This study aimed to investigate the effect and mechanism of Buyang Huanwu Decoction in regulating endoplasmic reticulum stress via the inositol-requiring enzyme 1α(IRE1α)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway to improve neurological function in rats with cerebral ischemia/reperfusion injury(CIRI). SPF-grade male sprague-dawley(SD) rats were randomly divided into Sham group, model group, Buyang Huanwu Decoction group, and edaravone group. Except for the Sham group, the other groups were subjected to the modified suture method to establish a middle cerebral artery occlusion/reperfusion(MCAO/R) model. After treatment, neurological function was assessed using the Zea Longa scoring system. Gait analysis was used to detect the motor function. Detection of relative infarct area in brain tissue using 2,3,5-triphenyltetrazolium chloride(TTC) staining. Nissl staining was used to observe the structure of neuronal cells. Western blot and real-time fluorescence quantitative PCR(RT-qPCR) were used to detect IRE1α, ASK1, JNK, B cell lymphoma-2(Bcl-2), Bcl-2 related X protein(Bax), and Caspase-3 in the brain tissue. Immunohistochemistry was used to detect the positive expression of IRE1α, ASK1, and JNK. Immunofluorescence was used to detect the fluorescence expression levels of Bax, Bcl-2, and Caspase-3. The results showed that compared with the Sham group, the model group exhibited increased neurological scores(P<0.01), increased ratio of ground contact area and strength in both forelimbs(P<0.01), enlarged relative infarct area of brain tissue(P<0.05), and a reduced number of Nissl staining-positive cells(P<0.01). The protein and mRNA expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 in brain tissue were significantly elevated, while those of Bcl-2 were decreased(P<0.05). Compared with the model group, both the Buyang Huanwu Decoction group and edaravone group showed reduced neurological scores(P<0.05), decreased ratio of ground contact area and strength in both forelimbs(P<0.05), smaller relative infarct area(P<0.05), alleviated neuronal damage, and increased number of Nissl staining-positive cells(P<0.05). The expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 protein and mRNA in brain tissue were significantly reduced, while those of Bcl-2 were significantly increased(P<0.05). The results indicated that Buyang Huanwu Decoction can effectively improve brain injury in CIRI rats, and its mechanism of action may be related to regulating the endoplasmic reticulum stress IRE1α/ASK1/JNK signaling pathway.
Animals ; Male ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; MAP Kinase Kinase Kinase 5/genetics* ; Ischemic Stroke/physiopathology* ; Humans ; MAP Kinase Signaling System/drug effects* ; Apoptosis/drug effects* ; Endoribonucleases/genetics* ; JNK Mitogen-Activated Protein Kinases/genetics* ; Endoplasmic Reticulum Stress/drug effects* ; Multienzyme Complexes

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

AIM To compare the in vivo pharmacokinetics of paeoniflorin,paeoniflorin,liquiritin,isoliquiritin,liquiritigenin and glycyrrhizic acid from Shaoyao Gancao Decoction in normal and gastric ulcer rats.METHODS Six rats were randomly assigned into two groups,after which the 75%ethanol-induced gastric ulcer model was established,the gastric tissues were collected.Twelve rats were randomly assigned into two groups and given intragastric administration(9.9 g/kg),after which blood collection was made at different time points,UPLC-MS/MS method was adopted in the determination of plasma concentrations,and main pharmacokinetic parameters were calculated.RESULTS Prolonged Tmax(P＜0.05,P＜0.01)of various active constituents,prolonged T1/2,MRT0-t(P＜0.05,P＜0.01),increased Cmax,AUC(P＜0.05,P＜0.01)and decreased Vd/F,CL/F(P＜0.05,P＜0.01)of paeoniflorin,increased Cmax,AUC(P＜0.05,P＜0.01)and decreased CL/F(P＜0.05)of albiflorin,prolonged MRT(P＜0.05),increased AUC(P＜0.05)and decreased CL/F(P＜0.01)of liquiritin,prolonged MRT(P＜0.05,P＜0.01)and decreased Vd/F(P＜0.05)of isoliquiritin,no obviously changed pharmacokinetic parameters(except for Tmax)of liquiritigenin(P＞0.05),and prolonged T1/2,MRT0-∞(P＜0.05,P＜0.01),increased Cmax,AUC(P＜0.05,P＜0.01)and decreased CL/F(P＜0.01)of glycyrrhizic acid were observable in the model group as compared with those in the normal group.CONCLUSION Gastric ulcer exhibits certain influences on the velocities and degrees of in vivo absorption and metabolism of active constituents from Shaoyao Gancao Decoction.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVE: To evaluate the clinical efficacy and safety of Wuziyuye Decoction in the treatment of type-II diabetes mellitus (DM) with qi-yin deficiency complicated by asthenospermia. METHODS: We selected 100 cases of type-II DM with qi-yin deficiency complicated by asthenospermia treated in the First Hospital Affiliated to Ningbo University from January 2023 to March 2024, and randomly assigned them to receive Wuziyuye Decoction (the trial group, n = 50) and oral L-carnitine solution (the control group, n = 50) in addition to Western medicine to reduce fasting blood glucose to normal in both groups. After 12 weeks of medication, we followed up the patients for 24 weeks, obtained their semen parameters, traditional Chinese medicine (TCM) syndrome scores and levels of reproductive hormones, and the clinical pregnancy outcomes of their partners, followed by comparison of the data collected between the two groups before and after treatment. RESULTS: After 12 weeks of treatment, the trial group showed significant improvement over the baseline in the percentage of progressive motility (PR%) (［35.5±6.1］% vs ［18.0±4.2］%, P<0.05), sperm concentration (［54.0±33.4］ vs ［40.0±36.1］ × 10⁶/ml, P<0.05), and TCM syndrome score (4.5±2.3 vs 18.5±5.2, P<0.05), but no statistically significant difference in the semen volume (［2.85±0.36］ vs ［2.84±0.59］ ml, P>0.05), while the controls exhibited markedly improved percentage of PR% (［29.5±6.2］% vs ［18.5±4.5］%, P<0.05) and sperm concentration (［45.0±34.1］ vs ［42.0±38.3］ × 10⁶/ml, P<0.05), but no statistically significant difference in the semen volume (［3.04±0.89］ vs ［2.90±0.78］ ml, P>0.05) and TCM syndrome score (17.2±4.5 vs 17.8±4.8, P>0.05). The patients treated with Wuziyuye Decoction achieved even more significant improvement than the controls in the percentage of PR%, sperm concentration and TCM syndrome score (P<0.05), but there were no statistically significant differences in the reproductive hormone levels and clinical pregnancy outcomes between the two groups of patients after treatment (P>0.05). And no severe adverse reactions were observed in either group. CONCLUSION Wuziyuye Decoction is safe and effective for the treatment of type-II DM with qi-yin deficiency complicated by asthenospermia by improving the sperm motility and concentration of the patient.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Asthenozoospermia/complications* ; Diabetes Mellitus, Type 2/drug therapy* ; Yin Deficiency/complications* ; Adult ; Medicine, Chinese Traditional ; Sperm Motility ; Qi ; Female ; Pregnancy

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

In recent years, the rapid increase in cancer treatment costs in China had brought a huge economic burden to society, and it was urgent to standardize the rational application of anti-tumor drugs. In the context of the reform of group payment related to disease diagnosis, a tertiary first-class hospital focused on the needs of patients and guided by value-based healthcare, established a professional and normalized refined anti-tumor drug management system, setted up a multidisciplinary diagnosis and treatment team, and promoted " Internet plus pharmaceutical services" in December 2018.From 2019 to 2021, the proportion of hospital drugs were 30.8%, 30.1%, and 27.3%, respectively. The amount of money spent on anti-tumor drugs were 83.25 million yuan, 76.41 million yuan, and 62.48 million yuan, respectively, showing a decreasing trend year by year. The practice of refined management of anti-tumor drugs fully reflected the core concept of value based healthcare, achieving closed-loop management of the entire process of drugs, improving the level of rational drug use, reducing the economic burden on patients, and providing reference for improving the level of rational use of anti-tumor drugs in public hospitals.

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O₂) or hypoxia condition (1%O₂). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×10⁶/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×10⁶/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD₃₁], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD₃₁ showed that, the expressions of VEGFA and CD₃₁ in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD₃₁ in BMSC-exo group and CD₃₁ in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD₃₁ in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.
Rats ; Female ; Humans ; Animals ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/metabolism* ; Vascular Endothelial Growth Factor A ; Exosomes/metabolism* ; Uterine Diseases/therapy* ; Collagen ; Hypoxia/therapy* ; Fibrosis ; Mesenchymal Stem Cells/metabolism* ; Oxygen

Aim To investigate the effect of methionine restriction on the proliferation, migration and invasion of human oral squamous carcinoma CAL-27 cells. Methods Cell proliferation and colony formation ability were detected by cell counting and colony forming assay. The changes in cell cycle and apoptosis were detected by propidium iodide (PI) staining flow cytometry and Annexin V/7-amino-actinomycin staining flow cytometry. The migration and invasion ability of CAL-27 was detected by scratch and Transwell assay. The expression levels of apoptosis proteins Bax and Bcl-2, cyclins CDK2 and CDK4 and migration and invasion proteins N-cadherin and E-cadherin were examined by Western blot. Results Methionine restriction significantly inhibited the proliferation and clone formation of oral squamous cancer cell CAL-27 (P < 0. 01), induced cell cycle arrest at G