Search

Mengxia Wang,1,&ast; Jieke Tang,1,&ast; Zhaojie Pan,2 Hongxue Jiang,1 Donghua Hu,1 Beibei Zhu,2 Zhaojia Liang,1 Xiangfeng Zhao,1 Yalan Li1 1Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Digestive Endoscopy Center, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yalan Li, Department of Anesthesiology, The First Affiliated Hospital of Jinan University, No. 613, Huangpu West Avenue, Tianhe District, Guangzhou, Guangdong Province, 510630, People’s Republic of China, Email tyalan@jnu.edu.cnPurpose: The provision of comfortable and safe environment for painless gastroscopy in obese patients is an urgent clinical problem. This study aimed to determine the efficacy and safety of the novel Li anesthetic protocol for obesity (LAPO) which included remifentanil-propofol regimen, manual right hypochondrial compression (MRHC), easy-to-create mask, and jaw thrust at preoperative painless gastroscopy in obese patients.Patients and Methods: This prospective, single-center, single-arm trial recruited 106 participants underwent LAPO for gastroscopy. The primary outcome was the incidence of hypoxemia (peripheral oxygen saturation [SpO2]: 75% ≤ SpO2 < 90%, for > 10 s and ≤ 60 s). Second outcomes included severe hypoxemia, the lowest SpO2 (L-SpO2), duration of hypoxemia, and other events.Results: The 98 obese patients under LAPO, the median body mass index (BMI) was 39.2 kg/m2 and the incidence of hypoxemia was 27.5%, while the conventional anesthetic protocol for obesity (CAPO) in the reference was 40.4% with BMI 31.4 kg/m2. With the increase of class of obesity, a significant rise in the incidence of hypoxemia was observed, from class I by 11.8%, to 15.1% in class II, and 41.7% in class III. Paired t test showed that the L-SpO2 was significantly higher than L-SpO2 in overnight polysomnography (Nadir SpO2) (92% vs 76%, P< 0.001). Moreover, severe obstructive sleep apnea (OSA) was associated with a 4.019-fold higher risk of hypoxemia (Odds ratios [OR], 4.019; 95% confidence interval [CI], 1.184 to 14.610; P=0.028); diabetes was associated with a 4.790-fold higher risk of hypoxemia (OR, 4.790; 95% CI, 1.288 to 23.600; P=0.030).Conclusion: Compared with CAPO, LAPO reduced the incidence of hypoxemia from 40.4% to 27.5%, so, LAPO was safe and effective for painless gastroscopy. The finding might provide some new schedules for anesthetic management in the absence of advanced airway support instruments.Clinical Trial Registration: ChiCTR2300077889.Plain Language Summary: With the advancement of comfortable-oriented medication, gastroscopy is mostly performed under sedation and anesthesia. However, for obesity, there are changes in airway anatomy structure such as short neck, round chin, and large tongue, which makes them prone to airway obstruction after sleep or anesthesia, blocking the passage of oxygen in and out, which will cause hypoxemia over time and further cause damage to the body. Therefore, it is necessary to explore a safe and effective anesthesia management for painless gastroscopy in obesity. Our team’s work demonstrates that the novel Li anesthetic protocol (strategic anesthesia management of remifentanil combined with propofol and effective respiratory support through MRHC and jaw thrust, increased oxygen reserve via a novel mask) for obesity for painless gastroscopy with lacking advanced airway management devices is safe and efficient. Furthermore, our findings contribute to the understanding of the lowest SpO2 values that obese patients can tolerate during such procedures, establishing Nadir SpO2 as the cut-off point. We also identified severe OSA and diabetes as independent predictive risk factors for hypoxemia. If these findings are supported by further research, LAPO could aid anesthesiologists in developing specific anesthesia protocols and managing the risk of hypoxemia during painless gastroscopy for obese patients. Ultimately, this could expand access to comfortable and safe medical treatment for a broader spectrum of patients with obesity.Keywords: compression, hypoxemia, obese patient, obstructive sleep apnea, painless gastroscopy, propofol, remifentanil

Yuxin Sun,1,&ast; Die Hu,1,&ast; Mingkun Yu,2 Shi-Bing Liang,3– 5 Youyou Zheng,6 Xin Wang,7 Guangdong Tong1,8 1Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Oncology, Binzhou Hospital of Traditional Chinese Medicine, Binzhou, People’s Republic of China; 3Clinical Study Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 4Centre for Evidence-Based Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 5Postdoctoral Research Station, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 6Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 7Department of Traditional Chinese Medicine, Sanbo Brian Hospital of Capital Medical University, Beijing, People’s Republic of China; 8Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangdong Tong, Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, People’s Republic of China, Email tgd755@163.comPurpose: In recent decades, numerous non-invasive tests (NITs) for diagnosing nonalcoholic fatty liver disease (NAFLD) have been developed, however, a comprehensive comparison of their relative diagnostic accuracies is lacking. We aimed to assess and compare the diagnostic accuracy of various NITs for NAFLD using network meta-analysis (NMA).Materials and Methods: We conducted a systematic search in seven databases up to April 2024 to identify studies evaluating the diagnostic values of NITs, with liver biopsy as the gold standard. The participants included patients with suspected or confirmed NAFLD, irrespective of age, sex, ethnicity. Statistical analysis was conducted using R 4.0.3 for Bayesian NMA and STATA 17.0 for pairwise meta-analysis. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the receiver operating characteristic curve (AUC), and superiority index were calculated. Bayesian calculations were performed using the Rstan package, specifying parameters like MCMC chain count, iteration count, and operational cycles. The methodological quality of included studies was assessed using the QUADAS-2 tool.Results: Out of 15,877 studies, 180 were included in the quantitative synthesis, and 102 were used in head-to-head meta-analyses. For diagnosing steatosis stage 1, Hydrogen Magnetic Resonance Spectroscopy (H-MRS, DOR 15,745,657.6, 95% CI 17.2– 1,014,063.59) proved to be the most accurate. For significant fibrosis, HRI leading (DOR 80.94, 95% CI 6.46– 391.41), For advanced fibrosis, CK-18 showed the highest performance (DOR 102654.16, 95% CI 1.6– 134,059.8). For high-risk NASH, Real-Time Elastography showing the highest performance (DOR 18.1, 95% CI 0.7– 96.33). Meta-regression analyses suggested that variability in the diagnostic accuracy of NITs for NAFLD may result from differences in study design, thresholds, populations, and performance indicators.Conclusion: We conducted a network meta-analysis to rank the accuracy of these tests. While some results are promising, not all NITs demonstrate substantial accuracy, highlighting the need for validation with larger datasets. Future research should concentrate on studying the thresholds of NITs and enhancing the clarity of methodological reporting.Keywords: NAFLD, NIT, obesity, NMA, diagnostic

Wen-Jie Zhou,1,2,&ast; Jin-Tao Huang,1,&ast; Xin Lu,3,&ast; Di Hu,1 Xin Hong,4 Fu-An Wang,2 Peng-Hua Lv,2 Xiao-Li Zhu1 1Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Interventional Radiology, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, People’s Republic of China; 3Department of Radiology, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 4Department of Interventional Radiology, Affiliated Hospital 2 of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, 215006, People’s Republic of China, Email zhuxiaoli90@163.comPurpose: Camrelizumab and rivoceranib together provide a new first-line treatment approach for unresectable hepatocellular carcinoma (HCC). Meanwhile, transarterial chemoembolization (TACE) is an effective method for the local control of the HCC. The study compared the clinical benefit and safety between TACE with camrelizumab-rivoceranib and camrelizumab-rivoceranib alone for Barcelona Clinic Liver Cancer (BCLC)-C HCC patients.Patients and Methods: This multi-center retrospective analysis included continuous BCLC-C HCC patients who received camrelizumab-rivoceranib with TACE and camrelizumab-rivoceranib alone from January 2020 to December 2022. The therapeutic response, progression-free survival (PFS), safety, and overall survival (OS) were compared. The quantitative data were compared via the t-test or Mann–Whitney U-test. Comparison of the categorical data was done by chi-square or Fisher’s exact tests. The comparison of PFS with OS was compared by Log rank test. A Multivariate Cox regression test was utilized to identify risk variables for both PFS and OS.Results: This analysis comprised 132 BCLC-C HCC patients who received camrelizumab-rivoceranib alone (n = 74) or combined treatment (n = 58). The combined group displayed higher partial response (44.8% vs 21.6%, p = 0.004) and total response (55.2% versus 36.5%, p = 0.032) rates than camrelizumab-rivoceranib alone group. The median PFS (13.5 months vs 10.3 months, p = 0.046) and OS (22.8 months vs 18.4 months, p = 0.041) for the combined group was significantly longer relative to the camrelizumab-rivoceranib alone group. Additional risk factors, excluding the therapy option, were a higher alpha-fetoprotein level and Eastern Cooperative Oncology Group performance status. The incident rates of camrelizumab-rivoceranib-related advents were comparable between combined and camrelizumab-rivoceranib alone groups (46.3% vs 51.4%, p = 0.572). The combined group contained 33 patients (56.9%) who experienced temporary post-embolization symptoms.Conclusion: For BCLC-C HCC patients, TACE may significantly increase the therapeutic effectiveness of camrelizumab-rivoceranib without increasing the risk of camrelizumab-rivoceranib-related complications.Keywords: hepatocellular carcinoma, camrelizumab, rivoceranib, TACE, survival

Xin Hong,1,&ast; Di Hu,2,&ast; Wen-Jie Zhou,3,&ast; Xiu-De Wang,4 Li-Hua Huang,5 Tian-An Huang,1 Yi-Wei Guan,1 Jingyu Qian,6 Wen-Bin Ding1 1Department of Interventional Radiology, Affiliated Hospital 2 of Nantong University, Nantong, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Interventional Radiology, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, People’s Republic of China; 4Department of Interventional Radiology, Nantong Second People’s Hospital, Nantong, People’s Republic of China; 5Department of Interventional Radiology, Nantong Haimen District People’s Hospital, Nantong, People’s Republic of China; 6Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen-Bin Ding, Department of Interventional Radiology, Affiliated Hospital 2 of Nantong University, Nantong, 226001, People’s Republic of China, Tel/Fax +86 15951302169, Email 15951302169@163.com Jingyu Qian, Department of Interventional Radiology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China, Tel/Fax +86 13004081388, Email jyqian1388@163.comObjective: To evaluate the baseline albumin-bilirubin (ALBI) grade’s role in advanced hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) plus anti-angiogenesis therapies and PD-1 inhibitors (TACE+TP) versus anti-angiogenesis therapies and PD-1 inhibitors (TP).Methods: This multicenter retrospective study enrolled advanced HCC undergoing TACE+TP or TP from January 2019 to June 2023 at three hospitals in China. The primary outcomes were time to progression of the ALBI grade and change in ALBI score between the initial baseline and the final assessment point available, the secondary outcomes consisted of overall survival (OS) as well as progression-free survival (PFS).Results: One hundred and eighty-three patients were ultimately enrolled in this study for analysis, of whom 44 were categorized as having an ALBI grade 1 (TACE+TP, n = 23; TP, n = 21) and 139 were classified as ALBI grade 2 (n = 77; n = 62). Time to progression of the ALBI grade, indicating liver function deterioration, was comparable between the TACE+TP and TP groups (median, 11.2 vs 19.3 months; P = 0.353). Change in ALBI score between the initial baseline and the final assessment point available was comparable among the two groups (difference in least squares mean, 0.084). Irrespective of the initial ALBI grade, patients in TACE+TP group exhibited a significant enhancement in OS and displayed a promising trend towards better PFS.Conclusion: TACE+TP had no negative influence on liver function and enhanced survival regardless of baseline ALBI grade when compared to TP in advanced HCC patients.Keywords: albumin-bilirubin grade, hepatocellular carcinoma, TACE, anti-angiogenesis therapies, PD-1 inhibitors

Xiang Tang,1,2,&ast; Jinbin Chen,1,2,&ast; Wei Peng,1,2,&ast; Zhoutian Yang,1,2 Li Hu,1,2 Zhiwei Ye,1,2 Yizhen Fu,1,2 Dandan Hu,1,2 Zhongguo Zhou,1,2 Minshan Chen,1,2 Yaojun Zhang,1,2 Jun-Cheng Wang1,2 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaojun Zhang; Jun-Cheng Wang, Department of Liver Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email zhangyuj@sysucc.org.cn; wangjch@sysucc.org.cnObjection: To report the efficacy and safety of triple combination therapy with bevacizumab plus anti-PD-1 (BP1) or anti-PD-L1 inhibitors (BPL) combined with hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment for initially unresectable hepatocellular carcinoma (uHCC).Methods: In this retrospective study, patients with initially uHCC received either BP1-HAIC or BPL-HAIC as first-line treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR).Results: Between January 2020 and December 2022, a total of 136 patients with initially uHCC received triple combination therapy, with 76 in the BP1-HAIC group and 60 in the BPL-HAIC group. The median PFS for the entire cohort was 11.1 months (95% CI, 8.0– 13.7 months), and the median OS was 22.4 months (95% CI, 21.3- not reached). Comparative analysis revealed no significant differences in PFS (HR, 0.91, P = 0.69) or OS (HR, 0.71, P = 0.31) between the BP1-HAIC and BPL-HAIC groups. The ORR was 46.3% per RECIST v1.1 and 66.9% per mRECIST, with a DCR of 83.1% under both criteria. Common adverse events (AEs) included hypoalbuminemia and elevated aspartate/alanine aminotransferase, with 5.1% (7/136) experienced upper gastrointestinal bleeding. Multivariate Cox analysis identified tumor number and BCLC stage as independent prognostic factors for OS, and tumor number for PFS.Conclusion: Triple combination therapy demonstrated significant therapeutic efficacy and tumor response in initially uHCC. No notable differences in outcomes were observed between the BP1-HAIC and BPL-HAIC groups. AEs were manageable in clinical practice.Keywords: hepatocellular carcinoma, immune checkpoint inhibitor, bevacizumab, hepatic arterial infusion chemotherapy, adverse event

Shi-liang Chen,1,&ast; Dan Hu,2,&ast; Tian-zhu Chen,3,&ast; Si-yu Shen,4,&ast; Chen-fei Zhao,1,&ast; Cong Wang,1 Shi-yuan Tong,5 Zhao Liu,6 Shao-hua Lin,1 Li-xia Jin,7 Yi-bo He,1 Zhe-zhong Zhang1 1Department of Clinical Lab, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, People’s Republic of China; 2Department of Clinical Lab, The Cixi Integrated Traditional Chinese and Western Medicine Medical and Health Group Cixi Red Cross Hospital, Cixi, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, People’s Republic of China; 4The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 5The Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, People’s Republic of China; 6Department of General Surgery, Shaoxing Central Hospital, Shaoxing, People’s Republic of China; 7School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhe-zhong Zhang; Yi-bo He, Department of Clinical Lab, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, People’s Republic of China, Email zhangzhezhong2023@163.com; heyb1992@126.comPurpose: Cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression and the development of resistance to therapies across a range of malignancies, notably breast cancer. This study aims to elucidate the specific role and prognostic relevance of CALU across multiple cancer types.Patients and Methods: The association between CALU expression and prognosis, along with clinical characteristics in BRCA, HNSC, KIRP, LGG, and LIHC, was analyzed using data from the TCGA, GTEx, and GEO databases. Transcriptomic analysis of TCGA BRCA project data provided insights into the interaction between CALU and epithelial-mesenchymal transition (EMT) marker genes. Using TIMER and TISCH databases, the correlation between CALU expression and tumor microenvironment infiltration was assessed, alongside an evaluation of CALU expression across various cell types. Furthermore, CALU’s influence on TNBC BRCA cell lines was explored, and its expression in tumor tissues was confirmed through immunohistochemical analysis of clinical samples.Results: This study revealed a consistent upregulation of CALU across several tumor types, including BRCA, KIRP, LIHC, HNSC, and LGG, with elevated CALU expression being associated with unfavorable prognoses. CALU expression was particularly enhanced in clinical contexts linked to poor outcomes. Genomic analysis identified copy number alterations as the principal factor driving CALU overexpression. Additionally, a positive correlation between CALU expression and CAF infiltration was observed, along with its involvement in the EMT process in both CAFs and malignant cells. In vitro experiments demonstrated that CALU is highly expressed in TNBC-BRCA cell lines, and knockdown of CALU effectively reversed EMT progression and inhibited cellular migration. Immunohistochemical analysis of clinical samples corroborated the elevated expression of CALU in tumors, along with alterations in EMT markers.Conclusion: This comprehensive pan-cancer analysis underscores CALU’s critical role in modulating the tumor microenvironment and facilitating cell migration via the EMT pathway, identifying it as a potential therapeutic target.Keywords: CALU, cancer-associated fibroblasts, epithelial-mesenchymal transition, breast cancer, prognosis, pan-cancer analysis

Shuqing Liang, Shuai Li, Zhao Zhong, Qichen Luo, Cai Nie, Donghua Hu, Yalan Li Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of ChinaCorrespondence: Yalan Li, Department of Anesthesiology, the First Affiliated Hospital of Jinan University, No. 613 Huangpu West Avenue, Tianhe District, Guangzhou, Guangdong Province, 510630, People’s Republic of China, Tel +86-20-38688779, Email tyalan@jnu.edu.cnPurpose: This study aimed to investigate patients’ expectative pain of spinal anesthesia puncture and anxiety pre-anesthesia, and to examine the effect of lidocaine-prilocaine cream and remimazolam prior to spinal anesthesia puncture on pain relief and anxiety release.Methods: Patients undergoing spinal anesthesia were divided into control, lidocaine-prilocaine cream, and lidocaine-prilocaine cream with remimazolam groups. A questionnaire consisting of The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and patient’s concerns and Visual Analog Scale (VAS) was used to evaluate patient’s anxiety and pain. The primary outcomes were differences in VAS and anxiety scores. Patient’s spinal anesthesia-related concerns, advent events and hemodynamic index were also recorded.Results: The expected spinal anesthesia puncture pain was 5.34± 0.27 and anxiety scores before spinal anesthesia was 10.88 ± 0.64. A statistically significant positive correlation of 31.3% was detected between VAS and APAIS scores (r = 0.313; P=0.003). The VAS score at the time of puncture decreased by 29.7% (3.78± 0.40, P=0.001) in lidocaine-prilocaine cream group and 29.2% (3.75± 0.39, P=0.001) in lidocaine-prilocaine cream with remimazolam group compared with the expected VAS score. Lidocaine-prilocaine cream combined with or without remimazolam reduced the percentage of moderate pain (21.4% and 31.3% vs 50.0%, P=0.0001) and increased mild pain (60.7% vs 59.4% vs 22.7%, P=0.03). Anxiety score in lidocaine-prilocaine cream group was reduced by 2.84 (8.04± 0.76 vs 10.88 ± 0.46, P=0.05) when compared with pre-anesthesia. Concerns about postoperative pain (P=0.03) and fear of the needle or intervention (P=0.000) both decreased post-anesthesia among groups.Conclusion: Approximately half of the patients scheduled for spinal anesthesia experienced a moderate level of preoperative anxiety. The patient’s pain expectation from the spinal anesthesia puncture was moderate, which was higher than the actual pain. Lidocaine-prilocaine cream with or without remimazolam sedative before spinal anesthesia puncture reduced the patient’s pain and anxiety scores after surgery.Keywords: preoperative anxiety, APAIS, spinal anesthesia, lidocaine-prilocaine, remimazolam

Xia Gu,1,2,&ast; Hui Zhou,1,&ast; Mengyue Miao,1 Daifeng Hu,1 Xinyue Wang,3 Jing Zhou,4 Alexander Tobias Teichmann,1 Youzhe Yang,1,5 Chunyan Wang1 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Leshan People’s Hospital, Leshan, 614003, People’s Republic of China; 3The Basic Medical College, Army Medical University, Chongqing, 400038, People’s Republic of China; 4Department of Endocrinology, Chengdu Third People’s Hospital, Chengdu, 610014, People’s Republic of China; 5Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youzhe Yang; Chunyan Wang, The Affiliated Hospital of Southwest Medical University, NO. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email yangyouzhe@swmu.edu.cn; wangchunyan6813@swmu.edu.cnAbstract: Endometriosis (EMS) is defined as the appearance, growth, infiltration, and repeated bleeding of endometrioid tissue (glands and stroma) outside the uterus cavity, which can form nodules and masses. Endometriosis is a chronic inflammatory estrogen-dependent disease and occurs in women of reproductive age. This disorder may significantly affect the quality of life of patients. The pathogenic processes involved in the development and maintenance of endometriosis remain unclear. Current treatment options for endometriosis mainly include drug therapy and surgery. Drug therapy mainly ties to the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal drugs. However, these drugs may produce adverse effects when used for long-term treatment of endometriosis, such as nausea, vomiting gastrointestinal reactions, abnormal liver and kidney function, gastric ulcers, and thrombosis. Although endometriosis lesions can be surgically removed, the disease has a high recurrence rate after surgical resection, with a recurrence rate of 21.5% within 2 years and 40% to 50% within 5 years. Thus, there is an urgent need to develop alternative or additional therapies for the treatment of endometriosis. In this review, we give a systematic summary of therapeutic multiple component prescriptions (including traditional Chinese medicine and so on), bioactive crude extracts of plants/herbs and purified compounds and their newly found mechanisms reported in literature in recent years against endometriosis.Keywords: endometriosis, treatment, multiple component prescriptions, extracts of plants/herbs, purified compounds, mechanisms

Shaoyan Shi, Leiming Hu, Dong Hu, Xuehai Ou, Yansheng Huang Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710000, People’s Republic of ChinaCorrespondence: Yansheng Huang, Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710000, People’s Republic of China, Email yshg1991@163.comAbstract: Diabetic wounds pose a significant challenge in modern healthcare due to their chronic and complex nature, often resulting in delayed healing, infections, and, in severe cases, amputations. In recent years, nanotherapeutic approaches have emerged as promising strategies to address the unique pathophysiological characteristics of diabetic wounds. This review paper provides a comprehensive overview of the latest advancements in nanotherapeutics for diabetic wound treatment. We discuss various nanomaterials and delivery systems employed in these emerging therapies. Furthermore, we explore the integration of biomaterials to enhance the efficacy of nanotherapeutic interventions. By examining the current state-of-the-art research, challenges, and prospects, this review aims to offer valuable insights for researchers, clinicians, and healthcare professionals working in the field of diabetic wound care.Keywords: diabetic wounds, nanoparticle, biomaterials, DELIVERY system

Ying Lan,1 Die Hu,1 Shijing Huang,1 Qing Ma,1 Li Chen,2,3 Min Xu,1 Qin He1 1Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2Department of Pharmacology, Faculty of Medicine, University of the Basque Country, UPV/EHU, Leioa, Spain; 3Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ying Lan; Li Chen, Email lanying0212@126.com; chenl_hxey@scu.edu.cnPurpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide.Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events.Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc.Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.Keywords: data mining, FAERS, ICS, INCs, pharmacovigilance, infections

Runting Ma, Lianhong Zhou, Wenping Li, Yuanjin Li, Diewenjie Hu, Yi Lu, Cancan Zhang, Beixi Yi Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Lianhong Zhou, Department of Ophthalmology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Tel +86 027-88041911-81219, Email zlh681102@aliyun.comPurpose: This study aimed to analyze myopia distribution in Hubei and the impact of regional Sunshine Duration on myopia in children and adolescents.Patients and Methods: The Cross-sectional study included students (kindergarten to grade 12) through multistage cluster stratified sampling in 17 cities (103 areas) of Hubei, China, who underwent ophthalmic examinations from September 2021 to November 2021. The association of sunshine duration with the prevalence and distribution of myopia was analyzed. Using Moran’s index to quantify the distribution relationship, a spatial analysis was constructed.Results: A total of 435,996 students (53.33% male; mean age, 12.16± 3.74 years) were included in the study. A negative association was identified between myopia prevalence and sunshine duration in the region, especially in population of primary students (r=− 0.316, p< 0.001). Each 1-unit increment in the sunshine duration was associated with a decreased risk of myopia prevalence (OR=0.996; 95% CI, 0.995– 0.998; P < 0.001). Regression showed a linear relationship between sunshine duration and myopia rates of primary school students [Prevalence%= (− 0.1331&ast;sunshine duration+47.73)%, p = 0.02]. Sunshine duration influenced the distribution of myopia rates among primary (Moran’s I=− 0.206, p< 0.001) and junior high school (Moran’s I=− 0.183, p=0.002). Local spatial analysis showed that areas with low sunshine duration had high myopia prevalence concentration.Conclusion: This study revealed sunshine duration associations with myopia prevalence at the regional and population levels. The results may emphasize the significance of promptly implementing myopia control in regions with poor sunshine. The effect of sunshine on myopia is pronounced in the early years of education, especially in primary students.Keywords: myopia, sunshine duration, children, Spatial Analysis, Moran’s Index, epidemiology

Daifeng Hu,1,&ast; Mengyue Miao,1,&ast; Hui Zhou,1 Xia Gu,1,2 Xuedan Wang,3 Alexander Tobias Teichmann,1 Qin Wang,1 Youzhe Yang1,2 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China; 3Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Wang; Youzhe Yang, The Affiliated Hospital of Southwest Medical University, NO. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email wangq@swmu.edu.cn; yangyouzhe@swmu.edu.cnAbstract: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors originating from perivascular epithelioid cells. In gynecological system, the uterus is one of the most common sites affected by PEComas. Most PEComas are benign, and patients usually have a good prognosis. However, malignant uterus PEComa is rare, and better comprehensive epidemiological investigations are needed. To date, there are a few reported cases of uterus PEComa. We herein report a rare case of malignant PEComa occurred in the uterine corpus and cervix, possibly accompanied by pulmonary lymphangioleiomyomatosis (PLAM). In addition, 55 cases of malignant uterus PEComa were picked out and collected in the data base of PubMed and Medline. On the one hand, the age of onset, population distribution, clinical manifestations, metastatic sites and routes of metastasis were analysed. On the other hand, a summary of the epidemiology, pathogenesis, diagnosis, and treatments of uterus PEComa was given.Keywords: perivascular epithelioid cell tumors, uterus, malignant, rare case, cervix

Wenxuan Li,1,&ast; Zhikai Zheng,2,3,&ast; Jiongliang Wang,2,3,&ast; Tianqing Wu,2,3,&ast; Juncheng Wang,2,3 Yangxun Pan,2,3 Jinbin Chen,2,3 Dandan Hu,2,3 Li Xu,2,3 Yaojun Zhang,2,3 Minshan Chen,2,3 Zhongguo Zhou2,3 1Cancer Center, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncheng Wang; Zhongguo Zhou, Department of Liver Surgery, Sun Yat-sen University Cancer Center, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-20-87343115 ; +86-20-87343117, Email wangjch@sysucc.org.cn; zhouzhg@sysucc.org.cnPurpose: The aim of this study was to investigate the efficacy and safety of conversion surgery for advanced hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC).Patients and Methods: Data from 172 HCC patients treated at Sun Yat-sen University Cancer Center between January 2016 and June 2021 with effective assessment of HAIC treatment response were retrospectively analyzed. Clinical pathological data, treatment process, survival, and occurrence of adverse events were recorded. Patients were grouped according to whether they achieved imaging remission after HAIC, underwent conversion surgery, and met the surgical resection criteria. Efficacy and safety were analyzed.Results: The median progression-free survival (PFS) and overall survival (OS) in the imaging remission group were 8.6 months and 26.3 months, respectively, which were longer than the 4.6 months (P< 0.05) and 15.6 months (P< 0.05) in the nonremission group. Compared with 6.7 months and 18.9 months in the HAIC maintenance group, the median PFS and median OS in the conversion surgery group were 16.5 months (P< 0.05) and 45.0 months (P< 0.05), but there was a higher risk of treatment-related hemoglobin decrease, alanine aminotransferase increase, aspartate aminotransferase increase, and total bilirubin increase (P< 0.05). The risk of biliary fistula, abdominal hemorrhage and ascites in the HAIC conversion surgery group was higher than that of the single surgery group (P< 0.05). Compared with the conversion surgery group, the median PFS and median OS of patients in the HAIC maintenance group who met the resection criteria were shorter: 7.1 months (P< 0.05) and 21.7 months (P< 0.05), respectively. All adverse events during the study were less than moderate, and no toxicity-related deaths occurred during follow-up.Conclusion: HAIC-based conversion therapy had acceptable toxic effects and could effectively stabilize intrahepatic lesions in advanced HCC, improve the survival benefit of patients, and provide some patients with the opportunity for conversion surgery to further improve prognosis.Keywords: hepatic arterial infusion chemotherapy, advanced hepatocellular carcinoma, conversion therapy

Jing Yang,1,&ast; Dixia Hu,2,&ast; Kaige Yin,3 Fang Li,4 Dongyan Shi5 1Hebei Provincial Center for Clinical Laboratories, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Clinical Lab, Zhangjiakou First Hospital, Zhangjiakou, People’s Republic of China; 3Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Department of Clinical Lab, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongyan Shi, Email shidongyan73@126.comBackground: Nocardia farcinica, a pathogen known for its strong pathogenicity, is frequently implicated in skin, central nervous system, and lung infections among immunosuppressed hosts, while intestinal nocardiosis is rare. We report the case of infectious diarrhea caused by N. farcinica in a child.Case Presentation: A 19-month-old female child was admitted to the hospital with fever and diarrhea after the consumption of oranges. The etiological agent responsible for the diarrhea was identified through the examination of fecal smears using weak acid-fast staining and conducting fecal cultures. Whole-genome sequencing was employed to analyze the causative gene. Subsequent to a 5-day treatment regimen with amoxicillin-clavulanate at a dosage of 30 mg/kg every 12 hours, the child’s condition improved significantly, leading to an uncomplicated discharge.Conclusion: This case illustrates the presence of intestine virulence factors in N. farcinica capable of causing diarrhea. The utilization of weak acid-fast staining in the examination of fecal smears is crucial for the accurate diagnosis of infectious diarrhea caused by Nocardia spp.Keywords: Nocardia farcinica, diarrhea, virulence factors

Dong Hu,1 Ruyue Yang,1 Guidan Wang,2 Hao Li,1 Xulong Fan,1 Gaofeng Liang1 1School of Basic Medicine and Forensic Medicine, Henan University of Science & Technology, Luoyang, 471023, People’s Republic of China; 2School of Medical Technology and Engineering, Henan University of Science & Technology, Luoyang, 471023, People’s Republic of ChinaCorrespondence: Gaofeng Liang, School of Basic Medicine and Forensic Medicine, Henan University of Science & Technology, Luoyang, 471023, People’s Republic of China, Email lgfeng990448@163.comAbstract: Adoptive T cells immunotherapy, specifically chimeric antigen receptor T cells (CAR-T), has shown promising therapeutic efficacy in the treatment of hematologic malignancies. As extensive research on CAR-T therapies has been conducted, various challenges have emerged that significantly hampered their clinical application, including tumor recurrence, CAR-T cell exhaustion, and cytokine release syndrome (CRS). To overcome the hurdles of CAR-T therapy in clinical treatment, cell-free emerging therapies based on exosomes derived from CAR-T cells have been developed as an effective and promising alternative approach. In this review, we present CAR-T cell-based therapies for the treatment of tumors, including the features and benefits of CAR-T therapies, the limitations that exist in this field, and the measures taken to overcome them. Furthermore, we discuss the notable benefits of utilizing exosomes released from CAR-T cells in tumor treatment and anticipate potential issues in clinical trials. Lastly, drawing from previous research on exosomes from CAR-T cells and the characteristics of exosomes, we propose strategies to overcome these restrictions. Additionally, the review discusses the plight in large-scale preparation of exosome and provides potential solutions for future clinical applications.Keywords: tumor, CAR-T cells, immune escape, exosome

Sisi Zhang,1 Miao Yu,2 Yu Zhang,2 Conying Liang,2 Dayi Hu,1 Dao Wen Wang,1 Xiaoping Meng2 1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Cardiology and Cardiac Rehabilitation, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, 130000, People’s Republic of ChinaCorrespondence: Xiaoping Meng, Department of Cardiology and Cardiac Rehabilitation, Affiliated Hospital of Changchun University of Chinese Medicine, &num;1473 Gongnong Road, Chaoyang District, Changchun, 130000, People’s Republic of China, Email xiopingmeng@126.comPurpose: This study aimed to translate and cross-culturally adapt the cardiac rehabilitation barriers scale to the Chinese, and examine its reliability and validity among the older population.Methods: An approach comprising translation, cultural adaptation, reliability, and validity examination in the Chinese version was conducted in two hospitals in Jilin, China. The t-tests were used to compare the sex differences between each item. Participants included Chinese individuals > 60 who were eligible for the cardiac rehabilitation program.Results: In total, 325 participants completed the questionnaire with an average age of 61.23 ± 9.68 years. The item-total correlations were 0.432 to 0.678. Factor analysis of CRBS-C (Kaiser Meyer Olkin = 0.867, Bartlett’s test p = 0.000) revealed four factors: logistical factors, comorbidities/functional status, perceived need/healthcare factors, and work/time conflict. The confirmatory factor analysis (CFA) indicated a good model fit (χ 2/df = 1.84, RMSEA = 0.051, CFI = 0.953, TLI = 0.945, SRMR=0.046). Cronbach’s alpha was 0.88 for the scale, ranging from 0.801 to 0.88 for each item, which indicates the internal reliability was acceptable.Conclusion: The Chinese version of the CRRS has acceptable reliability and validity in the Chinese elderly population.Keywords: cardiac rehabilitation, internal reliability, cross-cultural adaptation, exploratory factor analysis, confirmatory factor analysis

Zisha Yang,1,2,&ast; Jiajun Wang,1,2,&ast; Jiang Pi,1– 3,&ast; Di Hu,1,2 Junfa Xu,1,2 Yi Zhao,1,2,4 Yan Wang1,4 1Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, 523713, People’s Republic of China; 2Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China; 3The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, 524023, People’s Republic of China; 4Microbiology and Immunology Department, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Wang; Yi Zhao, Guangdong Medical University, No. 1 Xincheng Avenue, Songshan Lake, Dongguan, Guangdong Province, 523808, People’s Republic of China, Tel/Fax +86 769 2289 6038, Email wycomnet2023@163.com; zhaoyicomnet@gdmu.edu.cnPurpose: To investigate the correlation between M1/M2 macrophages (M1/M2 M&phis;) and cell death mode under Mycobacterium tuberculosis (Mtb) infection.Methods: Raw gene expression profiles were collected from the Gene Expression Omnibus (GEO) database. Genes related to different cell death modes were collected from the KEGG, FerrDb and GSEA databases. The differentially expressed genes (DEGs) of the gene expression profiles were identified using the limma package in R. The intersection genes of M1/M2 M&phis; with different cell death modes were obtained by the VennDiagram package. Hub genes were obtained by constructing the protein–protein interactions (PPI) network and Receiver Operating Characteristic (ROC) curve analysis. The expression of cell death modes marker genes and Hub genes were verified by Western Blot and Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).Results: Bioinformatics analysis was performed to screen Hub genes of Mtb-infected M1 M&phis; and different cell death modes, naming NFKB1, TNF, CFLAR, TBK1, IL6, RELA, SOCS1, AIM2; Hub genes of Mtb-infected M2 M&phis; and different cell death modes, naming TNF, BIRC3, MAP1LC3C, DEPTOR, UVRAG, SOCS1. Combined with experimental validation, M1 M&phis; under Mtb infection showed higher expression of death (including apoptosis, autophagy, ferroptosis, and pyroptosis) genes compared to M2 M&phis; and genes such as NFKB1, TNF, CFLAR, TBK1, IL6, RELA, AIM2, BIRC3, DEPTOR show differential expression.Conclusion: NFKB1, TNF, CFLAR, TBK1, IL6, RELA, AIM2 in Mtb-infected M1 M&phis;, and TNF, BIRC3, DEPTOR in Mtb-infected M2 M&phis; might be used as potential diagnostic targets for TB. At early stage of Mtb infection, apoptosis, autophagy, ferroptosis, and pyroptosis occurred more significantly in M1 M&phis; than that in M2 M&phis;, which may contribute to the transition of Mtb-infected M&phis; from M1-dominant to M2-dominant and contribute to the immune escape mechanisms of Mtb.Keywords: macrophage polarization, cell death modes, Mycobacterium tuberculosis, bioinformatics analysis, biomarkers

Dapeng Hu,1,2 Junwen Huang,1 Wenqu Zhao,1 Maosheng Xu,1 Yanyan Ma,1 Zhaoqian Gong,1 Qian Zhang,1 Haijin Zhao1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, NanFang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Emergency Medicine, Dalian Municipal Friendship Hospital, Dalian, Liaoning, 116001, People’s Republic of ChinaCorrespondence: Haijin Zhao, Chronic Airway Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel/Fax +86-2062787112, Email zhjin@smu.edu.cnPurpose: Identifying prognosis for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is challenging. Eosinophils and platelet are involved in the development of COPD, which may predict adverse events. The objective of this study was to determine the effect of the eosinophil to platelet ratio (EPR) in predicting adverse events in patients with AECOPD who visited the emergency department.Patients and Methods: The records of patients with AECOPD treated at Dalian Municipal Friendship Hospital from January 2018 to December 2020 were retrospectively reviewed. The relationship between the clinical characteristics and EPR, as cut-off value of 0.755, was evaluated.Results: A total of 508 patients with an AECOPD (316 male, 192 female) were included. An optimal AUC cutoff of 0.755 for the EPR segregated the patients into 2 groups with significantly different mortality (25.3% vs 5.5%, P < 0.001). The same mortality risk with lower EPR was observed among the patients with emergency room attendance (35.6% vs 11.1%, P < 0.001). A model including EPR < 0.755, exacerbation history, PaO2 < 60mmHg, PaCO2 > 50 mm Hg, hypoalbuminemia and age ≥ 80 was developed to predict death risk and showed good performance.Conclusion: During severe COPD exacerbation, an EPR < 0.755 preceding therapy can predict worse outcomes in patients with an AECOPD.Keywords: eosinophil, COPD, eosinophil to platelet ratio, emergency department

Min Dong,1,&ast; Xiumin Ma,2,&ast; Donglian Wang,3,&ast; Xiaobo Ma,4 Jin Zhang,5 Lianhua Yu,5 Qing Yang,6 Dakang Hu,5,7 Dengyan Qiao8 1Department of Pulmonary Diseases (Department of Respiratory and Critical Care Medicine), Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People’s Republic of China; 4Department of Clinical Laboratory, the First Affiliated Hospital of Xiamen University (Xiamen Key Laboratory of Genetic Testing), Xiamen, People’s Republic of China; 5Department of Laboratory Medicine, Taizhou Municipal Hospital, Taizhou, Zhejiang, People’s Republic of China; 6Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 7Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 8Department of Laboratory Medicine, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dakang Hu; Dengyan Qiao, Email 18111220048@fudan.edu.cn; 2985998299@qq.comObjective: To explore why serotype K2 accounts for a stable share in Klebsiella pneumoniae from pyogenic liver abscess (PLA).Methods: Totally 15 K2 K. pneumoniae strains from PLA, 21 K2 from non-PLA, and 31 K1 from PLA were collected from China. Sequence typing, molecular serotyping, regular PCR, and Galleria mellonella lethality were performed. A total of 12 virulence genes were detected: peg-344, allS, p-rmpA, p-rmpA2, c-rmpA, fimH, mrkD, iucA, iroN, irp2, entB, and wzi. The differences between K2 K. pneumoniae strains from PLA and non-PLA were investigated along with K1 ones.Results: Significant differences were found between K2 strains from PLA and non-PLA for the rates of virulence genes peg-344 and iucA. The latter group also showed more diverse sequence types than the former. Significant differences were only found for virulence genes allS and irp2 between K1 and K2 strains from PLA. Based on the equal virulence factors backgrounds other than serotypes, K2 strain is more virulent than K1 as G. mellonella lethality confirmed. Gene p-rmpA only brings equal virulence to p-rmpA plus p-rmpA2 in K2 strain.Conclusion: Based on the same virulence factors backgrounds except serotypes, K2 K. pneumoniae is more virulent than K1 from PLA, which provides a survival advantage to maintain a stable share.Keywords: Klebsiella pneumoniae, pyogenic liver abscess, serotype, virulence, gene

Tianqing Wu,1,2,&ast; Zhikai Zheng,1,2,&ast; Jiongliang Wang,1,2,&ast; Minrui He,1,2,&ast; Juncheng Wang,1,2 Yangxun Pan,1,2 Jinbin Chen,1,2 Dandan Hu,1,2 Yaojun Zhang,1,2 Li Xu,1,2 Minshan Chen,1,2 Zhongguo Zhou1,2 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongguo Zhou, Department of Liver Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Email zhouzhg@sysucc.org.cnPurpose: To assess the clinical value of the pretherapeutic systemic inflammation score (SIS) in predicting the prognosis of hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC).Methods: From February 2016 to April 2021, 415 advanced HCC patients who underwent HAIC at Sun Yat-sen University Cancer Center were randomly divided into training (n = 277) and validation cohorts (n = 138) and analyzed. The aspartate aminotransferase–alanine aminotransferase ratio (AAR), lymphocyte × albumin (L × A), and neutrophil × monocyte (N × M) were used to construct the SIS score based on a multivariate Cox analysis in the training cohort. A nomogram consisting of the SIS score was created and evaluated by calibration plot, areas under the receiver operating characteristic (AUC) curve, and decision curve analysis (DCA).Results: Univariate and multivariate Cox analyses revealed that the SIS score was an independent predictor of OS. A high SIS score was associated with large tumor size (P < 0.05), multiple lesions (P < 0.01), high AFP level (P < 0.01), extrahepatic metastasis (P < 0.05), and advanced BCLC stage (P < 0.01). Kaplan–Meier analysis showed that the patients with a high SIS had shorter OS than those with a low SIS in both the non-PD (p = 0.015) and PD group (p = 0.023). The calibration plots showed good concordance between the nomogram’s prediction and the actual observations in both the training and validation cohorts. In the training cohort, the AUCs of the nomogram predicting the 2-year and 3-year survival rates were 0.749 and 0.739, respectively; in the validation cohort, they were 0.760 and 0.681, respectively. Based on the AUC and DCA, the nomogram showed better predictive ability than other predictors.Conclusion: The pretherapeutic SIS score is a potential prognostic predictor for HCC patients undergoing HAIC.Keywords: HCC, systemic inflammation score, nomogram, prognosis

Zhikai Zheng,1,2,&ast; Jiongliang Wang,1,2,&ast; Tianqing Wu,1,2,&ast; Minrui He,1,2,&ast; Juncheng Wang,1,2 Yangxun Pan,1,2 Jinbin Chen,1,2 Dandan Hu,1,2 Li Xu,1,2 Yaojun Zhang,1,2 Minshan Chen,1,2 Zhongguo Zhou1,2 1Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongguo Zhou; Minshan Chen, Department of Liver Surgery, Sun Yat-sen University Cancer Center, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-20-87343117, Email zhouzhg@sysucc.org.cn; chenms@sysucc.org.cnPurpose: The efficacy of entecavir (ETV) versus tenofovir (TDF) on the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who underwent FOLFOX-hepatic arterial infusion chemotherapy (HAIC) remains unclear. In this study, we compared the outcomes between ETV and TDF in HBV-related advanced HCC patients who underwent FOLFOX-HAIC.Methods: A total of 683 patients diagnosed with HBV-related HCC who underwent FOLFOX-HAIC and received TDF or ETV between January 2016 and December 2021 were included. Overall survival (OS), progression-free survival (PFS), HBV reactivation, and liver function of patients were compared between the ETV and TDF groups by propensity score matching (PSM).Results: In the PSM cohort, for all patients and patients with ≥ 4 cycles of FOLFOX-HAIC, the median OS in the ETV group (15.2 months, 95% CI: 13.0– 17.4 months; 16.6 months, 95% CI: 14.8– 18.5 months; respectively) was shorter than that in the TDF group (23.0 months, 95% CI: 10.3– 35.6 months; 27.3 months, 95% CI: 16.5-NA months; p=0.024, p=0.028; respectively). The median PFS in the ETV group (8.7 months, 95% CI: 7.9– 9.5 months; 8.9 months, 95% CI: 8.0– 9.8 months; respectively) was also shorter than that in the TDF group (11.8 months, 95% CI: 8.0– 15.6 months; 12.7 months, 95% CI: 10.8– 14.6 months; p=0.036, p=0.025; respectively). The rate of HBV reactivation in the ETV group was higher than that in the TDF group (12.3% vs 6.3%, p=0.040; 16.5% vs 6.2%, p=0.037, respectively). For liver function, the rate of ALBI grade that remained stable or improved in the ETV group was lower than that in the TDF group (44.6% vs 57.6%, p=0.006; 37.2% vs 53.8%, p=0.019, respectively).Conclusion: Compared with ETV, TDF was associated with a better prognosis, lower proportion of HBV reactivation, and better preservation of liver function in advanced HBV-HCC patients who underwent FOLFOX-HAIC, especially those who received ≥ 4 cycles.Keywords: tenofovir, entecavir, hepatitis B virus, hepatocellular carcinoma, hepatic arterial infusion chemotherapy

BackgroundAsthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables.ResultsWe evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 233 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to quantify interaction effects using an information-theory metric known as Information Gain (IG). We performed analyses in the full dataset and in sex-stratified subsets. Our analyses identified several interaction models significantly, and suggestively, associated with BDR. The strongest interaction significantly associated with BDR was a pairwise interaction between pre-natal smoke exposure and socioeconomic status (full dataset IG: 2.78%, p = 0.001; female IG: 7.27%, p = 0.004)). Sex-stratified analyses yielded divergent results for females and males, indicating the presence of sex-specific effects.ConclusionsOur study identified novel interaction effects significantly, and suggestively, associated with BDR in African American children with asthma. Notably, we found that all of the interactions identified by ViSEN were "pure" interaction effects, in that they were not the result of strong main effects on BDR, highlighting the complexity of the network of biological and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods, thus emphasizing the importance of employing statistical methods optimized to detect both additive and non-additive interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies.

Jiao Peng,1– 3,&ast; Xi Li,4,&ast; Lin Zheng,3,5 Lifang Duan,1 Zhengxian Gao,2,5 Die Hu,1 Jie Li,6 Xiaofeng Li,6 Xiangchun Shen,5 Haitao Xiao2 1Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China; 3Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, People’s Republic of China; 4Department of Gastroenterology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 5School of Pharmacy, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haitao Xiao, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Email xhaitao@szu.edu.cn Xiangchun Shen, School of Pharmacy, Guizhou Medical University, Guizhou, 550004, People’s Republic of China, Email shenxiangchun@126.comPurpose: GLP-1 based therapy represents a new treatment option for inflammatory bowel disease. Ban-Lan-Gen (BLG) granule, a known anti-viral TCM formulation, exhibits potential anti-inflammatory activities in treating various kinds of inflammation. However, its anti-inflammatory effect on colitis and the underlying mechanisms remain unknown.Methods: Dextran sulfate sodium (DSS)-induced chronic relapsing colitis in mice was established. The disease activity index, histological sign of damage, and levels of proinflammatory cytokines were performed to assess the protective effects of BLG. Serum GLP-1 level and colonic Gcg, GPR41 and GRP43 expression, the community compositions of gut microbiota, the levels of SCFAs in the feces and GLP-1 release from primary murine colon epithelial cells were performed to characterize the effects of BLG on gut microbiota and gut SCFA derived-GLP-1 production.Results: BLG treatment significantly alleviated body weight loss, DAI, colon shortening, colon tissue damage, and pro-inflammatory cytokine levels of TNF-α, IL-1β and IL-6 in the colon tissues. Moreover, BLG treatment could observably restore colonic Gcg, GPR41 and GRP43 expression and serum GLP-1 level of colitic mice, as well as correct the alteration of gut microbiota in colitic mice by increasing the abundances of SCFA-producing bacteria, eg, Akkermansia and Prevotellaceae_UCG-001, and decreasing the abundances of bacteria, eg, Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas, and Oscillibacter. Furthermore, BLG treatment could markedly increase the levels of SCFAs in feces of colitic mice. In parallel, ex vivo assay also showed that and the extract of feces from BLG-treatment mice could greatly stimulate the secretion of GLP-1 from primary murine colon epithelial cells.Conclusion: These findings suggest that the anti-colitis effects of BLG are achieved at least partly by regulating gut microbiota and restoring gut SCFA derived-GLP-1 production, and BLG has the potential to be developed as a promising agent for the treatment of chronic relapsing colitis.Keywords: colitis, Ban-Lan-Gen granule, gut microbiota, short-chain fatty acids, GLP-1

BackgroundPAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma.ObjectiveWe sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level.MethodsWe studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function.ResultsThere was an interaction between asthma status and the PAI-1 polymorphism on FEV1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV1 /FVC in subjects with asthma (β=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV1 /FVC (P