Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

OBJECTIVE: To explore the application effect of self-developed anatomical main nail insertion guide in proximal femoral nail antirotation (PFNA) internal fixation for the treatment of intertrochanteric fractures (IFF) in elderly patients. METHODS: A retrospective analysis was performed on 62 patients with AO31-A2 intertrochanteric fractures who underwent PFNA surgery and met the inclusion criteria from January 2022 to December 2024. They were divided into the conventional PFNA insertion group (conventional operation group) and the anatomical main nail insertion guide-assisted PFNA insertion group(guide group). The conventional operation group (PFNA) included 31 patients, 14 males and 17 females, the age ranged from 64 to 90 with an average of (75.2±11.6) years old;the guide group (PFNA) included 31 patients, 10 males and 21 females, the age ranged fron 67 to 97 with an average of (78.6±13.4) years old. The incision length of the main nail entry, the number of fluoroscopies from satisfactory reduction to before main nail insertion, operation time, intraoperative blood loss, 3-day postoperative VAS score, postoperative hip function Harris score, complications, etc. were observed and compared between the two groups. RESULTS: All patients were followed up for a period ranging from 4 to 12 months, with an average follow-up duration of (6.8±1.6) months. Compared with the guide group, the conventional operation group showed significant differences in the following parameters:the entrance length of the main screw was (6.74±3.77) cm vs. (5.13±1.31) cm, the number of fluoroscopies before the insertion of the main screw was (10.32±3.08) times vs. (7.71±2.41) times, the operation time was (150.45±53.47) minutes vs. (127.48±30.37) minutes, and the intraoperative blood loss was (196.77±121.06) ml vs. (140.97±86.00) ml, with P<0.05 indicating statistical significance.There was no statistically significant difference in 3-day postoperative VAS between the two groups (P>0.05). There was a statistically significant difference in the Harris scores between the conventional operation group and the guided operation group one month post-surgery (60.61±6.60) vs. (65.48±5.19) points (P<0.05). and there was no statistically significant difference in hip Harris scores between the two groups at 3 months after operation (P>0.05). During the 3-month follow-up after operation, neither group had incision infection, screw loosening, cutting, pressure sores, deep vein thrombosis, etc., and there was no statistically significant difference in the complication rate between the two groups. CONCLUSION It is quickly and accurately to implant PFNA assisted by the anatomical major nail implant guide in treatment of osteoporotic intertrochanteric fracture in the elderly.Compared with the traditional operation, it can shorten the operation time and reduce the surgical and X-ray trauma, and beneficial to the rapid rehabilitation of patients.
Humans ; Male ; Female ; Aged ; Hip Fractures/surgery* ; Bone Nails ; Retrospective Studies ; Aged, 80 and over ; Middle Aged ; Fracture Fixation, Intramedullary/instrumentation* ; Fracture Fixation, Internal/instrumentation*

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.

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.

OBJECTIVE: Recent studies have overturned the traditional concept of the lung as a "sterile organ" revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins (SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis. METHODS: Lung pathology, SPs expression, and microbiota composition were evaluated in silica-exposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure. RESULTS: Silica exposure induced lung inflammation and fibrosis, along with increased expression of SP-A expression. Antibiotics (Abx)-induced microbiota depletion elevated SP-A and SP-D expression. Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa. However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation. CONCLUSION Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.
Animals ; Silicosis/prevention & control* ; Lung/metabolism* ; Mice ; Anti-Bacterial Agents/pharmacology* ; Microbiota/drug effects* ; Silicon Dioxide/toxicity* ; Mice, Inbred C57BL ; Male ; Pulmonary Surfactant-Associated Proteins/genetics*

Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally and poses a severe threat to human health. Surgical resection remains the cornerstone of CRC treatment. With the rapid advancement of minimally invasive techniques, the Da Vinci surgical robot has been increasingly adopted in CRC management. This article will systematically review the current application of the Da Vinci robotic system in minimally invasive CRC treatment, analyzes its advantages and limitations, and discusses future prospects, aiming to provide references for clinical practice and further research.

OBJECTIVE: To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 (CYP19A1) gene with risk of Breast cancer. METHODS: Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No. 2021-182). RESULTS: No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups (P > 0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group (P < 0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages III-IV were significantly higher than those at stage I-II (P < 0.05). CONCLUSION Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.
Humans ; Female ; Breast Neoplasms/genetics* ; Aromatase/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Middle Aged ; Genetic Predisposition to Disease ; Adult ; Genotype ; Case-Control Studies ; Alleles ; Gene Frequency ; Risk Factors ; Aged

ObjectiveTo analyze the long-term trends of the disease burden of diabetes attributed to metabolic factors in China from 1990 to 2019, and provide scientific recommendations for diabetes prevention and control in China. MethodsDescriptive analysis was conducted on the disease burden data of diabetes attributed to metabolic factors in China from 1990 to 2019, obtained from GBD 2019, encompassing death form diabetes, disability-adjusted life years (DALY), years of life lost (YLL), and years lived with disability (YLD). Joinpoint regression models were employed to analyze the long-term trends in mortality and DALY rates. Furthermore, the study examined the impact of two metabolic risk factors, high fasting plasma glucose (FPG) levels and high body mass index (BMI) levels, on the disease burden of diabetes. ResultsFrom 1990 to 2019, the overall standardized mortality and DALY rates attributed to metabolic factors for diabetes in the general population in China showed an upward trend, with both average annual percent changes (AAPCs) of 0.1% in the total population. The trend was upward in males with AAPCs of 0.9% and 0.6%, while it was downward in females with AAPCs of -0.4% and -0.3%. As age increased, the disease burden of diabetes attributed to metabolic factors showed an upward trend, with high FPG and high BMI ranking as the top two attributing risk factors. The disease burden of diabetes attributed to metabolic factors was higher in Chinese males than females. ConclusionThe disease burden of diabetes attributed to metabolic factors is increasing among the overall population and particularly among males, while the burden for female is declining. There is a need to increase intervention efforts for males aged 65 and above, provide scientific guidance on residents’ diet and lifestyle habits, and control blood glucose and body weight.

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.