Objective: To analyze the unregistered treatment situation and its influencing factors among pulmonary tuberculosis patients in Quzhou City, Zhejiang Province from 2017 to 2023, so as to provide a basis for promoting the management of tuberculosis patients and optimizing disease prevention and control strategies. Methods: Data of pulmonary tuberculosis patients including demographic information, etiological results, and mortality status were collected through the China Disease Prevention and Control Information System Infectious Disease Reporting and Surveillance System and the Tuberculosis Management Information System. Pulmonary tuberculosis patients not matched in the Tuberculosis Management Information System were defined as unregistered treatment patients, and the unregistered treatment rate was analyzed. Factors affecting unregistered treatment among pulmonary tuberculosis patients were analyzed using a multivariable logistic regression model. Results: A total of 10 779 pulmonary tuberculosis patients were reported in Quzhou City from 2017 to 2023, including 7 700 males (71.44%) and 3 079 females (28.56%). There were 5 484 cases aged <65 years, accounting for 50.88%. Among them, 630 cases were unregistered treatment, with an unregistered treatment rate of 5.84% (95%CI: 5.42%-6.38%). Multivariable logistic regression analysis showed pulmonary tuberculosis patients aged ≥65 years (OR=1.829, 95%CI: 1.512-2.212) had a higher risk of being unregistered treatment than those aged <65 years; patients with non-local household registration (OR=5.710, 95%CI: 4.724-6.901) had a higher risk than local patients; and patients engaged in housework/unemployed (OR=2.001, 95%CI: 1.421-2.818) or other occupations (OR=2.396, 95%CI: 1.789-3.137) had a higher risk than farmers. The mortality of unregistered treatment pulmonary tuberculosis patients was higher than the registered treatment patients (26.67% vs. 5.02%),with a significantly elevated mortality risk (OR=7.147, 95%CI: 5.738-8.902). Conclusions The unregistered treatment rate among pulmonary tuberculosis patients was well controlled in Quzhou City from 2017 to 2023, but the elderly, patients with non-local household registration, and those engaged in housework/unemployed had a higher risk of unregistered treatment. It is recommended to improve medical and social security policies, strengthen health education on tuberculosis prevention, enhance treatment adherence, and reduce mortality risk.

The molecular mechanism of verbascoside(OC1) in promoting acetylcholine(ACh) release in the pathogenesis of Alzheimer's disease(AD) was studied. Adrenal pheochromocytoma cells(PC12) of rats induced by β-amyloid protein(1-42)(Aβ_(1-42)) were used as AD models in vitro and were divided into control group, model group(Aβ_(1-42) 10 μmol·L~(-1)), OC1 treatment group(2 and 10 μg·mL~(-1)). The effect of OC1 on phosphorylated proteins in AD models was analyzed by whole protein phosphorylation quantitative omics, and the selectivity of OC1 for calcium channel subtypes was virtually screened in combination with computer-aided drug design. The fluorescence probe Fluo-3/AM was used to detect Ca~(2+) concentration in cells. Western blot analysis was performed to detect the effects of OC1 on the expression of phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ, Thr286) and synaptic vesicle-related proteins, and UPLC/Q Exactive MS was used to detect the effects of OC1 on ACh release in AD models. The effects of OC1 on acetylcholine esterase(AChE) activity in AD models were detected. The results showed that the differentially modified proteins in the model group and the OC1 treatment group were related to calcium channel activation at three levels: GO classification, KEGG pathway, and protein domain. The results of molecular docking revealed the dominant role of L-type calcium channels. Fluo-3/AM fluorescence intensity decreased under the presence of Ca~(2+) chelating agent ethylene glycol tetraacetic acid(EGTA), L-type calcium channel blocker verapamil, and N-type calcium channel blocker conotoxin, and the effect of verapamil was stronger than that of conotoxin. This confirmed that OC1 promoted extracellular Ca~(2+) influx mainly through its interaction with L-type calcium channel protein. In addition, proteomic analysis and Western blot results showed that the expression of p-CaMKⅡ and downstream vesicle-related proteins was up-regulated after OC1 treatment, indicating that OC1 acted on vesicle-related proteins by activating CaMKⅡ and participated in synaptic remodeling and transmitter release, thus affecting learning and memory. OC1 also decreased the activity of AChE and prolonged the action time of ACh in synaptic gaps.
Animals ; Rats ; Glucosides/administration & dosage* ; Acetylcholine/metabolism* ; Alzheimer Disease/genetics* ; PC12 Cells ; Phenols/chemistry* ; Neurotransmitter Agents/metabolism* ; Drugs, Chinese Herbal ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics* ; Humans ; Phosphorylation/drug effects* ; Calcium/metabolism* ; Polyphenols

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Objective: To investigate the relationship between depressive symptoms and frailty among middle-aged and elderly populations, so as to provide insights into the early identification and prevention of frailty. Methods: Based on the 2018 database of China Health and Retirement Longitudinal Study (CHARLS), demographic information, lifestyle and self-rated health status were collected from people aged 50 years and older. Depression symptoms were evaluated using the Short Version of Center for Epidemiological Studies Depression Scales (CES-D-10), and the frailty status was evaluated using frailty index. The relationship between depressive symptoms and frailty among middle-aged and elderly populations were using a multivariable logistic regression model, and the dose-response relationship was analyzed using a restricted cubic spline model. Results: A total of 5 172 individuals were enrolled, including 2 495 males (48.24%) and 2 677 females (51.76%), with a median age of 63.00 (interquartile range, 12.00) years, a median CES-D-10 score of 7.00 (interquartile range, 9.00) scores. There were 1 560 participants (30.16%) detected with mild depressive symptoms, 360 participants (6.96%) detected with moderate to severe depressive symptoms. Multivariable logistic regression analysis showed that after adjusting for gender, age, educational level, marital status, smoking, alcohol consumption and self-rated health status, participants who had mild depressive symptoms (OR=4.226, 95%CI: 3.625-4.928) and moderate to severe depressive symptoms (OR=10.737, 95%CI: 8.259-13.958) had a higher risk of frailty. The restricted cubic spline model showed a nonlinear relationship between depressive symptoms and frailty among middle-aged and elderly populations. When the CES-D-10 scores were greater than 7, the risk of frailty increased with higher CES-D-10 scores. Conclusion The degree of depressive symptoms in middle-aged and elderly people is associated with frailty, and there is a nonlinear relationship between the two.

Objective To analyze the incidence and mortality of malignant tumors among the middle-aged and elderly population in Chengguan district of Lanzhou from 2011 to 2021,and to discuss the related risk factors.Methods Using the research data of REACTION in Lanzhou,an epidemiological survey was conducted through cluster sampling in three communities in Chengguan district of Lanzhou since April 2011.The target population was middle-aged and elderly residents over 40 years old.Two follow-up surveys were carried out in 2014-2016 and 2021 successively,and 6543 people with complete follow-up data were finally included.The incidence and mortality rates of malignant tumors were calculated,as well as their age standardized rates with reference to the age composition of Segi's world standard population.Multivariate Cox regression analysis was used to screen the risk factors affecting the incidence and mortality of malignant tumors.Results After an average follow-up of 10.6 years,314 new cases of malignant tumors were found in middle-aged and elderly residents in Chengguan district of Lanzhou,with an incidence rate and age standardized incidence rate of 454.30/100 000 and 128.93/100 000,respectively.A total of 158 deaths were attributed to malignant tumors,with a mortality rate and age standardized rate of 228.41/100 000 and 607.9/100 000,respectively;The age standardized incidence rate and mortality rate of malignant tumors males were both higher than those females(P＜0.05).During the follow-up period,the age standardized incidence rate of malignant tumors in the general population showed an significant upward trend(P＜0.05),whereas the age standardized mortality rate gradually decreased after a brief increase(P＜0.05).Lung cancer,colorectal cancer,gastric cancer,and liver cancer were the main types of malignant tumors ranking in the top five in terms of incidence and mortality by gender.Multivariate Cox regression results indicate that male,age≥60 years old,college education level or above,smoking history,drinking history,having been hit by major stressful events,central obesity,hypertension,and coronary heart disease are risk factors for the onset or death of malignant tumors(HR＞1).Married,with family size≥4,frequent consumption of fresh fruit,frequent consumption of fresh vegetables,frequent consumption of grains and tubers are protective factors for the onset or death of malignant tumors(HR＜1).Conclusion The incidence of malignant tumors among middle-aged and elderly people in Chengguan district of Lanzhou from 2011 to 2021 showed an increasing trend,while the overall mortality was decreasing.Our study indicates early cancer screening in elderly populations,maintaining a healthy lifestyle and strengthening the management of chronic diseases are crucial for the prevention and treatment of malignant tumors.

Aim To develop and validate a dynamic nomogram to predict the risk of no-reflow phenomenon(NRP)after percutaneous coronary intervention(PCI)in patients with ST-segment elevation myocardial infarction(STE-MI)by constructing HALP based on haemoglobin(Hb),albumin(Alb),lymphocytes(LYM),and platelets(PLT).Methods A retrospective analysis of 449 STEMI patients admitted to Nanyang Central Hospital from January 2022 to Janu-ary 2024 was divided into 145 cases in the NRP group and 304 cases in the normal reflow group according to whether the patients developed NRP after surgery.HALP was calculated based on Hb,Alb,LYM and PLT observations.Independ-ent influences on NRP risk were determined by multivariate Logistic regression analysis.Dynamic nomogram of NRP risk after PCI in STEMI patients were developed using the R language correlation software package.Results The incidence of NRP was 32.3％(145/449)among 449 patients with NRP.The HALP of patients in the NRP group was lower than that of patients in the normal reflow group(P＜0.05).The area under the curve(AUC)of HALP for diagno-sis of NRP was 0.880(0.847-0.909),and the Kappa coefficient of its optimal cutoff value ≤3.04 versus patients with accurate diagnosis of NRP was 0.612.The results of multivariate Logistic regression analysis showed that age,diabetes mellitus,and high sensitivity C-reactive protein(hs-CRP)were independent risk factors for NRP after PCI in STEMI pa-tients(P＜0.05),and left ventricular ejection fraction(LVEF)and HALP were independent protective factors(P＜0.05).A dynamic nomogram(https://xz0311.shinyapps.io/DynNamicNRP/)based on HALP combined with age,di-abetes,LVEF,and hs-CRP was effective in predicting the risk of post-PCI NRP in STEM1 patients.Conclusion HALP is more effective than traditional risk factors in predicting NRP risk in STEMI patients after PCI,and the dynamic nomogram developed based on HALP will help develop personalized treatment strategies for patients with high NRP risk.

Objective:To investigate possible mechanism on protien LMP1 expressed by EBV inducing plasmablast differentiation of DLBCL cell via the mTORC1 pathway.Methods:The expression levels of LMP1 protein,CD38 and the phosphorylation levels of p70S6K in EBV+and EBV-DLBCL cell lines were detected by Western blot.Cell lines overexpressing LMP1 gene stablely were constructed and LMP1 gene was silenced by RNAi.The expression of LMP1 gene was verified by RT-qPCR.The expression levels of LMP1 and CD38 and the phosphorylation levels of p70S6K in each group were detected by Western blot.Results:Compared with EBV-DLBCL cells,the expression of LMP1 was detected on EBV+DLBCL cells(P=0.0008),EBV+DLBCL cells had higher phosphorylation levels of p70S6K(P=0.0072)and expression levels of CD38(P=0.0091).Compared with vector group,the cells of LMP1OE group had higher expression levels of LMP1 and CD38(P=0.0353;P＜0.0001),meanwhile molecular p70S6K was phosphorylated much more(P=0.0065);expression of LMP1 mRNA was verified(P＜0.0001).Compared with si-NC group,expression level of LMP1 protein(P=0.0129)was not detected and phosphorylated p70S6K disappeared of LMP1KO group(P=0.0228);meanwhile,expression of CD38 decreased,although there was no significant difference(P=0.2377).Conclusion:LMP1 promotes DLBCL cells plasmablast differentiation via activating mTORC1 signal pathway.