Objective To investigate the regulatory effects and molecular mechanisms of PUS3 on GBM cell malignant behaviors(proliferation,apoptosis,invasion)in vitro,providing potential therapeutic targets for GBM.Methods The expression of PUS3 in GBM was analyzed using the GEPIA2 database.Kaplan-Meier survival analysis evaluated the survival difference between PUS3 high-and low-expression patients.qRT-PCR and Western blot were performed to detect PUS3 expression in normal glial cells(HEB)and GBM cell lines(U87,LN229,U251,T98G).PUS3-stably overexpressing GBM cell lines were constructed.Colony formation,CCK-8 assay,and flow cytometry were used to assess proliferation and apoptosis.Transwell assay evaluated cell invasion.Immunohis-tochemistry(IHC)detected PUS3 expression in GBM patient tissues.Western blot analyzed tumor-related pathway proteins after PUS3 overexpression.Results The expression level of PUS3 is elevated in GBM patient tissues,and the mRNA and protein expression levels in GBM cells are significantly higher than those in HEB cells(P<0.01).After overexpression of PUS3,the proliferation ability of GBM cells was enhanced(P<0.05),the apoptosis rate decreased(P<0.01),and the number of invasive cells increased(P<0.001).Mechanistically,overexpression of PUS3 significantly activates the AKT pathway,and the use of AKT inhibitors in PUS3 overexpressing cells can reverse the pro cancer effect.Conclusion PUS3 is highly expressed in glioblastoma(GBM)and promotes tumor cell proliferation,invasion,and apoptosis inhibition by activating the AKT pathway,suggesting its potential as a therapeutic target for GBM treatment.

Objective:To construct an evaluation index system for rural order-oriented general practice residents based on Entrustable Professional Activities (EPAs) and conduct an empirical analysis. ?Methods:A mixed-methods study design was adopted (November 2022-April 2023). The preliminary draft of the index system was developed through literature review and group discussions, then refined and improved via two rounds of expert consultation using the Delphi method. The analytic hierarchy process (AHP) was applied to determine the weight of each index. Meanwhile, questionnaires were distributed to 181 participants, including general practitioners from general hospitals, general practitioners from community hospitals, and general practice residents. The scores of the three groups regarding the importance and feasibility of the indices were compared. Ten general practitioners of the above three types were selected for semi-structured interviews on their cognitive and practical aspects of the system. ?Results:The positive coefficients of the two rounds of expert consultation were 16/17 and 16/16, respectively. The expert authority degree was >0.70, and the test of coordination coefficient was statistically significant ( P<0.05). Finally, an index system consisting of 20 first-level indices and 56 second-level indices was established. In terms of weight, among the first-level indices,"EPA1: Information Acquisition"had the highest weight (0.11), while"EPA12: Clinical Research"had the lowest (0.02). Among the second-level indices, "Medical History Taking" and "Physical Examination" under EPA1 had the highest weight (both 0.056), while "Healthcare for Patients with Severe Mental Illness" and "Healthcare for Disabled and Handicapped Populations" under EPA15 had the lowest (both 0.003). The 181 participants gave scores ranging from 4.49 to 4.92 for the importance of the 20 first-level indices and from 4.16 to 4.81 for their feasibility. Only for" EPA19: Common Diseases in Primary Care and Health Management", the feasibility score given by general practitioners from community hospitals was higher than that from general hospitals ( t=2.157, P=0.032); no statistically significant differences were observed among the groups for the other indices ( P>0.05).The interview results showed that general practitioners have a relatively high level of recognition for this system, but there is still room for improvement in its practical application.? Conclusions:The evaluation index system for rural order-oriented general practice residents constructed based on EPAs has high reliability, and it is consistently recognized by different types of general practitioners. It can provide a reference for the cultivation of post competency of this group.?

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

In recent years, the wearable device market has been developing rapidly. Wearable devices with personalized health management and chronic disease monitoring are widely used in daily life by virtue of their powerful performance and convenience. However, with the popularization of these devices, skin adverse reactions caused by prolonged wearable wear are gradually increasing, among which allergic contact dermatitis (ACD) is the most common. Common allergens such as acrylates, methacrylates, rosin, chromium and nickel are widely present in adhesives and device components and are the main causes of ACD. Understanding the presence of potential sensitizers in wearable devices can help in diagnostic patch testing in users experiencing skin reactions caused by the device. Future innovations in wearable device materials will focus on the adoption of safer bonding technologies and biocompatible materials to reduce the risk of allergy. The introduction of new materials brings both development opportunities and challenges. Educating users on proper device usage, identifying specific allergens, selecting hypoallergenic materials, and optimizing device maintenance are important for reducing the risk of ACD.

Objective To investigate the regulatory effects and molecular mechanisms of PUS3 on GBM cell malignant behaviors(proliferation,apoptosis,invasion)in vitro,providing potential therapeutic targets for GBM.Methods The expression of PUS3 in GBM was analyzed using the GEPIA2 database.Kaplan-Meier survival analysis evaluated the survival difference between PUS3 high-and low-expression patients.qRT-PCR and Western blot were performed to detect PUS3 expression in normal glial cells(HEB)and GBM cell lines(U87,LN229,U251,T98G).PUS3-stably overexpressing GBM cell lines were constructed.Colony formation,CCK-8 assay,and flow cytometry were used to assess proliferation and apoptosis.Transwell assay evaluated cell invasion.Immunohis-tochemistry(IHC)detected PUS3 expression in GBM patient tissues.Western blot analyzed tumor-related pathway proteins after PUS3 overexpression.Results The expression level of PUS3 is elevated in GBM patient tissues,and the mRNA and protein expression levels in GBM cells are significantly higher than those in HEB cells(P<0.01).After overexpression of PUS3,the proliferation ability of GBM cells was enhanced(P<0.05),the apoptosis rate decreased(P<0.01),and the number of invasive cells increased(P<0.001).Mechanistically,overexpression of PUS3 significantly activates the AKT pathway,and the use of AKT inhibitors in PUS3 overexpressing cells can reverse the pro cancer effect.Conclusion PUS3 is highly expressed in glioblastoma(GBM)and promotes tumor cell proliferation,invasion,and apoptosis inhibition by activating the AKT pathway,suggesting its potential as a therapeutic target for GBM treatment.

Objective:To systematically review risk prediction models for frailty in maintenance hemodialysis (MHD) patients.Methods:Relevant literature on frailty risk prediction models for MHD patients were retrieved from PubMed, Web of Science, Embase, Cochrane Library, CINHAL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc from inception to March 25, 2024. Two researchers independently screened the literature and extracted data. The PROBAST tool was used to assess the methodological quality of the prediction models. Meta-analysis of predictive factors was conducted using Stata 16.0 software.Results:A total of 13 studies were included, comprising 19 frailty risk prediction models for MHD patients. All studies exhibited a high risk of bias. Six studies conducted internal validation, and three studies conducted external validation. The area under the receiver operating characteristic curve ( AUC) of the included prediction models ranged from 0.720 to 0.998. Meta-analysis revealed that age [ OR=1.149, 95% CI (1.070, 1.234), P<0.001], female gender [ OR=4.472, 95% CI (1.799, 11.117), P<0.001], nutritional score [ OR=2.650, 95% CI (1.010, 6.970), P=0.048], comorbidities [ OR=1.990, 95% CI (1.500, 2.650), P<0.001], and serum albumin [ OR=0.830, 95% CI (0.790, 0.880), P<0.001] were significant influencing factors for frailty in MHD patients. Conclusions:Risk prediction models for frailty in MHD patients are still in the research stage. Healthcare professionals should pay close attention to frailty risks in older patients, females, those with malnutrition, comorbidities, and low serum albumin levels, and implement timely interventions.

Objective:To investigate the molecular mechanism of Xiaoshuantongmai Decoction(XSTMD)targeting JAK2/STAT3 signaling pathway to regulate the function of dendritic cells(DCs)in treatment of deep vein thrombosis(DVT).Methods:After treatment of DVT with XSTMD,expressions of fibrinogen beta chain(FGB)and D-dimer(D2D)protein in plasma of patients with DVT were detected by ELISA,proportion of plasmacytoid dendritic cell(pDC)and conventional dendritic cell(cDC),and expression of HLA-DR protein in peripheral blood mononuclear cells(PBMCs)of patients with DVT were detected by flow cytometry,expressions of CD80 and CD86 mRNA were detected by qRT-PCR,Western blot was used to detect protein levels of JAK2,STAT3 and phosphory-lation(p-JAK2 and p-STAT3)in PBMC of DVT patients and mice.LPS-induced mouse DC2.4 cells were treated with XSTMD drug-containing serum.Western blot was used to determine the protein levels of JAK2,STAT3,p-JAK2 and p-STAT3.ELISA was used to detect protein levels of IL-6,TNF-α,IL-10 and TGF-β1 in cell culture supernatant.Results:After treatment with XSTMD,weight and length of thrombus were significantly reduced in mice with DVT(P<0.001).Compared with before treatment,expressions of FGB and D2D were significantly decreased in plasma of DVT patients(P<0.001),proportion of pDC was significantly increased,while pro-portion of cDC was significantly decreased in PBMC of DVT patients(P<0.01),expression of HLA-DR protein and mRNA levels of CD80 and CD86 were significantly decreased in PBMC of DVT patients(P<0.05,P<0.01,P<0.001)after treatment with XSTMD.Levels of p-JAK2 and p-STAT3 protein were significantly increased in PBMC from DVT patients and mice treated with XSTMD(P<0.05).After treatment with serum containing XSTMD,protein levels of p-JAK2 and p-STAT3 induced by LPS were significantly increased in murine DC2.4 cells(P<0.05).Protein expressions of IL-6 and TNF-α were significantly decreased,while protein expressions of IL-10 and TGF-β1 were significantly increased in cell supernatant(P<0.01,P<0.001).Conclusion:XSTMD effectively treats DVT by pre-cisely regulating the JAK2/STAT3 signaling pathway to promote the differentiation of DCs into pDC and alleviate inflammatory injury.

Objective:To systematically review and evaluate risk prediction models for radiation dermatitis in breast cancer patients, providing a reference for developing higher-quality prediction models.Methods:A systematic search was conducted in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and China Biomedical Literature Database for studies related to risk prediction models for radiation dermatitis in breast cancer patients. The search timeframe was from database inception to February 28, 2024. Two researchers independently screened relevant literature based on inclusion and exclusion criteria, extracted the basic characteristics of the studies, and performed analysis. The included models were assessed for risk of bias and applicability.Results:A total of 8 articles involving 9 models were included, covering a total sample size of 1 291 cases, with 10 to 144 outcome events. The number of predictors ranged from 2 to 10, with common predictors including body mass index, smoking history, and breast volume, radiation dose, etc. The AUC values of the included models ranged from 0.76 to 0.98. The overall risk of bias for the models was relatively high, mainly due to issues related to study design, missing data handling, variable selection, and model validation.Conclusions:Existing risk prediction models for radiation dermatitis in breast cancer patients have certain limitations. It is recommended that future research further improve study designs, validate and optimize existing models, and develop high-performance risk prediction models.

Objective:To systematically review and evaluate risk prediction models for radiation dermatitis in breast cancer patients, providing a reference for developing higher-quality prediction models.Methods:A systematic search was conducted in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and China Biomedical Literature Database for studies related to risk prediction models for radiation dermatitis in breast cancer patients. The search timeframe was from database inception to February 28, 2024. Two researchers independently screened relevant literature based on inclusion and exclusion criteria, extracted the basic characteristics of the studies, and performed analysis. The included models were assessed for risk of bias and applicability.Results:A total of 8 articles involving 9 models were included, covering a total sample size of 1 291 cases, with 10 to 144 outcome events. The number of predictors ranged from 2 to 10, with common predictors including body mass index, smoking history, and breast volume, radiation dose, etc. The AUC values of the included models ranged from 0.76 to 0.98. The overall risk of bias for the models was relatively high, mainly due to issues related to study design, missing data handling, variable selection, and model validation.Conclusions:Existing risk prediction models for radiation dermatitis in breast cancer patients have certain limitations. It is recommended that future research further improve study designs, validate and optimize existing models, and develop high-performance risk prediction models.

Objective:To systematically review risk prediction models for frailty in maintenance hemodialysis (MHD) patients.Methods:Relevant literature on frailty risk prediction models for MHD patients were retrieved from PubMed, Web of Science, Embase, Cochrane Library, CINHAL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc from inception to March 25, 2024. Two researchers independently screened the literature and extracted data. The PROBAST tool was used to assess the methodological quality of the prediction models. Meta-analysis of predictive factors was conducted using Stata 16.0 software.Results:A total of 13 studies were included, comprising 19 frailty risk prediction models for MHD patients. All studies exhibited a high risk of bias. Six studies conducted internal validation, and three studies conducted external validation. The area under the receiver operating characteristic curve ( AUC) of the included prediction models ranged from 0.720 to 0.998. Meta-analysis revealed that age [ OR=1.149, 95% CI (1.070, 1.234), P<0.001], female gender [ OR=4.472, 95% CI (1.799, 11.117), P<0.001], nutritional score [ OR=2.650, 95% CI (1.010, 6.970), P=0.048], comorbidities [ OR=1.990, 95% CI (1.500, 2.650), P<0.001], and serum albumin [ OR=0.830, 95% CI (0.790, 0.880), P<0.001] were significant influencing factors for frailty in MHD patients. Conclusions:Risk prediction models for frailty in MHD patients are still in the research stage. Healthcare professionals should pay close attention to frailty risks in older patients, females, those with malnutrition, comorbidities, and low serum albumin levels, and implement timely interventions.