ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats （SHRs） through the pathways of farnesoid X receptor （FXR）-myosin light chain kinase （MLCK）/phosphorylated myosin light chain （p-MLC） and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group， amlodipine besylate group （0.5 mg·kg^-1·d^-1）， and high， middle and low dose groups of Zhengan Xifengtang （34.5， 17.25， 8.625 g·kg^-1·d^-1）； eight age-matched male Wistar-Kyoto （WKY） rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks， and the blood pressure of the rats was measured regularly. After the intervention， the rats were euthanized to collect tissue samples. Hematoxylin and eosin （HE） staining and Alcian blue-periodic acid-Schiff （AB-PAS） staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay （ELISA） was employed to measure plasma lipopolysaccharide （LPS） and diamine oxidase （DAO） levels in each group of rats. Immunofluorescence （IF） assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 （ZO-1）， Occludin， Claudin-1， junctional adhesion molecule-1 （JAM-1）， mucin-2 （MUC2）， FXR， MLCK， and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of ZO-1， Occludin， Claudin-1， JAM-1， MUC2， FXR， MLCK， and MLC in colon tissue. ResultsCompared with the normal group， the blood pressure in the model group increased significantly （P<0.01）， the colonic mucosal structure was seriously damaged， and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly （P<0.01）， the relative fluorescence intensity of FXR in colon decreased， while that of p-MLC increased （P<0.01）. The protein and mRNA expressions of ZO-1， Claudin-1， JAM-1， Occludin， MUC2 and FXR decreased significantly （P<0.01）， whereas the protein expression of MLCK and p-MLC increased significantly （P<0.01）. Additionally， the mRNA expression of MLCK and MLC increased significantly （P<0.01）. Compared with the model group， the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure （P<0.01）. The damage of colonic mucosa structure was alleviated， the infiltration of inflammatory cells decreased， and the number of goblet cells increased. LPS and DAO levels were decreased （P<0.05， P<0.01）. In the colon， the relative fluorescence intensity of FXR increased， while that of p-MLC decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of ZO-1， Claudin-1， JAM-1， Occludin， and FXR increased significantly （P<0.05， P<0.01）， while the protein expression of MLCK and p-MLC decreased significantly （P<0.05， P<0.01）. Furthermore， the mRNA expression of MLCK and MLC decreased significantly （P<0.05， P<0.01）， and the protein expression of MUC2 increased significantly （P<0.05， P<0.01）. The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly （P<0.05， P<0.01）. ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein， thereby reducing intestinal mucosal permeability， promoting mucosal barrier repair， decreasing LPS release into the blood， and ultimately lowering blood pressure.

ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats （SHRs） through the pathways of farnesoid X receptor （FXR）-myosin light chain kinase （MLCK）/phosphorylated myosin light chain （p-MLC） and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group， amlodipine besylate group （0.5 mg·kg^-1·d^-1）， and high， middle and low dose groups of Zhengan Xifengtang （34.5， 17.25， 8.625 g·kg^-1·d^-1）； eight age-matched male Wistar-Kyoto （WKY） rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks， and the blood pressure of the rats was measured regularly. After the intervention， the rats were euthanized to collect tissue samples. Hematoxylin and eosin （HE） staining and Alcian blue-periodic acid-Schiff （AB-PAS） staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay （ELISA） was employed to measure plasma lipopolysaccharide （LPS） and diamine oxidase （DAO） levels in each group of rats. Immunofluorescence （IF） assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 （ZO-1）， Occludin， Claudin-1， junctional adhesion molecule-1 （JAM-1）， mucin-2 （MUC2）， FXR， MLCK， and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of ZO-1， Occludin， Claudin-1， JAM-1， MUC2， FXR， MLCK， and MLC in colon tissue. ResultsCompared with the normal group， the blood pressure in the model group increased significantly （P<0.01）， the colonic mucosal structure was seriously damaged， and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly （P<0.01）， the relative fluorescence intensity of FXR in colon decreased， while that of p-MLC increased （P<0.01）. The protein and mRNA expressions of ZO-1， Claudin-1， JAM-1， Occludin， MUC2 and FXR decreased significantly （P<0.01）， whereas the protein expression of MLCK and p-MLC increased significantly （P<0.01）. Additionally， the mRNA expression of MLCK and MLC increased significantly （P<0.01）. Compared with the model group， the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure （P<0.01）. The damage of colonic mucosa structure was alleviated， the infiltration of inflammatory cells decreased， and the number of goblet cells increased. LPS and DAO levels were decreased （P<0.05， P<0.01）. In the colon， the relative fluorescence intensity of FXR increased， while that of p-MLC decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of ZO-1， Claudin-1， JAM-1， Occludin， and FXR increased significantly （P<0.05， P<0.01）， while the protein expression of MLCK and p-MLC decreased significantly （P<0.05， P<0.01）. Furthermore， the mRNA expression of MLCK and MLC decreased significantly （P<0.05， P<0.01）， and the protein expression of MUC2 increased significantly （P<0.05， P<0.01）. The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly （P<0.05， P<0.01）. ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein， thereby reducing intestinal mucosal permeability， promoting mucosal barrier repair， decreasing LPS release into the blood， and ultimately lowering blood pressure.

Objective To explore the relationship between the head injury criterion(HIC)values in anterior-posterior(AP)collisions and lateral-medial(LM)collisions.Methods A total of 102 male SD rats were randomly divided into a control group of 0 m(6 rats),4 AP groups(12 rats/group)and 4 LM groups(12 rats/group).After adaptive training,the classical Marmarou model was used to execute the brain AP and LM collisions under a series of different height impacts,and the HIC values were calculated.The experimental group data of the walk-pole test and grip strength test were collected at 24 hours before and after injury,and the data of the proportion of hemorrhage in the corpus callosum and pyramidal tracts were collected at 24 hours after injury.Results As the collision heights increased in both AP and LM groups,there were positive correlations with changes in WP test time and peak GS,and corresponding increases in the proportion of hemorrhage in the cc and py.According to the mathematical relationships between the comprehensive injury degrees and HIC values,it was found that at the same injury degree,LM-HIC value was less than AP-HIC value.A mathematical relationship between AP-HIC and LM-HIC was fitted based on the comprehensive injury degrees.At the same HIC,LM group experienced more severe injuries,and AP group was more tolerant to head collision.Conclusion The injury severity in LM group is greater than that of AP group at the same HIC.Preliminary results show there is a linear mathematical relationship between AP-HIC and LM-HIC.These results can be expected to expand the application scope of HIC and achieve an accurate assessment of the LM collision severity.

Objective To explore the effect of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with unilateral upper limb mirror training on contralateral limb strength in patients with hemiplegia after ischemic stroke.Methods A total of 196 patients with hemiplegia after ischemic stroke were selected.All patients were divided into study group and control group via a random number table method,with 98 patients in each group.The control group received mirror training,while the study group received low-frequency rTMS treatment in addition to the control group.The neuroelectrophysiology,neurological function,limb motor function,and clinical efficacy of all patients were observed before and after treatment,and all patients were performed the resting-state functional MRI examination.A generalized estimating equation(GEE)model were used to analyze the improvement of contralateral limb strength.Results After treatment,the seed points in the study group showed a significant enhancement in connectivity with the whole brain function.The overall efficiency of the study group was significantly better than that of the control group.After treatment,the central motor conduction time(CMCT),neuron specific enolase(NSE),cortical latency(CL),and S100β of the two groups of patients were significantly reduced compared with before treatment,while the neurotrophin-3(NT-3),nerve growth factor(NGF),Fugl-Meyer assessment upper extremities(FMA-UE),Wolf motor function test(WMFT),modified Barthel index(MBI),and Berg balance scale(BBS)scores were significantly increased.Moreover,the study group showed a more significant improvement compared to the control group(P＜0.05).The GEE model analysis results showed that the improvement of contralateral limb strength in the study group was significantly better than that in the control group.Conclusion Low-frequency rTMS combined with unilateral upper limb mirror training can improve cortical excitability and upper limb motor function in hemiplegic patients after ischemic stroke,with good therapeutic effects.

Post-stroke cognitive impairment (PSCI) is one of the most common complications of stroke and an important reason for the poor prognosis of patients with motor and language dysfunction after stroke. However, its exact pathogenesis has not been fully clarified. An in-depth understanding of the pathophysiological process of PSCI is crucial for establishing effective prevention and treatment strategies. The cerebral lymphoid system is a key waste clearance pathway discovered in the central nervous system in recent years, and its potential role in neurodegenerative diseases has received extensive attention. More and more studies suggest that the cerebral lymphatic system may be closely related to the occurrence and development of PSCI. This article aims to explore the basic structure and function of the cerebral lymphatic system, as well as its mechanism of action in PSCI. We systematically reviewed the research progress on the potential connection between the cerebral lymphatic system and PSCI. Furthermore, this article also summarizes the potential applications of the cerebral lymphatic system in the treatment of PSCI and presents prospects for future research directions.

Objective:To identify the serotype and genotype characteristics of the first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province. Methods:The information of seven suspected cluster brucellosis cases reported in Lanping County, Nujiang Lisu Autonomous Prefecture in April 2023 were collected, blood samples were collected, and the strains were isolated and cultured. Serological methods were employed for brucellosis diagnosis, bacterial species identification was performed using BCSP31-PCR and AMOS-PCR. Multilocus locus variable-number tandem repeat analysis (MLVA) was conducted for strain genotyping, followed by phylogenetic analysis comparing the strains with those from other regions of China.Results:All seven cases were diagnosed with brucellosis, they were all villagers from the same village and had daily contact with sheeps. Four suspected Brucella strains were isolated, identified as Brucella melitensis biotype by BCSP31-PCR and AMOS-PCR. The four isolated strains exhibited identical MLVA-16 genotype, with MLVA-8 genotype 42 and MLVA-11 genotype 180, belonging to the Eastern Mediterranean lineage. Compared with the MLVA-16 of the isolated strains from other regions of China, the four isolated strains formed an independent cluster. Conclusion:The first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province is caused by Brucella melitensis biotype, and the four isolated strains have showed unique MLVA genotype.

Objective Auditory brainstem response(ABR)is an objective electrophysiological test that evalu-ates a patient's hearing,and the ABR is interpreted primarily by recognizing the latency of waves Ⅰ through Ⅴ.The latency of wave Ⅰ to wave Ⅴ has important reference value for clinicians to judge the status of patients' auditory neu-ral pathways,so accurate interpretation of the results of this examination is particularly important.However,the a-nalysis of the result of the ABR entirely depends on the auditory teacher's ability to recognize and interpret the hu-man eye,which makes it difficult for inexperienced auditory teachers to interpret ABR waveforms.In order to solve this problem,many scholars proposed to use machine learning(ML)model to objectively interpret ABR results.ML has strong learning ability and can independently complete an objective and accurate interpretation of ABR re-sults,which brings the dawn for the objective and accurate interpretation of ABR results.

BACKGROUND:During healing process of chronic wounds,excessive production of reactive oxygen species can impair the function of L929 fibroblasts,thereby delaying wound repair.Therefore,protecting fibroblasts from oxidative stress is important to promote wound healing. OBJECTIVE:To assess the protective effects of carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma(CMC-OCS/PRP)hydrogel on L929 cells under H2O2 stimulation. METHODS:CMC-OCS/PRP hydrogels were prepared,and the micromorphology,degradation performance,scavenging ability of H2O2 and hydroxyl radical and biocompatibility of the hydrogels were characterized.L929 cells with good growth state were taken and cultured in five groups.The control group was cultured conventionally.H2O2 was added to the H2O2 group.Carboxymethyl chitosan-oxidized chondroitin sulfate hydrogel extract+H2O2 was added to the CMC-OCS group.Platelet-rich plasma gel extract+H2O2 was added to the PRP group.The CMC-OCS/PRP group was treated with carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma hydrogel extract+H2O2.Each group was treated with hydrogel extract for 6 hours,and then H2O2 for 24 hours.After culture,the levels of active oxygen and malondialdehyde,apoptosis and expression of collagen fiber I protein were detected.In the presence of H2O2,the above hydrogel extracts were directly or indirectly co-cultured with L929 fibroblasts for 36 hours,respectively.Migration ability of the cells was detected by scratch test and Transwell chamber test. RESULTS AND CONCLUSION:(1)CMC-OCS/PRP hydrogels had uniform and interrelated porous structure and good degradation ability,could effectively remove H2O2 and hydroxyl radicals in vitro,and had good biocompatibility.(2)Compared with the control group,the apoptosis rate,reactive oxygen species,and malondialdehyde levels were increased(P<0.05);the spread area of cells was decreased(P<0.05),and the expression of collagen fiber I protein had no significant changes(P>0.05)in the H2O2 group.Compared with the H2O2 group,reactive oxygen species level was decreased in the CMC-OCS group(P<0.05),malondialdehyde level was decreased(P<0.05),and cell spread area was increased(P<0.05)in the PRP group,CMC-OCS group,and CMC-OCS/PRP group;apoptosis rate was decreased in the CMC-OCS/PRP group(P<0.05),and collagen fiber I protein expression was increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05).(3)Compared with the control group,the number of cell migration was decreased(P<0.05),and the migration area had no significant change(P>0.05)in the H2O2 group.Compared with the H2O2 group,the number and area of cell migration were increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05),and the increase was most significant in the CMC-OCS/PRP group.(4)Under oxidative stress,CMC-OCS/PRP hydrogel can improve the migration ability of fibroblasts,resist cell apoptosis,and preserve cell extension function.

BACKGROUND: There is growing evidence that the occurrence and severity of respiratory diseases in children are related to the concentration of air pollutants. Nonetheless, evidence regarding the association between short-term exposure to air pollution and outpatient visits for respiratory diseases in children remains limited. Outpatients cover a wide range of disease severity, including both severe and mild cases, some of which may need to be transferred to inpatient treatment. This study aimed to quantitatively evaluate the impact of short-term ambient air pollution exposure on outpatient visits for respiratory conditions in children. METHODS: This study employed data of the Second People's Hospital of Yichang from January 1, 2016 to December 31, 2023, to conduct a time series analysis. The DLNM approach was integrated with a generalized additive model to examine the daily outpatient visits of pediatric patients with respiratory illnesses in hospital, alongside air pollution data obtained from monitoring stations. Adjustments were made for long-term trends, meteorological variables, and other influencing factors. RESULTS: A nonlinear association was identified between PM_2.5, PM₁₀, O₃, NO₂, SO₂, CO levels and the daily outpatient visits for respiratory diseases among children. All six pollutants exhibit a hysteresis impact, with varying durations ranging from 4 to 6 days. The risks associated with air pollutants differ across various categories of children's respiratory diseases; notably, O₃ and CO do not show statistical significance concerning the risk of chronic respiratory conditions. Furthermore, the results of infectious respiratory diseases were similar with those of respiratory diseases. CONCLUSIONS Our results indicated that short-term exposure to air pollutants may contribute to an increased incidence of outpatient visits for respiratory illnesses among children, and controlling air pollution is important to protect children's health.
Humans ; China/epidemiology* ; Air Pollutants/analysis* ; Respiratory Tract Diseases/chemically induced* ; Child ; Child, Preschool ; Environmental Exposure/adverse effects* ; Air Pollution/analysis* ; Infant ; Male ; Particulate Matter/adverse effects* ; Female ; Ambulatory Care/statistics & numerical data* ; Outpatients/statistics & numerical data* ; Adolescent ; Infant, Newborn

Refractory inner ear disease refers to a spectrum of inner ear diseases that fail to achieve good therapeutic effects even after standardized treatment recommended by existing clinical practice guidelines. This disease spectrum is characterized by diverse etiological factors, high phenotypic heterogeneity, unclear subtype characteristics, unknown pathogenic mechanisms, and variable prognosis, making it difficult to define precisely. Refractory inner ear disease accounts for a significant proportion of the total population with inner ear diseases and has not been systematically summarized, refined, and deeply studied to date. This article, for the first time, clearly proposes the concept, definition, and scope of refractory inner ear disease, and elaborates on the current research status, challenges, and coping strategies for refractory inner ear disease. With the development and progress of science and technology, we believe that in the future we will witness more innovative technologies and new drugs applied to the treatment of refractory inner ear disease, bringing hope of cure to patients.
Humans ; Labyrinth Diseases/therapy*