Objective To investigate the effects of long non-coding RNA FGD5-AS1 on the proliferation,migration,and invasion of pituitary adenoma(PA)cells,and to analyze its potential mechanism of action.Methods Human PA cell lines HPAs,RC-4BC,HP75,and human astrocyte cell line NHA were cultured in vitro.The expression levels of FGD5-AS1 and miR-15a in the above cell lines were detected by RT-PCR.HP75 cells in the logarithmic growth phase were randomly divided into the silencing group and the negative control group.The silencing group was transfected with shRNA-FGD5-AS1,while the negative control group was transfected with shRNA-NC.The expression levels of FGD5-AS1 and miR-15a in the two groups of cells were detected by RT-PCR.The proliferation,migration and invasion abilities of the two groups of cells were determined by CCK-8 assay,wound healing assay,and Transwell assay.The expression of proteins related to the Wnt/β-catenin signaling pathway in the two groups of cells was detected by Western blot.The targeting relationship between FGD5-AS1 and miR-15a was verified by dual-luciferase reporter gene assay.Results Compared with the NHA cell,the expression level of FGD5-AS1 was significantly increased in the HPAs,RC-4BC,and HP75 cells((P<0.05),whereas the expression level of miR-15a was significantly decreased(P<0.05).Compared with the negative control group,the expression level of FGD5-AS1 was decreased(P<0.05),the expression level of miR-15a was increased(P<0.05),the OD value was decreased(P<0.05),the migration and invasion abilities of cells were reduced(P<0.05),and the expression of Wnt3a and β-catenin proteins was decreased in the silencing group of HP75 cells(P<0.05).FGD5-AS1 could specifically bind to miR-15a,leading to a decrease in cell luciferase activity(P<0.05).Conclusion FGD5-AS1 is overexpressed in PA cells,and silencing FGD5-AS1 can inhibit the proliferation,migration,and invasion of PA cells,and the mechanism is related to its targeted regulation of miR-15a.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective To investigate the effects of long non-coding RNA FGD5-AS1 on the proliferation,migration,and invasion of pituitary adenoma(PA)cells,and to analyze its potential mechanism of action.Methods Human PA cell lines HPAs,RC-4BC,HP75,and human astrocyte cell line NHA were cultured in vitro.The expression levels of FGD5-AS1 and miR-15a in the above cell lines were detected by RT-PCR.HP75 cells in the logarithmic growth phase were randomly divided into the silencing group and the negative control group.The silencing group was transfected with shRNA-FGD5-AS1,while the negative control group was transfected with shRNA-NC.The expression levels of FGD5-AS1 and miR-15a in the two groups of cells were detected by RT-PCR.The proliferation,migration and invasion abilities of the two groups of cells were determined by CCK-8 assay,wound healing assay,and Transwell assay.The expression of proteins related to the Wnt/β-catenin signaling pathway in the two groups of cells was detected by Western blot.The targeting relationship between FGD5-AS1 and miR-15a was verified by dual-luciferase reporter gene assay.Results Compared with the NHA cell,the expression level of FGD5-AS1 was significantly increased in the HPAs,RC-4BC,and HP75 cells((P<0.05),whereas the expression level of miR-15a was significantly decreased(P<0.05).Compared with the negative control group,the expression level of FGD5-AS1 was decreased(P<0.05),the expression level of miR-15a was increased(P<0.05),the OD value was decreased(P<0.05),the migration and invasion abilities of cells were reduced(P<0.05),and the expression of Wnt3a and β-catenin proteins was decreased in the silencing group of HP75 cells(P<0.05).FGD5-AS1 could specifically bind to miR-15a,leading to a decrease in cell luciferase activity(P<0.05).Conclusion FGD5-AS1 is overexpressed in PA cells,and silencing FGD5-AS1 can inhibit the proliferation,migration,and invasion of PA cells,and the mechanism is related to its targeted regulation of miR-15a.

ObjectiveTo analyze the epidemiological distribution and temporal trends of liver cancer incidence among Luzhou residents from 2016‒2022， and to provide a theoretical basis for improving liver cancer prevention and treatment strategies in Luzhou. MethodsData on liver cancer incidence among Luzhou residents from 2016 to 2022 were collected， and the incidence rate， age-specific incidence rate， and annual percentage change （APC） were calculated. A Joinpoint regression model was used to fit a time series segment to the monthly number of new cases in each district and county of Luzhou to explore the trend of liver cancer incidence rate. ResultsThe incidence rate of liver cancer in Luzhou increased from 22.96/10⁵ in 2016 to 32.31/10⁵ in 2022. The incidence rate of liver cancer in men was higher than that in women in both 2016 and 2022， and the incidence rate of liver cancer in men increased from 34.83/10⁵ in 2016 to 47.95/10⁵ in 2022， with an APC of 3.3%； the incidence rate of liver cancer in women increased from 10.50/10⁵ in 2016 to 15.95/10⁵ in 2022， with an APC of 3.0%， and the differences in the change trends were not statistically significant （P>0.05）.The incidence of liver cancer was low in the age group of 0‒<40 years from 2016 to 2022 and increased with age； the incidence of liver cancer in the age group of 55 years and above was increasing at an average annual rate of 16.4%. ConclusionThe overall incidence of liver cancer in Luzhou is on the rise， and the incidence of liver cancer in men is higher than that in women. Middle-aged and elderly men are the key population for liver cancer prevention and treatment， and liver cancer prevention and treatment should be carried out in a targeted manner， taking into account regional development differences.

BACKGROUND:The impact of anterior cervical surgery on the sagittal balance parameters of the cervical spine is gradually being paid attention to.Currently,there is a lack of clear and feasible clinical guidelines for the selection of surgical methods for two-level cervical spondylosis,aiming to find the most suitable fixation method that is more beneficial for this type of patient. OBJECTIVE:To compare the effects of different fusion devices for anterior cervical decompression on the changes of cervical sagittal parameters after surgery for adjacent two-level cervical spondylotic myelopathy. METHODS:A total of 44 patients with adjacent two-level cervical spondylotic myelopathy underwent anterior cervical discectomy and fusion from March 2018 to September 2020 in Liaocheng People's Hospital were retrospectively analyzed in the study,and they were divided into zero-p group(23 cases)and cage group(21 cases).All patients underwent anteroposterior X-ray,three-dimensional CT reconstruction and MRI examination before operation.At the last follow-up,the anteroposterior X-ray films of cervical spine were taken.The sagittal balance parameters of the cervical spine were measured before and after surgery,including cervical lordotic angle(C2-7 Cobb),C2-C7 sagittal vertical axis,segmented lordotic angle and T1 slope.The surgical time,intraoperative bleeding,last follow-up intervertebral fusion,and postoperative swallowing disorders were recorded,and Japanese Orthopaedic Association score on the patient was evaluated before and after surgery.The changes in cervical sagittal parameters before and after surgery were calculated and their differences were compared between the two groups. RESULTS AND CONCLUSION:(1)Both groups of patients successfully completed the surgery and received follow-up.The zero-p group had shorter surgical time and less intraoperative bleeding compared to the cage group,but the difference was not statistically significant(P>0.05).(2)The incidence rate of postoperative swallowing disorders in the cage group(7/21,33%)was higher than that in the zero-p group(3/23,13%),and the difference was statistically significant(P<0.05).(3)At the last follow-up,the clinical efficacy of the two groups was the same;all patients had bone fusion.Comparison within the group showed that the sagittal parameters of the cervical spine in both groups improved compared to before surgery(P<0.05).There was no statistically significant difference in sagittal parameters between groups(P>0.05),and there was no statistically significant difference in changes in C2-C7 sagittal vertical axis,C2-7 Cobb angle,and T1 slope between the two groups(P>0.05).However,the segmented lordotic angle changes in the zero-p group were smaller than those in the cage group,and the difference was statistically significant(P<0.05).(4)It is indicated that the use of zero-p and titanium plate combined with cage during anterior cervical discectomy and fusion surgery can effectively improve cervical sagittal balance.Titanium plate combined with cage intervertebral fusion can better reconstruct the patient's cervical lordosis and curvature.The selection of fusion devices should also comprehensively consider the occurrence of surgical complications.

The toad, known for its various medicinal properties including parotid gland secretion (toad venom), dried skin, and gallbladder (toad bile), holds considerable medicinal applications as a valuable traditional Chinese animal medicine. Currently, in-depth attentions have been paid to the chemical composition and pharmacological properties of toad venom and skin; however, a lesser number of detailed analyses were concentrated on the toad bile. This review provides an overview of the chemical constituents in the bile of the Bufo genus, with a special focus on the cholestane and bufadienolides, and highlights the progress in their biosynthetic pathway and pharmacological activities. The analysis uncovers a distinct category of unsaturated Δ²² or Δ²³-C₂₇/C₂₈ bile acids in the toad gallbladder, potentially acting as key intermediaries in forming C-17 α-pyrone of bufadienolides. Furthermore, the high presence of 3α-OH configured bufadienolides in toad bile, in contrast to the common 3β-OH configured found in toad venom or skin, indicates a possible link between their minimal toxicity and the toad's self-defensive or physiological control. This review provides scientific basis for the development and utilization of toad bile resources, and provides useful reference for the discovery of lead compounds, analysis of the biosynthetic pathway of bufadienolides, and research on toad physiology.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19/epidemiology* ; COVID-19 Drug Treatment ; Aged ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/adverse effects* ; SARS-CoV-2 ; Treatment Outcome ; China/epidemiology* ; Adult

OBJECTIVE: To provide an overview of the incidence of knee donor -site morbidity after autologous osteochondral mosaicplasty. METHODS: A comprehensive search was conducted in PubMed, EMbase, Wanfang Medical Network, and CNKI databases from January 2010 to April 20, 2021. Relevant literature was selected based on predefined inclusion and exclusion criteria, and data were evaluated and extracted. The correlation between the number and size of transplanted osteochondral columns and donor-site morbidity was analyzed. RESULTS: A total of 13 literatures were included, comprising a total of 661 patients. Statistical analysis revealed an incidence of knee donor-site morbidity at 8.6% (57/661), with knee pain being the most common complaint, accounting for 4.2%(28/661). There was no significant correlation between the number of osteochondral columns and postoperative donor-site incidence (P=0.424, N=10), nor between the diameter size of osteochondral columns and postoperative donor-site incidence(P=0.699, N=7). CONCLUSION Autologous osteochondral mosaicplasty is associated with a considerable incidence of knee donor-site morbidity, with knee pain being the most frequent complaint. There is no apparent correlation between donor-site incidence and the number and size of transplanted osteochondral columns. Donors should be informed about the potential risks.
Humans ; Incidence ; Cartilage/transplantation* ; Knee ; Knee Joint/surgery* ; Pain ; Cartilage, Articular ; Transplantation, Autologous ; Bone Transplantation

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.
Animals ; Rats ; Interleukin-6 ; Network Pharmacology ; Animal Experimentation ; Tumor Necrosis Factor-alpha ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Liver Cirrhosis/genetics* ; Medicine, Chinese Traditional ; Capsules ; Class I Phosphatidylinositol 3-Kinases ; Collagen ; Drugs, Chinese Herbal/pharmacology*