ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.

Objective To analyze the literature of leech in medicine using CiteSpace knowledge map,comprehensively understand the research status,hotspots and development trends of component analysis and pharmacological effects of leech,and provide reference for researchers in the field of leech.Methods CiteSpace 6.1 R3 software was used to analyze the relevant literature of leech in the field of medical research in CNKI and Web of Science databases from 1996 to 2022.The bibliometric and visual analysis of the number of articles,authors,research institutions,keyword co-occurrence,clustering and emergence were carried out.Results A total of 1 115 Chinese articles in CNKI database and 237 English articles in Web of Science database were included.The analysis of Chinese and English literature showed that the author Shi Hongzhuan had the largest number of Chinese articles,and the German author Hildebrandt had the largest number of English articles.Shandong University of Traditional Chinese Medicine and Chinese Academy of Sciences were the institutions with the largest number of articles in Chinese and English respectively.The country with the most published English literature is the United States.Chinese and English keyword co-occurrence and cluster analysis showed that Chinese literature focused on the study of its active ingredient hirudin,including molecular structure,pharmacological efficacy,mechanism of treating thrombosis,coronary heart disease,kidney disease and other diseases,and paid attention to the differences in the active ingredients of different types of leeches.In addition,English literature focused on the clinical external use of living leeches.The emergence of keywords suggested that the mechanism of action,the search and synthesis of hirudin analogues,and the pharmacodynamic mechanism of compatibility application were not only the current research hotspots,but also the future hot spots.Conclusion The analysis of leech components,the pharmacological mechanism of leech in the treatment of cardiovascular diseases,chronic kidney diseases and other diseases have always been the research hotspots.Hirudin analogues,the pharmacodynamic mechanism of compatibility application,network pharmacology,molecular docking and so on may be the future research hotspots and trends of leeches.

Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.

To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.

Objective:To explore the white matter structural characteristics in patients with bipolar disorder(BD)using diffusion tensor imaging(DTI)and investigate their relationship with cognitive function.Methods:A total of 15 patients with BD type Ⅰ and 26 patients with BD type Ⅱ who met the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)diagnostic criteria and 37 normal controls were included.Cognitive function was assessed with the Trail Making Test(TMT)and Repeatable Battery for the Assessment of Neuropsy-chological Status(RBANS).The tract-based spatial statistics(TBSS)method was used to explore the differences in fractional anisotropy(FA)and mean diffusivity(MD)among the three groups and perform correlation analyses with cognitive function.Results:Patients with BD Ⅰ and BD Ⅱ had lower scores in attention(P＜0.001),delayed memory(P＜0.01),and total scores(P＜0.001)on the RBANS compared to the normal control group.They also exhibited lower FA values in the corpus callosum and right superior corona radiata compared to the normal control group(P＜0.05).In the BD Ⅰ group,there was a positive correlation between FA values in the genu of corpus cal-losum and visuospatial/constructional scores(r=0.74,P＜0.05),while in the BD Ⅱ group,a positive correlation was found between FA values in the same region and language function scores(r=0.55,P＜0.05).Conclusion:It suggests that patients with bipolar disorder may have impaired white matter integrity in the corpus callosum and right superior corona radiata,which may be associated with cognitive impairment.

Objective:To explore the potential action mechanism of Huotu Jiji Pellets(HJP)in the treatment of erectile dys-function(ED)based on network pharmacology and molecular docking.Methods:We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine(TCMIP)and the therapeutic target genes of ED from the data-bases of Genecards.Then we obtained the common targets of HJP and ED using the Venny software,constructed a protein-protein in-teraction(PPI)network of HJP acting on ED,and screened out the core targets with the Cytoscape software.Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software.Results:A total of 64 effective compounds,822 drug-related targets,1 783 disease-related targets and 320 common targets were obtained in this study.PPI network analysis showed that the core targets of HJP for ED included ESR1,HSP90AA1,SRC,and STAT3.GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus,positive regulation of kinase activity,and positive regu-lation of MAPK cascade.KEGG pathway enrichment analysis suggested that PI3K-Akt,apoptosis,MAPK,HIF-1,VEGF,autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED.Molecular docking prediction exhibited a good doc-king activity of the key active molecules of HJP with the core targets.Conclusion:This study showed that HJP acted on ED through multi-components,multi-targets and multi-pathways,which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

AIM To study the protective effects and mechanism of pueraria isoflavones on myocardial injury in ovariectomized rats.METHODS Thirty-six rats were randomly divided into the sham operation group,the model group,the estradiol valerate group(0.1 mg/kg)and the low,medium and high dose pueraria isoflavones groups(55,110,220 mg/kg).In contrast to the rats of the sham operation group having their small pieces of adipose tissue removal around the ovaries,rats of the other groups had their bilateral ovaries excised,followed by the 16-week corresponding oral drug administration 2 weeks later at a once daily frequency for,6 days a week.At the end of the 16th week,the rats had their hemodynamics[systolic pressure(SBP),diastolic pressure(DBP),mean pressure(MBP),left ventricular systolic pressure(LVSP),left ventricular diastolic pressure(LVMP),and the maximum rate of increase and decrease of left ventricular pressure during isovolumic contraction(±dp/dtmax)]detected by PowerLab;their cardiac pathological changes observed by HE staining;their levels of creatine kinase(CK),lactate dehydrogenase(LDH),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and glucose(Glu)in plasma detected by biochemical analyzer;their myocardial level of adenosine triphosphate(ATP)detected by colorimetry;their mRNA expressions of glucose transporter 4(GLUT4),lactate dehydrogenase A(LDHA),carnitine palmitoyl transferase-1(CPT-1α),acyl coenzyme A carboxylase(ACC),liver kinase B1(LKB1),adenylate-activated protein kinase(AMPK)and peroxisome proliferator-activated receptor γ coactivator factor 1α(PGC-1α)detected by RT-qPCR;and their myocardial expressions of energy metabolism related proteins LKB1,p-AMPK/AMPK and PGC-1α detected by Western blot.RESULTS Compared with the model group,the pueraria isoflavones groups displayed decreased levels of SBP,DBP,MBP,LVSP,LVMP(P＜0.05,P＜0.01);increased-dp/dtmax(P＜0.05,P＜0.01);improved myocardial fibrinolysis,gap widening and inflammatory infiltration caused by ovariectomy;decreased activities of LDH and CK(P＜0.05);increased myocardial ATP level(P＜0.05,P＜0.01);decreased levels of TC,TG,LDL-C and Glu(P＜0.05,P＜0.01);increased HDL-C level(P＜0.05,P＜0.01);increased myocardial mRNA expressions of GLUT4,LDHA,CPT-1α,ACC,LKB1,AMPK and PGC-1α(P＜0.05,P＜0.01);and increased protein expressions of myocardial LKB1,p-AMPK/AMPK and PGC-1α(P＜0.05,P＜0.01).CONCLUSION Pueraria isoflavones are protective to myocardial injury in ovariectomized rats,and the mechanism may lie in the improvement of energy metabolism-related myocardial proteins via LKB1/AMPK/PGC-1α signaling pathway.

Objective:To explore the values of transcranial Doppler (TCD) characterized spectra oscillatory wave and nail wave in determining brain death in patients accepted decompressive craniectomy (DC).Methods:One hundred and eighty-nine patients with brain death caused by neurological severe diseases admitted to Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University from January 1, 2021 to December 31, 2023 were enrolled: 51 patients accepted DC (skull incomplete group) and 138 patients did not accept DC (skull intact group). TCD, electroencephalogram (EEG) and evoked potential (EP) were performed in all patients from the skull incomplete group and in 47 patients from the skull intact group. Differences in clinical data and detectable rate of TCD characterized spectra between the 2 groups were compared. Consistency of TCD results with EEG and EP results between the skull incomplete group and skull intact group was analyzed at time interval from brain death by clinical judgment to TCD<48 h or time interval from brain death by clinical judgment to TCD≥48 h. Univariate and multivariate Logistic regressions were used to analyze the influencing factors for consistency of TCD results with EEG and EP results in patients from the skull incomplete group.Results:No significant difference in age, gender, time interval from brain injury to brain death by clinical judgment, time interval from brain death by clinical judgment to TCD, or systolic blood pressure during TCD was noted between the skull incomplete group and skull intact group ( P>0.05). Detectable rate of TCD characterized spectra in skull incomplete group (92.16%) was significantly higher than that in the skull intact group (73.91%, χ2=7.428, P=0.006). Consistency of TCD results with EEG and EP results in the skull incomplete group and skull intact group was both 100% at time interval from brain death by clinical judgment to TCD≥48 h. Multivariate Logistic regression analysis showed that time interval from brain death by clinical judgment to TCD≥48 h was an independent influencing factor for consistency of TCD results with EEG and EP results in the skull incomplete group ( OR=7.313, 95% CI: 1.612-15.973, P=0.004). Conclusion:Oscillatory wave and nail wave in TCD observed at time interval from brain death by clinical judgment to TCD≥48 h are the characteristic performances for brain death in patients accepted DC.

Objective:To investigate the predictive value of a clinical imaging model based on multi-slice helical computer tomography (MSCT) examination in predicting prognosis of advanced gastric adenocarcinoma.Methods:The retrospective cohort study was conducted. The clinicopatho-logical data of 88 patients with advanced gastric adenocarcinoma who were admitted to the Ningbo Yinzhou No.2 Hospital from January 2019 to January 2021 were collected. There were 62 males and 26 females, aged (60±15)years. All patients underwent preoperative MSCT examination. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Univariate and multivariate analyses were conducted using the Logistic regression model. The receiver opera-ting characteristic curve was used to analyze the predictive efficacy of prognosis, and the area under the curve (AUC), sensitivity, and specificity were calculated. Results:(1) Surgical situations and follow-up. All 88 patients underwent radical gastrectomy for gastric cancer and were diagnosed with advanced gastric adenocarcinoma through postoperative pathological examination. All 88 patients were followed up after surgery for 41(range, 36?48)months, with a 3-year overall survival rate of 69.32%. (2) Analysis of factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. Results of multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) and extramural venous invasion (EMVI) were independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery ( odds ratio=1.10, 7.72, 95% confidence interval as 1.01?3.82, 1.42?15.42, P<0.05). (3) Construction and evaluation of predictive model. The AUC of predictive efficacy of prognosis for advanced gastric adenocarcinoma of preoperative CEA and EMVI were 0.90 (95% confidence interval as 0.82?0.97) and 0.80 (95% confidence intervalas 0.71?0.89), respectively, with sensitivity of 85.25% and 78.69% and specificity of 100.00% and 81.48%, respec-tively. A predictive model was constructed by combining preoperative CEA and EMVI based on the results of multivariate analysis, and the AUC of the predictive model was 0.93 (95% confidence interval as 0.87?0.98), with sensitivity and specificity of 86.89% and 96.30%. Conclusions:CEA and EMVI are independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. The predictive model constructed by combining preoperative CEA and EMVI has good predictive efficacy for patient prognosis.