The mechanism of L-perilla alcohol(L-POH) in intervening hypoxic pulmonary hypertension(HPAH) was discussed based on network pharmacology, and experimental verification. The active components and potential targets of the volatile oil of Rhodiola tangutica(VORA) in the intervention of HPAH were screened by network pharmacology. The biological process of Gene Ontology(GO) and the signaling pathway enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG) were analyzed for the core targets, and a "component-common target-disease" network was constructed. Four active components were screened from VORA: L-POH, linalool, geraniol, and(-)-myrtenol. The core targets for treating HPAH were HSP90AA1, AKT1, ESR1, PIK3CA, EP300, EGFR, and JAK2. GO enrichment analysis mainly involved biological processes such as reaction to hypoxia, heme binding, and steroid binding. KEGG enrichment analysis mainly involved hypoxia-inducing factor 1(HIF-1) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and Janus kinase/activator of signal transduction and transcription(JAK/STAT) signaling pathway. The vasodilation effects of the four active components were screened by perfusion experiment of extracorporeal vascular rings, and the mechanism of the main active component L-POH was studied by channel blockers. The inhibitory effects of the four active components on the proliferation of pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia were screened by cell proliferation experiment, and the mechanism of the main active component L-POH was studied by flow cytometry, cell cycle experiment, and Western blot. The results showed that L-POH could directly act on vascular smooth muscle to relax pulmonary arterioles, induce ATP-sensitive potassium channels to open, and inhibit extracellular Ca~(2+) influx through voltage-gated calcium channels to relax blood vessels. In addition, L-POH could inhibit the abnormal proliferation of PASMCs induced by hypoxia and promote its apoptosis, and its mechanism may be related to the increase in Bax protein expression and the decrease in p-JAK2, p-STAT3, Bcl-2, and cyclinA2 protein expression. In summary, L-POH can interfere with HPAH by relaxing pulmonary arterioles and inhibiting the proliferation of smooth muscle cells.
Network Pharmacology ; Animals ; Hypertension, Pulmonary/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Hypoxia/metabolism* ; Rhodiola/chemistry* ; Signal Transduction/drug effects* ; Humans ; Monoterpenes/chemistry* ; Male ; Cell Proliferation/drug effects* ; Rats, Sprague-Dawley

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

Objective To compare the efficacy and safety of Saccharomyces boulardii and other probiotics in the treatment of pediatric diarrhea.Methods Retrieved from PubMed,Embase,CBM,Wanfang data,CNKI and VIP,randomized controlled trial(RCTs)about Saccharomyces boulardii(treatment group)vs other probiotics(control group)were collected.After screening the literature,extracting data and evaluating the quality,Meta-analysis was performed by using RevMan 5.3 and Stata 17.0 software.Results A total of 30 RCTs were included,involving 3 082 children.Results of Meta-analysis showed there was no statistical significance in the duration of diarrhea[mean difference(MD)=-0.65,95％confidence interval(CI)=-1.44-0.14,P＞0.05]or the total incidence of adverse reactions[odds ratio(OR)=0.85,95％CI=0.44-1.62,P＞0.05].The total effective rate(OR=1.60,95％CI=1.08-2.36,P＜0.05)and the number of stools(MD=-0.66,95％CI=-1.00--0.32,P＜0.01)in the treatment group were significantly better than control group.There was statistically significant difference in the duration of diarrhea between the two groups treated with diarrhea with fever(MD=1.81,95％CI=1.12-2.49,P＜0.01)and rotavirus gastroenteritis(MD=-0.92,95％CI=-1.20--0.64,P＜0.01).In the treatment of diarrhea with fever,the duration of diarrhea in the control group was significantly shorter than that in the treatment group.The duration of diarrhea in the treatment group was significantly shorter than that control group.At the same time,the duration of diarrhea in children with diarrhea treated with treatment group was significantly shorter than that of control group Bifidobacterium tetragenous viable(MD=-0.84,95％CI=-1.09--0.58,P＜0.01)and control group combined Bacillus subtilis and Enterococcus faecium enteric-coated(MD=-1.35,95％CI=-2.30-0.39,P＜0.01).Conclusion The safety of Saccharomyces boulardii are similar to other probiotics.The efficacy and the number of stools with Saccharomyces boulardii are significantly better than other probiotics in the treatment of diarrhea.The duration of diarrhea in Saccharomyces boulardii group was significantly shorter than other probiotics,while in the treatment of antibiotic-associated diarrhea,the duration of diarrhea of Saccharomyces boulardii was the same as that of other probiotics.However,the duration of diarrhea in children with diarrhea treated with Saccharomyces boulardii was significantly longer than other probiotics.

Objective To explore the clinical efficacy and safety of probiotic-assisted chemotherapy in patients advanced colorectal cancer(CRC).Methods Patients with advanced CRC admitted to the First Affiliated Hospital of Hunan Normal University from March 2022 to March 2023 were enrolled.CRC patients were randomly divided into the test group(Bifidobacterium triple viable capsule,capecitabine+oxaliplatin)and the control group(capecitabine+oxaliplatin)by random number table method.The short-term efficacy(objective response rate and disease control rate),incidence of gastrointestinal adverse reactions,Karnofsky performance status(KPS)score,and serum tumor markers CA72-4,CA19-9 and CEA levels were compared between the two groups.Results A total of 120 patients with CRC were included,including 60 patients in the test group and 60 in the control group.Compared with the control group,the objective remission rate and disease control rate in the testl group were significantly higher(P<0.05).There was no significant difference in the incidence of nausea and acid reflux between the two groups(P>0.05),and the incidences of abdominal pain,bloating,constipation and diarrhea in the test group were significantly lower than those in the control group(P<0.05).There was no significant difference in KPS score,serum CA72-4,serum CA19-9 and serum CEA levels between the two groups before treatment(P>0.05),and after 4 weeks of treatment,the KPS score of the test group was significantly higher than that of the control group(P<0.05),and the serum levels of CA72-4,serum CA19-9 and serum CEA were lower than those of the control group(P<0.05).Conclusion Probiotics-assisted chemotherapy improve the near-term efficacy,reduce gastrointestinal adverse effects,and improve the quality of life in patients with advanced CRC.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective To compare the effects of transumbilical single-incision appendectomy and laparoscopic appendectomy in the treatment of acute appendicitis in pediatric patients.Methods The clinical data of 162 pediatric patients under 14 years old with acute appendicitis admitted to our department were retrospectively analyzed,and the pediatric patients were divided into the transumbilical single-incision surgery group(n=59)and the laparoscopic group(n=103)according to their surgeries.The completion of the operation was recorded,and the operation time,intraoperative blood loss,gastrointestinal function recovery time,hospitalization cost,hospital stay and complications were compared between the two groups.The postoperative wound healing was observed.The wound infection,abdominal pain,abdominal distension,vomiting and abnormal stool were observed during the 6-month follow-up after operation.Results The operations of pediatric patients in the laparoscopic group were successfully completed without conversion to open surgery.The appendixes of 2 cases in the transumbilical single-incision surgery group were found by transumbilical laparoscopy during the operation due to the difficulty in finding the appendixes.The operation time and hospital stay in the transumbilical single-incision surgery group were shorter than those in the laparoscopic group(P<0.05).There was no significant difference in the hospitalization cost,intraoperative blood loss,gastrointestinal function recovery time,or incidence of complications between the two groups(P>0.05).The incision healing in the transumbilical single-incision surgery group was more beautiful.During the follow-up period,the incision of the pediatric patients in the two groups healed well,and there was no abdominal pain,abdominal distension,vomiting or abnormal stool.Conclusion Compared with the traditional laparoscopic appendectomy,transumbilical single-incision appendectomy has the advantages of simple operation,short operation time and hospital stay,and more beautiful incision healing.

Aim To investigate the effect of Toddalia asiatica(TA)on bone destruction in rheumatoid ar-thritis(RA)and its possible mechanism by network pharmacology and in vitro experiments.Methods The active components and targets of TA against RA bone damage were analyzed by network pharmacology.Mo-lecular docking was performed by using AutoDock and PyMOL software pairs.MC3T3-e1 cells were cultured in vitro,and the effect of Toddalia asiatica alcohol ex-tract(TAAE)on cell viability was detected by CCK-8,and appropriate drug concentration and intervention time were screened.The osteoblast model was induced by osteogenic induction medium,and the osteogenic differentiation was detected by ALP staining,activity detection and alizarin red staining.The expression of pathway-related proteins Wnt3a and β-catenin was de-tected by Western blot,and the pathway inhibitor DKK-1 was used to further verify whether TAAE regulated osteoblast differentiation through the Wnt/β-catenin signaling pathway.Results A total of 158 anti-RA bone destruction targets and 56 core targets were se-lected.The enrichment of KEGG signaling pathway mainly included cancer pathway,phosphatidylinositol 3-kinase/protein kinase B signaling pathway and cAMP signaling pathway.The results of CCK-8 showed that 1 g·L-1 TAAE could significantly improve cell survival rate.The results of ALP staining and ALP activity de-tection showed that TAAE could significantly increase the staining positive rate and ALP activity of cells in-duced by osteogenic induction medium.Western blot showed that TAAE could increase the expression of Wnt3a and β-catenin.The expression of these proteins decreased after DKK-1 inhibitors were used.Conclu-sion TAAE can regulate osteoblast differentiation through Wnt/β-catenin signaling pathway to treat os-teodestruction in rheumatoid arthritis.

Objective To observe the therapeutic effect and mechanism of regulating conception vessel and unblocking governor vessel acupuncture in rats with polycystic ovary syndrome(PCOS).Methods Female SD rats were randomly divided into normal group,model group,metformin group,acupuncture group and acupuncture+Nigericin[NOD-like receptor pyrin domain-containing protein 3(NLRP3)activator]group,with 10 rats in each group.Except for the normal group,the PCOS model was constructed by subcutaneous injection of dehydroepiandrosterone(DHEA)in rats of all groups.After the intervention,the structural morphology of ovary and uterus was observed by hematoxylin-eosin(HE)staining,the levels of serum total testosterone(T),luteinizing hormone(LH),sex hormone-binding protein(SHBG),follicle-stimulating hormone(FSH)and fasting insulin(FINS)were detected by enzyme-linked immunosorbent assay(ELISA),the level of free plasma glucose(FPG)was detected by colorimetry,and the insulin resistance index(HOMA-IR)and free testosterone(FAI)were calculated,the mRNA expressions of insulin receptor substrate 1(IRS-1),NLRP3,apoptosis-associated speck-like protein(ASC),caspase-1,interleukin(IL)-1β and IL-18 in ovarian tissues were detected by using real-time fluorescence quantitative PCR(RT-qPCR).And protein immunoblotting(Western Blot)was used to detect protein expressions of IRS-1,NLRP3,ASC,caspase-1 precursor(pro-caspase-1),cleaved caspase-1,IL-1β and IL-18 in ovarian tissues.Results(1)Compared with the normal group,the number of corpus luteum and endometrial thickness were significantly decreased,and the number of cystic follicles was significantly increased in the model group(P＜0.05);compared with the model group,the number of corpus luteum and endometrial thickness were significantly increased,and the number of cystic follicles was significantly decreased in the metformin group and the acupuncture group(P＜0.05).(2)Compared with the normal group,the levels of FSH,LH,T,FAI,FINS,FPG,and HOMA-IR in rats in the model group were significantly increased,while the level of SHGB was significantly decreased(P＜0.05);compared with the model group,the levels of serum FSH,LH,T,FAI,FINS,FPG,and HOMA-IR were all significantly decreased in the metformin group and the acupuncture group,while SHGB level was significantly increased(P＜0.05).(3)Compared with the normal group,the mRNA and protein expression levels of IRS-1,NLRP3,ASC,caspase-1,IL-1β and IL-18 in the ovarian tissues were significantly reduced in the model group(P＜0.05);compared with the model group,the mRNA and protein expression levels of IRS-1,NLRP3,ASC,caspase-1,IL-1β,and IL-18 in the ovarian tissues were significantly reduced in the metformin group and the acupuncture group(P＜0.05).(4)The effects of regulating conception vessel and unblocking governor vessel acupuncture on ovarian function,endometrial receptivity,sex hormone secretion,IR and NLRP3 signaling pathway-related above indexes in PCOS rats were eliminated by Nigericin.Conclusion Regulating conception vessel and unblocking governor vessel acupuncture can improve ovarian morphology and function,increase endometrial thickness,regulate sex hormone metabolism disorders and insulin resistance in PCOS rats,and its mechanism may be related to the inhibition of NLRP3 inflammasome signaling pathway.

Objective:To assess the changes of selenium nutrition of school-age children in Kashin-Beck disease (KBD) areas of Linzhou County, Lhasa City and Xietongmen County, Shigatse City in Tibet Autonomous Region (referred to as Tibet), and provide a scientific basis for evaluating the effectiveness of prevention and control measures.Methods:According to the historical condition of KBD, a total of 344 children's hair samples were collected to determine the content of selenium in Kazi (KBD area) and Jiangxia townships (non-KBD area) of Linzhou County in 2013 and 2021, Renqinze (KBD area) and Tongmen townships (non-KBD area) of Xietongmen County in 2015 and 2021.Results:Compared to 2013/2015, in 2021, the hair selenium level of children in the four townships increased ( P < 0.001). The selenium nutritional level of more than 90% of the children reached medium or above (hair selenium > 0.25 μg/g) in 2021. The hair selenium levels of girls in the two KBD areas (Kazi and Renqinze townships) were lower than those of boys ( Z = - 2.83, - 2.83, P < 0.05). Conclusions:The selenium nutrition level of school-age children in KBD areas in Linzhou and Xietongmen counties has increased rapidly in recent years. However, the selenium nutrition level of girls is significantly lower than that of boys. It is necessary to strengthen prevention, controlling and monitoring, and to further improve the dietary structure of school-age children through the joint efforts of families and schools, to increase the proportion of exogenous high selenium food intake.

OBJECTIVE: To compare the clinical efficacy between Tiaoshen Jieyu acupuncture (acupuncture for regulating mind and relieving depression) combined with sertraline hydrochloride tablet and simple sertraline hydrochloride tablet for post-stroke depression (PSD). METHODS: A total of 76 patients with PSD were randomized into an observation group (38 cases, 6 cases dropped off) and a control group (38 cases, 4 cases dropped off). Both groups were treated with conventional treatment i.e. controlling blood pressure and anti-inflammation. Sertraline hydrochloride tablet was given orally in the control group, 20 mg a time, once a day. On the basis of the treatment in the control group, Tiaoshen Jieyu acupuncture was applied at Baihui (GV 20), Yintang (GV 24⁺), Neiguan (PC 6), Taichong (LR 3), etc. in the observation group, Baihui (GV 20) and Yintang (GV 24⁺) were connected to electroacupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 30 min a time, once a day, 6 times a week. Treatment of 8 weeks was required in both groups. Before and after treatment, the scores of Hamilton depression scale (HAMD), National Institutes of Health stroke scale (NIHSS), Barthel index (BI) and Pittsburgh sleep quality index (PSQI) were observed respectively, the therapeutic efficacy and rate of adverse reactions were evaluated in the two groups. RESULTS: After treatment, the scores of HAMD, NIHSS and PSQI were lower while BI scores were higher than those before treatment in both groups (P<0.05); the scores of HAMD, NIHSS and PSQI in the observation group were lower while BI score was higher than those in the control group (P<0.05). The total effective rate was 93.8% (30/32) in the observation group, which was higher than 70.6% (24/34) in the control group (P<0.05). The rate of adverse reactions was 9.4% (3/32) in the observation group, which was lower than 32.4% (11/34) in the control group (P<0.05). CONCLUSION Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet can improve the depression degree, neurological function, activity of daily living and sleep quality in patients with post-stroke depression, the clinical efficacy is superior to simple sertraline hydrochloride, and can alleviate the adverse reactions caused by medication.
Humans ; Sertraline/adverse effects* ; Depression/etiology* ; Acupuncture Therapy ; Electroacupuncture ; Stroke/complications* ; Acupuncture Points ; Treatment Outcome ; Tablets