OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension （PIH） rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α （Sirt1/PGC-1α） pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester （L-NAME） method. PIH rats were randomly divided into model group， L-pachymic acid （low-dose pachymic acid， 10 mg/kg） group， H-pachymic acid （high-dose pachymic acid， 20 mg/kg） group， and H-pachymic acid+EX527 （20 mg/kg pachymic acid+10 mg/kg EX527） group， with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily， once a day， for 28 consecutive days. After the last administration， 24 h urinary protein and tail artery systolic blood pressure （SBP） were measured in pregnant rats from each group， along with the levels of serum creatinine （Scr）， blood urea nitrogen （BUN），uric acid （UA）， and cystatin C （Cys-C）. The contents of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and 8-hydroxy-2′-deoxyguanosine （8-OHdG） in renal tissue， as well as the mRNA and protein expression levels of Sirt1 and PGC-1α， were also determined. Meanwhile， renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. RESULTS Compared with model group， L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification， tail artery SBP， Scr， BUN， UA， Cys-C levels， glomerulosclerosis index score of renal tissue， renal tubular injury score， the percentage of PAS positive area， MDA and 8-OHdG （P＜0.05）. Conversely， the contents of SOD and GSH-Px， along with the mRNA and protein expression levels of Sirt1 and PGC-1α， were significantly increased （P＜0.05）. Moreover， these improvements were more pronounced in H-pachymic acid group （P＜0.05）. Compared with H-pachymic acid group， the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal （P＜0.05）. CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats， potentially through activation of the Sirt1/PGC-1α pathway.

AIM To explore the clinical effects of Salvia miltiorrhiza Bunge combined with indobufen on restenosis in patients with autologous arteriovenous fistula after percutaneous transluminal angioplasty(PTA).METHODS Sixty-five patients were randomly assigned into control group(32 cases)for administration of indobufen,and observation group(33 cases)for administration of both Danshen Tablets and indobufen.The changes in internal fistula diameter,internal fistula blood flow,platelet aggregation rate,coagulation function indices(APTT,PT,TT,FIB),inflammatory factors(IL-6,IL-1β,TNF-α),restenosis rate and incidence of adverse reactions were detected.RESULTS At 3,6 months after surgery,the observation group demonstrated bigger internal fistula diameter and internal fistula blood flow than the control group(P＜0.05).At 6 months after surgery,the two groups displayed decreased platelet aggregation rate,FIB,inflammatory factors(P＜0.05),and prolonged APTT,PT,TT(P＜0.05),especially for the observation group(P＜0.05).No significant differences in restenosis rate and incidence of adverse reactions were found between the two groups(P＞0.05).CONCLUSION For the patients with autologous arteriovenous fistula after PTA,S.miltiorrhiza combined with indobufen can safely and effectively inhibit the reduced progresses of internal fistula diameter and internal fistula blood flow,maintenance the patency of internal fistula,and alleviate platelet aggregation and body inflammatory responses.

Objective:To explore the application value of integrated Chinese and western medicine in the treatment of sepsis-induced coagulopathy (SIC) induced by bacterial pneumonia sepsis.Methods:A total of 60 inpatients with bacterial pneumonia and sepsis admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from October 2023 to June 2024 were collected in a cross-sectional study. Serum samples were collected, and immune indexes, coagulation function and some laboratory test results of the patients were detected or recorded. Sepsis Associated Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score were evaluated.Results:Among the 60 patients, 71.7%( n=43) were associated with coagulation disorder, 65%( n=39) showed hemorrhagic SIC; A total of 37 patients (61.7%) were treated with integrated traditional Chinese and western medicine, and 23 patients (38.3%) were treated with Western medicine. The main types of syndrome differentiation were toxic-heat syndrome ( n=48, 80.0%) and blood-stasis syndrome ( n=11, 18.3%). Serum human monocyte chemoattractant protein-1 (MCP-1) and platelet count (PLT) in patients with blood stasis syndrome were significantly lower than those in toxic-heat syndrome (all P<0.05). In patients with bacterial pneumonia sepsis, the total score of syndrome of excess of fu-viscera (Fu-shi-zheng) was positively correlated with programmed death ligand-1 (PD-L1) ( r=0.293, P=0.023) and tumor necrosis factor-α (TNF-α) ( r=0.436, P=0.001). The total score of toxin-heat syndrome ( r=0.323, P=0.016) and excess of fu-viscera syndrome ( r=0.354, P=0.008) were positively correlated with prothrombin time (PT). PD-1 was positively correlated with SOFA score ( r=0.343, P=0.007) and APACHE Ⅱ score ( r=0.354, P=0.006). The PD-1 level and SOFA and APACHE Ⅱ scores of the patients treated with integrated Chinese and western medicine were significantly lower than those treated with Western medicine alone (all P<0.05). Conclusions:The combined intervention of traditional Chinese medicine and Western medicine based on " Fuzheng Touxie Jiedu (The method of strengthening the body and removing the toxin)" has strong clinical guiding significance, and can effectively improve the immune function and prognosis of bacterial pneumonia SIC.

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.

Objective:To explore the current status and influencing factors of quality of life in patients with thyroid-associated ophthalmopathy (TAO) .Methods:From January to July 2024, convenience sampling was used to select TAO patients of the Department of Ophthalmology of Peking University Third Hospital as research subjects. The patients were surveyed using the General Information Questionnaire, Graves' Ophthalmopathy Quality of Life Questionnaire (GO-QOL), Negative Physical Self Scale-Appearance (NPSS-A), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Perceived Social Support Scale (PSSS). Spearman correlation analysis was used to explore the correlation between GO-QOL scores and NPSS-A, SAS, SDS, and PSSS scores. Multiple linear regression was used to analyze the factors influencing the quality of life of TAO patients.Results:A total of 234 questionnaires were distributed, and 203 valid questionnaires were collected, with a valid response rate of 86.75%. The GO-QOL visual function and social function dimensions scores of 203 TAO patients were [78.57 (50.00, 100.00) ] and [43.75 (18.75, 62.50) ], respectively. Multiple linear regression analysis showed that age, eye movement disorders, eyelid retraction, and disease grading, were the influencing factors of the visual function dimension of GO-QOL ( P<0.05). Age, social support, and body image were the influencing factors on the social function dimension of GO-QOL ( P<0.05) . Conclusions:The quality of life of TAO patients is poor. Healthcare professionals should develop coping strategies based on factors affecting different dimensions of quality of life, so as to improve patients' quality of life.

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 investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To explore the application value of dynamic monitoring of serum thyroid hormone(THs)levels in assessing the condition changes and prognosis of elderly patients with sepsis.Methods:Using a retrospective cohort study,a total of 120 elderly critically ill patients hospitalized in the Department of Critical Care Medicine from April 2020 to April 2023 were selected as research subjects,divided into a sepsis group(60 cases)and a non-sepsis group(60 cases).Sepsis patients were further divided into a survival group(43 cases)and a death group(17 cases)based on 28-day survival status.Serum THs,PCT,IL-6,and Lac were measured on the 1st,5th,and 10th days of hospitalization(d1,d5,dl0)for sepsis patients,and the Sequential Organ Failure Assessment(SOFA)score and Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score were recorded.The datas of non-sepsis patients were sampled on d1.The incidence of non-thyroidal illness syndrome(NTIS)was statistically analyzed,and the dynamic changes of serum THs among different groups were compared.The correlation between THs and disease severity,as well as the predictive value of THs for 28-day mortality in sepsis,was analyzed.Results:①The incidence of NTIS was 78.33％(94/120),with a significantly higher incidence in sepsis patients(96.67％,58/60)compared to non-sepsis patients(60.00％),with statistical significance(P＜0.05).②Compared to non-sepsis patients,sepsis patients had significantly lower levels of TSH,T3,FT3,and T4 on d1,while rT3 was significantly elevated,with statistical significance(P＜0.05);the difference in FT4 levels was not statistically significant(P＞0.05).Pearson correlation analysis showed that T3 and T4 were negatively correlated with SOFA and APACHE Ⅱ scores(P＜0.05),while other THs indicators showed no correlation with SOFA and APACHE Ⅱ scores(P＞0.05).ANOVA results indicated that there was no statistically significant difference in T4 levels at the three time points,and its changes showed no obvious linear trend over time(P＞0.05);T3 was significantly lower on d1 than on d5 and d10,and showed an increasing trend with longer hospitalization,while SOFA and APACHE Ⅱ scores were significantly higher on d1 than on d5 and d10,showing a decreasing trend with longer hospitalization(all P＜0.05).③Compared to the survival group of sepsis patients,the death group had significantly higher levels of PCT on d10,IL-6 on d5 and d10,and Lac on d1,d5,and d10(P＜0.05).The death group had significantly lower levels of T3 and T4 on d1,significantly lower levels of TSH,T3,T4,and FT4 on d5,and significantly lower levels of TSH,T3,FT3,T4,and FT4 on d10,with statistical significance(P＜0.05).④Logistic regression analysis showed that independent risk factors for 28-day mortality in sepsis patients included T3 on d1 and T3,FT3,T4,FT4,and IL-6 on d10,with statistical significance(P＜0.05).ROC curve analysis indicated that serum levels of T3,FT3,T4,and FT4 on d10 had certain predictive value for 28-day mortality in sepsis patients(all P＜0.05),with T3,FT3,and FT4 showing good predictive value,and their AUCs were 0.875,0.872,and 0.861,respectively.The combined AUC for predicting 28-day mortality in sepsis patients using T3,FT3,and FT4 on d10 increased to 0.902.Conclusion:The incidence of NTIS was high in elderly sepsis patients,and the serum THs levels and their dynamic changes were closely related to the patients'condition changes.Continuous dynamic monitoring of serum THs levels could help to assess the progression of sepsis,and T3 may serve as an indicator for evaluating the progression and prognosis of sepsis.

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.

Aim To investigate the effects of circ_0071653 targeting miR-197-3p on the proliferation and metastasis of esophageal squamous cell carcinoma(ES-CC)cells.Methods The circular structure of circ_0071653 was confirmed by Sanger sequencing and ribo-nuclease R tolerance experiments.Real-time quantita-tive polymerase chain reaction(RT-qPCR)and tissue fluorescence in situ hybridization assay were performed to detect the circ_0071653 expression levels and ana-lyze its clinical relevance.Cell fluorescence in situ hy-bridization and nuclear cytoplasmic separation assays were used to verify the subcellular localization of circ_0071653 and miR-197-3p.Bioinformatics analysis,dual luciferase reporter gene and RT-qPCR assays were conducted to validate the interactions between circ_0071653 and miR-197-3p.Moreover,the cell counting Kit-8(CCK-8),colony formation,scratch,Transwell invasion and subcutaneous tumor formation in nude mice assays were used to evaluate the effects of circ_0071653 and miR-197-3p on cell viability,prolifera-tion,migration,and invasion and in vivo tumorigenesi-sability.Results Circ_0071653 was a circular RNA,which showed high expression in ESCC cell lines and tissues.The expression of circ_0071653 was signifi-cantly correlated with lymph node metastasis and clini-cal stage of ESCC patients.Circ_0071653 and miR-197-3p were mainly localized in the cytoplasm.The databases predict that circ_0071653 had complementa-ry binding sites with miR-197-3p,and their binding were confirmed by dual luciferase reporter geneand RT-qPCR assays.Moreover,the activity,proliferation,migration,invasion and in vivo tumorigenesis abilities of ESCC cells were significantly reduced after knocking down circ_0071653,and this effect could be reversed by downregulating the expression of miR-197-3p.Con-clusions Circ_0071653 promotes the malignant pro-gression of ESCC through targeted regulation of miR-197-3p.