OBJECTIVE: To investigate the effect of traditional Chinese Five-body balance exercise on patients with preserved ratio impaired spirometry (PRISm). METHODS: Fifteen patients with PRISm and 15 patients diagnosed with chronic obstructive pulmonary disease (COPD) were recruited from the Outpatient Department of Guang'anmen Hospital and Beijing Niujie Health Service Center from April to December, 2023. Participants in both groups attended supervised Five-body balance exercise training twice a week for 12 weeks. Patients with COPD continued their regular medication regimen during the intervention period. The endpoints were mean changes in the 6-min walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ) score, cardiopulmonary exercise testing (CPET), pulmonary function, and scores of COPD assessment test (CAT), modified British Medical Research Council, Self-Rating Anxiety Scale, and Self-Rating Depression Scale from baseline to 12 weeks. Adverse events were monitored throughout the study. RESULTS: The PRISm group showed a significant improvement from baseline to week 12 in 6MWT, SGRQ symptom score, and forced vital capacity (FVC) compared to the COPD group (P<0.05). No significant between-group changes were observed in other outcome measurements (P>0.05). In addition, compared with baseline, both groups exhibited improvements in 6MWT, SGRQ score, and CPET at week 12 (P<0.05). The PRISm group also showed a significant increase in forced expiratory volume in 1 s and FVC, as well as a significant decrease in CAT score at week 12 (P<0.05). No adverse events were reported. CONCLUSION Patients with PRISm may benefit from Five-body balance exercise training, which can improve the exercise capacity, health-related quality of life, and lung function. (Registration No. ChiCTR2200059290).
Humans ; Spirometry ; Male ; Female ; Pulmonary Disease, Chronic Obstructive/therapy* ; Lung/physiopathology* ; Middle Aged ; Exercise Tolerance/physiology* ; Exercise Therapy ; Aged ; Medicine, Chinese Traditional ; Respiratory Function Tests ; East Asian People

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can result in fatigue and post-exertional malaise; however, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exacerbates lower urinary tract symptoms (LUTS) is unclear. This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS. METHODS: A multicenter, retrospective cohort study was conducted at two tertiary hospitals in China from November 1, 2022, to November 1, 2023. Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results. LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form (IIQ-7). Pelvic floor muscle activity was measured using electromyography following the Glazer protocol. Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters, with stratified analyses conducted using SPSS version 26.0. RESULTS: Among 3,652 participants (681 infected, 2,971 uninfected), no significant differences in LUTS prevalence or IIQ-7 scores were observed. However, SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles (mean tonic contraction amplitudes), regardless of delivery mode ( P = 0.001). CONCLUSION Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity, suggesting potential neuromuscular effects.
Humans ; Female ; COVID-19/epidemiology* ; Retrospective Studies ; Adult ; Pregnancy ; Lower Urinary Tract Symptoms/virology* ; Postpartum Period ; Pregnancy Complications, Infectious/virology* ; China/epidemiology* ; Electromyography ; SARS-CoV-2/physiology* ; Pelvic Floor/physiopathology* ; Prevalence

Objective:To analyze the drug resistance status and related risk factors in elderly patients with pulmonary tuberculosis,and to construct and validate a drug resistance risk prediction model for elderly pulmonary tuberculosis patients,providing evidence for early clinical identification of high-risk populations.Methods:A retrospective study was conducted,consecutively enrolling 315 pulmonary tuberculosis patients aged ≥60 years from January 2019 to December 2021.Based on drug susceptibility test results,patients were divided into drug-resistant group(85 cases)and drug-sensitive group(230 cases).Data on demographic characteristics,clinical manifestations,comorbidities,imaging features,and previous treatment history were collected.Univariate and multivariate logistic regression analyses were performed to identify drug resistance-related factors,and a prediction model was constructed accordingly.The model was internally validated using the concordance index(C-index)and Bootstrap method.Results:Among 315 elderly pulmonary tuberculosis patients,the drug resistance rate was 26.98％,predominantly mono-resistance(48.24％)and multidrug-resistance(28.24％).Multivariate logistic regression analysis showed that previous anti-tuberculosis treatment history[OR=4.537,95％CI(1.962-10.498),P=0.005],diabetes mellitus[OR=3.286,95％CI(1.547-6.979),P=0.002],pulmonary cavitation[OR=4.158,95％CI(1.926-8.973),P＜0.001],pleural effusion[OR=2.563,95％CI(1.218-5.390),P=0.013],and tracheobronchial tuberculosis[OR=2.819,95％CI(1.352-5.876),P=0.006]were independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors had a C-index of 0.815(95％CI:0.762-0.868).Conclusion:The drug resistance rate is high among elderly pulmonary tuberculosis patients.Previous anti-tuberculosis treatment history,diabetes mellitus,pulmonary cavitation,pleural effusion,and tracheobronchial tuberculosis are independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors has good predictive value for identifying high-risk populations,which is helpful for early clinical intervention and individualized treatment strategy formulation.

Objective:To analyze the drug resistance status and related risk factors in elderly patients with pulmonary tuberculosis,and to construct and validate a drug resistance risk prediction model for elderly pulmonary tuberculosis patients,providing evidence for early clinical identification of high-risk populations.Methods:A retrospective study was conducted,consecutively enrolling 315 pulmonary tuberculosis patients aged ≥60 years from January 2019 to December 2021.Based on drug susceptibility test results,patients were divided into drug-resistant group(85 cases)and drug-sensitive group(230 cases).Data on demographic characteristics,clinical manifestations,comorbidities,imaging features,and previous treatment history were collected.Univariate and multivariate logistic regression analyses were performed to identify drug resistance-related factors,and a prediction model was constructed accordingly.The model was internally validated using the concordance index(C-index)and Bootstrap method.Results:Among 315 elderly pulmonary tuberculosis patients,the drug resistance rate was 26.98％,predominantly mono-resistance(48.24％)and multidrug-resistance(28.24％).Multivariate logistic regression analysis showed that previous anti-tuberculosis treatment history[OR=4.537,95％CI(1.962-10.498),P=0.005],diabetes mellitus[OR=3.286,95％CI(1.547-6.979),P=0.002],pulmonary cavitation[OR=4.158,95％CI(1.926-8.973),P＜0.001],pleural effusion[OR=2.563,95％CI(1.218-5.390),P=0.013],and tracheobronchial tuberculosis[OR=2.819,95％CI(1.352-5.876),P=0.006]were independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors had a C-index of 0.815(95％CI:0.762-0.868).Conclusion:The drug resistance rate is high among elderly pulmonary tuberculosis patients.Previous anti-tuberculosis treatment history,diabetes mellitus,pulmonary cavitation,pleural effusion,and tracheobronchial tuberculosis are independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors has good predictive value for identifying high-risk populations,which is helpful for early clinical intervention and individualized treatment strategy formulation.

Objective To form the in vitro diagnostic reagents(IVD)selection and optimization management plan and management database,and optimize the IVD management work.Methods Through the analysis of the policy background and the current management status of the IVD clinical laboratory in Beijing Hospital,the selection and optimization management plan for existing and newly applied laboratory IVD was formulated based on clinical needs.The IVD of the whole hospital was selected and optimized by combing projects,open bidding,innovative quotation methods,on-site review and other steps.The IVD management database and qualification database of Beijing Hospital was formed,and the effect from the aspects of compliance,work efficiency and cost control was evaluated.Results The selection and optimization of 1 737 IVDs in the whole hospital were completed according to the formulated IVD selection and optimization management plan.The implementation of management plan improved the work efficiency.The content of review in an average meeting was increased by more than 10 times,and the frequency of new applications for IVD access was accelerated,while the IVD cost was reduced,and the average purchase amount of the whole hospital was reduced by about 15％.The prices of key IVD products were lower after selection than before selection,and the difference was significant(t=2.493,P=0.034).Conclusion The management scheme of IVD selection and optimization was feasible,and it could achieve the goal of ensuring compliance,improving efficiency and reducing costs.

Objective:To explore the cost adjustment model based on age coefficient and to make the payment standard more consistent with the actual resource consumption in clinical settings partially address the issue of targeting elderly patients that may arise after the implementation of DRG-PPS payment.Methods:The study analyzed data from all discharged patients in a hospital in 2022.Case rate coefficients were calculated for different age groups(young-middle-aged group, early elderly group, and high-aged elderly group)using the DRG(Diagnosis-related Group)rate formula to adjust the payment standard.The statistical significance of the difference between the actual cost and the current payment standard(within-group difference)was determined using the paired t-test in SPSS software.The Wilcoxon rank sum test was then used to determine the statistical significance of the difference between the actual cost and the adjusted payment standard(between-group difference).To assess the applicability of the age coefficient adjustment model, 11 disease groups were selected, and the Wilcoxon rank sum test was used to determine if there was a statistical difference between the adjusted and non-adjusted groups.The effectiveness of the adjustment was judged based on the standard deviation. Results:There was no significant difference between the actual hospitalization costs and the current standards(Group 1)and the actual hospitalization costs and the adjusted payment standards(Group 2)( P values were 0.928 and 0.949, both greater than or equal to 0.05).The results of the rank sum test showed a statistical difference between the two groups( P value of less than 0.05).Group 1 had a median of -1 644.57, a mean of -999.04, a mean standard error of 70.35, and a standard deviation of 15 024.62.Group 2 had a median of -1 641.88, a mean of -998.50, a mean standard error of 70.32, and a standard deviation of 15 019.24. Conclusions:Both the current and adjusted rates accurately reflect the true cost of hospitalization for patients.However, the adjusted standard is more closely aligned with the actual costs and the model remains valid.partially address the issue of targeting elderly patients that may arise after the implementation of DRG-PPS payment.

Tomato (Solarium lycopersicum) is one of the most popular vegetables worldwide and is a classic model plant for studying fruit development and ripening due to its short growth cycle, clear genetic background and ease of molecular manipulation. This paper used virus-induced gene silencing (VIGS) to construct SlWRKY53b gene-silenced tomato fruits and analyzed the effect of SIWRKY531) gene silencing in the tomato fruit ripening process. We found that transient silencing of SIWRKY531) resulted indelayed in-broken color, higher chlorophyll contents (P<0.05) and reduced carotenoid contents (P<0.05) in tomato fruits, and color difference results indicated that the differences in L *, a * and b * values were consistent with fruit color changes. Further studies showed that genes significantly down-regulated (P<0.01) in SIWRKY531) gene-silenced tomato fruits include the chlorophyll degradation-related genes (AFCl, PAO, PPH, SGR1), carotenoid synthesis-related genes (PSYl, PDS, ZDS), ethylene synthesis pathway-related genes (ACOl, ACS2, NOR, AC03, EA, RIN), and cell wall degradation-related genes (PG, EXP, CELT.). Correlation analysis showed that the expression of SlWRKY53b was negatively correlated with chlorophyll contents and positively correlated with carotenoid contents and the expression of maturation-related genes. These results suggest that inhibition of SIWRKY531) expression at the transcrip-tional level can achieve the effect of delaying tomato fruit ripening, indicating that S1WRKY531) plays arole as a facilitator in the tomato fruit ripening process.

Taking lipophagy as the breakthrough point, we explored the mechanism of Zexie Decoction(ZXD) in improving lipid metabolism in the hepatocyte model induced by palmitic acid(PA) and in the animal model induced by high-fat diet(HFD) on the basis of protein kinase B(Akt)/transcription factor EB(TFEB) signaling pathway. Co-localization was carried out for the microtubule-associated protein light chain 3(LC3) plasmid labeled with green fluorescent protein(GFP) and lipid droplets(LDs), and immunofluorescence co-localization for liver LC3 of HFD mice and perilipin 2(PLIN2). The results showed that ZXD up-regulated the expression of LC3, reduced lipid accumulation in hepatocytes, and increased the co-localization of LC3 and LDs, thereby activating lipo-phagy. Western blot results confirmed that ZXD increased autophagy-related protein LC3Ⅱ/LC3Ⅰ transformation ratio and lysosome-associated membrane protein 2(LAMP2) in vivo and in vitro and promoted the degradation of sequestosome-1(SQSTM1/p62)(P<0.05). The results above jointly explained that ZXD regulated lipophagy. Furthermore, ZXD activated TFEB expression(P<0.05) and reversed the PA-and HFD-induced decrease of TFEB nuclear localization in hepatocytes(P<0.05). Meanwhile, ZXD activated liver TFEB to up-regulate the expression of the targets Lamp2, Lc3 B, Bcl2, and Atg5(P<0.05). Additionally, ZXD down-regulated the protein level of p-Akt upstream of TFEB in vivo and in vitro. In conclusion, ZXD may promote lipophagy by regulating the Akt/TFEB pathway.
Animals ; Mice ; Autophagy/drug effects* ; Hepatocytes/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

The present study investigated the pharmaceutical effect and underlying mechanism of Zexie Decoction(ZXD) on nonalcoholic fatty liver disease(NAFLD) in vitro and in vivo via the LKB1/AMPK/PGC-1α pathway based on palmitic acid(PA)-induced lipid accumulation model and high-fat diet(HFD)-induced NAFLD model in mice. As revealed by the MTT assay, ZXD had no effect on HepG2 activity, but dose-dependently down-regulated alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver cell medium induced by PA, and decreased the plasma levels of ALT and AST, and total cholesterol(TC) and triglyceride(TG) levels in the liver. Nile red staining showed PA-induced intracellular lipid accumulation, significantly increased lipid accumulation of hepatocytes induced by PA, suggesting that the lipid accumulation model in vitro was properly induced. ZXD could effectively improve the lipid accumulation of hepatocytes induced by PA. Oil red O staining also demonstrated that ZXD improved the lipid accumulation in the liver of HFD mice. JC-1 staining for mitochondrial membrane potential indicated that ZXD effectively reversed the decrease in mitochondrial membrane potential caused by hepatocyte injury induced by PA, activated PGC-1α, and up-regulated the expression of its target genes, such as ACADS, CPT-1α, CPT-1β, UCP-1, ACSL-1, and NRF-1. In addition, as revealed by the Western blot and immunohistochemistry, ZXD up-regulated the protein expression levels of LKB1, p-AMPK, p-ACC, and PGC-1α in vivo and in vitro. In conclusion, ZXD can improve NAFLD and its mechanism may be related to the regulation of the LKB1/AMPK/PGC-1α pathway.
AMP-Activated Protein Kinases/metabolism* ; Alanine Transaminase/metabolism* ; Animals ; Diet, High-Fat ; Liver/metabolism* ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/genetics* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha