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ObjectivesHigh-need, high-cost (HNHC) patients represent a small proportion of patients in the US, but result in disproportionately higher healthcare utilization. Teaching Internal Medicine (IM) resident trainees to provide high value care for HNHC patients is critical. We sought to improve resident attitudes and increase clinical skills associated with treating HNHC patients by creating a curriculum that leveraged the UCLA Extensivist Program, a patient-centered medical home for HNHC patients.MethodsWe developed a curriculum for PGY-2 and PGY-3 IM residents centered on caring for HNHC patients over the course of 6, 4h sessions during 1 academic year. Participants completed pre- and post-intervention surveys assessing self-rated attitudes and skills associated with caring for an HNHC patient population.ResultsTwenty-one IM residents completed the curriculum and 41 were in the control group. There were no statistically significant differences in assessed attitudes and skills, but there were trends of improvement, including a decrease in participants who agreed or strongly agreed they felt overwhelmed when seeing patients for posthospital discharge follow up (45.0% pre- to 41.7% post-intervention) and an increase in participants who agreed or strongly agreed they have the skills to successfully transition HNHC patients between inpatient and ambulatory settings (20.0% pre- to 33.3% post-intervention). Participants reported better understanding of resources available to HNHC patients, effective coordination of transitions of care, and comprehensive assessment of social determinants of health.ConclusionA curriculum to improve resident attitudes and skills associated with caring for HNHC patients was successfully implemented in an IM program at a large academic medical center. The curriculum may be adapted for other training programs; long-term training woven throughout training may be important to significantly improve resident education on how to care for HNHC patients.

Mengyue Sun,1 Yuanyuan Liu,2 Shan Tang,2 Yiming Li,2 Ridong Zhang,2 Li Mao2 1Department of Geratology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of China; 2Department of Endocrinology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of ChinaCorrespondence: Li Mao, Email maoli_mail@126.comAim: This study investigated differences in gut flora between osteoporosis (OP) patients and healthy individuals using 16S rDNA sequencing. The correlation between differential flora abundance and bone mineral density (BMD) was analyzed, and key flora and potential mechanisms associated with OP were explored.Methods: Forty-three OP patients and twenty-four healthy volunteers were recruited. Gender, age, height, weight, and BMD data were collected. DNA from fecal samples was extracted for 16S rDNA sequencing. The Kruskal–Wallis test assessed differences in gut flora composition, while LEfSe analysis identified significant flora. Spearman correlation analysis examined the relationship between differential flora and BMD, and PICRUSt predicted pathways involved in OP.Results: Significant differences in microbial composition were found between the two groups. Klebsiella, Escherichia-Shigella, and Akkermansia were biomarkers in OP patients, with Faecalibacterium in the healthy group. Akkermansia abundance negatively correlated with lumbar BMD, while Klebsiella and Escherichia-Shigella negatively correlated with femoral neck and hip BMD. Faecalibacterium showed a positive correlation with BMD. Functional predictions indicated differences in metabolism-related pathways between the groups.Conclusion: Gut flora differed significantly between OP patients and healthy individuals. Akkermansia, Klebsiella, and Escherichia-Shigella could serve as diagnostic biomarkers for OP, highlighting the potential of gut flora in OP diagnosis and treatment.Keywords: osteoporosis, intestinal flora, 16S rDNA

Mingyue Sun, Weiqiang Xiao, Qingxia Xu Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Qingxia Xu, Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Dongming Road No. 127, Zhengzhou, Henan Province, People’s Republic of China, Tel +860371-65587147, Email qxiaxu@126.comObjective: Klebsiella michiganensis is an emerging pathogen. In this context, we characterised a strain fxq isolated from a cerebrospinal fluid specimen of a patient with tentorial meningioma, and the K. michiganensis isolate produced carbapenemases of KPC and NDM types.Methods: The Phoenix 100 Automated Microbiology System, MALDI-TOF and whole-genome sequencing were used to identify the species. Anti-microbial susceptibility testing was also conducted with the Phoenix 100. The plasmid locations of the blaKPC-2 and blaNDM-1 genes were determined by S1-nuclease pulsed-field gel electrophoresis and Southern blot. The transfer capacity of plasmids carrying blaKPC-2 and blaNDM-1 was investigated by conjugation experiments, and the resistance plasmid stability was evaluated by culture and subculture. K. michiganensis subtypes were identified by multi-locus sequence typing. We performed whole-genome sequencing to confirm species, characterise plasmids and analyse core genes.Results: fxq was originally identified as Klebsiella oxytoca and showed resistance to imipenem and meropenem, but whole-genome sequencing identified it to be K. michiganensis. The strain fxq belonged to the novel sequence type 202 (ST202) and carried the blaKPC-2 and blaNDM-1 genes located on the pB_KPC InFIA and pE_NDM IncU plasmids, respectively. The blaKPC-2-carrying plasmid was successfully transferred to Escherichia coli EC600 by conjugation, whereas the blaNDM-1 gene on the pE_NDM plasmid was not. The pB_KPC and pE_NDM plasmids demonstrated high stability.Conclusion: This work is the first report on a carbapenem-resistant clinical isolate K. michiganensis ST202 harbouring the blaKPC-2 and blaNDM-1 genes encoded by the IncFIA and IncU plasmids, respectively.Keywords: Klebsiella michiganensis, IncU plasmid, carbapenemase gene, NDM, KPC

Mingjun Gong,1 Min Sun,1 Yaqi Sun,2 Lijuan Jin,1 Shen Li3 1Sports Training College, Tianjin University of Sport, Tianjin, People’s Republic of China; 2Mental Health Institute, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Psychoneuromodulation Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Shen Li, Psychoneuromodulation Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, No. 13, Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel +86-22-88188875, Email lishen@tmu.edu.cnObjective: Using meta-analysis to comprehensively and quantitatively evaluate the impact of acute sleep deprivation on different sports performance of athletes, this study aims to provide scientific guidance for coaches in optimizing and adjusting training and competition arrangements.Methods: Establishing literature inclusion and exclusion criteria, we conducted searches in both Chinese and English databases. Using stata 14.0, we analyzed 75 indicators from 27 included literature, focusing on three aspects: the impact of acute sleep deprivation on overall athletic performance, the impact on sporting performance across various athletic abilities, and the disparities in athletic performance between morning and afternoon following acute sleep deprivation.Results: The effect size of acute sleep deprivation on overall athletic performance was − 0.56 (P< 0.05). Sub-analyses revealed effect sizes of − 0.23 (P< 0.05) for whole night sleep deprivation, − 1.17 (P< 0.05) for partial sleep deprivation at the end of the night, and − 0.25 (P> 0.05) for partial sleep deprivation in the beginning of the night. The effect sizes of acute sleep deprivation on high intensity intermittent exercise, skill control, speed, aerobic endurance, and explosive power indicators were − 1.57, − 1.06, − 0.67, − 0.54, and − 0.39 respectively (P< 0.05). The effect sizes of acute sleep deprivation on the overall athletic performance in the morning and afternoon were − 0.30, and − 1.11, respectively (P< 0.05).Conclusion: Acute sleep deprivation significantly impairs the overall athletic performance of athletes, with a more pronounced negative impact observed with partial sleep deprivation at the end of the night. Various types of exercise performance are adversely affected by acute sleep deprivation, with magnitude of impact ranking high intensity intermittent, skill control, speed, aerobic endurance, and explosive power. Following acute sleep deprivation, athletes’ overall sporting performance in the afternoon is inferior to that in the morning.Keywords: acute sleep deprivation, athletes, athletic ability, sporting performance, meta-analysis

Weiwei Guan,1,2 Congyue Zhang,1 Tongguo Miao,1 Chen Dong,1 Lu Li,1 Xiwei Yuan,1 Dandan Zhao,1 Rong Ai,1 Xiaoxiao Zhang,1 Mengjiao Sun,1 Haiyan Kang,2,&ast; Yuemin Nan1,&ast; 1Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2Department of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, 050023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuemin Nan, Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, No. 139, Ziqiang Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 18533112266, Email nanyuemin@163.com Haiyan Kang, Department of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, No. 42, Tanan Road, Shijiazhuang, Hebei Province, 050023, People’s Republic of China, Tel +86 13315952782, Email kanghaiyan1976@126.comPurpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC.Materials and Methods: High‐throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated.Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors.Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.Keywords: ADAMTSL4-AS1, AC067931, SOCS2-AS1, HBV-associated HCC, diagnostic biomarkers

Min Sun,1 Guanchi Yan,2 Siming Sun,3 Xiaonan Li,1 Wei Sun,4 Yuehui Wang1 1Department of Geriatrics, The First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Clinical Research, The First Hospital of Jilin University, Changchun, People’s Republic of China; 4Education Department, The First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yuehui Wang, Department of Geriatrics, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130061, People’s Republic of China, Tel +86-13614303457, Email yuehuiwang300@jlu.edu.cn Wei Sun, Education Department, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130061, People’s Republic of China, Tel +86-16604302962, Email 18504381676@163.comBackground: Serum trace elements and oxidative stress factors are related to diabetic microvascular complications. The study was to investigate the complex relationship between trace elements, oxidative stress factors, and the severity of microvascular complications of diabetes in older adults.Methods: The present study included patients with or without type 2 diabetes, and blood glucose, blood lipids, trace elements (iron, magnesium, zinc), oxidative stress factors (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC)) were evaluated. Risk factors for the severity of diabetic microvascular complications in older adults with diabetes were also estimated.Results: There were statistically significant differences in fasting blood glucose (FBG), triglycerides (TG), low density lipoprotein (LDL), glycated hemoglobin (HbAlc), MDA, NO, SOD, T-AOC, magnesium, and zinc between the two groups (P< 0.05). Iron (rZinc = 0.147, rSOD = 0.180, rT-AOC = 0.193, P < 0.05) was positively correlated with zinc, SOD and T-AOC. Iron was negatively correlated with MDA (rMDA = − 0.146, P < 0.05). Magnesium was positively correlated with SOD (rMagnesium = 0.147, P < 0.05). Zinc (rSOD = 0.616, rT-AOC = 0.575, P < 0.01) was positively correlated with SOD and T-AOC. Zinc (rMDA =− 0.636, rNO=− 0.616, P< 0.01) was positively correlated with MDA and negatively correlated with NO. The course of disease (18.653, [5.726; 60.764], P < 0.01), FBG (1.265, [1.059; 1.511], P < 0.05), HbAlc (1.545, [1.431; 1.680], P < 0.01), MDA (2.989, [1.900; 4.702], P < 0.01) were risk factor for the severity of diabetic microvascular complications. Zinc (0.680, [0.503; 0.919], P < 0.05) and SOD (0.820, [0.698; 0.964], P < 0.05) were protective factors for the severity of diabetic microvascular complications.Conclusion: Serum trace elements are related to oxidative stress levels in older adults with type 2 diabetes. The more stable trace element in older adults with diabetes, the lower the oxidative stress and the fewer microvascular complications of diabetes.Keywords: type 2 diabetes mellitus, older adults, trace elements, diabetic microvascular complications, oxidative stress

Mingyue Sun, Zhuoyou Chen Department of Neurology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213000, People’s Republic of ChinaCorrespondence: Zhuoyou Chen, Email neuro1972@163.comAbstract: Alzheimer’s disease (AD) is the most common neurodegenerative illness, characterized by memory loss and cognitive decline, accounting for 60– 80% of dementia cases. AD is characterized by senile plaques made up of amyloid β (Aβ) protein, intracellular neurofibrillary tangles caused by hyperphosphorylation of tau protein linked with microtubules, and neuronal loss. Currently, therapeutic treatments and nanotechnological developments are effective in treating the symptoms of AD, but a cure for the illness has not yet been found. Recently, the increased study of extracellular vesicles (EVs) has led to a growing awareness of their significant involvement in neurodegenerative disorders, including AD. Exosomes are small extracellular vesicles that transport various components including messenger RNAs, non-coding RNAs, proteins, lipids, DNA, and other bioactive compounds from one cell to another, facilitating information transmission and material movement. There is growing evidence indicating that exosomes have complex functions in AD. Exosomes may have a dual role in Alzheimer’s disease by contributing to neuronal death and also helping to alleviate the pathological progression of the disease. Therefore, the primary aim of this review is to outline the updated understandings on exosomes biogenesis and many functions of exosomes in the generation, conveyance, distribution, and elimination of hazardous proteins related to Alzheimer’s disease. This review is intended to provide novel insights for understanding the development, specific treatment, and early detection of Alzheimer’s disease.Keywords: Alzheimer’s disease, exosomes, pathogenesis, diagnosis, treatment

Mengjuan Sun,1,&ast; Jun Wei,1,&ast; Yanhui Su,1,&ast; Yangjingwan He,1 Liang Ge,1 Yan Shen,1 Bohui Xu,2 Yanlong Bi,3 Chunli Zheng1 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China; 2School of Pharmacy, Nantong University, Nantong, People’s Republic of China; 3Pediatric Intensive Care Unit, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunli Zheng; Yanlong Bi, Email zhengchunli@cpu.edu.cn; pulong123@163.comPurpose: The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects.Methods: Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs).Results: The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug’s circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug’s efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions.Conclusion: RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM’s poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.Keywords: acute lung injury, simvastatin, respiratory distress syndrome, pH response

Ting Yang,1,2 Yanan Du,1 Mingzhen Sun,1 Jingjing Meng,1 Yiyi Li1 1School of Health Services Management, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 2Intelligent Interconnected Systems Laboratory of Anhui Province (Hefei University of Technology), Hefei, Anhui, 230009, People’s Republic of ChinaCorrespondence: Ting Yang, Email yangting@ahmu.edu.cnAbstract: Over the past decade, the global outbreaks of SARS, influenza A (H1N1), COVID-19, and other major infectious diseases have exposed the insufficient capacity for emergency disposal of medical waste in numerous countries and regions. Particularly during epidemics of major infectious diseases, medical waste exhibits new characteristics such as accelerated growth rate, heightened risk level, and more stringent disposal requirements. Consequently, there is an urgent need for advanced theoretical approaches that can perceive, predict, evaluate, and control risks associated with safe disposal throughout the entire process in a timely, accurate, efficient, and comprehensive manner. This article provides a systematic review of relevant research on collection, storage, transportation, and disposal of medical waste throughout its entirety to illustrate the current state of safe disposal practices. Building upon this foundation and leveraging emerging information technologies like Internet of Things (IoT), cloud computing, big data analytics, and artificial intelligence (AI), we deeply contemplate future research directions with an aim to minimize risks across all stages of medical waste disposal while offering valuable references and decision support to further advance safe disposal practices.Keywords: medical waste, safe disposal, major infectious diseases, progress and challenges

Yaohui Yi, Meng Sun, Jiachen Lu, Xiaofeng Dou, Yingying Yu, Ling Zhou School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of ChinaCorrespondence: Ling Zhou, School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of China, Tel +86-411-8611-0368, Email zhouling0609@163.comBackground: As future health workers, medical students’ attitudes towards tuberculosis (TB) patients can impact TB control. However, in China, there is a lack of well-quantified assessment regarding the stigma among medical students towards TB patients. Therefore, this study aimed to validate the Chinese version of the Tuberculosis related-Stigma Scale (TSS) in medical students and to apply the scale to measure stigma and its determinants.Methods: A total of 1035 eligible medical students participated in the cross-sectional questionnaire. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were first conducted to test Chinese version of the TSS construct validity, and then internal consistency was assessed using Cronbach’s α. Finally, multiple linear regression analyses were conducted to identify predictors of stigma.Results: EFA extracted two factors (“Social distance” and “Exclusionary sentiments”). The CFA further confirmed the two-factor construct. The internal consistency, convergent and divergent validity of the adapted Chinese version of the TSS was acceptable. Furthermore, Whether one has received TB health education and whether know a person with TB are associated with all dimensions of TB stigma, while differences in sex and place of residence play different roles in influencing the different dimensions of stigma.Conclusion: The adapted Chinese version of the TSS can be used to assess the level of stigma among medical students in China towards tuberculosis patients. When implementing future interventions to reduce stigma associated with TB, special attention should be given to medical students from urban areas, of male gender, who have not received TB health education, and no know a person with TB. However, these two dimensions (“Social distance” and “Exclusionary sentiments”) are impacted by different determinants and should therefore be addressed separately when designing, implementing, and evaluating measures to reduce stigma.Keywords: tuberculosis related-stigma scale, medical student, psychometrics, determinants

Chunyan Yang,&ast; Hao Tian,&ast; Guixing Xu, Qin Luo, Mingsheng Sun, Fanrong Liang Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fanrong Liang, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, No. 37 Shi’er Qiao Road, Chengdu, Sichuan, 610075, People’s Republic of China, Email acuresearch@126.comPurpose: The effect of acupuncture as adjunctive therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was controversial. Thus, we aimed to evaluate the effects of acupuncture for treating AECOPD.Methods: Eight databases were searched from database inception to July 30, 2023. All RCTs compared acupuncture plus conventional western medicine with conventional western medicine alone were included. Outcomes were quality of life, lung function, blood oxygen condition, exercise capacity, daily symptoms, duration of hospitalization, and adverse events. The statistical analyses were conducted using Stata 17.0, and methodological quality was measured by the Cochrane bias risk assessment tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence.Results: Twelve studies including 915 patients were included. Compared with conventional western medicine alone, acupuncture combined with conventional western therapy significantly improved quality of life (CAT: MD: − 3.25; 95% CI: − 3.73 to − 2.78, P< 0.001) and arterial blood gas (PaCO2: MD: − 1.85; 95% CI: − 2.74 to − 0.95, P< 0.001; PaO2: MD: 5.15; 95% CI: 1.22 to 9.07, P = 0.01). And for lung function, statistical benefits were found in FEV1/FVC (MD: 4.66; 95% CI: 2.21 to 7.12, P< 0.001), but no difference was seen for FEV1% (MD: 1.83; 95% CI: − 0.17 to 3.83, P = 0.073). There was no significant improvement in exercise capacity (6MWD: MD: 96.69; 95% CI: − 0.60 to 193.98, P = 0.051), hospitalization duration (MD: − 5.70; 95% CI: − 11.97 to 0.58, P = 0.075), and dyspnea (mMRC: MD: − 0.19; 95% CI: − 0.61 to 0.63, P = 0.376) between two groups. Overall bias for CAT and mMRC was in “high” risk, FEV1%, FEV1/FVC, PaCO2, and PaO2 was in “some concern” and 1 RCT assessing hospitalization duration was in “low” risk. And the overall assessments were either moderate, low or very low certainty. Seven trials performed safety assessment of acupuncture, and no serious adverse events were reported.Conclusion: Acupuncture might have auxiliary effects on AECOPD. However, the quality of the evidence is limited, and more high-quality RCTs are needed to be performed in the future.Keywords: acute exacerbation of chronic obstructive pulmonary disease, acupuncture, systematic review, meta-analysis

Hongjuan Wang,1 Rongzhi Li,1 Lin Ge,2 Fan Xu,1 James Allen Wiley,3 Siyuan Tang,1 Mei Sun1,4 1Xiangya School of Nursing, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Department of Alcohol Addiction and Internet Addiction, Brain Hospital of Hunan Province (The Second People’s Hospital of Hunan Province), Changsha, Hunan Province, People’s Republic of China; 3Department of Family and Community Medicine and Institute for Health Policy Research, University of California, San Francisco, CA, USA; 4School of Nursing, Changsha Medical University, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Siyuan Tang; Mei Sun, Xiangya School of Nursing, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China, Email sytang263@csu.edu.cn; smnjw2008@126.comBackground: Sleep-related outcomes in people with diabetes are poor, which is closely linked to reducing the development of diabetes. Cognitive behavioral therapy (CBT) based intervention presents innovative solutions that can help improve sleep-related outcomes.Aim: This synthesis aims to assess the effectiveness of CBT-based intervention compared to controls in Randomized Controlled Trials (RCTs) for sleep-related outcomes among people with diabetes.Methods: Eight electronic databases were systematically searched: PubMed, EMBASE, Cochrane library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), and Wan Fang database. We examined CBT-based intervention’s effectiveness on sleep-related outcomes in people with diabetes in RCTs identified in these databases from their inception to 1st November 2023, and updated on 15 January 2024. The risk of bias was assessed using the Cochrane Risk of Bias tool by two reviewers. The meta-analysis of included studies was conducted by RevMan 5.3 software.Results: Seven studies in total (n = 2633 participants) were included in this systematic review based on our inclusion criteria. The systematic review found CBT-based intervention significantly improved sleep quality (Pittsburgh Sleep Quality Index, PSQI scores) at immediate post-intervention [95% CI=(− 1.31 to -0.32), p = 0.001], six months [95% CI=(− 0.75 to − 0.22), p = 0.0003], and 12 months [95% CI=(− 0.72 to − 0.24), < 0.0001], compared to control groups. Furthermore, our findings demonstrated that six sessions [95% CI= (− 0.38 to − 0.13), p < 0.0001] or more than six sessions [95% CI=(− 1.76 to − 0.02), p = 0.05] of CBT-based intervention could improve sleep quality compared to controls (I2=0%). Interestingly, CBT-based intervention improves total sleep time at post-intervention in people with diabetes compared to the control group [95% CI= (− 0.57 to − 0.12), p = 0.003]. However, there was no significant that CBT-based intervention is beneficial to time to fall asleep [95% CI (− 1.89 to 0.43), p = 0.22] and sleep efficiency [95% CI (− 1.27 to 0.27), p = 0.20] after intervention, compared to control group.Conclusion: CBT-based intervention appears to have a beneficial effect on improving sleep quality and total sleep time among people with diabetes. CBT-based intervention could be considered a strategy among healthcare providers to enhance sleep quality and total sleep time for people with diabetes. More RCTs with rigorous designs and long-term follow-up are warranted to provide conclusive evidence of the CBT-based intervention on sleep-related outcomes and to explore the mechanisms by which the CBT-based interventions improve sleep-related outcomes.Keywords: diabetes, cognitive behavioral therapy, sleep, systematic review, meta-analysis

Man Sun,1 Huan Zhang,1 Jiayi Liu,1 Jiayi Chen,1 Yaxin Cui,1 Simiao Wang,1 Xiangyu Zhang,2 Zhaogang Yang1 1School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China; 2Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310020, People’s Republic of ChinaCorrespondence: Xiangyu Zhang; Zhaogang Yang, Tel/Fax +86-431-85155320, Email 3314023@zju.edu.cn; zhaogangyang@jlu.edu.cnAbstract: Recently, gene therapy has become a subject of considerable research and has been widely evaluated in various disease models. Though it is considered as a stand-alone agent for COVID-19 vaccination, gene therapy is still suffering from the following drawbacks during its translation from the bench to the bedside: the high sensitivity of exogenous nucleic acids to enzymatic degradation; the severe side effects induced either by exogenous nucleic acids or components in the formulation; and the difficulty to cross the barriers before reaching the therapeutic target. Therefore, for the successful application of gene therapy, a safe and reliable transport vector is urgently needed. Extracellular vesicles (EVs) are the ideal candidate for the delivery of gene drugs owing to their low immunogenicity, good biocompatibility and low toxicity. To better understand the properties of EVs and their advantages as gene drug delivery vehicles, this review covers from the origin of EVs to the methods of EVs generation, as well as the common methods of isolation and purification in research, with their pros and cons discussed. Meanwhile, the engineering of EVs for gene drugs is also highlighted. In addition, this paper also presents the progress in the EVs-mediated delivery of microRNAs, small interfering RNAs, messenger RNAs, plasmids, and antisense oligonucleotides. We believe this review will provide a theoretical basis for the development of gene drugs.Keywords: extracellular vesicles, gene therapy, drug delivery system, gene drugs

Miaomiao Sun,1– 3,&ast; Fuquan Wang,1– 3,&ast; Haopeng Li,1– 3 Mengyu Li,1– 3 Yu Wang,1– 3 Chenchen Wang,1– 3 Yan Zhang,1– 3 Dingyu Zhang,1– 4 Jianhua Li,5 Shanglong Yao1– 3 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, 430022, People’s Republic of China; 4Wuhan Jinyintan Hospital, Wuhan, 430023, People’s Republic of China; 5Department of Critical Care Medicine, Chongqing University Jiangjin Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanglong Yao; Jianhua Li, Email yaoshanglong@hust.edu.cn; jianhuali2022@cqu.edu.cnBackground: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation.Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay.Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1β and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1β also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1’s protective effects in septic mice.Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI.Keywords: Maresin-1, pyroptosis, AMPK/SIRT3, endoplasmic reticulum stress, sepsis-associated acute kidney injury, inflammation

OBJECTIVES High-need, high-cost (HNHC) patients represent a small proportion of patients in the US, but result in disproportionately higher healthcare utilization. Teaching Internal Medicine (IM) resident trainees to provide high value care for HNHC patients is critical. We sought to improve resident attitudes and increase clinical skills associated with treating HNHC patients by creating a curriculum that leveraged the UCLA Extensivist Program, a patient-centered medical home for HNHC patients. METHODS We developed a curriculum for PGY-2 and PGY-3 IM residents centered on caring for HNHC patients over the course of 6, 4h sessions during 1 academic year. Participants completed pre- and post-intervention surveys assessing self-rated attitudes and skills associated with caring for an HNHC patient population. RESULTS Twenty-one IM residents completed the curriculum and 41 were in the control group. There were no statistically significant differences in assessed attitudes and skills, but there were trends of improvement, including a decrease in participants who agreed or strongly agreed they felt overwhelmed when seeing patients for posthospital discharge follow up (45.0% pre- to 41.7% post-intervention) and an increase in participants who agreed or strongly agreed they have the skills to successfully transition HNHC patients between inpatient and ambulatory settings (20.0% pre- to 33.3% post-intervention). Participants reported better understanding of resources available to HNHC patients, effective coordination of transitions of care, and comprehensive assessment of social determinants of health. CONCLUSION A curriculum to improve resident attitudes and skills associated with caring for HNHC patients was successfully implemented in an IM program at a large academic medical center. The curriculum may be adapted for other training programs; long-term training woven throughout training may be important to significantly improve resident education on how to care for HNHC patients.

Abstract Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late‐stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes‐rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles‐rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early‐stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late‐stage PDAC patients undergoing chemotherapy, lower GPC1 tMV‐mProtein and Exo‐mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Jianwei Liu,1,&ast; Minmin Sun,2,&ast; Kunpeng Fang,3,&ast; Jie Wang,1,&ast; Bowen Ma,1 Li Song,1 Ting Liu,1 Ming Tang,4 Kui Wang,1 Yong Xia4 1Department of Hepatic Surgery II, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 2Department of Hepatic Surgery I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 3Department of Special Treatment I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 4Department of Hepatic Surgery IV, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Xia, Department of Hepatic Surgery (IV), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-2181875005, Fax +86-2165562400, Email xia.yong@126.com Kui Wang, Department of Hepatic Surgery (II), Eastern Hepatobiliary Surgery Hospital, Navy Medical University, &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel\Fax +86-2181875514, Email wangkuiykl@163.com

Objective: The objective of this study is to assess and compare the clinical efficacy of “Figure-8” banding and double-row anchor suture-bridge fixation techniques in the arthroscopic management of tibial intercondylar eminence avulsion fractures. Method: A retrospective analysis was conducted on the medical records of 42 patients who underwent arthroscopic surgery for tibial intercondylar eminence fractures at our institution from June 2017 to June 2022. This cohort included 20 cases treated with “Figure-8” banding and 22 cases managed using double-row anchor suture-bridge fixation. Comparative assessments were made regarding operative duration, duration of fracture consolidation, postoperative knee joint range of motion, joint stability as assessed by the Lachman test, Lysholm score, and International Knee Documentation Committee (IKDC) functional score for both treatment groups. Results: The mean follow-up duration was 13.8 months. The analysis indicated that the double-row anchor suture-bridge group had a significantly longer operative duration compared to the “Figure-8” banding group (p < 0.05). Postoperative computed tomography (CT) scans confirmed successful reduction in both groups, with fracture consolidation achieved within an average of three months. Both groups showed significant improvements in postoperative knee range of motion, joint stability, and functional scores compared to preoperative measurements (p < 0.05). During the initial two-month post-surgery, the double-row anchor suture-bridge group demonstrated superior knee joint range of motion and functional scores compared to the “Figure-8” banding group (p < 0.05); however, these differences were not statistically significant beyond three months post-surgery (p > 0.05). By the one-year postoperative mark, joint stability outcomes were comparable between the two treatment groups (p > 0.05). Conclusion: Both “Figure-8” banding and double-row anchor suture-bridge fixation techniques in the arthroscopic management of tibial intercondylar eminence avulsion fractures can achieve precise reduction and stable fixation. In addition, the figure-8 suture group has the characteristics of shorter surgery time and less cost. Notably, early postoperative knee function appears to be superior with double-row anchor suture-bridge fixation compared to “Figure-8” banding. [ABSTRACT FROM AUTHOR]

The association between periodontal diseases and the risk of gastrointestinal cancers, especially site-specific gastrointestinal cancers, remains unclear. Here, we comprehensively searched PubMed, EMBASE, Web of Science, and Google Scholar from inception to April 2024 to identify relevant studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Subgroup analyses and sensitivity analyses were conducted to confirm the robustness of the main findings in different populations. This study was reported according to PRISMA 2020 guidelines. In total, we identified 19 studies, including 16.6 million participants. Individuals with periodontal diseases had an increased risk of overall gastrointestinal cancers compared with those without periodontal diseases (HR 1.31, 95% CI 1.16–1.49). Periodontal diseases significantly increased the risk of esophageal cancer by 39% (HR 1.39, 95% CI 1.15–1.68), gastric cancer by 13% (HR 1.13, 95% CI 1.01–1.26), colorectal cancer by 21% (HR 1.21, 95% CI 1.05–1.39), pancreatic cancer by 35% (HR 1.35, 95% CI 1.00–1.82), and liver cancer by 9% (HR 1.09, 95% CI 1.04–1.13). The risk of gastrointestinal cancers was significantly increased by periodontitis (HR 1.45, 95% CI 1.14–1.85), gingivitis (HR 1.03, 95% CI 1.01–1.04), and periodontitis/gingivitis (HR 1.27, 95% CI 1.07–1.51). Furthermore, severe periodontal diseases showed a significantly increased risk of gastrointestinal cancer (HR 1.79, 95% CI 1.07–2.99). Results of sensitivity analyses for site-specific gastrointestinal cancers were robust with the main findings. In summary, periodontal diseases, especially severe periodontitis, increase the risk of overall and site-specific gastrointestinal cancers. Interventions to prevent and manage periodontal diseases may reduce the risk of developing gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Objective: To investigate the trimester‐specific associations between maternal total physical activity level vs moderate‐to‐vigorous exercise and fetal growth disorders. Methods: We analyzed 2062 mother–neonate pairs participating in the longitudinal China Medical University Birth Cohort Study. The Pregnancy Physical Activity Questionnaire was used to assess the physical activity level of women during the three trimesters. A higher level of total physical activity was defined as meeting or exceeding the cohort‐specific 75th percentile, and a higher level of exercise was defined according to the Physical Activity Guidelines for Americans. Fetal growth disorder was defined as small‐for‐gestational age (SGA) or large‐for‐gestational age (LGA) at birth. Results: Of the neonates included in this study, 7.1% were SGA and 15.5% were LGA. A higher level of total physical activity during the first trimester (adjusted relative risk (aRR), 0.62 (95% CI, 0.42–0.91)) and second trimester (aRR, 0.62 (95% CI, 0.41–0.95)) was associated with a lower risk of SGA, and a higher level of total physical activity during the third trimester was associated with a lower risk of LGA (aRR, 0.73 (95% CI, 0.54–0.97)). When analyzing physical activity by subtype, a higher level of occupational physical activity during the first and second trimesters was associated negatively with SGA risk, and higher levels of occupational and low‐intensity physical activity during the first trimester were associated negatively with LGA risk. No significant association was found between maternal adherence to the Physical Activity Guidelines for Americans and risk of fetal growth disorders. Conclusions: A higher total physical activity level during the first and second trimesters was associated with a decreased risk of SGA, whereas a higher total physical activity level in the third trimester was associated with a decreased risk of LGA. Pregnant women should be advised to increase their total physical activity levels instead of focusing on engaging in only moderate‐to‐vigorous exercise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Mine pollution causes a serious impact on the ecological environment surrounding the mine site. It provides great theoretical value to explore the effects of planting different plants on soil characteristics and bacterial community structure around the mine site for vegetation restoration. In this study, we mainly assessed the rhizosphere bacterial community structure and diversity of wheat and Chinese milk vetch seedlings in copper tailings by 16S rRNA high-throughput sequencing and also soil properties. The results showed that planting wheat and Chinese milk vetch seedlings led to a decrease in soil pH, but both could increase the content of total nitrogen, organic matter, and available nitrogen in the rhizosphere soil, as well as enhance the activities of urease and alkaline protease. In addition, a total of 1,133,919 active sequences and 13,199 operational taxonomic units were obtained. The microorganisms in the substrate samples belong to 34 phyla and 81 classes, Proteobacteria, Acidobacteria and Actinobacteria were the top three dominant group. In general, Chinese milk vetch or wheat enriched the diversity of bacterial community in rhizosphere soil, the results showed that the number of rhizosphere bacteria in Chinese milk vetch was higher than that in wheat. The structure of the rhizosphere bacterial community of wheat and Chinese milk vetch seedling was similar, but the bacterial abundance was different. Mantel tests showed that Chao index significantly correlated with ammonium nitrogen. These results not only expand our understanding of rhizosphere bacteriomes but also provide theoretical basis for improving the soil quality of industrial and crop yields. [ABSTRACT FROM AUTHOR]

Widening the martensitic hysteresis ( T Dhys ) in NiTiNb shape memory alloys (SMAs) holds potential for broadening their working temperature range while enabling the room-temperature storage. In this study, the T Dhys is divided into two parts: the thermal-induced hysteresis ( T hys ) and the deformation-induced hysteresis ( T hys ′ ). In addition to decreasing the martensitic transformation start temperature ( M S ), it is found that grain refinement is an effective method for widening both T hys and T hys ′ of the Ni47Ti44Nb9 alloy, a commercial SMA widely used for shape memory couplings. According to thermodynamic analysis, grain refinement increases the dissipation energy ( Δ E dis ) (caused by thermal friction at martensite/austenite interface), thereby widening T hys . Moreover, the Ni47Ti44Nb9 alloy with finer grains has the potential to release more elastic strain energy ( Δ E el ) after deformation, thereby exhibiting a wider T hys ′ . When deforming a large strain, the alloy with finer grains generates more dislocations which stabilize the martensitic phase, thus further widening T hys ′ . [ABSTRACT FROM AUTHOR]

The cellular Notch signal transduction pathway is intimately associated with infections by Kaposi’s sarcoma-associated herpesvirus (KSHV) and other gamma-herpesviruses. RBP-Jk, the cellular DNA binding component of the canonical Notch pathway, is the key Notch downstream effector protein in virus-infected and uninfected animal cells. Reactivation of KSHV from latency requires the viral lytic switch protein, Rta, to form complexes with RBP-Jk on numerous sites within the viral DNA. Constitutive Notch activity is essential for KSHV pathophysiology in models of Kaposi’s sarcoma (KS) and Primary Effusion Lymphoma (PEL), and we demonstrate that Notch1 is also constitutively active in infected Vero cells. Although the KSHV genome contains >100 RBP-Jk DNA motifs, we show that none of the four isoforms of activated Notch can productively reactivate the virus from latency in a highly quantitative trans-complementing reporter virus system. Nevertheless, Notch contributed positively to reactivation because broad inhibition of Notch1-4 with gamma-secretase inhibitor (GSI) or expression of dominant negative mastermind-like1 (dnMAML1) coactivators severely reduced production of infectious KSHV from Vero cells. Reduction of KSHV production is associated with gene-specific reduction of viral transcription in both Vero and PEL cells. Specific inhibition of Notch1 by siRNA partially reduces the production of infectious KSHV, and NICD1 forms promoter-specific complexes with viral DNA during reactivation. We conclude that constitutive Notch activity is required for the robust production of infectious KSHV, and our results implicate activated Notch1 as a pro-viral member of a MAML1/RBP-Jk/DNA complex during viral reactivation. IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) manipulates the host cell oncogenic Notch signaling pathway for viral reactivation from latency and cell pathogenesis. KSHV reactivation requires that the viral protein Rta functionally interacts with RBP-Jk, the DNA-binding component of the Notch pathway, and with promoter DNA to drive transcription of productive cycle genes. We show that the Notch pathway is constitutively active during KSHV reactivation and is essential for robust production of infectious virus progeny. Inhibiting Notch during reactivation reduces the expression of specific viral genes yet does not affect the growth of the host cells. Although Notch cannot reactivate KSHV alone, the requisite expression of Rta reveals a previously unappreciated role for Notch in reactivation. We propose that activated Notch cooperates with Rta in a promoter-specific manner that is partially programmed by Rta’s ability to redistribute RBP-Jk DNA binding to the virus during reactivation. [ABSTRACT FROM AUTHOR]

Background: Older major depressive disorder (MDD) patients have more complex clinical symptoms and higher abnormal lipid metabolism (ALM) rates. This study aimed to compare clinical differences between those with and without ALM in a sample of older first-episode drug naïve (FEDN) patients. Methods: We recruited 266 older MDD patients. Socio-demographic variables, clinical data, and lipid parameters were obtained. The Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS-P) were conducted to evaluate patients’ depression, anxiety and psychotic symptoms, respectively. Results: In this study, we found that the prevalence of comorbid ALM was 86.1% in older MDD patients. Compared with the non-abnormal lipid metabolism (NALM) group, the ALM group had a higher duration of illness, higher clinical global impression of severity scale (CGI-S) and HAMD scores, higher thyroid stimulating hormone (TSH) and glucose levels. Logistic regression analysis indicated that duration of illness (OR = 1.11, P = 0.023, 95%CI = 1.015–1.216) and CGI-S score (OR = 2.28, P = 0.014, 95%CI = 1.18–4.39) were associated with ALM in older MDD patients. Conclusion: The importance of regular lipid assessment in older MDD patients needs to be taken into account. [ABSTRACT FROM AUTHOR]

Background: To investigate the value of 3.0T magnetic resonance perfusion-weighted imaging (PWI) in the preoperative differential diagnosis and grading assessment of gliomas. Materials and Methods: The PWI features of 23 single brain metastases and 73 gliomas (32 low-grade and 41 high-grade) were retrospectively analyzed with postoperative pathological findings. The cerebral blood volume (CBV) values of the tumour parenchyma, the peritumoral oedema area and the contralateral normal brain tissue were measured, and the relative CBV (rCBV) values were calculated and statistically analysed. Results: A total of 96 patients, comprising 66 men and 30 women with a mean age of 47 ± 11 years, were included in the study. The time-signal curves of gliomas of different grades obtained by magnetic resonance perfusion have different characteristics. The rCBV values for tumor parenchyma and peritumoral edema were higher in the high-grade glioma group than in the low-grade glioma group and the single brain metastasis group ([6.01 ± 1.64] vs [2.16 ± 0.87] vs [4.37 ± 1.03]) and ([1.82 ± 0.47] vs [0.79 ± 0.34] vs [0.81 ± 0.21]), and the differences were significant (p < 0.05). The rCBV value of the tumour parenchyma in the single brain metastasis group was higher than that in the low-grade glioma group ([4.37 ± 1.03] vs [2.16 ± 0.87]), and the difference was significant (p < 0.05). Conclusion: Magnetic resonance PWI has high clinical value in the preoperative diagnosis and grading evaluation of gliomas. [ABSTRACT FROM AUTHOR]

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late‐stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes‐rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles‐rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early‐stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late‐stage PDAC patients undergoing chemotherapy, lower GPC1 tMV‐mProtein and Exo‐mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis. [ABSTRACT FROM AUTHOR]