamusi City, Hei longJiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhimei Jiang; Shuang Liu, Email 15704601990@163.com; 307692456@qq.comAbstract: We conducted an umbrella evaluation to quantitatively synthesize previous systematic reviews and meta-analyses, thereby collating evidence on the association between vitamin D and core symptoms in people with autism in anticipation of informing clinical vitamin D supplementation. Based on the pre-established protocol, we ended up with 9 studies. Based on rigorous analysis, we found that vitamin D deficiency early in life is a risk factor for the development of ASD and that vitamin D supplementation improves the core symptoms of ASD. Our study concludes that vitamin D supplementation is beneficial for individuals with autism, that vitamin D deficiency early in embryonic life increases the risk of ASD, and that our study supports the idea that prevention begins with vitamin D supplementation early in life. At the same time, we must recognize that our current conclusions support the benefits of vitamin D supplementation for children with ASD, but we are unable to determine the causal relationship, ie, how vitamin D works in ASD, and we need more basic research to explore the mechanisms involved.Keywords: autism spectrum disorders, vitamin D, core symptoms, 25(OH)D, umbrella review

Fan Zhao,1,2 Jitong Wang,1,2 Yu Zhang,1,2 Jinru Hu,1,2 Chenyang Li,3 Shuainan Liu,4,5 Ruixiang Li,2 Ruofei Du1,2 1Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai, 201203, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, People’s Republic of China; 4State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People’s Republic of China; 5Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Ruixiang Li, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email ruixiangli@shutcm.edu.cn Ruofei Du, Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai, 201203, People’s Republic of China, Email drf790101@shutcm.edu.cnAbstract: This review aimed to systematically investigate the intracellular and subcellular fate of various types of targeting carriers. Upon entering the body via intravenous injection or other routes, a targeting carrier that can deliver therapeutic agents initiates their journey. If administered intravenously, the carrier initially faces challenges presented by the blood circulation before reaching specific tissues and interacting with cells within the tissue. At the subcellular level, the car2rier undergoes processes, such as drug release, degradation, and metabolism, through specific pathways. While studies on the fate of 13 types of carriers have been relatively conclusive, these studies are incomplete and lack a comprehensive analysis. Furthermore, there are still carriers whose fate remains unclear, underscoring the need for continuous research. This study highlights the importance of comprehending the in vivo and intracellular fate of targeting carriers and provides valuable insights into the operational mechanisms of different carriers within the body. By doing so, researchers can effectively select appropriate carriers and enhance the successful clinical translation of new formulations.Plain language summary: Nowadays, scientists are actively researching nanocarrier drugs. After administration via injection or other methods, these drugs experience in the body and reach the target treatment site to relieve or cure symptoms. As research progresses, scientists are gaining more insights into the behavior of nanocarrier drugs in the body, which is useful in developing safer and more effective drugs. Historically, research has focused primarily on the drug itself. However, it is important to understand that the carrier that delivers and protects the drug (often described as the drug sitting in a “car” or under an “umbrella”) plays an essential role in the drug’s therapeutic effect. This paper aims to highlight the importance of the carrier’s role, which is vital for developing new drugs and advancing basic research. Keywords: drug carriers, targeted delivery, in vivo fate, subcellular fate

Yuan Zhuang,1,2 Ru Zhang,3,4 Miaomiao Li,3,4 Yaru Zou,1 Shui Jiang,1 Yanan Zhang,1 Shiguo Liu,3,4 Bo Yu1 1Dermatological Department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China; 2dermatological department, Women and Children’s hospital, Qingdao University, Qingdao, People’s Republic of China; 3Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Yu, Dermatological department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China, Email yubo@qduhospital.cn Shiguo Liu, Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email liushiguo@qdu.edu.cnIntroduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.Keywords: EDA, X-linked hypohidrotic ectodermal dysplasia, gene mutation

Shuangjin Liu, Zihao Zeng, Qi Qi, Qin Yang, Yiqiu Hu School of Educational Science, Hunan Normal University, Changsha, 410006, People’s Republic of ChinaCorrespondence: Yiqiu Hu, School of Educational Science, Hunan Normal University, Changsha, 410006, People’s Republic of China, Email fortune2000947@163.comBackground: Based on the gene-environment interaction paradigm, this study explored the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR).Methods: A survey was conducted in a sample of 619 adolescents, and their oral cells were collected for DNA extraction and genotyping.Results: The results showed that (1) both peer relationships and psychological resilience significantly affected adolescent loneliness; (2) psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; (3) OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. Specifically, carriers of the rs53576 polymorphism A/A genotype showed a significantly enhanced effect of peer relationships on adolescent psychological resilience, while carriers of the rs53576 polymorphism G/G genotype showed a significantly enhanced effect of psychological resilience on adolescent loneliness.Conclusion: These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.Plain Language Summary: A moderated mediation effects analysis was conducted to investigate the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR). The results revealed psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.Keywords: peer relationship, adolescents, loneliness, psychological resilience, OXTR gene

Qianfeng Li,1,&ast; Bo Wang,2,&ast; Jun Yang,3 Yuan Wang,1 Faliang Duan,1 Ming Luo,1 Chungang Zhao,4 Wei Wei,2 Lei Wang,3 Sha Liu2,5 1Department of Neurosurgery, Wuhan No.1 Hospital, Wuhan, People’s Republic of China; 2Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Huanggang Central Hospital of Yangtze University, Huanggang, People’s Republic of China; 4Jilin Jianda Modern Agricultural Research Institute, Changchun, People’s Republic of China; 5Department of General Practice, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Wang; Sha Liu, Email wanglei@hgyy.org.cn; sha.liu@whu.edu.cnBackground: Aging is recognized as the key risk for intracerebral hemorrhage (ICH). The detailed mechanisms of aging in ICH warrant exploration. This study aimed to identify potential aging-related genes associated with ICH.Methods: ICH-specific aging-related genes were determined by the intersection of differentially expressed genes (DEGs) between perihematomal tissues and corresponding contralateral parts of four patients with ICH (GSE24265) and 349 aging-related genes obtained from the Aging Atlas database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses were performed to identify the potential biological functions and pathways in which these ICH-specific aging-related genes may be involved. Then, PPI network was established to identify the hub genes of ICH-specific aging-related genes. Meanwhile, miRNA-mRNA and transcription factor (TF)-mRNA regulatory networks were constructed to further explore the ICH-specific aging-related genes regulation. The relationship between these hub genes and immune infiltration was also further explored. Additional single-cell RNA-seq analysis (scRNA-seq, GSE167593) was used to locate the hub genes in different cell types. Besides, expression levels of the hub genes were validated using clinical samples from our institute and another GEO dataset (GSE206971).Results: This study identified 24 ICH-specific aging-related genes, including 22 up-regulated and 2 down-regulated genes. The results of GO and KEGG suggested that the ICH-specific aging-related genes mainly enriched in immunity and inflammation-related pathways, suggesting that aging may affect the ich pathogenesis by regulating inflammatory and immune-related pathways.Conclusion: Our study revealed 24 ICH-specific aging-related genes and their functions highly pertinent to ICH pathogenesis, providing new insights into the impact of aging on ICH.Keywords: intracerebral hemorrhage, aging, immune infiltration, single-cell RNA sequencing, molecular docking

Ying Wang,1,&ast; Yiyan Xu,2,&ast; Jiayu Song,1 Xueting Liu,1 Sijia Liu,1 Nan Yang,1 Le Wang,1 Yujie Liu,1 Yiwei Zhao,1 Wenhu Zhou,3,4 Yunyan Zhang1 1Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Hunan Key Laboratory of The Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, 410219, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunyan Zhang, Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86 13604843878, Fax +86 451 85718392, Email zhangyunyan@hrbmu.edu.cn Wenhu Zhou, Xiangya School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of China, Tel +86 15111469284, Fax +86 731 88710591, Email zhouwenhuyaoji@163.comPurpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer.Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)–modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO2@ICG NP. In this structure, the HMnO2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects.Results: Mn2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO2@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO2@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility.Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.Keywords: phototherapy, reactive oxygen species, hypoxia relief, collaborative therapy

Sandip Patil,1,2,&ast; Xinye Li,3,&ast; Pai Liu,1 Yan Dai,3 Xiyi Zhu,3 Junjun Li,3 Sixi Liu,1 Feiqiu Wen1,2 1Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Paediatric Research Institute, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Paediatrics, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feiqiu Wen, Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-83009888, Email fwen62@163.comBackground: Syphilis, a prevalent sexually transmitted infection, poses severe risks, especially during pregnancy. This study aimed to elucidate the trends and impacts of syphilis in Guangxi, China, focusing on prevalence, clinical manifestations, and treatment outcomes in pregnant women and newborns. The objectives included understanding the demographic characteristics of affected pregnant women, analysing the clinical manifestations in newborns, and assessing the effectiveness of the treatment protocol.Methods: Conducted in adherence to ethical guidelines, a retrospective cohort study from January 2013 to December 2023 included 54,048 pregnant women tested for T. pallidum. Diagnosis involved a comprehensive approach, utilizing tests like the Toluidine Red Unheated Serum Test (TRUST) and the Treponema pallidum Particle Agglutination (TPPA) assay. Infant diagnosis and clinical manifestations were evaluated through a decade-long follow-up. Treatment protocols, including Benzathine penicillin, were implemented. Statistical analyses were conducted using SAS version 9.4.Results: Among 54,048 pregnant women, 0.10% were syphilis positive, correlating with a rise in hospitalizations. Newborns exhibited varied clinical manifestations, with neonatal pneumonia and jaundice being prevalent. The treatment protocol, especially with Benzathine penicillin, achieved a remarkable 100% cure success rate. The study noted a significant reduction in mother-to-child transmission. Syphilis in mothers and babies was diagnosed at different clinical stages, including primary, secondary, latent, and tertiary.Conclusion: This study underscores the escalating impact of syphilis on pregnant women and newborns in Guangxi, China. The findings highlight the necessity for robust preventive measures, early diagnosis, and effective treatment strategies. The observed 100% cure success rate with Benzathine penicillin emphasizes the importance of strict treatment protocols in mitigating the adverse effects of congenital syphilis and reducing its transmission.Keywords: congenital syphilis, mother-to-child transmission, diagnosis, antibiotic treatment

Xiuwen Chen,1,&ast; Meiyan Zou,1,&ast; Siquan Liu,1 Weilin Cheng,1 Weihong Guo,2 Xiaoli Feng1 1Stomatology Hospital, School of Stomatology, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihong Guo; Xiaoli Feng, Email drguowh@163.com; dentistfxl226@163.comAbstract: Graphene family nanomaterials (GFNs) have attracted considerable attention in diverse fields from engineering and electronics to biomedical applications because of their distinctive physicochemical properties such as large specific surface area, high mechanical strength, and favorable hydrophilic nature. Moreover, GFNs have demonstrated the ability to create an anti-inflammatory environment and exhibit antibacterial effects. Consequently, these materials hold immense potential in facilitating cell adhesion, proliferation, and differentiation, further promoting the repair and regeneration of various tissues, including bone, nerve, oral, myocardial, and vascular tissues. Note that challenges still persist in current applications, including concerns regarding biosecurity risks, inadequate adhesion performance, and unsuitable degradability as matrix materials. This review provides a comprehensive overview of current advancements in the utilization of GFNs in regenerative medicine, as well as their molecular mechanism and signaling targets in facilitating tissue repair and regeneration. Future research prospects for GFNs, such as potential in promoting ocular tissue regeneration, are also discussed in details. We hope to offer a valuable reference for the clinical application of GFNs in the treatment of bone defects, nerve damage, periodontitis, and atherosclerosis. Keywords: graphene, graphene oxide, regenerative medicine, scaffold, anti-inflammatory, bone regeneration, nerve, angiogenesis, dental pulp stem cells

Yongchao Li,1,&ast; Jinfeng Gao,2,&ast; Shuhua Liu,1 Shijian Chen,3 Xiaoyue Wei,3 Yalun Guan,1 Xuejiao Li,1 Yunfeng Li,1 Zhongqiang Huang,1 Ge Li,1 Yuhong Zhao,3 Pinghua Liu,4 Yu Zhang1 1Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, 510663, People’s Republic of China; 2Guangdong Quality Supervision and Testing Station for Medical and Health Care Appliances, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, 510632, People’s Republic of China; 3School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 4Department of Chemistry, Boston University, Boston, MA, 02215, USA&ast;These authors contributed equally to this workCorrespondence: Yu Zhang; Pinghua Liu, Email zhangyugzh@hotmail.com; pinghua@bu.eduBackground: Ergothioneine (EGT) is an antioxidant, which could be detected in human tissues, and human skin cells could utilize EGT and play an anti-oxidative role in keratinocytes. And in this study we are going to elucidate whether EGT could protect the skin from photoaging by Ultraviolet (UV) exposure in mice and its molecule pathway.Methods: Histological analysis was performed for evaluating the skin structure change. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured with biological assay for evaluating oxidative and antioxidative ability of skin exposed to UV light. And the level of marker molecules in mouse skin were detected by hydroxyproline (Hyp) assay, immunohistochemical analysis, Western blot, and quantitative real-time PCR (qRT-PCR). The markers of skin aging and cell death were tested by cell culture and treatment, Western blot and qRT-PCR.Results: EGT decreased the levels of inflammatory factors induced by UV exposure in mouse skin. MDA and SOD activity detection showed that EGT decreased MDA levels, increased SOD activity, and upregulated PI3K/Akt/Nrf2 signals in mouse skin exposed to UV, which further activated Nrf2 in the nucleus and enhanced the expression of Nrf2 target genes. In the cell model, we revealed that EGT could inhibit the increase in senescence-associated β-galactosidase-positive cells and p16 and γ-H2A.X positive cells induced by etoposide and activate PI3K/Akt/Nrf2 signaling. Moreover, a PI3K inhibitor blocked EGT protection against etoposide-induced cell death.Conclusion: The study showed EGT may play an important protective role against cell damage or death through the PI3K/Akt/Nrf2 signaling pathway in skin.Keywords: ergothioneine, skin aging, PI3K/Akt, Nrf2

Shanshan Liu,1,2 Xiaomeng Ge,3 Xizhan Xu,4 Kang Zhang,1 Xinxin Lu1 1Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Infection Management, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People’s Hospital of Lianyungang, Jiangsu, People’s Republic of China; 3Microbial Resources and Big Data Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xinxin Lu, Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, No. 1, Dongjiaomin Lane, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-13911682566, Fax +8610-65125617, Email luxinxin2009@126.comPurpose: The clinical manifestations of pyogenic liver abscess (PLA) vary between patients with and without diabetes mellitus (DM). However, the relationship between PLA and the gut microbiome remains unknown. This study analyzed the composition of gut microbiota in PLA patients with and without DM and healthy controls (HCs) with the goal of identifying potential reasons for the observed variations in clinical manifestations.Patients and Methods: Using 16S ribosomal RNA(16S rRNA) gene sequencing, we analyzed the compositions of gut microbiota in 32 PLA patients with DM, 32 PLA patients without DM, and 29 matched HCs.Results: In PLA patients with DM, the D-dimer level, fibrinogen degradation products, and thrombin time were significantly higher compared to the PLA patients without DM (P < 0.05). The abundance and diversity of intestinal flora were reduced in both groups of PLA patients compared with the HCs (P < 0.05). Specifically, the PLA patients with DM showed significant decreases in the relative abundances of Bacteroides, Blautia, Prevotella9, and Faecalibacterium, whereas Enterococcus and Escherichia-Shigella were relatively more abundant (P < 0.05). Compared to PLA patients without DM, those with DM had lower relative abundances of Lactobacillus and Klebsiella (P < 0.05) and showed different bacterial flora, including Anaerosporobacter and Megamonas.Conclusion: PLA patients with DM exhibited more severe clinical manifestations of PLA compared to patients without DM. It is important to monitor blood coagulation in PLA patients with DM to prevent the development of thrombotic diseases. Additionally, PLA patients with DM exhibit distinct differences in the composition and diversity of their intestinal flora compared to both PLA patients without DM and HCs.Keywords: Gut microbiota, Pyogenic liver abscess, type 2 diabetes mellitus, 16S rRNA sequencing

Rui Zhou,1,2,&ast; Lijuan Fu,2,&ast; Shu Liu,2,&ast; Sanjie Gao,2 Zhifu Zhao,2 Wencai Jiang,2 Li Liu,2 Weiqiao Ren,2 Dongmei Xiang,2 Xing You,2 Chunyong Tang,2 Yukai Zhou,2 Yanqing Song,2 Juan Xie,2 Li Xie,2 Ru Yu,2 Xianjie Zhang,2 Dan Zhou,2 Jia Han,2 Leqiang Xia,2 Lize Xiong1 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Center for Anesthesiology and Perioperative Medicine, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology, Deyang People’s Hospital, Deyang, 618000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leqiang Xia, Department of Anesthesiology, Deyang People’s Hospital, No. 173, Section 1, North Taishan Road, Deyang, Sichuan, 618000, People’s Republic of China, Tel +8613547098458, Email xialq123184@163.com Lize Xiong, Shanghai Fourth People’s Hospital, No. 1279, Sanmen Road, Shanghai, 200434, People’s Republic of China, Tel +86-21-55603002, Fax +86-21-56660851, Email mzkxlz@126.com; lizexiong@tongji.edu.cnPurpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy.Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected.Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups.Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.Keywords: propofol, ciprofol, remimazolam, endoscopic sedation, dreaming

Fei Li,1,&ast; Feifei Yan,2,&ast; Shengnan Liu,1,&ast; Rewaan Baheti,1 Yujia Feng,1 Jing Wan1 1Department of Cardiovascular Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China; 2Cardiac Ultrasound Department, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wan, Department of Cardiology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, Hubei Province, 430071, People’s Republic of China, Tel +86-027-67813477, Email wanjing_zn@163.comPurpose: In essential hypertensive patients, cardiac remodeling may be associated with the risk of renal damage in the future which can be reflected by the estimated glomerular filtration rate (eGFR). Through retrospective analysis, we evaluated the potential of cardiac remodeling based on echocardiographic measurements to predict the risk of renal damage in the future with hypertensive patients.Methods: We retrospectively analyzed the relationship between the changes of left heart structure and function and renal damage for 510 patients with hypertension, who were diagnosed between 2016 to 2022. Demography data, clinical data, blood samples and echocardiographic variables were used for survival analysis, and the Cox proportional hazards regression model was used.Results: In our study, we found that age, serum creatinine (SCR), creatine kinase isoenzyme MB (CK MB), abnormal high-sensitivity troponin I (TNI), interventricular septum thickness (IVST) and left ventricular ejection fraction (LVEF) could be used as independent predictors in risk of renal impairment in hypertensive patients (p< 0.05). Combined in a score where one point was given for the presence of each of the parameters above, this score could strongly predict renal function damage in the future (p< 0.05). In receiver operating characteristics (ROC) curve analyses, the area under the curve of the risk factor score was 0.849 (P< 0.001).Conclusion: In essential hypertensive patients, LVEF and IVST can predict the risk of future adverse renal outcomes. Moreover, combining risk variables into a simplified score may enable to assess the risk of renal impairment in hypertensive patients at an early stage.Keywords: hypertension, echocardiography, changes of cardiac structure and function, progression of renal damage, hypertensive nephropathy

Di Zhang,1,&ast; Yu Guan,1,&ast; Xiuxiu Zhou,1 Mingzi Zhang,2 Yu Pu,1 Pengchen Gu,2 Yi Xia,1 Yang Lu,2 Jia Chen,2 Wenting Tu,1 Kunyao Huang,2 Jixin Hou,2 Hua Yang,2 Chicheng Fu,2 Qu Fang,2 Chuan He,2 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Second Affiliated Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Scientific Research Department, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Fan; Shiyuan Liu, Department of Radiology, Second Affiliated Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +13564684699 ; +13761304518, Fax +86 21 63587668, Email czyxfl@smmu.edu.cn; radiology_cz@163.comPurpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD.Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted.Results: The RSA and RSA% were significantly different among the three groups (p< 0.05) and related to FEV1/FVC (r = − 0.70, p < 0.001; r = − 0.67, p < 0.001), FEV1% predicted (r = − 0.60, p = 0.002; r = − 0.57, p = 0.004), MEF50% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001), MEF75% predicted (r = − 0.71, p < 0.001; r = − 0.60, p = 0.002) and MMEF 75/25% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001).Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.Keywords: COPD, small airway disease, CT, fluid dynamics

Si Liu, Dan Yang, Wen Li, Qiuping Chen, Danni Lu, Liang Xiong, Junjie Wu, Hui Ao, Lihua Huang State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of ChinaCorrespondence: Lihua Huang; Hui Ao, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China, Email huanglihua@cdutcm.edu.cn; aohui2005@126.comPurpose: Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer’s disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT.Methods: Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques.Results: MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas).Conclusion: MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.Keywords: polygala tenuifolia, PI3K/AKT/NF-κB, gut microbiota, inflammation, intestinal injury