Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective To investigate the therapeutic efficacy of the combination of upper limb rehabilitation robots(ULRR)and ultrasound-guided extracorporeal shock wave(ESW)in the treatment of mild to moderate rotator cuff injuries.Methods A total of 90 patients with mild to moderate rotator cuff injuries,who were admitted to the Second Affiliated Hospital of Anhui Medical University between January 2023 and March 2024,were selected and randomly assigned to three groups:Group A(basic rehabilitation),Group B(basic rehabilitation+ESW),and Group C(basic rehabilitation+ESW+ULRR),with 30 patients in each group.Before and after treatment,shoulder pain was assessed using the visual analogue scale(VAS).Proprioception was evaluated based on shoulder joint position reproduction error.The integral electromyography(iEMG)and root mean square(RMS)values of the median tract,supraspinatus,infraspinatus,and deltoid muscles on the affected side were measured using surface electromyography(sEMG).The active range of motion(AROM)for external rotation,abduction,and forward flexion of the affected shoulder was measured using a standard goniometer.Overall shoulder function was evaluated using the Constant-Murley Shoulder Score(CMS).The clinical efficacy rate and patient satisfaction levels were compared among the three groups.Results After treatment,the VAS score and shoulder position reproduction deviation angle in all three groups significantly decreased.Additionally,the iEMG and RMS values of the middle deltoid,supraspinatus,and infraspinatus muscles;the AROM of shoulder external rotation,abduction,and forward flexion;and the CMS scores(including pain,activities of daily living,active range of motion,and muscle strength)all showed significant improvement.Furthermore,the degree of improvement in all evaluated parameters in Group C was significantly greater than that observed in Groups A and B(P<0.05).Moreover,Group C demon-strated a significantly higher clinical response rate and greater patient satisfaction compared to Groups A and B(P<0.05).Conclusion For patients with mild to moderate rotator cuff injuries,the integration of an upper limb rehabilitation robot with extracorporeal shock wave therapy demonstrates superior therapeutic outcomes,effectively alleviating pain,enhancing motor function and proprioception,and increasing overall patient satisfaction.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective:To investigate the expressions of serum cytokines in patients with autoimmune retinopathy (AIR), and their association with disease diagnosis as well as clinical features.Methods:A prospective case-control study was conducted.A total of 90 eyes of 45 AIR patients were consecutively collected in Beijing Tongren Hospital from September 2018 to December 2023.Additionally, age-matched 43 controls (86 eyes) were enrolled, consisting of 21 patients (42 eyes) with retinitis pigmentosa as a disease control group and 22 healthy subjects (44 eyes) as a normal control group.The main clinical outcome measures included best-corrected visual acuity (BCVA), mean deviation (MD) of visual field, central retinal thickness and the maximal response amplitude and implicit time of full-field electroretinography (ff-ERG). A total of 21 serum cytokines were detected by Luminex multiple cytokines assay or ELISA.Differences in serum cytokine concentrations of among groups, the correlation between cytokine levels and clinical outcomes, and the contribution of cytokines to the diagnosis of AIR were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital (No.TRECKY2018-048). Written informed consent was obtained from each subject.Results:In AIR patients, the expression levels of Th1-type cytokines or receptors (including interferon-γ[IFN-γ], interleukin [IL]-8, C-X-C motif chemokine ligand [CXCL]9, and CXCL10) and Th17-type cytokines (including IL-17 and IL-6) were elevated.There were statistically significant overall differences in pro-inflammatory cytokines/chemokines (IL-6, IL-8, CXCL10, IL-10, IFN-γ, IL-17, C-X3-C motif chemokine ligand 1 [CX3CL]1, CXCL9) among the three groups ( H=10.823, 10.816, 9.633, 10.103, 23.670, 16.493, 9.050, 9.253; all P<0.05). Compared with the disease control group and the healthy control group, the IFN-γ level was significantly increased in the AIR group (both P=0.001). Compared with the healthy control group, the serum levels of IL-6, IL-8, CXCL10, IL-10, IL-17, and CXCL9 in the AIR group were significantly elevated (all P<0.05). The serum level of CX3CL1 was significantly higher in the AIR group than in the disease control group ( P=0.039). The serum level of IFN-γ was significantly higher in the AIR group than in the healthy control and disease control groups, but no association with AIR diagnosis was found ( OR=1.402, 95% CI: 0.710-2.870, P=0.245). Multilevel mixed-effects regression modeling analysis showed that the serum levels of IL-8 and CXCL9 in AIR patients were positively correlated with LogMAR BCVA ( β=0.028, P=0.033; β=0.023, P=0.003). The C-C motif chemokine ligand 11 level was positively correlated with implicit time of ERG a-wave ( β=13.950, P<0.001). The tumor necrosis factor-α level was positively correlated with MD value of visual field ( β=6.310, P=0.002). Granulocyte-macrophage colony-stimulating factor was negatively correlated with the amplitude of ERG a-wave and granulocyte colony-stimulating factor was negatively correlated with ERG b-wave amplitude ( β=-152.700, P<0.001; β=-14.790, P=0.003). Conclusions:Serum Th1 and Th17-type cytokines/chemokines may be involved in the pathogenesis of AIR and are related to disease severity.

Objective To investigate the therapeutic efficacy of the combination of upper limb rehabilitation robots(ULRR)and ultrasound-guided extracorporeal shock wave(ESW)in the treatment of mild to moderate rotator cuff injuries.Methods A total of 90 patients with mild to moderate rotator cuff injuries,who were admitted to the Second Affiliated Hospital of Anhui Medical University between January 2023 and March 2024,were selected and randomly assigned to three groups:Group A(basic rehabilitation),Group B(basic rehabilitation+ESW),and Group C(basic rehabilitation+ESW+ULRR),with 30 patients in each group.Before and after treatment,shoulder pain was assessed using the visual analogue scale(VAS).Proprioception was evaluated based on shoulder joint position reproduction error.The integral electromyography(iEMG)and root mean square(RMS)values of the median tract,supraspinatus,infraspinatus,and deltoid muscles on the affected side were measured using surface electromyography(sEMG).The active range of motion(AROM)for external rotation,abduction,and forward flexion of the affected shoulder was measured using a standard goniometer.Overall shoulder function was evaluated using the Constant-Murley Shoulder Score(CMS).The clinical efficacy rate and patient satisfaction levels were compared among the three groups.Results After treatment,the VAS score and shoulder position reproduction deviation angle in all three groups significantly decreased.Additionally,the iEMG and RMS values of the middle deltoid,supraspinatus,and infraspinatus muscles;the AROM of shoulder external rotation,abduction,and forward flexion;and the CMS scores(including pain,activities of daily living,active range of motion,and muscle strength)all showed significant improvement.Furthermore,the degree of improvement in all evaluated parameters in Group C was significantly greater than that observed in Groups A and B(P<0.05).Moreover,Group C demon-strated a significantly higher clinical response rate and greater patient satisfaction compared to Groups A and B(P<0.05).Conclusion For patients with mild to moderate rotator cuff injuries,the integration of an upper limb rehabilitation robot with extracorporeal shock wave therapy demonstrates superior therapeutic outcomes,effectively alleviating pain,enhancing motor function and proprioception,and increasing overall patient satisfaction.

Objective:To investigate the expressions of serum cytokines in patients with autoimmune retinopathy (AIR), and their association with disease diagnosis as well as clinical features.Methods:A prospective case-control study was conducted.A total of 90 eyes of 45 AIR patients were consecutively collected in Beijing Tongren Hospital from September 2018 to December 2023.Additionally, age-matched 43 controls (86 eyes) were enrolled, consisting of 21 patients (42 eyes) with retinitis pigmentosa as a disease control group and 22 healthy subjects (44 eyes) as a normal control group.The main clinical outcome measures included best-corrected visual acuity (BCVA), mean deviation (MD) of visual field, central retinal thickness and the maximal response amplitude and implicit time of full-field electroretinography (ff-ERG). A total of 21 serum cytokines were detected by Luminex multiple cytokines assay or ELISA.Differences in serum cytokine concentrations of among groups, the correlation between cytokine levels and clinical outcomes, and the contribution of cytokines to the diagnosis of AIR were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital (No.TRECKY2018-048). Written informed consent was obtained from each subject.Results:In AIR patients, the expression levels of Th1-type cytokines or receptors (including interferon-γ[IFN-γ], interleukin [IL]-8, C-X-C motif chemokine ligand [CXCL]9, and CXCL10) and Th17-type cytokines (including IL-17 and IL-6) were elevated.There were statistically significant overall differences in pro-inflammatory cytokines/chemokines (IL-6, IL-8, CXCL10, IL-10, IFN-γ, IL-17, C-X3-C motif chemokine ligand 1 [CX3CL]1, CXCL9) among the three groups ( H=10.823, 10.816, 9.633, 10.103, 23.670, 16.493, 9.050, 9.253; all P<0.05). Compared with the disease control group and the healthy control group, the IFN-γ level was significantly increased in the AIR group (both P=0.001). Compared with the healthy control group, the serum levels of IL-6, IL-8, CXCL10, IL-10, IL-17, and CXCL9 in the AIR group were significantly elevated (all P<0.05). The serum level of CX3CL1 was significantly higher in the AIR group than in the disease control group ( P=0.039). The serum level of IFN-γ was significantly higher in the AIR group than in the healthy control and disease control groups, but no association with AIR diagnosis was found ( OR=1.402, 95% CI: 0.710-2.870, P=0.245). Multilevel mixed-effects regression modeling analysis showed that the serum levels of IL-8 and CXCL9 in AIR patients were positively correlated with LogMAR BCVA ( β=0.028, P=0.033; β=0.023, P=0.003). The C-C motif chemokine ligand 11 level was positively correlated with implicit time of ERG a-wave ( β=13.950, P<0.001). The tumor necrosis factor-α level was positively correlated with MD value of visual field ( β=6.310, P=0.002). Granulocyte-macrophage colony-stimulating factor was negatively correlated with the amplitude of ERG a-wave and granulocyte colony-stimulating factor was negatively correlated with ERG b-wave amplitude ( β=-152.700, P<0.001; β=-14.790, P=0.003). Conclusions:Serum Th1 and Th17-type cytokines/chemokines may be involved in the pathogenesis of AIR and are related to disease severity.

AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P＜0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P＜0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P＜0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P＜0.05,P＜0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P＜0.05,P＜0.01);mitigated inflammation and collagen deposition(P＜0.05,P＜0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.05,P＜0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND:Mongolian medicine Echinops sphaerocephalus L.is a commonly used medicine for bone injury in Mongolian medicine.It is effective for tendon injury,fracture,bone nonunion,bone fever,tingling,sore and other diseases.Our previous studies have confirmed that Mongolian medicine Echinops sphaerocephalus L.can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,but its effect on angiogenesis in the process of bone defect repair is unknown.OBJECTIVE:To investigate the effect of Echinops sphaerocephalus L.on in vitro angiogenesis in human umbilical vein vascular endothelial cells and to explore the angiogenesis-promoting active ingredients and their mechanisms of action of Echinops sphaerocephalus L.using network pharmacology technology.METHODS:The ethanol extract of Echinops sphaerocephalus L.was prepared and preserved by freeze-drying.The proliferation,migration,chemotaxis and angiogenesis of human umbilical vein endothelial cells were observed after treatment with different concentrations(1 000,100,and 10 μg/mL)of Echinops sphaerocephalus L.The active components and possible signaling pathways that promoted angiogenesis were enriched and analyzed by network pharmacology.RESULTS AND CONCLUSION:(1)The effect of Echinops sphaerocephalus L.on angiogenesis was regulated by its mass concentration:at low mass concentration(10 μg/mL),Echinops sphaerocephalus L.could promote the proliferation,migration,chemotaxis and angiogenesis of human umbilical vein vascular endothelial cells;on the contrary,Echinops sphaerocephalus L.inhibited the proliferation,migration,and chemotaxis of human umbilical vein endothelial cells at high mass concentration(1 000 μg/mL).However,the inhibitory effect of Echinops sphaerocephalus L.on angiogenesis was not significant at high mass concentration due to the limitation of experimental time.10 μg/mL Echinops sphaerocephalus L.could up-regulate the mRNA expression of angiogenesis-associated factors,including kinase insert domain receptor,vascular endothelial growth factor A,and hypoxia-inducible factor α,and thereby influenced angiogenesis during bone repair.(2)Network pharmacological analyses indicated that Echinops sphaerocephalus L.may bind to eight core targets(TGFB1,TNF,IL-6,STAT3,CTNNB1,IL-1B,AKT1,and HIF-1A)through four core active components(apigenin,caffeic acid,quercetin,and chlorogenic acid)to exert an effect on angiogenesis,atherosclerosis,multiple viral infections,and tumor angiogenesis-related signaling pathways.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*