Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study.

OBJECTIVE: Several observational studies have revealed a potential relationship between menstrual reproductive factors (MRF) and osteoarthritis (OA). However, the precise causal relationship remains elusive. This study performed Mendelian randomization (MR) to provide deeper insights into this relationship. METHODS: Utilizing summary statistics of genome-wide association studies (GWAS), we conducted univariate MR to estimate 2 menstrual factors (Age at menarche, AAM; Age at menopause, AMP) and 5 reproductive factors (Age at first live birth, AFB; Age at last live birth, ALB; Number of live births, NLB; Age first had sexual intercourse, AFSI; Age started oral contraceptive pill, ASOC) on OA (overall OA, OOA; knee OA, KOA and hip OA, HOA). The sample size of MRF ranged from 123846 to 406457, and the OA sample size range from 393873 to 484598. Inverse variance weighted (IVW) method was used as the primary MR analysis methods, and MR Egger, weighted median was performed as supplements. Sensitivity analysis was employed to test for heterogeneity and horizontal pleiotropy. Finally, multivariable MR was utilized to adjust for the influence of BMI on OA. RESULTS: After conducting multiple tests (P<0.0023) and adjusting for BMI, MR analysis indicated that a lower AFB will increase the risk of OOA (odds ratio [OR] = 0.97, 95% confidence interval [CI]: 0.95-0.99, P = 3.39×10-4) and KOA (OR = 0.60, 95% CI: 0.47-0.78, P = 1.07×10-4). ALB (OR = 0.61, 95% CI: 0.45-0.84, P = 2.06×10-3) and Age AFSI (OR = 0.66, 95% CI: 0.53-0.82, P = 2.42×10-4) were negatively associated with KOA. In addition, our results showed that earlier AMP adversely affected HOA (OR = 1.12, 95% CI: 1.01-1.23, P = 0.033), and earlier ASOC promote the development of OOA (OR = 0.97, 95% CI: 0.95-1.00, P = 0.032) and KOA (OR = 0.58, 95% CI: 0.40-0.84, P = 4.49×10-3). ALB (OR = 0.98, 95% CI: 0.96-1.00, P = 0.030) and AFSI (OR = 0.98, 95% CI: 0.97-0.99, P = 2.66×10-3) also showed a negative association with OOA but they all did not pass multiple tests. The effects of AAM and NLB on OA were insignificant after BMI correction. CONCLUSION: This research Certificates that Early AFB promotes the development of OOA, meanwhile early AFB, ALB, and AFSI are also risk factors of KOA. Reproductive factors, especially those related to birth, may have the greatest impact on KOA. It provides guidance for promoting women's appropriate age fertility and strengthening perinatal care.

Molecular mechanisms of Tetrastigma hemsleyanum Diels&Gilg against lung squamous cell carcinoma: From computational biology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum （T. hemsleyanum）, valued in traditional medicine for its potential to boost immunity and combat tumors, contains uncharacterized active compounds and mechanisms. This represents a significant gap in our understanding of its ethnopharmacological relevance. AIM OF THE STUDY: To involve the mechanism of anti-lung cancer effect of T. hemsleyanum by means of experiment and bioinformatics analysis. MATERIALS AND METHODS: The anticancer mechanism of T. hemsleyanum against lung squamous carcinoma (LUSC) in zebrafish was investigated. The LUSC model was established by injecting NCI-H2170 cells in the zebrafish and evaluating its anti-tumor efficacy. Next, component targets and key genes were obtained by molecular complex detection (MCODE) analysis and protein-protein interaction (PPI) network analysis. Component analysis of T. hemsleyanum was performed by UPLC-Q-TOF-MS. Molecular docking was used to simulate the binding activities of key potential active components to core targets were simulated using. Prognostic and pan-cancer analyses were then performed to validate the signaling pathways involved in the prognostic genes using gene set enrichment analysis (GSEA). Subsequently, Molecular dynamics simulations were then performed for key active components and core targets. Finally, cellular experiments were used to verify the expression of glutamate metabotropic receptor 3 (GRM3) and glutamate metabotropic receptor 7 (GRM7) in the anticancer effect exerted of T. hemsleyanum. RESULTS: We experimentally confirmed the inhibitory effect of T. hemsleyanum on LUSC by transplantation of NCI-H2170 cells into zebrafish. There are 20 main compounds in T. hemsleyanum, such as procyanidin B1, catechin, quercetin, and kaempferol, etc. A total of 186 component targets of T. hemsleyanum and sixteen hub genes were screened by PPI network and MCODE analyses. Molecular docking and molecular dynamics simulation results showed that Gingerglycolipid B and Rutin had higher affinity with GRM3 and GRM7, respectively. Prognostic analysis, Pan-cancer analysis and verification experiment also confirmed that GRM3 and GRM7 were targets for T. hemsleyanum to exert anti-tumor effects and to participate in immune and mutation processes. In vitro experiments suggested that the inhibitory effect of T. hemsleyanum on cancer cells was correlated with GRM3 and GRM7. CONCLUSION: In vivo, in vitro and in silico results confirmed the potential anticancer effects against LUSC of T. hemsleyanum, which further consolidated the claim of its traditional uses.

Mechanical force induced luminescence ratiometric thermometry in CaZnOS:Dy3.

The 4I15/2-6H15/2 and 4F9/2-6H15/2 transitions of Dy3+ are usually used for luminescent ratiometric thermometry in the form of photoluminescence. However, here we demonstrate the possibility of using this pair of lines for luminescent ratiometric thermometry in the model of mechanoluminescence (ML) in CaZnOS:Dy3+. Upon stimulation of an external mechanical force rather than light, CaZnOS:Dy3+ emits bright yellow luminescence. The intensity ratio of 4I15/2-6H15/2 to 4F9/2-6H15/2 transitions of Dy3+ is found to increase gradually with the rise of temperature, which makes Dy3+ a qualified temperature indicator. Our work enriches the family of optical thermometry.

Treatment of Parkinson disease by acupuncture combined with medicine based on syndrome differentiation from the perspective of modern medicine: A review.

As a multifactorial degenerative disease, Parkinson disease (PD) causes tremor, gait rigidity, and hypokinesia, which interfere with normal life. Because the disease is usually discovered in the late stage of complete degeneration of neurons, it can greatly delay treatment and even eventually lead to death. Therefore, the diagnosis of this disease is very challenging, and it is gratifying that substantial progress has been made in the development of optical coherence tomography (OCT) as a diagnostic biomarker for this disease, and genetic and imaging tests have become part of routine protocols in clinical practice. In the cognition of traditional Chinese medicine (TCM), this disease belongs to deficiency in origin and excess in superficiality, which is always caused by deficiency of liver and kidney, deficiency of qi and blood, and is closely related to wind, fire, phlegm and blood stasis. A large number of studies have shown that TCM can effectively treat motor and non-motor symptoms of PD, combat oxidative stress and reduce inflammatory response, and improve the quality of life of patients. Based on the pathophysiological mechanism of PD, this paper discusses the treatment of PD by TCM acupuncture combined with medicine based on syndrome differentiation.

Mechanically induced photons from ultraviolet-C to near-infrared in Tm3+-doped MgF2.

Mechanoluminescence (ML) plays a vital role in various fields, and has gained increasing popularity over the past two decades. The widely studied materials that are capable of generating ML can be classified into two groups, self-powered and trap-controlled. Here, we demonstrate that both self-powered ML and trap-controlled ML can be achieved simultaneously in MgF2:Tm3+. Upon stimulation of external force, the 1I6→3H6 and 3H4→3H6 transitions of Tm3+ are observed, ranging from the ultraviolet-C to near-infrared. After exposure to X-rays, MgF2:Tm3+ presents a stronger ML than the uncharged sample. After cleaning up at high temperatures, the ML returns to the initial level, which is a typical characteristic of trap-controlled ML. In the end, we demonstrate the potential applications of MgF2:Tm3+ in dynamic anti-counterfeiting, and structure inspection.

Mechanism of new optimized Sheng-Mai-San Formula to regulate cardiomyocyte apoptosis through NMDAR pathway.

Background and objectives: Ischemic heart failure (HF) has become a disease that seriously endangers people's life and health. As a herbal formula widely used in clinical practice, new optimized Sheng-Mai-San (NO-SMS) has been shown to be significantly effective in improving cardiac function, increasing exercise tolerance, and slowing the progression of myocardial fibrosis in heart failure patients in multi-center clinical studies in various regions of China. In our previous pharmacodynamic and toxicological studies, we found that a medium-dose formulation (8.1 g of raw drug/kg) was the most effective in the treatment of heart failure, but its mechanism of action is still being investigated. The present study is exploring its relationship with cardiomyocyte apoptosis. Materials and methods: We investigated and verified this through two parts of experiments, in vivo and in vitro. Firstly, we prepared male SD rats with heart failure models by ligating the left anterior descending branch of the coronary artery (EF ≤ 50%), which were treated with NO-SMS Formula (8.1 g of raw drug/kg/d), Ifenprodil (5.4 mg/kg/d) or Enalapril (0.9 mg/kg/d) prepared suspensions by gavage for 4 weeks. The cardiac and structural changes were evaluated by echocardiography, H&E, and MASSON staining. The apoptosis of cardiomyocytes in each group was detected by Western blot, qRT-PCR, and ELISA. In vitro cell experiments include H9c2 cardiomyocyte injury induced by H2O2 and NMDA respectively, and the groups were incubated with NO-SMS and Ifenprodil-containing serum for 24 h. Apoptosis was detected by Annexin V-FITC/PI double-staining method, and the rest of the assays were consistent with the in vivo experiments. Results: Compared with the model group, the NO-SMS formula group and the Ifenprodil group could significantly improve cardiac function, delay myocardial fibrosis, reduce the expression of pro-apoptotic proteins, mRNA, and the concentration levels of Ca2+ and ROS in heart failure rats and H9c2 cardiomyocytes with H2O2 and NMDA-induced injury, which could significantly reduce the apoptosis rate of damaged cardiomyocytes and effectively inhibit the apoptosis of cardiomyocytes. Conclusion: NO-SMS Formula improved cardiac function, inhibited ventricular remodeling and cardiomyocyte apoptosis in HF rats, and its mechanism may be related to the regulation of the NMDAR signaling pathway, inhibition of large intracellular Ca2+ inward flow, and ROS production in cardiomyocytes.

Effects of electroacupuncture therapy on intractable facial paralysis: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to assessment effects of electroacupuncture (EA) therapy on intractable facial paralysis. METHODS: The articles of EA treatment for intractable facial paralysis were retrieved from seven databases, the publication period was from its inception to November 30, 2022. Primary measure was the total effective rate, and other measures included the cure rate, Portmann scores, House-Brackmann scores, Sunnybrook scores and adverse events. The effect size of meta-analysis was expressed using relative risk (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: A total of 18 studies with 1,119 participants were included, all of them had various aspects of bias risk. Meta-analysis results revealed that EA ways improved total effective rate more effectively compared with non-EA counterparts (RR 1.23, 95% CI 1.17-1.31, I2 = 0%, 18 studies, 1119 participants), and improved cure rate more significantly than non-EA groups (RR 2.04, 95% CI 1.70-2.44, I2 = 0%, 18 studies, 1119 participants). None of studies reported adverse events. CONCLUSION: EA therapy is more beneficial for patients with intractable facial paralysis than non-EA, but we lack sufficient evidence to evaluate its safety and follow-up effect. Therefore, more clinical trials with high quality methodologies are needed to further verify long-term effects of EA for IFP and improve the level of evidence. TRIAL REGISTRATION: Registration number: CRD42021278541.

Effect of optimized new Shengmai powder on exercise tolerance in rats with heart failure by regulating the ubiquitin-proteasome signaling pathway.

Introduction: Decreased exercise tolerance is a common symptom in patients with heart failure, which is closely related to protein degradation and apoptosis regulated by the ubiquitin-proteasome signaling (UPS) pathway. In this study, the effect of Chinese medicine, optimized new Shengmai powder, on exercise tolerance in rats with heart failure was investigated via the UPS pathway. Methods: The heart failure model was prepared by ligating the left anterior descending branch of the coronary artery in rats, in which the sham-operated group was only threaded and not ligated. Rats (left ventricular ejection fraction ≤ 45%) were randomly divided into the following groups: model group, YHXSMS group, Benazepril group, and proteasome inhibitor Oprozomib group, and they were administered the corresponding drugs by gavage for 4 weeks. The cardiac function of rats was evaluated by performing an echocardiography examination and a hemodynamic test and the exercise tolerance was done by conducting an exhaustive swimming test. The mechanism was revealed by TUNEL detection, immunohistochemistry, immunofluorescence analysis, Western blot, and quantitative real-time PCR. Results: The study showed that there was a decrease in cardiac function and exercise tolerance of rats in the model group and also destruction of cardiac and skeletal muscle fibers, a proliferation of collagen tissue, and an increment of apoptosis. Our study suggested that optimized new Shengmai powder could exert antiapoptotic effects on myocardial and skeletal muscle cells and improve myocardial contractility and exercise tolerance by inhibiting the overactivation of the UPS pathway, downregulating MAFbx, and Murf-1 overexpression, inhibiting the activation of the JNK signaling pathway, upregulating bcl-2 expression, and decreasing bax and caspase-3 levels. Conclusions: The study showed that the optimized new Shengmai powder could improve cardiac function and exercise tolerance in rats with heart failure through the UPS pathway.

[Professor SUN Shen-tian's experience in acupuncture treatment of depression based on "psychosomatic medicine"].

This paper introduces professor SUN Shen-tian's clinical thoughts and his characteristics of acupuncture techniques for the treatment of depression based on "psychosomatic medicine". Professor SUN, the master of traditional Chinese medicine, believes that depression refers to comorbidity of "heart mind" and "body", resulting from the "body-mind" disharmony, specially dominated by the emotional disorder. This disease is located in the brain, with the injury of mind and closely related to the heart and liver dysfunction. In pathogenesis, the dysfunction of brain mind and the unhealthy conditions of body and mind are involved. The treatment should focus on "regulating the mind, improving the intelligence, co-modulating the abdominal and brain functions and treating the physical and mental disorders". Baihui (GV 20), Ningshen (Extra) and emotional area on the head are selected as the main points to benefit the intelligence and calming down the mind; the abdominal region 1 and region 8 of "Sun's abdominal acupuncture" are used as the main points of the abdomen to regulate the brain functions. The point prescription is modified according to the symptoms and etiologies. The repeated transcranial acupuncture stimulation and electroacupuncture at low frequency (2 Hz) are crucial to the therapeutic effect. Reliving anxious emotions is specially considered before acupuncture, and the mind is protected and deqi is consolidated during acupuncture.

[Advances in N-methyl-D-aspartate Receptor Signaling Pathway and Mechanism of the Pathway-mediated Apoptosis].

N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.

[Value of ultrasound shear wave elasticity imaging in diagnosis of Hashimoto's thyroiditis].

OBJECTIVE: To investigate the correlation between Young's modulus of the thyroid tissue measured by in shear wave elastography (SWE) and the clinical manifestations of Hashimoto's thyroiditis in different stages. METHODS: A total of 104 patients with the clinical diagnosis of Hashimoto's thyroiditis were enrolled in this study, including 26 with hyperthyroidism, 29 with normal thyroid function, 27 with subclinical hypothyroidism, 22 with clinical hypothyroidism, with 50 healthy volunteers serving as the healthy control group. All the subjects underwent SWE to obtain the Young's modulus value of the thyroid tissue. Univariate analysis of variance was used to compare the Young's modulus among the groups, and Pearson correlation analysis was used to analyze the correlation between the Young's modulus of the thyroid tissue and serum levels of thyroid microsomal antibody (TMAb) and thyroid globulin antibody (TGAb). RESULTS: In the 4 groups of patients, the Young's modulus increased significantly in the order of hyperthyroidism group, normal thyroid function group, subclinical hypothyroidism group and clinical hypothyroidism group (F=60.983, P<0.01). The Young's modulus was significantly lower in hyperthyroidism group than in the other 3 groups (P<0.05), and was significantly lower in normal thyroid function group than in subclinical hypothyroidism group and clinical hypothyroidism group (P<0.05). CONCLUSION: The Young's modulus of the thyroid tissue measured by shear wave elastography is related with the clinical manifestations of Hashimoto's thyroiditis in different stages, but the relevance needs to be further confirmed by multi-center, randomized, controlled studies involving a larger sample size.

Isolation of Clostridium perfringens type A from wild bharals (Pseudois nayaur) following sudden death in Tibet, China.

Dozens of wild bharals died suddenly in Tibet. Necropsy showed severe congestion and hemorrhage in multiple organs, with large numbers of Gram-positive bacilli. Strains of Clostridium perfringens type A were isolated from the different organs and the intestinal contents. The other possible pathogens were ruled out by PCR.