AIM:To explore the way and mecha-nism of cell death induced by Fructus Akebiae in non-small cell lung cancer(NSCLC)cells.METH-ODS:CCK-8,Hochest33342/PI staining,and colony formation experiments were used to detect cell via-bility and proliferation.Western blot was used to detect the expression of cell death-related proteins ATG5,HMGB1,GPX4,apoptosis-related proteins,and PI3K-Akt signaling pathway-related proteins.Flow cytometry was used to detect the apoptosis rate.DCFH-DA fluorescent probes were used to de-tect the levels of total intracellular ROS under a flu-orescence microscope.RESULTS:Fructus Akebiae significantly inhibited the cell viability and prolifera-tion of human NSCLC cells(P＜0.05).The expression of apoptosis-related proteins BAX,Cleaved cas-pase3,and Cleaved caspase9 in NSCLC cells was sig-nificantly increased(P＜0.05),while p-PI3K,p-Akt,and BCL2 were markedly decreased(P＜0.05).Fruc-tus Akebiae was found to clearly increase the apop-tosis rate and the levels of total intracellular ROS(P＜0.05).The antioxidant NAC significantly reversed apoptosis,ROS production and regulation of PI3K-Akt pathway related proteins induced by Fructus Akebiae(P＜0.05).CONCLUSION:Fructus Akebiae in-duces apoptosis via regulating ROS-mediated PI3K-Akt signaling pathway in non-small cell lung cancer cells.

AIM:To explore the way and mecha-nism of cell death induced by Fructus Akebiae in non-small cell lung cancer(NSCLC)cells.METH-ODS:CCK-8,Hochest33342/PI staining,and colony formation experiments were used to detect cell via-bility and proliferation.Western blot was used to detect the expression of cell death-related proteins ATG5,HMGB1,GPX4,apoptosis-related proteins,and PI3K-Akt signaling pathway-related proteins.Flow cytometry was used to detect the apoptosis rate.DCFH-DA fluorescent probes were used to de-tect the levels of total intracellular ROS under a flu-orescence microscope.RESULTS:Fructus Akebiae significantly inhibited the cell viability and prolifera-tion of human NSCLC cells(P＜0.05).The expression of apoptosis-related proteins BAX,Cleaved cas-pase3,and Cleaved caspase9 in NSCLC cells was sig-nificantly increased(P＜0.05),while p-PI3K,p-Akt,and BCL2 were markedly decreased(P＜0.05).Fruc-tus Akebiae was found to clearly increase the apop-tosis rate and the levels of total intracellular ROS(P＜0.05).The antioxidant NAC significantly reversed apoptosis,ROS production and regulation of PI3K-Akt pathway related proteins induced by Fructus Akebiae(P＜0.05).CONCLUSION:Fructus Akebiae in-duces apoptosis via regulating ROS-mediated PI3K-Akt signaling pathway in non-small cell lung cancer cells.

ObjectiveTo analyze the reported cases of infectious diseases across different tiers of public medical and healthcare institutions in Minhang District, Shanghai from 2013 to 2023, to investigate the status and changes in reported infectious diseases in this district from a temporal, etiological, and demographic perspectives, so as to provide a scientific basis for the construction of a hierarchica early-warning surveillance system under the grading diagnosis and treatment model in medical institutions, as well as for optimizing sentinel surveillance at facilities of different levels. MethodsA retrospective analysis was performed using surveillance data from the China Disease Prevention and Control Information System in Minhang District from 2013 to 2023. Reported infectious diseases were categorized into three categories based on transmission routes: respiratory infectious diseases, intestinal infectious diseases, and sexually transmitted and blood borne infectious diseases. According to the implementation phase of the grading diagnosis and treatment policy, the research time was divided into four time periods: 2013‒2016, 2017‒2019, 2020‒2022, and 2023. The distribution and temporal changes of reported cases of infectious diseases were compared across community health service centers (CHCs), secondary hospitals, tertiary grade-A hospitals and tertiary grade-B hospitals. Chi-square test was used for univariate analysis of differences in the number of reported cases. Quantitative data with normal distribution were analyzed using parametric tests, otherwise, Kruskal⁃Wallis H tests were used. ResultsThe proportions of total reported cases of infectious diseases in medical institutions at all levels in Minhang District, Shanghai from 2013 to 2023 were 10.66% in CHCs, 9.10% in secondary hospitals, 64.95% in tertiary grade-B hospitals, and 15.29% in tertiary grade-A hospitals, with an overall decline and then rebound trend in the reported cases. After the implementation of grading diagnosis and treatment policy, the number of reported cases in CHCs and secondary hospitals showed a trend of first decreasing and then increasing, while that in tertiary grade-B hospitals showed a steady decreasing trend and that in tertiary grade-A hospitals showed an increasing trend. In terms of the research periods divided above, a total of 10 392 cases were reported in 2013‒2016 (70.34% from tertiary grade-B hospitals and 12.59% from CHCs), including 2 922 cases of respiratory infectious diseases, 1 241 cases of intestinal infectious diseases, and 6 229 cases of sexually transmitted and blood-borne infectious diseases. Between 2017 and 2019, a total of 6 967 cases were reported (73.49% from tertiary grade-B hospitals and 11.84% from tertiary grade-A hospitals), including 2 983 cases of respiratory infectious diseases, 279 cases of intestinal infectious diseases, and 3 705 cases of sexually transmitted and blood-borne infectious diseases. Between 2020 and 2022, a total of 4 599 cases were reported (69.92% from tertiary grade-B hospitals and 24.57% from tertiary grade-A hospitals), including 1 627 cases of respiratory infectious diseases, 123 cases of intestinal infectious diseases, and 2 849 cases of sexually transmitted and blood-borne infectious diseases. In 2023, a total of 4 648 cases were reported (35.20% from tertiary grade-B hospitals and 27.50% from tertiary grade-A hospitals), including 3 165 cases of respiratory infectious diseases, 69 cases of intestinal infectious diseases, and 1 414 cases of sexually transmitted and blood-borne infectious diseases. The proportion of reported cases from tertiary grade-B hospitals was the highest in all the four research periods, but exhibited an obvious decrease in 2023. The differences in the reported cases of infectious diseases with different transmission routes among medical institutions at all levels were statistically significant (χ²=3 225.628, P<0.05). The differences in the mean age of patients among medical institutions at all levels were statistically significant (H=1 325.927, P<0.05). ConclusionThere are significant differences in the number of reported cases of infectious disease in the medical institutions at different levels. Tertiary grade-B hospitals have historically dominated the number of reported cases, but its share has declined recently. Whereas, CHCs and tertiary grade-A hospitals have played an increasingly important role in the surveillance and early warning of respiratory and intestinal infectious diseases. Therefore, it is recommended to leverage the strengths of grading diagnosis and treatment to establish targeted sentinel sites and deploy specialized teams tailored to the epidemiological characteristics of specific disease categories.

Secondary osteoporosis is common in patients with early breast cancer, manifesting as low back pain, bone and joint symptoms, and osteoporotic fractures. Bisphosphonate and denosumab can reduce the incidence of fractures by minimizing bone loss, though they differ in efficacy, treatment course, and side effects. Patients should consider the pros and cons when selecting a drug. Recent studies also focus on decreasing the incidence of bone metastases. This article reviews recent advancements in the use of these two drugs for managing bone health in early breast cancer.

Secondary osteoporosis is common in patients with early breast cancer, manifesting as low back pain, bone and joint symptoms, and osteoporotic fractures. Bisphosphonate and denosumab can reduce the incidence of fractures by minimizing bone loss, though they differ in efficacy, treatment course, and side effects. Patients should consider the pros and cons when selecting a drug. Recent studies also focus on decreasing the incidence of bone metastases. This article reviews recent advancements in the use of these two drugs for managing bone health in early breast cancer.

Objective:To investigate the correlation between fat distribution and the composite indices of femoral neck strength in obese postmenopausal women.Methods:A total of 293 postmenopausal women with non-low body weight were selected, laboratory tests, body composition analyzer test and double-energy X-ray absorptiometry scan were performed. Based on the body mass index(BMI), they were divided into three groups, the normal BMI group(18.5 kg/m 2≤BMI<24.0 kg/m 2, n=91), the overweight group(24.0 kg/m 2≤BMI<28.0 kg/m 2, n=115), and the obese group(BMI≥28.0 kg/m 2, n=87). The measurement results were analyzed. Results:In the obese group, bone mineral density(BMD) of all sites was higher than that in the normal BMI group and overweight group( P<0.005), compression strength index(CSI), bending strength index(BSI), and impact strength index(ISI) were significantly lower than those in the normal BMI group( P<0.001, P=0.008, P=0.001). In the obese group, waist circumference, waist-hip ratio, total fat mass, appendicular fat mass, and trunk fat mass were risk factors for CSI, BSI and ISI independent of age, fasting blood glucose, and BMI( P<0.05). Visceral fat grade and Chinese visceral adiposity fat index were the risk factors for CSI, BSI, and ISI( P<0.05). Conclusion:The composite indices of femoral neck strength decreased in obese postmenopausal women, and both subcutaneous fat and visceral fat were negatively associated with the composite indices of femoral neck strength.

Objective To investigate the expression of miR-6768-5p in lung cancer tissue and its effect on the proliferation and invasion of lung cancer cells through targeted regulation of carboxypeptidase A4(CPA4).Methods The expression of miR-6768-5p in lung cancer tissues and adjacent tissues was analyzed u-sing the TCGA database.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-6768-5p in human lung cancer cell lines(HCC1588,H1650,H1299,A549,HCC827)and normal alveolar epithelial cells(HPAEpiC cells).Lung cancer cells were transfected with NC mimics and miR-6768-5p mimics,respec-tively,and divided into NC group and miR-6768-5p group.The MTS assay and Matrigel invasion assay were used to detect the cell proliferation and invasion ability of each group,respectively.The putative binding sites of miR-6768-5p and CPA4 were verified using RNAhybrid software and dual-luciferase reporter gene experi-ment.The expression of CPA4 mRNA in each group of cells was detected by qPCR.The expression of AKT/c-MYC signaling pathway proteins in the cells of each group was analyzed by Western blot.Results Com-pared with the adjacent tissues,the relative expression level of miR-6768-5p in lung cancer tissues was signifi-cantly decreased,and the difference was statistically significant(P＜0.05).Compared with HPAEpiC cells,the relative expression level of miR-6768-5p was significantly decreased in lung cancer cell lines,and the differ-ence was statistically significant(P＜0.05).Compared with the NC group,the cell proliferation rate of miR-6768-5p group was significantly decreased(P＜0.05).The number of invasive cells in NC group and miR-6768-5p group was(131.30±12.55)and(37.45±7.77),respectively,and the number of invasive cells in miR-6768-5p group was significantly lower than that in NC group(P＜0.05).The relative expression level of CPA4 mRNA in H1299 cells of miR-6768-5p group was significantly lower than that in NC group(t=4.93,P＜0.05).Compared with the NC group,the expressions of AKT/c-myC signaling pathway proteins p-AKT,p-mTORC1,XIAP,MDM2 and C-myC proteins in miR-6768-5p group were significantly decreased.Conclusion The expression of miR-6768-5p is decreased in lung cancer tissues,and miR-6768-5p may inhibit the activation of AKT/c-MYC signaling pathway by targeting CPA4,and reduce the proliferation and invasion ability of lung cancer H1299 cells.

Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L⁻¹ permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L⁻¹ permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L⁻¹ permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L⁻¹ permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L⁻¹ permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L⁻¹ compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L⁻¹ permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L⁻¹ permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L⁻¹ permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L⁻¹ permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

Objective:To analyze the research status of scleral lenses by bibliometric method based on the relevant collection of scleral lenses in the Web of Science database.Methods:Using the scleral lens-related literature collected in the Web of Science Core Collection database in the past 10 years (January 2013 to December 2022) as the object of analysis, bibliometric method and CiteSpace tools were used to conduct visual analysis of the literature.A comprehensive analysis of the volume of literature published, the distribution of countries and institutions, the information of core authors, the distribution of journals, and keyword clustering was performed.Results:A total of 340 articles were retrieved, which were published in 54 journals, with an average of 6.3 articles per journal, involving 301 authors.Research in this area covered 35 countries or regions, and 256 research institutions were involved.Discipline development was mainly in the United States, India, Spain and Australia.The main focus was on scleral lens (scleral contact lens), ocular surface disease, corneal edema, miniature scleral lens, etc.In the past 10 years, the trend of research hot topics in scleral lenses had shifted from the initial study of combining scleral contact lenses with ocular surface diseases to the subsequent study of prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape.From 2013 to 2021, the main focuses were ocular surface diseases, scleral contact lenses, and corneal edema.After 2021, research on ocular surface diseases and keratoplasty declined.From January 2013 to December 2022, emergent keywords related to scleral lens mainly included scleral contact lens, transplantation, anti-host disease, prosthetic device in the first stage, artificial replacement of ocular surface ecosystem and irregular cornea in the second stage, and the research on corneal gap and characteristic shape in the third stage.Optical coherence tomography and corneal topography were commonly used examinations for scleral lens research and fitting.Conclusions:At present, the scleral lens is mainly used for dry eye, corneal diseases, corneal ectasia, keratitis, and corneal transplantation, especially after penetrating keratoplasty and refractive errors.Prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape are the research hotspots in scleral lenses.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.