Objective: To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme (GBM). Methods: GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47 (TRIM47) in GBM patients. RT-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM cells. LN-229 cell proliferation, migration as well as invasion were estimated by CCK- 8, colony formation, wound healing, and Transwell assays following interference with NUDT5. ECAR assay, L-lactic acid kit, glucose detection kit, and ATP detection kit were applied for the detection of glycolysis-related indexes. Co-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and TRIM47. Results: GEPIA database showed that NUDT5 expression was significantly increased in GBM patients. Inhibiting the expression of NUDT5 in GBM cells significantly suppressed the viability, proliferation, invasion, migration, and glycolysis of GBM cells. Moreover, TRIM47 was highly expressed in GBM cells and interacted with NUDT5. Overexpression of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation, metastasis, and glycolysis of GBM cells. Conclusions: NUDT5 promotes the growth, metastasis, and Warburg effect of GBM cells by upregulating TRIM47. Both NUDT5 and TRIM47 can be used as targets for GMB treatment.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Although indigenous malaria has been eliminated in Wuhan since 2013,imported malaria remains a potential threat as an infectious source of local malaria transmission.The epidemiological and clinical characteristics of imported malaria are particularly important in areas where local malaria has been eliminated.This study was aimed at analyzing the epidemiological and clinical characteristics of imported malaria in Wuhan from 2012 to 2019,to provide a basis for further improving the preven-tion and control of imported malaria.Patients in Wuhan diagnosed with imported malaria from January 1,2012,to December 31,2019,were included in this study.A case-control study was con-ducted to analyze the features of patients with severe malaria.Uni-variate and multivariate logistic regression was used to identify risk factors for prolonged hospital length of stay(LOS).Among 229 imported malaria cases,212(92.6％)were in Chinese citizens,and most cases were in men(96.5％).The gender ratio is 28:1,and the age of cases is mainly concertrated between 18 and 50 years old(89.1％).More than 80％of patients were mi-grant workers,and most cases were infections from African countries(92.6％).Plasmodium falciparum(80.8％)was the dominant species.Fifty-three severe malaria cases were identified during the study period.Compared with uncomplicated cases,severe cases tended to occur in patients with no history of malaria(P=0.008),patients infected with Plasmodium falciparum(P=0.009),and patients who were initially misdiagnosed(P＜0.001).The median LOS was 6 days,and the species of infec-tion(Plasmodium falciparum),the use of antimalarial drugs(group B),antipyretic time(longer than 3 days),and the turn-around time of blood smear microscopy(longer than 3 days)were significantly associated with longer LOS(all P＜0.05).Al-though malaria has been eradicated in Wuhan for many years,imported cases continue to pose a threat.Efforts should be made to strengthen malaria knowledge education for outbound personnel.Additionally,medical institutions must enhance diagnosis and treatment capabilities for malaria,and adhere to standardized treatment processes,and the development of drug resistance and occurrence of severe malaria must be prevented.

Aim To design the pyrimidoindole deriva-tive N-butyl-9H-pyrimido[4,5-b]indole-2-carboxamide(BFPI)and synthesize it to investigate whether it in-hibits macrophage pyroptosis and foaming effects through the NLRP3/Caspase-1 pathway.Methods BFPI was synthesized using 2,4,6-triethoxycarbonyl-l,3,5-triazine and 2-aminoindole as starting materials and structurally characterized by 1H NMR,13C NMR,and ESI-MS.The in vitro cultured mouse monocyte macro-phage cell line RAW264.7 was divided into blank,model(PA)and therapeutic(BFPI)groups,and the cells in each group were treated with the corresponding culture medium for 24 h.The proliferative viability was detected by MTT assay,and the formation of intracel-lular lipid droplets was detected by oil red O staining,and NLRP3 was detected by Western-blot and RT-qPCR,caspase-1 and MCP-1 mRNA and protein ex-pression levels by Western blot and RT-qPCR.Results Compared with the blank group,the proliferation vi-ability of cells in the model group significantly de-creased and the formation of lipid droplets significantly increased;compared with the model group,the prolif-eration viability of cells in the treatment group signifi-cantly increased and the formation of lipid droplets sig-nificantly decreased,and the differences were statisti-cally significant(P＜0.01);compared with the blank group,the cellular NLRP3,caspase-1 and MCP-1 mR-NA and protein expression levels of cells in the model group significantly increased;compared with the model group,the expression levels of the above indexes of the cells in the treatment group significantly decreased,and the difference was statistically significant(P＜0.01).Conclusions BFPI contributes to delaying macrophage-derived foam cell formation during athero-genesis by inhibiting macrophage NLRP3,caspase-1,and MCP-1 expression and thereby promoting their pro-liferation and inhibiting lipid phagocytosis.

Objective:To explore the effect of psychological nursing on the prognosis of male patients with urethral riding inju-ry treated by ureteroscopic urethral catheter implantation(UCI).Methods:This study included 63 male patients with urethral strad-dle injury treated in the General Hospital of Southern Theater Command from February 2020 to March 2023.We divided the patients into a control(n=29)and an experimental group(n=34)according to the odd-or even-numbered days of admission and treated them by ureteroscopic UCI.Meanwhile those of the former group received routine nursing care and the latter underwent psychological nursing intervention in addition.We obtained the Self-Rating Anxiety Scale(SAS)and Self-Rating Depression Scale(SDS)scores of the patients,recorded their postoperative pain scores,catheter-removal time,hospitalization days,postoperative complications and o-verall recovery status,and compared the data collected between the two groups.Results:At 3 days after surgery,both the SAS and SDS scores were significantly lower in the experimental group than in the control(SAS:45.2±2.9 vs 50.4±3.6,P<0.05;SDS:41.9±2.5 vs 48.3±4.0,P<0.05),and so were the pain scores at24 hours(6.2±0.6 vs 6.8±0.9,P<0.05),48 hours(4.9±0.7 vs 6.1±0.8,P<0.05)and 72 hours after surgery(2.5±0.6 vs 3.9±0.9,P<0.05).The hospitalization time was remarkably shorter in the experimental than in the control group([14.1±2.9]vs[16.1±3.4]d,P<0.05),but there was no statistically significant difference in the time of postoperative catheterization between the two groups of patients([19.3±3.7]vs[19.6±4.4]d,P>0.05).A30-day postoperative follow-up found2 cases of difficult urination in the control group but no com-plications in the experimental group.Conclusion:Ureteroscopic UCI is a safe,effective and minimally invasive treatment method for male urethral riding injury,and psychological nursing helps not only shorten the time of catheterization and hospitalization but also a-void postoperative complications.

AIM To control the quality of Bupleurum chinense DC.METHODS The analysis was performed on a 35℃ thermostatic Venusil XBP C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-water flowing at 1.0 mL/min,and the detection wavelength was set at 210 nm.The HPLC fingerprints were established,after which the contents of saikosaponin A,saikosaponin B2,saikosaponin C,saikosaponin D,saikosaponin E,saikosaponin F and 6″-O-acetylsaikosaponin A were determined,and principal component analysis was made.RESULTS There were thirteen common peaks in the fingerprints for twelve batches of medicinal materials with the similarities of 0.970-0.995.Seven constituents showed good linear relationships within their own ranges(R2≥0.999 8),whose average recoveries were 90.75%-100.91% with the RSDs of 1.6%-4.0% .Various constituents demonstrated similar contents in medicinal materials originated in Inner Mongolia and Shanxi.CONCLUSION This precise,accurate and stable method can be used for the quality evaluation of B.chinense.

AIM To investigate the effects and mechanism of Shenxiao Jiedu Tongluo Recipe on renal AIM 2-mediated pyroptosis of a golden hamster model of diabetic nephropathy(DN).METHODS Fifty male golden hamsters of SPF grade were randomly divided into the control group and the model group.The golden hamsters of the model group successfully developed into DN models by feeding of high glucose and high fat diet and intraperitoneal injection of STZ were further randomly assigned into the model group,the enagliflozin group(10 mg/kg),and the low-dose and the high-dose Shenxiao Jiedu Tongluo Recipe groups(12.8,25.6 g/kg)for 8 weeks gavage of the corresponding administration.The golden hamsters had their levels of fasting blood glucose,24 h-UTP,serum TC,LDL-C,Scr,and Sur detected by automatic biochemical analyzer;their serum SOD activity and MDA level detected by biochemical method;their serum levels of IL-1β,IL-18,and TNF-α detected by ELISA method;their pathomorphological changes of kidney tissue observed by HE and PAS staining;their protein expressions of ROS and γH2AX detected by immunofluorescence or immunohistochemistry;and their renal protein expressions of AIM 2,caspase-1 and GSDMD detected by Western blot and immunohistochemistry.RESULTS Compared with the control group,the model group showed atrophic glomeruli;enlarged glomerular capsule cavity;mesangial expansion;edema and necrosis in the dilated renal tubules;increased levels of fasting blood glucose,24 h-UTP,serum TC,LDL-C,Scr,Sur,IL-1β,IL-18,TNF-α,MDA and renal protein expressions of ROS,γH2AX,AIM2,caspase-1,GSDMD(P＜0.01);and decreased serum SOD activity(P＜0.01).Compared with the model group,the high-dose Shenxiao Jiedu Tongluo Recipe group and the enagliflozin group displayed improved renal histopathology,decreased levels of 24 h-UTP,serum TC,LDL-C,Scr,Sur,IL-1β,IL-18,TNF-α,MDA and renal protein expressions of ROS,γH2AX,AIM2,caspase-1,GSDMD(P＜0.05,P＜0.01);and increased serum SOD activity(P＜0.01).CONCLUSION Shenxiao Jiedu Tongluo Recipe can inhibit AIM 2-mediated cell death and alleviate renal inflammatory damage in golden hamsters by inhibiting their expression of ROS-dsDNA-AIM 2 signal pathway to attain reduction of their renal ROS level,DNA damage of renal intrinsic cells,and synthesis of AIM 2 inflammatory corpuscles as well.

Objective To explore the effect of melatonin ( MLT) on the initiation of puberty in female mice and on the expression level of phosphatidylinositol-3-kinases ( PI3K)/protein kinase B ( Akt)/mammalian target of rapamycin (mTOR) signaling pathway in the frypothalamus. Methods Seventy-eight 20-day-old female KM mice were randomly divided into melatonin (MLT) group and normal saline (NS) group, with 39 mice in each group. Starting at 22 days of age, the MLT group was given a subcutaneous injection of 1 mg/kg melatonin and the NS group was given an equal volume of saline. Thirty-two days of age were selected as the sampling point before puberty initiation and 13 mice were executed in each of the two groups, while 37 and 42 days of age were selected as the sampling point after puberty initiation and 13 mice were executed in each of the two groups. Observation of vaginal opening time in mice, weighing of ovaries and uterus to calculate organ indices. HE staining to observe the number of ovarian corpora lutea. The levels of serum luteinizing hormone (LH)were determined by ELISA. The mRNA and protein expression levels of PI3K/Akt/mTOR pathway in frypothalamus were detected by Real-time PCR and Western blotting. Results Compared with the normal saline group, mice in the melatonin group had significantly delayed vaginal opening time ( P < 0. 05 ) , decreased significantly ovarian and uterine volume and index (P<0. 05) , decreased significantly serum LH levels (P<0. 05) , and decreased significantly mRNA and protein expression levels of the frypothalamic PI3K/Akt/mTOR pathway (P<0. 05). Conclusion Melatonin delays puberty initiation in mice by a mechanism that ma)' be related to inhibition of the hypothalamic PI3K/Akt/mTOR signalling pathway.

Objective: By identifying different metabolites in the serum and clarifying the potential metabolic disorder pathways in metabolic syndrome (MS) and stable coronary artery disease patients, to evaluate the predictive value of specific metabolites based on serum metabolomics for the occurrence of MS and coronary heart disease in overweight or obese populations. Methods: This is a retrospective cross-sectional study. Patients with Metabolic Syndrome (MS group), patients with stable coronary heart disease (coronary heart disease group), and overweight or obese individuals (control group) recruited from the Central District of the First Affiliated Hospital of Zhengzhou University from 2017 to 2019 were assigned to the training set, meanwhile, the corresponding three groups of people recruited from the East District of the hospital during the same period were assigned to the validation test. The serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Clinical characteristics (age, gender, body mass index (BMI), blood pressure, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glomerular filtration rate (eGFR), creatinine (CR)) were also collected. Based on the orthogonal partial least-squares discrimination analysis (OPLS-DA) model, the significantly changed metabolites for MS and coronary artery disease patients were screened according to variable important in projection (VIP), and the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of changed metabolites. Results: A total of 488 subjects were recruited in this study, the training set included 40 MS, 249 coronary artery disease patients and 148 controls, the validation set included 16 MS, 18 coronary artery disease patients and 17 controls. We made comparisons of the serum metabolites of coronary artery disease vs. controls, MS vs. controls, and coronary artery disease vs. MS, and a total of 22 different metabolites were identified. The disturbed metabolic pathways involved were phospholipid metabolism, amino acid metabolism, purine metabolism and other pathways. Through cross-comparisons, we identified 2 specific metabolites for MS (phosphatidylcholine (18∶1(9Z)e/20) and pipecolic acid), 4 specific metabolites for coronary artery disease (lysophosphatidylcholine (17∶0), PC(16∶0/16∶0), hypoxanthine and histidine), and 4 common metabolites both for MS and coronary artery disease (isoleucine, phenylalanine, glutathione and LysoPC(14∶0)). Based on the cut-off values from ROC curve, the predictive value of the above metabolites for the occurrence of MS in overweight or obese populations is 100%, the predictive value for the occurrence of coronary heart disease is 87.5%, and the risk predictive value for coronary heart disease in MS patients is 82.1%. Conclusions: The altered serum metabolites suggest that MS and coronary heart disease may involve multiple metabolic pathway disorders. Specific metabolites based on serum metabolomics have good predictive value for the occurrence of MS and coronary heart disease in overweight or obese populations.
Humans ; Metabolic Syndrome ; Overweight ; Coronary Artery Disease ; Retrospective Studies ; Cross-Sectional Studies ; Obesity ; Cholesterol, HDL ; Biomarkers

OBJECTIVE: To retrospectively analyze clinical data of patients under 40 years old who underwent surgical treatment for renal tumors with tumor thrombus from January 2016 to December 2022 at Peking University Third Hospital, and to evaluate the surgical effect and investigate the relationship between clinicopathological characteristics and prognosis. METHODS: The clinical data of 17 young patients with renal tumor thrombus were retrospectively analyzed, and the clinicopathological features and prognosis were summarized. The patients were grouped according to the presence or absence of symptoms, 2017 American Joint Committee on Cancer (AJCC) clinical stage, and postoperative combined adjuvant therapy. Kaplan-Meier method was used to plot the survival curve, and Log-rank test was used to compare the differences in postoperative survival time and progression-free survival time between the different groups. The relationship between clinicopathological features and prognosis was analyzed. RESULTS: All the 17 patients received venous tumor thrombectomy, including 16 patients (94.1%) who underwent radical nephrectomy and 1 patient (5.9%) who underwent partial nephrectomy. Twelve patients (70.6%) had symptoms and 5 (29.4%) had no symptoms before operation. A total of 17 renal tumors were observed, with 2 patients (11.8%) identified as benign and 15 patients (88.2%) classified as malignant. Among the malignant tumors, 1 patient (6.7%) was diagnosed as clear cell carcinoma, while the remaining 14 patients (93.3%) were categorized as non-clear cell carcinoma. In terms of tumor stage, 8 patients (53.3%) were classified as stage Ⅲ according to the AJCC classification, while 7 patients (46.7%) were categorized as stage Ⅳ. Additionally, 6 patients (40%) received multiple adjuvant therapy, while 9 patients (60%) did not undergo such treatment. The follow-up period ranged from 2 to 78 months, with a median follow-up of 41 months. During this time, 3 patients (20%) died. The median survival time after surgery was 39.0 (2.3, 77.8) months, and the progression-free survival time was 16.4 (2.3, 77.8) months. There was no significant difference in postoperative survival time and progression-free survival time among young patients with renal tumor with tumor thrombus, based on the presence of symptoms before surgery (P=0.307, P=0.302), clinical stage of AJCC (P=0.340, P=0.492), and postoperative adjuvant therapy (P=0.459, P=0.253) group. CONCLUSION The pathological types of young patients with renal tumor with tumor thrombus are more complex and varied due to symptoms, and the proportion of non-clear cell carcinoma in malignant tumor with tumor thrombus is higher. Symptomatic and non-clear cell carcinoma may be potentially associated with poor prognosis. Surgical operation combined with adjuvant therapy is a relatively safe and effective treatment for young patients with renal tumor and tumor thrombus.
Humans ; Adult ; Carcinoma, Renal Cell/surgery* ; Retrospective Studies ; Vena Cava, Inferior/surgery* ; Kidney Neoplasms/surgery* ; Prognosis ; Thrombosis/surgery* ; Thrombectomy/methods* ; Nephrectomy/methods*