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Hui Peng,1,2,* Qian Jiang,1,* Wenhao Mao,1,3,* Zhonglan Hu,1,* Qi Wang,4 Zhuo Yu,1 Li Zhang,1 Xinyan Wang,5 Chunbo Zhuang,1 Jia Mai,6 Zhiyuan Wang,7 Ting Sun1 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Center for Clinical Laboratory, General Hospital of the Yangtze River Shipping Wuhan Brain Hospital, Wuhan, Hubei, 430010, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 4Department of Pharmacy, Kaifeng Hospital of Traditional Chinese Medicine, Kaifeng, 475000, People’s Republic of China; 5Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 6Department of Laboratory Medicine, West China Second Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 7Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ting Sun, Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Email sunting@zzu.edu.cn Zhiyuan Wang, Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China, Email wangzhiy@zzu.edu.cnBackground: The hypoxic tumor microenvironment and single mechanisms severely limit the photodynamic therapy (PDT) efficiency of covalent organic framework (COF) nanoparticles in cancer treatment.Purpose: Here, we propose an iron-loaded, hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000)-modified hollow covalent organic framework (HCOF), Fe-HCOF-PEG2000, for use in hypoxic PDT and ferroptosis therapy owing to its type I and II photodynamic ability and iron nanoparticle loading property.Results: Fe-HCOF-PEG2000 nanoparticles (Fe-HCOFs-PEG2000) with semiconducting polymers and microporous skeletons allow efficient photophysical properties. Moreover, the iron nanoparticles on Fe-HCOF-PEG2000 caused ferroptosis and further enhanced tumor elimination under normoxic and hypoxic conditions. DSPE-PEG2000 endowed Fe-HCOF-PEG2000 with hydrophilicity, allowing it to circulate and accumulate in organs rich in blood supply, especially tumors. 808 nm NIR activated Fe-HCOF-PEG2000 aggregated in tumors and significantly inhibited tumor growth under hypoxia.Conclusion: To our knowledge, Fe-HCOF-PEG2000 is the leading combination of type I/II PDT and ferroptosis. The strong antitumor effects of this nanomaterial suggest prospects for clinical translation as a tumor nanotherapy drug. Keywords: HCOFs, PDT, ROS, hypoxia, ferroptosis, cancer cells

Juanzhi Yang,1 Huanxia Qu,2 Qi Liu,1 Yixing Wang,1 Jiaxin Cao,1 Feng Jiang,3 Qian Wang,4 Jin Shu1 1Department of Pediatrics, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 2Department of Blood Transfusion, Zhenjiang First People’s Hospital, Zhenjiang, People’s Republic of China; 3Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 4Department of Pediatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Jin Shu, Department of Pediatrics, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212008, People’s Republic of China, Email zjshujin@163.com Feng Jiang, Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China, Email dxyjiang@163.comBackground: Premature infants, defined as those born before 37 weeks of gestation, face numerous health challenges due to their underdeveloped systems. One critical aspect of their health is the gut microbiota, which plays a vital role in their immune function and overall development. This study provides a comprehensive bibliometric analysis of research trends, influential contributors, and evolving themes in the study of gut microbiota in premature infants over the past two decades.Methods: We conducted a bibliometric analysis using the Web of Science Core Collection database, covering publications from January 1, 2004, to June 17, 2024. We employed VOSviewer, the R package “bibliometrix”, and Citespace for data visualization and analysis, focusing on co-authorship, co-citation, and keyword co-occurrence networks.Results: The temporal analysis revealed a significant increase in research output on gut microbiota in premature infants, particularly in the last decade. Early research primarily focused on characterizing the gut microbiota of premature infants, identifying less diversity and a higher prevalence of pathogenic bacteria compared to full-term infants. Key research themes identified include probiotics, necrotizing enterocolitis (NEC), and breastfeeding. Probiotic studies highlighted the potential of strains like Bifidobacterium and Lactobacillus in reducing NEC and sepsis incidences. Breastfeeding research consistently showed the benefits of human milk in fostering a healthier gut microbiota profile. Co-authorship and co-citation analyses identified key contributors and influential studies, emphasizing strong international collaborations, particularly among researchers from the United States, China, and European countries.Conclusion: This bibliometric analysis underscores the growing recognition of the gut microbiota’s crucial role in the health of premature infants. The field has seen significant advancements, particularly in understanding how interventions like probiotics and breastfeeding can modulate gut microbiota to improve health outcomes. Continued research and international collaboration are essential to further unravel the complexities of gut microbiota in premature infants and develop effective therapeutic strategies.Keywords: premature infants, gut microbiota, web of science, bibliometric analysis

Qian Wang,1,2,&ast; Guimin Huang,3,&ast; Ruikun Wang,4 Zhilong Cao,5 Jieqiong Liang,1 Mengyao Li,1 Qinglong Gu1,2 1Department of Otolaryngology-Head and Neck Surgery, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Beijing, People’s Republic of China; 3Child Health Big Data Research Center, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 4Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, People’s Republic of China; 5School of Software, Beihang University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinglong Gu, Department of Otolaryngology-Head and Neck Surgery, Capital Institute of Pediatrics, No. 2 Yabao Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86-13146836613, Email gql71@163.comPurpose: This study investigates the prevalence, risk factors, and clinical characteristics of positional obstructive sleep apnea (POSA) among pediatric patients diagnosed with obstructive sleep apnea (OSA).Patients and Methods: A total of 1,236 children aged 0 to 17 years who underwent nocturnal polysomnography (PSG) and completed the Sleep Questionnaire were included. After excluding those with an AHI < 1, neurological or muscular disorders, or insufficient sleep time in specific positions, 908 patients remained: 158 with POSA and 750 with non-positional OSA (NPOSA). Propensity score matching (PSM) was applied at a 1:2 ratio, resulting in a final sample of 153 POSA and 306 NPOSA patients. Data analyses were performed using R software (version 4.2.3).Results: The prevalence of POSA was 12.8%. After PSM, patients with POSA had a lower overall AHI (8.66 vs 10.30), REM-AHI (14.30 vs 17.40), and NREM-AHI (7.43 vs 8.77) compared to those with NPOSA. POSA patients also had a shorter total sleep time (411 vs 427 minutes), spent less time in the supine position (168 vs 225 minutes), and more time in non-supine positions (241 vs 202 minutes) than NPOSA patients. Additionally, while the supine AHI was higher in POSA patients (15.60 vs 10.30), the non-supine AHI was lower (5.00 vs 11.00) compared to NPOSA patients. The minimum oxygen saturation was slightly higher in POSA patients (0.88 vs 0.87). All differences were statistically significant (P < 0.05). Risk factors for POSA included mild OSA, allergic rhinitis, non-allergic rhinitis, and obesity.Conclusion: The prevalence of POSA in children is lower than in adults, and its severity is less than that of NPOSA. Compared to NPOSA patients, POSA patients had significantly higher AHI during supine sleep and lower AHI during non-supine sleep. POSA patients also spent more time in non-supine positions, suggesting that avoiding supine sleep may help reduce apnea events. These findings highlight the importance of monitoring and managing sleep posture in POSA patients.Keywords: obstructive sleep apnea, pediatric patients, risk factors, polysomnography, sleep position, sleep-disordered breathing

Yanli Guo,1,&ast; Dinggui Huang,2,&ast; Jingxia Sun,3,&ast; Zhenwei Zhai,3,&ast; Hewei Xiao,4,&ast; Weiguang Hao,5 Qiu Wang,3 Jianhao Huang,3 Miaomiao Jin,1 Wensheng Lu3,&ast; 1Department of Endocrinology, Heji Affiliated Hospital of Changzhi Medical College, Changzhi, Shanxi, 046011, People’s Republic of China; 2Project Fund Supervision Center, Health Commission of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 4Scientific Research Cooperation Department, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 5Department of Endocrinology, Tongde Hospital, Yuncheng, Shanxi, 044000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email Lwswxqz@163.comAim: This study aimed to assess the efficacy of antithyroid drugs (ATDs) and radioactive iodine-131 (RAI) therapies in reducing the risk of major adverse cardiovascular events (MACEs) and all-cause mortality in patients with hyperthyroidism complicated with type 2 diabetes mellitus (T2DM).Methods: Between January 2013 and December 2021, 540 subjects were included in the analysis. All participants were followed up for 9 years, with a median of 54 months (2451 person-years). The subjects were categorized into two groups: the ATDs group (n = 414) and the RAI group (n = 126). According to the free triiodothyronine (FT3) tertiles, the patients receiving RAI were further grouped as follows: low-level (≤ 4.70 pmol/L, n = 42), moderate-level (4.70– 12.98 pmol/L, n = 42), and high-level (≥ 12.98 pmol/L, n = 42). The efficacy of ATDs and RAI therapies in reducing the risk of MACEs and all-cause mortality was assessed.Results: Of the 540 participants, 163 experienced MACEs (30.19%), 25 (15.34%) of whom died. Multivariate Cox regression analyses revealed that RAI was associated with a 38.5% lower risk of MACEs (P = 0.016) and a 77.1% lower risk of all-cause mortality (P = 0.046). Stratified analyses indicated that RAI had a protective effect on MACEs in patients aged ≥ 60 years (P = 0.001, P for interaction = 0.031) and patients with a duration of diabetes mellitus ≥ 6 years (P = 0.013, P for interaction = 0.002). Kaplan‒Meier analysis revealed a lower cumulative incidence of MACEs and all-cause mortality in the RAI group (log-rank, all P < 0.05). Moreover, the ROC curve suggested an optimal FT3 cut-off value of 5.4 pmol/mL for MACE (P < 0.001).Conclusion: Our findings suggested that RAI therapy effectively reduced the risk of MACEs and all-cause mortality in elderly patients with hyperthyroidism combined with T2DM.Keywords: hyperthyroidism, type 2 diabetes mellitus, radioactive iodine-131, major adverse cardiovascular events, all-cause mortality

Yichen Wang,1,&ast; Yibo Zhang,1,&ast; Qun Wang,1 Wenhui Li,1 Dake Shi,1 Yumin Xu1,2 1Department of Hospital Infection Management, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumin Xu, Email xym121@163.comPurpose: Hospital-acquired infections (HAIs) caused by multidrug-resistant organisms (MDROs) pose a significant challenge to healthcare systems. The present study aimed to evaluate the impact of the infection policy to COVID-19 on the incidence of HAIs caused by MDROs.Methods: We conducted an eight-years retrospective analysis at a hospital in Shanghai, China. Bloodstream, sputum, and urinary tract cultures of MDROs obtained 48h after admission were collected monthly from January 2016 to Dec 2023. Occupied bed days (OBDs) were used to generate monthly HAI incidences per 10,000 OBDs. The study period was divided into pre-control, in-control, and post-control cohorts, in January 2020 and January 2022. The incidence was compared using interrupted time-series regression.Results: In total, 6763 MDRO cultures were identified, comprising 1058 bloodstream, 4581 sputum, and 1124 urine cultures derived from 4549 patients. The incidence rates of all HAIs were 8.68 per 10,000 OBDs in the pre-control cohort, 9.76 per 10,000 OBDs in the in-control cohort and 12.58 per 10,000 OBDs in the post-control cohorts, respectively. A downward trend in the incidence of HAI was observed in the post-control cohort (p< 0.05).Conclusion: This study demonstrates that while the COVID-19 pandemic poses a significant challenge to infection control within hospitals, it provides a unique opportunity to enhance infection control measures and evaluate their effectiveness. In addition, these findings highlight the need for more targeted prevention and control strategies against different pathogens in future epidemics.Keywords: hospital required infection, multidrug-resistant organism, infection control, policy, Covid-19, surveillance

Yang Xie, Xiangyang Sun, Fubo Xie, Wencheng Jian, Qingliang Wang, Xiaochen Ma, Caixia Li, Kai Zhang Department of Radiology, Qilu Hospital of Shandong University, Shandong, People’s Republic of ChinaCorrespondence: Kai Zhang, Department of Radiology, Qilu Hospital of Shandong University, Shandong, People’s Republic of China, Tel +8618560081593, Email fifa6107@126.comPurpose: To examine the relationship between lactate dehydrogenase (LDH) levels and soluble programmed cell death-ligand 1 (sPD-L1) levels in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE).Methods: A total of 83 hCC patients participated in this study. Patients were categorized into subgroups based on their alpha-fetoprotein (AFP) levels, presence or absence of extrahepatic metastasis, vascular invasion, Barcelona Clinic Liver Cancer (BCLC) stage, tumor response, tumor size, and number LDH and sPD-L1 levels were compared before and after TACE (3, 7, and 30 days post-TACE).Results: LDH and sPD-L1 levels were significantly higher at 3 and 7 days post-TACE than at baseline. Positive correlations were observed between changes in LDH levels and sPD-L1 levels at 3 and 7 days post-TACE. LDH levels were higher in patients with elevated AFP compared to those in the normal AFP group at 3 and 7 days post-TACE, in the stable disease (SD) group compared to complete response (CR) and partial response (PR) groups at 7 days post-TACE, and in those with tumor > 5 cm compared with those with tumor ≤ 5 cm at 3 and 7 days after TACE (all P < 0.05). sPD-L1 levels were higher in patients with vascular invasion than those without vascular invasion at 3 and 7 days post-TACE, in the SD group compared to CR and PR groups at 3 and 7 days post-TACE, and in those with tumor > 5 cm compared to those with tumor < 5 cm at 3 and 7 days after TACE (all P < 0.05).Conclusion: A positive correlation was found between LDH expression and sPD-L1 levels, suggesting LDH as a potential biomarker for assessing immune status in HCC patients following TACE.Keywords: hepatocellular carcinoma, immunotherapy, lactate dehydrogenase, soluble programmed cell death ligand-1, transarterial chemoembolization

Tianyu Chen,1 Jing Xue,2 Qian Wang2 1School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2The Institute of Dermatology and Venereology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of ChinaCorrespondence: Jing Xue; Qian Wang, The Institute of Dermatology and Venereology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, Western 2nd Section, 1st Ring Road, Chengdu, Sichuan Province, 610072, People’s Republic of China, Email xuejings@sina.com; wqian1111@126.comAbstract: Tranexamic acid (TXA), a synthetic lysine analog, is a commonly used antifibrinolytic and procoagulant agent. Based on its good hemostatic efficacy, it is mainly used clinically for bleeding in trauma, various types of surgical and dental procedures and prevention of bleeding in patients with hemophilia. In recent years, studies have shown that TXA has the effects of anti-melanogenesis, anti-inflammation, anti-angiogenesis and promotes the recovery of the skin barrier, so it has been tried to be used as a treatment for hyperpigmentation and telangiectatic diseases. Oral, topical, intradermal injections and microneedling are all commonly used modes of administration. TXA for melasma is the most studied and has achieved indications in some countries, whereas it is still an off-label drug for many other dyschromia. We review the clinical use of TXA in hyperpigmentation and telangiectatic disorders other than melasma, such as post-inflammatory hyperpigmentation, Riehl’s melanosis, rosacea, and post-acne erythema, to provide more evidence for the use of TXA in these disorders, and to provide safer and more cost-effective alternatives for the treatment of these diseases.Keywords: tranexamic acid, hyperpigmentation, erythema, telangiectatic disorder

Ben Wang,1,2 Peilin Cheng,2 Bingjie Jin,2 Ying Jiang,2 Qingcai Wang,1 Hongwei Xu2 1Department of Gastroenterology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, People’s Republic of China; 2Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Hongwei Xu, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Email xuhongwei@sdfmu.edu.cnBackground & Aims: The metabolic pathways of tryptophan (TRP) have been implicated in the pathophysiology of irritable bowel syndrome (IBS), positing that the strategic modulation of TRP consumption may exert regulatory effects on serotonin levels, consequently altering the clinical manifestation of IBS. This systematic review was meticulously orchestrated to evaluate the effect of TRP restriction on IBS.Methods: A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and Embase databases was conducted. Controlled trials that compared the efficacy of TRP restriction in IBS patients were scrutinized. The primary outcomes were gastrointestinal symptoms, quality of life, and pain, whereas the secondary outcomes included anxiety, mood, and safety. The risk of bias was meticulously assessed according to the guidelines recommended by the Cochrane Collaboration.Results: A total of five trials, enrolling 135 participants, were incorporated into the qualitative synthesis. Low-TRP intake attenuated gastrointestinal discomfort and enhanced psychological well-being in IBS patients, while the effects of acute TRP depletion were controversial. Safety data from one randomized controlled trial reported no occurrence of adverse events.Conclusion: This systematic review suggests that moderating, rather than depleting, TRP intake may potentially be a feasible and safe adjunctive treatment for patients with IBS. Future research incorporating a high-quality study design and consensus on clinical outcome measurements for IBS is warranted.Keywords: irritable bowel syndrome, reduced tryptophan diet, acute tryptophan depletion, systematic review

Xugang Tang,1 Qiang Wang,1 Shuang Li,1 Xiuchuan Li,1 Qian Xin,2 Yongjian Yang1 1Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China; 2Department of Cardiology, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yongjian Yang, Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China, Tel/Fax +86 28 8657 1255, Email yyjcdzyy@sina.comPurpose: The Athens Insomnia Scale (AIS) is a widely used and authorized questionnaire for evaluating insomnia symptoms. However, its reliability and validity at high altitudes are uncertain. Therefore, this study aimed to confirm the validity and reliability of AIS during a 3658 m altitude exposure.Patients and Methods: A total of 387 young Chinese males were enlisted in the acute high-altitude exposure group. They flew for about two hours, climbing from 400 m to 3658 m. The high-altitude-acclimated group consisted of 86 young Chinese men who had lived at least six months at 3658 m altitude. The sleep quality of the acute high-altitude exposure group was evaluated using the AIS before the ascent and after exposure to 3658 m for 24 hours, and one week. The sleep quality of the high-altitude-acclimated group was also assessed. The AIS’s internal consistency, reliability, and validity were evaluated.Results: The respondents’ quality of sleep significantly decreased after being exposed to 3658 m as opposed to 400 m. Two factors comprised the AIS, according to an exploratory factor analysis: “sleep problem” (items 1– 5) and “daytime dysfunction” (items 6– 8). The Cronbach’s α internal consistency coefficients exceeded 0.8, and the corrected item-total correlations were all greater than 0.5 when the subjects were exposed to 3658 m. The model fit index was well within the criterion. The average variance extracted and composite reliability were all higher than 0.5 and 0.7, respectively. The interclass correlation coefficient was deemed “fair to good” at 0.482, which is greater than the 0.4 threshold. The AIS has satisfactory discriminant validity, as shown by the Fornell-Larcker criterion and cross-loading results. The daytime dysfunction R-square values (> 0.33) show that the frameworks have considerable predictive accuracy.Conclusion: The AIS exhibits strong consistency, reliability, and validity. The AIS’s features and simplicity make it an essential psychometric tool for high-altitude sleep research.Keywords: athens insomnia scale, high altitude, internal consistency, reliability, sleep, validity

Xueen Liu,1 Fang Pan,1 Qingmei Wang,1 Shuai Wang,1 Jiale Zhang2 1Department of Nursing, Beijing Hepingli Hospital, Beijing, People’s Republic of China; 2Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Jiale Zhang, Email zhang_tcm@163.comAbstract: Myofascial as a holistic structure emphasizes a holistic approach to intervention and treatment of fascial-related disorders such as neck pain (NP), low back pain (LBP), and knee pain. There are currently adverse effects of medication for diseases related to myofascial. Traditional Chinese rehabilitation exercise (TCRE) is a practical approach to traditional Chinese medicine and is a valuable option for intervening in myofascial-related pain. This article found some research evidence for Baduanjin, Wuqinxi, and Yijinjing in clinical studies of myofascial chain-related pain. The article summarizes the current evidence and finds that TCRE can enhance limb movement function through breathing and slow movements, increase joint movement and flexibility, and reduce joint pathology and stress-induced pain. As for future directions, focus on TCRE in improving the health of older adults and treating long-COVID syndrome, and integrate robotic and TCRE training to frame safe and effective exercise models. Relevant studies have already been registered in the Clinical Trials Registry, and some clinical study protocols have been published. TCRE can be an alternative nonpharmacological rehabilitation therapy to alleviate chronic rheumatic pain symptoms and augment public health management.Keywords: traditional Chinese rehabilitation exercise, pain, myofascial chain, rehabilitation

Kehua Jiang,1 Qing Wang,1 Xiao-Long Chen,1 Xiaodong Wang,1 Xiaoya Gu,1 Shuangshuang Feng,1 Jian Wu,2 Haojie Shang,2 Xiaozhuo Ba,2 Yanlong Zhang,1 Kun Tang2 1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 2Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Yanlong Zhang, Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China, Email ylzhang3030@163.com Kun Tang, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Qiaokou District, Wuhan, 430030, People’s Republic of China, Email tangsk1990@163.comAbstract: Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.Keywords: indoleamine 2, 3-dioxygenase 1, IDO1, IDO1 inhibitors, nanodrugs, nanodelivery, cancer immunotherapy, combination therapy

Zaifeng Si,1,2,&ast; Shengmei Zhao,3,&ast; Yingying Hao,3 Qian Wang,3 Yanfa Zhong,2 Yue Liu,3 Ran Chen,3 Yan Jin,3 Zhiming Lu1,3 1Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Clinical Laboratory, Dezhou Municipal Hospital of Traditional Chinese Medicine, Dezhou, Shandong, People’s Republic of China; 3Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Jin; Zhiming Lu, Email sdjinyan@163.com; luzhiming@sdu.edu.cnBackground: Enterobacter cloacae complex (ECC), which includes major nosocomial pathogens, causes urinary, respiratory, and bloodstream infections in humans, for which colistin is one of the last-line drugs.Objective: This study aimed to analyse the epidemiology and resistance mechanisms of colistin-resistant Enterobacter cloacae complex (ECC) strains isolated from Shandong, China.Methods: Two hundred non-repetitive ECC strains were collected from a tertiary hospital in Shandong Province, China, from June 2020 to June 2022. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of the colistin-resistant ECC strains. The nucleotide sequences of heat shock protein (hsp60) were analyzed by using BLAST search to classify ECC. The gene expression levels of ramA, soxS, acrA, acrB, phoP, and phoQ were assessed using RT-qPCR. MALDI-TOF MS was used to analyse the modification of lipid A.Results: Twenty-three colistin-resistant strains were detected among the 200 ECC clinical strains (11.5%). The hsp60 cluster analysis revealed that 20 of the 23 ECC strains belonged to heterogeneous resistance clusters. Variants of mgrB, phoPQ, and pmrAB, particularly phoQ and pmrB, were detected in the 23 ECC strains. The soxS and acrA genes were significantly overexpressed in all 23 colistin-resistant ECC strains (P < 0.05). Additionally, all 23 ECC strains contained modified lipid A related to colistin resistance, which showed five ion peaks at m/z 1876, 1920, 1955, 2114, and 2158. Among the 23 ECC strains, 6 strains possessed a phosphoethanolamine (pETN) moiety, 16 strains possessed a 4-amino-4-deoxy-L-arabinose (−L-Ara4N) moiety, and one strain had both pETN and −L-Ara4N moieties.Conclusion: This study suggests that diverse colistin resistance existed in ECC, including unknown resistance mechanisms, exist in ECC. Mechanistic investigations of colistin resistance are warranted to optimise colistin use in clinical settings and minimise the emergence of resistance.Keywords: Enterobacter cloacae complex, ECC, epidemiology, colistin, resistance mechanism

Ting Dai,&ast; Qimeihui Wang,&ast; Lingyu Zhu, Qiang Luo, Jiayu Yang, Xia Meng, Hui Wang, Zhixia Sun Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Wang; Zhixia Sun, Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China, Email whui66@jlu.edu.cn; sunzx@jlu.edu.cnIntroduction: The effective accumulation of nanoparticles (NPs) in the tumour area is an important goals of current nanotechnology research, and a targeted nanoplatform is an effective solution. So we designed a multifunctional sound-sensitive targeted NP that combines a sonosensitizer to enable precisely targeted, deep-penetration sonodynamic therapy (SDT) in combination with multimodal imaging for the diagnosis and monitoring of renal cell carcinoma (RCC).Methods: ZnPP@PP NPs (ZnPP@PLGA- PFP NPs) were prepared via a double emulsion method, and G250 was covalently attached to the NPs shell via the carbon diimide method. Physicochemical property tests were conducted on the ZnPP@G-PP NPs, including tests of particle size, potential distribution, encapsulation efficiency and drug loading capability. We assessed the targeting ability, the production of reactive oxygen species (ROS) and permeability of the NPs in vitro. Moreover, we evaluated the nanoparticle’s multimodal imaging capabilities and therapeutic ability against RCC, both in vitro and in vivo.Results: The Znpp@G-PP NPs were successfully constructed, and their general properties showed uniform particle size, negative potential and good stability. The nanoparticles were successfully loaded with ZnPP and connected with G250, showing tumor-specific targeting ability. Under LIFU irradiation, the nanoparticles produced 1O2 by SDT. For RCC, PA/US multi-modal imaging of Znpp@G-PP NPs provide diagnostic information and monitor therapies in real time in 786-O RCC xenografts, with good biocompatibility. With the UTMD, nanoparticles can be effectively targeted into the tumor cells and penetrate into the tumor interior, significantly improving the SDT effect. Experiments in vitro and in vivo showed that the combination of the nanoparticles and LIFU could suppress the tumor, and the therapeutic effect was confirmed by immunohistochemistry.Conclusion: ZnPP@G-PP NPs provide a promising theranostic strategy for RCC and a platform for further research on improving the efficacy of diagnosis and treatment.Keywords: targeted therapy, deep-penetration, sonodynamic therapy, multimodal imaging

Xiaoyan Huang,1,2 Xiangrong Zhao,1,2 Yaping Li,1,2 Yangmeng Feng,1,2 Guoan Zhang,3 Qiyu Wang,4 Cuixiang Xu1,2 1Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 2Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 3Department of Cardiovascular Surgery, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 4Department of Graduate School, Yan’an University, Yan’an, People’s Republic of ChinaCorrespondence: Cuixiang Xu, Email xucuixiang1129@163.comBackground: Dilated cardiomyopathy (DCM) is the second leading cause of heart failure, with intricate pathophysiological underpinnings. In order to shed fresh light on the mechanistic research of DCM, we combined bulk RNA-seq and single-cell RNA-seq (scRNA-seq) data to examine significant cells and genes implicated in the disease.Methods: This analysis employed publicly accessible bulk RNA-seq and scRNA-seq DCM datasets. The scRNA-seq data underwent normalization, principal component, and t-distribution stochastic neighbor embedding analysis. Cell-to-cell communication networks and activity analysis were conducted using CellChat. Utilizing enrichment analysis, the marker genes’ role in the active cells was evaluated. After screening by limma software and weighted gene co-expression network analysis, the differentially expressed genes (DEGs) served as hub genes. Furthermore, these hub genes were subjected to immunological studies, transcription factor expression, and gene set enrichment. Lastly, the expression of the four hub genes and their connection to DCM were verified using the rat models.Results: Fibroblasts and monocytes were chosen as hub cells from among the eight identified cell clusters; their marker genes intersected with DEGs to yield six hub genes. In addition, the six hub genes and the essential module genes intersected to yield four essential genes (ASPN, SFRP4, LUM, and FRZB) that were connected to the Wnt signaling pathway and highly expressed in fibroblast. The four hub DEGs had an expression pattern in the DCM rat model experiment results that was in line with the findings of the bioinformatics study. Additionally, there was a strong correlation between decreased cardiac function and the up-regulation of ASPN, SFRP4, LUM, and FRZB.Conclusion: Ultimately, bulk RNA-seq and scRNA-seq data identified fibroblasts and monocytes as the main cell types implicated in DCM. The highly expressed genes ASPN, FRZB, LUM, and SFRP4 in fibroblasts may aid in the mechanistic investigation of DCM.Keywords: dilated cardiomyopathy, single cell RNA-seq, bulk RNA-seq, weighted gene co-expression network analysis, wnt signaling pathway, fibroblasts

Qi Wang,1,2,&ast; Wen-Na Li,3,&ast; Wuxiyar Otkur,4 Yu Cui,1 Hui-Sheng Chen1,2 1Department of Neurology, General Hospital of Northern Theater Command, Shenyang, 110016, People’s Republic of China; 2Dalian Medical University, Dalian, People’s Republic of China; 3Department of Neurology, Tangshan Central Hospital, Tangshan, People’s Republic of China; 4School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui-Sheng Chen, Department of Neurology, General Hospital of Northern Theater Command, 83 Wen Hua Road, Shenyang, 110016, People’s Republic of China, Tel +86 024 28897511, Email chszh@aliyun.comBackground: We conducted a post-hoc analysis of the RICAMIS trial to investigate the effect of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) on the efficacy of remote ischemic conditioning treatment.Methods: In this post-hoc analysis, NLR, PLR, and SII were measured before randomization. Patients were divided into two groups based on their cut-off values: high vs low NLR, high vs low PLR, and high vs low SII groups. Each group was further subdivided into RIC and control groups. The primary endpoint was a poor outcome (mRS 2– 6 at 90 days). Differences in the primary endpoint between the RIC and control subgroups were compared, and the interactions of treatment assignment with NLR, PLR, and SII were evaluated.Results: A total of 1679 patients were included in the final analysis. Compared with the control group, RIC significantly improved functional outcomes regardless of the inflammation status. The improved probability of poor outcome in the RIC vs control group was numerically greater in the high vs low inflammation group (NLR, 7.8% vs 5.1%; PLR, 7% vs 6.5%; SII, 9% vs 5.3%). However, we did not find an interaction effect of an intervention (RIC or control) with different NLR, PLR, or SII on clinical outcomes (P > 0.05). In addition, the NLR and SII were independently associated with functional outcomes in all patients, regardless of whether they received RIC.Conclusion: Inflammation may not affect the efficacy of RIC in patients with acute moderate ischemic stroke, although a lower probability of poor outcome at 90 days was identified in patients with a high vs low inflammatory status.Keywords: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, remote ischemic conditioning, ischemic stroke

Haotian Chen, Juan Zhi, Lei Wang, Zibin Jin, Jin Xu, Fei Xing, Chao Wen, Qianyu Wang, Chunmei Chen, Weiou Li, Ermeng Xu, Jie An, Lingxin Wei Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lingxin Wei, Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, 100144, People’s Republic of China, Tel +86 010 85557917, Email weilx3934@sina.comPurpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15– 0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction.Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62– 0.79), anxiety level (OR, 0.77; 95% CI, 0.62– 0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56– 0.98) were identified as significant predictors associated with patient satisfaction.Conclusion: A subanesthetic dose of esketamine (0.15– 0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Clinical Trial Registration: ChiCTR2400080363.Keywords: esketamine, sedation, analgesia, satisfaction, liposuction

Yuan Cheng,1 Qingqing Wang,2 Chuanxi Sun,3 Di Cui1 1Fuyang Medical College, Fuyang Normal University, Fuyang, Anhui, People’s Republic of China; 2Department of Neurology, The Affiliated Fuyang People’s Hospital of Anhui Medical University, Fuyang, Anhui, People’s Republic of China; 3Clinical Laboratory, The Second Hospital Affiliated to Fuyang Normal University, Fuyang, Anhui, People’s Republic of ChinaCorrespondence: Di Cui, Fuyang Medical College, Fuyang Normal University, Fuyang, Anhui, 236000, People’s Republic of China, Email fycuidi1990@163.comBackground: The atherogenic index of plasma (AIP) is a biomarker for coronary heart disease, atherosclerosis, and metabolic syndrome. However, the mechanism of its action in the acute phase of acute pontine infarction remains unclear. This study investigated the association between the AIP and the short-term prognosis of acute pontine infarction.Methods: Clinical and laboratory index data of patients admitted to the hospital for acute pontine infarction were continuously included, and these patients were followed up for 90 days after disease onset. The modified Rankin Scale (mRS) was used to evaluate the 90-day clinical outcomes of the patients, and an mRS score ≥ 3 was used to define adverse functional outcomes. Univariate analysis was used to detect differences in the indicators between the two groups. Patients were then divided into three groups according to the quantile of the AIP (T1: AIP ≤ 0.029; T2, 0.029 < AIP ≤ 0.248; T3, AIP > 0.248), and a binary logistic regression model was used to assess risk factors for prognosis shortly after acute pontine infarction.Results: A total of 260 patients with acute pontine infarction (mean age=64.5± 11.8 years) were included during the study period, and 68 (26.2%) patients had a poor 90-day prognosis. The AIP in the poor 90-day prognosis group was significantly greater (P < 0.05) than that in the good 90-day prognosis group. The multivariate logistic regression analysis revealed that the AIP (OR=9.829; 95% CI: 2.837– 34.051; p < 0.001), baseline NIHSS score (OR=1.663; 95% CI: 1.400– 1.975; p < 0.001) and infarct volume (OR=1.762; 95% CI: 1.013– 3.062; p=0.045) were significantly associated with poor 90-day prognosis in patients with acute pontine infarction.Conclusion: In patients with acute pontine infarction, the AIP may serve as an important biological marker of poor clinical prognosis and is independently associated with poor 90-day prognosis.Keywords: lipid metabolism, atherogenic index of plasma, pontine infarction, risk factors, outcome

Jing Ren,1,&ast; Jiahua Zhou,2,&ast; Qinhui Wang,1,&ast; Linna Liu,1 Wei Liu,3 Shan Wang,4 Yao Zheng,1 Li Luo,1 Qi Yang1 1Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Orthopedics, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Pharmacy, New York University Langone Hospital – Long Island, Mineola, NY, USA&ast;These authors contributed equally to this workCorrespondence: Qi Yang; Li Luo, Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China, Tel +86 15829673096, Fax +86 029-84777154, Email 376230719@qq.com; luolixueshu@163.comAbstract: Aseptic abscess (AA) syndrome is a rare inflammatory disorder often associated with inflammatory bowel disease (IBD). Cases of IBD-associated AA have been reported in Japan, India, and Canada, but rarely in China. Herein, we present the case of a Chinese patient with IBD-associated AAs and review the literature on AA with underlying IBD. We report the case of a 48-year-old male patient with multiple AAs on his left hand and lungs who was successfully treated with prednisone. He had undergone cutaneous abscess incision and drainage twice in the previous 2 years. The patient presented to our hospital with ulcerative colitis and pain in the dorsum of the left hand. Pus from his hand and blood cultures revealed sterile cutaneous abscesses. Chest computed tomography examination during hospitalization revealed a lung abscess. The AA was unresponsive to cefotiam or cefoperazone-sulbactam. The patient’s left hand and lung conditions did not improve until prednisone was administered. The patient was followed up as an outpatient for 3 months and recovered without any clinical symptoms. We retrieved 17 cases of IBD-associated AA from the literature. None of the patients showed evidence of infection and failed antibiotic treatment, and all improved with corticosteroid use. AA may be an extra-intestinal manifestation of IBD. Effective medications include corticosteroids and immunosuppressive agents. This case may increase the awareness of AA and aid in early identification.Keywords: aseptic abscess, inflammatory bowel disease, ulcerative colitis, extra-intestinal manifestation

Qingyang Liu,1,&ast; Jian Wang,2,&ast; Chunhui Ding,3 Ying Chu,1 Fengying Jiang,1 Yunxia Hu,4 Haifeng Li,2 Qiubo Wang1 1Department of Clinical Laboratory, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People’s Republic of China; 3Department of Pharmacy, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People’s Republic of China; 4Department of Rheumatology and Immunology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiubo Wang, Department of Clinical Laboratory, Wuxi Ninth People’s Hospital Affiliated to Soochow University, No. 999 Liang Xi Road, Binhu District, Wuxi, Jiangsu, 214000, People’s Republic of China, Email wangqiubo2020@suda.edu.cn Haifeng Li, Department of orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, No. 999 Liang Xi Road, Binhu District, Wuxi, Jiangsu, 214000, People’s Republic of China, Email lihaifeng2008@suda.edu.cnPurpose: Sinomenine (SIN) is commonly used in Traditional Chinese Medicine (TCM) as a respected remedy for rheumatoid arthritis (RA). Nevertheless, the therapeutic mechanism of SIN in RA remains incompletely understood. This study aimed to delve into the molecular mechanism of SIN in the treatment of RA.Methods: The potential targets of SIN were predicted using the TCMSP server, STITCH database, and SwissTarget Prediction. Differentially expressed genes (DEGs) in RA were obtained from the GEO database. Enrichment analyses and molecular docking were conducted to explore the potential mechanism of SIN in the treatment of RA. In vitro and in vivo studies were conducted to validate the intervention effects of SIN on rheumatoid arthritis, as determined through network pharmacology analyses.Results: A total of 39 potential targets associated with the therapeutic effects of SIN in RA were identified. Enrichment analysis revealed that these potential targets are primarily enriched in PI3K-Akt signaling pathway, and the molecular docking suggests that SIN may act on specific proteins in the pathway. Experimental results have shown that exposure to SIN inhibits cytokine secretion, promotes apoptosis, reduces metastasis and invasion, and blocks the activation of the PI3K-Akt signaling pathway in RA fibroblast-like synoviocytes (RA-FLS). Moreover, SIN treatment alleviated arthritis-related symptoms and regulated the differentiation of CD4+ T cells in the spleen of collagen-induced arthritis (CIA) mice.Conclusion: By utilizing network pharmacology, molecular modeling, and in vitro/in vivo validation, this study demonstrates that SIN can alleviate RA by inhibiting the PI3K-Akt signaling pathway. These findings enhance the understanding of the therapeutic mechanisms of SIN in RA, offering a stronger theoretical foundation for its future clinical application. Keywords: sinomenine, rheumatoid arthritis, network pharmacology, PI3K-Akt signaling pathway

Hailing Yu,1,&ast; Yongquan Huang,2,&ast; Zhisheng Nong,3,&ast; Xi Lin,1 Kexin Tang,1 Zeyu Cai,1 Kaichen Huang,4 Ting Yu,1 Huimin Lan,1 Qianqian Zhang,1 Qiang Wang,5 Lei Yang,6 Jingchuan Zhu,7 Lili Wu,8 Hui Luo1 1Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3School of Materials Science and Engineering, Shenyang Aerospace University, Shenyang, Liaoning, People’s Republic of China; 4Department of Clinical laboratory, The Third People’s Hospital of Zhuhai, Zhuhai, Guangdong, People’s Republic of China; 5The Green Aerotechnics Research Institute of Chongqing Jiaotong University, Chongqing, People’s Republic of China; 6Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 7School of Materials Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 8Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, School of Physics and Electronic Engineering, Harbin Normal University, Harbin, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Luo; Lili Wu, Email luoh53@mail.sysu.edu.cn; wll790107@hotmail.comIntroduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo.Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth.Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment.Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.Keywords: nanozyme, sonodynamic therapy, Ti3C2/TiO2, ROS

Zhaoyong Li,1,&ast; Yanping Lin,1,&ast; Ting Qiu,2,&ast; Junsheng Liang,1 Yintao Lan,3 Fan Meng,4 Chaohao Liang,4 Yiqing Zhang,4 Qingyun Wang,1 Da Shi,1 Changli Zhang,1 Yanan Shi,1 Liujun Liu,1 Yanlan Yang,1 Jian Zhang4,5 1Department of Radiology, DongGuan Tungwah Hospital, Dongguan Key Laboratory of Radiology and Molecular Imaging, DongGuan, Guangdong, 523000, People’s Republic of China; 2Department of Radiology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 3Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, 510030, People’s Republic of China; 4School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 5Department of Oncology, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guangdong, 511500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang; Zhaoyong Li, Email jianzhang@gzhmu.edu.cn; lizhaoyong2003@163.comBackground: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC).Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC.Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT.Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.Keywords: nasopharyngeal carcinoma, photoacoustic imaging, photothermal therapy, PATQ-DPP nanoparticles

Yanhong Liu,1 Qi Wang,1 Chuanlei Zheng,1,2 Zhengchun Huang,3 Jian Li,3 Ming Hao,1 Minghua Dong,1,2 Xiaoting Luo,2,4 Qingfeng Wu1,2 1School of Public Health & Healthcare Management, Gannan Medical University, Ganzhou, People’s Republic of China; 2Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, People’s Republic of China; 4School of General Practice Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Qingfeng Wu, Gannan Medical University, Rongjiang New District College Park, Ganzhou, Jiangxi, 341000, People’s Republic of China, Tel +86-797-8169713, Fax +86-797-8169600, Email wuqf2006@gmu.edu.cnPurpose: The prevalence of diabetes in China is increasing, influenced by economic and genetic factors, with varying rates across regions. The Hakka population in Ganzhou city has unique exposures compared to surrounding districts, while limited research reported the epidemiological characteristics of type 2 diabetes mellitus (T2DM) in this population. This study aims to investigate the prevalence and influencing factors of T2DM among the population, thereby establishing a robust foundation for disease prevention and control measures.Patients and Methods: In 2017, a multistage random sampling method selected 3028 individuals from Ganzhou City’s permanent resident population. Physical examinations, blood tests, and questionnaire surveys were conducted for data collection, with binary logistic regression analysis used to examine factors affecting T2DM prevalence.Results: A total of 2978 valid samples were included in this study. The average age of the surveyed population was 52.83± 7.88 years, comprising 966 males and 2012 females. The prevalence rates of T2DM were 11.8% and 12.9% in males and females, respectively, while the standardized prevalence rate was recorded as 9.1%. Logistic regression analysis revealed that age (Odds Ratio[OR]=1.05, 95% Confidence Interval [CI]:1.03– 1.06), hypertension (OR=2.22, 95% CI:1.71– 2.93), family history of diabetes (OR= 3.54, 95% CI: 2.58– 4.85), overweight (OR=1.73, 95% CI: 1.20– 2.48), high total cholesterol (OR=1.17, 95% CI:1.09– 1.27), elevated low-density lipoprotein cholesterol (OR=1.19, 95% CI:1.00– 1.40) and serum insulin (OR=1.05, 95% CI:1.03– 1.06) were identified as significant risk factors for T2DM, Conversely, a higher level of high-density lipoprotein cholesterol (OR=0.55, 95% CI:0.36– 0.84) was found to be inversely related to T2DM development.Conclusion: The prevalence of T2DM in Ganzhou city has significantly increased. The effective implementation of comprehensive management strategies aimed at addressing hypertension, overweight, dyslipidemia, and abnormal serum insulin level is essential for promoting overall well-being and efficiently controlling the prevalence of T2DM.Keywords: type 2 diabetes mellitus, cross-sectional studies, epidemiology, influence factors

Yunpeng Cui,1 Qiwei Wang,1 Chuan Mi,1 Bing Wang,1 Yuanxing Pan,1 Yunfei Lin,1 Rui He,2 Liying Sun,3 Bo Zheng,4 Xuedong Shi1 1Department of Orthopaedics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Plastic Surgery and Burn, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Clinical Pharmacology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xuedong Shi, Department of Orthopedic, Peking University First Hospital, Beijing, People’s Republic of China, Email pku_ortho@163.comBackground: This retrospective cohort study explores a practical approach to acquiring pathogenic microorganisms in patients with bone and joint infections.Methods: From Aug 2018 to Mar 2022, 68 consecutive patients (87 cultures) with bone and joint infection were recruited in this study. All cultures followed the Peking University First Hospital Procedure of Culturing Pathogenic microorganisms for bone and joint infection. Tissue samples were obtained through fluoroscopy-guided biopsy or open debridement. Tissue samples were divided into manual homogenization (MH), manual mixture (MM), and pathological examination. The baseline, antibiotic exposure, laboratory, surgical, and microbial data were reviewed. Independent sample T-test, Mann–Whitney U-test, and Chi-square test were used to detect the difference between patients who received different processing measures.Results: The average age was 55.8± 2.4 years old. Thirty-nine patients were male. The total positive culture rate of the manual homogenization group was 80.5% (70/87). Thirty-five patients had mixed infections with more than one microorganism cultured. Staphylococci accounted for 60.23% of all microorganisms. Staphylococcus aureus (18.2%) and Staphylococcus epidermidis (15.9%) were the two most common bacteria cultured in this study. Patients with positive culture in the manual mixture group had significantly higher WBC (p = 0.006), NE% (p = 0.024), ESR (p = 0.003), CRP (p = 0.020) and IL6 (0.050) compared to patients with negative culture. After tissue homogenization, only ESR is still statistically different. Patients without SIRS had a low positive culture rate (59.4%). Tissue homogenization could significantly increase the positive culture rate of patients without SIRS. Pre-culture antibiotic exposure was not an independent risk factor for culture results.Conclusion: Peking University First Hospital Procedure for Culturing Pathogenic microorganisms for Bone and Joint Infections was a practical approach for obtaining pathogenic microorganisms.Keywords: bone and joint infection, systemic inflammatory response syndrome, antibiotic, tissue homogenization

Xiaofan Liu,1 Jianji Zeng,2 Liuxiang Li,2 Qixiu Wang,2 Junyi Chen,2 Li Ding2 1School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2School of Medical Business, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jianji Zeng, School of Medical Business, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Email zengjianji2006@163.comPurpose: To investigate the influence mechanism of doctor-patient communication on patients’ trust, especially the mediating role of patient-physician consistency and the moderating role of perceived threat of disease.Methods: A total of 699 patients in Guangzhou, China was investigated by questionnaire. The main effect, mediating effect, and moderating effect of the model was verified by SPSS23.0 and LISREL8.71 statistical software.Results: It was revealed that doctor-patient communication has a significant positive effect on patients’ trust. The consistency between patient and physician partially mediates the relationship between doctor-patient communication and patients’ trust. Additionally, the perceived threat of the disease moderates the psychological process through which doctor-patient communication affects patients’ trust.Conclusion: Both doctor-patient communication and patient-physician consistency have predictive effects on patients’ trust. Doctor-patient communication is not only a direct influence on patient trust but also an indirect influence mediated by patient-physician consistency. Perceived threat of disease moderates the psychological process through which doctor-patient communication affects patients’ trust. Specifically, compared to a high level of perceived threat of disease, a low level of perceived threat of disease can enhance the effect of doctor-patient communication on patients’ trust. The results of this study underscore the importance of doctor-patient communication and the value of patient-physician consistency for building patients’ trust. To foster a harmonious doctor-patient relationship, medical colleges should place great emphasis on cultivating medical students’ communication skills. Hospitals should enhance on-the-job training and provide institutional support for doctors, encourage agreements between doctors and patients regarding disease diagnosis and decision-making, and be attentive to patients’ perceived threat of disease, particularly for those with high level of perceived threat of disease.Keywords: doctor-patient communication, patient-physician consistency, perceived threat of disease, patients’ trust, doctor-patient relationship

Benchi Cai,&ast; Qitong Wang,&ast; Lifan Zhong, Fang Liu, Xinyu Wang, Tao Chen Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Chen, Email chentao@hnyxy15.wecom.workBackground: Parkinson’s disease (PD) is the most prevalent movement disorder. Curcumin, a polyphenol with hydrophobic properties, has been proved against Parkinson. Our previous study suggested that curcumin’s effectiveness in treating Parkinson’s disease may be linked to the gut-brain axis, although the specific mechanism by which curcumin exerts neuroprotective effects in the brain remains unknown.Methods: The therapeutic efficacy of curcumin was evaluated using behavioral tests, immunofluorescence of tyrosine hydroxylase (TH). Network pharmacology and transcriptomics predicted the mechanisms of curcumin in PD. Activation of the phosphatidylinositol 3-kinase PI3K/AKT pathway was confirmed by quantitative polymerase chain reaction (qPCR) and immunofluorescence.Results: Curcumin restored the dyskinesia and dopaminergic neurons damage of MPTP-induced mice. Curcumin against Parkinson’s disease by regulating inflammation, oxidative stress, and aging. The mechanisms of these were associated with activation of PI3K / AKT pathway.Conclusion: In conclusion, the neuroprotective mechanisms of curcumin activate PI3K / AKT pathway in Parkinson’s disease was revealed by our study.Keywords: Parkinson’s disease, curcumin, network pharmacology, transcriptomics, PI3K / AKT pathway

Hang Jin,1,2,&ast; Zhongqiang Yan,3,&ast; Xin Ge,4,&ast; Qi Wang,2 Hui Wang,2 Xinying Du,2 Hongbo Liu,2 Chaojie Yang,2 Ying Xiang,2 Sai Tian,2 Shaofu Qiu,1,2 Yu Zhou5 1School of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Infectious Disease Control and Prevention, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China; 3Department of Disease Prevention and Control, The Second Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 4School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaofu Qiu, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China, Email qiushf0613@hotmail.com Yu Zhou, Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Email zhouy427@163.comPurpose: This study conducted an phenotypic and whole-genome sequencing analysis with Klebsiella aerogenes to elucidate its clinical epidemiological characteristics, antimicrobial resistance (AMR) phenotype, biofilm formation ability and hemolytic activity testing, AMR genes and phylogenetic relationships, so as to provide a further understanding of the intra-hospital strain transmission.Methods: Samples were collected from a hospital in Beijing between 2020 and 2022. All strains underwent bacterial identification, antimicrobial susceptibility testing (AST) using the VITEK-2 compact system. Biofilm formation ability and hemolytic activity were tested. Second-generation sequencing was applied to all strains, with those carrying the blaKPC gene were selected for third-generation sequencing. Whole-genome analysis identified resistance genes, plasmid types, MLST typing, and phylogenetic relationships. Plasmids were assembled to detect plasmid structures and AMR gene location.Results: Among the 42 K. aerogenes isolates, 21 were carbapenem-resistant K. aerogenes (CRKA). All strains exhibited strong biofilm formation and no hemolytic activity. Most were sourced from sputum (83.3%). CRKA demonstrated extensive resistance to antibiotics, particularly β-lactamase inhibitors and Cefotetan. This resistance pattern was closely associated with the presence of an IncFII(pHN7A8) plasmid, which carried multiple resistance genes, including blaKPC-2, blaCTX-M-65, blaTEM-1, rmtB and a large number of mobile elements. The majority of CRKA strains clustered within the same branch of the phylogenetic tree, exhibiting minimal single nucleotide polymorphism (0– 13 SNPs) differences, and they shared the same sequence type (ST292), resistance genes, and plasmids, originating from different departments, suggesting clonal transmission among the hospital.Conclusion: Our research reveals that the clonal transmission of CRKA occurs across various departments within the hospital. The widespread resistance observed in CRKA, attributed to the presence of blaKPC and ESBLs genes, underscores the need for heightened vigilance to prevent the further dissemination of CRKA within the hospital and, potentially, throughout the wider community.Keywords: Klebsiella aerogenes, carbapenem resistance, blaKPC-2, clonal transmission

Shanshan Li,1,2 Le Zhang,3 Boyi Yang,3 Yi Huang,3 Yuqi Guan,3 Nanbo Huang,1 Yingnan Wu,1 Wenshuo Wang,1 Qing Wang,1 Haochen Cai,1 Yong Sun,1 Zijun Xu,1 Qin Wu1,2 1Medical College, Jiangsu Vocational College of Medicine, Yancheng, People’s Republic of China; 2Jiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Jiangsu Vocational College of Medicine, Yancheng, People’s Republic of China; 3Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Qin Wu, Medical College, Jiangsu Vocational College of Medicine, No. 283, South Jiefang Road, Yancheng, 224005, People’s Republic of China, Tel +86-515-88159750, Email hhwuq@163.comBackground: In elderly diabetic patients, depression is often overlooked because professional evaluation requires psychiatrists, but such specialists are lacking in the community. Therefore, we aimed to create a simple depression screening model that allows earlier detection of depressive disorders in elderly diabetic patients by community health workers.Methods: The prediction model was developed in a primary cohort that consisted of 210 patients with diabetes, and data were gathered from December 2022 to February 2023. The independent validation cohort included 99 consecutive patients from February 2023 to March 2023. Multivariable logistic regression analysis was used to develop the predictive model. We incorporated common demographic characteristics, diabetes–specific factors, family structure characteristics, the self–perceived burden scale (SPBS) score, and the family APGAR (adaptation, partnership, growth, affection, resolution) score. The performance of the nomogram was assessed with respect to its calibration (calibration curve, the Hosmer–Lemeshow test), discrimination (the area under the curve (AUC)), and clinical usefulness (Decision curve analysis (DCA)).Results: The prediction nomogram incorporated 5 crucial factors such as glucose monitoring status, exercise status, monthly income, sleep disorder status, and the SPBS score. The model demonstrated strong discrimination in the primary cohort, with an AUC of 0.839 (95% CI, 0.781– 0.897). This discriminative ability was further validated in the validation cohort, with an AUC of 0.857 (95% CI, 0.779– 0.935). Moreover, the nomogram exhibited satisfactory calibration. DCA suggested that the prediction of depression in elderly patients with diabetes mellitus was of great clinical value.Conclusion: The prediction model provides precise and user–friendly guidance for community health workers in preliminary screenings for depression among elderly patients with diabetes.Keywords: prediction model, depression, elderly, diabetes, community–based

Lin Qi,1,&ast; Yanglei Li,2,&ast; Chengqi Kong,2,&ast; Siqi Li,2 Qinyue Wang,2 Hanqin Pan,2 Shuyi Zhang,3 Xinkai Qu,2 Ming Li,1 Mingxuan Li,2,4 Kailei Shi2 1Department of Computed Tomography, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiac Care Unit, Tongren Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Cardiology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kailei Shi; Mingxuan Li, Email shikailei@fudan.edu.cn; 19211280015@fudan.edu.cnBackground: Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI.Patients and Methods: 60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests.Results: The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (− 74.84± 6.93 HU vs − 79.04± 8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (− 78.46± 8.56HU vs − 83.13± 8.34 HU) and LCXs (− 73.83± 10.63 HU vs − 81.38± 7.88 HU) of lesion related vessel in stable angina.Conclusion: We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.Keywords: peri-coronary adipose tissue, neutrophil-to-lymphocyte ratio, fat attenuation index, acute myocardial infarction

Xinyan Hu,1,&ast; Yanling Sui,1,&ast; Xinhao Yang,1 Zhengyu Yang,2 Qiuting Wang,2 Jiehong Yuan,2 Maoyu Li,1 Xiaotong Ma,1 Chengxuan Qiu,3 Qinjian Sun1 1Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 3Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden&ast;These authors contributed equally to this workCorrespondence: Qinjian Sun, Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Neurology, Shandong Provincial Hospital affiliated to Shandong First Medical University, No. 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, People’s Republic of China, Email sqj1210@163.comBackground: The inflammatory response is a pivotal factor in accelerating the progression of atherosclerosis. The high-sensitivity C-reactive protein-to-albumin ratio (CAR) has emerged as a novel marker of systemic inflammation. However, few studies have shown the CAR to be a promising prognostic marker for carotid atherosclerotic disease. This study aimed to analyse the predictive role of the CAR in carotid atherosclerotic disease.Methods: This community-based cohort study recruited 2003 participants from the Rose asymptomatic IntraCranial Artery Stenosis (RICAS) study who were free of stroke or transient ischemic attack. Carotid atherosclerotic plaques and their stability were identified via carotid ultrasound. Logistic regression models were utilized to investigate the association between CAR and the presence of carotid atherosclerotic plaques.Results: The prevalence of carotid atherosclerotic plaques was 38.79% in this study. After adjusting for clinical risk factors, including sex, age, dyslipidemia, hypertension, diabetes mellitus (DM), and smoking and drinking habits, a high CAR-level was independently associated with carotid plaque (odds ratio [OR] of upper: 1.46, 95% confidence interval [CI]: 1.13– 1.90, P = 0.004; P for trend = 0.011). The highest CAR tertile was still significantly associated with carotid plaques among middle-aged (40– 64 years) or female participants. Notably, an elevated CAR may be an independent risk factor for vulnerable carotid plaques (OR of upper: 2.06, 95% CI: 1.42– 2.98, P < 0.001; P for trend < 0.001).Conclusion: A high CAR may be correlated with a high risk of carotid plaques, particularly among mildly aged adults (40– 64 years) or females. Importantly, the CAR may be associated with vulnerable carotid plaques, suggesting that the CAR may be a new indicator for stroke prevention. Keywords: C-reactive protein, albumin, plaque, atherosclerotic, cohort study

Chun Wang,1,&ast; Xiaohong Fan,1,&ast; Li Nie,2 Qing Wang,1 Shanshan Li,1 Wen Zheng,1 Wei Zhang,1 Wangshu Dai,1 Minmin Chen1 1Department of Geriatric Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing, Jiangsu, People’s Republic of China; 2Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wangshu Dai; Minmin Chen, Department of Geriatric Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing, Jiangsu, 210008, People’s Republic of China, Email daysue1213@163.com; minminchen_2006@126.comBackground: Rivaroxaban, a non-vitamin K antagonist oral anticoagulant, has become widely used for the management of venous thromboembolism (VTE) in adult patients. However, few trials have explored the efficacy and safety of rivaroxaban in VTE patients over 80 years of age. This necessitates further real-world studies of rivaroxaban across elderly populations.Methods: We performed a retrospective single center study involving extremely aged VTE sufferers treated with rivaroxaban. The sample comprised 121 patients newly initiated on rivaroxaban diagnosed between January 2018 and January 2020. Patients were followed up for no less than 2 years. The effectiveness outcome was the disappearance of thromboembolism. The safety outcome was the incidence of major bleeding events. Comorbidities and complications were recorded throughout the entire study.Results: The efficacy outcome occurred in 114 of 121 patients (94.21%) and the safety outcome occurred in 12 of 121 patients (9.91%). Increased hemorrhages were observed in patients with infection (15.15% vs 7.80%), but no significant difference was observed due to limited sample size (P=0.3053). Patients with an age-adjusted Charlson comorbidity index score higher than 6 points exhibited higher bleeding rates (14.08% vs 4.00%; P=0.0676) and lower thrombus cure rates (88.73% vs 100%; P=0.0203).Key conclusions: Patients with infection should be more careful of bleeding events during rivaroxaban therapy. An age-adjusted Charlson comorbidity index score higher than 6, which predicted poor survival, indicated inferior safety and efficacy of rivaroxaban.Aim: To investigate the efficacy and safety of Rivaroxaban in an aged venous thromboembolism patient population under real-world conditions.Keywords: rivaroxaban, anticoagulation, venous thromboembolism, retrospective trial, extremely old

Cunxin Zhang,1,&ast; Qian Wang,1,&ast; Kang Li,1 Maoqing Fu,1 Kai Gao,2 Chaoliang Lv1 1Department of Spine Surgery, Jining No. 1 People’s Hospital, Jining, 272011, People’s Republic of China; 2Department of Orthopaedics, Jining No. 1 People’s Hospital, Jining, 272011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoliang Lv, Department of Spine Surgery, Jining No. 1 People’s Hospital, No. 6 Healthy Road, Rencheng District, Jining, 272011, People’s Republic of China, Tel +86 15265775628, Fax +86-0537- 2253252, Email lvchaolianggk@163.com Kai Gao, Department of Orthopaedics, Jining No. 1 People’s Hospital, Jining, No. 6 Healthy Road, Rencheng District, Jining, 272011, People’s Republic of China, Tel +86 15853760330, Fax +86-0537- 2253252, Email gaohaikai88@126.comBackground: Intervertebral disc degeneration (IDD) underlies the pathogenesis of degenerative diseases of the spine; however, its exact molecular mechanism is unclear.Purpose: To explore the molecular mechanism of mechanical pressure (MP)-induced IDD and to assess the role and mechanism of Rosuvastatin (RSV) inhibits MP-induced IDD.Methods: SD rat nucleus pulposus cells (NPCs) were cultured in vitro and an apoptosis model of NPCs was constructed using MP. Proliferative activity, reactive oxygen species content, apoptosis, and wound healing were detected in each group of NPCs, respectively. The expression of relevant proteins was detected by qPCR and Western Blot techniques. 18 SD rats were randomly divided into control, pressure and RSV groups. Elisa, qPCR, Western Blot and immunohistochemical staining techniques were used to detect changes in the content of related proteins in the intervertebral discs of each group. HE staining and Modified Saffron-O and Fast Green Stain Kit were used to assess IDD in each group.Results: MP treatment at 1.0 MPa could significantly induce apoptosis of NPCs after 24 h. MP could significantly inhibit the proliferative activity and wound healing ability of NPCs, and increase the intracellular reactive oxygen species content and apoptosis rate; pretreatment with RSV could significantly activate the Nrf2/HO-1 signaling pathway and reverse the cellular damage caused by MP; when inhibit the Nrf2/HO-1 signaling pathway activation, the protective effect of RSV was reversed. In vivo MP could significantly increase the content of inflammatory factors within the IVD and promote the degradation of extracellular matrix, leading to IDD. When the intervention of RSV was employed, it could significantly activate the Nrf2/HO-1 signaling pathway and improve the above results.Conclusion: RSV may inhibit MP-induced NPCs damage and IDD by activating the Nrf2/HO-1 signaling pathway.Keywords: rosuvastatin, intervertebral disc, nucleus pulposus cells, oxidative stress, nuclear factor E2-related factor 2, heme oxygenase-1, quinone oxidoreductase 1

Jiejie Guo,1– 3 Yanzi Cao,1 Ting Zhang,2 Chunshuang Xu,1 Zhitao Liu,1,4 Wanyi Li,1 Qinwen Wang1 1Zhejiang Key Laboratory of Pathophysiology, NBU Health Science Center, Ningbo University, Ningbo, People’s Republic of China; 2Department of Clinical Laboratory, The First People’s Hospital of Wenling, Taizhou, People’s Republic of China; 3Department of Neurology, The First People’s Hospital of Wenling, Taizhou, People’s Republic of China; 4Fujian Normal University, Fuzhou, People’s Republic of ChinaCorrespondence: Qinwen Wang, Zhejiang Key Laboratory of Pathophysiology, NBU Health Science Center Ningbo University, Ningbo, People’s Republic of China, Email wangqinwen@nbu.edu.cnBackground: There is growing interest in the role of physical activity in patients with of Alzheimer’s disease (AD), particularly regarding its impact of cognitive function, gut microbiota, metabolites, and neurotrophic factors.Objective: To investigate the impact of multisensory fusion training (MSFT) combined with 7, 8-dihydroxyflavone (DHF) on the behavioral characteristics, protein expression, microbiome, and serum metabolome using the AD model in mice induced with amyloid-β (Aβ).Methods: We assessed cognitive ability, anxiety-like and depression-like behaviors in Aβ mice using behavioral measures. Western blotting was employed to detect the expression of relevant proteins. The 16S rRNA gene sequencing and metabolomics were used to analyze changes in the intestinal microbial composition and serum metabolic profile, respectively, of Aβ mice.Results: The behavioral outcomes indicated that a 4-week intervention combining DHF and MSFT yielded remarkable improvements in cognitive function and reduced anxiety and depression-like behaviors in Aβ mice. In the hippocampus of Aβ mice, the combined intervention increased the levels of BDNF, VGF, PSD-95, Nrf2, p-GSK3β and p-CREB proteins. Analyses of sequence and metabolomic data revealed that Bacteroides and Ruminococcaceae were remarkably more abundant following the combined intervention, influencing the expression of specific metabolites directly linked to the maintenance of neuronal and neurobehavioral functions. These metabolites play a crucial role in vital processes, such as amino acid metabolism, lipid metabolism, and neurotransmitter metabolism in mice.Conclusion: Our study highlighted that MSFT combined with DHF improves cognitive impairment, anxiety, and depression-like behavior in Aβ mice through multiple mechanisms, and further validated the correlation between the gut microbiome and serum metabolome. These findings open up a promising avenue for future investigations into potential treatment strategies for AD.Keywords: Alzheimer’s disease, brain-derived neurotrophic factor, cognitive impairment, acousto-optic stimulation, treadmill exercise

Dan Qi,1– 9 Xi Zhang,1– 8 Fangli Li,10 Shengrui Zhao,2– 8 Qiumin Wang,1– 8 Wen Liu,2– 8 Lei Yan,1– 8 Yanbo Du1– 8 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, People’s Republic of China; 2National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, People’s Republic of China; 3Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, People’s Republic of China; 4Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 5Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 6Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 7Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan, Shandong, People’s Republic of China; 8Medical Integration and Practice Center, Shandong University, Jinan, Shandong, People’s Republic of China; 9Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China; 10Department of Gynecology and Obstetrics, Public Health Clinical Center Affiliated to Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yanbo Du, Center for Reproductive Medicine, Shandong University, Jinan, 250012, Shandong, People’s Republic of China, Tel +86 1 301 173 4515, Email duyanboivf@163.comPurpose: The objective of this study was to assess reproductive outcomes of D6 blastocysts transferred on day 6 in comparison to those transferred on day 7 of progesterone exposure in frozen-thawed embryo transfer cycles.Patients and Methods: This retrospective cohort study included 2029 D6 single blastocysts from the first frozen-thawed embryo transfer cycles of patients at the Hospital for Reproductive Medicine Affiliated to Shandong University from February 2017 to January 2020. Participants were divided into Group A (blastocyst transferred on the 6th day of progesterone exposure, n=1634) and Group B (blastocyst transferred on the 7th day of progesterone exposure, n=395).Results: The live birth rate was comparable between Group A and Group B (38.7% versus 38.7%, P=0.999). Subgroup analysis revealed a significantly higher preterm birth rate in D6 single blastocysts transferred on the 7th day than in those transferred on the 6th day of progesterone exposure for natural cycle frozen-thawed embryo transfer (5.2% versus 11.3%, P=0.020). After adjustment for potential confounders, the differences in the preterm birth rate in natural cycles persisted (adjusted odds ratio 2.347, 95% confidence interval 1.129– 4.877, P=0.022).Conclusion: In frozen-thawed embryo transfer cycles, transferring on the 6th or 7th day of progesterone exposure of D6 blastocysts did not affect the live birth rate; however, when a natural cycle protocol is adopted, the possible preterm risk of transferring D6 blastocysts on the 7th day of progesterone exposure should be noted.Keywords: frozen-thawed embryo transfer, blastocyst transfer, endometrium preparation, live birth rate

Xiaoxing Wei,1,2,&ast; Shengteng Guo,1,&ast; Qinghua Wang1 1School of Nursing (School of Gerontology), Binzhou Medical University, Binzhou, Shandong, People’s Republic of China; 2Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinghua Wang, Email pingxing05@126.comPurpose: To evaluate troponin I, creatine kinase isoenzyme, and the new Japanese Severity Score(JSS) for predicting Severe Acute Pancreatitis-Associated myocardial Injury(SACI).Patients and Methods: This retrospective study included 136 patients with Severe Acute Pancreatitis, hospitalized in grade-III hospital from June 1, 2015, to October 31, 2022; selected using convenience sampling method and divided into SACI occurrence (n =34) and SACI non-occurrence (n =102) groups. New JSS evaluated predictive value of each SACI index. Binary logistic regression model compared risk factors and constructed a prediction model. Area under receiver operating characteristic curve (AUC) and Hosmer–Lemeshow goodness of fit test evaluated model’s prediction efficiency and calibration ability.Results: The incidence of SACI was 25%. Univariate analysis found that troponin I and creatine kinase isoenzyme were significantly different (P < 0.05) and independent risk factors for SACI. The new JSS, troponin I, and creatine kinase isoenzyme were included in the prediction model. The prediction model had a good calibration ability, and its predicted value and the actual observed value were not significantly different (Hosmer–Lemeshow χ 2 = 5.408, P = 0.368). AUC of the model was 0.803 (95% CI: 0.689– 0.918), and the optimal threshold of the prediction model was 0.318 with the maximum Youden index (0.488). The AUC for internal validation was 0.788 (95% CI: 0.657– 0.876), and external validation was 0.761 (95% CI: 0.622– 0.832).Conclusion: Troponin I and creatine kinase isoenzymes combined with the new JSS have a high predictive value for SACI, improving the early prediction and treatment of at-risk patients.Keywords: acute pancreatitis, new Japanese severity score, myocardial injury, prediction model, pancreatic heart syndrome

Jingyi Lao,1,&ast; Yijie Zeng,1,&ast; Zhangying Wu,1 Gaohong Lin,1 Qiang Wang,1 Mingfeng Yang,1 Si Zhang,1 Danyan Xu,1 Min Zhang,1 Kexin Yao,1 Shuang Liang,1 Qin Liu,1 Jiafu Li,1 Xiaomei Zhong,1 Yuping Ning1– 4 1Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 4Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuping Ning; Xiaomei Zhong, The Affiliated Brain Hospital of Guangzhou Medical University, No. 36, Mingxin Road, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Email ningjeny@126.com; lovlaugh@163.comBackground: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear.Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed.Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items.Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.Keywords: late-life depression, microstate, electroencephalogram, resting-state networks

Wei Ao,1 Ping Duan,2 Ping Luo,1 Dikai Xiang,1 Qin Wang,1 Yanjiao Ren,1 Qiwei He1 1Department of Cardiology, Yueyang People’s Hospital, Hunan Normal University, Yueyang City, Hunan Province, 414000, People’s Republic of China; 2Department of Cardiology, Shanghai Seventh People’s Hospital, Shanghai City, 200000, People’s Republic of ChinaCorrespondence: Qiwei He, Department of Cardiology, Yueyang People’s Hospital, Hunan Normal University, No. 263 Baling East Road, Yueyanglou District, Yueyang City, Hunan Province, 414000, People’s Republic of China, Tel +8615173044525, Email Yueshao1990@163.comObjective: To explore the clinical application of PTEN-induced kinase 1 (PINK1) and acyl-CoA synthetase long chain family 4 (ACSL4) protein levels in patients with acute myocardial infarction (AMI) and the prognosis evaluation after percutaneous coronary intervention (PCI).Methods: 152 AMI patients who underwent PCI at our hospital from October 2021 to February 2023 were selected as the study group. They were divided into a MACE group (31 cases) and a non MACE group (121 cases) based on the major adverse cardiovascular events (MACE) within 28 days after PCI. Additionally, 152 angina pectoris patients admitted during the same period were selected as the control group. Measure and analyze the levels and clinical significance of PINK1 and ACSL4 proteins in all study subjects.Results: The PINK1 protein level in the study group was lower than that in the control group, while the PINK1 protein level in the MACE group was lower than that in the non MACE group (P< 0.05), while the ACSL4 protein level was the opposite (P< 0.05); PINK1 expression was negatively correlated with SYNTAX score (r=− 0.602, P< 0.05), while ACSL4 expression was positively correlated with SYNTAX score (r=0.683, P< 0.05); Age, LVEF, and ACSL4 were risk factors for poor prognosis in AMI patients after PCI, while PINK1 was a protective factor (P< 0.05); The combined prediction of PINK1 and ACSL4 for the postoperative prognosis of AMI patients after PCI was superior to the individual detection of PINK1 and ACSL4 (P< 0.05).Conclusion: The expression levels of PINK1 and ACSL4 are related to the occurrence of AMI, and their combined detection has high predictive power for the prognosis of AMI patients after PCI.Keywords: acute myocardial infarction, PTEN-induced kinase 1, Acyl-CoA synthetase long chain family 4, percutaneous coronary intervention, prognosis

Jingliang Wu,1,&ast; Qiao Lu,1,2,&ast; Jialin Zhao,3,&ast; Wendi Wu,3 Zhihua Wang,1 Guohua Yu,4 Guixiang Tian,2 Zhiqin Gao,2 Qing Wang5 1School of Medicine, Weifang University of Science and Technology, Weifang, 262700, People’s Republic of China; 2School of Life Science and Technology, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 4Department of Oncology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China; 5Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wang, Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China, Tel +86 158 6362 6389, Email wfwq8899@163.comPurpose: Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells.Methods: Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro “condition medium of fibroblasts + MCF-7” cell model and in vivo “ 4T1/NIH-3T3” co-implantation mice model were established to evaluate the anti-tumor effect of drugs.Results: The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect.Conclusion: In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.Keywords: drug delivery, cancer-associated fibroblasts, glucocorticoids, combination therapy

Qiaoli Wang,1,&ast; Tao Liang,2,&ast; Yuexi Li,1,&ast; Xiaoqin Liu1 1Department of Health Screening Center, Deyang Peoples’ Hospital, Deyang, Sichuan, 618000, People’s Republic of China; 2Department of Gastroenterology, Deyang Peoples’ Hospital, Deyang, Sichuan, 618000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqin Liu, Email 66823572@qq.comPurpose: The aim of this study was to evaluate the potential benefit of blood inflammation in the diagnosis of non-small cell lung cancer (NSCLC) and propose a machine-learning-based method to predict NSCLC in asymptomatic adults.Patients and Methods: A cross-sectional study was evaluated using medical records of 139 patients with non-small cell lung cancer and physical examination data from May 2022 to May 2023 of 198 healthy controls. The NSCLC cohort comprised 128 cases of adenocarcinoma, 3 cases of squamous cell carcinoma, and 8 cases of other NSCLC subtypes. The correlation between inflammatory and nutritional markers, such as monocytes, neutrophils, LMR, NLR, PLR, PHR and non-small cell lung cancer was examined. Features were selected using Python’s feature selection library and analyzed by five algorithms. The predictive ability of the model for non-small cell lung cancer diagnosis was assessed by precision, accuracy, recall, F1 score, and area under the curve (AUC).Results: The results showed that the top 14 important factors were PDW, age, TP, RBC, HGB, LYM, LYM%, RDW, PLR, LMR, PHR, MONO, MONO%, gender. Additionally, the naive Bayes (NB) algorithm demonstrated the highest overall performance in predicting adult NSCLC among the five machine learning algorithms, achieving an accuracy of 0.87, a macro average F1 score of 0.85, a weighted average F1 score of 0.87, and an AUC of 0.84.Conclusion: In feature ranking, platelet distribution width was the most important feature, and the NB algorithm performed best in predicting adult NSCLC diagnosis.Keywords: machine learning, non-small cell lung cancer, inflammatory indicators, nutritional indicators, ratio, diagnosis

Jianing Tang,1,2,&ast; Yuexin Luo,1,2,&ast; Qirui Wang,1,2 Juntao Wu,1,2 Yulong Wei1 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2First Clinic School, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulong Wei, Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, People’s Republic of China, Email yulongwei_HUST@163.comAbstract: As a major cause of low back pain, intervertebral disc degeneration is an increasingly prevalent chronic disease worldwide that leads to huge annual financial losses. The intervertebral disc consists of the inner nucleus pulposus, outer annulus fibrosus, and sandwiched cartilage endplates. All these factors collectively participate in maintaining the structure and physiological functions of the disc. During the unavoidable degeneration stage, the degenerated discs are surrounded by a harsh microenvironment characterized by acidic, oxidative, inflammatory, and chaotic cytokine expression. Loss of stem cell markers, imbalance of the extracellular matrix, increase in inflammation, sensory hyperinnervation, and vascularization have been considered as the reasons for the progression of intervertebral disc degeneration. The current treatment approaches include conservative therapy and surgery, both of which have drawbacks. Novel stimuli-responsive delivery systems are more promising future therapeutic options than traditional treatments. By combining bioactive agents with specially designed hydrogels, scaffolds, microspheres, and nanoparticles, novel stimuli-responsive delivery systems can realize the targeted and sustained release of drugs, which can both reduce systematic adverse effects and maximize therapeutic efficacy. Trigger factors are categorized into internal (pH, reactive oxygen species, enzymes, etc.) and external stimuli (photo, ultrasound, magnetic, etc.) based on their intrinsic properties. This review systematically summarizes novel stimuli-responsive delivery systems for intervertebral disc degeneration, shedding new light on intervertebral disc therapy.Keywords: stimulus response, delivery system, intervertebral disc degeneration, biomaterial

Qiang Wang,&ast; Pinduan Bi,&ast; Ding Luo, Pingli Cao, Weihong Chen, Bin Yang Department of Hepatobiliary Surgery, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Yang, Department of Hepatobiliary Surgery, the First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Wuhua District, Kunming, People’s Republic of China, Tel +86 013987642890, Email yangbin@kmmu.edu.cnBackground: Gallstone disease (GS) is an important risk factor for Gallbladder cancer (GBC). However, the mechanisms of the progression of GS to GBC remain unclear. Long non-coding RNA (lncRNA), modulates DNA/RNA/proteins at epigenetic, pre-transcriptional, transcriptional and posttranscriptional levels, and plays a potential therapeutic role in various diseases. This study aims to identify lncRNAs that have a potential impact on GS-promoted GBC progression.Methods and Results: Six GBC patients without GS, six normal gallbladder tissues, nine gallstones and nine GBC patients with GS were admitted to our hospital. The next-generation RNA-sequencing was performed to analyze differentially expressed (DE) lncRNA and messenger RNA (mRNA) in four groups. Then overlapping and specific molecular signatures were analyzed. We identified 29 co-DEGs and 500 co-DElncRNAs related to gallstone or GBC. The intersection and concatenation of co-DEGs and co-DElncRNA functionally involved in focal adhesion, Transcriptional misregulation in cancers, Protein digestion and absorption, and ECM-receptor interaction signaling pathways may contribute to the development of gallbladder cancer. Further exploration is necessary for early diagnosis and the potential treatment of GBC. FXYD2, MPZL1 and PAH were observed in both co-DEGs and co-DElncRNA and validated by qRT-PCR.Conclusion: Our data identified a series of DEGs and DElncRNAs, which were involved in the progression of GBC and GS-related metabolism pathways. Compared to GBC, the GS profile was more similar to para-tumor tissues in transcriptome level and lower risk of cancer. Further exploration is necessary from GBC patients with different periods of follow-up gallstone.Keywords: gallstone, gallbladder cancer, long non-coding RNA, next-generation sequencing analysis, computational biology

Shulin Wei,1,2,&ast; Mingxing Li,1,2,&ast; Qin Wang,1,2,&ast; Yueshui Zhao,1,2 Fukuan Du,1,2 Yu Chen,1,2 Shuai Deng,1,2 Jing Shen,1,2 Ke Wu,1,2 Jiayue Yang,1,2 Yuhong Sun,1 Li Gu,1 Xiaobing Li,1 Wanping Li,1 Meijuan Chen,1 Xiao Ling,3 Lei Yu,3 Zhangang Xiao,1,2 Lishu Dong,3 Xu Wu1,2 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, 646100, People’s Republic of China; 3Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lishu Dong, Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China, Email 1275607519@qq.com Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@126.comAbstract: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.Keywords: mesenchymal stem cells, immunomodulation, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, cell therapy

Minli Hu,1,&ast; Hao Fang,2,&ast; Yibing Hu,1 Chong Lu,1 Yuan Chen,1 Zhifeng Zhong,3 Hongqi Shi,4 Qunying Wang1 1Department of Gastroenterology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China; 2Department of Traumatology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China; 3Department of Anus & Intestine Surgery, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China; 4Department of Pathology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qunying Wang, Department of Gastroenterology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China, Email wqy616717@126.comBackground: Allied disorders of Hirschsprung’s disease (ADHD) exhibit symptoms akin to those of Hirschsprung’s disease, primarily characterized by intestinal obstruction, bowel dilatation, and chronic constipation. The occurrence of amyloid complications in patients with ADHD is infrequent. In this report, we present a case of ADHD with intestinal ulcers as the initial gastrointestinal manifestation, and subsequent pathological examination revealed the presence of amyloid deposits in the colonic mucosa.Case Report: A male patient, aged 20, exhibited recurring abdominal distension and intestinal obstruction for a duration of three years. Multiple colonoscopies revealed the presence of recurrent colonic ulcers, with pathological examination indicating the existence of amyloid deposits within the mucosal layer of the colon. Abdominal CT scans suggested colonic dilatation. Following a multidisciplinary consultation, a subtotal resection of the colon was performed, and subsequent postoperative pathology confirmed a decrease and absence of myenteric plexus ganglion cells. Considering the patient’s symptoms and the findings from the postoperative pathology, a diagnosis of ADHD was made. The patient’s symptoms resolved postoperatively and he was discharged from the hospital and followed up for 1 year in stable condition.Conclusion: Our study highlights the potential association between ADHD and the initial presentation of recurrent colonic ulcers, accompanied by amyloid deposition in the intestinal mucosa. This finding suggests a possible pathogenic mechanism for ADHD and offers a novel perspective on its diagnosis.Keywords: allied disorders of Hirschsprung’s disease, colonic ulcer, amyloid, intestinal obstruction, colonoscopy biopsy colonic

Guangtian Wang,1,2,&ast; Zhihui Li,3,&ast; Gongchen Wang,4,&ast; Qixu Sun,5 Peng Lin,1 Qian Wang,2 Huishu Zhang,6 Yanyan Wang,7 Tongshuai Zhang,8 Feiyun Cui,9 Zhaohua Zhong1,2 1Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 3Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 4Department of Vascular Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 5Department of Gastroenterology, Penglai People’s Hospital, Yantai, Shandong, 265600, People’s Republic of China; 6Teaching Center of Biotechnology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 7Teaching Center of Morphology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 8Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 9Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaohua Zhong; Feiyun Cui, Email zhongzh@hrbmu.edu.cn; feiyun@hrbmu.edu.cnAbstract: Angiogenesis, or the formation of new blood vessels, is a natural defensive mechanism that aids in the restoration of oxygen and nutrition delivery to injured brain tissue after an ischemic stroke. Angiogenesis, by increasing vessel development, may maintain brain perfusion, enabling neuronal survival, brain plasticity, and neurologic recovery. Induction of angiogenesis and the formation of new vessels aid in neurorepair processes such as neurogenesis and synaptogenesis. Advanced nano drug delivery systems hold promise for treatment stroke by facilitating efficient transportation across the the blood-brain barrier and maintaining optimal drug concentrations. Nanoparticle has recently been shown to greatly boost angiogenesis and decrease vascular permeability, as well as improve neuroplasticity and neurological recovery after ischemic stroke. We describe current breakthroughs in the development of nanoparticle-based treatments for better angiogenesis therapy for ischemic stroke employing polymeric nanoparticles, liposomes, inorganic nanoparticles, and biomimetic nanoparticles in this study. We outline new nanoparticles in detail, review the hurdles and strategies for conveying nanoparticle to lesions, and demonstrate the most recent advances in nanoparticle in angiogenesis for stroke treatment. Keywords: angiogenesis, ischemic stroke, nanoparticles, blood brain barrier, neurogenesis, neuroprotection therapy

Boyong Wang,1,&ast; Qiaojie Wang,1,&ast; Mingzhang Li,1 Jinlong Yu,1 Feng Jiang,1 Yujie Hu,1 Geyong Guo,1 Xiaohua Chen,2 Jin Tang,3 Pei Han,1 Hao Shen1 1Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 2Department of Infectious Diseases, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 3Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Shen, Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China, Email shenhao7212@sina.comObjective: The diagnosis of tubercular orthopedic implant-associated infection (TB-IAI) is challenging. This study evaluated the value of metagenomic next-generation sequencing (mNGS) for the diagnosis of TB-IAI and developed a standardized diagnostic procedure for TB-IAI.Methods: The records of all patients with TB-IAI diagnosed and treated at our institution between December 2018 and September 2022 were retrospectively reviewed. Patient demographic characteristics, medical history, laboratory test, microbial culture, histopathology, and mNGS results, and time to diagnosis were recorded. The diagnostic efficiency of mNGS for TB-IAI was assessed by comparing the results and diagnostic time with that of other diagnostic modalities.Results: Ten patients were included in the analysis, including eight with prosthetic joint infections and two with fracture-related infections. The mNGS positivity rate was 100% (10/10), which was higher than that of TB-antibody (11%, 1/9), real-time quantitative polymerase chain reaction (22%, 2/9), T-SPOT.TB (25%, 2/8), purified protein derivative (50%, 4/8), microbial culture (50%, 5/10), and histopathology (20%, 2/10). mNGS shortened the time to diagnosis of TB-IAI. A standardized diagnostic procedure for TB-IAI was developed based on the findings.Conclusion: mNGS is useful for the diagnosis of TB-IAI. mNGS is recommended in cases where it is difficult to identify a pathogen using routine diagnostic tests. The standardized diagnostic procedure might improve TB-IAI diagnosis.Importance: TB-IAI is a rare infection, which occurs after orthopedic surgery and hard to diagnose microbiologically. mNGS is a new detection technique not yet discussed in current literature as a means for TB-IAI diagnostics. Here we describe a cohort of patients with TB-IAI diagnosed by mNGS show high efficiency of mNGS for detection of this pathology and present a clinical algorithm supplementing conventional methods for TB-IAI assessment.Keywords: metagenomic next-generation sequencing, implant-associated infection, Mycobacterium tuberculosis complex, orthopedic infection, diagnosis

Jian Sun,1,&ast; Zhaochun Tian,2,&ast; Jing Wu,3 Jiafei Li,3 Qixia Wang,3 Shuhong Huang,2,3 Meng Wang4 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Science and Technology Innovation Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3School of Clinical and Basic Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Department of General Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meng Wang, Department of general surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369, Jingshi Road, Jinan, Shandong, 250014, People’s Republic of China, Email wangmtcm@163.com Shuhong Huang, School of Clinical and Basic Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 6699, Qingdao Road, Jinan, Shandong, 250117, People’s Republic of China, Email shuhonghuang@sdfmu.edu.cnAbstract: Pristimerin, a natural triterpenoid isolated from the plants of southern snake vine and Maidenwood in the family Weseraceae, is anti-inflammatory, insecticidal, antibacterial, and antiviral substance and has been used for its cardioprotective and antitumor effects and in osteoporosis treatment. These qualities explain Pristimerin’s therapeutic effects on different types of tumors and other diseases. More and more studies have shown that pristimerin acts in a wide range of biological activities and has shown great potential in various fields of modern and Chinese medicine. While Pristimerin’s wide range of pharmacological effects have been widely studied by others, our comprehensive review suggests that its mechanism of action may be through affecting fundamental cellular events, including blocking the cell cycle, inducing apoptosis and autophagy, and inhibiting cell migration and invasion, or through activating or inhibiting certain key molecules in several cell signaling pathways, including nuclear factor κB (NF-κB), phosphatidylinositol 3-kinase/protein kinase B/mammalian-targeted macromycin (PI3K/Akt/mTOR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 1/2 (ERK1/2), Jun amino-terminal kinase (JNK1/2/3), reactive oxygen species (ROS), wingless/integrin1 (Wnt)/β-catenin, and other signaling pathways. This paper reviews the research progress of Pristimerin’s pharmacological mechanism of action in recent years to provide a theoretical basis for the molecular targeting therapy and further development and utilization of Pristimerin. It also provides insights into improved treatments and therapies for clinical patients and the need to explore pristimerin as a potential facet of treatment.Keywords: pristimerin, signaling pathway, pharmacological effects, review

Xiaomei Cui,1,2 Ting Zhang,2 Tao Xie,2 Fang-xi Guo,2 Yu-ying Zhang,2 Yuan-jia Deng,2 Qi Wang,1,2 Yi-xing Guo,1,2 Ming-hua Dong,1,2 Xiao-ting Luo1,3 1Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 2School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of General Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Xiao-ting Luo, Golden Campus of Gannan Medical University, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Tel +86 13677975578, Email xtluo76@163.comAbstract: Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut–brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations. Keywords: blood pressure, metabolites, gut-brain, treatment

Xiaomeng Tang,1– 4,&ast; Qi Wang,2– 4,&ast; Ronghua Jin,2– 4 Caixia Hu1 1Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Infectious Diseases, Beijing, People’s Republic of China; 3National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Caixia Hu, Interventional therapy center for oncology; Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, People’s Republic of China, Tel/Fax +86-13811395702, Email hucaixia1217@126.com Ronghua Jin, Beijing Ditan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, Beijing, People’s Republic of China, Tel/Fax +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer. Early diagnosis is crucial for improving prognosis. Elderly HCC patients often have underlying liver diseases such as chronic hepatitis and cirrhosis, leading to impaired liver function and suboptimal liver reserve. Radiofrequency ablation (RFA) has rapidly become one of the most important methods for treating early-stage hepatocellular carcinoma (EHCC) due to its advantages, including minimal trauma, short operation time, less intraoperative bleeding, quick postoperative recovery, cost-effectiveness, and few postoperative-complications. However, the prognostic model for early recurrence after local ablation in elderly EHCC patients has not been widely evaluated. We have developed a prognostic model for the recurrence of local RFA in elderly EHCC patients. This is expected to provide a new early warning system for preventing early recurrence in elderly EHCC patients, prolonging patient’s life, and improving overall quality of life.Methods: In this study, we included 661 EHCC patients who underwent local ablation, dividing them into a Primary cohort and a Validation cohort in a 7:3 ratio. We characterized the cohorts and utilized the primary cohort to develop a prognostic nomogram model for recurrence after local ablation in elderly EHCC patients. Additionally, the validation cohort was used to assess the potential of the nomogram as a non-invasive biomarker for post-ablation recurrence in EHCC.Results: The user-friendly nomogram incorporates common clinical variables including gender, BCLC stage, tumor number, tumor size, red blood cell (RBC), gamma-glutamyl transferase (GGT), and prothrombin time activity (PTA). The nomogram constructed using the identified seven variables exhibits robust discriminatory capabilities, favorable predictive performance, and noteworthy clinical utility.Conclusion: We developed a user-friendly nomogram based on the BCLC stage classification, which may provide prognostic assessments for elderly EHCC patients at 1, 3, and 5 years post-RFA.Keywords: hepatocellular carcinoma, elderly, radiofrequency ablation, EHCC, relapse, prognostic model

Jie Liu, Lijuan Lu, Yu Wei, Yu Li, Qiong Wang, Lei Yu, Langen Zhuang, Guoxi Jin, Xiaoyan Pei Department of Endocrinology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui Province, People’s Republic of ChinaCorrespondence: Guoxi Jin; Xiaoyan Pei, Department of Endocrinology, the First Affiliated Hospital of Bengbu Medical University, No. 287 Changhuai Road, Bengbu, Anhui Province, 233000, People’s Republic of China, Email jyzjyz1999@163.com; 245899985@qq.comAbstract: Pseudohypoparathyroidism (PHP) is a rare genetic disease characterized by hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) in serum. Here, we report a case of a patient with pseudohypoparathyroidism type IB (PHPIB) and subclinical hypothyroidism, analyze the clinical and genetic data of his family members, review the relevant literature, and classify and discuss the pathogenesis and clinical characteristics of each subtype. Finally, we discuss the treatment approach to improve clinicians’ understanding of the disease.Keywords: hypocalcemia, parathyroid hormone resistance, GNAS, STX16, molecular genetic mechanism

Fang Zhai,1 Fulei Han,2 Qiulin Wang1 1College of Physical Education, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China; 2Kunshan No. 1 Vocational School in Jiangsu Province, Kunshan, Jiangsu, 215300, People’s Republic of ChinaCorrespondence: Qiulin Wang, Email wangql@yzu.edu.cnPurpose: The continuous spread of the epidemic has inflicted serious harm upon individual’s mental well-being, and effective coping mechanisms are associated with positive mental health outcomes. Prosocial behavior and a sense of meaning in life can enhance individuals’ subjective well-being, which can subsequently positively impact their mental health. Thus, in the context of epidemic prevention and control, this study investigates the relationship between the meaning in life, prosocial behavior, and coping styles of outstanding physical education students and the impact on their mental health.Methods: The study involved a questionnaire survey on 498 outstanding physical education students, consisting of 297 boys (mean age = 13.16) and 201 girls (mean age = 12.87 years). Subsequently, the data was analyzed using the mediating effect and Bootstrap tests.Results: The coping style positively predicted the meaning in life (β=0.294) and prosocial behavior (β=0.293). Conversely, mental health was predicted in a negative direction (β=– 0.494). Mental health negatively predicted prosocial behavior (β=– 0.810), although prosocial behavior positively predicted meaning in life (β=0.644). Finally, prosocial behavior negatively predicted mental health (β=– 0.513). Additionally, the interplay between prosocial behavior and meaning in life is established in terms of both the individual and chain mediating roles.Conclusion: This study demonstrates that coping styles during a normalized epidemic prevention and control situation directly impact the mental health of Shanghai’s outstanding physical education students. Additionally, these coping styles indirectly influence mental health through the mediating effects of meaning in life and prosocial behaviors. Furthermore, meaning in life and prosocial behaviors act as chain mediators in this relationship.Keywords: coping style, mental health, meaning in life, prosocial behavior

Nan Jiang,1,&ast; Wei Jin,2,&ast; Zhenghui Fu,3,&ast; He Cao,1 Hong Zheng,3 Quqing Wang,1 Qiongting Zhang,3 Kang Ju,3 Jiwei Wang1 1Key Laboratory of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Department of Patriotic Public Health and Health Promotion instruction, Shanghai Municipal Center for Health Promotion, Shanghai, People’s Republic of China; 3Shanghai Changning Mental Health Center (Affiliated to East China Normal University), Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiwei Wang, Key Laboratory of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China, Email jiweiwang@fudan.edu.cn Kang Ju, Shanghai Changning Mental Health Center (Affiliated to East China Normal University), Shanghai, People’s Republic of China, Email jukang2009@163.comPurpose: This study aims to explore the serial mediating effect of stigma and depression on the association between social support and medication adherence.Patients and Methods: A cross-sectional survey was undertaken in the Changning District of Shanghai using a five-part questionnaire from August to December 2023. A convenient sampling method was employed, and 35 patients with schizophrenia were invited from each of the 9 streets in Changning District to participate in the survey, resulting in a total of 305 valid questionnaires collected. The questionnaire measured social support, stigma, depression, medication adherence, and demographic characteristics. Data analysis involved descriptive statistics, independent samples t-tests, ANOVA, Pearson correlation analysis, and the bootstrap method.Results: There was a direct and significantly positive association between social support and medication adherence (β = 0.69, p < 0.001). Moreover, increased levels of stigma (β = - 0.45, p = 0.013) and depression (β = - 0.09, p = 0.017) were both associated with a decline in medication adherence. Bootstrapping analysis revealed that the association between social support and medication adherence operated indirectly through stigma (β = 0.11, 95% CI: 0.03, 0.18). Additionally, social support was indirectly associated with medication adherence through depression (β = 0.15, 95% CI: 0.04, 0.30). Further analysis indicated that social support had an indirect association with medication adherence through both stigma and depression (β = 0.04, 95% CI: 0.01, 0.07).Conclusion: Stigma and depression serially mediate the association between social support and medication adherence among patients with schizophrenia. This serial multiple mediation model underscores the importance of integrating social support interventions with psychological interventions aimed at reducing stigma and depression, thereby effectively enhancing medication adherence in patients with schizophrenia.Keywords: social support, stigma, depression, medication adherence, schizophrenia