ObjectiveTo analyze the metabolomic characteristics of platelets in fibrinogen（FIB） overexpression rats of coronary heart disease with blood stasis syndrome（CHD-BSS）， explore potential biomarkers， and investigate the mechanism of FIB overexpression on CHD-BSS. MethodsSD rats were randomly divided into BSS group and BSS+FIB overexpression group（BSS+FIB group）， with 10 rats in each group. Both the BSS+FIB group and the BSS group were fed a high-fat diet combined with oral administration of vitamin D₃ and subcutaneous injection of isoproterenol， but rats in the BSS+FIB group were overexpressed with FIB during the initial modeling stage by transfection with adeno-associated virus（AAV）. The overexpression level of FIB in rat liver and plasma samples was detected by enzyme-linked immunosorbent assay（ELISA） and real-time fluorescence quantitative polymerase chain reaction（Real time PCR）， as well as the expression level of liver FIB A（FGA） mRNA. The characteristics of metabolites in rat platelet samples were analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， and the differential metabolites between groups were screened by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and the enriched pathways were analyzed. The accuracy of potential biomarkers in the diagnosis of CHD-BSS was evaluated by receiver operating characteristic（ROC） curve. The expression of autophagy related proteins phosphorylated adenosine monophosphate（AMP） activated protein kinase（p-AMPK）/AMPK， phosphorylated mammalian target of rapamycin（p-mTOR）/mTOR， microtubule-associated protein 1 light chain 3（LC3） Ⅱ/Ⅰ and p62 in platelets were detected by Western blot. ResultsCompared with the BSS group， the expression levels of FIB in liver and plasma samples of the BSS+FIB group were significantly increased（P<0.05， P<0.01）， and the expression level of FIB mRNA in the liver was remarkably increased（P<0.01）， indicating successful overexpression of FIB. Platelet metabolomics results showed significant differences in metabolic profiles between the BSS+FIB group and the BSS group， and a total of 25 significantly enriched metabolic pathways and 8 metabolites involved in these metabolic pathways， among which uric acid， guanosine and ribose 1-phosphate levels were up-regulated， while adenosine diphosphate（ADP）， AMP， guanosine diphosphate（GDP）， adenylosuccinate and norepinephrine levels were down-regulated. The diagnostic ability analysis of differential metabolites showed that all 8 differential metabolites had good diagnostic ability， with an area under the curve（AUC）>0.85. Western blot results showed that compared with the BSS group， the expression levels of p-mTOR/mTOR and p62 proteins in platelets of the BSS+FIB group was significantly reduced（P<0.01）， while the expression levels of p-AMPK/AMPK and LC3Ⅱ/Ⅰ proteins were increased， but the difference was not statistically significant. ConclusionOverexpression of FIB can change the metabolic characteristics of CHD-BSS rat model， involving multiple aspects such as vascular endothelial injury， platelet activation and myocardial function damage. Among them， overexpression of FIB may enhance the occurrence of platelet autophagy， thereby inducing platelet activation and promoting thrombus formation.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

OBJECTIVE To study the protective effect of saikosaponin b2(SSb2)on corticosterone(CORT)induced PC12 cell injury and its mechanism.METHODS ① PC12 cells were divided into the cell control group(24 h of culture with RPMI-1640 medium),CORT group(24 h of culture with CORT 100-800 μmol·L-1)and SSb2 group(24 h of culture with SSb2 1.5625,3.125,6.25,12.5,25,50 and 100 μmol·L-1).MTT assay was used to detect the cell survival rate.②PC12 cells were divided into the cell control group(24 h of culture with RPMI 1640 medium),model group(24 h of culture with CORT 400 μmol·L-1),and model+SSb2 group(3 h pretreatment with SSb2 1.5625,3.125,6.25,12.5 and 25 μmol·L-1,removal of the supernatant before cells were co-incubated with CORT 400 μmol·L-1 and corresponding concentrations of SSb2 for 24 h).MTT assay was used to detect the cell survival rate while micro-plate assay was used to detect the lactate dehydrogenase(LDH)leakage rate of PC12 cells.③PC12 cells were divided into the cell control group,model group and model+SSb2 12.5 μmol·L-1 group.AnnexinV-FITC/PI flow cytometry assay was used to detect PC12 cell apoptosis,ultra-perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)cell metabonomics was used to detect metabolic profile changes and colorimetric assay was employed to detect the glutamic acid content and glutaminase activity in PC12 cells.RESULTS Compared with the cell control group,the cell viability decreased to(55±6)%(P<0.01)when the concentration of CORT was 400 μmol·L-1.When the concentration of SSb2 was higher than 50 μmol·L-1,there was significant toxicity to PC12 cells(P<0.01).②Compared with the cell control group,the cell survival rate was signif-icantly decreased(P<0.01),while the release rate of LDH was significantly increased(P<0.01)in the model group.Compared with the model group,the cell survival rate significantly increased(P<0.05,P<0.01),while the LDH release rate significantly decreased(P<0.01)in the model+SSb2 group.③ Com-pared with the cell control group,cell apoptosis was significantly increased in the model group(P<0.05).Compared with the model group,cell apoptosis was significantly decreased(P<0.05)in the model+ SSb2 group.Metabolomics results show that SSb2 significantly back-regulated nine differential metabo-lites of glutamate,creatine,N-acetylaspartate,L-tyrosine,citric acid,L-isoleucine,lactic acid,glutamine and choline.Further network analysis of the key metabolites regulated by SSb2 yielded five major metabolic pathways:D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,alanine,aspartate and glutamate metabolism,tyrosine metabolism and arginine biosynthesis.Compared with the cell control group,the content of glutamate and activity of glutaminase were significantly decreased in the model group(P<0.01).Compared with the model group,the content of glutamate(P<0.01)and activity of glutaminase(P<0.05)were significantly increased in the model+SSb2 group.CONCLUSION SSb2 has a neuroprotective effect on CORT-injured PC12 cells,and the mechanism of which is related to inhibition of apoptosis and regulation of metabolic disorders.

The application of artificial intelligence(AI)in medical diagnosis and treatment is becoming increasingly widespread,providing doctors and patients with more high-quality,efficient and personalized medical services.However,it also raised a series of ethical issues such as data security,algorithm transparency,responsibility definition,fairness and justice,doctor-patient relationships,and other aspects.Based on the combing of existing research results,this paper analyzed the research status of medical ethics in the application of AI in diagnosis and treatment,as well as expected that future medical ethics research can further explore the ethical issues of AI technology in medical treatment in greater depth,thus ensuring the rational application of AI in the medical field and maximizing the protection of patients'rights and interests.

Objective To explore the relationship between serum lipoxygenin A4(LXA4)and S100 calc-binding protein A4(S100A4)levels and disease and disease outcome in children with primary nephrotic syn-drome(PNS).Methods A total of 168 children with PNS admitted to Nanjing Mingji Hospital from March 2020 to March 2022 were selected as the study objects,and 150 healthy children who came to Nanjing Mingji Hospital for physical examination were selected as the control group.The children with PNS were divided into remission group(n=73)and attack group(n=95)according to disease activity.Serum LXA4 and S100A4 levels were detected by enzyme-linked immunosorbent assay.The patients were followed up for 1 year after discharge and were divided into good prognosis group(n=138)and poor prognosis group(n=30)according to the prognosis.Spearman correlation analysis was used to investigate the relationship between serum LXA4,S100A4 levels and disease activity.The predictive value of serum LXA4 and S100A4 in the prognosis of PNS children was evaluated by receiver operating characteristic(ROC)curve.Multivariate Logistic regression was used to analyze the prognostic factors of PNS children.Results The serum levels of LXA4 and S100A4 in the remission group and the attack group were higher than those in the control group,and the serum levels of LXA4 and S100A4 in the attack group were higher than those in the remission group(P＜0.05).The serum levels of LXA4 and S100A4 were positively correlated with disease activity in children with PNS(r=0.593,0.546,P＜0.05).The good prognosis group had significantly lower serum levels of LXA4 and S100A4 than the poor prognosis group(P＜0.05).The area under the curve(95％CI)of serum LXA4 and S100A4 for pre-dicting the outcome of PNS in children was 0.767(0.756-0.888)and 0.846(0.824-0.863),respectively.The area under the curve of the joint(95％CI)was 0.905(0.879-0.924).Compared with the good progno-sis group,the poor prognosis group had significantly higher proportion of nephritis type,24 h urinary protein,hematuria,and urine protein clearance time,and significantly lower proportion of simple type,total protein,and IgM levels(P＜0.05).The multivariate Logistic regression analysis showed that hematuria(OR=2.300,95％CI 1.598-3.312),24 h urinary protein 121.25 mg/24 h(OR=2.098,95％CI 1.489-2.956),LXA4≥95.64 ng/L(OR=2.627,95％CI 1.737-3.973),and S100A4≥248.15 ng/L(OR=2.729,95％CI 1.777-4.192)were risk factors for poor prognosis in children with PNS(P＜0.05).Conclusion The serum levels of S100A4 and LXA4 are increased in children with PNS,and are related to disease activity and progno-sis,which may be used as potential markers for evaluating the condition and prognosis of PNS.

Objective:To investigate the efficacy and safety of the application of microwave ablation assisted clamp-less suture-less nephron sparing surgery technique in the management of cystic renal cell carcinoma.Methods:The data of 21 consecutive patients with cystic renal cell carcinoma who underwent microwave ablation assisted clamp-less suture-less laparoscopic nephron sparing surgery (MACS-LNSS) in Renji Hospital, Shanghai Jiaotong University School of Medicine from January 2017 to December 2020, were retrospectively analyzed. There were 17 males and 4 females with a mean age of (58.0±2.6) years old. There were 19 cases with Eastern Cooperative Oncology Group (ECOG) score 0 and 2 with score 1. The mean diameter of the tumor was (3.6±0.4) cm, and the mean distance from the collecting system was (10.7±0.9) mm with 12 located on the left and 9 on the right side. There were 5 cases of Bosniak Ⅲ with mean CT value (27.6±4.6) HU and 16 of Bosniak Ⅳ and the mean estimated glomerular filtration rate(eGFR) was (84.1±4.1 ) ml/(min·1.73 m 2). The American Society of Anesthesiology (ASA) graded 17 cas as grade 1, 3 cases as grade 2 and 1 cases as grade 3. MACS-LNSS was performed for all patients. The microwave ablation probe was introduced via the laparoscopic trocar and inserted into the tumor. Then all tumors were resected after microwave ablation was performed for 1 to 3 cycles lasting 2 to 5 minutes for each tumour with a power output of 60 to 100 W using an MTC-3C microwave ablation system. Results:MACS-LNSS was successfully performed in 20 cases. Another one converted to conventional laparoscopic partial nephrectomy because of intraoperative bleeding with 14 min renal artery branch clamped. No case converted to open surgery or radical nephrectomy. The mean operative time was (92.0±6.3) min, with a mean estimated blood loss of (60.0±7.2) ml. The mean length of postoperative hospital stay was (2.7±0.1) d. No case required perioperative transfusion. One case with fever and one case with urine leakage were observed postoperatively and recovered after conservative treatment. Pathologic results revealed 18 cases of clear cell carcinoma, 3 of low grade malignant potential multilocular cystic renal cell tumors. The median eGFR at 6 months postoperative was (82.9±3.8) ml/(min·1.73 m 2).No local recurrence and distant metastasis was observed with a mean follow-up of (41.3±1.5)(range from 32 to 58) months. Conclusions:MACS-LNSS which has the advantages of controllable complications is an alternative, safe and feasible technique for cystic renal cell carcinoma less than 7 cm, with regular tumor base, and the distance from the collecting system more than 5 mm.

Background/Aims: Inflammatory bowel disease (IBD) may contribute to the development of hematologic malignancies. In this study, the potential relationship between IBD and hematologic malignancies was investigated. Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for all cohort studies comparing the incidence of hematologic malignancies in non-IBD populations with that in IBD patients, and we extracted relevant data from January 2000 to June 2023 for meta-analysis. Results: Twenty cohort studies involving 756,377 participants were included in this study. The results showed that compared with the non-IBD cohort, the incidence of hematologic malignancies in the IBD cohort was higher (standardized incidence ratio [SIR]=3.05, p<0.001). According to the specific types of IBD, compared with the non-IBD patients, the incidences of hematologic malignancies in ulcerative colitis patients (SIR=2.29, p=0.05) and Crohn's disease patients (SIR=3.56, p=0.005) were all higher. In the subgroup analysis of hematologic malignancy types, compared with the control group, the incidences of non-Hodgkin's lymphoma (SIR=1.70, p=0.01), Hodgkin's lymphoma (SIR=3.47, p=0.002), and leukemia (SIR=3.69, p<0.001) were all higher in the IBD cohort. Conclusions The incidence of hematologic malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and leukemia is higher in patients with IBD (ulcerative colitis or Crohn's disease) than in non-IBD patients.

The pathogenesis of Sjögren's syndrome （SS） was considered to involve external dryness， internal injured essence and blood， yin-deficiency endowment， and abnormal emotion and spirit， and it was believed that SS has the characteristics of dryness and impassability， and the pathogenesis of deficiency-excess in complexity. According to the theory “upper dryness treats qi， and lower dryness treats blood” in YE Gui's monograph “Medical Records for Clinical Guidance”， the dryness was divided into upper dryness and lower dryness syndromes to be differentiated and treated. When treating dryness syndrome， the patient should follow the characteristics of the five zang organs， using soft and cool medicines， avoiding warm and dry medicines， and valuing the animal products. The upper dryness could be treated with Sangxiang Decoction （桑杏汤） to clear the qi and moisten the dryness， Qiaohe Decoction （翘荷汤） to clear the upper with pungent-cool， and Shashen Maidong Decoction （沙参麦冬汤） to nourish yin and promote the production of body fluid. The lower dryness could be treated with Fumai Decoction （复脉汤） to enrich and nourish the five kinds of fluid. Liuwei Dihuang Pill （六味地黄丸） to nourish the kidneys and supplement essence， and Wuren Pill （五仁丸） to moisten the dryness and nourish the blood， which provided a new way of thinking for differentiation of the dryness syndrome.

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals ; Mice ; Male ; Cell Line ; Rats ; Kidney/physiology* ; Fibrosis/drug therapy* ; Renal Insufficiency, Chronic/drug therapy* ; Adenine ; Epithelial-Mesenchymal Transition ; Aquaporin 1/metabolism*

Objective : To investigate the cross⁃sectional associations of serum interleukin( IL) Ⅳ18 with cartilage volume , cartilage defects , bone marrow lesions ( BML) and biomarkers of cartilage degradation in patients with knee osteoarthritis (OA) , and to provide new ideas and new methods for clinical diagnosis and treatment. Methods: The study included 151 patients with knee OA , a general questionnaire survey was conducted , and the knee strucral was photographed by magnetic resonance imaging (MRI) . The cartilage volume was measured by OsiriX software in 3D⁃FLASH sequence , and cartilage defect and BML were determined in T2⁃weighted sequence. Serum IL-18 and matrix metalloproteinase ( MMP) Ⅳ3 , 13 levels were measured by enzyme⁃linked immunosorbent assay(ELISA) . SPSS software was used for statistical analysis. Results : In multivariable analyses , serum IL⁃18 level was consistent at divided part of joint (femorotibial joint and the patella femoral joint , all P < 0. 05) . Serum IL⁃18 level was positively associated with cartilage defect and BML at media femorotibial area (all P < 0. 01) . Serum IL⁃18 level was positively associated with MMP⁃3 (β = 0. 31 , 95% CI:0. 001 - 0. 010) and MMP⁃13 (β = 0. 86 , 95% CI:0. 08 - 0. 10 , all P < 0. 01) . CI:0. 08 - 0. 10 , all P < 0. 01) . Conclusion Serum IL⁃18 level is negatively associated with cartilage volume and Serum IL⁃18 level is negatively associated with cartilage volume and positively associated with cartilage defect , BML , MMP⁃3 and MMP⁃13 , suggesting IL⁃18 may play a significant role duce the injury of article cartilage in patients with knee OA and delay the progression of disease.