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Fangyuan Lai,1,* Xiuqiong Huang,2,* Jiao Peng,3 Nannan He,4 Zhongqiang Cao,1 Yuhui Wu,4 Wei Li,5 Zebin Chen,1 Xuejuan Li1 1Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Pharmacy, The First People’s Hospital of Zhaoqing, Zhaoqing, People’s Republic of China; 3Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 5Department of Pharmacy, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuejuan Li, Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China, Email xuejuanli@126.comObjective: The first-line treatment for severe Pneumocystis carinii pneumonia (PCP) is trimethoprim-sulfamethoxazole (TMP/SMZ). Here, we report a case involving 6-month-old child with a PCP infection, highlighting the role of clinical pharmacists in providing individualized pharmaceutical care and guidance through the process of therapeutic drug monitoring (TDM).Methods: The clinical pharmacist monitored the concentration of TMP/SMZ in the serum, urine and sputum of a 6-month-old child with PCP infection. To improve the serum levels of TMP/SMZ, the dose of TMP/SMZ was increased, while infusions of other medications were reduced to decrease the rate of drug excretion. Additionally, the patient received other supportive medications to enhance clinical therapeutic efficacy.Results: Clinical pharmacists observed that, despite administration of a sufficient dose of TMP/SMZ, plasma concentration of TMP/SMZ remained below the therapeutic window, while urine concentrations were extremely high. This phenomenon was attributed to Augmented Renal Clearance (ARC), often seen in critically ill patients and associated with increased renal clearance. Throughout treatment, the concentrations of SMZ remained below the minimum effective concentration, while the concentrations of TMP fell within the effective target range. However, sufficient therapeutic effects were ultimately achieved and observed in the patient, likely due to improved drug distribution in lung tissue (sputum) and the patient’s recovering immune functions. Finally, thanks to individualized pharmaceutical care from clinical pharmacists and the combined efforts of clinicians, the patient was discharged after 58 days of hospitalization.Conclusion: Throughout treatment, the clinical pharmacist played a vital role in optimizing the treatment plan based on the serum, urine and sputum concentrations of TMP/SMZ and providing pharmaceutical care to ensure a safe, rational and effective medications in children. Individualized dose adjustments, particularly high-dose TMP/SMZ guided by TDM, can significantly enhance the management of PCP in pediatric patients and support clinical pharmacists in delivering individualized pharmaceutical care.Keywords: Pneumocystis carinii pneumonia, trimethoprim/sulfamethoxazole, therapeutic drug monitoring, plasma drug concentration

Yang Liu,1,* Chunan Wang,1,* Sitong Liu,1,* Hangzhan - Ma,2 Jiayun Xu,3 Kai Jiang,1 Ruitao Lu,4 Xintao Shuai,5 Jinming Wang,3 Zhong Cao1 1School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China; 4Shenzhen International Institute for Biomedical Research, Shenzhen, Guangdong, People’s Republic of China; 5Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong Cao; Jinming Wang, Email caozhong@mail.sysu.edu.cn; wjinm@mail.sysu.edu.cnBackground: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence.Methods: In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs’ anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer.Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.Keywords: magnetic resonance imaging, photothermal therapy, anti-inflammatory therapy, mesoporous polydopamine, cancer therapy

Shiya Zeng,1,* Yanyue Tan,1,2,* Zhiwei Cao,3 Yunhao Zheng,1 Tiqian Liu,1 Yifei Deng,1 Xin Xiong1 1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Nursing, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3School of Stomatology, Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Xiong, State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 15, West Section 3, Second Ring Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 028 85501425, Email drxiongxin@scu.edu.cnObjective: Growing researches explore vitamin D’s role in temporomandibular disorders (TMDs), but the link between vitamin D and TMDs remains debated. To clarify the causal relationship, we conducted a Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS).Subjects and Methods: The GWAS dataset of vitamin D (GWAS ID: ukb-d-30890_irnt; sample size: 329247) was obtained from the IEU Open GWAS project. And that of TMDs (GWAS ID: finn-b-TEMPORO; sample size: 134280), initiated on August 25th, 2017 and publicly released on December 18th, 2023, was extracted from the FinnGen dataset, whose cases were diagnosed based on the revised International Classification of Diseases, 10th Edition (ICD-10) code K07.6. Both datasets were obtained from the European population. According to three assumptions of MR analysis, a bi-directional MR analysis was performed to measure the causal relationship, with Inverse variance weighted (IVW) as the primary method and MR Egger and Weighted median as supplement. Moreover, diverse sensitivity analyses, including Cochran’s Q test, MR Egger intercept, Mendelian randomized polymorphism RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis, were used to verify the stability of the findings.Results: The MR analysis supported causal effects of vitamin D levels on TMDs risks within the European population using IVW method [odds ratio = 1.316; 95% confidence interval = 1.086 to 1.595; P = 0.005], supported by MR Egger and Weighted median. While there was no indication that TMDs have a direct impact on vitamin D levels [β: − 0.00738, standard error = 0.00665; P = 0.568].Conclusion: The study revealed that within the European population higher levels of vitamin D led to higher risks of developing temporomandibular disorders, but found no obvious evidence that TMDs are causally associated with vitamin D. The conclusion should be cautiously interpreted, given the selection bias of TMDs patients sample.Keywords: Mendelian randomization analysis, temporomandibular joint disorders, vitamin D, 25-hydroxyvitamin D

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

Zhenghua Cao,1 Shengkun Zhao,1 Shaodan Hu,2 Tong Wu,3 Feng Sun,2 LI Shi2 1Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People’s Republic of China; 2Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People’s Republic of China; 3Geriatric Department, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of ChinaCorrespondence: LI Shi, Email shili0648@163.comPurpose: To employ bioinformatics and machine learning to predict the characteristics of immune cells and genes associated with the inflammatory response and ferroptosis in chronic obstructive pulmonary disease (COPD) patients and to aid in the development of targeted traditional Chinese medicine (TCM). Mendelian randomization analysis elucidates the causal relationships among immune cells, genes, and COPD, offering novel insights for the early diagnosis, prevention, and treatment of COPD. This approach also provides a fresh perspective on the use of traditional Chinese medicine for treating COPD.Methods: R software was used to extract COPD-related data from the Gene Expression Omnibus (GEO) database, differentially expressed genes were identified for enrichment analysis, and WGCNA was used to pinpoint genes within relevant modules associated with COPD. This analysis included determining genes linked to the inflammatory response in COPD patients and analyzing their correlation with ferroptosis. Further steps involved filtering core genes, constructing TF-miRNA‒mRNA network diagrams, and employing three types of machine learning to predict the core miRNAs, key immune cells, and characteristic genes of COPD patients. This process also delves into their correlations, single-gene GSEA, and diagnostic model predictions. Reverse inference complemented by molecular docking was used to predict compounds and traditional Chinese medicines for treating COPD; Mendelian randomization was applied to explore the causal relationships among immune cells, genes, and COPD.Results: We identified 2443 differential genes associated with COPD through the GEO database, along with 8435 genes relevant to WGCNA and 1226 inflammation-related genes. A total of 141 genes related to the inflammatory response in COPD patients were identified, and 37 core genes related to ferroptosis were selected for further enrichment analysis and analysis. The core miRNAs predicted for COPD include hsa-miR-543, hsa-miR-181c, and hsa-miR-200a, among others. The key immune cells identified were plasma cells, activated memory CD4 T cells, gamma delta T cells, activated NK cells, M2 macrophages, and eosinophils. Characteristic genes included EGF, PLG, PTPN22, and NR4A1. A total of 78 compounds and 437 traditional Chinese medicines were predicted. Mendelian randomization analysis revealed a causal relationship between 36 types of immune cells and COPD, whereas no causal relationship was found between the core genes and COPD.Conclusion: A definitive causal relationship exists between immune cells and COPD, while the prediction of core miRNAs, key immune cells, characteristic genes, and targeted traditional Chinese medicines offers novel insights for the early diagnosis, prevention, and treatment of COPD.Keywords: bioinformatics analysis, Mendelian randomization, machine learning, COPD, characteristic genes, targeted traditional Chinese medicine, early diagnosis

Yi Zhou,1 Weina Gao,2 Zhijiao Cao,3 Shumin Gao,2 Xutong Guo,2 Meng Liu,2 Congjie Cao4 1School of Nursing, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Orthopedics, Baoding No.1 Central Hospital, Baoding, Hebei, People’s Republic of China; 3Department of Nursing, Baoding No.1 Central Hospital, Baoding, Hebei, People’s Republic of China; 4Nursing Department, Langfang Health Vocational College, Langfang, Hebei, People’s Republic of ChinaCorrespondence: Weina Gao, Department of Orthopedics, Baoding No.1 Central Hospital, No. 320, Changcheng North Street, Lianchi District, Baoding, Hebei, 071000, People’s Republic of China, Tel +86 0312-5975023, Email gaoweina984926@163.comBackground: Kinesiophobia is common in patients after total knee arthroplasty and is an important risk factor for post-operative recovery outcomes. Little is known about the complex intercorrelations between different components of pain catastrophizing, self-efficacy, and kinesiophobia. This study aimed to identify the central components of kinesiophobia and to explore the interconnectedness between components of pain catastrophizing, self-efficacy, and kinesiophobia.Methods: A total of 216 patients after total knee arthroplasty were recruited in this study. Pain Catastrophizing Scale, Self-efficacy of Rehabilitation Outcome Scale and Tampa Scale for Kinesiophobia were used to assess pain catastrophizing, self-efficacy and kinesiophobia. R software was used to visualize the networks and analyze the centrality of the networks. The index “strength” and “bridge expected influence” were employed to identify the central components and the bridge components of the networks.Results: In the item network of kinesiophobia, three items (“Simply being careful that I do not make any unnecessary movements is the safest thing I can do to prevent my pain from worsening”, “My accident has put my body at risk for the rest of my life”, and “My body is telling me I have something dangerously wrong”) had the highest strength centrality. In the pain catastrophizing/self-efficacy–kinesiophobia network, rumination had the highest positive bridge expected influence, while coping self-efficacy had the highest negative value.Conclusion: The three central components of kinesiophobia identified in this study, as well as two bridge variables (rumination and coping self-efficacy), could be promising and effective targets for prevention and intervention of kinesiophobia.Keywords: pain catastrophizing, self-efficacy, kinesiophobia, total knee arthroplasty, network analysis

Zhen Cao,1 Xiaoyu Liu,2 Xiangzhen Wang,3 Moning Guo,4 Zhongjun Guan1,5 1School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2School of Statistics, Capital University of Economics and Business, Beijing, People’s Republic of China; 3School of Public Health, Peking University Health Science Center, Beijing, People’s Republic of China; 4Beijing Municipal Health Big Data and Policy Research Center, Beijing, People’s Republic of China; 5Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Moning Guo, Beijing Municipal Health Big Data and Policy Research Center, No. 277, Zhao Dengyu Road, Xicheng District, Beijing, 100053, People’s Republic of China, Email guomoning@wjw.beijing.gov.cn Zhongjun Guan, Beijing Tiantan Hospital, Capital Medical University, No. 119, South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Email guanzhj@ccmu.edu.cnPurpose: As one of the pioneering pilot cities in China’s extensive Diagnosis Related Groups (DRG) -based prepayment reform, Beijing is leading a comprehensive overhaul of the prepayment system, encompassing hospitals of varying affiliations and tiers. This systematic transformation is rooted in extensive patient group data, with the commencement of actual payments on March 15, 2022. This study aims to evaluate the effectiveness of DRG payment reform by examining how it affects the cost, volume, and utilization of care for patients with neurological disorders.Patients and Methods: Utilizing the exogenous shock resulting from the implementation of the DRG-based prepayment system, we adopted the Difference-in-Differences (DID) approach to discern changes in outcome variables among DRG payment cases, in comparison to control cases, both before and following the enactment of the DRG policy. The analytical dataset was derived from patients diagnosed with neurological disorders across all hospitals in Beijing that underwent the DRG-based prepayment reform. Strict data inclusion and exclusion criteria, including reasonableness tests, were applied, defining the pre-reform timeframe as March 15th through October 31st, 2021, and the post-reform timeframe as the corresponding period in 2022. The extensive dataset encompassed 53 hospitals and encompassed hundreds of thousands of cases.Results: The implementation of DRG-based prepayment resulted in a substantial 12.6% decrease in total costs per case and a reduction of 0.96 days in length of stay. Additionally, the reform was correlated with significant reductions in overall in-hospital mortality and readmission rates. Surprisingly, the study unearthed unintended consequences, including a significant reduction in the proportion of inpatient cases classified as surgical patients and the Case Mix Index (CMI), indicating potential strategic adjustments by providers in response to the introduction of DRG payments.Conclusion: The DRG payment reform demonstrates substantial effects in restraining cost escalation and enhancing quality. Nevertheless, caution must be exercised to mitigate potential issues such as patient selection bias and upcoding.Keywords: diagnosis-related groups, payment reform, neurological disorders, DID, China

Jingjing Wei,1 Chunhong Zhang,1 Yi Leng,1 Mingming Li,1 Lingyun Du,1 Zhiqiang Cao,2 Xia Zhu,1 Changyu Han,1 Liya Meng1 1Department of Dermato-Venereology, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Liya Meng, Department of Dermato-venereology, The Second Hospital of Shandong University, 247 Beiyuan Dajie Street, Jinan, 250033, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email mly0706@sina.comObjective and Design: The treatment of recurrent rosacea has always been a problem. Oral minocycline has been widely used in the treatment of rosacea. However, the efficacy and safety of ozonated hydrotherapy combined with LED yellow light irradiation and oral minocycline for mild to moderate papulopustular rosacea (PPR) has not been thoroughly studied.Methods: Patients with rosacea who met the criteria and had complete clinical statistic admitted to our hospital from April 2021 to September 2022 were retrospectively collected and divided into combined therapy group and oral only group. The patients in the two groups were treated with minocycline for 8 weeks. In addition, the patients in combined therapy group were treated with ozone hydrotherapy once a week, followed by LED yellow light irradiation for a total of 4 weeks. The Investigator’ s global assessment (IGA) score was used to assess the condition. The efficacy was evaluated using the patients’ subjective symptom scores. Skin lesion images and adverse reactions were recorded. The recurrence rate was observed after 24 weeks of follow-up.Results: A total of 39 patients included in the study. After 4 weeks of treatment, the effective rate was 90% in combined therapy group and 52.63% in oral only group (p< 0.05). After 8 weeks of treatment, the total score of the patients’ subjective symptom scores and the scores of itching and burning sensation in combined therapy group were lower than those in oral only group (p< 0.05). After 24 weeks of follow-up, the recurrence rate of combined therapy group was 5%, and that of oral only group was 26.32%. The mild adverse reactions experienced by both groups disappeared during follow-up.Conclusion: This combination therapy has a significant, rapid and safe therapeutic effect, especially in relieving itching and burning sensations, and may reduce the recurrence rate.Keywords: papulopustular rosacea, ozonated hydrotherapy, LED yellow light, minocycline, combined therapy

Lingyun Du,1 Zhiqiang Cao,2 Changyu Han,1 Jingjing Wei,1 Mingming Li,1 Chunhong Zhang1 1Department of Dermato-venereology, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, People’s Republic of ChinaCorrespondence: Chunhong Zhang, Department of Dermato-venereology, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email aliu133@163.comObjective: Dermatological consultation plays an important role in diagnosing and treating skin diseases in the Department of Geriatrics. The objective of this study is to provide an analysis of the factors leading geriatric inpatients to seek dermatological consultation, aiming to facilitate accurate diagnosis and effective treatment of skin diseases by healthcare professionals specializing in geriatrics and dermatology.Methods: The electronic health records of hospitalized patients in the Department of Geriatrics who applied for dermatological consultation at the Second Hospital of Shandong University from June 1, 2022, to June 1, 2023, were retrieved. Sex, age, number of consultations, reason for dermatology consultation, and final diagnosis by dermatologists were reviewed.Results: A total of 216 consultations of 178 patients (n=178, 95 men and 83 women) were collected in this study, of whom 153 (86.0%) required only one consultation, 19 (10.7%) required two consultations, and 4 (2.2%) required three consultations. The reasons for dermatology consultations were divided into three categories: the first was for the definitive diagnosis of a new skin condition that developed during the patient’s hospitalization (n=165, 76.4%), the second was for the follow-up of the condition and adjustment of medication (n=40, 18.5%), and the third was for the evaluation of the patient’s disease that existed before admission to the hospital (n=11, 5.1%). In 165 consultations, most of these diseases (n=131, 79.4%) can be diagnosed by patients’ conscious symptoms and clinical manifestations. Some of them need to be diagnosed or differentially diagnosed with the help of supplementary examinations, such as microscopic examination of scabies or fungi, and pathological examination.Conclusion: This study summarized the reasons for dermatology consultations for geriatric inpatients and found that dermatitis/eczema and infectious diseases were the common types of diseases consulted. The findings of this study contribute to the enhanced comprehension and management of dermatological conditions in hospitalized patients by geriatricians, as well as facilitating more efficient diagnosis and treatment by dermatologists.Keywords: geriatrics, dermatology consultation, skin diseases

Xiaoling Long,1,&ast; Huan Zeng,1,&ast; Yun Zhang,1 Qiulong Lu,1 Zhao Cao,2 Hong Shu1 1Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Shu, Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86 7715640296, Email shuhong@gxmu.edu.cn Zhao Cao, Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86 7715356724, Email river_79@126.comPurpose: Developing a high-value, convenient, and validated differential diagnosis model to differentiate alpha-fetoprotein (AFP) negative hepatic occupying lesions and assist clinicians in early identification and intervention.Patients and Methods: A total of 340 patients with AFP-negative hepatic occupying lesions who were admitted to the Guangxi Medical University Cancer Hospital between August 2021 and April 2023 were included in the final retrospective analysis. The data were randomly divided into training and validation sets in a 7:3 ratio after performing multiple interpolations. In the training set, laboratory variables and models were screened using least absolute shrinkage and selection operator regression analysis, comparison of five machine learning algorithms, and univariate, as well as multivariate logistic regression analysis. A diagnostic prediction nomogram model was developed. We evaluated and validated the model using the receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA).Results: We identified six significant predictive factors from the results of multivariate logistic analysis in the training set and incorporated them into the nomogram model for diagnosing AFP-negative hepatic malignant occupying lesions (HMOL). The diagnostic nomogram, including gender, age, des-gamma-carboxy prothrombin (DCP), serum ferritin (SF), AFP, and hepatitis B surface antigen (HBsAg), achieved an area under the curve of 0.905 discriminated patients with HMOL from those with benign occupying lesions. Additionally, calibration curves demonstrated the close alignment between the nomogram predictions and the ideal curve, along with the consistency between predictions and actual results. Moreover, the DCA curves illustrated indicated benefit for all patients. These finding were confirmed by the validation set.Conclusion: The GADSAH model specifically targets the discrimination of malignant and benign liver lesions in AFP-negative patients. It offers a noninvasive, cost-effective, and efficient approach for diagnosing such cases.Keywords: hepatic occupying lesions, alpha-fetoprotein-negative, nomogram, diagnostic model

Qiong Ge,1,&ast; Zhewen Zhang,2,&ast; Zhiming Cao,2 Dan Wu,3 Changping Xu,1 Jianbiao Yao,3 Jian Gao,1 Yan Feng1 1Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China; 2College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Zhejiang Conba Pharmaceutical Co., Ltd, Hangzhou, Zhejiang, 310057, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Feng, Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China, Tel/Fax +86-571-87115204, Email yfeng@cdc.zj.cnPurpose: This study aims to investigate the in vitro antiviral effects of the aqueous solution of Changyanning (CYN) tablets on Enterovirus 71 (EV71), and to analyze its active components.Methods: The in vitro anti-EV71 effects of CYN solution and its herbal ingredients were assessed by testing the relative viral RNA (vRNA) expression level and the cell viability rates. Material basis analysis was performed using HPLC-Q-TOF-MS/MS detection. Potential targets and active components were identified by network pharmacology and molecular docking. The screened components were verified by in vitro antiviral experiments.Results: CYN solution exerted anti-EV71 activities as the vRNA is markedly reduced after treatment, with a half maximal inhibitory concentration (IC50) of 996.85 μg/mL. Of its five herbal ingredients, aqueous extract of Mosla chinensis (AEMC) and leaves of Liquidambar formosana Hance (AELLF) significantly inhibited the intracellular replication of EV71, and the IC50 was tested as 202.57 μg/mL and 174.77 μg/mL, respectively. Based on HPLC-Q-TOF-MS/MS results, as well as the comparison with the material basis of CYN solution, a total of 44 components were identified from AEMC and AELLF. Through network pharmacology, AKT1, ALB, and SRC were identified as core targets. Molecular docking performed between core targets and the components indicated that 21 components may have anti-EV71 effects. Of these, nine were selected for in vitro pharmacodynamic verification, and only rosmarinic acid manifested in vitro anti-EV71 activity, with an IC50 of 11.90 μg/mL. Moreover, rosmarinic acid can stably bind with three core targets by forming hydrogen bonds.Conclusion: CYN solution has inhibitory effects on EV71 replication in vitro, and its active component was identified as rosmarinic acid. Our study provides a new approach for screening and confirmation of the effective components in Chinese herbal preparation.Keywords: antiviral effects, material basis analysis, component-target-pathway-disease network, protein–protein interaction network, core targets, rosmarinic acid

Yan Ding,1,&ast; Banqin Wang,2,&ast; Yongjun Liu,1 Shengjie Dong,1 Xuri Sun,1 Zhilin Cao,1 Leisheng Wang1 1Department of Orthopedics, Yantaishan Hospital, Yantai, People’s Republic of China; 2Department of Blood Transfusion, Shandong Provincial Qianfoshan Hospital Affiliated with Shandong First Medical University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leisheng Wang, Department of Orthopedics, Yantaishan Hospital, No. 10087 Keji Road, Yantai, 264003, People’s Republic of China, Tel +86-13792566016 ; +86-0535-6863898, Email 37724148@qq.comPurpose: Percutaneous pedicle screw fixation is a common minimally invasive treatment for traumatic thoracolumbar and lumbar fractures; however, research on hardware removal after successful healing is limited. We aimed to introduce a rapid, safe, minimally invasive, and cost-effective method for percutaneous pedicle screw removal.Patients and Methods: We conducted a retrospective analysis of demographic (age, sex, body mass index, alcohol use, and current smoking), clinical (hypertension and diabetes mellitus), surgical (affected levels, number of screws, time of surgery, and blood loss), and treatment cost characteristics of 92 patients who had undergone percutaneous pedicle screw removal between May 2016 and February 2023. The first 57 patients underwent the conventional method, and the remaining 35 underwent the modified method. Independent-sample t-tests and chi-square tests were used to compare continuous and categorical variables, respectively, between the two groups.Results: No significant differences were observed in the demographic parameters, complications, or affected levels between the groups. However, the average surgical time (P=0.000) was significantly shorter, and the average blood loss volume (P=0.002) and total cost (P=0.000) were significantly lower in the modified group than in the conventional group.Conclusion: Compared with the conventional method, our modified method can shorten the surgical time, reduce blood loss, and reduce the total cost of treatment. It is a quick and safe minimally invasive method that does not require additional surgical instruments and is suitable for implementation in primary hospitals.Keywords: bone screw, device, Kirschner wire, surgery, control

Qing Song, Xi Wang,&ast; Zhenhuan Cao,&ast; Chun Xin,&ast; Jingyuan Zhang,&ast; Suwei Li Intensive Care Unit, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Suwei Li, Tel +86 180 9887 5867, Email lisuweicn@163.comAbstract: Apelin is the native ligand for the G protein-coupled receptor APJ. Numerous studies have demonstrated that the Apelin/APJ system has positive inotropic, anti-inflammatory, and anti-apoptotic effects and regulates fluid homeostasis. The Apelin/APJ system has been demonstrated to play a protective role in sepsis and may serve as a promising therapeutic target for the treatment of sepsis. Better understanding of the mechanisms of the effects of the Apelin/APJ system will aid in the development of novel drugs for the treatment of sepsis. In this review, we provide a brief overview of the physiological role of the Apelin/APJ system and its role in sepsis.Keywords: apelin, sepsis, organ dysfunction, hemodynamics, fluid homeostasis

Ziran Wang,1,&ast; Lingjun Kong,1,&ast; Rui Zhang,1 Xiaobo Yang,2 Zhe Cao,3 Tengda Xu,4 Han Zhang,1 Yaling Dou1 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Hunan Light of Life Biotechnology Co., Ltd., Ningxiang, Hunan, People’s Republic of China; 4Department of Health Management, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaling Dou, Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email douyl@pumch.cnObjective: To evaluate the diagnostic performance of aldo-keto reductase family 1 member B10 (AKR1B10) in a Beijing cohort with hepatocellular carcinoma (HCC).Methods: This study included 521 subjects who visited Peking Union Medical College Hospital from June 2017 to May 2023, including 109 cases of HCC, 165 cases of healthy controls, 106 cases of benign liver diseases, and 141 cases of other cancers. Serum AKR1B10 levels were measured and compared across various groups. Diagnostic performances of serum AKR1B10 and other tumor markers were assessed using receiver operator characteristic (ROC) curves. In addition, a subset of HCC patients who underwent surgical resection were recruited for clinical follow-up study.Results: We found that serum AKR1B10 expression was higher in patients with HCC relative to other control groups. The association between serum AKR1B10 and clinical features of HCC was not observed. Serum AKR1B10 showed a high diagnostic performance for HCC, and when combined with AFP, the diagnostic effectiveness was significantly improved. Specifically, serum AKR1B10 showed superior diagnostic effectiveness for AFP-negative HCC. The clinical follow-up study indicated a gradual decrease in serum AKR1B10 after surgery.Conclusion: Our study demonstrated that serum AKR1B10 is a promising biomarker for HCC, and when used in combination with AFP can significantly improve the detection rate of HCC.Keywords: AKR1B10, AFP, hepatocellular carcinoma, diagnostic performance

Jingjing Wei, Lingyun Du, Zhiqiang Cao, Mingming Li, Chunhong Zhang, Chunmin Zhang, Liya Meng Department of Dermato-Venereology, The Second Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Liya Meng, Department of Dermato-venereology, The Second Hospital of Shandong University, 247 Beiyuan Dajie Street, Jinan, 250033, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email mly0706@sina.comBackground: Acne is a chronic inflammatory disease of the pilosebaceous unit. Improper treatment of acne can lead to skin lesions in some people. Acne hypertrophic scar is relatively rare, but it significantly affects the appearance and beauty, and usually has a great psychological and social impact on patients.Objective: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with 5-fluorouracil (5-FU) injection and triamcinolone acetonide (TAC) solution in the treatment of acne hypertrophic scars.Methods: This article included 13 outpatients with acne accompanied by acne hypertrophic scar who were treated from September 2018 to September 2022. All patients received ALA-PDT combined with intralesional injection of 5-FU and TAC. At first, patients received ALA-PDT once every two weeks. After the third ALA-PDT, 5-FU and TAC were mixed in a ratio of 3:7, and then immediately injected in the local scars. The effect was observed after 1 month. If the effect is not obvious, a further injection of 5-FU and TAC to the lesion is necessary. The patients were followed up for 6 months. The Vancouver Scars Scale (VSS) was used to evaluate the efficacy before and after treatment and photos of patients were collected.Results: After ALA-PDT combined with intralesional 5-FU and TAC, all patients achieved good clinical efficacy. 23.08% of patients received one local injection and 76.92% received two local injections. After treatment, the scar lesions were reduced and flattened, and the scars became soft. The total score of VSS after treatment was significantly lower than before, and the difference was statistically significant (P< 0.05). The main adverse reactions were pain, erythema, and pigmentation, which can subside within 3 weeks. There was no recurrence after 6 months of follow-up.Conclusion: ALA-PDT combined with intralesional injection of 5-FU and TAC significantly affects acne hypertrophic scars, which is worthy of further in-depth and large-scale research.Keywords: acne hypertrophic scars, ALA-PDT, 5-FU, TAC, acne

Zhiyu Li,1 Zhongying Cao,1 Nanxi Li,2 Luying Wang,2 Cong Fu,2 Ran Huo,1,2 Guangqi Xu,2 Chonglin Tian,2,&ast; Jianhai Bi1– 3,&ast; 1Department of Plastic and Aesthetic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Plastic and Aesthetic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianhai Bi, Department of Plastic and Aesthetic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 324, Jingwu Road, Huaiyin District, Jinan, Shandong Province, 250021, People’s Republic of China, Tel +86-15110080702, Email bijianhai@126.com Chonglin Tian, Department of Plastic and Aesthetic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Huaiyin District, Jinan, Shandong Province, 250021, People’s Republic of China, Tel +86-15666966900, Email chonglin2014@126.comPurpose: Infantile hemangiomas (IHs) are commonly observed benign tumors that can cause serious complications. M2-polarized macrophages in IHs promote disease progression. In this study, we investigated the role of M2 macrophage-derived exosomal lncRNA MIR4435-2HG in IHs.Patients and Methods: Exosomes derived from M2 polarized macrophages were extracted. Next, using cell co-culture or transfection, we investigated whether M2 polarized macrophage-derived exosomes (M2-exos) can transport MIR4435-2HG to regulate the proliferation, migration, invasion, and angiogenesis of hemangioma-derived endothelial cells (HemECs). RNA-seq and RNA pull-down assays were performed to identify targets and regulatory pathways of MIR4435-2HG. We explored the possible mechanisms through which MIR4435-2HG regulates the biological function of HemECs.Results: M2-exos significantly enhanced the proliferation, migration, invasion, and angiogenesis of HemECs. Thus, HemECs uptake M2-exos and promote biological functions through the inclusion of MIR4435-2HG. RNA-seq and RNA pull-down experiments confirmed that MIR4435-2HG regulates of HNRNPA1 expression and directly binds to HNRNPA1, consequently affecting the NF-κB signal pathway.Conclusion: MIR4435-2HG of M2-exos promotes the progression of IHs and enhances the proliferation, migration, invasion, and angiogenesis of HemECs by directly binding to HNRNPA1. This study not only reveals the mechanism of interaction between M2 macrophages and HemECs, but also provides a promising therapeutic target for IHs.Graphical Abstract: Keywords: hemangioma-derived endothelial cell, infantile hemangioma, M2-polarized macrophage, MIR4435-2HG, HNRNPA1

Haiyang Meng,1,2 Yongmei Zhao,1,2 Qi An,1,2 Baoling Zhu,3 Zhe Cao,4 Jingli Lu1,2 1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of pharmacy, Xiangcheng Hospital of Chinese Medicine, Xiangcheng, People’s Republic of China; 4Department of pharmacy, Zhenping People’s Hospital, Zhenping, People’s Republic of ChinaCorrespondence: Jingli Lu, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, People’s Republic of China, Tel +86 371 66913047, Email lujingli123@163.comBackground: The incidence of carbapenem-resistant organism (CRO) infections is increasing in children. However, pediatric-specific treatment strategies present unique challenges. Ceftazidime/avibactam is a β-lactam/β-lactamase inhibitor combination, showing adequate efficiency against CRO isolates. However, clinical data on the efficacy of ceftazidime/avibactam in children are still lacking.Methods: This was a retrospective study of children (aged < 18 years) infected with confirmed or suspected carbapenem-resistant pathogens and treated with ceftazidime-avibactam at the First Affiliated Hospital of Zhengzhou University between 2020 and 2022.Results: We identified 38 children aged 14 (5.0– 16.3) years; 20 (52.6%) had hematologic malignancies. 25 children with confirmed CRO infections were administered ceftazidime-avibactam as targeted therapy. The median treatment was 10 (6.0– 16.5) days. Among them, 24 had infections caused by carbapenem-resistant Enterobacterales (CRE) (18 carbapenem-resistant Klebsiella pneumoniae and six carbapenem-resistant Escherichia coli species) and one with carbapenem-resistant Pseudomonas aeruginosa strains. The source of infection was the bloodstream in 60.0% of the cases (15/25). The clinical response rate was 84.0% (21/25), and 30-day mortality rate was 20% (5/25). 13 children were administered ceftazidime-avibactam as empiric therapy for suspected infections. The median treatment was 8 (6.0– 13.0) days. No deaths occurred and clinical response was achieved in 12 of the 13 patients (92.3%) who empirically treated with ceftazidime-avibactam.Conclusion: Ceftazidime-avibactam is important for improving survival, and clinical response in children with infections caused by CRO.Keywords: ceftazidime-avibactam, carbapenem-resistant organisms, children

Jianquan Li, Yongyang He, Xi Lei, Zhongqiang Cao, Yuwei Liao, Guoqiang Wang, Zebin Chen, Xuejuan Li, Xiaoya Liu Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Xiaoya Liu, Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, 518026, Guangdong Province, People’s Republic of China, Tel +86 075583008256, Email liuxy2949@163.comBackground: Antimicrobial agents’ wastage is a huge problem, especially for pediatric patients, resulting in excessive drug expenditure and increasing the economic burden on patients’ families. Moreover, the cost of disposing of antimicrobial agents’ waste and the risk of environmental and occupational exposure also increased. This study aimed to explore the cost-effectiveness of the vial-sharing strategy combined with the daily-rate charge mode for pediatric inpatients to provide a strategy for reducing patients’ expenditures, saving medical costs, and reducing drug proportion.Methods: This retrospective study was conducted at Pharmacy Intravenous Admixture Service (PIVAS), Shenzhen Children’s Hospital, Guangdong Province, China, in 2022. Data on prescription drugs were collected from the PIVAS system. Ten antimicrobial drugs with a frequency of prescriptions no less than twice once daily were selected, and the drug costs, drug weight, and drug saved were further analyzed according to the combination of real-time vial sharing strategy and daily-rate charge mode. Traditional single vial charge mode without vial sharing was set as a control strategy. The actual expenditure of the hospital was also calculated and analyzed.Results: During 2022, ¥ 4,122,099 (34.4%) was saved for inpatients by applying a vial-sharing strategy on ten antibacterial agents, and more than 46,343,750 mg (24.6%) of drugs were totally saved. The top 5 drugs saved by the real-time vial-sharing strategy were cefoperazone-sulbactam, vancomycin, amoxicillin-sulbactam, ceftazidime, and meropenem. Taken the price into consideration, the top five payment-saved drugs were vancomycin (¥ 1,522,385), meropenem (¥ 1,311,475), cefoperazone-sulbactam (¥ 736,697), imipenem-cilastatin (¥ 406,092), and amoxicillin-sulbactam (¥ 51,394). Moreover, the account balance of the hospital was up to ¥ 426,499.Conclusion: The real-time vial sharing strategy combined with the daily-rate charge mode greatly reduces drug wastage and patients’ payments. It may be useful for hospitals with PIVAS to achieve vial-sharing while protecting the best interest of inpatients.Keywords: real-time vial sharing strategy, daily-charge mode, antimicrobial drugs, inpatients, PIVAS

Mingming Li, Xia Zhu, Zhiqiang Cao, Lingyun Du, Jingjing Wei, Chunhong Zhang Department of Dermato-Venereology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Chunhong Zhang, Department of Dermato-Venereology, the Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan, Shandong, 250033, People’s Republic of China, Fax +86-531-88962544, Email aliu133@163.comBackground: Skin abscesses are a common skin condition usually caused by bacterial infections and their incidence is increasing in children. Its current management strategy is still mainly incision and drainage, sometimes with antibiotics. In pediatric patients, surgical incision and drainage of skin abscesses is challenging compared to in adults because of their specific age and psychological characteristics and high aesthetic requirements. Therefore, it is important to seek better treatment options.Patients and methods: We reported 17 cases of skin abscesses in pediatric patients aged 1 to 9 years. Ten cases had lesions on the face and neck and 7 cases on the trunk and limbs. They all received treatment based on fire needle combined with topical mupirocin.Results: The lesions of all 17 pediatric patients healed within 4 to 14 days, with a median time of 6 days, and all achieved satisfactory results with no scarring left behind. No adverse events were observed in all patients, and no recurrence occurred within 4 weeks.Conclusion: For skin abscesses in pediatric patients, early application of a combination therapy based on fire needle is convenient, aesthetic, economical, safe and clinically important as an alternative to incision and drainage, and deserves further clinical promotion.Keywords: fire needle combined therapy, simple skin abscesses, pediatric patients, mupirocin

Qian Zhang,1,2 Pan Fu,2 Zhanglei Cao,2 Hua Huang,3 Qinwen Wen,3 Kaizhe Wang,2 Tong Kong,2 Xiudi Wu,3 Jianping Zheng2 1Jiangxi Key Laboratory for Rare Earths Magnetic Materials and Devices, College of Rare Earths, Jiangxi University of Science and Technology, Ganzhou, 341000, People’s Republic of China; 2Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences (CAS), Ningbo, 315300, People’s Republic of China; 3Department of Rheumatology and Immunology, Ningbo First Hospital, Ningbo, 315010, People’s Republic of ChinaCorrespondence: Jianping Zheng; Xiudi Wu, Tel +86– 18091984088 ; +86– 13857826442, Email zhengjianping@nimte.ac.cn; awu1100@aliyun.comPurpose: Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms.Patients and Methods: In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy.Results: The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups.Conclusion: Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.Keywords: MTHFR, MTRR, methotrexate, rheumatoid arthritis, DAS28

Ziyi Cao,1,&ast; Li Guan,1,&ast; Runzhi Yu,1 Fan Yang,2 Jie Chen1 1Department of Gastroenterology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Chen; Fan Yang, Email laugh_chenjie@fudan.edu.cn; fdyangfan@fudan.edu.cnPurpose: Hepatocellular carcinoma (HCC) represents one of the most common tumors in the world. Our study aims to explore new markers and therapeutic targets for HCC. Heterogeneous Nuclear ribonucleoprotein A1 (hnRNPA1) has recently been found to be involved in the progression of several types of cancer, but its role in HCC remains uncovered.Methods: We performed bioinformatic analysis to preliminarily show the relationship between hnRNPA1 and liver cancer. Then the correlation of the hnRNPA1 gene expression with clinicopathological characteristics of HCC patients was verified by human liver cancer tissue microarrays. The functional role of this gene was evaluated by in vivo and vitro experiments.Results: Results showed that the expression of hnRNPA1 was upregulated in HCC tissues and was associated with pathological stage of HCC patients. Knockdown of hnRNPA1 gene markedly inhibited tumor growth in vivo, and reversed the effects on proliferation, migration and invasion and promoted apoptosis in vitro. Furthermore, down-regulation of hnRNPA1 gene expression can inhibit the activity of the MEK/ERK pathway.Conclusion: In our work, we combined bioinformatic analysis with in vivo and in vitro experiments to initially elucidate the function of hnRNPA1 in liver cancer, which may help to explore biomarkers and therapeutic targets for HCC patients.Keywords: hepatocellular carcinoma, WGCNA, hnRNPA1, proliferation, MEK/ERK

Sun W, Luo Z, Jin J, Cao Z, Ma Y. Int J Chron Obstruct Pulmon Dis. 2021;16:2267–2277. The authors have advised the author list on page 2267 is incorrect. The text “Yingmin Ma2” should read “Yingmin Ma1,2”. The authors apologize for this error.

Jingnan Jia, Chaoqun Yan, Xiancheng Zheng, Anqi Shi, Zhijun Li, Lufan Xu, Zhiyuan Hui, Yichao Chen, Zimin Cao, Jun Wang Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Chaoqun Yan; Jun Wang, Department of Acupuncture and Moxibustion, Dongzhimen Hospital, Beijing University of Chinese Medicine, Hai Yun Cang on the 5th Zip, Dongcheng District, Beijing, 100700, People’s Republic of China, Tel +86-10-84013161, Email yanchaoqun857@126.com; wangjunee@yeah.netPurpose: Acupuncture has been recognized as an effective and safe alternative therapy for migraine, but its central mechanism has not yet been adequately explained. Meanwhile, research into the clinical efficacy and central mechanism of true acupuncture (TA) and sham acupuncture (SA) is lacking. It is necessary to investigate whether TA has better efficacy than SA, and how they achieve different effects. This study aims to evaluate the efficacy of TA and SA, observe the brain response caused by TA and SA, and further investigate the central nervous mechanism of TA and SA treatment for patients with migraine.Patients and Methods: This is a randomized controlled neuroimaging trial combining acupuncture treatment with functional magnetic resonance imaging, with patients and outcome assessors blinded. A total of 60 patients with migraine will be randomly allocated to receive 12 sessions of either TA or SA treatments (three sessions per week for 4 weeks), and 30 healthy participants will be recruited as the healthy control (HC) group. Outcome assessment and neuroimaging will be conducted before and after the entire intervention. A headache diary and questionnaires of life quality and psychological properties will be used to evaluate clinical efficacy. Multimodal magnetic resonance imagining data analysis will be used to investigate the central mechanism of TA or SA in treating migraine. Pearson’s correlation analysis will be used to reveal the relationship between the brain response and clinical improvements.Conclusion: The results of this study will reveal the brain response to TA and SA in patients with migraine and contribute to further expanding the knowledge of their central mechanism.Study Registration: This trial has been approved by the ethics committee of Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine (DZMEC-KY-2020-38) and registered in the Chinese Clinical Trial Registry (registration number ChiCTR2000033995).Keywords: migraine, acupuncture, functional magnetic resonance imaging, protocol

Lingyun Du,&ast; Zhiqiang Cao,&ast; Zhaoyang Liu, Xia Zhu, Chunhong Zhang Department of Dermato-Venereology, The Second Hospital of Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhong Zhang, Department of Dermato-Venereology, The Second Hospital of Shandong University, Jinan, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email aliu133@163.comAbstract: Periungual wart is a kind of verruca vulgaris that occurs alongside or underlying the nails, which is challenging to treat and prone to recurrence, seriously affecting the quality of patients’ life. We report a 6-year-old boy with periungual warts who had experienced various treatments with no improvement and even worsening. Therefore, we tried to treat the patient with local hyperthermia which uses a patented device that has an infrared emission source. The heat generated by infrared rays acts on the local skin surface. The mechanism of this therapy may be to establish a specific immune response against human papillomavirus-infected tissues, thereby facilitating the clearance of human papillomavirus at irradiated and non-irradiated sites. Local hyperthermia has the advantages of non-contact, safety, noninvasive, less pain, and so on. After 5 treatments, the irradiated periungual warts completely cleared after 2 weeks. The unirradiated sites were almost cured after 7 weeks. This case suggests that local thermotherapy has shown great advantages in the treatment of these refractory periungual warts and offers a new and effective therapy in patients with periungual warts.Keywords: child, local hyperthermia, periungual warts, refractory warts

Dandan Wang,1,2 Zhentang Cao,3 Zixiao Li,1,2,4 Hongqiu Gu,2 Qi Zhou,2 Xingquan Zhao,1,2,4 Yongjun Wang1,2,4 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Xingquan Zhao; Yongjun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86-010-59978891 ; +86-010-59978330, Email zxq@vip.163.com; yongjunwang@ncrcnd.org.cnObjective: Elevated homocysteine (Hcy) levels play a detrimental role in ischemic stroke. Acute spontaneous intracerebral hemorrhage (ICH) accounts for nearly 25% of all stroke cases. However, the influence of Hcy levels and ICH severity on clinical outcomes is unclear.Participants and Study Location: Data were obtained from 85,705 ICH patients enrolled in the China Stroke Center Alliance (CSCA) study, a national, hospital-based, multicenter, voluntary, quality assessment and improvement initiative performed in China. Patients were divided into high and normal Hcy groups according to their Hcy levels observed at admission.Outcome Measures: The outcome indices included severe ICH, in-hospital mortality, and a poor functional outcome at discharge. Multivariable logistic regression was used to analyze the association of different Hcy levels with outcomes.Results: The final analysis included 55,793 ICH patients. High homocysteine (HHcy) levels had higher adjusted odds ratios for severe ICH (OR 1.09, 95% CI 1.01– 1.10, P< 0.0001) and a poor functional outcome at discharge (OR 1.06, 95% CI 1.01– 1.10, P=0.0100) compared with normal Hcy levels. There was no significant difference between HHcy and in-hospital mortality. In the subgroup analysis, stratified by sex and history of hypertension, significant interactions were observed between HHcy and severe ICH (P for interactions was 0.0138 and 0.0120, respectively). HHcy levels exhibited greater associations for severe ICH in female patients (OR 1.07, 95% CI 1.02– 1.12) and patients without hypertension (OR 1.20, 95% CI 1.09– 1.33).Conclusion: An elevated Hcy level exhibited significant association with severe ICH on admission and a poor functional outcome at discharge. The relationship between HHcy and ICH severity on admission was more robust in female patients and patients without hypertension. Hcy might be a valuable biomarker for ICH patients to predict severity at onset and functional outcome at discharge.Keywords: intracerebral hemorrhage, homocysteine, stroke severity, outcome

Zhiqiang Cao, Chunhong Zhang, Jingjing Wei, Guo Wei Department of Dermato-venereology, the Second Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Guo Wei, Department of Dermato-venereology, the Second Hospital of Shandong University, 247 Beiyuan Street, Tianqiao District, Jinan, 250033, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email weiguopfk@163.comBackground: Herpetic folliculitis (HF) is a rare manifestation of herpes virus infection of the skin, which has different presentations causing frequent misdiagnosis. Previous literature has reported follicular infections caused by herpes simplex virus (HSV) in the beard area, called herpetic sycosis, but only a few cases presented facial extensive folliculitis.Purpose: This case series aimed to describe the clinical features of facial generalized herpetic folliculitis.Methods: We retrospectively collected a case series of 20 patients with facial diffused herpetic folliculitis diagnosed clinically or experimentally from outpatients between 2012 and 2022. The reported cases similar to HF of literature were concluded.Results: There were 19 females and 1 male in this study. Disease duration varied from 1 to 10 days, and lesion manifestations were predominantly papules and maculopapules. Most patients suffered spontaneous pain or pruritus and recovered with antiviral treatment. All cases achieved great improvements in lesions after antiviral and topical medication therapy.Conclusion: This case series suggests that in patients with infectious folliculitis of the face when the lesions develop acutely and diffusely, dermatologists should take into account the possibility of herpetic folliculitis, especially in cases where antibacterial or antifungal therapy is resistant, and actively administer antiviral therapy after diagnosis.Keywords: clinical presentations, face, herpetic folliculitis, herpes simplex virus, diagnosis

Wei Sun,1 Zhixin Cao,1 Yingmin Ma,2 Jing Wang,1 Liming Zhang,1 Zujin Luo1 1Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zujin Luo, Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email xmjg2002@163.comBackground: Fibrinogen is increasingly being studied as an inflammatory biomarker in chronic obstructive pulmonary disease (COPD), but there are limited data on the role of fibrinogen in assessing the severity of acute exacerbation of COPD (AECOPD). This study aimed to explore whether circulating fibrinogen could be used as a surrogate to measure the severity and predict the prognosis of AECOPD.Methods: A total of 535 AECOPD patients diagnosed at our center from January 2016 to June 2021 were retrospectively enrolled in this study. The electronic medical record of each patient was retrieved to collect data on baseline characteristics and laboratory parameters, as well as the use of noninvasive positive-pressure ventilation (NPPV) and prognosis. Multiple linear regression analysis was used to identify independent factors associated with circulating fibrinogen values. Receiver-operating characteristic curve and multivariate logistic regression analysis were applied to further verify the use of fibrinogen to predict NPPV failure.Results: Compared to patients with fibrinogen < 4 g/L, patients with increased fibrinogen levels (> 4 g/L) tended to have elevated inflammatory response and higher incidence of DVT/PTE, emphysema, pneumonia, and atherosclerosis. In addition, fibrinogen levels in NPPV-failure patients were significantly higher than non-NPPV patients and NPPV-success ones. The presence of emphysema, pneumonia, and history of long-term oxygen therapy and higher CRP levels and leukocyte counts were independent risk factors associated with increased fibrinogen levels in AECOPD. Furthermore, our data indicated that fibrinogen could be considered as a reliable biomarker to predict NPPV failure (AUC, 0.899, 95% CI 0.846– 0.952), with an OR of 7.702 (95% CI 2.984– 19.875; P< 0.001).Conclusion: The level of circulating fibrinogen can be used to measure severity of AECOPD, and among AECOPD patients managed with NPPV, fibrinogen > 3.55 g/L can independently predict NPPV failure.Keywords: COPD, noninvasive positive-pressure ventilation, acute exacerbation, fibrinogen, predictor

Zhipeng Wu,1,&ast; Zujin Luo,2,&ast; Zengtao Luo,2 Jingyi Ge,3 Jiawei Jin,4 Zhixin Cao,2 Yingmin Ma1 1Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Respiratory Medicine, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, People’s Republic of China; 4The Clinical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingmin Ma, Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China, Tel +86 10-13501185982, Email mayingmin@ccmu.edu.cnPurpose: The evidence of long-term home noninvasive positive pressure ventilation (LTHNIPPV) in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD) is controversial. In this meta-analysis study, we sought to establish whether a baseline level and reduction in partial pressure of arterial carbon dioxide (PaCO2) were associated with the treatment effect of LTHNIPPV in these patients.Patients and Methods: Six electronic databases were comprehensively searched from January 1980 until June 2020. Randomized clinical trials (RCTs) comparing LTHNIPPV with control treatment were included. Two authors independently extracted data, assessed the study quality, and used the GRADE approach to evaluate evidence quality. The main outcome was mortality.Results: Nineteen studies involving 1482 patients (LTHNIPPV, n = 730; control, n = 752) were included. LTHNIPPV significantly reduced mortality (relative risk [RR] = 0.76; 95% confidence interval [CI]: 0.61– 0.95; p = 0.02; I2 = 14%), the frequency of hospital admissions, PaCO2, and improved partial pressure of oxygen (PaO2) compared to control treatment. LTHNIPPV also relieved dyspnea and improved exercise capacity and health-related quality of life (HRQL) but showed no significant benefit for improving the forced expiratory volume in one second in predicted (FEV1% pred). Subgroup analysis revealed that the baseline level and reduction in PaCO2 were associated with decreased mortality (baseline PaCO2 ≥ 55 mmHg RR = 0.69, P = 0.02; vs baseline PaCO2 < 55 mmHg RR = 0.87, P = 0.32; and higher dPaCO2 RR = 0.42, P < 0.0001; vs lower dPaCO2 RR = 0.91, P = 0.38).Conclusion: LTHNIPPV significantly reduced mortality. The baseline level and reduction in PaCO2 were associated with the treatment effect of LTHNIPPV in patients with stable hypercapnic COPD. Large-scale, multicenter RCTs are needed to confirm our results.Keywords: COPD, long-term home noninvasive positive pressure ventilation, mortality, meta-analysis study, RCTs, stable hypercapnic

Zubai Cao,1 Chengcheng Yue,1 Qinxiang Kong,2 Yanyan Liu,1,3,4 Jiabin Li1,3,4 1Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Infectious Diseases, The Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Center for Surveillance of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Jiabin Li Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Jixi road 218, Hefei, Anhui, 230022, People’s Republic of China Tel +86-551-62922713 Fax +86-551-62922281 Email lijiabin@ahmu.edu.cnPurpose: This study aimed to describe trends in Klebsiella pneumoniae (KP) resistance in bloodstream infections (BSI) and to identify risk factors for a hospital-acquired carbapenem-resistant Klebsiella pneumoniae (CRKP) BSI and 28-day mortality from a hospital-acquired KP BSI.Patients and Methods: We recorded the results of antimicrobial susceptibility testing of 396 KP-positive blood cultures from January 2016 to December 2020. A total of 277 patients with a KP BSI were included in this study, of which 171 had a hospital-acquired infection and 84 had a hospital-acquired CRKP BSI. Multivariate logistic regression analysis was used to identify risk factors for a hospital-acquired CRKP BSI and 28-day mortality from a hospital-acquired KP BSI.Results: The proportion of hospital-acquired infections among KP BSI patients increased from 53.1% in 2016 to 72.8% in 2020. The detection rate of CRKP among KP BSI patients increased from 18.8% in 2016 to 37.7% in 2020. Multivariate logistic regression showed that β-lactam/β-lactamase inhibitor combinations (BLBLIs) exposure (P = 0.022, OR 2.863), carbapenems exposure (P = 0.007, OR 3.831) and solid organ transplantation (P < 0.001, OR 19.454) were independent risk factors for a hospital-acquired CRKP BSI. Risk factors for a 28-day mortality from hospital-acquired KP BSI were CRKP BSI (P =0.009, OR 5.562), septic shock (P =0.002, OR 4.862), mechanical ventilation> 96 hours (P =0.020, OR 8.765), and platelet counts < 100× 109/L (P =0.003, OR 4.464).Conclusion: The incidence of hospital-acquired KP BSI continues to rise and the proportion of CRKP BSI is also increasing. We believe that the use of the BLBLIs needs to be carefully evaluated in hospital-acquired infection. Hospital-acquired KP BSI Patients with CRKP BSI, septic shock, mechanical ventilation and deficiency of platelets are more likely to have a poor prognosis.Keywords: Klebsiella pneumoniae, bloodstream infection, carbapenem resistance, hospital-acquired infection, risk factors

Kwanza Price,1 Zhun Cao,2 Craig Lipkin,2 Deb Profant,1 Scott Robinson2 1Jazz Pharmaceuticals, Palo Alto, CA, USA; 2Premier Inc., Charlotte, NC, USACorrespondence: Deb ProfantJazz Pharmaceuticals, 3170 Porter Dr., Palo Alto, CA, 94304, USATel/Fax +1 971 409 6166Email deb.profant@jazzpharma.comPurpose: CPX-351 is dual-drug liposomal encapsulation of daunorubicin and cytarabine at a fixed synergistic 1:5 molar ratio. This study determined current real-world use of CPX-351 versus conventional 7+3 (cytarabine+daunorubicin) therapy and evaluated hospital length of stay (LOS) and supportive care utilization in t-AML and AML-MRC.Patients and Methods: This retrospective, observational study utilized the Premier Healthcare Database and included patients who were aged ≥ 18 years with t-AML or AML-MRC and treated with CPX-351 or 7+3 between August 1, 2017 and February 28, 2019. All patients treated with 7+3 were required to be eligible for CPX-351 based on its FDA-approved indication. Outcome variables were annualized and adjusted for patient, hospital, and clinical confounding factors. The primary outcome was inpatient LOS. Secondary outcomes included use of blood products and use of anti-infectives.Results: The study included 195 qualifying patients treated with CPX-351 and 160 patients treated with 7+3 who were eligible for CPX-351. Approximately one-third of the patients treated with CPX-351 were administered therapy in a hospital-based outpatient setting, and all patients treated with 7+3 received it in the inpatient setting. The regression-adjusted annualized inpatient LOS was shorter with CPX-351 than 7+3 (mean of 183.7 vs 197.1 days, p< 0.001). The difference in mean-adjusted LOS was most pronounced for t-AML, with a mean-adjusted LOS of 168.9 versus 192.5 days for CPX-351 versus 7+3, respectively (nominal p< 0.001). Supportive care utilization, including the number of administrations of red blood cells, the number of administrations of platelets, and the number of days on anti-infectives, was similar between treatment groups.Conclusion: CPX-351 was associated with a shorter inpatient LOS than 7+3. Supportive care use, including blood products and anti-infectives, was similar for CPX-351 and 7+3. These findings suggest CPX-351 conveys resource advantages over 7+3 in patients with newly diagnosed t-AML and AML-MRC.Keywords: acute myeloid leukemia, chemotherapy, cytarabine, daunorubicin, anthracycline, healthcare resource utilization

Zhang Cao,1 Yichao Chen,2 Wenjie Jiang,1 Wei Li3 1School of Law, Zhejiang University of Finance and Economics, Hangzhou, Zhejiang Province, People’s Republic of China; 2School of Law, Jinan University, Guangzhou, Guangdong Province, People’s Republic of China; 3Intellectual Property Institute, Jinan University, Guangzhou, Guangdong Province, People’s Republic of ChinaCorrespondence: Wei Li Email iprecht@126.comAbstract: Compulsory licensing for drug patents is of great significance to ensure the accessibility of drugs. Although the development of China’s compulsory licensing system for drug patents has been gradually improved, there are still problems. For example, the scope of the object is not realistic, the setting of the initiating subject is unreasonable, the reasons for issuance are not clear, the duration and scope of the license are not refined, and the provisions on the exploitation fee are missing. Consequently, in order to improve China’s compulsory licensing system for drug patents, it is necessary to expand reasonably the scope of the object, remove the restrictions on the initiating subject, adjust the initiating rights of different subjects, determine the duration and scope of the license and the applicability of the hearing on a case-by-case basis, and determine a reasonable exploitation fee by taking into account the national income, patent cost, market share and other factors, in consideration of the flexibly international norms and the actual situation in China.Keywords: drug patents, compulsory licensing, public health

Wei Sun,1,&ast; Zujin Luo,1,&ast; Jiawei Jin,1 Zhixin Cao,1 Yingmin Ma2 1Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingmin MaDepartment of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel +86-10-13501185982Email ma.yingmin@163.comPurpose: To determine the effectiveness of neutrophil/lymphocyte ratio (NLR), compared to traditional inflammatory markers, for predicting noninvasive mechanical ventilation (NIMV) failure in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Patients and Methods: We conducted this retrospective observational study including 212 AECOPD patients who required NIMV during hospitalization from January 2015 to December 2020 in the department of respiratory and critical care medicine of Beijing Chao-Yang Hospital (west campus). We reviewed the medical record to determine if NIMV succeeded or failed for each patient, and compared NLR with traditional markers (leukocyte, C-reactive protein [CRP] and procalcitonin [PCT]) between NIMV failure and NIMV success group. Receiver-operating characteristic (ROC) curve and multivariate logistic regression analysis were used to assess the accuracy of these markers for predicting NIMV failure.Results: A total of 38 (17.9%) patients experienced NIMV failure. NLR was a more sensitive biomarker to predict NIMV failure (AUC, 0.858; 95% CI 0.785– 0.931) than leukocyte counts (AUC, 0.723; 95% CI 0.623– 0.823), CRP (AUC, 0.670; 95% CI 0.567– 0.773) and PCT (AUC, 0.719; 95% CI 0.615– 0.823). There was statistically positive correlation between NLR and leukocytes count (r=0.35, p< 0.001), between NLR and CRP (r=0.258, p< 0.001), between NLR and PCT (r=0.306, p< 0.001). The cutoff value of NLR to predict NIMV failure was 8.9 with sensitivity 0.688, specificity 0.886 and diagnostic accuracy 0.868. NLR> 8.9 (odds ratio, 10.783; 95% CI, 2.069– 56.194; P=0.05) was an independent predictor of NIMV failure in the multivariate logistic regression model.Conclusion: NLR may be an effective marker for predicting NIMV failure in AECOPD patients, and the patients with NLR> 8.9 should be handled with caution since they are at higher risk of NIMV failure and require intubation. Further study with a larger sample size and with more data is necessary to confirm our study.Keywords: COPD, noninvasive mechanical ventilation, neutrophil/lymphocyte ratio, predictor, failure, NIMV, NLR, chronic obstructive pulmonary disease

Jushan Sun,1 Yibiao He,1 Lei Bai,1 Zhipeng Wang,1 Zhu Cao,1 Yingmei Shao,2 Jinming Zhao1 1Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China; 2Xinjiang Uyghur Autonomous Region Clinical Research Center for Echinococcosis and Hepatobiliary Diseases, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of ChinaCorrespondence: Jinming ZhaoDepartment of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137 of Liyushan Street, Xinshi District, Urumqi, Xinjiang, 830054, People’s Republic of ChinaTel/Fax +86-991-4364529Email zhaojm_m@outlook.comObjective: To investigate the risk factors related to new-onset diabetes mellitus (NODM) and the significance of IL-6.Methods: A retrospective analysis was conducted on clinical data from 64 patients who received either a living donor liver transplantation or a donation after circulatory death from September 2013 to October 2020 and attended regular follow-up visits for six or more months. During follow-up, patients were randomized into groups and followed up until the completion of the study or the death of the patient.Results: The incidence of NODM was 31.25% (n = 20). The median age in the NODM group was 52.15 years (p < 0.01). Age (OR = 1.089; 95% CI: 0.0211– 0.1495, p = 0.003) and elevated preoperative IL-6 (OR = 1.122; 95% CI: 0.0619– 0.1677, p = 0.029) were found to be independent risk factors for NODM. HBV-induced liver cirrhosis, warm ischemia time (WIT), body mass index (BMI), and high preoperative fasting blood glucose (FBG) were also found to be risk factors for NODM. The recipient had a higher risk of NODM if the donor had a high BMI and poor hepatic function. The concentrations of IL-6, procalcitonin (PCT), FBG, and tacrolimus (TAC) in the first month postoperatively were significantly higher in the NODM group than in the NO-NODM group. The survival rate of the patients was not affected by NODM.Conclusion: HBV-induced liver cirrhosis, WIT, BMI, and high preoperative FBG levels are risk factors for NODM, and age and preoperative IL-6 levels are independent risk factors. To a certain extent, higher BMI and poor hepatic function had reference significance for the incidence of NODM. Patients with a high concentration of FBG, IL-6, and TAC in the first month postoperatively had an increased risk of suffering from NODM.Keywords: liver transplantation, HBV, IL-6, immunosuppressants, NODM

Yuequn Song,1,2 Lifang Meng,3 Jian Yu,1 Zhi Cao,1 Jizhou Sun,1 Hongyu Zhao2 1Department of Neurosurgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Scientific Research, China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Hongyu ZhaoDepartment of Neurosurgery, Shengjing Hospital of China Medical University, 36 Sanhao St, Heping District, Shenyang, Liaoning, 110004, People’s Republic of ChinaTel +86 18900912293Email hongyu_zhao2020@163.comObjective: Tripartite motif 66 (TRIM66) is reported to be closely associated with human cancers. However, the roles of TRIM66 in glioma remain unclear. The present study aimed to investigate the clinical significance and biological roles of TRIM66 in human glioma.Methods: TRIM66 expression in glioma tissues was examined by immunohistochemistry. TRIM66 overexpression and siRNA knockdown were performed in glioblastoma cell lines. CCK8, colony formation assay, transwell assay, Annexin V and JC1 staining, glucose uptake assay, and Western blotting were used to explore the biological roles and potential underlying mechanisms of TRIM66 in glioma progression.Results: Our results showed that TRIM66 was overexpressed in 52/95 glioma cases. The rates of TRIM66 overexpression in Grade I, Grade II, Grade III, and Grade IV gliomas were 16.6%, 41.3%, 58.6%, and 70.9%, respectively. Oncomine data showed that TRIM66 was upregulated in glioblastoma and oligodendroglioma compared with normal brain tissues. TRIM66 expression was higher in glioblastoma cell lines compared with normal SVG p12 glial cell line. TRIM66 promoted in vitro and in vivo proliferation, invasion, and inhibited temozolomide (TMZ)-induced apoptosis. Notably, TRIM66 increased glucose metabolism by upregulating glucose uptake, glucose consumption, and ATP production. Western blotting showed that TRIM66 positively regulated cMyc and GLUT3. Depletion of cMyc by siRNA abolished the effect of TRIM66 on GLUT3. Chromatin immunoprecipitation (ChIP) assay showed that cMyc could bind to the promoter regions of GLUT3 in glioblastoma cells.Conclusion: TRIM66 was upregulated in human gliomas, where it promoted cell growth and chemoresistance. Our data also identified novel roles of TRIM66 in glioma progression. TRIM66 upregulates glucose uptake and mitochondrial function through the cMyc/GLUT3 signaling, which makes it a potential therapeutic target.Keywords: TRIM66, glioma, cMyc, GLUT3

Hui Ye,1,* Xiaoying Chu,1,* Zhensheng Cao,2,* Xuanxuan Hu,1,* Zihan Wang,2 Meiqi Li,1 Leyu Wan,2 Yongping Li,3 Yongge Cao,4 Zhanqiu Diao,2 Fengting Peng,2 Jinsong Liu,2 Lihua Xu5 1School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 2School of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 3Department of Surgery, Chengdu Shuangliu District Maternal and Child Health Hospital, ChengDu, Sichuan, 610200, People’s Republic of China; 4Department of Stomatology, Haiyuan College, Kunming, Yunnan, 650106, People’s Republic of China; 5Department of General Medicine, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui YeSchool of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of ChinaEmail wmcyh@wmu.edu.cnLihua XuDepartment of General Medicine, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, ChinaEmail lihuaxu@wmu.edu.cnBackground: This study was aimed to prepare a novel magnetic thermosensitive cationic liposome drug carrier for the codelivery of Oxaliplatin (OXA) and antisense lncRNA of MDC1 (MDC1-AS) to Cervical cancer cells and evaluate the efficiency of this drug carrier and its antitumor effects on Cervical cancer.Methods: Thermosensitive magnetic cationic liposomes were prepared using thin-film hydration method. The OXA and MDC1-AS vectors were loaded into the codelivery system, and the in vitro OXA thermosensitive release activity, efficiency of MDC1-AS regulating MDC1, in vitro cytotoxicity, and in vivo antitumor activity were determined.Results: The codelivery system had desirable targeted delivery efficacy, OXA thermosensitive release, and MDC1-AS regulating MDC1. Codelivery of OXA and MDC1-AS enhanced the inhibition of cervical cancer cell growth in vitro and in vivo, compared with single drug delivery.Conclusion: The novel codelivery of OXA and MDC1-AS magnetic thermosensitive cationic liposome drug carrier can be applied in the combined chemotherapy and gene therapy for cervical cancer.Keywords: magnetic thermosensitive cationic liposome, oxaliplatin, antisense lncRNA of MDC1, targeted therapy, cervical cancer

Since the first plasma realized in 2020, a series of key systems on HL-3 (known as HL-2M before) tokamak have been equipped/upgraded, including in-vessel components (the first wall, lower divertor, and toroidal cryogenic/water-cooling/baking/glow discharge systems, etc.), auxiliary heating system of 11 MW, and 28 diagnostic systems (to measure the plasma density electron temperature, radiation, magnetic field, etc.). Magnet field systems were commissioned firstly for divertor plasma discharges. During the 2nd experimental campaign of HL-3 tokamak, several great progresses have been achieved. Firstly, the successful operation with plasma current larger than 1 MA was achieved under a divertor configuration. Secondly, the advanced divertor concept with two distinct snowflake configurations was realized. It is found that the distribution of ion saturation current and heat flux on bottom plate becomes wide due to magnetic surface expansion, demonstrating the advantage of such configuration in the heat flux mitigation. In addition, using the combination of NBI, ECRH and LHCD, the standard sawtoothing high confinement mode of megampere plasma was firstly accessed on the HL-3. The successful commissioning of HL-3 is beneficial for the initial operation of ITER.

Zhiwen Cao,1 Wen Li,1 Rui Liu,1 Chenxi Li,1 Yurong Song,1 Guangzhi Liu,1 Youwen Chen,1 Cheng Lu,2 Aiping Lu,3 Yuanyan Liu1 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 3School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hongkong, People’s Republic of ChinaCorrespondence: Yuanyan Liu; Aiping Lu Tel +86 10 84738658Email yyliu_1980@163.com; lap64067611@126.comIntroduction: Auraptene (AUR), a natural bioactive prenyloxy coumarin, is a highly pleiotropic molecule that can bind to the MT1 receptor and can effectively reduce the proliferation and migration of breast cancer cells. Cisplatin (CDDP), as the first synthetic platinum-based anticancer drug, is widely used in the clinic due to its definite mechanism and therapeutic effect on diverse tumors. However, both of AUR and CDDP exhibit some disadvantages when used alone, including poor solubility, low bioavailability, lack of selectivity and systemic toxicity when they are used singly.Methods: Therefore, the biodegradable materials hyaluronic acid (HA) and β-cyclodextrin derivative (mono-(6-amino-mono-6-deoxy)-β-CD, CD) were employed as carriers to load AUR and CDDP to form nanogel (CDDPHA-CD@AUR) capable of dual-targeted delivery and synergistic therapy for breast cancer and cell imaging.Results: With the help of the CDDP-crosslinked CD-loaded structure, the newly synthesized nanogel exhibited excellent physiological stability and fluorescence effects. The release of AUR and CDDP was affected by the pH value, which was beneficial to the selective release in the tumor microenvironment. Cell experiments in vitro demonstrated that the nanogel could be selectively internalized by MCF-7 cells and exhibited low cytotoxicity to HK-2 cells. Antitumor experiments in vivo showed that the nanogel have better antitumor effects and lower systemic toxicity.Conclusion: Based on these, the nanogel loaded with AUR and CDDP have the potential for targeted delivery against breast cancer.Keywords: auraptene, cisplatin, cell imaging, tumor targeting, pH-responsive

Dong Fang,1,* Nirmish Singla,2,* Zhengqing Bao,1,3,* Syed M Jafri,4 Xiaohong Su,1 Zhenpeng Cao,1 Gengyan Xiong,1 Lei Zhang,1 Solomon Woldu,2 Ryan Hutchinson,2 Arthur Sagalowsky,2 Yair Lotan,2 Xuesong Li,1 Jay D Raman,4 Vitaly Margulis,2 Liqun Zhou1 1Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, People’s Republic of China; 2Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Department of Urology, Beijing Jishuitan Hospital, The Fourth Medical College of Peking University, Beijing, People’s Republic of China; 4Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA*These authors contributed equally to this workCorrespondence: Liqun ZhouDepartment of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, No. 8 Xishiku Street, Xicheng District, Beijing 100034, People’s Republic of ChinaTel +86-10-83575006Fax +86-10-66551726Email zhoulqmail@sina.comPurpose: To analyze the effect of preoperative serum sodium and hemoglobin on oncologic outcomes in upper tract urothelial carcinoma (UTUC) based on a multi-center cohort from China and the United States (U.S.).Methods: We retrospectively reviewed the records of 775 patients with UTUC treated surgically at tertiary care medical facilities in China or the US from 1998 to 2015. We analyzed associations of preoperative serum sodium and hemoglobin with clinicopathological characteristics, overall survival (OS), cancer-specific survival (CSS) and intravesical recurrence free survival (IVRFS).Results: The US patients had comparatively lower serum sodium and similar hemoglobin at baseline. Preoperative low serum sodium value was associated with tumor multifocality, lymph node metastasis (LNM) and lymphovascular invasion (LVI); preoperative anemia was associated with advanced age, tumor multifocality, high tumor grade and LVI. Preoperative low serum sodium was an independent predictor of worse OS in the entire cohort; preoperative anemia was an independent predictor of worse OS and CSS in the US cohort alone, Chinese cohort alone and the combined cohort. We developed a predictive nomogram for OS which exhibited better prognostic value when it included the values of sodium and anemia, and successfully validated it in different cohorts.Conclusion: Preoperative low serum sodium and anemia could be informative in predicting worse pathologic and survival outcomes in different UTUC patient ethnic groups.Keywords: upper tract urothelial carcinoma, serum sodium, anemia, survival, China, the United States

Yan Ding,1,* Shengjie Dong,1,* Jingjie Wang,1 Jinpeng Cui,2 Zhilin Cao,1 Shiqiao Lv1 1Department of Orthopaedics, Yantaishan Hospital, Yantai 264000, People’s Republic of China; 2Clinical Laboratory, Yantaishan Hospital, Yantai 264000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shiqiao LvDepartment of Orthopaedics, Yantaishan Hospital, No. 91 Jiefang Road, Yantai 264000, People’s Republic of ChinaTel +86-13001612636Email 68402128@qq.comPurpose: This study aimed to compare the demographic features (including total cost), surgical effects, radiographic parameters, and complications of kyphoplasty (KP) and vertebroplasty (VP) in the hyperextension (HP) and neutral positions (NP) and to assess their efficacy and cost-effectiveness for treating single-level osteoporotic vertebral compression fractures (OVCF).Patients and Methods: This was a retrospective analysis of 245 consecutive patients who underwent KP or VP from February 2018 to February 2019 with observation on postoperative day 2 and at the one-year follow-up. The first 122 patients (86 KP and 36 VP cases) were treated in the neutral position, and the remaining 123 in the hyperextension position (90 VP and 33 KP cases). Back pain and impact on daily life were evaluated. Cobb’s angle and the ratio of the anterior (AR) and middle vertebral (MR) bodies were the main radiographic parameters. The chi-square test, one-way analysis of variance (ANOVA), repeated measurement ANOVA, and post hoc tests (Bonferroni adjustments) were used for statistical analysis.Results: There were no significant differences in the demographic features, operation time, or rate of re-fracture at the one-year follow-up among the groups. The rate of cement leakage was significantly lower in the HPVP group than in the NPKP group. The total cost was significantly lower in the VP groups than in the KP groups. At the one-year follow-up, back pain was significantly lower in the HPVP group than in the NPKP group. The Oswestry Disability Index, Cobb’s angle, AR, and MR in the HPVP group were similar to those in the NPKP and HPKP groups, but better than those in the NPVP group.Conclusion: HPVP can achieve better pain relief, and similar disability scores, Cobb’s angle, AR and MR recovery, with a lower total cost, compared with NPKP. HPVP is the most economically efficacious treatment for OVCF.Keywords: cement leakage, Cobb’s angle, kyphosis, surgical outcome, vertebral height

Shizhou Yang,1,* Tingting Chen,1,* Lu Huang,2 Shanshan Xu,1 Zhu Cao,1 Songfa Zhang,1 Junfen Xu,1 Yang Li,1 Yongfang Yue,1 Weiguo Lu,1,3 Xiaodong Cheng,1,3 Xing Xie1,3 1Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing Xie Tel +86 571 8706 1501Fax +86 571 8706 1878Email xiex@zju.edu.cnPurpose: To determine whether early proteins from high-risk human papillomavirus (HPV) have the capacity to maintain cellular stemness.Patients and methods: First, we isolated cancer stem cell like cells from two cervical cancer cell lines, SiHa and CaSki, using non-adhesive culture with serum-free medium. Second, we knocked down HPV16 E7 in SiHa sphere cells and overexpressed HPV16 E7 in U2OS sphere cells. Third, we used RNA-seq analysis and Western blotting to screen and identify the expression of differentially expressed genes in SiHa cells with HPV16 E7 knockdown.Results: We found that both SiHa and CaSki cells grew as cell spheres (oncospheres) and shared the properties of cancer stem cells, including high expression of stem cell marker OCT4 and SOX2, self-renew, and resistance to chemotherapeutic drugs. The stem-like properties were deprived when HPV16 E7 was knocked down in SiHa sphere cells and maintained when HPV16 E7 was over-expressed in U2OS sphere cells. APH1B was up-regulated, among differential expression genes, in SiHa cells with HPV16 E7 knockdown and modulated cellular stemness and SiHa sphere cells with APH1B knockdown regained the stem-like properties deprived by E7 inhibition.Conclusion: HPV16 E7 possesses the capacity to maintain cellular stemness and APH1B may participate in this process in cervical cancer sphere cells.Keywords: cervical cancer, HPV, cancer stem cell, APH1B

Zhimin Cao,1 Yuanbo Lan,1 Ling Chen,1 Min Xiang,1 Zhiyuan Peng,1 Jianyong Zhang,1 Hong Zhang1,2 1Tuberculosis Division, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, People’s Republic of China; 2Department of R & D, Z-BioMed, Inc, Rockville, MD, 20855, USACorrespondence: Ling Chen; Hong ZhangTuberculosis Division, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou 563003, People’s Republic of ChinaTel +86 851 2860 9237Fax +86 851 2860 8239Email lingjuncd@163.com; hzhang@zbiomed.comBackground: China is one of the high-burden countries for multidrug-resistant tuberculosis (MDR-TB), and pyrazinamide is one of the anti-TB drugs used for the shorter MDR-TB treatment regimen. The aim of this study was to determine the correlation between pncA gene mutations and resistance to four first-line anti-TB drugs as well as treatment history in clinical isolates of Mycobacterium tuberculosis.Patients and methods: M. tuberculosis clinical isolates were collected from 318 in-patients with smear-positive TB between October 2008 and September 2016 at a major hospital in Zunyi, Guizhou Province of China, and used for drug susceptibility testing against four first-line anti-TB drugs. Genomic DNA extracted from clinical isolates was used for PCR amplification and DNA sequencing of the pncA gene.Results: Among 318 clinical isolates, 129 (40.6%), 170 (53.5%), 66 (20.8%) and 109 (34.3%) were resistant to rifampicin, isoniazid, ethambutol and streptomycin respectively. In addition, 124 clinical isolates were MDR-TB and 71.8% of them were previously treated cases. Sequencing results showed that 46.8% of MDR-TB and 2.2% of drug susceptible isolates harbored a pncA mutation, and 52 types of pncA mutations were detected from 64 isolates. The prevalence of pncA mutations in isolates resistant to first-line anti-TB drugs and previously treated TB cases was significantly higher than that in drug-susceptible isolates and new cases of TB.Conclusion: High prevalence of pncA mutations in clinical isolates of M. tuberculosis from Zunyi, Guizhou Province of China, is correlated with resistance to four first-line anti-TB drugs, MDR-TB and previously treated TB cases.Keywords: Mycobacterium tuberculosis, pyrazinamide, drug resistance, pncA mutation

Panpan Zhai,1–3 Qian Li,1–3 Ali Hassan Gillani,4 Khezar Hayat,1–3,5 Li Shi,1–3 Siyi Wang,1–3 Fei Peng,1–3 Sen Xu,1–3 Qianqian Du,1–3 Zeyu Cao,1–3 Donald E Morisky,6 Yu Fang1–31Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Center for Drug Safety and Policy Research, Xi’an, People’s Republic of China; 3Shaanxi Center for Health Reform and Development Research, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Department of Pharmacy, Yusra Institute of Pharmaceutical Sciences, Islamabad, Pakistan; 5Institute of Pharmaceutical Sciences, University of Veternary and Animal Sciences, Lahore, Pakistan; 6Department of Community Health Sciences, UCLA Fielding School of Public Health, Los Angeles, CA 90095-1772, USAPurpose: Hypertension prevalence is mounting at a great pace in the People’s Republic of China and poses a serious threat to health care systems. Medication nonadherence is one of the key factors in controlling high blood pressure. Our study uses two-arm cluster randomized controlled trial to investigate whether personal consultation by postgraduate pharmacy students and short message services (SMS) is effective in improving medication adherence and blood pressure control.Patients and methods: The trial will involve 384 treated patients in 8 community health care centers (CHCs). The 8 CHCs will be randomly assigned to intervention and control group in a ratio of 1:1. Patients in the intervention group will receive a personal consultation which identifies the barriers to medication adherence and SMS reminders which will be sent at 3-day intervals while patients in the control group will receive standard pharmaceutical care. Personal consultation by pharmacy students will be delivered at months 0 and 3. SMS messages will include educational information about normal blood pressure, complications of hypertension, salt intake, healthy diet, smoking cessation, regular exercise, weight control, antihypertensive medication schedule and treatment. Both groups will be followed for 6 months in order to compare their medication adherence and blood pressure at months 0, 3 and 6. The primary clinical outcome is the change in mean blood pressure and medication adherence measured at baseline, months 3 and 6. Secondary outcome is the proportion of patients reaching controlled blood pressure at months 3 and 6.Discussion: Pharmacy students led consultation will be conducted in the process of physical examination and SMS reminders which is at low cost, may be a feasible way to address the high prevalence of hypertension in the People’s Republic of China.Keywords: medication adherence, hypertension, blood pressure, SMS reminders, personal consultation, community health care centers

The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 2,717 new measurements from 869 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. Particle properties and search limits are listed in Summary Tables. We give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Most of the 120 reviews are updated, including many that are heavily revised. The Review is divided into two volumes. Volume 1 includes the Summary Tables and 97 review articles. Volume 2 consists of the Particle Listings and contains also 23 reviews that address specific aspects of the data presented in the Listings. The complete Review (both volumes) is published online on the website of the Particle Data Group (pdg.lbl.gov) and in a journal. Volume 1 is available in print as the PDG Book. A Particle Physics Booklet with the Summary Tables and essential tables, figures, and equations from selected review articles is available in print, as a web version optimized for use on phones, and as an Android app. The 2024 edition of the Review of Particle Physics should be cited as: S. Navas et al. (Particle Data Group), Phys. Rev. D 110, 030001 (2024)

Fei Bai,1–4,* Juan Ling,1–3,* Gloria Esoimeme,5 Liang Yao,1–3 Mingxia Wang,1,6 Jiajun Huang,1,7 Anchen Shi,1,6 Zehui Cao,1,7 Yaolong Chen,1–3 Jinhui Tian,1–3 Xiaoqin Wang,1–3 Kehu Yang1–3 1Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; 2Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China; 3WHO Collaborating Center for Guideline Implementation and Knowledge Translation, Lanzhou 730000, China; 4National Center for Medical Administration Service, Beijing, China; 5University of South Carolina, Arnold School of Public Health, Columbia, SC, USA; 6The Second Clinical Medical College of Lanzhou University, Lanzhou, China; 7The First Clinical Medical College of Lanzhou University, Lanzhou, China *These authors contributed equally in this work Objective: We conducted a systematic review to evaluate questionnaires about patient’s values and preferences to provide information on the most appropriate questionnaires to be used when developing clinical practice guidelines. Methods: A systematic literature search of the Cochrane Library, MEDLINE, Embase, Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure, and the Wanfang Database was performed to identify studies on questionnaires evaluating patient’s values and preferences. The articles that used fully structured questionnaires or scales with standardized questions and answer options were included. We assessed the questionnaires’ construction and content with a psychometric methodology and summarized the domains and items about patient’s preferences and values. Results: A total of 7,008 records were retrieved by the search strategy and scanned, and 20 articles were finally included. Of these, 10 (50%) articles described the process of item generation and only four questionnaires (20%, 4/20) mentioned the pilot testing. Regarding “validity”, seven questionnaires (35%, 7/20) assessed validity and only one (5%, 1/20) questionnaire assessed internal consistency, with Cornbrash’s α values of 0.74–0.87. For “acceptability”, the time to complete the questionnaires ranged from 10 to 30 minutes and only nine studies (45%, 9/20) reported the response rates. In addition, the results of domains and items about patient’s preferences and values showed that the “effectiveness” domain was the most considered item in the patient’s value questionnaire followed by “safety”, “prognosis”, and others, whereas the least considered domain was “physician’s experience”. Conclusion: Only a few studies have developed questionnaires with rigorous psychometric methods to measure patient’s preferences and values. Currently, still there is no valid or reliable questionnaire for patient’s preferences and values for use when developing clinical practice guidelines. Further study should be conducted to develop standardized instruments to measure patient’s preferences and values. This study provides the domains and items that may be used in formulating questionnaires about patient’s preferences and values. Keywords: questionnaires, guideline, patient’s values and preferences, systematic review, Patient Satisfaction

Simone Eliane Schwank,1 Chunyi Gu,2 Zhouli Cao,3 Ewa Andersson,4 Hongli Jiang,5 Yan Ding,2 Helena Lindgren4 1Karolinska Institutet, Women’s and Children’s Health, Reproductive Health, Columbia University, Center for Psychoanalytic Training and Research, Solna, Sweden; 2Nursing Department, Fudan University, Obstetrics and Gynecology Hospital, Shanghai, China; 3School of Social Science, Hangzhou Normal University, Qianjiang College, Hangzhou, China; 4Karolinska Institutet, Women’s and Children’s Health, Reproductive Health, Solna, Sweden; 5Department of Health Economics, Fudan University, School of Public Health, Shanghai, ChinaObjectives: The Chinese government launched the two-child policy in 2015 to counteract the demographic changes, skewed sex ratio, and decreasing number of labor force. The policy shift has a significant impact on all levels of society and economy. This study aimed to describe how Mainland Chinese women face this new decision-making on their reproduction and family planning and captures factors contributing to the judgment and decision-making.Method: The present qualitative study included a sample of 37 women, with an average age of 29.51 years, and well educated with bachelor degrees from urban areas of Shanghai and Hangzhou cities. The women were interviewed by social science students, using a 26-item interview targeting the women’s decision-making, expectations, and wishes with regard to the two-child policy.Results: The contributors include the status of women, career, benefits, and challenges of two children, one-child generation, governmental support, and restrictions of reproductive freedom. These factors contribute to the women’s prolonged decision-making on whether to have a second child. These factors highlight the impact of the policy on perinatal health, societal, and economic changes. The study illustrates the need to continue understanding the impact of the child policy shift for families and the society of the China on multiple levels.Conclusion: With the outcomes of research on the families’ judgment and decision-making with regard to a second child, support can be targeted where it is needed the most. The acquired knowledge may serve as a prognosis for the child policy’s future development and used to target perinatal care and education of health care specialists, essential to governmental planning and resource allocation.Keywords: Chinese child policy, perinatal health, reproduction, women, decision-making