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Chenwei Zhang,1,2 Xuesen Su,1,2 Yukai Zhang,2 Peiyun He,2 Xiaomei Kong,1 Zhenxia Zhang,1 Yangyang Wei,1 Yiwei Shi1,2 1NHC Key Laboratory of Pneumoconiosis, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2First School of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Yangyang Wei; Yiwei Shi, NHC Key Laboratory of Pneumoconiosis, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China, Email 512266595@qq.com; shiyw@sxmu.edu.cnBackground: The bidirectional relationship between pulmonary hypertension (PH) and sleep disorders has attracted significant research attention. The concept of the lung-brain axis has further highlighted the need for a holistic approach to managing these diseases.Methods: This study used bidirectional two-sample Mendelian Randomization (MR) to explore the genetic-level causal relationships between PH, sleep disorders, and structural brain changes. GWAS data for PH were pooled from four cohorts; data on four sleep disorder subtypes were sourced from the FinnGen database; and data on 15 structural brain changes were obtained from the ENIGMA Consortium. To ensure reliability, we applied strict data selection, multiple corrections, heterogeneity assessments, and sensitivity tests. Visualizations included forest plots, scatter plots, funnel plots, and leave-one-out plots.Results: MR analysis revealed a significant causal relationship between PH and both obstructive sleep apnea (OSA) (OR = 1.022, 95% CI = 1.006– 1.039, P = 0.006, PBonferroni = 0.025) and general sleep disorders (OR = 1.018, 95% CI = 1.003– 1.033, P = 0.018, PFDR = 0.036), with no evidence of reverse causation and multivariable MR analyses also demonstrated significant results. PH was linked to changes in total brain volume (P = 0.032) and cerebral white matter (P = 0.035). Amygdala changes appeared to reduce the risk of sleep disorders (P = 0.008) and OSA (P = 0.014). Sensitivity analyses showed no heterogeneity, pleiotropy, or significant outliers.Conclusion: This study identifies significant causal links between PH, sleep disorders, and structural brain changes, establishing a triangular cyclic relationship that supports the lung-brain axis concept. These findings inform clinical management of PH and its comorbidities. Keywords: pulmonary hypertension, sleep disorders, obstructive sleep apnea, brain structure, lung-brain axis, genetic associations

Yonghui Hu,&ast; Rengna Yan,&ast; Yun Shen, Huiqin Li, Jianhua Ma, Xiaofei Su Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianhua Ma; Xiaofei Su, Email majianhua196503@126.com; suxiaofeifei@126.comObjective: To explore the efficacy and safety of intermittent use of flash glucose monitoring (FGM) for improving glycemic control in Chinese elderly patients with type 2 diabetes mellitus (T2DM).Methods: This is a prospective observational study involving patients with T2DM aged ≥ 60 years. The study period spans 12 weeks, with participants wearing FGM at weeks 0, 5, and 10. Participants were divided into two subgroups based on HbA1c at enrollment: < 7.0% and ≥ 7.0%. The primary outcome of the study was HbA1c level. Secondary outcomes included time in range (3.9– 10mmol/L) (TIR), time below range (< 3.9mmol/L) (TBR), time above range (> 10.0mmol/L) (TAR), and glycemic variability (GV).Results: A total of 68 patients completed the 12-week FGM follow-up (age 67.9 ± 5.2 years; BMI 25.4 ± 3.3kg/m²). Overall findings revealed that compared to baseline, HbA1c decreased from 7.81 ± 1.25% to 7.44± 1.10% after 12 weeks of intermittent wearing of FGM (p < 0.001). In the subgroup analysis with HbA1c ≥ 7.0%, the results showed a significant reduction in HbA1c of 0.51mmol/L after 12 weeks (8.36 ± 0.95% vs 7.75 ± 0.97%, p < 0.001). And there was a significant reduction in TBR in the subgroup with HbA1c < 7% (p = 0.028). Multiple linear regression analysis showed that the baseline HbA1c (β = − 0.529, P< 0.001), duration of T2DM (β = 0.341, P = 0.001), and the frequency of sensor use (β = − 0.269, P = 0.043) were associated with the reduction in HbA1c level.Conclusion: Intermittent use of FGM is associated with an improvement in glycemic outcomes and reduces the risk of hypoglycemia in Chinese elderly patients with T2DM.Keywords: flash glucose monitoring, type 2 diabetes mellitus, HbA1c, time in range

Dan Li,1– 3,&ast; Qingling Li,4,&ast; Zhen Huang,2 Wenhao Wu,2 Xinyuan Fan,2 Jing Liu,2 Ruoran Li,2 Qi Zhang,2 Xin Su1 1Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, 210000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221000, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Xuzhou First People’s Hospital, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Su, Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, 210000, People’s Republic of China, Email suxinjs@163.com Qi Zhang, Department of Respiratory and Critical Care Medicine, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221000, People’s Republic of China, Email zhangqi1107@126.comBackground: tNGS and mNGS are valuable tools for diagnosing pathogens in lower respiratory tract infections (LRTIs), which subsequently influence treatment strategies. However, the impact of tNGS and mNGS on antimicrobial stewardship in patients with LRTIs remains unclear.Methods: Patients diagnosed with LRTIs who underwent tNGS or mNGS between June 2021 and January 2024 were included. Patients who underwent both tNGS and conventional microbiologic tests (CMTs) were grouped into the tNGS group, the others were divided into the mNGS group. Then, the diagnostic efficacy of tNGS and mNGS was compared, along with their impact on antimicrobial management and clinical outcomes.Results: 548 patients with an initial diagnosis of LRTIs who underwent tNGS or mNGS were evaluated. Finally, 321 patients were analyzed, with 117 patients in tNGS group and 204 patients in mNGS group. The overall pathogen detection rates for tNGS and mNGS were 89.74% and 89.71% (P=0.991). The distribution of detected pathogens was similar between tNGS and mNGS, with bacteria being the predominant microorganisms. The proportions of patients who underwent antimicrobial agent changes and received targeted therapy were not significantly different between tNGS and mNGS groups (P=0.270; P=0.893). Additionally, no significant differences were noted in the rates of antibiotic de-escalation, escalation, or changes in the opposite direction (all P> 0.05). The same results was observed in the proportions of patients with addition or reductions in antiviral, antifungal, and antibacterial agents (all P> 0.05). Hospital stays, improvement rate and mortality rate were also similar (all P> 0.05).Conclusion: tNGS and mNGS demonstrate comparable overall pathogen yield rates in patients with LRTIs. Furthermore, tNGS is also comparable to mNGS in terms of adjusting antimicrobial treatments and clinical outcomes, tNGS meets the clinical needs of most patients with LRTIs and can be firstly used for these patients.Keywords: tNGS, mNGS, antimicrobial management, lower respiratory tract infection

Yuxuan Cai,1 Weiwei Wang,1 Qinlian Jiao,1 Tangbin Hu,1 Yidan Ren,1 Xin Su,2 Zigan Li,2 Maoxiao Feng,1 Xiaoyan Liu,1 Yunshan Wang1 1Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, People’s Republic of ChinaCorrespondence: Yunshan Wang, Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China, Email wangyunshansd@sdu.edu.cnAbstract: Liver cancer has become a major global health challenge due to its high incidence, high rate of late diagnosis and limited treatment options. Although there are many clinical treatments available for liver cancer, the cure rate is still very low, and now researchers have begun to explore new aspects of liver cancer treatment, and nanotechnology has shown great potential for improving diagnostic accuracy and therapeutic efficacy and is therefore a promising treatment option. In diagnosis, nanomaterials such as gold nanoparticles, magnetic nanoparticles, and silver nanoparticles can realize highly sensitive and specific detection of liver cancer biomarkers, supporting diagnosis and real-time monitoring of the disease process. In terms of treatment, nanocarriers can realize precise targeted delivery of drugs, improve the bioavailability of liver cancer therapeutic drugs and reduce systemic toxic side effects. In addition, advanced technologies such as nanoparticle-based photothermal therapy and photodynamic therapy provide innovative solutions to overcome drug resistance and local tumor ablation. Therefore, in this paper, we will introduce nanotechnology for hepatocellular carcinoma in terms of tumor marker detection, targeted drug delivery, and synergistic PDT/CDT therapy.Keywords: nanoparticles, tumor marker detection, drug delivery system, tumor therapy

Fang Wang, Anliu Nie, Shaona Liao, Zhisheng Zhang, Xiangfen Su The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Xiangfen Su, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China, Email suxianfengfy@163.comAim: To investigate the current status of the sense of coherence in lung cancer patients undergoing chemotherapy and explore the mediating role of social support and hope in the relationship between therapy-related symptoms and sense of coherence.Methods: We conducted a cross-sectional study to investigate lung cancer chemotherapy patients aged 18 years or older who completed at least two cycles of chemotherapy. Patients were recruited from the First Affiliated Hospital of Guangzhou Medical University’s chemotherapy day ward from May to December 2023. Patients were required to complete a questionnaire that included the Sense of Coherence Scale, the Perceived Social Support Scale, the Herth Hope Index, and the Therapy-related Symptoms Checklist. The structural equation model was used to test the mediating role of social support and hope between therapy-related symptoms and the sense of coherence.Results: A total of 241 patients were included. The scores of the sense of coherence, hope level, therapy-related symptoms, and social support were 68.79 ± 11.24, 38.94 ± 4.25, 11.53 ± 8.15, and 69.49 ± 8.15, respectively. Sense of coherence, social support, hope, and therapy-related symptoms were significantly related (P< 0.01). Therapy-related symptoms had a direct negative influence on the sense of coherence [B=− 0.144, 95% CI (− 0.209, − 0.070)]. Meanwhile, therapy-related symptoms influenced the sense of coherence via three pathways: independent mediation of social support [B=− 0.021, 95% CI (− 0.065, − 0.002)], independent mediation of hope [B=− 0.022, 95% CI (− 0.057, − 0.000)], and chain mediation of social support and hope [B=− 0.012, 95% CI (− 0.035, − 0.002)].Conclusion: Lung cancer patients undergoing chemotherapy experience a medium sense of coherence. This study’s findings indicate that the relationship between therapy-related symptoms and sense of coherence is affected by the independent mediating effect of social support and hope and the chain mediating effect of social support and hope. Therefore, reducing the burden of their therapy-related symptoms, providing them with social support, and fostering their hope can enhance patients’ sense of coherence and improve their quality of life.Keywords: lung cancer, chemotherapy, sense of coherence, therapy-related symptoms, social support, hope, mediation analysis

Kun Qin,1,2,&ast; Ting Gong,3,&ast; Shi-Fan Ruan,1,&ast; Min Lin,1 Xinhong Su,1 Xiaoqing Lv,1 Bo Cheng,1,4 Chao Ji1,4 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 2Department of Dermatology, Jiangmen Central Hospital, Jiangmen, Guangdong, 529000, People’s Republic of China; 3Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 4Key Laboratory of Skin Cancer of Fujian Higher Education Institutions, The Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Ji; Bo Cheng, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, 350000, People’s Republic of China, Tel +86 18651619908 ; Tel +86 13859024296, Email jichaofy@fjmu.edu.com; chengbo630415@126.comPurpose: Immune checkpoint inhibitors (ICIs) can cause life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Large-scale original research on ICI-induced SJS/TEN is limited. This study aimed to explore the unique clinical characteristics and potential pathophysiological mechanisms of SJS/TEN induced by ICIs.Methods: This cross-sectional study compared the clinical features of SJS/TEN induced by ICIs and non-ICIs, and reviewed the case characteristics of ICI-induced SJS/TEN. Clinical features were analyzed using independent t-tests, Mann–Whitney U-tests, and multivariable regression models.Results: This study enrolled 41 cases of ICI-induced SJS/TEN and 107 non-ICI-induced cases from January 22, 2015, to May 28, 2024. ICI-induced SJS/TEN patients exhibited a trend towards a longer latency period (β: 17, 95% CI: − 1.49 to 35.48), a smaller affected body surface area (BSA) (β: − 40.68, 95% CI: − 71.59 to − 9.77), and milder oral and ocular mucositis than non-ICI-induced cases. A literature review identified PD-1 inhibitors as the primary ICIs involved and systemic corticosteroids as the most frequent intervention. No statistically significant difference in mortality rate was observed between patients treated with systemic corticosteroids alone and those receiving combination therapies (P= 0.85). The mortality rate for ICI-induced SJS/TEN was 24.5%.Conclusion: This study offered the largest comparative analysis to date, highlighting the unique clinical features of ICI-induced SJS/TEN, including a smaller affected BSA, a prolonged latency period trend, and milder oral and ocular mucositis. We described the epidemiology, clinical presentation, and therapeutic strategies for ICI-induced SJS/TEN. These findings not only contribute to a deeper understanding of the complex immune-inflammatory pathways in severe immune-related cutaneous adverse events (ircAEs) but also may inform the development of more targeted and effective treatments.Keywords: comparative analysis, clinical characteristic, latency period, body surface area, treatment

Shi-Fan Ruan,1– 3,&ast; Xinhong Su,1,2,&ast; Zhixun Xiao,1,2,&ast; Yihua Zhang,1,2,&ast; Tingting Lin,1,2 Renwei Luo,1,2 Niu Xiang,1,2 Bo Cheng,1– 3 Ting Gong,4 Chao Ji1– 3 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 2Key Laboratory of Skin Cancer of Fujian Higher Education Institutions, Fuzhou, Fujian, 350000, People’s Republic of China; 3Fujian Provincial Clinical Research Center for Immune Skin Diseases, Fuzhou, Fujian, 350000, People’s Republic of China; 4Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Gong, Central Laboratory, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350000, People’s Republic of China, Email gongtingfy@fjmu.edu.cn Chao Ji, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350000, People’s Republic of China, Email jichaofy@fjmu.edu.cnPurpose: Recent studies have shown that novel biologics may provide significant clinical benefits for patients with generalized pustular psoriasis (GPP). Ustekinumab and secukinumab have been approved in Japan for GPP treatment in adult patients. However, the differences in efficacy and safety of these two drugs in GPP are not known.Aim: Based on the genetic background, we aimed to compare the efficacy and safety of secukinumab and ustekinumab in patients with GPP.Methods: Patients with moderate to severe GPP who were treated with ustekinumab/secukinumab at our department from July 2019 to May 2022 were included in this study and followed up for 48 weeks. The difference in efficacy between ustekinumab and secukinumab was evaluated by assessing changes in body temperature, laboratory indices, recovery of skin lesions, and changes in quality of life. Additionally, we collected patients’ saliva for genotyping and explored the effect of CARD14 genetic mutations on clinical efficacy.Results: A total of 65 patients (32 adults and 33 children) with moderate to severe GPP were included in this study. 31 patients received ustekinumab therapy, and 34 patients were treated with secukinumab. Secukinumab demonstrated superiority to ustekinumab, as evidenced by a higher GPPASI 90 response at week 2. Additionally, the efficacy of ustekinumab and secukinumab was found to be independent of the presence of the CARD14 mutation.Conclusion: Secukinumab is superior to ustekinumab in rapidly clearing the skin and improving health-related quality of life. Moreover, the responses to ustekinumab/secukinumab in patients were not influenced by CARD14 gene mutations.Keywords: generalized pustular psoriasis, secukinumab, ustekinumab, clinical efficacy, safety, gene mutations

Chunliu Hou,1,&ast; Ying Liu,2,&ast; Xuesen Su,1 Shouyuan Tian,1 Yan Li1,2 1College of Anesthesia, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Anesthesiology, Tianjin Jizhou People’s Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shouyuan Tian; Yan Li, Email chinatsyjj@sxmu.edu.cn; drliyan@163.comBackground: Due to the global prevalence of opioid drugs, postsurgical prescriptions can lead to substantial opioid consumption, highlighting the increasing need for alternative medications. Alternative medicines can markedly lessen the usage of opioids after surgery, but the variety and notable side effects of these alternatives require meticulous experimental support.Objective: This study explored the efficacy and safety of ulinastatin for alleviating postsurgical pain, for reducing the need for opioids, and for inclusion in conventional treatment methods.Methods: A total of 108 patients undergoing elective hip replacement were randomly allocated into either the experimental group (56 cases, standard pain relief treatment plus 60 IU ulinastatin) or the control group (40 cases, standard pain relief treatment). The main outcomes measured were the total consumption of opioids at 24, 48, and 72 h postoperatively. Secondary outcomes comprised patient-reported pain indices and levels of satisfaction with pain control. The frequency of adverse events evaluated medication safety.Results: There were no statistically significant differences in age, sex, or underlying diseases between the two groups. Over 24 hours, opioid consumption was higher in the standard treatment group (66.6 mg; mean difference [MD]: 4.43 mg; 95% CI: 57.6– 75.5) than in the intervention group (54.5 mg; MD: 1.91 mg; 95% CI: 50.7– 58.3). The standard treatment group exhibited a notably higher incidence of adverse reactions. However, there was no disparity in post-discharge satisfaction between the groups, with an odds ratio of 1.058 (95% CI: 0.62– 1.82; P > 0.05). Additionally, significant differences in C-reactive protein levels were observed immediately and 6 h after surgery between the two groups.Conclusion: Within 72 h post-surgery, ulinastatin was effective in substantially reducing the use of opioids while maintaining adequate pain control. Ulinastatin may be beneficial for postoperative pain management and for reducing the risks associated with opioid use.Registered: ClinicalTrials.gov ChiCTR2300072126.Keywords: ulinastatin, postoperative pain, pain management, opioid

Jian Li,1,&ast; Li Liu,2,&ast; Zhiyun Gao,1 Xia Chuai,3 Xiaokun Liu,4 Xiaobo Zhang,2 Xinyu Zhang,2 Xiaoqing Su,2 Qian Xu,2 Zhuojun Deng2 1Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega Science, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China; 4Department of Ophthalmology, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuojun Deng, Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email dengzhuojun@126.com; 37700469@hebmu.edu.cnPurpose: The incidence of visceral leishmaniasis (VL), a global infectious disease, has been on the rise in China’s Hebei province. When patients achieve clinical cure, they often do not reach an etiological cure, which may lead to recurrence of the disease. Here, we report a case of visceral leishmaniasis with a negative blood smear and bone marrow cytology.Patients and Methods: A 65-year-old man and bronchoalveolar lavage fluid mNGS.Results: A 65-year-old man developed a chronic fever, anorexia, splenomegaly, and pancytopenia. The blood metagenomic second-generation sequencing (mNGS) revealed Leishmania sequence readings, which led to the diagnosis of VL. After sodium antimony gluconate treatment, the blood smear and bone marrow cytology revealed no Leishmania bodies. However, pancytopenia and respiratory failure did not fully subside, and cardiotoxic damage emerged. The bronchoalveolar lavage fluid (BALF) mNGS was performed to detect the pathogen. Through BALF mNGS, Leishmania sequence was still detectable. Therefore, after the ECG returned to normal, antimony sodium gluconate was administered as a next course of treatment.Conclusion: BALF mNGS may assist in evaluating the therapeutic efficacy of VL with respiratory failure, especially in patients with negative blood and bone marrow cytology.Plain Language Summary: Accurate detection of visceral leishmaniasis is essential for clinical diagnosis.It is uncommon to use alveolar lavage fluid mNGS in etiological diagnosis.Patient with negative bone marrow cytology may refer to alveolar lavage fluid mNGS. Keywords: visceral leishmaniasis, metagenomic second-generation sequencing, bronchoalveolar lavage fluid, parasite diseases, case report

Qiming Gan,1,&ast; Quanzhen Liu,1,2,&ast; Yanjuan Wu,1,&ast; Xiaofeng Zhu,1,2 Jingcun Wang,1 Xiaofen Su,1 Dongxing Zhao,1 Nuofu Zhang,1 Kang Wu1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Disease, Department of Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2Nanshan School, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kang Wu; Nuofu Zhang, Department of Pulmonary and Critical Care Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No. 28 Qiaozhong Mid Road, Guangzhou, Guangdong, 510160, People’s Republic of China, Email d102_wk@126.com; nfzhanggird@163.comPurpose: Obstructive sleep apnea (OSA) had been associated with asthma in observational studies, but the effect of OSA on the onset of asthma in childhood or adulthood remains unclear, and the causal inferences have not been confirmed. This study aims to investigate the potential causal association between OSA with asthma, including different age-of-onset subtypes, providing reliable basis for the clinical treatment of OSA and asthma.Patients and Methods: Causality between OSA and asthma was assessed using a two-sample bi-directional Mendelian randomization (MR) analysis. OSA data were obtained from the FinnGen consortium R9, while asthma and its subtypes (adult-onset asthma, child-onset asthma, and moderate-to-severe asthma) were sourced from the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was chosen as the primary analysis and was complemented by various sensitivity analyses. The MR-PRESSO outlier test was employed to systematically identify and remove outlier variants, mitigating heterogeneity and potential effects of horizontal pleiotropy.Results: The MR analyses provided evidence of genetically predicted OSA having a promoting effect on child-onset asthma (OR,1.49; 95% CI, 1.05– 2.11; P=0.025) and moderate-to-severe asthma (OR,1.03; 95% CI, 1.00– 1.06; P=0.046). However, no causal association between OSA with asthma and adult-onset asthma was observed.Conclusion: Our study revealed a causal association between OSA and child asthma, but not in adults. Moderate-to-severe asthma may have a potential promoting effect on OSA. These findings underscore the importance of age-specific considerations in managing asthma and suggests the need for personalized approaches in clinical practice.Keywords: asthma, obstructive sleep apnea, Mendelian randomization, genetic

Xinlyu Huang,1 Pengxiang Zhao,2 Gongjie Zhang,1 Xiangxi Su,1 Hanlin Li,1 Huizi Gong,1 Xuemei Ma,2 Fang Liu1 1Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2College of Chemistry and Life Science, Beijing University of Technology, Beijing, People’s Republic of ChinaCorrespondence: Fang Liu, Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email roseliufang@qq.comPurpose: Alopecia significantly affects the appearance and psychology of patients, and pharmacological therapies and hair transplantation are the main treatments for alopecia, but both have limitations. This review aimed to summarize the non-pharmacological therapies that promote hair growth and regeneration.Patients and Methods: This is a non-systematic review. Multiple databases was searched with relevant data published between 1997 and 2024. Searching and screening followed the PRISMA guidelines.Results: Novel therapeutic modalities, such as gas molecules, platelet-rich plasma, laser, and microneedling, can change the microenvironment of hair follicles, activate hair follicle stem cells, and promote hair growth and regeneration.Conclusion: This paper reviews research on the application of non-pharmacological therapies in alopecia treatment and hair regeneration, with a view to providing an important basis for future research on alopecia treatment and the postoperative treatment of patients after hair transplantation.Keywords: alopecia, hair regrowth, non-pharmacologic, gas therapy, regenerative cellular therapy, laser therapy, microneedle therapy

Jie Jin,1 Jie Lu,1 Xinyang Su,2 Yinhuan Xiong,3 Shasha Ma,4 Yang Kong,5 Hongmei Xu1 1School of Nursing, Binzhou Medical University, Binzhou, People’s Republic of China; 2Department of Spine Surgery, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 3Department of Nursing, Binzhou People’s Hospital, Binzhou, People’s Republic of China; 4Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 5School of Health Management, Binzhou Medical University, Yantai, People’s Republic of ChinaCorrespondence: Hongmei Xu, School of Nursing, Binzhou Medical University, No. 525 Huanghe 3rd Road, Binzhou, 256600, People’s Republic of China, Tel +86-13754689536, Email hmx58@163.com Yang Kong, School of Health Management, Binzhou Medical University, No. 346 Guanhai Road, Yantai, 264003, People’s Republic of China, Tel +86-13773576163, Email kongyang@bzmc.edu.cnPurpose: The purpose of this study was to establish and validate machine learning-based models for predicting the risk of venous thromboembolism (VTE) in intensive care unit (ICU) patients.Patients and Methods: The clinical data of 1494 ICU patients who underwent Doppler ultrasonography or venography between December 2020 and March 2023 were extracted from three tertiary hospitals. The Boruta algorithm was used to screen the essential variables associated with VTE. Five machine learning algorithms were employed: Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Gradient Boosting Decision Tree (GBDT), and Logistic Regression (LR). Hyperparameter optimization was conducted on the predictive model of the training dataset. The performance in the validation dataset was measured using indicators, including the area under curve (AUC) of the receiver operating characteristic (ROC) curve, specificity, and F1 score. Finally, the optimal model was interpreted using the SHapley Additive exPlanation (SHAP) package.Results: The incidence of VTE among the ICU patients in this study was 26.04%. We screened 19 crucial features for the risk prediction model development. Among the five models, the RF model performed best, with an AUC of 0.788 (95% CI: 0.738– 0.838), an accuracy of 0.759 (95% CI: 0.709– 0.809), a sensitivity of 0.633, and a Brier score of 0.166.Conclusion: A machine learning-based model for prediction of VTE in ICU patients were successfully developed, which could assist clinical medical staff in identifying high-risk populations for VTE in the early stages so that prevention measures can be implemented to reduce the burden on the ICU patients.Keywords: venous thromboembolism, machine learning, algorithm, prediction model, intensive care unit

Donghao Wang,1,&ast; Yuting Zhang,1,&ast; Qiming Gan,1,&ast; Xiaofen Su,1,&ast; Haojie Zhang,1,2,&ast; Yanyan Zhou,1 Zhiyang Zhuang,1 Jingcun Wang,1 Yutong Ding,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang; Dongxing Zhao, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86-13600460056 ; +86-13650901411, Email nfzhanggird@163.com; rieast@163.comObjective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea–hypopnea index (AHI).Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR).Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07– 1.62, P < 0.01) and 1.45 (95% CI = 1.01– 2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02– 3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes.Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.Keywords: obstructive sleep apnea, arousal threshold, apnea–hypopnea index, hypertension, diabetes

Dengyun Pan, Xin Di, Bingdi Yan, Xiaomin Su Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Bingdi Yan; Xiaomin Su, Department of Respiratory Medicine, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, People’s Republic of China, Email yanbingdi@jlu.edu.cn; suxiaomin@jlu.edu.cnAbstract: Pulmonary fibrosis is a group of chronic, progressive, and irreversible interstitial lung diseases, which are common to most end-stage lung diseases and are one of the most difficult diseases of the respiratory system. In recent years, due to the frequent occurrence of air pollution and smog, the incidence of pulmonary fibrosis in China has increased year by year, the morbidity and mortality rates of pulmonary fibrosis have gradually increased and the age of the disease tends to be younger. However, the pathogenesis of pulmonary fibrosis is not yet fully understood and is needed to further explore new drug targets. Studies have shown that non-coding RNAs play an important role in regulating the process of pulmonary fibrosis, non-coding RNAs and their specifically expressed can promote or inhibit the process. Here, we review the role of some in the regulation of pulmonary fibrosis signaling pathways and provide new ideas for the clinical diagnosis and treatment of pulmonary fibrosis.Keywords: pulmonary fibrosis, MicroRNA, LncRNA, CircRNA, signaling pathways

Min Lin,1,&ast; Ting Gong,2,&ast; Shifan Ruan,1,&ast; Xiaoqing Lv,1 Rongying Chen,1 Xinhong Su,1 Bo Cheng,1 Chao Ji1 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000, People’s Republic of China; 2Department of Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Cheng; Chao Ji, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Taijiang District, Fuzhou, 350000, People’s Republic of China, Tel +86 13859024296 ; +86 18651619908, Email bochengg@163.com; jichaofy@fjmu.edu.cnObjective: Anticancer drugs have revolutionized tumor therapy, with cutaneous toxicities such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) being common immune-related adverse events. The debate over the efficacy of systemic corticosteroids in treating these conditions persists, while tumor necrosis factor (TNF)-alpha inhibitors show promise. This study aims to evaluate the effectiveness and safety of combination therapy involving the TNF-α inhibitor adalimumab for SJS/TEN induced by anticancer drugs.Methods: A literature review of SJS/TEN cases induced by anticancer drugs from 1992 to 2023 was conducted, alongside an analysis of patients admitted to the First Affiliated Hospital of Fujian Medical University during the same period. Clinical characteristics, skin healing time, mortality, and adverse events were evaluated in two treatment groups: SJS/TEN patients treated with targeted anticancer therapies and immunotherapies.Results: Among the 27 patients studied (18 with SJS or SJS-TEN overlapping and 9 with TEN), combination therapy with adalimumab significantly reduced mucocutaneous reepithelization time and healing duration compared to corticosteroid monotherapy. Patients receiving adalimumab combined with corticosteroids had lower actual mortality rates than those on corticosteroid monotherapy. The combination therapy also showed a trend towards reducing standardized mortality rates based on the Score of Toxic Epidermal Necrolysis (SCORTEN).Conclusion: The findings suggest that adalimumab in combination with corticosteroids provides significant clinical benefits and is safer than corticosteroids alone for treating SJS/TEN induced by targeted anticancer therapies and immunotherapies. This study contributes valuable insights into potential treatment strategies for severe cutaneous adverse reactions to anticancer drugs, highlighting the importance of exploring alternative therapies such as TNF-α inhibitors in managing these conditions effectively.Keywords: anti-TNF-α, adalimumab, treatment, Stevens-Johnson syndrome, toxic epidermal necrolysis

Lihua Zhu,1,&ast; Lingling Zhou,2,3,&ast; Liang Wang,4,&ast; Cunte Chen,2 Jie Qiao,1 Xinran Huang,1 Xiaoyan Su,1 Shaohua Chen,2 Bo Li,2 Xiuli Wu,2 Yangqiu Li2 1Department of Rheumatology and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510632, People’s Republic of China; 4Department of Oncology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangqiu Li, Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, People’s Republic of China, Tel +86 20 85226877, Fax +86 20 85226877, Email yangqiuli@hotmail.com Lihua Zhu, Department of Rheumatology and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China, Email zhulihua20121113@163.comBackground: There have been several studies regarding the susceptibility of A20 gene SNPs (rs2230926 and rs5029937) in rheumatoid arthritis (RA). However, little is known about the association between polymorphisms in the A20 promoter and RA. The aim of this study was to investigate the characteristics of A20 promoter polymorphisms and the association between these polymorphisms and clinical significance in Chinese RA patients.Methods: PCR and sequencing were used to identify A20 gene polymorphisms in peripheral blood mononuclear cells (PBMCs) from 123 RA cases and 31 healthy individuals.Results: Only one SNP (rs5029924) in the A20 gene promoter was identified in RA patients and healthy individuals. 6 patients who carried heterozygous rs5029924 (3918C>T) together with heterozygous rs5029937 (11,571 G>T) and rs2230926 (12,486 T>G, Phe127Cys) suffered from joints deformity or refractory RA.Conclusion: We reported the A20 promoter polymorphism rs5029924 in RA patients for the first time. rs5029924 concomitant with rs2230926 and rs5029937 may be a prognostic predictor for joint deformity or refractory RA.Keywords: A20, promoter, polymorphism, RA, deformity, refractory, predictor

Xu Su,1,&ast; Yimei Zhang,1,&ast; Huilin Zhou,1 Fang Ma,1 Xiaorong Jin,1 Yangjuan Bai,2 Wei Wei,3 Xiong Zhang,1 Min Zhou1 1Department of Nursing, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Cardiology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Digestive Surgery Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Ma, Department of Nursing, The First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Kunming, 650032, People’s Republic of China, Email rebeccamalei@126.comPurpose: Studies had reported some influencing factors of health behavior among patients with coronary heart disease(CHD) after percutaneous coronary intervention(PCI). However, considering that human perceptions are complex, unrestricted and dynamically changing. A longitudinal qualitative study was conducted to explore the determinants of health-related behaviors of patients after PCI and dynamic changes of these determinants at the 1st, 3rd, and 6th months.Patients and Methods: Using purposive sampling, 18 patients undergoing PCI were interviewed. The conventional content analysis method was used to identify categories and subcategories. Semi-structured, face-to-face or telephone in-depth interviews were conducted at the cardiology unit of a tertiary referral hospital in Yunnan Province, China from March 2022 to January 2023.Results: Seven categories with some subcategories were constructed from the data, categorized into three domains. Firstly, individual factors include (i) Personal coping with healthy lifestyle requirements (tried but failed; I can do it), (ii) individual perception and feeling toward disease (knowing about the disease; belief of cure; fears of relapse), and (iii) personal benefits (improved health; meaning of life). Secondly, social factors include (i) social facilitators (family resources; healthcare support), (ii) social barriers (inconvenient medical care service; conflicting information). Finally, cultural factors include (i) way of living (dietary habits; key roles of yan (cigarette) and jiu (alcohol) in Chinese society), (ii) way of thinking (fatalism and Confucian familism).Conclusion: The determinants of health-related behaviors of patients after PCI are multifaceted and dynamic. Different interventions should be formulated to promote patients’ adherence to health behaviors. Moreover, priority should be given to the impact of traditional Chinese philosophy on the health behaviors of patients after PCI, and the health promotion program for these patients should be culturally sensitive. In addition, future research should further explore the determinants of health behaviors among diverse ethnic minorities after PCI, which has not been fully inquired in this study.Keywords: coronary heart disease, percutaneous coronary intervention, health behavior adherence, qualitative research, Chinese traditional culture

Jianmei Lu,1,2,&ast; Yongzhu Zeng,1,&ast; Huashuai Zhong,1 Wei Guo,1 Yuyan Zhang,1 Wanting Mai,3 Yucui Qin,4 Xiaodan Su,3 Bo Zhang,5 Weisen Wu,1 Yu Zhu,1 Qiujie Huang,6 Yong Ye1,7– 9 1Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China; 2The Second Nanning People’s Hospital, Nanning, People’s Republic of China; 3The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 4Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 5Scientific Research Center, Guilin Medical University, Guilin, People’s Republic of China; 6Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China; 7Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Nanning, People’s Republic of China; 8Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Nanning, People’s Republic of China; 9Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujie Huang, Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China, Email hqj8@163.com Yong Ye, Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China, Email yong-ye@163.comBackground and Purpose: Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease.Methods: The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing.Results: The nanoparticles prepared in this study have an average particle size of (255.9± 5.10) nm, with an encapsulation rate of (72.83± 2.13) % and a drug loading of (4.65± 0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice.Conclusion: This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.Keywords: nanoparticles, colonic targeting, metabolic disorders, gut microbiota

Jinxin Ma,1,&ast; Peng Yu,1,&ast; Shang Ma,1,&ast; Jinjin Li,1 Zhen Wang,1 Kunpeng Hu,1 Xinzhe Su,1 Bei Zhang,1 Shao Cheng,1– 3 Shangzeng Wang1– 3 1School of Osteopathy, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Department of Arthropathy, Henan Province Hospital of Chinese Medicine (The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, People’s Republic of China; 3School of Osteopathy, Henan Province Engineering Research Center of Basic and Clinical Research of Bone and Joint Repair in Chinese Medicine, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shao Cheng; Shangzeng Wang, 156 Jinshui East Road, Zhengzhou, Henan, People’s Republic of China, Tel +86 15093141825 ; +86 13838527504, Fax +0371-86667366, Email chengshao4476@163.com; wangsz74@163.comPurpose: Osteoarthritis (OA) is the most common joint disease worldwide and is the primary cause of disability and chronic pain in older adults.Ferroptosis is a type of programmed cell death characterized by aberrant iron metabolism and reactive oxygen species accumulation; however, its role in OA is not known.Methods: To identify ferroptosis markers co-expressed in articular cartilage and synovium samples from patients with OA, in silico analysis was performed.Signature genes were analyzed and the results were evaluated using a ROC curve prediction model.The biological function, correlation between Signature genes, immune cell infiltration, and ceRNA network analyses were performed. Signature genes and ferroptosis phenotypes were verified through in vivo animal experiments and clinical samples. The expression levels of non-coding RNAs in samples from patients with OA were determined using qRT-PCR. ceRNA network analysis results were confirmed using dual-luciferase assays.Results: JUN, ATF3, and CDKN1A were identified as OA- and ferroptosis-associated signature genes. GSEA analysis demonstrated an enrichment of these genes in immune and inflammatory responses, and amino acid metabolism. The CIBERSORT algorithm showed a negative correlation between T cells and these signature genes in the cartilage, and a positive correlation in the synovium. Moreover, RP5-894D12.5 and FAM95B1 regulated the expression of JUN, ATF3, and CDKN1A by competitively binding to miR-1972, miR-665, and miR-181a-2-3p. In vivo, GPX4 was downregulated in both OA cartilage and synovium; however, GPX4 and GSH were downregulated, while ferrous ions were upregulated in patient OA cartilage and synovium samples, indicating that ferroptosis was involved in the pathogenesis of OA. Furthermore, JUN, ATF3, and CDKN1A expression was downregulated in both mouse and human OA synovial and cartilage tissues. qRT-PCR demonstrated that miR-1972, RP5-894D12.5, and FAM95B1 were differentially expressed in OA tissues. Targeted interactions between miR-1972 and JUN, and a ceRNA regulatory mechanism between RP5-894D12.5, miR-1972, and JUN were confirmed by dual-luciferase assays.Conclusion: This study identified JUN, ATF3, and CDKN1A as possible diagnostic biomarkers and therapeutic targets for joint synovitis and OA. Furthermore, our finding indicated that RP5-894D12.5/miR-1972/JUN was a potential ceRNA regulatory axis in OA, providing an insight into the connection between ferroptosis and OA.Keywords: osteoarthritis, ferroptosis, synovitis, bioinformatics, JUN, ATF3, CDKN1A, GPX4

Donghao Wang,1,&ast; Yating Chen,1,&ast; Yutong Ding,1,&ast; Yongkang Tang,1,&ast; Xiaofen Su,1,&ast; Shiwei Li,1 Haojie Zhang,1,2 Yanyan Zhou,1 Zhiyang Zhuang,1 Qiming Gan,1 Jingcun Wang,1 Yuting Zhang,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China, Tel +86-13600460056, Email nfzhanggird@163.comBackground: Obstructive sleep apnea (OSA) is a common chronic disease with various comorbidities. The cardiometabolic index (CMI) reflects visceral fat tissue distribution and function, assessing the risk of obesity-related conditions such as metabolic syndrome (MetS) and stroke, which are strongly connected to OSA. The relationship between CMI with OSA and OSA combined with MetS (OMS) remains unclear. This study aims to evaluate the screening value of CMI for OSA and OMS, compared to the lipid accumulation product (LAP).Methods: A total of 280 participants who underwent polysomnography were finally included, with the measurements of metabolic-related laboratory test results such as total cholesterol and triglyceride. Receiver operating curve (ROC) analysis and calculation of the area under the curve (AUC) were conducted to assess the screening potential of CMI, LAP, and the logistic regression models established based on them for OSA and OMS. The Youden index, sensitivity, and specificity were used to determine the optimal cutoff points.Results: ROC curve analysis revealed that the AUCs for CMI in screening OSA and OMS were 0.808 and 0.797, and the optimal cutoff values were 0.71 (sensitivity 0.797, specificity 0.776) and 0.89 (sensitivity 0.830, specificity 0.662), respectively, showing higher Youden index than LAP. The AUCs of screening models based on CMI for OSA and OMS were 0.887 and 0.824, respectively.Conclusion: CMI and LAP can effectively screen for OSA and OMS, while CMI has more practical cutoff values for identifying the diseased states. Screening models based on CMI demonstrate a high discriminatory ability for OSA and OMS, which needs verification in a large-scale population.Keywords: obstructive sleep apnea, metabolic syndrome, cardiometabolic index, lipid accumulation products, screening model

Xia Su,1,2 Shuli Ma,3 Xiaoxi Yang,4 Can Zhang,1 Weiwei Chen5 1Hepatobiliary and Pancreatic Center, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2School of Nursing & Public Health, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 4School of Health and Wellness, Panzhihua University, Panzhihua, Sichuan, People’s Republic of China; 5Medical College of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Weiwei Chen, Tel +86 18051062900, Email cww1984@126.comBackground: The incidence and recurrence rate of acute pancreatitis (AP) continues to increase worldwide. The risk of AP attack and recurrence is closely related to the patient’s health literacy. Previous studies have shown that AP patients had low levels of health literacy. Understanding patients’ experience in AP’s diagnosis and treatment process and their health literacy needs might significantly improve their health status.Objective: This study aims to understand the experience of acute pancreatitis (AP) patients in the diagnostic and treatment process and explore their health literacy needs at various phases of this process.Methods: This study utilized a qualitative approach based on Timing It Right theory. A purposive sampling strategy was employed to select 31 participants diagnosed with AP at various phases of the diagnosis and treatment process. These patients were selected from the Pancreatitis Treatment Centers of two tertiary hospitals in Eastern China. Subsequently, semi-structured in-depth interviews were conducted with the selected participants. The qualitative data was analyzed using the Colaizzi’s method.Results: The themes of AP patients’ experiences and health literacy needs at various phases of the diagnosis and treatment process were presented as follows. 1. Diagnosis phase: inability to obtain disease information, psychological support seeking, and change unhealthy lifestyle; 2. Hospitalization phase: disease treatment information needs and medical professionals’ healthcare. 3. Discharge Preparation phase: fear of recurrence, individualized healthy lifestyle instruction. 4. Home Recovery phase: self-management, continuous healthcare needs, and family support.Conclusion: AP patients’ HL needs and health-related problems vary during the diagnosis and treatment process. Medical professionals should comprehend AP patients’ changing needs and individual differences, provide continuous healthcare, and involve families in patient management. These factors support patients’ long-term self-management and preserve their overall health.Keywords: acute pancreatitis, Timing It Right, health literacy need, qualitative study

Xin Su,1,&ast; Hengqiong Gu,1,&ast; Fajun Li,2 Donglei Shi,3 Zhaojun Wang3 1Department of Respiratory, Hainan Hospital of PLA General Hospital, Sanya, People’s Republic of China; 2Department of Critical Care Medicine, The First People’s Hospital of Kunshan, Kunshan, People’s Republic of China; 3Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Donglei Shi; Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, 518107, People’s Republic of China, Tel/Fax +86-755-81206874, Email shidlei@mail.sysu.edu.cn; wangzhj55@mail.sysu.edu.cnBackground: A study aimed to estimate the burden of Chronic obstructive pulmonary disease (COPD) caused by occupational exposure to particulate matter, gases, and fumes in 204 countries from 1990 to 2019.Methods: Data on the deaths number, age-standardized mortality rates (ASMR), and age-standardized disability-adjusted life years (DALYs) rates (ASDR) of COPD attributable to occupational particulate matter, gases, and fumes were collected from the GBD study 2019. We also investigated the association between the ASDR and SDI.Results: There were 517.7 thousand deaths [95% UI: 413.9 to 634.5] in 2019. The number of deaths increased from 1990 to 2019. The ASMR and ASDR were 6.61 (5.24 to 8.17) and 143.02 (118.56 to 168.69) in 2019, respectively, representing a 46% and 44.5% decrease since 1990. China had the highest number of deaths [200,748.4 (151,897.6 to 260,703.9)], while Nepal had the highest ASMR [39 (27.7 to 50)] and ASDR [724.5 (549 to 894.2)]. Males and females 75– 79 and 80– 84 years old had the highest number of COPD deaths. A negative correlation was observed when SDI > 0.4, whereas a positive correlation was found when SDI < 0.4.Conclusion: From 1990 to 2019, there was an increase in the number of deaths, but a decline in ASMR and ASDR globally. Besides, there was a heterogeneous burden of COPD attributable to occupational particulate matter, gases, and fumes across regions and countries. It is important to develop and implement strategies to prevent and reduce the burden of COPD attributable to occupational particulate matter, gases, and fumes.Keywords: chronic obstructive pulmonary disease, occupational particulate matter, gases, fumes, global burden of disease, deaths number, age-standardized rates

Yuming Wang,1,2,&ast; Yunting Zhou,2,&ast; Xiao Zhou,2,&ast; Xiaofei Su,2,&ast; Xiaohua Xu,2 Huiqin Li,2 Jianhua Ma2 1Department of Geriatrics, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 2Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqin Li; Jianhua Ma, Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China, Email Lihuiqin496@126.com; majianhua196503@126.comAim: To evaluate the changes in bone mineral density (BMD) and body composition in untreated patients with type 2 diabetes mellitus (T2DM) before and after chiglitazar or sitagliptin treatment.Methods: A total of 81 patients with T2DM were randomly divided to receive chiglitazar or sitagliptin treatment for 24 weeks (54 in the chiglitazar group and 27 in the sitagliptin group). We measured the spine lumbar BMD, hip BMD, fat mass (FM), fat-free mass (FFM), percent body fat (%BF), android FM, gynoid FM and skeleton muscle mass (SMM) using dual-energy X-ray absorptiometry (DEXA) and examined serum adiponectin (ADP) levels at baseline and the end of the study.Results: There were no significant changes in the BMD of the L2-4, femoral neck, trochanter or total hip as well as in the BMC after 24 weeks of treatment with chiglitazar or sitagliptin. After chiglitazar administration, the FM, gynoid FM and gynoid to total FM ratio were higher, while the android to total FM ratio and the android to gynoid FM ratio (AOI) were significantly lower. Sitagliptin intervention did not result in statistically significant differences in total fat loss, but it did cause significant decreases in %BF and AOI as well as increases in the FFM, gynoid to total FM ratio and SMM. The ADP levels had significantly negative associations with AOI in all eligible patients.Conclusion: The chiglitazar had no deleterious effects on BMD and resulted in body fat redistribution in untreated patients with T2DM.Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02173457).Keywords: type 2 diabetes mellitus, chiglitazar, PPAR, bone mineral density, body composition

Xueyao Su,1,&ast; Yanyan Huang,1,&ast; Wei Dai,2 Yubo Zhang,3 Lijun Zhang,1 Jiayuan Zhang,3 Ruoyan Gong,1 Jingwen Yu,3 Dan Kang,1 Rumei Xiang,1 Jiaojiao Chen,1 Qiuling Shi1– 3 1School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 3State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuling Shi, School of Public Health, Chongqing Medical University, No. 1, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-18290585397, Fax +86-28-85420116, Email qshi@cqmu.edu.cnPurpose: This study aimed to evaluate the presence of recall bias when patients retrospectively report cough scores.Patients and Methods: Patients who underwent lung surgery between July 2021 and November 2021 were recruited for this study. We retrospectively assessed the severity of cough within the past 24 hours and the past 7 days using a 0– 10 numerical rating scale. Recall bias was defined as the difference between the scores reported on the two assessments. Patients were grouped based on the longitudinal change in cough scores from pre-operation to 4 weeks after discharge using group-based trajectory models. Using generalized estimating equation to explore the factors influencing recall bias.Results: Overall, 199 patients were analyzed and demonstrated the three distinct trajectories of post-discharge cough: high (21.1%), medium (58.3%), and low (20.6%). Significant recall bias was found in week 2 for the high-trajectory patients (6.26 vs 5.10, P< 0.01) and in week 3 for the medium-trajectory patients (2.88 vs 2.60, P=0.01). Among all recall bias, 41.8% were of underestimation, and 21.7% of overestimation. The high trajectory group (β=1.14, P< 0.01) and measurement interval (β=0.36, P< 0.01) were risk factors for underestimation, while post-discharge time (β=− 0.57, P< 0.01) and measurement interval (β=− 0.13, P=0.02) were protective factors for overestimation.Conclusion: Retrospective assessment of post-discharge cough in patients who underwent lung surgery will introduce recall bias, with a tendency of underestimation. The high-trajectory group, interval time and post-discharge time are influencing factors of recall bias. For patients with severe cough at discharge, a shorter recall periods should be employed for monitoring, due to the large bias that results from a longer recall period.Keywords: patient-reported outcome, lung surgery, cough measurement, recall bias

Yu Gu,1,2,&ast; Pei Li,3,&ast; Yongying Xiao,2 Jiaojiao Zhang,2 Xin Su1,2 1Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Taikang Xianlin Drum Tower Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Su, Nanjing Drum Tower Hospital, 321 Zhongshan Road, Nanjing, 210008, People’s Republic of China, Email suxinjs@163.comBackground: Pentraxin 3 (PTX3) is an acute-phase protein and an important inflammatory mediator. We hypothesized plasma PTX3 could be a valuable diagnostic biomarker in acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods: In this prospective controlled study, 458 COPD patients and 71 healthy controls from May 2019 to December 2020 in two hospitals were enrolled. COPD patients were divided into AECOPD group (n = 173) and stable COPD group (n = 285). AECOPD patients were subdivided into mild or moderate group (n = 43) and severe group (n = 130) based on severity. Plasma PTX3 levels were detected by ELISA.Results: Plasma PTX3 levels were significantly higher in AECOPD (2.8 ng/mL) compared to stable COPD (0.87 ng/mL) and healthy controls (0.83 ng/mL). In the analysis of AECOPD subgroups, plasma PTX3 level of severe group (4.51 ng/mL) was significantly higher than that of mild or moderate group (1.25 ng/mL). Patients with respiratory failure had higher PTX3 than those without respiratory failure. No difference was observed between stable COPD patients and healthy controls. ROC analysis showed that plasma PTX3 had a considerable ability to distinguish AECOPD from stable COPD [AUC: 0.85, 95% CI (0.81– 0.88), P < 0.0001; cut-off 1.25 ng/mL, sensitivity 77.5%, specificity 74%]. AUC of PTX3 was better than CRP regarding diagnosis of AECOPD. Combination of PTX3 and CRP was superior to either of them in diagnosing AECOPD.Conclusion: Plasma PTX3 levels were significantly higher in AECOPD than stable COPD. The level was associated with the severity of exacerbation. Plasma PTX3 has potential value as a biomarker to diagnose and evaluate AECOPD.Keywords: pentraxin 3, AECOPD, diagnosis, severity, C-reactive protein

Yuhui Geng,1,&ast; Furong Li,2,&ast; Chen Chen,3 Zhuo Liu,1 Xiaojuan Ma,1 Xinya Su,1 Hua Meng,1 Wenwen Lu,1 Xingtian Wang,1 Dongfeng Pan,4 Peifeng Liang5 1School of Public Health, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Clinical Laboratory, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China; 3Department of Public Health, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China; 4Department of Emergency Medicine, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China; 5Department of Medical Records and Statistics, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peifeng Liang, Department of Medical Records and Statistics, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China, Tel +86 951 13895085519, Email doctor_pf@126.comPurpose: To investigate changes in the incidence of infections by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and analyzed whether there was an association between endogenous changes in the organism due to COVID-19 infection and the infections by ESBL-E.Patients and Methods: The study was a single-center retrospective case-control design. A total of 107 patients infected by ESBL-E during the COVID-19 pandemic were selected as the case group, while 214 uninfected patients selected by 1:2 propensity score matching (PSM) acted as the control group. Univariate analysis, LASSO logistic regression, and multivariate logistic regression were used to determine the risk factors for ESBL-E infection. An interrupted time series was used to analyze the changes in the incidence of ESBL-E infections in hospitalized patients during the COVID-19 pandemic.Results: The incidence of infection with ESBL-E showed a significant increase during COVID-19 (3.42 vs 4.92 per 1000 patients, p = 0.003). The incidence of ESBL-E infections increased at an average rate of 0.45 per 1000 patients per week compared to the pre-pandemic period (p = 0.022). Multivariate logistic regression analysis showed that a length of hospitalization ≥ 15 days (OR: 2.98 (1.07– 8.28), chronic kidney disease (OR: 4.25 (1.32– 13.70), white blood cell (WBC) > 9.5× 10^9/L (OR: 3.04 (1.54– 6.01), use of hormonal drugs (OR: 2.38 (1.04– 5.43), antibacterial drug use 1 type (OR: 5.38 (2.04– 14.21), antibacterial drug use 2 types (OR: 23.05 (6.71– 79.25) and antibacterial drug use ≥ 3 types (OR: 88.35 (8.55– 912.63) were independent risk factors for infection with ESBL-E, while chronic obstructive pulmonary disease (COPD) was a protective factor (OR: 0.14 (0.03– 0.66). COVID-19 was not an independent risk factor for infection by ESBL-E.Conclusion: During the COVID-19 pandemic, the incidence of infections by ESBL-E increased significantly. Increased exposure to traditional risk factors were the main reasons, however, COVID-19 was not an independent risk factor for ESBL-E infection.Keywords: β-lactamases, COVID-19, risk factor, antibacterial drugs, case-control study, LASSO

Yuanyuan Zhao,1 Wenjing Le,1 Caroline A Genco,2 Peter A Rice,3 Xiaohong Su1 1Sexually Transmitted Disease Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China; 2Department of Immunology, Tufts University School of Medicine, Boston, MA, USA; 3Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USACorrespondence: Xiaohong Su, Sexually Transmitted Disease Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 12, Jiangwangmiao Road, Nanjing, 210042, Jiangsu Province, People’s Republic of China, Email suxh@ncstdlc.orgBackground: Since the first Chinese report of the ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone in 2016, additional FC428-like, penA 60.001 isolates have been identified in China.Objective: To document the rise in penA 60.001 isolates in Nanjing, China, and characterize their molecular and epidemiological features.Methods: N. gonorrhoeae minimum inhibitory concentrations (MICs, mg/L) for ceftriaxone, cefixime, penicillin, tetracycline, ciprofloxacin, azithromycin, spectinomycin, gentamicin and zoliflodacin were determined by agar dilution. MICs for ertapenem were measured by E-test. N. gonorrhoeae antimicrobial sequence typing (NG-STAR) of seven loci (penA, mtrR, porB, ponA, gyrA, parC and 23S rRNA) was analyzed together with N. gonorrhoeae multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST). Phylogenetic analysis was also performed using whole genomic sequencing (WGS).Results: Fourteen FC428-related penA 60.001 N. gonorrhoeae infections were identified out of 677 infections from 2017 to 2020, in Nanjing, representing an incremental yearly rise in the percentage of the city’s N. gonorrhoeae isolates that were FC428-related. Seven FC428-related N. gonorrhoeae infections were acquired in Nanjing, proper; four others in eastern Chinese cities and three from unknown locations. All FC428-related isolates were resistant to ceftriaxone, cefixime, ciprofloxacin, tetracycline and penicillin but susceptible to spectinomycin, gentamicin, ertapenem and zoliflodacin; three strains were resistant to azithromycin. penA 60.001 isolates displayed closely related MLST types and NG-STAR types but relatively distant NG-MAST types. WGS showed a phylogenetic analysis that intermingled with other international isolates.Conclusion: penA 60.001 N. gonorrhoeae isolates emerged in Nanjing, China, beginning in 2017, and have continued to rise.Keywords: Neisseria gonorrhoeae, penA 60.001, ceftriaxone-resistance, FC428, WGS phylogenetic analysis

Xinrong Geng, Kang Liu, Jinlei Wang, Xiangchen Su, Yijie Shi, Liang Zhao School of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, People’s Republic of ChinaCorrespondence: Yijie Shi; Liang Zhao, Tel +86 (0)416 4673430, Fax +86 (0)416 4673439, Email shiyijie119@163.com; liangzhao79@163.comBackground: Bacterial invasion, protracted inflammation, and angiogenesis inhibition are hallmarks of chronic diabetic wounds, bringing about patient morbidity and rising healthcare costs. For such wounds, there are currently few efficient therapies available.Methods: We reported the development of carboxymethyl chitosan (CMCS)-based self-healing hydrogel loaded with ultra-small copper nanoparticles (Cunps) for local treatment of diabetic wound healing. The structure of Cunps was identified by XRD, TEM, XPS and other methods, and the characterization of the synthesized Cunps-loaded self-healing carboxymethyl chitosan (CMCS)-protocatechualdehyde (PCA) hydrogel (Cunps@CMCS-PCA hydrogel) was further investigated. The therapeutic effect of Cunps@CMCS-PCA hydrogel in diabetic wound healing was explored in vitro and in vivo.Results: The findings showed that a kind of ultra-small size copper nanoparticles with excellent biocompatibility was prepared. CMCS was chemically conjugated to PCA to form self-healing hydrogels via the formation of an amide bond followed by the loading of ultra-small copper nanoparticles. The obtained Cunps@CMCS-PCA hydrogel showed a typical three-dimensional interlinked network structure with self-healing ability and porosity. It exhibited good biocompatibility in diabetic wounds. Furthermore, Cunps@CMCS-PCA hydrogel group significantly prevented bacterial growth in the skin wound of diabetic rats as compared to model group and CMCS-PCA hydrogel-treated group. After 3 days, no visible bacterial proliferation was observed. It also increased angiogenesis through Cunps mediated activation of ATP7A to prevent induction of autophagy. Furthermore, Cunps@CMCS-PCA hydrogel mainly depended on PCA-induced inhibition on inflammation of macrophage via JAK2/STAT3 signaling pathway. As a result, compared with delayed wound healing process with lower wound healing rate valued at 68.6% within 7 days in the model group, Cunps@CMCS-PCA significantly accelerated wound healing recovery and increased wound healing rate to 86.5%, suggesting that Cunps@CMCS-PCA hydrogel effectively accelerated wound healing.Conclusion: Cunps@CMCS-PCA hydrogel offered a new therapeutic approach for quickening diabetic wound healing.Keywords: chronic diabetic wounds, wound healing, copper nanoparticles, carboxymethyl chitosan, protocatechualdehyde, hydrogel

Xiaojie Su,1,2 Ting Lei,1,2 Haichuan Yu,1,2 Lu Zhang,1,2 Zhouzhou Feng,1,2 Tiankui Shuai,1,2 Hong Guo,1,2 Jian Liu1,2 1The First Clinical Medical College of Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of China; 2Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Clinical Medicine, the First Clinical Medical College of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou City, Gansu Province, People’s Republic of China, Tel +86 136 0935 4197, Email medecinliu@sina.comPurpose: NT-proBNP, a peptide biomarker synthesized and secreted by cardiomyocytes in response to cardiac load, has gained attention in recent years for its potential role in respiratory diseases. Chronic Obstructive Pulmonary Disease (COPD), a chronic and progressive inflammatory condition affecting the respiratory system, is frequently associated with comorbidities involving the cardiovascular system. Consequently, the aim of this systematic review and meta-analysis was to evaluate the variations in NT-proBNP levels across distinct patient groups with COPD and establish a foundation for future investigations into the precise clinical significance of NT-proBNP in COPD.Methods: The search databases for this study were conducted in PubMed, Excerpt Medica database (Embase), Web of Science (WOS), and Cochrane Library databases. Databases were searched for studies on the predictive value of NT-proBNP in adult COPD patients.Results: A total of 29 studies (8534 participants) were included. Patients with stable COPD exhibit elevated levels of NT-proBNP [standardized mean difference(SMD) [95CI%]=0.51 [0.13,0.89]; p=0.0092]. COPD patients with predicted forced expiratory volume in 1 s (FEV1) < 50% exhibit significantly elevated levels of NT-proBNP compared to those with FEV1 ⩾50%[SMD [95CI%]=0.17 [0.05,0.29]; p=0.0058]. NT-proBNP levels were significantly higher in acute exacerbations (AECOPD) compared to patients with stable COPD [SMD [95CI%]=1.18 [0.07,2.29]; p=0.037]. NT-proBNP levels was significantly higher in non-survivors than in survivors of hospitalised AECOPD patients [SMD [95CI%]=1.67 [0.47,2.88]; p=0.0063]. Both COPD patients with pulmonary hypertension(PH) [SMD [95CI%]=0.82 [0.69,0.96]; p< 0.0001] and chronic heart failure(CHF) [SMD [95CI%]=1.49 [0.96,2.01]; p< 0.0001] showed higher NT-proBNP level.Conclusion: NT-proBNP, a biomarker commonly used in clinical practice to evaluate cardiovascular disease, demonstrates significant variations in different stages of COPD and during the progression of the disease. The fluctuations in NT-proBNP levels could be indicative of the severity of pulmonary hypoxia and inflammation and cardiovascular stress among COPD patients. Therefore, assessing NT-proBNP levels in COPD patients can aid in making informed clinical decisions.Keywords: amino-terminal pro-brain natriuretic peptide, chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, chronic heart failure, meta-analysis

Zhongbao Wang,1 Yunshao Zheng,2 Yunli Fan,2 Yunming Fan,2 Xianbiao Su,2 Bingrui Wang,2 Jing Li,2 Diancai Chen,2 Fengxia Sun,2 Shen Li,2 Jiashu Ma,1 Xianwei Li,2 Ludong Bai,2 Ranran Li2 1Department of Psychiatry, Jining Medical University, Jining, People’s Republic of China; 2Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Ranran Li, Department of Psychiatry, Shandong Mental Health Center, Shandong University, 49 East Wenhua Road, Jinan, Shandong, 250014, People’s Republic of China, Tel +86 18678777190, Email dtlrr113@126.comBackground: Most antipsychotic drugs are dopamine receptor antagonists that usually lead to abnormal increases in prolactin concentrations and the development of hyperprolactinemia (HPRL), which in turn causes sexual dysfunction in patients. Peony-Glycyrrhiza Decoction (PGD) enhanced dopamine D2 receptors (DRD2) and dopamine transporter (DAT) and significantly reversed the expression of DRD2 and DAT. Therefore, we hypothesized that PGD might effectively improve hyperprolactinemia and alleviate sexual dysfunction in patients.Methods: We performed an 8-week randomized controlled study on 62 subjects with schizophrenia who were randomized into two groups. The experimental group was treated with the PGD intervention, and the control group did not receive treatment. The primary outcome indicators were the levels of sex hormones and the total Arizona Sexual Experience Scale (ASEX) score.Results: There was a significant difference in PRL levels between the two groups at weeks 4 and 8. From the beginning to the end of the experiment, there was a significant increase in PRL levels in the control group, while there was no significant change in the experimental group. The ASEX scale assessed sexual function in both groups, and patients in the experimental group showed an improvement in sexual function at week 8. During the experiment, the two groups found no differences between Positive and Negative Syndrome Scale (PANSS) scores and Treatment Emergent Symptom Scale (TESS) scores.Conclusion: PGD significantly improved the patient’s sexual function but was less effective in reducing prolactin levels and may prevent further increases in prolactin levels.Keywords: hyperprolactinemia, antipsychotics, Peony-Glycyrrhiza Decoction, schizophrenia, sexual function, adverse effects

Donghao Wang,1,&ast; Yingying Ren,2,&ast; Riken Chen,1,&ast; Xiangxia Zeng,1,&ast; Qiming Gan,1,&ast; Zhiyang Zhuang,1 Xiaofen Su,1 Kang Wu,1 Sun Zhang,1 Yongkang Tang,1 Shiwei Li,1 Haojie Zhang,1,3 Yanyan Zhou,1 Nuofu Zhang,1 Dongxing Zhao1 1State Key Laboratory of Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Medical Records and Statistics Room, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongxing Zhao; Nuofu Zhang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86-13650901411 ; +86-13600460056, Email rieast@msn.com; nfzhanggird@163.comObjective: Obstructive sleep apnea (OSA) is a common sleep-disordered breathing disease. We aimed to establish an improved screening questionnaire without physical examinations for OSA named the CNCQ-OSA (Chinese community questionnaire for OSA).Methods: A total of 2585 participants who visited sleep medicine center and underwent overnight polysomnography were grouped into two independent cohorts: derivation (n = 2180) and validation (n = 405). The CNCQ-OSA was designed according to the baseline of patients in derivation cohort. We comprehensively analyzed the data to evaluate the predictive value of the CNCQ-OSA, compared to the GOAL questionnaire, STOP-Bang questionnaire (SBQ) and NoSAS questionnaire.Results: The CNCQ-OSA included seven variables: loud snoring, BMI ≥ 25 kg/m2, male gender, apnea, sleepiness, hypertension and age ≥ 30, with a total score ranging from 7 to 16.7 points (≥ 13.5 points indicating high risk of OSA, ≥ 14.5 points indicating extremely high risk). In the derivation and validation cohorts, the areas under the curve of the CNCQ-OSA were 0.761 and 0.767, respectively. In the validation cohort, the sensitivity and specificity of a CNCQ-OSA score ≥ 13.5 points for the apnea–hypopnea index (AHI) ≥ 5/h were 0.821 and 0.559, respectively (Youden index, 0.380), and the score ≥ 14.5 points were 0.494 and 0.887, respectively (Youden index, 0.375). The CNCQ-OSA had a better predictive value for AHI ≥ 5/h, AHI > 15/h and AHI > 30/h, with the highest Youden index, compared to the other questionnaires.Conclusion: The CNCQ-OSA can effectively identify the risk of OSA, which is appropriate for self-screening at home without physical examinations.Keywords: obstructive sleep apnea, screening, GOAL, STOP-Bang, NoSAS

Ruojing Qian,1– 3,&ast; Zhaoyu Xu,4,&ast; Xingyu Hu,1– 3 Suru Liu,1– 3 Yao Mai,1– 3 Xinzhi Tan,1– 3 Xiaofan Su,1– 3 Mingyan Jiang,1– 3 Wei Tang,1– 3 Weidong Tian,1– 3 Li Xie1– 3 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 4Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Tian; Li Xie, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85502156 ; +86-28-85503499, Email drtwd@sina.com; samuel@163.comPurpose: A synergistic antibacterial system employing photocatalytic performance and low-temperature photothermal effect (LT-PTT) with the potential for infectious skin wound healing promotion was developed.Methods: Ag/Ag2O was synthesized with a two-step method, and its physicochemical properties were characterized. After its photocatalytic performance and photothermal effect were evaluated under 0.5 W/cm2 808 nm NIR laser irradiation, its antibacterial activities in both planktonic and biofilm forms were then studied in vitro targeting Staphylococcus Aureus (S. aureus), and the biocompatibility was tested with L-929 cell lines afterward. Finally, the animal model of dorsal skin wound infection was established on Sprague-Dawley rats and was used to assess infectious wound healing promotion of Ag/Ag2O in vivo.Results: Ag/Ag2O showed boosted photocatalytic performance and local temperature accumulation compared with Ag2O when exposed to 0.5 W/cm2 808 nm NIR irradiation, which therefore endowed Ag/Ag2O with the ability to kill pathogens rapidly and cleavage bacterial biofilm in vitro. Furthermore, after treatment with Ag/Ag2O and 0.5 W/cm2 808 nm NIR irradiation, infectious wounds of rats realized skin tissue regeneration from a histochemical level.Conclusion: By exhibiting excellent NIR-triggered photocatalytic sterilization ability enhanced by low-temperature photothermal effect, Ag/Ag2O was promising to be a novel, photo-responsive antibacterial agent.Keywords: semiconductor/metal hybrid, antibacterial agent, photo-responsive antibacterial activity, reactive oxygen species, infectious wound skin model

Xiangyu Su,1,2 Guoqing Wang,3 Shiya Zheng,2 Chang Ge,4 Fei Kong,4 Cailian Wang1,2 1School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 3Department of Pathology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 4Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of ChinaCorrespondence: Cailian Wang, Email wangcailian@seu.edu.cnBackground: Chemokines have been reported to play an important role in cancer immunotherapy. This study aimed to explore the chemokines involved in lung cancer immunotherapy.Methods: All the public data were downloaded from The Cancer Genome Atlas Program database. Quantitative real time-PCR was used to detect the mRNA level of specific molecules and Western blot was used for the protein level. Other experiments used include luciferase reporter experiments, flow cytometric analysis, Chromatin immunoprecipitation assay, ELISA and co-cultured system.Results: We found that the CCL7, CCL11, CCL14, CCL24, CCL25, CCL26, CCL28 had a higher level, while the CCL17, CCL23 had a lower level in immunotherapy non-responders. Also, we found that immunotherapy non-responders had a higher level of CD56dim NK cells, NK cells, Th1 cells, Th2 cells and Treg, yet a lower level of iDC and Th17 cells. Biological enrichment analysis indicated that in the patients with high Treg infiltration, the pathways of pancreas beta cells, KRAS signaling, coagulation, WNT BETA catenin signaling, bile acid metabolism, interferon alpha response, hedgehog signaling, PI3K/AKT/mTOR signaling, apical surface, myogenesis were significantly enriched in. CCL7, CCL11, CCL26 and CCL28 were selected for further analysis. Compared with the patients with high CCL7, CCL11, CCL26 and CCL28 expression, the patients with low CCL7, CCL11, CCL26 and CCL28 expression had a better performance of immunotherapy response and this effect might partly be due to Treg cells. Furthermore, biological exploration and clinical correlation of CCL7, CCL11, CCL26 and CCL28 were conducted, Finally, CCL28 was selected for validation. Experiments showed that under the hypoxia condition, HIF-1α was upregulated, which can directly bind to the promoter region of CCL28 and lead to its higher level. Also, CCL28 secreted by lung cancer cells could induce Tregs infiltration.Conclusion: Our study provides a novel insight focused on the chemokines in lung cancer immunotherapy. Also, CCL28 was identified as an underlying biomarker for lung cancer immunotherapy.Keywords: chemokines, lung adenocarcinoma, immunotherapy, Tregs, HIF-1&#x03B1

Peng Li,1 Xiaonan Su,2 Xiaotong Zhang,3 Lijiang Sun,1 Guiming Zhang1 1Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Department of Urology, Zoucheng People’s Hospital, Jining, 273500, People’s Republic of China; 3Department of Vascular Surgery, Qingdao Eighth People’s Hospital, Qingdao, 266100, People’s Republic of ChinaCorrespondence: Guiming Zhang, Email zhangguiming9@126.comObjective: This study aimed to summarize and analyze the clinical and pathological features and prognostic risk factors of adrenocortical carcinoma (ACC).Methods: We retrospectively analyzed clinical and pathological data and the prognoses of 39 adult ACC patients confirmed by pathologic diagnosis at the Affiliated Hospital of Qingdao University between August 2009 and October 2021. Kaplan–Meier curves and univariate and multivariate Cox regression models were used to analyze correlations between clinical and pathological parameters and prognosis. A nomogram prediction model was constructed for overall survival (OS) based on the independent prognostic factors and externally validated it with The Cancer Genome Atlas (TCGA) dataset.Results: The mean age of the patient cohort was 53.87 ± 11.1 years (range: 29– 80 years), which included 17 men and 22 women. The 1-, 2-, and 5-year OS rates were 83.7%, 64.4%, and 59.8%, respectively; the recurrence-free survival (RFS) rates at the same time points were 76.1%, 45.8%, and 23.5%, respectively. Kaplan–Meier curves showed that patients with poor OS were associated with M1 stage (P = 0.008), late ENSAT stage (P = 0.017), presence of venous tumor thrombus (P = 0.015), Ki67 > 20% (P = 0.006), R1/R2 status (P = 0.018), and poorly differentiated tumors (P = 0.047). Patients with late ENSAT stage (P = 0.017), combined with venous tumor thrombus (P = 0.008), Ki67 > 20% (P = 0.022) were more likely to have tumor recurrence. However, age, gender, BMI, tumor diameter, clinical symptoms and postoperative treatment were not correlated with OS or RFS (P > 0.05). Univariate and multivariate COX analyses showed that Ki67 > 20% (P = 0.013) and R1/2 status (P = 0.040) were independent risk factors for OS, while only Ki67 > 20% (P = 0.032) was an independent risk factor for RFS. A nomogram for predicting OS was constructed based on the above factors, and the area under the receiver characteristic curve (ROC)-1, 3, and 5-year survival were 0.8, 0.825 and 0.902, respectively. The C-index of the predicted nomogram was 0.813 and a high C-index value of 0.846 could still be achieved in the external validation of TCGA.Conclusion: ACC is a rare and deadly endocrine malignancy with a high rate of recurrence. High Ki67 index (> 20%) and R1/R2 resection status were independent risk factors for poor prognosis in ACC patients. A novel nomogram with a relatively good accuracy was established to assist clinicians in assessing the risk of OS in patients with ACC.Keywords: adrenocortical carcinoma, clinical diagnosis, survival, recurrence, risk factors, prognosis, nomogram

Jingyu Zhang,1,&ast; Yinxia Zhan,2,&ast; Jiaojiao Chen,2 Dan Kang,2 Rumei Xiang,2 Ruoyi Zhang,2 Yubo Zhang,1 Yang Pu,2 Jiayuan Zhang,1 Lijun Zhang,2 Yanyan Huang,2 Ruoyan Gong,2 Xueyao Su,2 Yuxian Nie,1 Qiuling Shi1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China; 2School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuling Shi, State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Medical University, No. 1, Medical College Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-18290585397, Email qshi@cqmu.edu.cnBackground: Patients with hepatobiliary or pancreatic cancers often experience severe symptoms, resulting in a sharp decline in functioning, poor quality of life, and increased mortality risk. Early and effective management of symptoms allows a better quality of life and reduced mortality, depending on the selection of appropriate assessment of specific symptoms for a defined purpose. We aimed to develop a symptom measurement item bank for hepatobiliary or pancreatic cancers.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was applied to organize this systematic review. The articles validated patient-reported outcome measures (PROMs) for hepatobiliary or pancreatic cancer and published before December 2021 were retrieved from the Web of Science, PubMed, Embase databases and Cochrane Library. Items from the existing PROMs were selected and classified into different patient-reported symptoms based on the concepts and specific underlying constructs of the objects measured.Results: Sixteen unique PROMs were identified across the 29 eligible studies included in our analysis. Items from the literature review (14 PROMs with 421 items for which information was obtained) were selected and classified. As a result of this study, we developed a symptom item bank with 40 patient-reported symptoms and 229 assessment items for hepatobiliary or pancreatic cancer, and fatigue, pain and nausea were the most common symptom items.Conclusion: We developed an item bank to assess the patient-reported symptoms of hepatobiliary or pancreatic cancer. This item bank could allow researchers to select appropriate measures of symptom and provide a basis for the development of a single-item symptom-measurement system.Keywords: patient-reported outcome measures, symptom, item bank, pancreatic carcinoma, hepatocellular carcinoma, cholangiocarcinoma, systematic review

Xin Su,1,&ast; Haifeng Li,2,&ast; Fajun Li,3 Hongsen Liang,4 Li Wei,4 Donglei Shi,4 Junhang Zhang,4 Zhaojun Wang4 1Department of Respiratory, Hainan Hospital of PLA General Hospital, Sanya, People’s Republic of China; 2Department of Anesthesiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3Department of Critical Care Medicine, The First People’s Hospital of Kunshan, Kunshan, People’s Republic of China; 4Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junhang Zhang; Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, No. 628, Zhenyuan Road, Guangming (New) Dist, Shenzhen, 518107, People’s Republic of China, Email zhangjh33@mail.sysu.edu.cn; wangzhj55@mail.sysu.edu.cnObjective: Exposure to ambient particulate matter (PM2.5) is the leading risk factor for developing chronic obstructive pulmonary disease (COPD) in China. The present study aimed to investigate the trends in COPD mortality attributable to ambient PM2.5 exposure in China from 1990 to 2019.Methods: Data on COPD burden attributable to ambient PM2.5 exposure in China were extracted from the Global Burden of Disease (GBD) study 2019. The estimated annual percentage change (EAPC) was used to assess COPD mortality from 1990 to 2019. The APC model was used to analyze the temporal trends in the rate of COPD mortality attributable to ambient PM2.5 exposure according to age, period, and cohort.Results: Exposure to ambient PM2.5 contributed to 192.4 thousand deaths in 1990 and 263.6 thousand deaths in 2019. The age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life year rate (ASDR) due to ambient PM2.5 exposure showed a gradual downward trend, the ASMR and ASDR in 2019 decreased to 16.6 per 100,000 with an EAPC of − 2.82 (95% CI: − 8.61 to 3.34) and 278.6 per 100,000 with an EAPC of − 2.02 (95% CI: − 7.85 to 4.19), compared to those in 1990, respectively. The relative risk (RR) of COPD increased with age in females, while in males, mortality significantly increased from the levels among those in the 60– 64 age group to that among those in the 90– 94 age group. In the period group, the RR of COPD in males remained above 1.0 from the 2000 to 2004 period, but it gradually decreased in females. The cohort effect showed an overall downward trend.Conclusion: Although the ASMR and ASDR are decreasing in Chinese patients with COPD, the number of deaths due to COPD is increasing. Ambient PM2.5 exposure is more harmful in males and older people above 60 years of age.Keywords: chronic obstructive pulmonary disease, PM2.5, age-period-cohort model

Guangda He,1 Runqing Ji,1 Xiqian Huo,1 Xiaoming Su,1 Jinzhuo Ge,1 Wei Li,1 Lubi Lei,1 Boxuan Pu,1 Aoxi Tian,1 Jiamin Liu,1 Lihua Zhang,1 Yongjian Wu2 On behalf of the China PEACE Collaborative Group1National Clinical Research Center for Cardiovascular Diseases, NHC Key Laboratory of Clinical Research for Cardiovascular Medications, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lihua Zhang, National Clinical Research Center for Cardiovascular Diseases, NHC Key Laboratory of Clinical Research for Cardiovascular Medications, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, 167 Beilishi Road, Beijing, 100037, People’s Republic of China, Email zhanglihua@fuwai.com Yongjian Wu, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China, Email wuyongjian@fuwai.comBackground: Inflammation contributes to the progression of heart failure (HF). However, long-term inflammatory trajectories and their associations with outcomes in patients with acute HF remain unclear.Methods: Data was obtained from the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, and high-sensitivity C-reactive protein (hsCRP) was used to reflect the inflammatory level. Only patients who survived over 12-month and had hsCRP data at admission, 1-, and 12-month after discharge were included. The latent class trajectory modeling was used to characterize hsCRP trajectories. Multivariable Cox regression models were used to explore the association between hsCRP trajectories and following mortality.Results: Totally, 1281 patients with a median 4.77 (interquartile range [IQR]: 4.24– 5.07) years follow-up were included. The median age was 64 years (IQR: 54– 73 years); 453 (35.4%) were female. Four distinct inflammatory trajectories were characterized: persistently low (n = 419, 32.7%), very high-marked decrease (n = 99, 7.7%), persistently high (n = 649, 50.7%), and persistently very high (n = 114, 8.9%). Compared with the persistently low trajectory, the all-cause mortality was increased in a graded pattern in the persistently high (hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.23– 2.07) and persistently very high (HR: 2.56, 95% CI: 1.83– 3.70) trajectories; nevertheless, the mortality was not significantly increased in very high-marked decrease trajectory (HR: 0.94, 95% CI: 0.57– 1.54).Conclusion: Four distinct inflammatory trajectories were identified among patients with acute HF who survived over 12-month. Patients with persistently high and very high trajectories had significantly higher mortality than those with the persistently low trajectory.Keywords: heart failure, high-sensitivity C-reactive protein, trajectory, latent class trajectory modeling, mortality

Jieying Chen,1,&ast; Mingchen Lv,2,&ast; Xiaolian Su,1 Sizhu Wang,1 Yitong Wang,1 Zhen Fan,2,3 Lin Zhang,1 Guangyu Tang1 1Department of Radiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, People’s Republic of China; 3Institute for Advanced Study, Tongji University, Shanghai, China; Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangyu Tang; Lin Zhang, Tel +86-18917683528, Email tgy17@tongji.edu.cn; lynn122500@hotmail.comPurpose: Owing to the lack of effective biomarkers, triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes of breast cancer. Meanwhile, tremendous progress has been made to identify biomarkers for TNBC. However, limited number of biomarkers still restrain the specifically targeting outcomes against TNBC. Here, to solve the obstacle, we designed and synthesized a new type of biocompatible nanoparticles to amplify the targeting effects for TNBC theranostics.Methods: To identify the biomarker of TNBC, the expression of intercellular adhesion molecule-1 (ICAM1) was assessed by real-time polymerase chain reaction and western blot among all subtypes of breast cancer and normal breast epithelium. Then, vesicular nanoparticles based on poly(ethylene glycol)-poly(&epsiv;-caprolactone) copolymers were prepared by the double emulsion method and modified with anti-ICAM1 antibodies through click chemistry to conjugate with related antigens on TNBC cell membranes and then loaded with magnetic resonance imaging (MRI) contrast agent gadolinium and chemotherapeutic drug doxorubicin. The targeting capability, diagnostic and therapeutic efficacy of this nanoparticle were validated through cell-based and tumor model-based experiments.Results: ICAM1 was expressed significantly higher on TNBC than on other subtypes of breast cancer and normal breast epithelium in both mRNA and protein level. Theranostic nanoparticle modified with anti-ICAM1 was proved to be able to specifically target to TNBC in vitro experiments. Such theranostic nanoparticle also displayed enhanced diagnostic and therapeutic efficacy by specifically targeting capability and extending circulation time in tumor models. The biocompatibility and biosafety of this nanoparticle was also confirmed in vitro and in vivo.Conclusion: Overall, this new nanoparticle has been demonstrated with effective therapeutic outcomes against TNBC, providing a promising theranostic approach for MRI-guided therapy of TNBC.Keywords: breast carcinoma, nanoparticles, magnetic resonance imaging, theranostics, intercellular adhesion molecule-1

Ting Lei,1,2,&ast; Tingting Lu,3,4,&ast; Haichuan Yu,1,2,&ast; Xiaojie Su,1,2 Chuchu Zhang,1,2 Lei Zhu,1,2 Kehu Yang,4,5 Jian Liu1,2 1Department of Clinical Medicine, The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, People’s Republic of China; 2Department of Critical Care Medicine, the First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China; 3Institute of Clinical Research and Evidence Based Medicine, Gansu Provincial Hospital, Lanzhou, 730000, People’s Republic of China; 4Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, People’s Republic of China; 5Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Liu, No. 1, Donggang West Road, Chengguan District, Lanzhou, Gansu Province, Tel +86 136 0935 4197, Email medecinliu@sina.com; Kehu Yang, Evidence-Based Medicine Center, Lanzhou University, 199 West Donggang R.D, Lanzhou, 730000, People’s Republic of China, Email kehuyangebm2020@163.comBackground: In recent years, the pleiotropic roles of antioxidants have drawn extensive attention in various diseases. Vitamin C is a well-known antioxidant, and it has been used to treat patients with chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis aim to demonstrate the impact of vitamin C supplementation in patients with COPD.Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), SinoMed, Wanfang, and China Science and Technology Journal Database (cqvip.com) for eligible randomized controlled trials (RCTs) from their respective inception to May 18th, 2021, by using the searching terms of COPD, vitamin C, and RCTs. A meta-analysis was performed to evaluate the effects of vitamin C on lung function, antioxidant levels, and nutritional conditions in COPD patients by using Review Manager (Version 5.4).Results: Ten RCTs including 487 participants were eligible for our study. Meta-analysis results showed that vitamin C supplementation (≥ 400 mg/day) can significantly improve the forced expiratory volume in one second as a percentage (FEV1%) in COPD (SMD:1.08, 95% CI:0.03, 2.12, P=0.04). Moreover, vitamin C supplementation significantly improved the ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) (WMD:0.66, 95% CI: 0.26, 1.06, P=0.001), vitamin C level in serum (SMD:0.63, 95% CI: 0.02, 1.24, P=0.04) and glutathione (GSH) level in serum (SMD:2.47, 95% CI: 1.06, 3.89, P=0.0006). While no statistically significant difference was observed in body mass index (BMI), fat-free mass index (FFMI), vitamin E level and superoxide dismutase (SOD) level in serum.Conclusion: Vitamin C supplementation could increase the levels of antioxidation in serum (vitamin C and GSH) and improve lung function (FEV1% and FEV1/FVC), especially in patients treated with vitamin C supplementation greater than 400 mg/day. However, further prospective studies are needed to explore the role of vitamin C in improving nutritional status.Keywords: vitamin C, COPD, RCTs, lung function, meta-analysis

Li Liu,1,2 Mingjuan Yuan,3 Siqing Sun,4 Jinrong Wang,5 Yi Shi,6 Yamin Yu,7 Xin Su1,6 1Department of Respiratory and Critical Care Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, People’s Republic of China; 2Department of Infectious Disease, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, People’s Republic of China; 3Department of Infectious Disease, The Central Hospital of Yueyang, Yueyang, Hunan Province, People’s Republic of China; 4Department of General Medicine, The Second Hospital of Nanjing, Nanjing Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Hengshui People’s hospital, Hengshui, Hebei Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 7Department of Nephrology, Ningxiang People’s Hospital, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Xin Su, Email suxinjs@163.comBackground: For acquired immunodeficiency syndrome (AIDS) patients with suspected opportunistic infections, the rapid and accurate identification of pathogens remains a challenge. Metagenomic next-generation sequencing (mNGS) has emerged as a pan-pathogen assay for infectious diseases diagnosis, but its guiding significance for diagnosis and antimicrobials treatment in AIDS patients with suspected opportunistic infections is still not well established. In this study, we compared the microbiological diagnostic value of mNGS with that of conventional microbiological tests (CMTs) in AIDS patients with suspected opportunistic infections.Methods: From January 2018 to February 2021, a retrospective study was performed at four tertiary teaching hospitals in China and data of 86 AIDS patients with suspected opportunistic infections were collected. The pathogen detection performance of mNGS and CMTs were compared.Results: Positive agreement between mNGS and clinical diagnosis was significantly higher than that of CMTs (65/86 (75.6%) vs 37/86 (43.0%)). In addition, mNGS identified more bacterial (25 vs 2), fungal (5 vs 3), viral (9 vs 2) organisms compared with CMTs. Mixed infection were detected in 34 patients by mNGS combined with CMTs. Viruses (94.1%, 32/34) and fungi (94.1%, 32/34) were commonly seen in the mixed infection cases. mNGS helped identify the pathogen or guide appropriate treatment in 49/86 (57%) patients. Meanwhile, CMTs also contributed in the decision of appropriate treatment in 28 patients. The successful de-escalation or discontinuation of treatment was supported in 37 patients with the help of mNGS. We observed a significant reduction in the number of patients being prescribed foscarnet (52.3% vs 23.26%, p < 0.001), moxifloxacin (34.9% vs 10.5%, p = 0.005), and levofloxacin (32.6% vs 14%, p = 0.001) before and after mNGS.Conclusion: For AIDS patients with suspected opportunistic infections, mNGS can provide early, noninvasive, and rapid microbiological diagnosis. mNGS may lead to a more precise antimicrobial treatment and reduced the unreasonable use of antimicrobials.Keywords: mNGS, AIDS, opportunistic infections

Donghe Chen,1 Chengdong Chang,2 Yafei Zhang,1 Shuye Yang,1 Guolin Wang,1 Lili Lin,1 Xin Zhao,1 Kui Zhao,1 Xinhui Su1 1Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Kui Zhao; Xinhui Su, Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, People’s Republic of China, Tel/Fax +86-571-87236428, Email zhaokui0905@zju.edu.cn; suxinhui@zju.edu.cnBackground: Recurrence and metastasis are important causes of postoperative death in most HCC patients. Conventional imaging modalities such as 18F-FDG PET/CT and enhanced MRI are still unsatisfactory in evaluating these patients in the clinical setting. PET/CT imaging with a radiolabeled fibroblast activation protein inhibitor (FAPI) has emerged as a new imaging technique for the diagnosis and radiotherapy of malignant tumors. While many studies have focused on the diagnostic accuracy of intrahepatic primary HCC, the evaluation of recurrent and metastatic HCC remains only poorly investigated.Case Presentation: A 71-year-old man with a five-year history of HCC after radical resection underwent 18F-FDG PET/CT due to further surgery for tumor recurrence, which revealed two iso-metabolic lesions in the right peritoneum and a hypo-metabolic lesion in the right liver. 18F-FAPI PET/CT was performed to further complement 18F-FDG PET/CT in the detection of these suspected metastatic lesions. Importantly, multiple diffuse intense radioactivity was shown in the hepatic capsule, suggesting metastatic lesions, but a wedge-shaped elevated 18F-FAPI uptake disorder around the FDG-unavid necrotic lesion after radiofrequency ablation (RFA) demonstrated benign stromal fibrosis.Conclusion: This case suggested that 18F-FAPI may have an advantage over 18F-FDG in detecting peritoneal metastasis even in tiny or early hepatic capsules of HCC, but its false positives due to postoperative stromal fibrosis should be noted. Wedge- or strip-shaped FAPI-avid lesions with sharp edges may be post-treatment stromal fibrosis.Keywords: 18F-FAPI, 18F-FDG, PET/CT, magnetic resonance imaging, hepatocellular carcinoma, false-positive, stromal fibrosis

Zhouzhou Feng, Lu Zhang, Haichuan Yu, Xiaojie Su, Tiankui Shuai, Lei Zhu, De Chen, Jian Liu The First Clinical Medical College, Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Jian Liu, The first clinical medical college, Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of China, Email medecinliu@sina.comObjective: To evaluate the clinical efficacy of high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) after extubation.Research Methods: This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: reintubation rate, mortality, complication rate, and ICU length of stay.Results: Eight studies were included, with a total of 612 subjects, including 297 in the HFNC group and 315 in the NIV group. The effect of HFNC and NIV on the reintubation rate of AECOPD patients after extubation, RR (1.49 [95% CI,0.95 to 2.33], P = 0.082). Subgroup analysis with or without hypercapnia according to the included AECOPD population, with hypercapnia, RR (0.69 [95% CI,0.33 to 1.44], P=0.317), without hypercapnia, RR (2.61 [95% CI,1.41 to 4.83], P=0.002). Mortality, RR (0.92 [95% CI,0.56 to 1.52], P = 0.752). ICU length of stay, MD (− 0.44 [95% CI,-1.01 to 0.13], P = 0.132). Complication rate, RR (0.22 [95% CI,0.13 to 0.39], P = 0.000). After subgroup analysis, the reintubation rate of HFNC and NIV has no statistical difference in patients with hypercapnia, but NIV can significantly reduce the reintubation rate in patients without hypercapnia. In the outcome measures of complication rate, HFNC significantly reduced complication rate compared with NIV. In mortality and ICU length of stay, analysis results showed that HFNC and NIV were not statistically different.Conclusion: According to the available evidence, the application of HFNC can be used as an alternative treatment for NIV after extubation in AECOPD patients with hypercapnia, but in the patients without hypercapnia, HFNC is less effective than NIV.Keywords: nasal high-flow oxygen therapy, acute exacerbation of chronic obstructive pulmonary disease, non-invasive ventilation, meta-analysis

Haifeng Li,1,&ast; Hongsen Liang,2,&ast; Li Wei,2 Donglei Shi,2 Xin Su,3 Fajun Li,4 Junhang Zhang,2 Zhaojun Wang2 1Department of Anesthesiology, Guangdong Provincial People’s Hospitall, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Department of Respiratory, Hainan Hospital of PLA General Hospital, Sanya, People’s Republic of China; 4Department of Critical Care Medicine, The First People’s Hospital of Kunshan, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junhang Zhang; Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, People’s Republic of China, Tel/Fax +86-755-81206874, Email zhangjh33@mail.sysu.edu.cn; wangzhj55@gmail.sysu.edu.cnBackground: This study assessed health inequality in the global burden of chronic obstructive pulmonary disease (COPD) between 1990 and 2019 using data extracted from the Global Burden of Diseases (GBD 2019) study.Methods: Data were extracted from the GBD 2019 study. A series of comparative and descriptive analyses of the disease burden between women and men in countries with different socioeconomic development (SDI) status were performed. The slope index of inequality (SII), relative index of inequality (RII), and concentration index (CI) were calculated to measure the socioeconomic-related cross-national health inequity between 1990 and 2019.Results: The global health burden caused by COPD increased by 25.7% in terms of disability-adjusted life years (DALY) from 59.2 million years in 1990 to 74.4 million years in 2019. Global age-standardized DALY rate (ASDR) associated with COPD decreased by 40.0%, from 1537.7 per 100,000 population in 1990 to 926.1 per 100,000 population in 2019. The highest sex-specific DALY number was at age 70– 74 in male and female, and female is lower than male. However, after controlling for population size, the burden of COPD is more concentrated in the population living in low SDI countries, relative health inequality indicators (RII and CI) supported this conclusion.Conclusion: The health inequalities caused by the disparity of socioeconomic status are increasing, and the increasing concentration of wealth worldwide is likely to aggravate health inequalities associated with COPD.Keywords: chronic obstructive pulmonary disease, disease burden, health inequality

Liu L, Yuan M, Sun S, et al. Infect Drug Resist. 2022;15:5645–5653. The authors have advised that affiliation 1 on page 5645 is incorrect. The correct affiliation should read “The First School of Clinical Medicine, Southern Medical University, Guangzhou, China”. The authors apologize for this error.

Yuxin Fan,1– 3 Jingjing Chen,1,4 Meixiao Liu,1,2 Xin Xu,1,2 Yu Zhang,1– 3 Peng Yue,1,4 Wenjing Cao,1,4 Zhenhua Ji,1,2 Xuan Su,1,2 Shiyuan Wen,1– 3 Jing Kong,1,2 Guozhong Zhou,1,2 Bingxue Li,1,2 Yan Dong,1,2 Aihua Liu,1,3,4 Fukai Bao1– 3 1The Institute for Tropical Medicine, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, 650500, People’s Republic of China; 2Department of Microbiology and Immunology, Kunming Medical University, Kunming, 650030, People’s Republic of China; 3Yunnan Province Key Laboratory of Children’s Major Diseases Research, The Affiliated Children Hospital, Kunming Medical University, Kunming, 650030, People’s Republic of China; 4Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, 650030, People’s Republic of ChinaCorrespondence: Aihua Liu; Fukai Bao, The Institute for Tropical Medicine, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, 650500, People’s Republic of China, Email liuaihua@kmmu.edu.cn; baofukai@kmmu.edu.cnAbstract: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB) infection, which has seriously endangered human health for many years. With the emergence of multidrug-resistant and extensively drug-resistant MTB, the prevention and treatment of TB has become a pressing need. Early diagnosis, drug resistance monitoring, and control of disease transmission are critical aspects in the prevention and treatment of TB. However, the currently available diagnostic technologies and drug sensitivity tests are time consuming, and thus, it is difficult to achieve the goal of early diagnosis and detection drug sensitivity, which results in limited control of disease transmission. The development of molecular testing technology has gradually achieved the vision of rapid and accurate diagnosis of TB. Droplet digital PCR (ddPCR) is an excellent nucleic acid quantification method with high sensitivity and no need for a calibration curve. Herein, we review the application of ddPCR in TB diagnosis and drug resistance detection and transmission monitoring.Keywords: Mycobacterium tuberculosis, tuberculosis, droplet digital PCR, diagnosis, drug resistance test, disease transmission

Haichuan Yu,1,2 Xiaojie Su,1,2 Ting Lei,1,2 Chuchu Zhang,1,2 Meng Zhang,1,2 Yalei Wang,1,2 Lei Zhu,1,2 Jian Liu1,2 1Department of Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China; 2The First Clinical Medical College of the First Hospital of Lanzhou University, Lanzhou City, People’s Republic of ChinaCorrespondence: Jian LiuDepartment of Intensive Care Unit, The First Hospital of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou City, Gansu Province, People’s Republic of ChinaTel +86 136 0935 4197Email medecinliu@sina.comPurpose: Omega-3 fatty acid is an emerging hotspot on anti-inflammation and chronic obstructive pulmonary disease (COPD) is known as a chronic inflammatory disease. The effect of Omega-3 fatty acid supplement on patients with COPD remains mixed for insufficient evidence. This systematic review and meta-analysis is based on neat randomized controlled trials trying to give a clearer impression on the effect of Omega-3 on patients with COPD.Methods: This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. Randomized clinical trials (RCTs) published in electronic databases including Medline, Embase, Cochrane Library, ClinicalTrials.gov and China National Knowledge Infrastructure (CNKI) by May 10, 2021 were searched. Data extracted from 6 predetermined domains (nutritional condition, lipid composition, inflammatory biomarker, lung function, physical endurance and quality of life [QoL]) were reviewed and analyzed.Results: A total of 8 RCTs evaluating 418 patients (age, mean [SD] = 67.3 [10.2] years) were included. Statistical differences were found in 3 parameters of 3 domains – weight (Wt) (0.25 [95% CI, 0.02 to 0.48], P = 0.03) in nutritional condition, low-density lipoprotein (LDL) (0.70 [95% CI, 0.30 to 1.10], P = 0.00) in lipid composition and interleukin-6 (IL-6) level (− 0.32 [95% CI, − 0.60 to − 0.05], P = 0.02) in inflammatory biomarker – while no significant difference was found in lung function, physical endurance or QoL.Conclusion: Comparing with placebo, Omega-3 intake was associated with more weight-gaining, LDL increase and IL-6 reduction. These results should be interpreted cautiously for the quality and quantity of available evidence are limited.Keywords: COPD, omega-3 fatty acids, systematic review and meta-analysis

Lianghua Guo,1 Bin Song,1 Jianhong Xiao,1 Hui Lin,1 Junhua Chen,1 Xianghua Su2 1Department of Respiratory Medicine, Mindong Hospital of Fujian Medical University, Fuan City, 355000, People’s Republic of China; 2Department of Neurosurgery, Mindong Hospital of Fujian Medical University, Fuan City, 355000, People’s Republic of ChinaCorrespondence: Xianghua SuDepartment of Respiratory Medicine, Mindong Hospital of Fujian Medical University, No. 89 Heshan Road, Fuan City, 355000, Fujian Province, People’s Republic of ChinaEmail Suxianghua505@126.comBackground: Survival in non-small cell lung cancer (NSCLC) remains poor. Early detection of NSCLC is of great significance to provide a chance to improve survival.Aim: We constructed predictive models to evaluate the predictive value of four tumor biomarkers by including serum human epididymis protein 4 (HE4), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), and cytokeratin 19 fragment (CY21-1) on detecting NSCLC in a Chinese elderly population.Methods: A total of 363 patients with NSCLC and 433 subjects without cancer (healthy control group) were admitted to the respiratory department in our hospital. We assessed serum levels of these four tumor biomarkers in the two groups and then the predictive value of predictive models was evaluated.Results: Serum median values of HE4 (143.3 pmol/L), CEA (4.60 ng/mL), SCCA (1.52 ng/mL), and CY21-1 (5.36 ng/mL) in patients with NSCLC were significantly higher than the healthy control group, respectively (all P< 0.05). A multivariate logistic regression model showed that HE4 (OR=2.10, 95% CI=1.22– 4.42, P=0.013), CEA (OR=2.30, 95% CI=1.44– 4.53, P=0.004), SCCA (OR=2.20, 95% CI=1.29– 4.55, P=0.011), and CY21-1 (OR=2.60, 95% CI=1.56– 6.25, P< 0.001) were significantly and independently associated with increased risk of NSCLC on admission after confounding factors were corrected. Importantly, the ROC curve suggested HE4 had a good value on predicting NSCLC in the Chinese elderly population. Additionally, the predictive model (CEA+SCCA+CY21-1+HE4) had better idea capability to detecting the existence of NSCLC (AUC=0.954, 95% CI=0.927– 0.999, P< 0.001).Conclusion: Our study showed that several lung cancer-related biomarkers were used to build prediction models, which has good value for early prediction of NSCLC.Keywords: NSCLC, HE4, CEA, SCCA, CY21-1, Chinese elderly population, predictive value

Xiaohong Quan,1,* Huihui Liu,1,* Dongmei Ye,2 Xinling Ding,3 Xiulan Su4 1Experiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 2Core Facility Center for Functional Experiments, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 3Department of Human Anatomy, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 4Clinical Research Center for Medical Sciences, IMMU, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong QuanExperiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, No. 1 Yingbin Road, Chifeng City, Inner Mongolia, 024000, People’s Republic of ChinaEmail quanxiaohongxh@163.comBackground: Podocyte injury serves an important role during the progression of diabetic nephropathy (DN). The aim of this study was to investigate the effects of forsythoside A (FA) on high glucose (HG)-induced podocyte injury and to identify the possible mechanisms.Methods: MPC-5 podocytes were cultured under HG conditions. After exposure to different doses of FA, cell viability and apoptosis were respectively evaluated with CCK-8 assay and flow cytometry. Then, the levels of oxidative stress-related markers and inflammatory factors were examined by corresponding kits. Western blot analysis was employed to detect the expression of Nox2, Nox4, COX-2, iNOS and matrix metalloproteinases 12 (MMP12). Subsequently, MMP12 was overexpressed to assess whether the effects of FA on HG-stimulated podocyte injury were mediated by MMP12 and MAPK signaling.Results: Results indicated that FA dose-dependently elevated cell viability, reduced cell apoptosis in HG-induced MPC-5 cells. Additionally, FA significantly inhibited oxidative stress, which could be certified by decreased content of malondialdehyde (MDA), enhanced activities of superoxide dismutase (SOD) and catalase (CAT), and downregulated expression of Nox2 and Nox4. Moreover, notably reduced levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were observed in FA-treated MPC-5 cells under HG conditions, accompanied by decreased COX-2 and iNOS expression. Remarkably, FA suppressed MMP12 expression in a dose-dependent manner, and the effects of FA on MPC-5 cells exposed to HG were partially counteracted by MMP12 overexpression. Mechanically, FA inactivated the expression of phospho-ERK (p-ERK), p-p38 and p-JNK, which was restored after MMP12 overexpression.Conclusion: These findings demonstrate a protective mechanism of FA by inactivating MAPK signaling via MMP12 inhibition in HG-induced podocyte injury, providing a promising therapeutic candidate for the treatment of DN.Keywords: diabetic nephropathy, high glucose, oxidative stress, inflammation, apoptosis

Weichi Wei,1 Xin Peng,2 Xuan Su3 1Acupuncture and Rehabilitation Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2The Eighth Clinical School of Medicine, Guangzhou University of Chinese Medicine, Foshan, People’s Republic of China; 3The Ninth People’s Hospital of Nanhai District, Foshan, People’s Republic of ChinaCorrespondence: Xuan Su, Email suxuan2022@126.com

Lin-Man Weng,1,* Xuan Su,1,* Xue-Qiang Wang1,2 1Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, People’s Republic of China; 2Department of Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue-Qiang WangDepartment of Sport Rehabilitation, Shanghai University of Sport, Shanghai, People’s Republic of ChinaTel/Fax +86 02165503470Email Qiang897@163.comPurpose: On 11 March, 2020, the coronavirus disease (COVID-19) outbreak was declared as a global pandemic by the World Health Organization. It brought substantial physical and psychological burden on individuals and financial loss across countries. Patients with COVID-19 may exhibit various symptoms, such as fever, cough, dyspnea, muscle pain, sore throat, headache, chest pain, and abdominal pain, at 2– 14 days after exposure to the novel coronavirus (severe acute respiratory syndrome [SARS]-CoV-2). Pain symptoms present important challenge to clinicians’ diagnosis when treating COVID-19 patients with mild symptoms. Considering the increasing number of confirmed COVID-19 cases, the pain symptoms should be systematically summarized.Results: The virus can invade different tissues of the body and cause different pain manifestations. SARS-CoV-2 primarily invades the respiratory system, and patients develop sore throat, fever, cough, and other pneumonia-associated symptoms. Moreover, it infects the nervous system (eg, headache, dizziness, and confusion), digestive system (eg, abdominal pain, diarrhea), and cardiovascular system (eg, chest pain, palmus, and cardiac injury). The incidence rate is 1.7– 33.9% for headache, 0.7– 47.1% for sore throat, 1.5– 61.0% for myalgia/arthralgia, 1.6– 17.7% for chest pain, and 1.9– 14.5% for abdominal pain. In comparison with chest and abdominal pain, COVID-19 patients are more likely to develop headache, sore throat, and myalgia/arthralgia.Conclusion: Different pain reflects the damage of different body systems. Therefore, the summary of pain symptoms for COVID-19 patients can help doctors improve the accuracy and efficiency of diagnosis when treating COVID-19 patients with atypical or mild symptoms and adopt more targeted treatment methods.Keywords: pain, COVID-19, SARS-CoV-2, symptom