ObjectiveTo characterize the seasonal patterns of influenza in Kunming City, Yunnan Province before, during, and after the COVID-19 pandemic, and provide scientific evidence for optimizing influenza prevention and control strategies. MethodsInfluenza-like illness (ILI) and etiological surveillance data for influenza from the 14^th week of 2010 to the 13^th week of 2024 in Kunming City of Yunnan Province were collected. Harmonic regression models were constructed to analyze the epidemic characteristics and seasonal patterns of influenza before (2010/2011‒2019/2020 influenza seasons), during (2020/2021‒2022/2023 influenza seasons), and after (2023/2024 influenza season) the COVID-19 pandemic. ResultsBefore the COVID-19 pandemic, influenza in Kunming City mainly exhibited an annual cyclic pattern without a significant semi-annual periodicity, peaking from December to February of the next year, with an epidemic duration of 20‒30 weeks. During the pandemic, influenza seasonality shifted, with an increase in semi-annual periodicity and an approximate one month delay in annual peaks. However, after the pandemic, the annual amplitude of influenza increased compared with that before the pandemic, and the epidemic duration extended by about one month. Although the annual peak largely reverted to the pre-pandemic levels, the annual peaks for different influenza subtypes/lineages had not fully recovered. ConclusionInfluenza seasonality in Kunming City underwent substantial alterations following the COVID-19 pandemic and has not yet fully reverted to pre-pandemic levels. Continuous surveillance on different subtypes/lineages of influenza viruses remains essential, and prevention and control strategies should be adjusted and optimized in a timely manner based on current epidemic trends.

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

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective To investigate the risk factors for pneumonia complicating infectious mononucleosis(IM)in adults and construct a nomogram prediction model.Methods A retrospective analysis was conducted on 198 IM patients admitted to the Second Affiliated Hospital of Air Force Medical University from January 2015 to December 2021.Patients were divided into pneumonia group(n=52)and non-pneumonia group(n=146)based on whether pulmonary infection occurred during hospitalization.The baseline data(age,gender,place of onset,etc.),clinical manifestations(maximum body temperature,lymph node enlargement,splenomegaly,etc.),and inflammatory indicators[white blood cell count(WBC),C-reactive protein(CRP),etc.]were compared between the two groups.Kaplan-Meier curves were plotted to analyze the key indicators affecting the hospital stay of IM patients.Multivariate logistic regression was used to analyze the independent risk factors for pneumonia complicating IM in adults and construct a nomogram prediction model based on the identified risk factors.The predictive efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve and the consistency of the model was assessed using the calibration curve.The fit of the model was evaluated using the Hosmer-Lemeshow test.Additionally,the sensitivity,specificity,and accuracy of the model were assessed using confusion matrix.Results Compared with non-pneumonia group,the pneumonia group had a significantly higher proportion of patients from rural areas,with body mass index(BMI)≥24 kg/m2,smoking history,hepatomegaly,fever duration of≥7 d,as well as increased total hospitalization costs and average daily hospitalization costs,and prolonged hospital stay(P<0.05).The proportion of patients with a history of antibiotic use was lower in the pneumonia group(P<0.05).Kaplan-Meier survival analysis showed that patients from rural areas,with BMI≥24 kg/m2,smoking history,no prophylactic use of antibiotics,fever duration≥7 d,and hepatomegaly had significantly prolonged hospital stays(P<0.05).Multivariate logistic regression analysis revealed that living in a rural area(OR=4.089,P<0.05),hepatomegaly(OR=4.082,P<0.05),and elevated WBC(OR=1.205,P<0.05)were independent risk factors for pneumonia complicating IM in adults,while the prophylactic use of antibiotics(OR=0.142,P<0.05)was an independent protective factor.The area under the ROC curve of the constructed nomogram prediction model was 0.827(95%CI 0.762-0.892),and the slope of the calibration curve was close to 1,and the Hosmer-Lemeshow test showed χ2=5.299,P=0.725,indicating good consistency and fit of the prediction model.The results of the confusion matrix assessment showed that the sensitivity of the model was 0.669(0.624-0.773),the specificity was 0.827(0.724-0.930),and the accuracy was 0.732(0.665-0.793).Conclusion The nomogram prediction model based on place of onset,hepatomegaly,the prophylactic use of antibiotics and WBC has excellent fit and discrimination,providing an effective quantitative tool for prognosis assessment of IM.

Objective:The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) .Methods:This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared.Results:①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD ( P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM ( R2=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion:sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.

Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.

Aim To investigate the risk factors of death after acute Stanford type A aortic dissection(ATAAD)complicated with malperfusion syndrome(MPS).Methods 244 patients with ATAAD complicated with MPS who ad-mitted to Nanchong Central Hospital from June 2020 to June 2023 were selected as the study objects.The postoperative survival of the patients was followed up and they were classified into survival group(156 cases)and death group(88 ca-ses).After propensity score matching(PSM)was applied in 1 ∶1 matching,there were 54 cases in both groups.Uni-variate and Logistic regression analysis was performed to analyze the risk factors of postoperative death in patients with ATA-AD complicated with MPS.Area under curve(AUC)of receiver operating characteristics(ROC)was used to analyze the prognosis of ATAAD complicated with MPS.The prediction model was established by using the regression equation y=1-1/(1+e-z)and the stability of the model was verified by cross-checking method.Results After matching,compared with the survival group(n=54),in the death group(n=54),the proportion of sex(male),the proportion of alcohol con-sumption,acute physiology and chronic health status Ⅱ(APACHE Ⅱ)score,sequential organ failure(SOFA)score,al-anine aminotransferase(ALT),aspartate aminotransferase(AST),total serum bilirubin(TSB),cholinesterase,serum creatinine(SCr),blood urea nitrogen(BUN),N-terminal pro-brain natriuretic peptide(NT-proBNP),D-dimer(D-D),white blood cell(WBC),neutrophile granulocyte(NEU),fibrinogen degradation product(FDP),platelet(PLT),fi-brinogen(FIB),C-reactive protein(CRP),hypersensitive troponin,operation time,ICU stay time,ventilator stay time,hospital stay,distal extremity hypoperfusion,renal hypoperfusion were significantly increased(P＜0.05).Logistic analy-sis displayed that gender(male),history of drinking,NT-proBNP ≥271.86 ng/L,D-D≥0.74 mg/L and NEU≥13.06× 109 L-1 were independent risk factors in ATAAD patients complicated with MPS for postoperative death(P＜0.05).The combination of NT-proBNP,D-D,gender(male),alcohol drinking history and NEU(referred to as"five factors")had the highest value in predicting ATAAD patients with MPS.The AUC of its ROC curve was 0.979(95％CI:0.937～0.984),the sensitivity was 94.3％,and the specificity was 91.8％,which was higher than the independent predictor.The best critical value predicted by the five factors was 5.02.The survival rate of the group＞5.02 was significantly high-er than that of the group ≤5.02.Log Rank test P＜0.01.A prediction model was established based on the important factors of postoperative death in ATAAD patients with MPS.The results showed that the model had good prediction accu-racy.Conclusion NT-proBNP≥271.86 ng/L,D-D≥0.74 mg/L,gender(male),history of alcohol consumption,and NEU≥×109 L-1 were independent risk factors for long-term prognosis in patients with ATAAD combined with MPS,and their combined application could effectively increase the accuracy of prognosis assessment.

Objective To observe the effects of ritodrine hydrochloride,phloroglucinol and magnesium sulfate on serum sex hormones and fetal protection effect in patients with threatened abortion after 20 gestational weeks.Methods Patients with threatened abortion(after 20 gestational weeks)underwent fetal protection treatment were retrospectively enrolled.According to cohort method,they were divided into group A(ritodrine hydrochloride injection 100 mg+5％glucose injection 500 mL for intravenous drip,continued infusion after uterine contraction inhibition for 12-18 h,oral ritodrine hydrochloride tablets),group B(of phloroglucinol injection 40 mg+5％glucose injection 500 mL for intravenous drip,drug withdrawal after uterine contraction inhibition)and group C(magnesium sulfate injection 20 mL+5％glucose injection 100 mL,magnesium sulfate injection 40 mL+5％glucose injection 500 mL for intravenous drip after rapid intravenous drip,continued infusion after uterine contraction inhibition for 12 h).The onset time,disappearance time of uterine contraction,levels of serum sex hormones[progesterone(P),estradiol(E2),human chorionic gonadotrophin β-subunit(β-hCG)],adverse drug reactions and response rate of fetal protection in the three groups were observed.Results There were 40 cases in group A,38 cases in group B and 42 cases in group C.The onset time in group A,group B and group C were(1.71±0.34),(2.29±0.23)and(4.51±1.12)h,and the difference was statistically significant(P＜0.05).The disappearance time of uterine contraction in groups A,B and C were(1.34±0.32),(2.24±0.26)and(2.36±0.28)d,and the difference between group B and group A,between group C and group A were statistically significant(all P＜0.05).After 3 d of treatment,levels of serum P in group A,group B and group C were(78.64±10.34),(69.35±10.52)and(68.76±11.13)ng·mL-1;E2 levels were(672.25±85.63),(623.25±92.31)and(624.12±93.65)pg·mL-1;β-hCG levels were(6.95×104±1 258.65),(6.75×104±1 274.43)and(6.70×104±1 327.59)mU·mL-1;the difference between group B and group A,between group C and group A were statistically significant(all P＜0.05).The incidence rates of palpitation in groups A,B and C were 25.00％,0 and 9.52％,the difference between group A and group B was statistically significant(P＜0.05).The incidence rates of headache in groups A,B and C were 2.50％,2.63％and 26.19％;the difference between group A and group C,and between group B and group C was statistically significant(P＜0.05).The incidence rates of fatigue in groups A,B and C were 5.00％,0 and 19.05％,and the difference between group B and group C was statistically significant(P＜0.05).The incidence rates of gastrointestinal discomfort were 5.00％,0 and 11.90％,and the difference between group B and group C was statistically significant(all P＜0.05).The response rates of fetal protection in groups A,B and C were 92.50％,94.74％and 73.81％,and the difference between group A and group C,between group B and group C was statistically significant(all P＜0.05).Conclusion The onset time of ritodrine hydrochloride is short,which can be the first choice for disease control.Phloroglucinol is comparable to ritodrine hydrochloride in terms of fetal protection effect,which has better advantages in adverse drug reactions.Clinically,phloroglucinol can be considered for patients with poor tolerance to ritodrine hydrochloride.