ObjectiveTo investigate the effects of hypoxia-treated mesenchymal stem cell （MSCs） exosomes （Exo） and their loading with curcumin on microglial inflammatory responses， and to explore the enhancing effect of hypoxia treatment on the function of MSCs Exo. MethodsThe supernatants of human umbilical cord （hUC）-MSCs cultured under normal and hypoxic conditions were collected， and Exo were isolated using ultracentrifugation. After identification by transmission electron microscopy and Western blot， curcumin was loaded using the co-incubation method. The lipopolysaccharide （LPS）-induced microglial inflammation model was treated with dimethyl sulfoxide （DMSO）， curcumin， normoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin， respectively. The expression of the M1-type marker inducible nitric oxide synthase （iNOS） in BV2 cells was detected by immunofluorescence （IF）. Western blot and enzyme-linked immunosorbent assay （ELISA） were used to measure the expression and secretion levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in the cells and their culture supernatants. ResultsNormoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin exhibited a "saucer-like" shape with a diameter ranging from 30~150 nm， and the expression of exosomal markers CD9， CD81， and TSG101 were positive. After treating the BV2 cell inflammation model， IF results showed that， compared with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression of iNOS. Moreover， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， the expression level of iNOS significantly decreased after treatment with hypoxic Exo loaded with curcumin. The results of Western blot and ELISA indicated that， in comparison with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression and secretion of the inflammatory cytokines TNF-α， IL-1β， and IL-6. Additionally， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， both the expression and secretion of TNF-α， IL-1β， and IL-6 significantly decreased after treatment with hypoxic Exo loaded with curcumin. ConclusionHypoxia preconditioning can enhance the ability of hUC-MSCs-Exo in the inhibition of microglial polarization and inflammatory factors’ secretion. Additionally， using Hypoxia-MSCs-Exo as a drug-delivery carrier of curcumin can improve its solubility and stability， facilitating its absorption by cells and exerting the therapeutic effect of combination therapy.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Premature ovarian insufficiency(POI)is a disease that seriously affects the health and life of women,which is also one of the main causes of female infertility.The incidence of POI is increasing in recent years.The diagnostic criteria of POI are not uniform,and different diagnostic criteria have inconsistent thresholds for various indicators.Strict diagnostic criteria are more conducive to early detection and treatment of POI.At present,complementary and alternative therapies such as traditional Chinese medicine,acupuncture and moxibustion are widely used in the treatment of POI.This article reviewed the recent studies on the complementary and alternative therapy of traditional Chinese medicine in the treatment of POI,and finds that the dialectical treatment of traditional Chinese medicine is based on the perspective of traditional Chinese medicine theory and puts forward corresponding treatment plans for different dialectical types.For example,treatment from the kidney,tonifying kidney filling essence,regulating chongren;Treatment from the liver,soothing the liver,regulating qi,nourishing blood and softening the liver;Treatment from the heart and spleen,nourishing Yangming,tonifying the spleen and nourishing the heart.In terms of acupuncture treatment,regulating menstruation and promoting pregnancy and regulating the conception vessel and toning the governor vessel and toning the kidney are often used to treat POI.In addition,moxibustion regulates body function by stimulating the bladder meridian and conception vessel and governor vessel acupoints.Other methods,such as ear acupoint bean-pressing,acupoint thread-embedding and acupoint injection,have also shown potential in the treatment of POI.This article summarizes the role and characteristics of traditional Chinese medicine in the treatment of POI,in order to provide ideas and basis for clinical treatment of POI.

Objective:To explore the risk assessment and intervention effect of WeChat platform-based health management in high-risk populations for cardiovascular diseases (CVD).Methods:It was a randomized controlled trial. A total of 480 individuals at high risk of CVD who underwent physical examinations at the Health Management Center of Sichuan Provincial People′s Hospital from February to April in 2023 were selected using a simple random sampling method. The participants were randomly assigned to either the intervention group or the control group (240 cases each) using a random number table. The control group received routine follow-up and health assessments, while the intervention group received an additional 12-month WeChat-based health management intervention. During the study, 28 participants were lost to follow-up, resulting in 227 participants in the intervention group and 225 in the control group being included in the final analysis. The 10-year CVD risk was assessed using the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) model, and psychological status was evaluated using the self-rating anxiety Scale (SAS) and the self-rating depression scale (SDS). Changes in health behaviors, adherence, life style, blood pressure, metabolic indicators, psychological status, and CVD risk were compared before and after the intervention in both groups to evaluate the intervention′s effectiveness.Results:Among the 452 high-risk participants analyzed, the intervention group included 227 individuals [mean age: (53.16±10.81) years; 117 males and 110 females], and the control group included 225 individuals [mean age: (52.60±10.25) years; 118 males and 107 females]. There was no significant differences in baseline characteristics between the two groups (all P>0.05). After 12 months of intervention, the intervention group showed significant improvements in medication adherence, intake of vegetables and fruits, exercise duration, sleep time, proportion of regular lifestyle, and high density lipoprotein cholesterol (HDL-C) levels, all of which were all higher than both the baseline values and those in the control group (all P<0.05). Conversely, the intervention group showed reductions in medical visit rate, smoking and drinking rates, high-salt diet, meat intake, body mass index (BMI), fasting blood glucose, systolic and diastolic blood pressure, low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, SAS and SDS scores when compared to the baseline values and those in the control group (all P<0.05). The proportions of participants with 10-year CVD risk levels of 10%-<20%, 20%-<30%, 30%-<40%, and ≥40% significantly decreased in the intervention group after intervention (18.94% vs 36.12%, 12.78% vs 26.43%, 7.93% vs 19.82%, 3.96% vs 17.63%), and were also significantly lower than those in the control group (18.94% vs 40.45%, 12.78% vs 30.67%, 7.93% vs 22.67%, 3.96% vs 16.89%) (all P<0.001). After 12 months, the intervention group showed significantly higher improvement rates in both medication adherence and non-medication-related compliance behaviors, including smoking, alcohol consumption, meat and salt intake, fruit and vegetable intake, exercise duration, sleep duration, and lifestyle regularity, when compared to those in the control group (16.74% vs -3.11%, 14.54% vs -0.89%, 16.74% vs -0.44%, 57.71% vs 8.44%, 21.15% vs -0.44%, 56.83% vs -6.67%, 51.54% vs -3.56%, 60.79% vs -7.11%, 26.87% vs -13.78%, 22.91% vs -1.78%) (all P<0.001). Conclusion:The WeChat platform-based health management intervention can effectively improve the behavioral patterns, compliance, control of CVD risk factors and psychological status of high-risk populations for CVD, and help reduce their 10-year risk of CVD.

Objective To evaluate answers to typical clinical questions related to neuro-ophthalmology generated by Artificial Intelligence(AI)Large Language Models(LLM)and to explore the performance of neuro-ophthalmology-related questions on LLM in a multidimensional manner using objective and expert assessment.Methods Multicenter,random-ized,cross-sectional pilot study.Thirty typical questions related to neuro-ophthalmology were selected based on four per-spectives:definition,etiology,clinical manifestations and signs,and treatment and prognosis,and were analyzed quantita-tively using Deepseek,Wenxin Yiyin 4.0,Doubao,and Kimi 1.5,which are four open-source LLMs in China,and quantita-tively analyzed with objective assessment;and quantitatively rated by three ophthalmologists using expert assessment for 120 answer texts.Three ophthalmology experts quantitatively scored the 120 answer texts.Three ophthalmologists quantita-tively scored the 120 answer texts.Level 3,5,and 4 Likert scales were developed according to the completeness,accura-cy,professionalism,relevance,and criticality of the question texts,respectively.The best-performing LLM was selected,and its performance was observed across the four types of questions.Additionally,three other experts assessed whether the best-performing one could be evaluated as a substitute for real-world doctor-patient communication.Results In the objective Chinese text reading difficulty analysis,the differences in total word count among the four LLMs were statistically significant(all P＜0.001).Of the four LLMs,Kimi 1.5 performed the best,with frequencies of 61％,29％,and 41％for the highest scores in completeness(3),accuracy and professionalism(5),and relevance and usefulness(4),respective-ly.Kimi 1.5 performed more consistently on the questions on the four areas of neuro-ophthalmologic disorders:definition,etiology,clinical manifestations and signs,treatment,and prognosis,with no between-group differences(P＞0.05).Con-clusion Chinese language LLMs have great potential in the clinical application of neuro-ophthalmology.Kimi 1.5 outper-forms other LLMs in terms of completeness,accuracy,professionalism,relevance,and usefulness,but it still cannot re-place real-world doctor-patient communication.There is a need to explore new diagnostic and therapeutic model of AI+physician in the future.

Objective To evaluate answers to typical clinical questions related to neuro-ophthalmology generated by Artificial Intelligence(AI)Large Language Models(LLM)and to explore the performance of neuro-ophthalmology-related questions on LLM in a multidimensional manner using objective and expert assessment.Methods Multicenter,random-ized,cross-sectional pilot study.Thirty typical questions related to neuro-ophthalmology were selected based on four per-spectives:definition,etiology,clinical manifestations and signs,and treatment and prognosis,and were analyzed quantita-tively using Deepseek,Wenxin Yiyin 4.0,Doubao,and Kimi 1.5,which are four open-source LLMs in China,and quantita-tively analyzed with objective assessment;and quantitatively rated by three ophthalmologists using expert assessment for 120 answer texts.Three ophthalmology experts quantitatively scored the 120 answer texts.Three ophthalmologists quantita-tively scored the 120 answer texts.Level 3,5,and 4 Likert scales were developed according to the completeness,accura-cy,professionalism,relevance,and criticality of the question texts,respectively.The best-performing LLM was selected,and its performance was observed across the four types of questions.Additionally,three other experts assessed whether the best-performing one could be evaluated as a substitute for real-world doctor-patient communication.Results In the objective Chinese text reading difficulty analysis,the differences in total word count among the four LLMs were statistically significant(all P＜0.001).Of the four LLMs,Kimi 1.5 performed the best,with frequencies of 61％,29％,and 41％for the highest scores in completeness(3),accuracy and professionalism(5),and relevance and usefulness(4),respective-ly.Kimi 1.5 performed more consistently on the questions on the four areas of neuro-ophthalmologic disorders:definition,etiology,clinical manifestations and signs,treatment,and prognosis,with no between-group differences(P＞0.05).Con-clusion Chinese language LLMs have great potential in the clinical application of neuro-ophthalmology.Kimi 1.5 outper-forms other LLMs in terms of completeness,accuracy,professionalism,relevance,and usefulness,but it still cannot re-place real-world doctor-patient communication.There is a need to explore new diagnostic and therapeutic model of AI+physician in the future.

Premature ovarian insufficiency(POI)is a disease that seriously affects the health and life of women,which is also one of the main causes of female infertility.The incidence of POI is increasing in recent years.The diagnostic criteria of POI are not uniform,and different diagnostic criteria have inconsistent thresholds for various indicators.Strict diagnostic criteria are more conducive to early detection and treatment of POI.At present,complementary and alternative therapies such as traditional Chinese medicine,acupuncture and moxibustion are widely used in the treatment of POI.This article reviewed the recent studies on the complementary and alternative therapy of traditional Chinese medicine in the treatment of POI,and finds that the dialectical treatment of traditional Chinese medicine is based on the perspective of traditional Chinese medicine theory and puts forward corresponding treatment plans for different dialectical types.For example,treatment from the kidney,tonifying kidney filling essence,regulating chongren;Treatment from the liver,soothing the liver,regulating qi,nourishing blood and softening the liver;Treatment from the heart and spleen,nourishing Yangming,tonifying the spleen and nourishing the heart.In terms of acupuncture treatment,regulating menstruation and promoting pregnancy and regulating the conception vessel and toning the governor vessel and toning the kidney are often used to treat POI.In addition,moxibustion regulates body function by stimulating the bladder meridian and conception vessel and governor vessel acupoints.Other methods,such as ear acupoint bean-pressing,acupoint thread-embedding and acupoint injection,have also shown potential in the treatment of POI.This article summarizes the role and characteristics of traditional Chinese medicine in the treatment of POI,in order to provide ideas and basis for clinical treatment of POI.

Objective:To explore the risk assessment and intervention effect of WeChat platform-based health management in high-risk populations for cardiovascular diseases (CVD).Methods:It was a randomized controlled trial. A total of 480 individuals at high risk of CVD who underwent physical examinations at the Health Management Center of Sichuan Provincial People′s Hospital from February to April in 2023 were selected using a simple random sampling method. The participants were randomly assigned to either the intervention group or the control group (240 cases each) using a random number table. The control group received routine follow-up and health assessments, while the intervention group received an additional 12-month WeChat-based health management intervention. During the study, 28 participants were lost to follow-up, resulting in 227 participants in the intervention group and 225 in the control group being included in the final analysis. The 10-year CVD risk was assessed using the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) model, and psychological status was evaluated using the self-rating anxiety Scale (SAS) and the self-rating depression scale (SDS). Changes in health behaviors, adherence, life style, blood pressure, metabolic indicators, psychological status, and CVD risk were compared before and after the intervention in both groups to evaluate the intervention′s effectiveness.Results:Among the 452 high-risk participants analyzed, the intervention group included 227 individuals [mean age: (53.16±10.81) years; 117 males and 110 females], and the control group included 225 individuals [mean age: (52.60±10.25) years; 118 males and 107 females]. There was no significant differences in baseline characteristics between the two groups (all P>0.05). After 12 months of intervention, the intervention group showed significant improvements in medication adherence, intake of vegetables and fruits, exercise duration, sleep time, proportion of regular lifestyle, and high density lipoprotein cholesterol (HDL-C) levels, all of which were all higher than both the baseline values and those in the control group (all P<0.05). Conversely, the intervention group showed reductions in medical visit rate, smoking and drinking rates, high-salt diet, meat intake, body mass index (BMI), fasting blood glucose, systolic and diastolic blood pressure, low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, SAS and SDS scores when compared to the baseline values and those in the control group (all P<0.05). The proportions of participants with 10-year CVD risk levels of 10%-<20%, 20%-<30%, 30%-<40%, and ≥40% significantly decreased in the intervention group after intervention (18.94% vs 36.12%, 12.78% vs 26.43%, 7.93% vs 19.82%, 3.96% vs 17.63%), and were also significantly lower than those in the control group (18.94% vs 40.45%, 12.78% vs 30.67%, 7.93% vs 22.67%, 3.96% vs 16.89%) (all P<0.001). After 12 months, the intervention group showed significantly higher improvement rates in both medication adherence and non-medication-related compliance behaviors, including smoking, alcohol consumption, meat and salt intake, fruit and vegetable intake, exercise duration, sleep duration, and lifestyle regularity, when compared to those in the control group (16.74% vs -3.11%, 14.54% vs -0.89%, 16.74% vs -0.44%, 57.71% vs 8.44%, 21.15% vs -0.44%, 56.83% vs -6.67%, 51.54% vs -3.56%, 60.79% vs -7.11%, 26.87% vs -13.78%, 22.91% vs -1.78%) (all P<0.001). Conclusion:The WeChat platform-based health management intervention can effectively improve the behavioral patterns, compliance, control of CVD risk factors and psychological status of high-risk populations for CVD, and help reduce their 10-year risk of CVD.

OBJECTIVES: Pelvic floor sensory training is commonly used in clinical practice for the treatment of stress urinary incontinence (SUI); however, there is a lack of comparative studies evaluating pelvic floor sensation between women with SUI and healthy controls. Additionally, normative data for two-point discrimination thresholds in the female pelvic floor region remain scarce. This study aims to compare the results of 4 sensory tests in the pelvic floor region between women with mild SUI and healthy women, in order to provide reference values for two-point discrimination thresholds in this area. METHODS: From April 1 to October 30, 2023, 108 healthy women [(32.5±3.6) years] and 90 women with mild SUI [(32.9±3.3) years] were recruited from the Third Xiangya Hospital, Central South University. Participants underwent 4 sensory tests in the pelvic floor region: Two-dot discrimination, weight perception, shape recognition, and 9-grid localization. The results were compared between the 2 groups. RESULTS: Compared with healthy women, those with mild SUI had lower sensitivity and higher thresholds in 2-dot discrimination tests in the pelvic floor region (all P<0.001). No significant differences were found between groups in weight perception, shape recognition, or grid localization tests (P>0.05). CONCLUSIONS Women with mild stress urinary incontinence have impaired two-point discrimination ability in the pelvic floor region.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Adult ; Sensory Thresholds/physiology*

Objective:To explore the effect of family empowerment model on the improvement of swallowing care ability and care preparedness of primary caregivers of first-episode stroke dysphagia patients, further to explore its impact on patients′s wallowing function and life quality.Methods:This study was a randomized controlled study. From January 2021 to December 2022, 80 main caregivers of patients with dysphagia caused by manual stroke admitted to the Department of Acupuncture and Moxibustion, Shenzhen Hospital of Traditional Chinese Medicine were selected as the research objects, and 40 cases in the control group and 40 cases in the observation group were selected by random number table method. The control group were treated with conventional nursing care of first-episode stroke dysphagia patients in the acupuncture and moxibustion Department. On the basis of the conventional care in the control group, the observation group were treated with family empowerment model intervention for 14 days and was followed up for 28 days. Primary caregivers′ swallowing care ability, Caregiver Preparedness Scale (CPS), patients′ swallowing function rate, Swallowing Related Quality of Life (SWALQOL) were used to evaluate the effects before intervention and at the end of intervention.Results:There were 18 males and 19 females primary caregivers in the control group, aged (55.61 ± 7.43) years old. There were 18 males and 21 females primary caregivers in the observation group, aged (58.23 ± 8.22) years old. The swallowing care ability score showed a statistically significant difference between the observation group (143.47 ± 3.96) and the control group (107.74 ± 1.43) ( t=-26.76, P<0.05). After intervention, the caregiver preparedness scale was (26.11 ± 3.81) in the observation group, and (18.35 ± 4.54) in the control group, and the difference was statistically significant ( t=-4.11, P<0.05).The patients′ swallowing function rate and SWALQOL score were respectively 97.44% (38/39) and (91.41 ± 8.08) points in the observation group, and 72.97% (27/37) and (80.33 ± 4.21) points in the control group, and the difference was both statistically significant ( χ2=10.76, t=-2.54, both P<0.05). Conclusions:The implementation of family empowerment model could enhance the swallowing care ability and care preparedness of primary caregivers of the first-episode stroke dysphagia patients, which could further improve patients′ swallowing function and life quality.