Objective: To systematically evaluate the relationship of exposure to five heavy metals, namely lead, arsenic, cadmium, mercury and aluminum with obesity in children and adolescents, so as to provide a scientific basis for subsequent research in the area. Methods: Four Chinese databasesc (CBM, VIP, CNKI and Wanfang) and four foreign databases (OVID, PubMed, Web of Science and EBSCO), were searched to collect relevant studies, and the search period was from the establishment of the database to May 5, 2024. After 2 investigators independently screened the literature, extracted the data and evaluated the risk of bias of the included studies, the results were analyzed quantitatively and summarized qualitatively. Results: A total of 5 cohort studies on lead exposure and 17 cross sectional studies involving exposure to lead ( n =13), cadmium ( n =8), mercury ( n =8), arsenic ( n =4), and aluminum ( n =1) were included. Meta analysis of the 2 cohort studies showed that lead exposure was not associated with the risk of overweight and obesity in children ( RR=0.76, 95%CI=0.50-1.16, P ＞0.05). The cross sectional study Meta-analysis results showed that lead exposure was negatively associated with the risk of childhood overweight ( OR=0.70, 95%CI =0.59-0.84, 2 studies) and obesity ( OR=0.71, 95%CI =0.58-0.87, 3 studies); cadmium exposure was negatively associated with the risk of childhood overweight ( OR=0.83, 95%CI =0.73-0.95, 2 studies) and obesity risk( OR=0.70, 95%CI =0.63-0.78, 3 studies); mercury exposure increased the risk of overweight/obesity ( OR=1.42, 95%CI =1.14-1.76, 2 studies) and abdominal obesity ( OR= 1.99, 95%CI =1.45-2.73, 2 studies) in children; the group with the highest concentration of arsenic in urine had a lower risk of developing obesity compared to the group with the lowest concentration ( OR=0.39, 95%CI =0.23-0.65, 1 study), and the group with the highest concentration of aluminum in urine had a lower risk of obesity compared with the group with the lowest concentration ( OR=0.52, 95%CI =0.31-0.86, 1 study)(all P <0.05). Conclusion Heavy metal exposure may be a risk factor for overweight and obesity in children and adolescents, but the conclusions are inconsistent and need to be validated in further high quality prospective cohort studies.

The interactions between microorganisms and medicinal plants are crucial to the quality improvement of medicinal plants. Medicinal plants attract microorganisms to colonize by secreting specific compounds and provide niche and nutrient support for these microorganisms, with a symbiotic network formed. These microorganisms grow in the rhizosphere, phyllosphere, and endophytic tissues of plants and significantly improve the growth performance and medicinal component accumulation of medicinal plants by promoting nutrient uptake, enhancing disease resistance, and regulating the synthesis of secondary metabolites. Microorganisms are also widely used in the ecological planting of medicinal plants, and the growth conditions of medicinal plants are optimized by simulating the microbial effects in the natural environment. The interactions between microorganisms and medicinal plants not only significantly improve the yield and quality of medicinal plants but also enhance their geoherbalism, which is in line with the concept of green agriculture and eco-friendly development. This study reviewed the research results on the interactions between medicinal plants and microorganisms in recent years and focused on the analysis of the great potential of microorganisms in optimizing the growth environment of medicinal plants, regulating the accumulation of secondary metabolites, inducing systemic resistance, and promoting the ecological planting of medicinal plants. It provides a scientific basis for the research on the interactions between medicinal plants and microorganisms, the research and development of microbial agents, and the application of microorganisms in the ecological planting of medicinal plants and is of great significance for the quality improvement of medicinal plants and the green and sustainable development of TCM resources.
Plants, Medicinal/metabolism* ; Bacteria/genetics* ; Symbiosis

OBJECTIVE: To compare the clinical efficacy of unilateral biportal endoscopic discectomy(UBE) and percutaneous interlaminar endoscopic discectomy(PIED) in the treatment of highly migrated lumbar disc herniation (LDH). METHODS: A retrospective analysis was conducted on 43 patients with highly migrated LDH who underwent spinal endoscopic surgery between January 2022 and December 2023. In the UBE group 22 patients included 8 males and 14 females, aged 49 to 59 years old with a mean of (54.13±2.07) years old. In the PIED group 21 patients included 11 males and 10 females, aged 49 to 59 years old with a mean of (55.04±2.80) years old. Perioperative parameters including intraoperative blood loss, operative time, and fluoroscopic exposures were compared between groups. Clinical outcomes were assessed using the visual analogue scale (VAS) for pain, Oswestry disability index (ODI), and modified MacNab criteria. Complications during the perioperative period and follow-up were recorded. RESULTS: In the PIED group, there were 3 cases of nerve injury, 1 case of residual nucleus pulposus, and 1 case of dural injury. In the UBE group, there was 1 case of nerve injury and 1 case of cerebrospinal fluid leakage. No infections or major bleeding occurred in either group. All patients completed surgery and were followed up for at least 12 months. The UBE group had significantly more intraoperative blood loss (39.09±6.10) ml and more fluoroscopic exposures (6.45±0.26) than the PIED group (34.05±5.62) ml and (3.24±0.28) with significant difference (P<0.05). Preoperative VAS and ODI showed no significant differences between two groups (P>0.05). Both groups demonstrated significant improvements in VAS and ODI postoperatively (P<0.001). At the 3rd days postoperatively, the UBE group had a significantly lower leg pain VAS (2.27±0.20) than the PIED gruop(2.95±0.24) with significant difference (P<0.05), but no significant differences were observed at the first or 12th months (P>0.05). No significant differences in ODI were found between two groups during follow-up (P>0.05). At the 1st month postoperatively, according to modified MacNab criteria, 15 patients got excellent results, 4 good, and 2 fair in PIED group;and 18 patients got excellent results, 2 good, and 2 fair in UBE group, with no significant difference between two groups(P>0.05). CONCLUSION Both PIED and UBE are effective surgical methods for treating highly migrated LDH. Compared with PIED, UBE involves slightly longer operative time, more blood loss, and more fluoroscopic exposures, but carries a lower risk of nerve injury.
Humans ; Male ; Female ; Middle Aged ; Intervertebral Disc Displacement/surgery* ; Endoscopy/methods* ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Diskectomy, Percutaneous/methods* ; Treatment Outcome

The adverse effects of obesity on male reproductive function are mainly manifested as the abnormal development of the reproductive system, decrease of testosterone level, decline of sperm quality, and impact on the health of offspring, while its regulatory mechanism is far from being clarified. This paper expounds the influence of obesity on the male reproductive system in the aspects of population epidemiology and animal experiments, presents an overview on the action mechanisms of obesity from the perspectives of the hypothalamus-pituitary-testis axis, blood-testis barrier, inflammatory reaction, oxidative stress, testicular germ cell apoptosis, and impact of paternal obesity on the health of offspring, aiming to shed some light on the clinical treatment and prevention of obesity-related male reproductive dysfunction.
Male ; Obesity/physiopathology* ; Humans ; Animals ; Hypothalamo-Hypophyseal System ; Testis/physiopathology* ; Oxidative Stress ; Infertility, Male/etiology* ; Reproduction ; Blood-Testis Barrier

OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics. Our endeavor involved the implementation of a bioisosterism strategy, leading to the discovery of an assemblage of halogen-containing biphenyl-diarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Notably, compound A12 demonstrated exceptional efficacy against both WT HIV-1 (EC₅₀ = 1.9 nmol/L) and seven mutant strains (EC₅₀ = 1.7-157 nmol/L), surpassing that of the lead compound 6 and comparable to etravirine. Furthermore, this analog exhibited minimal adverse effects with significantly reduced cytotoxicity (CC₅₀ = 195 μmol/L) and a high selectivity index (SI = 102,608), superior to those of etravirine (CC₅₀ > 4.6 μmol/L, SI > 1436) and rilpivirine (CC₅₀ = 3.98 μmol/L, SI = 3989). It displayed low inhibition of CYP (IC₅₀ = 6.99-25 μmol/L) and hERG (IC₅₀ > 40 μmol/L), indicating a safer profile compared to etravirine and rilpivirine. No acute toxicity or organ pathological damage was observed at a single dose of 2 g/kg. Additionally, A12 exhibited favorable oral bioavailability (F = 29.2%) and an extended elimination half-life (T _1/2 = 13.56 h), enabling convenient oral administration at minimal doses. These findings indicated that A12 could serve as a promising drug candidate for HIV treatment.

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

ObjectiveThe traditional Chinese medicine Strychnos nux-vomica L. (SN) has the clinical effect of reducing swelling and relieving pain; however, SN is toxic due to its alkaloid components. Little is known about the endogenous metabolic changes induced by SN toxicity in rats and their potential effects on the metabolic dysregulation of intestinal microbiota. Therefore, toxicological investigation of SN is of great significance to its safety assessment. In this study, the toxic mechanisms of SN were explored using a combination of metabonomics and 16S rRNA gene sequencing. MethodsThe toxic dose, intensity, and target organ of SN were determined in rats using acute, cumulative, and subacute toxicity tests. UHPLC-MS was used to analyze the serum, liver, and renal samples of rats after intragastric SN administration. The decision tree and K Nearest Neighbor (KNN) model were established based on the bootstrap aggregation (bagging) algorithm to classify the omics data. After samples were extracted from rat feces, the high-throughput sequencing platform was used to analyze the 16S rRNA V3-V4 region of bacteria. ResultsThe bagging algorithm improved the accuracy of sample classification. Twelve biomarkers were identified, where their metabolic dysregulation may be responsible for SN toxicity in vivo. Several types of bacteria such as Bacteroidetes, Anaerostipes, Oscillospira and Bilophila, were demonstrated to be closely related to physiological indices of renal and liver function, indicating that SN-induced liver and kidney damage may be related to the disturbance of these intestinal bacteria. ConclusionThe toxicity mechanism of SN was revealed in vivo, which provides a scientific basis for the safe and rational clinical use of SN.