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.

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.

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 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 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.

Objective To investigate the research hotspot and development trend of noise-induced hearing loss(NIHL)in the past 30 years.Methods The CNKI(China national knowledge infrastructure)database,Wanfang Medical network and VIP database.NoteExpress were used for literature screening.CiteSpace 6.1.R6 software were used for bibliometric analysis and data visualization.Results A total of 3 823 articles were included for analy-sis.The top 3 keywords were:"noise","hearing loss",and"noise-induced deafness".A total of 358 literatures were published on the pathogenesis of NIHL.The pathogenesis included oxidative stress,genetic susceptibility,mechanical damage,microcirculation disturbance,calcium overload,etc.Conclusion The number of papers pub-lished in the field of NIHL has increased year by year,and the overall development can be divided into three stages:exploration of the influence of noise,research on etiology,and prevention and assessment of occupational noise-in-duced hearing loss.In terms of pathogenesis,the oxidative stress mechanism has been widely recognized by schol-ars,and genetic susceptibility has become a research hotspot.

Objective To investigate the characteristics of Chinese medicine syndromes and the possible metabolic substance basis of spontaneously hypertensive rat(SHR).Methods 10-week-old SPF SHR and WKY of the same strain were divided into SHR group and WKY group with 8 rats in each group.The general state,temperament,peripheral vascular filling,tongue characteristics,diet,water intake,urine and feces volume and characteristics,blood pressure,heart rate,respiratory rate,pain threshold,and open field behavior of SHR rats were observed and tested comprehensively to identify the possible syndrome types of Chinese medicine.At the same time,liquid chromatography tandem mass spectrometry was used to analyze non-targeted serum metabolites to preliminarily reveal the material basis of blood pressure elevation and Chinese medicine syndrome manifestations.Results Compared with WKY group,the scores of dark yellow hair color,irritable degree and peripheral capillary filling were higher in SHR group(P＜0.0001).Red tongue color,dry tongue,little body fluid;24 h diet and water intake,urine volume and fecal volume were less(P＜0.05),fecal water content was lower(P＜0.001);systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),heart rate(HR)and respiratory rate(RR)were significantly higher(P＜0.05);Lower pain threshold(P＜0.0001);The open field experiment shows that the moving distance and residence time of the edge are longer(P＜0.001).Serum non-targeted metabolomics result showed that,compared with WKY group,the SHR group had 114 metabolites with significant differences(P＜0.05).These differential metabolites were mainly lipids and lipid-like molecules(40.35％),organic acids and derivatives(22.8％),and organoheterocyclic compounds(15.79％).A total of 25 metabolic pathways were identified by KEGG enrichment analysis.Further differential abundance analysis showed that 16 pathways were activated,only 4 pathways were inhibited,and 5 pathways were not significantly changed.The glutamatergic synapse and GABAergic synapse were activated,while the serotonergic synapse was inhibited.Conclusions The symptoms of SHR include impatience and irritability,peripheral vascular dilation and collateral circulation formation,bulbar conjunctival congestive swelling,red tongue coloration,a dry tongue,constipation,red-yellow urine of low volume,and a rapid heart rate and high respiratory rate.All these suggest that SHR is a syndrome of hypertension with hyperactivity of liver-yang.The material basis of SHR is not only related to lipid,amino acid,and carbohydrate metabolism disorders,but also may be related to metabolic disorders of glutaminergic,GABAergic,and serotonergic neural pathways.

Objective:The purpose of this study was to investigate the diagnostic value and clinical significance of cochlear microphonics (CM) combined with otoacoustic emission (OAE) in patients with auditory neuropathy (AN).Methods:The study included patients who were diagnosed with bilateral AN and had CM originating from both sides. The CM amplitude, latency, duration and intensity-amplitude (I/O) function curve were recorded by CM test. According to whether the distortion product otoacoustic emissions (DPOAE) passed through, the patients were divided into three groups: bilateral OAE passed group (OAE PP Group), bilateral OAE failed group (OAE RR Group), and unilateral OAE passed through one side failed group (OAE PR Group). OAE was elicited by four or more frequencies of 750-8 000 Hz. The characteristics of CM and its related influencing factors were analyzed, and data were processed and analyzed by SPSS 26.0 software. Results:(1) A total of 256 patients (512 ears) with AN were enrolled, including 161 patients (322 ears) in OAE PP group, 32 patients (64 ears) in OAE PR group and 63 patients (126 ears) in OAE RR group. OAE failed in 30.9% of patients with AN. (2) When the stimulation intensity was 100 dB nHL, the CM amplitude of OAE passing ear (OAE P+CM P group) in AN patients aged 3 years was 0.43±0.17μV, which was significantly higher than that of OAE not passing ear (OAE R+CM P group) (0.29±0.15) μV ( t=4.876， P<0.001). The CM duration of the OAE P+CM P group was (5.18±1.04) ms, which was longer than that of the OAE R+CM P group at 4.60±1.12 ms ( P=0.005). The I/O function curve of OAE P+CM P group showed a nonlinear trend, while, that of OAE R+CM P group showed a linear trend. (3) In the OAE P+CM P group of AN patients, the amplitude of CM was negatively correlated with the onset age, test age, disease course, PTA, and ASSR threshold ( P<0.001), with correlation coefficients of r=-0.475, r=-0.519, r=-0.367, r=-0.374, and r=-0.494, respectively. In the OAE R+CM P group of AN patients, the amplitude of CM was negatively correlated with the onset age, test age, and ASSR threshold ( P<0.05), with correlation coefficients of r=-0.271, r=-0.240, and r=-0.287, respectively. Conclusions:Excluding patients with high-frequency steeply sloping hearing loss, when ABR is absent or abnormal and OAE is absent, CM detection can reduce the rate of missed diagnosis of AN. The analysis of CM amplitude and I/O function curve is helpful to determine the lesion site of AN patients, which is convenient for early diagnosis and effective intervention.

Objective To analyze the relationship between hypertension combined with obstructive sleep apnea hypopnea syndrome(OSAHS)and intima-media thickness(IMT)and explore the correlation between the risk of IMT and hypertension with OSAHS patients.Methods Select 50 patients with hypertension and OSAHS patients who were treated in Jiaxing Hospital of Traditional Chinese Medicine during January 2020 to February 2024 as observation group,while 50 patients with simple hypertension were used as control groups to collect two groups of patients'sleep respiratory monitoring disorders(AHI),lowest blood oxygen saturation(L-SaO2)at night,average hemodium oxygen saturation(M-SaO2)at night,dynamic blood pressure 24h,daytime and night's average diastolic blood pressure,IMT,conducting relevant statistical analysis,compares correlation between IMT of two groups and the severity of OSAHS.Results Compared with control group,observation group AHI,IMT,average systolic blood pressure voltage and average diastolic blood pressure increased significantly(P＜0.01),L-SaO2,M-SaO2 decreased significantly(P＜0.01).Observation group AHI and average systolic blood voltage and average diastolic pressure of average systolic blood pressure at 24h,daytime,and night were positively correlated(P＜0.01),L-SaO2,24h and daytime average contraction pressure were negatively correlated(P＜0.05).Observation group AHI and IMT were positive,and L-SaO2,M-SaO2 and IMT were negatively related(P＜0.01).Conclusion Severity of the disease of hypertension combined with OSAHS patients is closely related to patient's blood pressure level and change of IMT.Actively controlling blood pressure and IMT may help improve prognosis of patients,reduce the occurrence of cardiovascular events.The prognostic evaluation has certain clinical value.