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Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) continues its significant health and economic impact globally. Despite the success of spike-protein vaccines in preventing severe disease, long-lasting protection against emerging variants and the prevention of breakthrough infections and transmission remain elusive. We generate an intranasal live-attenuated SARS-CoV-2 vaccine, CDO-7N-1, using codon deoptimization. CDO-7N-1 shows highly attenuated replication and minimal or no lung pathology in vivo over multiple passages. It induces robust mucosal and systemic neutralizing antibody and T-cell subset responses, in mice (female K18-hACE2 and male HFH4-hACE2 mice), hamsters, and macaques triggered by a single immunization. Mice and hamsters vaccinated with CDO-7N-1 are protected from challenge with wild-type (WT) SARS-CoV-2 and other variants of concern. Serum from vaccinated animals neutralizes WT SARS-CoV-2, variants of concern (beta and delta), variants of interest (omicron XBB.1.5) and SARS-CoV-1. Antibody responses are sustained and enhanced by repeated immunization or infection with WT SARS-CoV-2. Immunity against all SARS-CoV-2 proteins by CDO-7N-1 should improve efficacy against future SARS-CoV-2 variants.

Feng Yao,1,* Chenguang Wang,2,* Jie Ding,1 Qian Zhang,1 Liang Zheng,1 Qin Zhang,1 Tianshu Yang,2 Xunmin Zhang,2 Yong Shan,2 Sheng Hou,2 Hao Wang,2 Renpeng Zhou,1 Wei Hu1 1Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Taizhou Mabtech Pharmaceutical Co., Ltd, Taizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Hu; Renpeng Zhou, Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, Anhui, 230601, People’s Republic of China, Tel/Fax + 86 0551 65997164, Email huwei@ahmu.edu.cn; zhourenpeng@ahmu.edu.cnPurpose: Secukinumab, a monoclonal antibody targeting interleukin (IL)-17A, is approved for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa. This study compared the pharmacokinetics (PK), safety, and immunogenicity of CMAB015, a candidate secukinumab biosimilar, with the reference product secukinumab (Cosentyx®) in healthy Chinese male subjects.Patients and methods: This double-blind, parallel-group study randomized healthy Chinese male subjects (N=130) to receive either a single dose of 150 mg CMAB015 or secukinumab subcutaneously. Primary study endpoints were PK parameters such as the maximum concentration (Cmax) and area under the curve from zero to infinity (AUC0-inf), while safety and immunogenicity were secondary endpoints.Results: The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of Cmax and AUC0-inf for CMAB015 to secukinumab were all within the bioequivalence limits (80.00– 125.00%). Other PK parameters were comparable between the groups. The safety profile of CMAB015 was similar to that of secukinumab, with no serious adverse events related to treatment. The incidence of TEAEs was slightly higher in the CMAB015 group, but these events were mild to moderate in severity and did not lead to any withdrawals from the study. Immunogenicity analysis revealed low rates of anti-drug antibody (ADA) positivity, with similar rates between CMAB015 and secukinumab.Conclusion: This study demonstrated equivalent PK, comparable safety, and immunogenicity of CMAB015 to secukinumab in healthy Chinese male subjects. These findings support further clinical evaluation of CMAB015 as a secukinumab biosimilar.Trial Registration: The trial was registered on Clinicaltrials.gov (Identifier No. NCT05734482) and Chinadrugtrials.org.cn (Identifier No. CTR20230105).Keywords: CMAB015, secukinumab, biosimilar, pharmacokinetics, safety, immunogenicity

Yawen Mo,1,&ast; Wenjuan Zhang,1,&ast; Xiangcheng Tang,1 Rui Zhang,2 Yinghuan Wang,1 Lingling Zheng3 1Department of Strabismus and Amblyopia, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of China; 2Department of Anesthesia, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of China; 3Department of Nursing Administration, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingling Zheng, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 7 Jinsui Road, Guangzhou, People’s Republic of China, Email zhenglingling@gzzoc.comPurpose: Strabismus surgery is most commonly performed on children under general anesthesia. However, few studies have focused on the postoperative discomfort in children after strabismus surgery. This study aimed to evaluate postoperative discomfort and the associated risk factors in children who underwent strabismus surgery under general anesthesia.Patients and Methods: A single-center prospective observational study including 300 children who underwent strabismus surgery after general anesthesia was conducted. Patients’ characteristics, preoperative anxiety, surgical and anesthesia data, discomfort within 24 hours after postanesthesia care unit were recorded. The primary outcome was the incidence of postoperative discomfort.Results: Approximately 51.33% of the children complained of at least one of the following types of postoperative discomfort: postoperative nausea and vomiting (PONV) (23.00%), headache (4.33%), dizziness (20.33%) and emergence agitation (EA) (5.33%). Multivariate analysis indicated that history of motion sickness (P< 0.001, odds ratio [OR]=3.72), and surgery in the dominant eye (P=0.010, OR=2.00) were independent predictors of postoperative discomfort; age was an independent predictor of EA (P< 0.001, OR=0.36); prism diopter≥ 40 was an independent predictor of headache (P=0.005, OR=5.53); age (P=0.020, OR=1.12) and history of motion sickness (P=0.001, OR=2.80) were independent predictors of dizziness; history of motion sickness (P=0.001, OR=2.63) and surgery of inferior oblique anterior transposition (IOAT) (P=0.004, OR=3.10) were independent predictors of PONV.Conclusion: The most frequent postoperative symptoms in children after undergoing strabismus surgery under general anesthesia are PONV, dizziness, EA, and headache. Younger age, larger angle of strabismus, history of motion sickness, surgery on the dominant eye, and surgery of IOAT may be additional risk factors for postoperative discomfort.Keywords: strabismus surgery, discomfort, postoperative nausea, vomiting, general anesthesia

Longyi Zheng,1,&ast; Chengjing Zhang,2,&ast; Shichang Bu,1,&ast; Wencheng Guo,3,&ast; Tongtong Li,4 Ying Xu,5 Yunan Liu,4 Caimei Yuan,4 Chengwu Feng,4 Geng Zong,4 Jingwen Zhu,4 Maoying Xing,5 Xin Geng5 1Department of Endocrinology, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Nutrition, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 3Department of General Surgery and Vascular Surgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5National Center for Liver Cancer, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maoying Xing; Xin Geng, Email xmyxing@sina.com; gxouc@hotmail.comBackground: Neuregulin 4 (NRG4) was known to be associated with serum lipid levels and atherosclerosis. However, it is unknown whether the role of NRG4 in lipid homeostasis is causal to atherosclerosis and whether the effect is beneficial across different atherosclerosis subtypes.Methods: We investigated the causal role of the levels of serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides regulated by NRG4 in subtypes of atherosclerosis through two sample Mendelian randomization. Aggregated genome-wide association study (GWAS) summary data for serum lipid level of 1.32 million individuals with European ancestry were obtained from the Global Lipids Genetics Consortium. GWAS summary data for four atherosclerosis subtypes (peripheral, coronary, cerebral and the other atherosclerosis) were obtained from FinnGen Consortium. Generalized inverse-variance–weighted Mendelian randomization and several sensitivity analyses were used to obtain the causal estimates.Results: A 1-SD genetically elevated LDL-C level mediated by NRG4 was validated to be nominally associated with the risk of peripheral atherosclerosis (log (odds ratio)= 4.14, 95% confidence interval 0.11 to 8.17, P = 0.04), and the other associations were not significant or could not be validated by sensitivity analyses.Conclusion: LDL-C lowering mediated by NRG4 is likely to prevent peripheral atherosclerosis.Keywords: Mendelian randomization analysis, NRG4, atherosclerosis, lipid

Weimin Xu,1 Xinyu Wang,2 Lei Yang,2 Muzi Meng,3,4 Chenyu Sun,1 Wanwan Li,1 Jia Li,1 Lu Zheng,1 Tong Tang,1 WenJun Jia,1 Xiao Chen1 1Department of Thyroid and Breast Surgery, The Affiliated Second Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2School of Second Clinical Medicine, AnHui Medical University, Hefei, People’s Republic of China; 3School of Medicine, American University of the Caribbean, Sint Maarten, Kingdom of the Netherlands; 4General Surgery, BronxCare Health System, New York, NY, USACorrespondence: WenJun Jia; Xiao Chen, Email jiawenjun@smail.nju.edu.cn; chenxiao950616@Gmai.comBackground: The Chinese Society of Clinical Oncology Artificial Intelligence System (CSCO AI) serves as a clinical decision support system developed utilizing Chinese breast cancer data. Our study delved into the congruence between breast cancer treatment recommendations provided by CSCO AI and their practical application in clinical settings.Methods: A retrospective analysis encompassed 537 breast cancer patients treated at the Second Affiliated Hospital of Anhui Medical University between January 2017 and December 2022. Proficient senior oncology researchers manually input patient data into the CSCO AI system. “Consistent” and “Inconsistent” treatment categories were defined by aligning our treatment protocols with the classification system in the CSCO AI recommendations. Cases that initially showed inconsistency underwent a second evaluation by the Multi-Disciplinary Treatment (MDT) team at the hospital. Concordance was achieved when MDTs’ treatment suggestions were in the ‘Consistent’ categories.Results: An impressive 80.4% concurrence was observed between actual treatment protocols and CSCO AI recommendations across all breast cancer patients. Notably, the alignment was markedly higher for stage I (85.02%) and stage III (88.46%) patients in contrast to stage II patients (76.06%, P=0.023). Moreover, there was a significant concordance between invasive ductal carcinoma and lobular carcinoma (88.46%). Interestingly, triple-negative breast cancer (TNBC) exhibited a high concordance rate (87.50%) compared to other molecular subtypes. When contrasting MDT-recommended treatments with CSCO AI decisions, an overall 92.4% agreement was established. Furthermore, a logistic multivariate analysis highlighted the statistical significance of age, menstrual status, tumor type, molecular subtype, tumor size, and TNM stage in influencing consistency.Conclusion: In the realm of breast cancer treatment, the alignment between recommendations offered by CSCO AI and those from MDT is predominant. CSCO AI can be a useful tool for breast cancer treatment decisions.Keywords: Chinese Society of clinical oncology artificial intelligence system, CSCO AI, breast cancer, multi-disciplinary treatment, MDT, consistency

Bo Jin,1 Kexin Lu,2 Wenna Gao,1 Yixian Liu,3 Mengfei Wang,2 Xiaojun Zhang,3 Huiping Chen,3 Liyun Zheng,3 Min Zou3 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Hennan, 450052, People’s Republic of China; 2BGI College, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 3Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Min Zou; Liyun Zheng, Email Minzou1980@126.com; zhengliyun@zzu.edu.cnBackground: At present, the few photothermal/chemotherapy studies about retinoblastoma that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. However, eyeball is unique physiological structure, the blood-retina barrier (BRB) hinders the absorption of drug molecules through the systemic route. Moreover, the abundant blood circulation in the fundus accelerates drug metabolism. To uphold the required drug concentration, patients must undergo frequent chemotherapy sessions.Purpose: To address these challenges above, we need to develop a secure and effective drug delivery system (FA-PEG-PDA-DOX) for the fundus.Methods: We offered superior therapeutic efficacy with minimal or no side effects and successfully established orthotopic mouse models. We evaluated cellular uptake performance and targeting efficiency of FA-PEG-PDA-DOX nanosystem and assessed its synergistic antitumor effects in vitro and vivo. Biodistribution assessments were performed to determine the retention time and targeting efficiency of the NPs in vivo. Additionally, safety assessments were conducted.Results: Cell endocytosis rates of the FA-PEG-PDA-DOX+Laser group became 5.23 times that of the DOX group and 2.28 times that of FA-PEG-PDA-DOX group without irradiation. The fluorescence signal of FA-PEG-PDA-DOX persisted for more than 120 hours at the tumor site. The number of tumor cells (17.2%) in the proliferative cycle decreased by 61.6% in the photothermal-chemotherapy group, in contrast to that of the saline control group (78.8%). FA-PEG-PDA-DOX nanoparticles(NPs) exhibited favorable biosafety and high biocompatibility.Conclusion: The dual functional targeted nanosystem, with the effects of DOX and mild-temperature elevation by irradiation, resulted in precise chemo/photothermal therapy in nude mice model.Keywords: retinoblastoma, orthotopic model, nanoparticle, synergistic therapy

Peigang Zhang,1,2,&ast; Lingling Zheng,1,3,4,&ast; Xiaorui Zhang,1,3 Miao Liu,1,3 Mingli Li,2 Mengting Zhang,1 Jian-Lin Wu,4 Martin MF Choi,5 Wei Bian1– 3 1Department of Medical Chemistry, School of Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China; 2Department of Cardiothoracic Surgery, People’s Hospital of Lvliang, Lvliang, Shanxi, 033099, People’s Republic of China; 3Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan, Shanxi, 030000, People’s Republic of China; 4State Key Laboratory for Quality Research of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, People’s Republic of China; 5Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Bian, Department of Medical Chemistry, School of Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China, Email weibian@sxmu.edu.cnIntroduction: Lung cancer is the most common cancer worldwide, among which non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Chemotherapy, a mainstay modality for NSCLC, has demonstrated restricted effectiveness due to the emergence of chemo-resistance and systemic side effects. Studies have indicated that combining chemotherapy with phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), can enhance efficacy of therapy. In this work, an aminated mesoporous graphene oxide (rPGO)-protoporphyrin IX (PPIX)-hyaluronic acid (HA)@Osimertinib (AZD) nanodrug delivery system (rPPH@AZD) was successfully developed for combined chemotherapy/phototherapy for NSCLC.Methods: A pH/hyaluronidase-responsive nanodrug delivery system (rPPH@AZD) was prepared using mesoporous graphene oxide. Its morphology, elemental composition, surface functional groups, optical properties, in vitro drug release ability, photothermal properties, reactive oxygen species production, cellular uptake and cell viability were evaluated. In addition, the in vivo therapeutic effect, biocompatibility, and imaging capabilities of rPPH@AZD were verified by a tumor-bearing mouse model.Results: Aminated mesoporous graphene oxide (rPGO) plays a role as a drug delivery vehicle owing to its large specific surface area and ease of surface functionalization. rPGO exhibits excellent photothermal conversion properties under laser irradiation, while PPIX acts as a photosensitizer to generate singlet oxygen. AZD acts as a small molecule targeted drug in chemotherapy. In essence, rPPH@AZD shows excellent photothermal and fluorescence imaging effects in tumor-bearing mice. More importantly, in vitro and in vivo results indicate that rPPH@AZD can achieve hyaluronidase/pH dual response as well as combined chemotherapy/PTT/PDT anti-NSCLC treatment.Conclusion: The newly prepared rPPH@AZD can serve as a promising pH/hyaluronidase-responsive nanodrug delivery system that integrates photothermal/fluorescence imaging and chemo/photo combined therapy for efficient therapy against NSCLC. Keywords: NSCLC, mesoporous graphene oxide, combination therapy, hyaluronidase/pH dual-response, nanodrug delivery system

Yifan Wang,1,2,&ast; Lei Zhang,3,&ast; Chenggong Wang,4 Min Lin,1 Li Zheng,5,6 Xiuyan Guo5,6 1Mental Health Education Center, Zhengzhou University, Zhengzhou, People’s Republic of China; 2School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of China; 3School of Physical Education (Main Campus), Zhengzhou University, Zhengzhou, People’s Republic of China; 4College of Science and Technology, Ningbo University, Ningbo, People’s Republic of China; 5Fudan Institute on Ageing, Fudan University, Shanghai, People’s Republic of China; 6Ministry of Education (MOE) Laboratory for National Development and Intelligent Governance, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Zheng, Fudan Institute on Ageing, Ministry of education (MOE) Laboratory for National Development and Intelligent Governance, Fudan University, No. 220 Handan Road, Yangpu District, Shanghai, 200433, People’s Republic of China, Email zheng_l@fudan.edu.cnIntroduction: People are generally characterized by a self-serving bias which describes the tendency to ascribe positive outcomes or success to internal or personal causes (self-enhancement motivation) and ascribe negative outcomes or failure to external or situational causes (self-protection motivation). It has been found that the individuals with internet gaming disorder (IGD) who have low self-esteem and high depression exhibit an attenuated self-serving bias. However, the relationships among self-esteem, depression and self-serving bias are not clearly identified.Methods: A sample of 138 IGD participants completed self-esteem and depression scales and a causal attribution task (Study 1) to examine the relationships among self-esteem, depression and self-serving bias (both self-enhancement and self-protection). In follow-up Study 2, 28 IGD participants were recruited to undertake self-affirmation intervention which can affirm one’s sense of global self-view and bolster self-esteem to explore whether self-affirmation would trigger a reduction of depression and a raise of self-serving bias.Results: The results of path analysis in Study 1 showed that the self-serving bias was predicted by self-esteem and depression, and the depression played a mediating role between self-esteem and self-serving bias. The results of Study 2 showed that the IGD participants reported higher self-esteem, lower depression and engaged in more self-protection motivation after affirming-self manipulation as compared with affirming-other manipulation.Conclusion: These findings suggest that self-esteem predicts self-serving bias through depression and self-affirmation could trigger an increase of self-esteem, further decrease depression and improve self-serving bias for the individuals with IGD. The present article clearly identified the relationships among these factors and provided a new approach to promote positive self-concept in individuals with IGD. Future research is warranted to explore the lasting benefits of self-affirmation on domains of education, relationships and gaming withdrawal for the individuals with IGD among different populations.Keywords: internet gaming disorder, self-serving bias, self-esteem, depression

Xinfang Cao, Jun Zhang, Jie Shao, Yonggang Zhang, Li Zheng Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Jun Zhang, Email zhangjun@mskyk.onaliyun.comPurpose: To evaluate the effectiveness of Zhang and Zheng’s InnovEyes (ZZ InnovEyes) strategy for optimizing outcomes of ray-tracing-guided laser in situ keratomileusis (LASIK) compared to the standard automated strategy.Methods: A total of 38 patients (71 eyes) undergoing therapeutic refractive surgery at Hangzhou MSK Eye Hospital were randomly assigned to the ZZ InnovEyes and automated groups using double-masked randomization. The study assessed visual acuity, refractive outcomes, and higher-order aberrations preoperatively and at 1-day, 2-week, 1-month, and 3-month follow-ups. Statistical analysis was done with Microsoft Excel and SPSS 19.0.Results: The exposure and control groups comprised 36 and 35 eyes, respectively. The ZZ InnovEyes group demonstrated significant advantages in manifest refraction spherical equivalent (MRSE) correction compared to the automated approach group (0.13 ± 0.30 D vs 0.62 ± 0.40 D, p < 0.001), achieving 97.22% uncorrected distance visual acuity (UDVA) of 20/16 or better compared to 85.71% in the automated group at the 3-month follow-up (p = 0.08), and achieving 50.00% UDVA of 20/12.5 or better compared to 28.57% in the automated group at the 3-month follow-up (p = 0.06). Loss lines from preoperative corrected distance visual acuity to postoperative UDVA were lower in the ZZ InnovEyes group (0.00%) than the automated group (8.57%; p = 0.07). Both groups exhibited similar astigmatism corrections and higher-order aberrations.Conclusion: The ZZ InnovEyes strategy, which incorporates manifest and wavefront refraction for ray-tracing-guided LASIK, demonstrated superior MRSE correction and potential advantages in visual acuity outcomes compared to the standard automated strategy. This study highlights the need for ongoing optimization and research in refractive surgery.Clinical Trial Registration Number: ChiCTR2300078709.Keywords: LASIK, refractive surgery, ray-tracing, higher-order aberrations, visual acuity

Jianchun Xiao,1,&ast; Fangyu Zhao,1,&ast; Wenhao Luo,1,&ast; Gang Yang,1 Yicheng Wang,1 Jiangdong Qiu,1 Yueze Liu,1 Lei You,1 Lianfang Zheng,2 Taiping Zhang1,3 1Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taiping Zhang, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China, Email zhangtaiping@pumch.cnAim: This article aimed to find appropriate pancreatic cancer (PC) patients to treat with Gemcitabine with better survival outcomes by detecting hENT1 levels.Methods: We collected surgical pathological tissues from PC patients who received radical surgery in our hospital from September 2004 to December 2014. A total of 375 PC tissues and paired adjacent nontumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of the 4 TMAs was examined by HE staining. We performed immunohistochemistry analysis to evaluate hENT1 expression in the TMAs. Moreover, we detected hENT1 expression level and proved the role of hENT1 in cell proliferation, drug resistance, migration and invasion in vivo and vitro.Results: The results indicated that low hENT1 expression indicated a significantly poor outcome in PC patients, including shortened DFS (21.6± 2.8 months versus 36.9± 4.0 months, p< 0.001) and OS (33.6± 3.9 versus 39.6± 3.9, p=0.004). Meanwhile, patients in stage I/II of TNM stage had a longer OS (40.2± 3.4 versus 15.4± 1.7, p=0.002) and DFS (31.0± 3.1 versus 12.4± 1.9, p=0.016) than patients in stage III/IV. Patients in M0 stage had a longer OS (39.7± 3.4 versus 16.2± 1.9, p=0.026) and DFS(30.7± 3.0 versus 11.8± 2.2, p=0.031) than patients in M1 stage, and patients with tumors not invading the capsule had a better DFS than those with tumor invasion into the capsule (30.8± 3.0 versus 12.6± 2.3, p=0.053). Patients with preoperative CA19-9 values ≤ 467 U/mL have longer DFS than that of patients who had preoperative CA19-9 values > 467 U/mL (37.9± 4.1 versus 22.9± 4.0, p=0.04). In the subgroup analysis, a high hENT1 expression level was related to a longer OS(39.4± 4.0 versus 31.5± 3.9, p=0.001) and DFS(35.7± 4.0 versus 20.6± 2.7; p< 0.0001) in the Gemcitabine subgroup.Conclusion: PC patients with high hENT1 expression have a better survival outcomes when receiving Gemcitabine. hENT1 expression can be a great prognostic indicator for PC patients to receive Gemcitabine treatment.Keywords: pancreatic cancer, human equilibrative nucleoside transporter 1, hENT1, gemcitabine chemoresistance, prognostic indicator, survival improvement

Tianshu Liu, Mengfan Zhang, Jin Zhang, Naijin Kang, Linlin Zheng, Zhiying Ding School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Zhiying Ding, School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, People’s Republic of China, Tel/Fax +86 13843180286, Email dzy@jlu.edu.cnPurpose: Ginsenoside Rg3 (Rg3) and Panax notoginseng saponins (PNS) can be used for ischemic stroke treatment, however, the lack of targeting to the ischemic region limits the therapeutic effect. To address this, we leveraged the affinity of macrophage membrane proteins for inflamed brain microvascular endothelial cells to develop a macrophage membrane-cloaked liposome loaded with Rg3 and PNS (MM-Lip-Rg3/PNS), which can precisely target brain lesion region through intranasal administration.Methods: MM-Lip-Rg3/PNS was prepared by co-extrusion method and was performed by characterization, stability, surface protein, and morphology. The cellular uptake, immune escape ability, and blood-brain barrier crossing ability of MM-Lip-Rg3/PNS were studied in vitro. The in vivo brain targeting, biodistribution and anti-ischemic efficacy of MM-Lip-Rg3/PNS were evaluated in MACO rats, and we determined the diversity of the nasal brain pathway through the olfactory nerve blockade model in rats. Finally, the pharmacokinetics and brain targeting index of MM-Lip-Rg3/PNS were investigated.Results: Our results indicated that MM-Lip-Rg3/PNS was spherical with a shell-core structure. MM-Lip-Rg3/PNS can avoid mononuclear phagocytosis, actively bind to inflammatory endothelial cells, and have the ability to cross the blood-brain barrier. Moreover, MM-Lip-Rg3/PNS could specifically target ischemic sites, even microglia, increase the cumulative number of drugs in the brain, improve the inflammatory environment of the brain, and reduce the infarct size. By comparing olfactory nerve-blocking rats with normal rats, it was found that there are direct and indirect pathways for nasal entry into the brain. Pharmacokinetics demonstrated that MM-Lip-Rg3/PNS exhibited stronger brain targeting and prolonged drug half-life.Conclusion: MM-Lip-Rg3/PNS might contribute to the accumulation of Rg3 and PNS in the ischemic brain area to improve treatment efficacy. This biomimetic nano-drug delivery system provides a new and promising strategy for the treatment of ischemic stroke. Keywords: macrophage-membrane coating, biomimetic liposome, brain targeting, ischemic stroke, intranasal delivery

Changxiu Ma,1 Ying Zhang,1 Tingchao Tian,2 Ling Zheng,1 Jing Ye,1 Hui Liu,1 Dahai Zhao1 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Huoqiu First People’s Hospital, Huoqiu, 237400, People’s Republic of ChinaCorrespondence: Dahai Zhao, Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Tel +86-13721027959, Email zhaodahai@ahmu.edu.cnPurpose: To explore the role of the mean apnea–hypopnea duration (MAD) and apnea–hypopnea duration per hour (HAD) in hypoxemia and evaluate whether they can effectively predict the occurrence of hypoxemia among adults with OSA.Patients and Methods: A total of 144 participants underwent basic information gathering and polysomnography (PSG). Logistic regression models were conducted to evaluate the best index in terms of hypoxemia. To construct the prediction model for hypoxemia, we randomly divided the participants into the training set (70%) and the validation set (30%).Results: The participants with hypoxemia tend to have higher levels of obesity, diabetes, AHI, MAD, and HAD compared with non-hypoxemia. The most relevant indicator of blood oxygen concentration is HAD (r = 0.73) among HAD, MAD, and apnea–hypopnea index (AHI). The fitness of HAD on hypoxemia showed the best. In the stage of establishing the prediction model, the area under the curve (AUC) values of both the training set and the validation set are 0.95. The increased HAD would elevate the risk of hypoxemia [odds ratio (OR): 1.30, 95% confidence interval (CI): 1.13– 1.49].Conclusion: The potential role of HAD in predicting hypoxemia underscores the significance of leveraging comprehensive measures of respiratory disturbances during sleep to enhance the clinical management and prognostication of individuals with sleep-related breathing disorders.Keywords: mean apnea–hypopnea duration, obstructive sleep apnea, apnea–hypopnea duration per hour, polysomnography, apnea–hypopnea index

Xinfang Cao, Jie Shao, Yonggang Zhang, Li Zheng, Jun Zhang Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Jun Zhang, Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 571 85068587, Email zhangjun@mskyk.onaliyun.comPurpose: To examine the visual outcomes, particularly at 33 cm, and assess patient satisfaction following the implantation of a diffractive trifocal intraocular lens (IOL) and its toric variant.Patients and Methods: This prospective single-arm observational study involved 45 Chinese patients (90 eyes) underwent bilateral cataract surgery and PanOptix or PanOptix toric intraocular lenses (IOLs) implantation. Postoperatively, visual acuity was evaluated at various distances, including 40 cm and 33 cm, for both monocular and binocular outcomes. Patient satisfaction was evaluated using the VF-14 questionnaire.Results: 72 eyes underwent PanOptix IOLs implantation, and 18 eyes received PanOptix toric IOLs. At 3-month postoperative mark, the mean monocular UDVA, UIVA, and UNVA at 40 cm and 33 cm were − 0.02± 0.09, 0.00± 0.07, 0.02± 0.07, and 0.07± 0.14 logMAR, respectively, with proportions of visual acuity exceeding 0.1 logMAR were 96.7%, 96.7%, 94.4%, and 74.4%, respectively. The mean binocular UDVA, UIVA, and UNVA at 40 cm and 33 cm were − 0.05± 0.06, − 0.03± 0.05, 0.00± 0.05, and 0.04± 0.07 logMAR, respectively, with proportions of visual acuity exceeding 0.1 logMAR were 97.8%, 100.0%, 100.0%, and 91.1%, respectively. When the near point shifted from 40cm to 33cm, some patients showed a decline for UDVA, but the average reduction was less than one line. The overall VF-14 questionnaire score was 4.02± 4.19.Conclusion: PanOptix can provide Chinese patients with a full range of satisfying visual acuity, near to 33cm. Though the visual acuity of some patients at 33 cm did not match the level at 40 cm, the gap of one line may not carry clinical significant.Keywords: trifocal IOL, PanOptix, visual acuity at 33 cm

Lihan Zheng,1 Lixia Gao,1 Yaohui Hu,1 Liqun Zhang,2,&ast; Ye Guan1,&ast; 1Savaid Stomatology School, Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Department of Periodontics, Stomatological Hospital of Lin’an District, Hangzhou, Zhejiang, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Guan, 211, Building 3, Linan Campus, Hangzhou Medical College, Linan District, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +86 18868105499, Email 21818734@zju.edu.cn Liqun Zhang, Department of Periodontics, Stomatological Hospital of Lin’an District, Hangzhou, Zhejiang 310053, People’s Republic of China, Email zlqjuice@icloud.comAbstract: With the continuous development and progress of medicine, there are many methods for the treatment of temporomandibular disorders, among which temporomandibular joint lavage is also constantly developed. In the past century, through the efforts of some scholars and clinical summary, the understanding of this disease has been deepened and broadened. At present, through continuous exploration of the treatment methods, the lavage is relatively mature, and has achieved good clinical results. In this paper, the application of temporomandibular joint lavage in the treatment of temporomandibular joint disorders, its treatment methods, treatment mechanism, the auxiliary of other drugs, indications, complications and so on were discussed.Keywords: temporomandibular joint lavage, temporomandibular joint disorder, arthrocentesis

Xinfang Cao, Jie Shao, Yonggang Zhang, Li Zheng, Jun Zhang Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Jun Zhang, Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 571 85068587, Email zhangjun@mskyk.onaliyun.comPurpose: To assess long term changes of the surgically induced astigmatism (SIA) and corneal higher-order aberrations (HOAs) after 2.2 mm clear corneal incisions (CCIs) in femtosecond laser-assisted cataract surgery and compare them between 2 types of CCIs: temporal and superior approach.Patients and Methods: Patients received the temporal CCIs (Group A) or the superior CCIs (Group B). Outcome measures included visual acuity, manifest refraction, corneal astigmatism, SIA, flattening effect, and corneal HOAs. Correlation between postoperative corneal HOA and SIA at each follow-up were analysed.Results: This study assessed data from 106 eyes, of which 64 in Group A and 42 in Group B. The two groups had similar postoperative visual acuity of distance, intermediate and near (all P > 0.05). SIA and corneal HOAs were significantly lower in Group A than Group B in the early postoperative period, while there was no significant difference in the late postoperative period. At 6 months after surgery, the arithmetic mean of SIA over corneal 4mm zone was 0.33 ± 0.19D for temporal incision, and 0.37 ± 0.25D for superior incision. For Group A, the correlations of HOAs and SIA persisted from 1 week to 6 months after surgery. For Group B, the changes in corneal HOAs were significantly related to the SIA at 1 week and 1 month postoperatively.Conclusion: This study suggested the consistency of increasing and recovering process of corneal HOAs and SIA after surgery. Compared to the superior incisions, temporal incisions might induce quicker corneal recovery and less change in SIA and corneal HOAs.Keywords: surgically induced astigmatism, higher-order aberrations, clear corneal incision, femtosecond laser-assisted, cataract surgery

Shipeng Chen,1– 3 Mengna Li,1– 3 Changning Xue,1– 3 Xiangting Zhou,1– 3 Jianxia Wei,1– 3 Lemei Zheng,1– 3 Yumei Duan,1– 3 Hongyu Deng,1 Faqing Tang,1 Wei Xiong,1– 3 Bo Xiang,1– 3 Ming Zhou1– 3 1NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People’s Republic of China; 2Cancer Research Institute, Central South University, Changsha, 410078, People’s Republic of China; 3The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, People’s Republic of ChinaCorrespondence: Ming Zhou; Bo Xiang, Email zhouming2001@163.com; xiangbolin@csu.edu.cnPurpose: Cinobufotalin injection has obvious curative effects on liver cancer patients with less toxicity and fewer side effects than other therapeutic approaches. However, the core ingredients and mechanism underlying these anti-liver cancer effects have not been fully clarified due to its complex composition.Methods: Multidimensional network analysis was used to screen the core ingredients, key targets and pathways underlying the therapeutic effects of cinobufotalin injection on liver cancer, and in vitro and in vivo experiments were performed to confirm the findings.Results: By construction of ingredient networks and integrated analysis, eight core ingredients and ten key targets were finally identified in cinobufotalin injection, and all of the core ingredients are tightly linked with the key targets, and these key targets are highly associated with the cell cycle-related pathways, supporting that both cinobufotalin injection and its core ingredients exert anti-liver cancer roles by blocking cell cycle-related pathways. Moreover, in vitro and in vivo experiments confirmed that either cinobufotalin injection or one of its core ingredients, cinobufagin, significantly inhibited cell proliferation, colony formation, cell cycle progression and xenograft tumor growth, and the key target molecules involved in the cell cycle pathway such as CDK1, CDK4, CCNB1, CHEK1 and CCNE1, exhibit consistent changes in expression after treatment with cinobufotalin injection or cinobufagin. Interestingly, some key targets CDK1, CDK4, PLK1, CHEK1, TTK were predicted to bind with multiple of core ingredients of cinobufotalin injection, and the affinity between one of the critical ingredients cinobufagin and key target CDK1 was further confirmed by SPR assay.Conclusion: Cinobufotalin injection was confirmed to includes eight core ingredients, and they play therapeutic effects in liver cancer by blocking cell cycle-related pathways, which provides important insights for the mechanism of cinobufotalin injection antagonizing liver cancer and the development of novel small molecule anti-cancer drugs. Keywords: cinobufotalin injection, liver cancer, cinobufagin, network pharmacology, cell cycle, core ingredients

Lin Zheng,1,&ast; Yusi Yang,2,&ast; Jie Liu,3 Tianliang Zhao,3 Xin Zhang,3 Lihua Chen3 1Department of Vascular Surgery, the Second Hospital, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Department of Cardiology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China; 3Department of Cardiac Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua Chen, The Second Hospital of Hebei Medical University, 215 Hepingxi Street, Shijiazhuang, 050000, People’s Republic of China, Tel +86 188 4679 1714, Fax +86 0311-87045297, Email lin0928@fjmu.edu.cnPurpose: Immune microenvironment plays an important role in aortic dissection (AD). Therefore, novel immune biomarkers may facilitate AD prevention, diagnosis, and treatment. This study aimed at mining key immune-related genes and relevant mechanisms involved in AD pathogenesis.Patients and Methods: Key immune cells in AD were identified by ssGESA algorithm. Next, genes associated with key immune cells were screened by weighted gene coexpression network analysis (WGCNA). Then hub immune genes were picked from protein-protein interaction network of overlapped genes from differential expression and WGCNA analyses by cytohubba plug-in. Their diagnostic potential was evaluated in two independent cohorts from GEO database. In addition, the expressions of hub immune genes were determined by quantitative RT-PCR, immunohistochemistry, and Western blotting in dissected and normal aortic tissues.Results: Activated B cells, CD56dim natural killer cells, eosinophils, gamma delta T cells, immature B cells, natural killer cells and type 17 T helper cells were identified as key immune cells in AD. Thereafter, a gene module significantly correlated with key immune cells were found by WGCNA method. Subsequently, KDR, IGF1, NOS3, PECAM1, GAPDH, FLT1, DLL4, CDH5, VWF, and TEK were identified as hub immune cell related genes by PPI network analysis, which may be potential diagnostic markers for AD, as evidenced by ROC curves. Moreover, the decreased expression of VWF in AD was validated at both mRNA and protein levels, and its expression was significantly positive correlated with the marker of smooth muscle cells, ACTA2, in AD. Further immunofluorescent results showed that VWF was colocalized with ACTA2 in aortic tissues.Conclusion: We identified key immune cells and hub immune cell-related genes involved in AD. Moreover, we found that VWF was co-expressed with the smooth muscle cell marker ACTA2, indicating the important role of VWF in smooth muscle cell loss in AD pathogenesis.Keywords: aortic dissection, infiltrating immune cells, diagnosis, smooth muscle cells

Chun-Yu Zhao,1 Wan-Hong Shi,2 Zheng-Qi Wen,3 Yong-Mei Jin,4 Yun-Bo Shang,5 Lei Zheng,3 Juan Li,2 Xin-Min Chen2 1School of Nursing, Dali University, Dali, 671000, People’s Republic of China; 2Department of General Surgery, Third People’s Hospital of Yunnan Province, Kun Ming, 650000, People’s Republic of China; 3Department of Surgical Oncology, the First Affiliated Hospital of Kunming Medical University, Kun Ming, 650000, People’s Republic of China; 4Department of Nursing, Shanghai Seventh People’s Hospital, Shanghai, 200137, People’s Republic of China; 5Department of Emergency, Third People’s Hospital of Yunnan Province, Kun Ming, 650000, People’s Republic of ChinaCorrespondence: Yun-Bo Shang, Department of Emergency, Third People’s Hospital of Yunnan Province, No. 292 of Beijing Road, Guandu District, Kun Ming, 650000, People’s Republic of China, Tel +86-13708876606, Fax +8663196549, Email shangyunbo9@sina.com Zheng-Qi Wen, Department of Surgical oncology, The First Affiliated Hospital of Kunming Medical University, Kun Ming, 650000, People’s Republic of China, Tel +86-13888079932, Email 1292333927@qq.comObjective: The objective of this study was to search for, evaluate, and summarize data related to a faster postoperative recovery in patients with colorectal cancer (CRC) based on literature from China as well as internationally. This will serve as an evidence-based foundation for the clinical implementation of enhanced postoperative recovery of gastrointestinal function in patients with CRC.Methods: Based on the hierarchical “ 6S” evidence model, we conducted a systematic search of computerized decision-support systems, guideline websites, as well as domestic and international databases for evidence, guidelines, expert consensus statements, clinical decision-making, best practices, evidence summaries, and systematic reviews of interventions focusing on accelerating gastrointestinal function rehabilitation after CRC surgery. The time limit for the search was from the date of creation of the database to January 2023. Two researchers evaluated the quality of the literature that was included, and we extracted data and summarized the evidence from those publications that fulfilled the quality criteria.Results: The review included a total of 21 publications, comprising 6 guidelines, 6 systematic reviews, 3 expert consensus statements, 4 randomized controlled trials, and 2 evidence summaries. We summarized 51 best evidence findings across five areas: organizational management, preoperative risk assessment, education, intraoperative monitoring, and postoperative management.Conclusion: There is a wide variety and wealth of information available on interventions to promote enhanced postoperative recovery of gastrointestinal function in patients with CRC. The use of evidence is discussed, keeping in mind the practical situation in China.Keywords: colorectal cancer, evidence-based nursing, evidence summary, gastrointestinal function recovery, postoperative

Zixia Wu,1,&ast; Weibo Xia,1,&ast; Liling Ou,1 Ling Zheng,1 Bingying Hou,1 Tonghe Pan,2 Wenjie Sun,1 Leo H Koole,1 Yongqing Shao,2 Lei Qi1 1National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, the People’s Republic of China; 2Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongqing Shao, Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China, Tel +86-574 87862193, Email sunniesyq@163.com Lei Qi, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, the People’s Republic of China, 325027, Tel +86-577-88067973, Email imdoll@163.comPurpose: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.Methods: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.Results: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.Conclusion: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.Keywords: dry eye disease, antioxidant, nitrogen doped graphene quantum dots, Nrf2 antioxidant pathway

Longbin Zheng,1,&ast; Tao Fang,2,&ast; Wei Zhang,1 Xiaojing Zhang,1 Zhiqiang Ren,1 Weimin Qin,1 Wenbo Liang,1 Qing Ma,1 Ning Yin1 1Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, Xinchang County People’s Hospital, Xinchang, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yin, Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing, Jiangsu Province, 211112, People’s Republic of China, Email yinning882000@126.comPurpose: Dexmedetomidine (Dex) is a potent and highly selective α 2-adrenergic receptor agonist. Within an appropriate dose range, Dex can effectively attenuate the surgical stress response, provide intraoperative hemodynamic stability, and improve the patient recovery quality. High-dose Dex can delay patient awakening from anesthesia and increase the incidence of bradycardia. This randomized controlled trial aimed to investigate the effects of low-dose intravenous Dex premedication in patients undergoing laparoscopic cholecystectomy (LC).Material and Methods: In total, 100 patients undergoing LC were equally randomized into Group C (premedication with saline) and Group D (premedication with 0.5 μg/kg Dex). The patients were premedicated with saline or Dex, depending on the group, before anesthesia induction. Following this, anesthesia induction and endotracheal intubation was performed, and anesthesia was maintained during surgery. Following the completion of the surgery, the patients were transferred the post-anesthesia care unit (PACU) and stayed there until they met the PACU discharge criteria. The hemodynamic parameters, consumption of anesthetics, surgical duration, postoperative awakening time, extubation time, postoperative pain, and complications were recorded.Results: No significant differences were observed in the heart rate (HR) and mean arterial pressure (MAP) between the two groups before premedication (P> 0.05). The MAP and HR immediately after endotracheal intubation and immediately after extubation were significantly lower in Group D than in Group C (P< 0.05 for both). The incidence of bradycardia was significantly higher in Group D than in Group C (P< 0.05), while atropine was used in neither group. Propofol and remifentanil consumption was significantly lower in Group D than in Group C (P< 0.05). The postoperative awakening and extubation times were significantly shorter in Group D than in Group C (P< 0.05). The postoperative visual analog scale scores for pain and incidence of nausea, vomiting, and cough were significantly lower in Group D than in Group C (P< 0.05 for all).Conclusion: Our data suggest that premedication with dexmedetomidine (0.5 μg/kg) before general anesthesia induction can effectively attenuate intraoperative stress response and postoperative pain, maintain perioperative hemodynamic stability, and decrease the incidence of adverse events, which might be an effective and safe anesthetic protocol during LC worthy of further clinical application.Keywords: dexmedetomidine, laparoscopic cholecystectomy, general anesthesia, premedication

Lei Zheng,1 Xiaofei Yu,1 Zehai Xia,1 Yehao Guo,2 Yifan Dai1 1Respiratory Department, The Affiliated Hospital of Hangzhou Normal University, Hangzhou City, Zhejiang Province, People’s Republic of China; 2Postgraduate Training Base Department, Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yifan Dai, Department of Respiratory and Critical Care Medicine, Hangzhou Normal University, No. 126, Wenzhou Street, Gongshu District, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86-571-13208000079, Email 181207576@qq.comPurpose: Vitamins and carotenoids are essential in preventing and treating chronic obstructive pulmonary disease (COPD). This study investigated the associations between serum vitamins, carotenoids, and COPD in adults aged ≥ 40 years in the United States.Methods: We selected 3487 participants aged ≥ 40 from the NHANES (2017– 2018) and used demographic analysis, sensitivity tests, and different weighted multivariate regression models to investigate the relationship between serum vitamins, carotenoids, and COPD.Results: Subjects in the highest tertile of serum vitamin C, vitamin E (α-tocopherol), α-carotene, trans-β-carotene, and cis-β-carotene had a 50%, 35%, 51%, 54%, and 51% lower risk of COPD than those in the lowest tertile (P for trend: P=0.0005, < 0.0001, 0.0054, 0.0066, and 0.0049). Unfortunately, no significant correlation was found for serum vitamin D levels.Conclusion: Our analysis of nationally representative data from 3487 participants showed that serum levels of vitamin C, vitamin E (α-tocopherol), α-carotene, and β-carotene were negatively associated with the incidence of COPD in adults over 40 years of age in the US The findings highlighted the importance of antioxidant vitamins and carotenoids in respiratory health, while the data showed no significant correlation between vitamin D (25-OHD) and the incidence of COPD.Keywords: chronic obstructive pulmonary disease, morbidity, serum vitamins, serum carotenoids, anti-oxidation

Jun Zhang, Jie Shao, Xinfang Cao, Yonggang Zhang, Li Zheng Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Jun Zhang, Hangzhou MSK Eye Hospital, No. 384, Fengqi Road, Gongshu District, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 18667046602, Fax +86 85068587, Email zhangjun@mskyk.onaliyun.comPurpose: To investigate the visual acuity and satisfaction of patients after Zhang & Zheng’s corneal laser-enhanced accommodation refraction Q (ZZ-CLEAR-Q) surgery utilizing differential modulation of binocular longitudinal spherical aberration and determine its clinical significance.Patients and Methods: This prospective observational study enrolled a consecutive cohort of patients with presbyopia who underwent ZZ-CLEAR-Q surgery between December 2020 and January 2023. The study assessed visual acuity, distance-corrected defocus curve, satisfaction, Q factor, manifest spherical equivalent, and primary spherical aberration, among others, at 3 months postoperatively. Additionally, the study conducted a binocular comparison to analyze the clinical significance of setting the different longitudinal spherical aberrations.Results: A total of 232 eyes of 116 patients were included. The binocular uncorrected distance visual acuity was 20/20 for all patients. At 3 months postoperatively, the binocular uncorrected near visual acuity was Jaeger 1 for 96% of the patients and Jaeger 2 for 100% of the patients. Furthermore, 93.1% of the patients expressed satisfaction. The monocular distance-corrected defocus curve revealed that the dominant eyes had significantly better visual acuity at 0 D (P< 0.001), while the non-dominant eyes had significantly better visual acuity across various defocus levels except 0 and − 0.50 D (All P< 0.05). At 3 months, there were no significant differences between the expected and achieved manifest spherical equivalents, corneal Q factor values, and ocular primary spherical aberration values of both groups.Conclusion: Patients with presbyopia who underwent ZZ-CLEAR-Q surgery were likely to achieve normal uncorrected visual acuity and be satisfied. The increased depth of field has clinical significance for assisting near vision.Keywords: defocus curve, LASIK, presbyopia, Q factor, spherical aberration

Abstract Arthritogenic alphaviruses are positive-strand RNA viruses that cause debilitating musculoskeletal diseases affecting millions worldwide. A recent discovery identified the four-and-a-half-LIM domain protein 1 splice variant A (FHL1A) as a crucial host factor interacting with the hypervariable domain (HVD) of chikungunya virus (CHIKV) nonstructural protein 3 (nsP3). Here, we show that acute and chronic chikungunya disease in humans correlates with elevated levels of FHL1. We generated FHL1−/− mice, which when infected with CHIKV or o’nyong-nyong virus (ONNV) displayed reduced arthritis and myositis, fewer immune infiltrates, and reduced proinflammatory cytokine/chemokine outputs, compared to infected wild-type (WT) mice. Interestingly, disease signs were comparable in FHL1−/− and WT mice infected with arthritogenic alphaviruses Ross River virus (RRV) or Mayaro virus (MAYV). This aligns with pull-down assay data, which showed the ability of CHIKV and ONNV nsP3 to interact with FHL1, while RRV and MAYV nsP3s did not. We engineered a CHIKV mutant unable to bind FHL1 (CHIKV-ΔFHL1), which was avirulent in vivo. Following inoculation with CHIKV-ΔFHL1, mice were protected from disease upon challenge with CHIKV and ONNV, and viraemia was significantly reduced in RRV- and MAYV-challenged mice. Targeting FHL1-binding as an approach to vaccine design could lead to breakthroughs in mitigating alphaviral disease.

Taoying Li,1,2 Long Zheng,3 Jianjiang Zhang,1 Qiang Chen1 1Law School, Xinjiang University, Urumqi, People’s Republic of China; 2Department of Law, Jiangxi Police College, Nanchang, People’s Republic of China; 3Graduate School and Open Learning College, Cavite State University, Indang, PhilippinesCorrespondence: Jianjiang Zhang, Law School, Xinjiang University, No. 666 Shengli Road, Tianshan District, Urumqi, People’s Republic of China, Tel +8618099276105, Email zjjzqc@163.comPurpose: Reproductive rights represent an intrinsic and pivotal human entitlement, encompassing legal protection for procreation. Essential to this framework is the recognition that single women equally deserve reproductive rights. Although Chinese legislation refrains from overtly disallowing reproductive rights for single women, the interplay of conventional marriage norms and family planning policies has inadvertently tied these rights to marital status, consequently constraining single women’s ability to assert them. The establishment of a robust legal structure to ensure reproductive rights for single women would profoundly contribute to advancing a harmonious evolution of China’s population dynamics.Patients and Methods: We employ meticulous textual scrutiny to analyze comprehensively the stipulations concerning women’s reproductive liberties within the framework of Chinese jurisprudence. Furthermore, we engage in empirical inquiry to enumerate and elucidate the multifarious constraints placed upon the reproductive freedoms of unmarried women in the Chinese context. This endeavor entails a detailed exposition and incisive examination of China’s limitations imposed upon the reproductive rights of single women, encompassing both legal strictures and policy dimensions.Results: The absence of legal endorsement and safeguarding has given rise to substantial impediments to the exercise of reproductive rights among single women in China. Not only do endeavors to assert reproductive rights on behalf of single women encounter intricate challenges in judicial implementation, but they also encounter manifold barriers within national policies. This predicament not only subjects single women to considerable psychological strain but also contradicts the overarching objective of achieving a harmonized population development trajectory in China.Conclusion: China should expedite the development of a legal framework for protecting reproductive rights that includes provisions for supporting single women to have children. This legal apparatus should efficaciously enshrine and shield the reproductive rights of single women, thus playing a pivotal role in advancing a more equitable and well-balanced trajectory of population development.Keywords: single women, reproductive rights, reproductive limitations, psychological, reproductive justice, Chinese law

Haiting Xu,1 Lina Zheng,2 Leilei Wang,1 Huanqin Gao,1 Yanyan Wei,1 Jingxu Chen1 1Psychology and Psychiatric Department, Beijing Hui-Long-Guan Hospital, Peking University, Beijing, People’s Republic of China; 2Psychology and Psychiatric Department, Liaocheng People’s Hospital, Liaocheng, People’s Republic of ChinaCorrespondence: Jingxu Chen, Email chenjx1110@163.comBackground: Inflammation is relevant to the pathophysiology of severe neuropsychiatric disorders, schizophrenia (SCZ) and bipolar disorders (BD). Multiple pathophysiological biomarkers are valuable for the study of inflammatory processes. This study investigated albumin-related biomarkers in SCZ and BD to explore their roles in disease.Methods: A total of 5,577 SCZ, 3442 BD-manic (BD-M) and 1405 BD-depression (BD-D) in acute stage and 5000 health controls (HCs) were enrolled. The differences in these biomarker levels among different groups were compared, and the contributing factors for the occurrence of SCZ, BD, and subgroups of BD were analyzed.Results: Both SCZ and BD exhibit lower prognostic nutritional index (PNI), but higher neutrophil percentage-to-albumin ratio (NPAR) and creatinine–albumin ratio (CRA) compared with HC. Compared with BD-D, BD-M had higher NPAR and platelet-to-albumin ratio (PAR) and lower CRA. In logistic regression, lower prognostic nutritional index (PNI) and higher CRA were associated with both SCZ and BD, while higher NPAR was associated with BD. In the subgroup of BD, higher NPAR, CRA and lower PNI were associated with BD-M; lower PAR, PNI and higher CRA were associated with BD-D.Conclusion: Our study reaffirmed the role of inflammation in the pathophysiology of SCZ and BD. Diagnostic value has been demonstrated in NPAR, PAR, PNI and CRA for BD and SCZ.Keywords: schizophrenia, bipolar disorder, inflammation, albumin, neutrophil percentage-to-albumin ratio, platelet to albumin ratio, prognostic nutritional index