OBJECTIVE: To assess the impacts of electroacupuncture (EA) on the gait, oxidative stress, inflammatory reaction, and protein degradation in the rats of denervated skeletal muscle atrophy, and explore the potential mechanism of EA for alleviating denervated skeletal muscle atrophy. METHODS: Forty male SD rats, 8 weeks old, were randomly assigned to a sham-surgery group, a model group, an EA group, and a p38 MAPK inhibitor group, with 10 rats in each group. The right sciatic nerve was transected to establish a rat model of denervated skeletal muscle atrophy in the model group, the EA group and the p38 MAPK inhibitor group. In the sham-surgery group, the nerve was exposed without transection. One day after successful modeling, the rats in the EA group received EA at "Huantiao" (GB30) and "Zusanli" (ST36) on the right side, using a continuous wave with a frequency of 2 Hz and current intensity of 1 mA, for 15 min in each session, EA was delivered once a day, 6 times a week. In the p38 MAPK inhibitor group, the rats received the intraperitoneal injection with SB203580 (5 mg/kg), once a day, 6 times a week. The intervention was composed of 3 weeks in each group. After the intervention completion, the CatWalk XT 10.6 animal gait analysis system was used to record the gait parameters of rats. The wet weight ratio of the gastrocnemius muscle was calculated after the sample collected. Using HE staining, the fiber morphology and cross-sectional area of the gastrocnemius muscle were observed; ELISA was employed to measure the content of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in the gastrocnemius muscle; the biochemical hydroxyamine method was adopted to detect the content of superoxide dismutase (SOD) and malondialdehyde (MDA) in the gastrocnemius muscle; with immunohistochemistry and Western blot used, the expression of p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated (p)-p38 MAPK, muscle atrophy F-box gene (Atrogin-1), muscle RING finger 1 (Murf-1), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) was detected in the gastrocnemius muscle. RESULTS: Compared to the sham-surgery group, in the model group, the standing duration, the swing time and the step cycle were increased (P<0.001), the footprint area of the maximum contact time, the print area, the average intensity of the maximum contact time, the average intensity, the swing speed, and the step length were decreased (P<0.001); the wet weight ratio of gastrocnemius muscle and fiber cross-sectional area were reduced (P<0.001); the content of IL-6, IL-1β, TNF-α and MDA in gastrocnemius muscle elevated (P<0.001), and that of SOD reduced (P<0.001); the positive and protein expression of p-p38 MAPK, Atrogin-1 and Murf-1 elevated (P<0.001) and that of Nrf2 and HO-1 dropped (P<0.001). When compared with the model group, in the EA group and the p38 MAPK inhibitor group, the standing duration, the swing time and the step cycle decreased (P<0.01), the footprint area of the maximum contact time, the print area, the average intensity of the maximum contact time, the average intensity, the swing speed, and the step length increased (P<0.01); the wet weight ratio of gastrocnemius muscle and fiber cross-sectional area were improved (P<0.01, P<0.05); the content of IL-6, IL-1β, TNF-α and MDA in gastrocnemius muscle dropped (P<0.05, P<0.01), and that of SOD elevated (P<0.01, P<0.05); the positive and protein expression of p-p38 MAPK, Atrogin-1 and Murf-1 dropped (P<0.01, P<0.05) and that of Nrf2 and HO-1 increased (P<0.01, P<0.05). CONCLUSION Electroacupuncture may alleviate skeletal muscle atrophy in denervated skeletal muscle atrophy rats by mediating the p38 MAPK activity, thereby suppressing oxidative stress, inflammatory reaction, and protein degradation.
Animals ; Electroacupuncture ; Male ; Rats ; p38 Mitogen-Activated Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Muscular Atrophy/metabolism* ; Muscle, Skeletal/metabolism* ; Humans ; Signal Transduction ; Superoxide Dismutase/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Oxidative Stress ; MAP Kinase Signaling System ; Acupuncture Points

AIM To investigate the clinical effects of Supplemented Gegen Qinlian Decoction combined with acupuncture on patients with ulcerative colitis of Large Intestinal Dampness-heat Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 1-month administration of Pefikang Capsules and Mesalazine Sustained Release Granules,and observation group(60 cases)for 1-month administration of Supplemented Gegen Qinlian Decoction,acupuncture,Pefikang Capsules and Mesalazine Sustained Release Granules.The changes in clinical effects,symptom remission time,TCM syndrome scores,Geboes index,lesion activity index,Baron score,inflammatory factors(IL-6,IL-8,TNF-α),immune function indices(IgA,IgG,IgM),IBDQ score and recurrence rate were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05),along with shorter symptom remission time(P＜0.05)and lower recurrence rate(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,Geboes index,lesion activity index,Baron score,inflammatory factors,IgG,IgM(P＜0.05),and increased IBDQ score(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients with ulcerative colitis of Large Intestinal Dampness-heat Pattern,Gegen Qinlian Decoction combined with acupuncture can improve clinical symptoms,promote disease recovery,enhance immune functions and life quality,and reduce recurrence rate.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P＜0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P＜0.05,P＜0.01);decreased levels of TNF-α and IL-1β(P＜0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P＜0.01);increased protein expressions of PSD95 and SYN(P＜0.05,P＜0.01);and decreased CD86/Iba1(P＜0.01)and increased CD206/Iba1(P＜0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

Objective To explore the relationship between blood pressure at baseline and significant decline in cognitive function after 4 years in middle-aged and elderly people in rural Xi'an,and the potential effect of age on the relationship.Methods Data were collected from a cohort of middle-aged and elderly people with cognitive impairment in rural Xi'an,Shaanxi Province.The cohort consisted of people aged≥40 years from a village in Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.Blood pressure parameters studied included hypertension and high systolic blood pressure(≥140 mmHg vs.＜140 mmHg),and high diastolic blood pressure(≥90 mmHg vs.＜90 mmHg).The Mini-Mental State Examination(MMSE)was used to assess the whole cognitive function,and the decline of MMSE score ≥4 points in 4 years was defined as significant decline of cognitive function.Multivariate Logistic regression was used to analyze the relationship between blood pressure and cognitive function at baseline.Subgroup analysis was used to study the effect of age(＜65 vs.≥65 years)on the relationship.Results We recruited a total of 1 350 subjects in the analysis,including 235 subjects(17.4％)with baseline age ≥65 years and 533 male subjects(39.5％);671 subjects(49.7％)had hypertension,with systolic blood pressure of(131.71±17.79)mmHg;840 subjects(62.2％)had high systolic blood pressure,with diastolic blood pressure of(82.18±10.56)mmHg;395(29.3％)had high diastolic blood pressure.During the 4-year follow-up,56 cases(4.2％)met the criteria for significant decline of cognitive function.We did not find significant association of hypertension and high systolic blood pressure with cognitive decline in the general population,＜65-year-old subgroup,or ≥ 65-year-old subgroup.The incidence of significant cognitive decline was not statistically significant in the total population(3.6％vs.5.6％,P=0.092),the ≥65-year-old subgroup(7.5％vs.8.2％,P=0.855),the normal diastolic blood pressure group,or the high diastolic blood pressure group.However,in the subgroup＜65 years,the incidence of cognitive decline was higher in the high diastolic blood pressure group than in the normal diastolic blood pressure group(2.7％vs.5.1％,P=0.043).Multivariate analysis showed that high diastolic blood pressure was not found to be associated with significant cognitive decline in the total population(OR=1.744,95％CI:0.953-3.192,P=0.071),the subgroup of ≥65 years old(OR=0.858,95％CI:0.221-3.338,P=0.825),or the subgroup of ≥65 years old.In the＜65 age group,high diastolic blood pressure was significantly associated with cognitive decline(OR=2.051,95％CI:1.005-4.186,P=0.048).Conclusion High diastolic blood pressure is associated with 4-year cognitive decline in people aged 40-65 years,but not in those aged ≥65.No association is found between hypertension or high systolic blood pressure and significant cognitive decline.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.