BACKGROUND: There is little literature describing the artificial intelligence (AI)-aided diagnosis of severe pneumonia (SP) subphenotypes and the association of the subphenotypes with the ventilatory treatment efficacy. The aim of our study is to illustrate whether clinical and biological heterogeneity, such as ventilation and gas-exchange, exists among patients with SP using chest computed tomography (CT)-based AI-aided latent class analysis (LCA). METHODS: This retrospective study included 413 patients hospitalized at Xinhua Hospital diagnosed with SP from June 1, 2015 to May 30, 2020. AI quantification results of chest CT and their combination with additional clinical variables were used to develop LCA models in an SP population. The optimal subphenotypes were determined though evaluating statistical indicators of all the LCA models, and clinical implications of them such as guiding ventilation strategies were further explored by statistical methods. RESULTS: The two-class LCA model based on AI quantification results of chest CT can describe the biological characteristics of the SP population well and hence yielded the two clinical subphenotypes. Patients with subphenotype-1 had milder infections ( P <0.001) than patients with subphenotype-2 and had lower 30-day ( P <0.001) and 90-day ( P <0.001) mortality, and lower in-hospital ( P = 0.001) and 2-year ( P <0.001) mortality. Patients with subphenotype-1 showed a better match between the percentage of non-infected lung volume (used to quantify ventilation) and oxygen saturation (used to reflect gas exchange), compared with patients with subphenotype-2. There were significant differences in the matching degree of lung ventilation and gas exchange between the two subphenotypes ( P <0.001). Compared with patients with subphenotype-2, those with subphenotype-1 showed a relatively better match between CT-based AI metrics of the non-infected region and oxygenation, and their clinical outcomes were effectively improved after receiving invasive ventilation treatment. CONCLUSIONS A two-class LCA model based on AI quantification results of chest CT in the SP population particularly revealed clinical heterogeneity of lung function. Identifying the degree of match between ventilation and gas-exchange may help guide decisions about assisted ventilation.
Humans ; Tomography, X-Ray Computed/methods* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Artificial Intelligence ; Aged ; Pneumonia/diagnosis* ; Latent Class Analysis ; Adult

G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

Objective Tto analyze the spatial distribution and characteristics of the national AIDS/HIV epidemics from 2009 to 2020 to discover its distribution, aggregation, and hot spots, and provide corresponding suggestions for AIDS prevention and control. Methods Spatial autocorrelation analysis, hot spot analysis, and Kriging interpolation prediction were used to describe, analyze, and predicting the spatial distribution of AIDS epidemics across the country. Results The national AIDS incidence and mortality rate increased yearly, but the growth rate shows a downward tendency with uneven spatial distribution,focusing on the southwest and northwest regions; the average annual incidence rate of AIDS ( Moran's I> 0, P < 0. 01) and the average annual mortality rate (Moran's I> 0, P < 0. 01) of the distribution had a positive global spatial correlation, with Sichuan, Yunnan, Guangxi, Chongqing,Hunan and Guizhou being the areas with ^“high-high^” clusters of AIDS incidence; Sichuan, Yunnan, Guangxi,Hunan,Xinjiang and Guizhou were the areas with ^“high-high^” clusters of average annual mortality. The ^“hot spot^” areas were mainly concentrated in the southwestern part of China, and the ^“cold spot^” areas were mainly concentrated in the eastern coastal and northern parts of China; Kriging interpolation predicted that Xinjiang would be the new hot spot area for future epidemics. Conclusion The spatial distribution of AIDS in China is uneven, showing spatial aggregation, hot spots and cold spots coexist, and the high-risk areas will continue to expand in the future.So the prevention and control work should be carried out in a targeted and localized manner.

Objective:To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) after pancreaticoduodenectomy and endoscopic selection strategies.Methods:Clinical data of 34 patients treated with ERCP after pancreaticoduodenectomy at the Endoscopic Center of the First Affiliated Hospital of Air Force Medical University from January 2013 to December 2021 were retrospectively analyzed. The success rates of endoscopic insertion, diagnosis, treatment and ERCP, and the incidence of adverse events were analyzed.Results:Fifty ERCP treatments were performed in 34 patients. The success rates of endoscopic insertion, diagnosis, treatment, and ERCP after pancreaticoduodenectomy were 92.0% (46/50), 93.5% (43/46), 88.4% (38/43) and 76.0% (38/50), respectively. The success rates of ERCP assisted with colonoscope and balloon-assisted enterosocpe were 76.0% (19/25) and 75.0% (18/24), respectively. There were 3 adverse events, including 1 case of anastomotic mucosa tear during surgery, 1 case of cardiopulmonary arrest and 1 case of postoperative cholangitis.Conclusion:ERCP is effective and safe after pancreaticoduodenectomy in general. ERCP assisted with colonoscope and balloon-assisted colonoscope shows similar success rate after pancreaticoduodenectomy.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Humans ; NF-kappa B/metabolism* ; Lipopolysaccharides/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Acute Lung Injury/metabolism* ; Lung ; Phosphate-Binding Proteins/therapeutic use* ; Pore Forming Cytotoxic Proteins/therapeutic use*

This study aimed to explore the prevalence and risk factors of cardiovascular disease (CVD) and psychological distress among female scientists and technicians in China. Accordingly, we included scientists and technicians from representative research institutions, medical institutions, colleges, universities, and businesses in China, and the data were collected from July 1, 2019 to March 31, 2021 via online questionnaires. The parameters evaluated in this study included age, sex, marital status, educational background, monthly income, sleep hours, sleep problems, smoking, alcohol consumption, work-related stress, work burnout, cardiovascular symptoms, CVD, family history, and depressive and anxiety symptoms. A total of 14 530 scientists and technicians were included, comprising 7144 men and 7386 women. We found 34.9% men and 16.6% women with CVD, 35.1% men and 21.4% women with depressive symptoms, 28.7% men and 13.8% women with anxiety symptoms, and 22.0% men and 9.5% women with CVD combined with depressive or anxiety symptoms. This study focused on the details of women. Younger women (age≤35 years) had the highest prevalence of depressive symptoms (24.9%), anxiety symptoms (16.2%), and comorbidity (11.2%). It was established that, despite traditional risk factors, unmanageable work burnout, depressive symptoms, and anxiety symptoms were associated with a higher risk of CVD in women; insomnia, overwhelming work stress, unmanageable work burnout, and CVD were linked to a higher risk of depressive symptoms and anxiety; insomnia, overwhelming work stress, and unmanageable work burnout were related to CVD combined with depressive or anxiety symptoms. A bidirectional relationship was noted between CVD and depression or anxiety in female scientists and technicians, and insomnia and overwhelming work stress were positively associated with comorbidity. It is suggested that effective measures should be taken to protect female scientists and technicians from CVD and psychological distress.
Male ; Female ; Humans ; Adult ; Cardiovascular Diseases/epidemiology* ; Prevalence ; Depression/complications* ; Sleep Initiation and Maintenance Disorders/epidemiology* ; Anxiety/epidemiology* ; Risk Factors ; Psychological Distress ; Stress, Psychological/psychology*

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis

Background Diabetic retinopathy (DR) has become the main cause of blindness in the world,But the etiology of DR is still not clear,and the results of the studies on the risk factors of DR are not completely consistent.Fully understanding the risk factors of DR has an important clinical value for the prevention and treatment of DR.Objective This study was to analyze the prevalence rate and risk factors of DR inpatients with type 2 diabetes and provide a basis for the establishment of ophthalmic intervention programs and measures for diabetic inpatients.Methods Cross sectional study was performed.Four hundred and seventy three patients with type 2 diabetes in the department of endocrinology,Dongguan People's Hospital from July 2011 to July 2012 were included.The patients were divided into DR group and non diabetic retinopathy (NDR) group.The DR group was subdivided into mild,moderate and severe non-proliferative DR (NPDR) group and proliferative DR (PDR) group.The sex and age of patients,course of diabetes,body mass index (BMI),systolic blood pressure,diastolic blood pressure,fasting blood glucose (FBG),2 hours postprandial blood glucose (2 h PBG),glycosylated hemoglobin (HbA1 c),fasting insulin,2 hours postprandial insulin,high density lipoprotein cholesterol,low density lipoprotein cholesterol,apolipoprotein A1 (APOA1),APOB,alpha lipoprotein,total cholesterol,three glycerol,urea nitrogen,creatinine,uric acid,percentage of neutrophil,24 hours urinary albumin total (ALBU-24 h) and ALBU were detected.Logistic regression was used to analyze the relationship between DR and various factors,and the risk factors of DR were screened out.Results The prevalence of DR inpatients with type 2 diabetes was 28.33％,the prevalence of mild,moderate and severe NPDR were 2.54％,16.28％ and 4.23％,respectively,the prevalence of PDR was 5.29％.The prevalence of DME was 10.36％ in the DR patients.The course of diabetes,the levels of serum lipoprotein,creatinine,ALBU-24 h and ALBU were statistically significant between DR group and NDR group (all at P＜0.05).By stepwise Logistic regression analysis,the course of disease,FBG were identified as the independent risk factors of DR (course of disease:odds ratio [OR] =1.155,95 ％ confidence interval [CI]:1.067-1.251;FBG:OR =1.313,95％ CI:1.071-1.610).Conclusions The course of diabetes,lipoprotein,creatinine,ALBU-24h,ALBU are closely related to the occurrence and development of DR.The course of diabetes and FBG are the independent risk factors of DR.

Objective To investigate the clinicopathological features of gastric cardia cancer with neuroendo-crine cell differentiation(NED).Methods From September 2007 to October 2014,the clinicopathological features of 70 gastric cardia cancer patients with NED and 76 cases without NED confirmed by surgical pathology specimens and immunohistochemistry (Syn and CgA)in the First Affiliated Hospital of Shantou University Medical College were ret-rospectively analyzed and compared.Results The positive expression rates of synaptophysin(Syn)and chromogranin A(CgA)were 43.2% and 22.6%,respectively.Tumor differentiation was significantly related with NED (χ2 =4.989,P =0.026).Tumors with NED were larger and had deeper invasion,but they were not statistically significant. Conclusion Immunohistochemistry is important to the diagnosis of NED.Gastric cardia cancer with NED has poorer differentiation.