Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Objective: To investigate the association between screen time (ST) during leisure time and anxiety-depression symptoms among middle school students, so as to provide a basis for formulating relevant intervention measures. Methods: From November to December 2023, a stratified cluster random sampling method was used to select 2 542 students from junior and senior high school in Taiyuan City. A self designed questionnaire, the Generalized Anxiety Disorder Scale (GAD-7), and the Patient Health Questionnaire (PHQ-9) were used to investigate ST and anxiety/depression symptoms among middle school students. The Logistic regression model was used to explore the association of ST with symptoms of anxiety and depression, as well as with anxiety and depression comorbiditles (CAD). Results: The detection rates of anxiety symptoms, depression symptoms, and CAD were 13.69%, 15.77%, and 10.11%, respectively. The median ST was 2.00 h/d [interquartile range ( IQR =2.38) for weekly averages], with 0.33 h/d ( IQR =1.67) on work days and 5.00 h/d ( IQR=5.50) on rest days. Logistic regression analysis indicated that the total ST of mobile phones during rest days ( OR =1.07, 1.10, 1.11) and the averages ST of mobile phones over a week ( OR = 1.20 , 1.22, 1.29), as well as the total ST of all screen types during rest days ( OR =1.04, 1.04, 1.05) and the averages ST of all screen types over a week ( OR =1.08, 1.09, 1.21) were positively correlated with anxiety symptoms, depression symptoms, and CAD (all P <0.01). Conclusions Among middle school students in Taiyuan City, screen time is positively correlated with symptoms of anxiety or depression and the comorbidity of anxiety and depression, especially smartphone screen time and weekend screen use. Therefore, measures should be implemented to reduce unnecessary screen time among middle school students, especially the use of mobile phones, in order to mitigate the occurrence of anxiety and depression.

Aromatic traditional Chinese medicine(TCM) has played an important role against epidemics and viruses, and volatile components are the main components that exert the pharmacological effects of aromatic TCM. By screening the related monomer components in aromatic TCM against epidemic and viruses and analyzing and endowing TCM with medicinal properties based on its clinical application and pharmacological research according to the theoretical thinking of TCM, the key technical issues of compatibility of TCM monomer components were solved from a theoretical perspective, providing new ideas and methods for screening raw materials and formulas for the development of new TCM drugs. Based on the conditions of antiviral activity, clinical application foundation, definite therapeutic effect, and high safety, a gradient screening of aromatic TCM was carried out. Firstly, 30 aromatic TCM were screened from anti-epidemic literature and clinical trial formulas, and seven volatile monomers were further screened from them. Then, four monomer components with significant effects, namely patchouli alcohol, carvacrol, p-cymene, and eucalyptol were screened. By adopting the "four-step method for a systematic study of TCM properties", the four monomer components were endowed with medicinal properties, and compatibility and combination studies were conducted to explore the theoretical basis of monomer formulas and form monomer formulas guided by TCM theory. The screening results of volatile monomers in aromatic TCM against viral pneumonia included patchouli alcohol, carvacrol, p-cymene, and eucalyptol. The medicinal properties and compatibility theory of volatile monomer components in TCM were explored. Patchouli alcohol was the main herb, with a cool and pungent nature. It entered the lung meridian to dispel evil Qi and has the effects of aromatization, detoxification, and epidemic prevention. Carvacrol was a minister drug with a cool and pungent taste. It had the effects of aromatizing, moistening, and dissolving the exterior, as well as strengthening the spleen and stomach. p-Cymene was an adjunctive medicine with a mild and pungent nature. It entered the lungs and kidneys and had the effects of aromatic purification, cough relief, and asthma relief. Eucalyptol was also an adjunctive medicine with a pungent and warm taste. It had the functions of aromatic purification, cough relief, phlegm reduction, and pain relief. The combination of the four medicines had the effects of aromatizing, moistening, detoxifying, and epidemic prevention, as well as relieving cough and asthma and strengthening the spleen and stomach. They were used to treat viral pneumonia caused by upper respiratory tract viral infections, with symptoms such as chest tightness, cough, wheezing, fatigue, nasal congestion, runny nose, nausea, and vomiting. This study has laid a literature and theoretical foundation for further drug efficacy verification experiments, compatibility efficacy experiments, and subsequent product development and clinical applications, and it serves as an innovative practice that combines literature research, theoretical research, experimental research, and clinical practice to develop new products.
Drugs, Chinese Herbal/therapeutic use* ; Antiviral Agents/pharmacology* ; Humans ; Pneumonia, Viral/virology* ; Medicine, Chinese Traditional ; Volatile Organic Compounds/pharmacology* ; Animals

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

Objective:To analyze the phenotypes and gene mutations of the three families with hereditary protein S (PS) deficiency caused by frameshift heterozygous variants.Methods:Case report and case series study. We investigate three probands and their family members (14 people from three generations) who registrated in Beijing Jishuitan Hospital of Capital Medical University from Feb 1st to 28th, 2025. The clinical data of the three probands and their family members were collected. The related coagulation tests of all members were detected. Protein S activity (PS:A) was determined using coagulation assay, and total protein S antigen (TPS:Ag) and free protein S antigen (FPS:Ag) were measured using ELISA. All exons and their flanking sequences of the probands were amplified using PCR technique, and gene analysis by direct sequencing, and variant genes were searched which were then verified by cloning sequencing, meanwhile, the corresponding variant loci of the family members were analyzed. A calibrated automated thrombin generation (CAT) method was used to study thrombin production. ClustalX-2.1-win software was used to analyze the conservatism of the mutant loci; Mutation Taster and Franklin.genoox online bioinformatics software were used to predict the pathogenicity of the mutant loci; PyMol software was used to analyze the changes in protein spatial structure before and after mutation.Results:The PS:A, TPS:Ag and FPS:Ag of the three probands with hereditary PS deficiency were decreased. Genetic sequencing identified a total of three PROS1 genetic variants, and all the three probands were heterozygous frameshift variants: p.Gln51Argfs*2 in Proband A; p.Met251Valfs*17 in Proband B; and Thr478tyrfs*21 in Proband C. Conservative analysis showed that p.Gln51, p.Met251 and p.Thr478 loci were not conserved among the homologous species; Mutation Taster and Franklin.genoox analysis showed that these variants were pathogenic; protein structure model analysis showed that p.Gln51Argfs*2, p.Met251Valfs*17 and p. Thr478Tyrfs*21 variants may result in altered protein spatial structure.Conclusion:The heterozygous frameshift variations of PS p.Gln51Arg fs*2, p.Met251Valfs*17 and p.Thr478Tyrfs*21 would alter the spatial structure of PS molecules, and reduce their structural stability, leading to PS deficiency.

Objective:To analyze the liver histological characteristics and clinically related factors in inactive hepatitis B surface antigen (HBsAg) carriers (IHC), and also explore whether antiviral treatment is necessary for IHC, as defined in the 2022 version of the hepatitis B prevention and treatment guidelines.Methods:A multicenter, retrospective cohort study was conducted. Two hundred and thirty-one IHC cases who underwent liver biopsy histopathological examination in nine medical institutions, including Beijing Youan Hospital affiliated with Capital Medical University, from January 2018 to December 2023 were included. General informative data, clinical serological markers, and transient elastography (TE) examination results were collected. Patients were divided into a positive (148 cases) and a negative group (83 cases) according to the results of hepatitis B virus (HBV) DNA detection. The differences in liver pathological inflammatory activity (G) and liver fibrosis stage (S) were analyzed between the two groups to explore the correlation between liver tissue conditions and clinically related factors. Comparsions of normally distributed continwous data, skeukd continuous data, and categorical data between groups are performed using t tests, Mann-Whitney U tests and χ2 tests, respectively. Results:The age of 231 IHC cases was 43 (38, 51) years old, with 95.2% (220/231) aged ≥30 years, and males accounted for 64.9% (150/231). HBsAg and HBV DNA levels were 131.9 (20.8, 400.9) IU/mL and 94.0 (0, 448.5) IU/mL, respectively, of which 35.9% (83/231) were HBV DNA negative (<20 IU/mL). The remarkable proportions of G≥2, S≥2, and liver injury (G≥2 and/or S≥2) in liver tissue were 16.5% (38/231), 29% (67/231), and 35.9% (83/231), respectively. The S≥2 proportion was significantly higher in the HBV DNA-negative group than the positive group (42.2% vs. 21.6%, P<0.001), and it mainly occurred in the population cohort over 30 years old (44.9% vs. 31.0%, P=0.04). The liver stiffness measurement (LSM), aspartate transaminase to platelet ratio index (APRI), and platelet (PLT) were significantly higher in the S≥2 group than the S<2 group ( P<0.05). Conclusion:Clinicians can comprehensively evaluate the degree of liver fibrosis in IHC based on clinical factors such as age, PLT, APRI, and LSM, even if the liver histological results are lacking. The China 2022 version guidelines define that nearly half of IHC has histological indications for antiviral therapy, and liver biopsy and prompt treatment can be recommended.

OBJECTIVE To investigate the prevalence of tinnitus and hearing loss in otology patients,and to analyze the characteristics and relationship of tinnitus and hearing loss in different age groups.METHODS A total of 4 716 patients who visited otology clinic were enrolled.Age,gender,and presence or absence of tinnitus were recorded.All patients completed pure tone audiometry.The characteristics and relationship between tinnitus and pure tone audiometry threshold were analyzed after age grouping.RESULTS 1.Among the 4 716 patients,2 772 patients had tinnitus,accounting for 58.78%,and the incidence was highest in the 41-70 years old group.3 521 cases(74.66%)had hearing loss.2.Among the patients with tinnitus,2 227 cases(80.34%)had hearing loss,which was higher than that of patients without tinnitus(66.56%,1 294/1 944 cases).There was a difference in the incidence of hearing loss between those with and without tinnitus in each age group from 11 to 70 years(P<0.05).3.The average hearing threshold of patients with tinnitus was higher than that of patients without tinnitus.There was a difference in the average hearing threshold between patients with and without tinnitus in each age group over 30 years old(P<0.05).4.The incidence of high frequency hearing loss with tinnitus was 24.57%(681/2 772),and the incidence of without tinnitus was 21.66%(421/1 944).The rate of high-frequency hearing loss in the 21-40 years old group with tinnitus was higher than that in the non-tinnitus group(P<0.05).CONCLUSION The incidence of hearing loss is higher and more severe in patients with tinnitus.Particular attention should be paid to tinnitus in young patients.The incidence of high-frequency hearing loss was higher in the young and middle-aged group of patients with tinnitus.Therefore,the evaluation of hearing threshold in patients with tinnitus is very important,which can provide a basis for clinical diagnosis and treatment.