OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

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 To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Mitral annular calcification(MAC)is an age-related,chronic,degenerative change in localized fibrous support structures,and current research suggests that it is a process similar to the active onset of atherosclerosis and aortic valve calcification,both of which are accompanied by the deposition of lipoprotein(α)[Lp(α)]and the formation of chronic inflammatory foci.Among them,Lp(α)is the hot spot of research.In recent years,the relationship between Lp(α)and aortic valve calcification has received extensive attention.A large number of studies have demonstrated that elevated Lp(α)and its associated oxidized phospholipids(OxPL)can promote aortic valve calcification and stenosis through multiple calcium-regulated pathways,but the pathophysiological process of MAC is much more complex and unclear,and there has been a preliminary exploration of the relationship between Lp(α)and MAC.To make the current relationship between the two clearer,and thus provide new possibilities for preventing or delaying MAC,the paper will review the three aspects of MAC,Lp(α),and the research progress between the two.

OBJECTIVE: To explore the immunological mechanisms underlying spermatogenetic malfunction in patients with non-obstructive azoospermia (NOA) based on bioinformatics and machine learning, and to screen out the key genes associated with spermatogenesis failure. METHODS: NOA-related datasets were obtained from the GEO database, and the differentially expressed genes identified by differential analysis and weighted gene co-expression network analysis (WGCNA). A model of spermatogenesis scoring was established for analysis of the immunological microenvironment and cell interaction networks related to spermatogenesis failure. The key genes were screened out by machine learning, followed by analysis of their correlation with T cells and macrophages. An NOA mouse model was constructed for validation of transcriptome sequencing. RESULTS: Seventy-five differentially expressed genes were identified for the establishment of the spermatogenesis scoring model. The low spermatogenesis score group showed a higher infiltration of the immune cells, with an increased proportion of T cells and macrophages and a correlation of cell interaction signals with immunity. SOX30, KCTD19, ASRGL1 and DRC7 were identified by machine learning as the key genes related to spermatogenesis, with down-regulated expressions in the NOA group, and their expression levels negatively correlated with the infiltration of T cells and macrophages. The accuracy of the spermatogenesis scoring and machine learning models, as well as the trend of the expression levels of the key genes, was successfully validated with the transcriptome sequencing data on the NOA mouse testis. CONCLUSION The development of NOA is closely associated with enhanced immunological microenvironment in the testis. T cells and macrophages may play important roles in spermatogenesis failure. SOX30, KCTD19, ASRGL1 and DRC7 are potential biomarkers for the diagnosis and treatment of NOA.
Male ; Azoospermia/genetics* ; Machine Learning ; Animals ; Computational Biology ; Mice ; Humans ; Spermatogenesis/genetics* ; Gene Expression Profiling ; Macrophages/immunology* ; Gene Regulatory Networks ; T-Lymphocytes/immunology* ; Transcriptome

Sepsis is a systemic inflammatory syndrome induced by infection and other factors， with the number of patients worldwide exceeding 10 million each year. The pathophysiological mechanism is of this disease complex. Sepsis is often accompanied by endotoxin translocation， gastrointestinal dysfunction， inflammatory cytokine activation， immune dysregulation， coagulation disorder， multiple organ function impairment and many other body imbalances， as well as systemic inflammation， apoptosis， oxidative stress injury and other cell damage mechanisms. This disease causes a heavy medical burden due to the difficult diagnosis and treatment and the poor prognosis. Great progress has been achieved in the diagnosis and treatment of sepsis with traditional Chinese medicine （TCM） and western medicine. The value of western medicine in the diagnosis and treatment of sepsis is limited due to antibiotic resistance， hormone abuse， and high medical costs. Sepsis is classified as a warm disease or typhoid fever in TCM. Da Chengqitang is a classical formula in the Treatise on Typhoid Fever to deal with the excess syndrome of Yang brightness Fu-organ. Modern medicine has proved that Da Chengqitang has the effect of inhibiting oxidative stress， reducing inflammation， and delaying apoptosis by improving gastrointestinal dynamics and regulating intestinal microecology. On the basis of the previous theoretical basis and the rich experience in the medication， medical practitioners have proposed a new therapeutic concept of using Da Chengqitang in combination with western drugs from a holistic view involving both bacteria and toxicity for treating both the symptoms and the root cause， which has a wide range of application. The article reviews the classical research and latest findings of Da Chengqitang in the treatment of sepsis， with a view to clarifying the mechanism and advantages of this formula in the adjuvant treatment of sepsis， exploring its potential efficacy， and providing timely， adequate， and scientific theoretical support for the promotion of this formula in the clinical practice.

To compare the impact of the scrotal vs inguinal orchidopexy approach on the testicular function of infants with cryptorchidism, a randomized controlled trial was conducted involving boys who were 6-12 months old at surgery and were diagnosed with clinically palpable, inguinal undescended testis. Between June 2021 and December 2021, these boys at Fujian Maternity and Child Health Hospital (Fuzhou, China) and Fujian Children's Hospital (Fuzhou, China) were enrolled. Block randomization with a 1:1 allocation ratio was employed. The primary outcome was testicular function assessed by testicular volume, serum testosterone, anti-Müllerian hormone (AMH), and inhibin B (InhB) levels. Secondary outcomes included operative time, amount of intraoperative bleeding, and postoperative complications. Among 577 screened patients, 100 (17.3%) were considered eligible and enrolled in the study. Of the 100 children who completed the 1-year follow-up, 50 underwent scrotal orchidopexy and 50 underwent inguinal orchidopexy. The testicular volume, serum testosterone, AMH, and InhB levels in both groups increased markedly after surgery (all P < 0.05), but there were no apparent differences between groups at 6 months and 12 months after operation (all P > 0.05). No differences between the scrotal and inguinal groups were noted regarding the operative time ( P = 0.987) and amount of intraoperative bleeding ( P = 0.746). The overall complication rate (2.0%) of the scrotal group was slightly lower than that of the inguinal group (8.0%), although this difference was not statistically significant ( P > 0.05). Both scrotal and inguinal orchiopexy exerted protective effects on testicular function in children with cryptorchidism, with similar operative status and postoperative complications. Scrotal orchiopexy is an effective alternative to inguinal orchiopexy in children with cryptorchidism.
Female ; Pregnancy ; Male ; Infant ; Humans ; Child ; Cryptorchidism/surgery* ; Orchiopexy ; Scrotum/surgery* ; Postoperative Complications ; Anti-Mullerian Hormone ; Testosterone

Objective: To examine the association between smoking status and related mortality among elderly people aged 60 and above in urban and rural areas of Beijing City. Methods: Based on Beijing City Elderly Comprehensive Health Cohort Study from 2009 to 2014, a total of 4 499 eligible older adults included in the baseline survey were followed up and investigated to collect information on survival and death. The Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs), and the dose-response relationship was estimated between the smoking index, the years of quitting and mortality. Results: The median (IQR) age of 4 499 subjects was 70.00 (10.00) years old, including 1 814 (40.32%) males. The proportion of non-smokers, former smokers and current smokers was 69.50% (3 127/4 499), 13.20% (594/4 499) and 17.30% (778/4 499), respectively. After adjusting for confounding factors such as demographic and sociological characteristics, lifestyle, etc., the results of multivariate Cox regression analysis showed that, compared to non-smokers, former smokers had a 30.6% increased risk of all-cause mortality [HR (95%CI): 1.306 (1.043-1.636)] and the HR (95%CI) of all-cause, malignant tumor and lung cancer mortality among current smokers has increased by 50.0% [HR (95%CI): 1.500 (1.199-1.877)], 80.3% [HR (95%CI): 1.803 (1.226-2.652)] and 212.6% [HR (95%CI): 3.126 (1.626-6.012)], respectively. The smoking index was positively associated with the increased risk of all-cause, malignant tumor and lung cancer mortality, while the years of smoking cessation were negatively associated with that risk (P<0.05). Conclusion: Smoking is associated with tobacco-related mortality among elderly people in Beijing City.
Aged ; Male ; Humans ; Child ; Female ; Beijing ; Cohort Studies ; Lung Neoplasms ; Smoking ; Tobacco Smoking