Objective·To investigate the effects of rutin on proliferation,apoptosis,migration and invasion of osteosarcoma cells and its possible molecular mechanisms.Methods·Human osteosarcoma MG63 and U2OS cells were treated with rutin at concentrations of 10,20 and 40 μmol/L,respectively.The effects of rutin on proliferation,apoptosis,migration,and invasion of MG63 and U2OS cells were assessed by using CCK-8 assay,colony formation assay,flow cytometry,scratch closure assay,and Transwell assay.The expression levels of cell proliferation antigen Ki67,B-cell lymphoma-2(Bcl-2),and Bcl-2 associated X protein(Bax)proteins were detected by Western blotting.Twelve BALB/c nude mice were subcutaneously injected with osteosarcoma MG63 cells to establish a subcutaneous transplant tumor model.The mice were randomly divided into two groups:a control group and a rutin 40 mg/kg group(6 mice in each group).The rutin 40 mg/kg group was intraperitoneally injected with rutin(40 mg/kg),and the control group was intraperitoneally injected with an equal volume of saline,once every other day for 4 weeks.The tumor volume was measured every week.After 4 weeks,the mice were euthanized,and the tumors were excised and weighed.Immunohistochemistry was used to detect the expression of Ki67 and vascular endothelial growth factor(VEGF)in tumor tissues.TUNEL was used to detect tumor cell apoptosis.Results·Compared with MG63 and U2OS cells not treated with rutin,MG63 and U2OS cells treated with rutin at 20 and 40 μmol/L showed a significant decrease in proliferation rate,an increase in apoptotic rate,a decrease in migration and invasion abilities,a significant downregulation of Ki67 protein,and a significant increase in Bax/Bcl-2 ratio,with statistically significant differences(all P＜0.05).In addition,rutin significantly inhibited the in vivo growth of osteosarcoma cells,reduced the expression of Ki67 and VEGF in tumor tissues,and promoted cell apoptosis(all P＜0.05).Conclusion·Rutin can inhibit the proliferation,migration,and invasion of osteosarcoma cells,and promote apoptosis.

Objective:To investigate the diversity, temporal dynamics and influencing factors of serotypes of Salmonella among asymptomatic workers in Yulin, Guangxi Zhuang Autonomous Region, from 2013 to 2023, and provide reference for controlling the hidden transmission of Salmonella and for disease prevention among healthy populations. Methods:Anal rectal swabs were collected from asymptomatic workers in Yulin from 2013 to 2023 for the isolation and identification of Salmonella. The diversity of serotypes of Salmonella was evaluated by using Shannon index, while the isolation rates and composition ratio of different serotypes were compared with χ2 test. Spearman correlation analysis was used to evaluate the correlation of natural and social factors with serotype isolation rates for more than eight years, and stepwise multiple linear regression analysis were used to evaluate the impact of social factors on the serotype isolation rates for more than 8 years. Results:A total of 8 073 strains of Salmonella were isolated from 2013 to 2023, with an overall isolation rate of 18.88‰ During the 11-year period, 135 serotypes of Salmonella were identified, and the serotype diversity increased first and then decreased. The serotype with the highest isolation rate was Salmonella Typhimurium (3.04‰), followed by Salmonella Rissen (1.70‰), Salmonella Corvallis (1.41‰), Salmonella Agona (1.36‰), Salmonella Derby (1.22‰), and Salmonella London (1.02‰), accounting for 51.67% of the total Salmonella serotypes isolated. There was no significant trend in isolation rate of Salmonella over the years ( χ2=0.67, P=0.415); however, season significantly influenced the isolation rate, with lower rate being observed in winter and higher rate in summer ( χ2=615.91, P<0.001). The isolation rate of different serotypes of Salmonella was influenced by social and natural factors, showing a positive correlation with temperature, precipitation, and poultry consumption and production levels. Conclusions:The serotypes of Salmonella carried by asymptomatic workers were complex and diverse in Yulin, Guangxi Zhuang Autonomous Region, from 2013 to 2023, and the isolation rates of multi-serotypes increased from 2013 to 2023. Higher isolation rate was observed in summer and the isolation rate was widely influenced by natural factors such as temperature and precipitation, as well as social factors such as economic conditions. It is necessary to pay attention to the Salmonella serotype carriage in healthy population, and strengthen monitoring of both healthy individuals and pathogenic bacteria.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Objective:To investigate the diversity, temporal dynamics and influencing factors of serotypes of Salmonella among asymptomatic workers in Yulin, Guangxi Zhuang Autonomous Region, from 2013 to 2023, and provide reference for controlling the hidden transmission of Salmonella and for disease prevention among healthy populations. Methods:Anal rectal swabs were collected from asymptomatic workers in Yulin from 2013 to 2023 for the isolation and identification of Salmonella. The diversity of serotypes of Salmonella was evaluated by using Shannon index, while the isolation rates and composition ratio of different serotypes were compared with χ2 test. Spearman correlation analysis was used to evaluate the correlation of natural and social factors with serotype isolation rates for more than eight years, and stepwise multiple linear regression analysis were used to evaluate the impact of social factors on the serotype isolation rates for more than 8 years. Results:A total of 8 073 strains of Salmonella were isolated from 2013 to 2023, with an overall isolation rate of 18.88‰ During the 11-year period, 135 serotypes of Salmonella were identified, and the serotype diversity increased first and then decreased. The serotype with the highest isolation rate was Salmonella Typhimurium (3.04‰), followed by Salmonella Rissen (1.70‰), Salmonella Corvallis (1.41‰), Salmonella Agona (1.36‰), Salmonella Derby (1.22‰), and Salmonella London (1.02‰), accounting for 51.67% of the total Salmonella serotypes isolated. There was no significant trend in isolation rate of Salmonella over the years ( χ2=0.67, P=0.415); however, season significantly influenced the isolation rate, with lower rate being observed in winter and higher rate in summer ( χ2=615.91, P<0.001). The isolation rate of different serotypes of Salmonella was influenced by social and natural factors, showing a positive correlation with temperature, precipitation, and poultry consumption and production levels. Conclusions:The serotypes of Salmonella carried by asymptomatic workers were complex and diverse in Yulin, Guangxi Zhuang Autonomous Region, from 2013 to 2023, and the isolation rates of multi-serotypes increased from 2013 to 2023. Higher isolation rate was observed in summer and the isolation rate was widely influenced by natural factors such as temperature and precipitation, as well as social factors such as economic conditions. It is necessary to pay attention to the Salmonella serotype carriage in healthy population, and strengthen monitoring of both healthy individuals and pathogenic bacteria.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

OBJECTIVE: To investigate the effect of acupuncture on advanced cancer patients by meta-analysis. METHODS: Nine databases (the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure, the Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and WanFang Data) were searched for randomized controlled trials (RCTs) on acupuncture in advanced cancer patients published from inception to February 13, 2023 and updated to June 1, 2023. Primary outcomes were quality of life (QOL), while secondary outcomes were pain, fatigue, and adverse events (side effects). Data synthesis was performed using RevMan V.5.3 to calculate pooled effect sizes. RoB-2 was used for the risk of bias, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. RESULTS: Totally 17 RCTs involving 1,178 participants were included, 15 of which were pooled for meta-analysis. Most studies demonstrated some concern for the overall risk of bias. The pooled data indicated that acupuncture was associated with improved QOL [mean difference (MD)=6.67, 95% confidence interval (CI): 5.09 to 8.26], pain (MD=-1.18, 95% CI -2.28 to -0.08), and adverse events (risk ratio=0.30, 95% CI: 0.26 to 0.57) compared with control groups. Fatigue outcome was not included. Heterogeneity was substantial, and GRADE evidence was very low for both QOL and pain. CONCLUSIONS Acupuncture could benefit patients with advanced cancer and is considered safe compared with usual care. However, the evidence regarding QOL and pain outcomes requires further validation. It is crucial to encourage the development of high-quality studies to strengthen this evidence. (Registry No. CRD42023423539).
Humans ; Acupuncture Therapy ; Neoplasms/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome

Objective·To investigate the effects of rutin on proliferation,apoptosis,migration and invasion of osteosarcoma cells and its possible molecular mechanisms.Methods·Human osteosarcoma MG63 and U2OS cells were treated with rutin at concentrations of 10,20 and 40 μmol/L,respectively.The effects of rutin on proliferation,apoptosis,migration,and invasion of MG63 and U2OS cells were assessed by using CCK-8 assay,colony formation assay,flow cytometry,scratch closure assay,and Transwell assay.The expression levels of cell proliferation antigen Ki67,B-cell lymphoma-2(Bcl-2),and Bcl-2 associated X protein(Bax)proteins were detected by Western blotting.Twelve BALB/c nude mice were subcutaneously injected with osteosarcoma MG63 cells to establish a subcutaneous transplant tumor model.The mice were randomly divided into two groups:a control group and a rutin 40 mg/kg group(6 mice in each group).The rutin 40 mg/kg group was intraperitoneally injected with rutin(40 mg/kg),and the control group was intraperitoneally injected with an equal volume of saline,once every other day for 4 weeks.The tumor volume was measured every week.After 4 weeks,the mice were euthanized,and the tumors were excised and weighed.Immunohistochemistry was used to detect the expression of Ki67 and vascular endothelial growth factor(VEGF)in tumor tissues.TUNEL was used to detect tumor cell apoptosis.Results·Compared with MG63 and U2OS cells not treated with rutin,MG63 and U2OS cells treated with rutin at 20 and 40 μmol/L showed a significant decrease in proliferation rate,an increase in apoptotic rate,a decrease in migration and invasion abilities,a significant downregulation of Ki67 protein,and a significant increase in Bax/Bcl-2 ratio,with statistically significant differences(all P＜0.05).In addition,rutin significantly inhibited the in vivo growth of osteosarcoma cells,reduced the expression of Ki67 and VEGF in tumor tissues,and promoted cell apoptosis(all P＜0.05).Conclusion·Rutin can inhibit the proliferation,migration,and invasion of osteosarcoma cells,and promote apoptosis.

Hypoxic injury (HI) in the prenatal period often causes neonatal neurological disabilities. Due to the difficulty in obtaining clinical samples, the molecular and cellular mechanisms remain unclear. Here we use vascularized cerebral organoids to investigate the hypoxic injury phenotype and explore the intercellular interactions between vascular and neural tissues under hypoxic conditions. Our results indicate that fused vascularized cerebral organoids exhibit broader hypoxic responses and larger decreases in panels of neural development-related genes when exposed to low oxygen levels compared to single cerebral organoids. Interestingly, vessels also exhibit neural protective effects on T-box brain protein 2⁺ intermediate progenitors (IPs), which are markedly lost in HI cerebral organoids. Furthermore, we identify the role of bone morphogenic protein signaling in protecting IPs. Thus, this study has established an in vitro organoid system that can be used to study the contribution of vessels to brain injury under hypoxic conditions and provides a strategy for the identification of intervention targets.
Organoids/pathology* ; Animals ; Mice ; Hypoxia, Brain/metabolism* ; Brain/blood supply* ; Neurons/metabolism*

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome