BACKGROUND:Buqi Huoxue Compounds have significant clinical efficacy in treating ischemic stroke with Qi deficiency and phlegm stasis;however,the exact mechanism of action is not clear. OBJECTIVE:To observe the effect of Buqi Huoxue Compounds on the expression of vascular endothelial growth factor,basic fibroblast growth factor,brain-derived neurotrophic factor and autophagy related protein Beclin1 and p62 in a rat model of cerebral ischemia/reperfusion. METHODS:Forty male Sprague-Dawley rats were randomly divided into sham operation group,model group,Buqi Huoxue Compounds group and autophagy inhibitor group,with 10 rats in each group.In the latter three groups,a rat model of cerebral ischemia/reperfusion injury was established.The Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion;the autophagy inhibitor group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion and intraperitoneally given 3-methyladenine 2 hours before gavage and at days 1-3 of gavage.The sham operation group and model group were given equal amounts of saline by gavage for 7 consecutive days.Neurological function,cerebral infarct volume,brain tissue morphology and expression of vascular endothelial growth factor,basic fibroblast growth factor,brain-derived neurotrophic factor and autophagy-related proteins Beclin1 and p62 in the ischemic cortical region of rats were detected at 24 hours after the final administration. RESULTS AND CONCLUSION:Zea-Longa scoring results showed that the neurological function of rats was severely damaged after modeling and neurological deficit of rats in the Buqi Huoxue Compounds group was less than that in the model group and the autophagy inhibitor group(P＜0.05).TTC staining showed that cerebral infarct foci were observed in the model group,Buqi Huoxue Compounds group,and autophagy inhibitor group,and the cerebral infarct volume in the Buqi Huoxue Compounds group was lower than that in the model group and the autophagy inhibitor group(P＜0.05).The results of hematoxylin-eosin staining in ischemic brain tissues showed that there were large gaps between nerve cells in the model group and cell arrangement was not neat,and cytoplasmic agglutination and pyknosis were observed.Immunohistochemical staining results showed that vascular endothelial growth factor was mostly expressed in neuronal cells,glial cells and capillary endothelium;basic fibroblast growth factor and brain-derived neurotrophic factor were mostly expressed in neuronal cells and glial cells;and there was no significant difference in the expression of vascular endothelial growth factor,basic fibroblast growth factor,and brain-derived neurotrophic factor among the four groups(P＞0.05).The results of western blot assay showed that compared with the sham operation group,Beclin1 protein expression was decreased(P＜0.05)and p62 protein expression was elevated(P＜0.05)in the model group;compared with the model group,Beclin1 protein expression was increased(P＜0.05)and p62 protein expression was reduced(P＜0.05)in the Buqi Huoxue Compounds group;compared with the Buqi Huoxue Compounds group,Beclin1 protein expression was decreased(P＜0.05)and p62 protein expression was elevated(P＜0.05)in the autophagy inhibitor group.To conclude,Buqi Huoxue Compounds attenuate cerebral ischemia-reperfusion injury in rats by promoting autophagy.

ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C₁₈（2） （4.6 mm × 250 mm, 5 µm） column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability .

Aim To investigate the role and potential mechanism of methyltransferase-like 5 (METTL5) in triple-negative breast cancer (TNBC) . Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot. After shRNA targeting METTL5 (shRNAMETTL5) was transfected into TNBC cells, cell proliferation, migration and invasion were detected by CCK-8, colony formation, wound healing and Transwell assays, respectively. Western blot was used to detect the expression of Wnt/p-catenin signaling-related key proteins. A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/p-catenin signaling activity in vivo. Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines (P < 0. 01) . Knockdown of METTL5 significantly inhibited the proliferation, migration and invasion of TNBC cells and reduced the expression of Wnt/p-catenin signaling molecules (3-catenin, cyclin Dl, matrix metalloproteinase (MMP) -2 and MMP-7 (all P < 0. 01) . Knockdown of METTL5 reduced tumor growth and Wnt/pcatenin signaling activity in vivo. Conclusions Knockdown of METTL5 can inhibit the proliferation, migration and invasion of TNBC cells, which may be related to the inhibition of Wnt/p-catenin signaling pathway.

Based on the literature review and the analysis of specific cases of postpartum frequent micturition,pediatric enuresis,elderly uremia complicated with bradyarrhythmia in clinic,the clinical application of the action of Ephedrae Herba in stimulating yang qi is discussed.Ephedrae Herba has the meridian tropism of the lung and bladder meridians,and is pungent,warm and dispersing,which is the most important medicine for the treatment of external contraction.Ephedrae Herba has the actions of inducing diaphoresis,calming asthma and inducing diuresis,and is widely used for the treatment of external contraction,coughing and asthma,and edema.For the patients with deficiency of both kidney yin and kidney yang without obvious bias of yin-yang consumption which result from the postpartum impairment of qi and blood,deficient innate endowment,and gradually exhaustion of essence in the kidney in the elderly or during chronic illness,a small dosage of Ephedrae Herba can stimulate yang qi during the treatment of warming kidney yang,which is helpful for promoting the drug arriving at the back shu-points of the internal organs distributed along the bladder meridian and enhancing the recovery of zang-fu organ function.Ephedrae Herba is strong in inducing diaphoresis with an intense action.When Ephedrae Herba is used to stimulate yang,the dosage of 3～9 g is appropriate,and medicines for warming yang are needs to be used together.The course of treatment with Ephedrae Herba should be avoided to be too long,in order to prevent the vital energy from the damage by its large cumulative dose.

Objective To determine whether four-and-a-half LIM-only protein 2(FHL2)can affect macrophage foa-ming by regulating nuclear factor kappa-B(NF-κB)signaling pathway.Methods FHL2 over-expression plasmids and siRNA of FHL2 were constructed and transfected into human monocyte/macrophages cell line THP-1.Western blot was used to detect the expression of FHL2.The cells were stimulated with oxidized low density lipoprotein(ox-LDL)and the expression of IL-6,IL-1β,TNF-α and other cytokines were detected by ELISA.Oil red O staining was used to detect the degree of cell foaming.The protein expression of NF-κB signaling pathway was detected by Western blot.Results The expression of FHL2 increased after transfected with FHL2 over-expression plasmids while decreased in si-FLH2 transfected cells.FHL2 down-regulated secretion of inflammatory cytokines.Down-regulation of FHL2 allevi-ated THP-1 macrophage foaming.The down-regulation of FHL2 inhibited activation of NF-κB signaling pathway,while the over-expression FHL2 showed an opposite trend.Conclusions FHL2 down-regulation inhibits the activation of NF-κB signaling pathway,reduces the secretion of inflammatory cytokines and alleviates foaming of macrophages.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Objective:To systematically evaluate the effectiveness and feasibility of aerobic exercise intervention in schizophrenia patients.Methods:Randomized controlled trials on exercise interventions for patients with schizophrenia were searched in eight databases from built up to March 2023, including China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP), WanFang Data, China Biomedical Literature Database, PubMed, Cochrane Library, EMBASE and Web of Science. The positive and negative symptom scale (PANSS) and its sub-scales were used as primary outcome indicators, and the negative symptom scale (SANS) and body mass index (BMI) were used as secondary indicators, and Meta-analysis was performed using R 4.1.0 and Stata 14.0.Results:Forty-seven studies including 3 139 patients with schizophrenia were included. Results of a network Meta-analysis based on 24 studies showed that aerobic exercise may be the most effective measure for reducing total PANSS scores in patients with schizophrenia. Compared to conventional treatment, combining aerobic exercise intervention improved patients' PANSS total score (MD= -5.09, 95% CI: -5.90~-4.28), SANS (MD= -12.17, 95% CI: -14.25~-10.10), and BMI (MD=-1.59, 95% CI: -1.93~-1.25). Meanwhile, subgroup analysis showed that 2 months of intervention was more appropriate (MD=-6.12, 95% CI: -7.22~-5.02) and the weekly total exercise time for 140-260 min was more appropriate (MD=-8.59, 95% CI: -12.93~-4.25) in terms of total PANSS score. The adherence rates between the trial and control groups showed no significant difference between the aerobic exercise intervention combined with conventional treatment and conventional treatment alone( P>0.05). Conclusion:Aerobic exercise intervention is an effective measure to relieve the symptoms of schizophrenia patients and has good compliance among inpatients.

Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P＜0.001),while MAP was not significantly correlated with gestational week(P＞0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.