BACKGROUND:Semen cuscutae has the effect of tonifying the liver and kidney system and benefiting the essence.The main pathogenesis of osteoarthritis is deficiency of the liver and kidneys.Therefore,it is hypothesized that there is a link between semen cuscutae and osteoarthritis. OBJECTIVE:To explore the potential relationship between osteoarthritis and semen cuscutae and validate the mechanism of semen cuscutae based on the network pharmacology and molecular docking analysis. METHODS:First,the active ingredients and targets of semen cuscutae were screened in TCMSP,and the genes related to osteoarthritis were collected in the disease databases GeneCard's,OMIM and TTD.The intersected genes were taken and then subjected to a series of analyses and screened for hub genes.Through the enrichment analysis of hub genes,the pathway of semen cuscutae acting on osteoarthritis was selected.The role of hub genes was verified by molecular docking.Therefore,the appropriate active ingredients of semen cuscutae were selected for experimental verification. RESULTS AND CONCLUSION:There were 11 active ingredients of semen cuscutae,66 intersection target genes of semen cuscutae and osteoarthritis,and 12 hub genes,including tumor necrosis factor,interleukin 1B,TP53,RAC-alpha serine/threonine protein kinase(AKT1),vascular endothelial growth factor A,matrix metalloproteinase 9,prostaglandin peroxidase 2,cystatinase 3,epidermal growth factor,peroxisome proliferator-activated receptor gamma,interleukin 10,vascular cell adhesion factor 1.After the enrichment analysis of the hub genes,the classical inflammatory pathway,nuclear factor-κB signaling pathway,was selected for subsequent validation of semen cuscutae to alleviate osteoarthritic inflammation.Through the results obtained after molecular docking of each active ingredient and the hub gene of the pathway prostaglandin peroxidase 2,sesamin with the highest affinity was selected for subsequent cell experiments,and the experimental results confirmed that sesamin,the active ingredient of semen cuscutae,could reduce the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β.To conclude,sesamin,the active ingredient of semen cuscutae,reduces the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β,thereby improving inflammation in osteoarthritis and expanding the therapeutic effect of semen cuscutae in osteoarthritis.

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Objective To investigate the effect of Xuebijing injection on the inflammatory and coagulation response of complicated intra-abdominal infection by sepsis.Methods A retrospective study was conducted.A total of 274 patients with complicated intra-abdominal infection by sepsis admitted to Yidu Central Hospital of Weifang from June 2020 to July 2023 were enrolled.According to whether Xuebijing was used or not,the patients were divided into an observation group(141 cases)and a control group(133 cases).The patients in both groups were treated with conventional western medicine,and those in the observation group were additionally given Xuebijing(Xuebijing injection 100 mL in 0.9%NaCl solution 100 mL via intravenous infusion,twice per day for a continuous application of 5 days).The differences of clinical prognosis and the serum levels of inflammatory indicators[interleukin-6(IL-6),procalcitonin(PCT),C-reactive protein(CRP)and endotoxin]and coagulation indexes[D-dimer,fibrinogen(FIB),prothrombin time(PT)and activated partial thromboplastin time(APTT)before treatment and on the 2nd,3rd,5th day respectively after treatment were compared,and the clinical prognosis was observed.Results There were no significant differences in the indexes of inflammation and coagulation function between the two groups before treatment.With the extension of therapy duration,following treatment in two groups,the serum levels of inflammatory indicators and coagulation indexes(D-dimer,FIB)decreased,as did coagulation indexes(PT,APTT),reaching the lowest levels on the 5th day.The inflammatory markers and coagulation indexes of observation group were significantly lower than those of control group[IL-6(ng/L):18.89±8.22 vs.24.59±10.39,PCT(μg/L):0.30±0.16 vs.0.52±0.20,CRP(mg/L):13.13±6.54 vs.28.87±8.66,endotoxin(kEU/L):0.17±0.06 vs.0.22±0.08,D-dimer(mg/L):1.75±0.61 vs.1.96±0.77,FIB(g/L):2.50±0.78 vs.3.10±0.94,PT(s):14.16±1.90 vs.15.05±1.46,APTT(s):34.52±5.40 vs.36.21±4.72,both P<0.05].The intensive care unit(ICU)stay time and total hospitalization time were shortened in the observation group than those in the control group[ICU stay time(days):5.71±2.22 vs.6.86±2.99,hospitalization time(days):15.50±6.39 vs.17.02±5.70,both P<0.05];the mortality was significantly lower in the observation group than that in the control group[21.27%(30/141)vs.32.33%(43/133),P<0.05].Conclusion The treatment of complicated intra-abdominal infection by sepsis with Xuebijing injection while receiving conventional western medicine treatment can effectively decrease inflammatory and coagulation response,have high efficacy of inflammatory and coagulation co-treatment,and have some important clinical values.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

OBJECTIVE To study the effect and mechanism of N1,N2 bis(2,3-dihydroxy-4,6-disul-fonic acid benzyl)ethylenediamine sodium salt(NBED)on uranium excretion.METHODS ICR mice were divided into the blank control group,uranium exposure group(0.03 mg·mouse-1),uranium expo-sure+diethylenetriamine pentaacetic acid(DTPA-CaNa3)(150 mg·kg-1)group,and the uranium expo-sure+NBED(45,90,180 mg·kg-1)group.After uranyl acetate was injected into the tail vein of mice,appro-priate doses of NBED or DTPA-CaNa3 were injected into the tail vein.After 24 h,the uranium contents in the kidney,bone and liver+spleen+muscle were determined by inductively coupled plasma mass spectrometry(ICP-MS).The dissociation constant of NBED and the complexation constant of NBED with uranyl were determined via potentiometric titration.RESULTS Animal experiments showed that NBED 45,90 and 180 mg·kg-1 could significantly reduce the uranium accumulation in the kidney by 48.2%-66.5%,in the bone by 21.4%-54.8%,and in liver+spleen+muscle by 38.2%(P<0.01),compared to the uranium exposure group,47.8%,21.4%and 22.7%respectively by DTPA-CaNa3(P<0.05),and the effect in the NBED 180 mg·kg-1 group was significantly better than in the DTPA-CaNa3 group(P<0.05).The results of potentiometric titration showed that there was about 22.3%LH5,59.8%LH4 and 17.85%LH3(L means NBED)in NBED at pH 7.4,and the secondary dissociation LH4 was the main form.In the range of pH 3-11,there were four complex compounds of NBED and uranyl,and their step-wise complex cumulative constants were logβ111(12.5),logβ101(9.8),logβ102(15.3),logβ1-12(6.5)respectively.The(UO2)L22-was the main species(75.3%)at physiological pH 7.4,and the-log[UO22+free]value(pUO2)of free uranyl ion in solution was 9.57.CONCLUSION NBED mainly exists in the form of secondary dissociated LH4in vivo,and chelates with uranyl 2:1 to form uranyl complex,which is excreted in vitro.Intravenous administration of NBED can more effectively promote excretion than DTPA-CaNa3.

Radiation-induced brain injury (RBI) is one of the complications after radiotherapy for head and neck malignant tumors, which seriously affects the quality of life of patients. The pathophysiological mechanism of RBI is not completely clear. Current studies suggest that it is involved in a variety of cells in the central nervous system (CNS), whereas astrocyte, as the largest number of glial cells in the CNS, plays an important role in maintaining the CNS homeostasis and responding to CNS injury. In this article, the role of astrocytes in RBI was reviewed.

Since the enrollment in 2002, the cultivation model of "4+4" program of clinical medicine in Shanghai Jiao Tong University School of Medicine has been continuously explored and practiced. With the goal of cultivating high-level compound outstanding medical innovative talents with multi-disciplinary cross-capacity, through strengthening the heuristic teaching, establishing the medical-engineering cross-course, emphasizing the training of scientific research ability, and taking teaching reform in the basic clinical single-circulation organ system integration course, we have established a talent training system with the characteristics of Shanghai Jiao Tong University School of Medicine, which is characterized by "thick foundation, strong practice, re-transformation, shaping norms, and international integration", and intend to make further exploration in the field of post-graduation education convergence.

Objective To investigate the predictive value of peripheral blood LMR and LMR/LDH on the prognosis of primary Waldeyer's Ring DLBCL patients. Methods We collected 71 patients with primary Waldeyer's Ring DLBCL. The ROC curve was used to determine the optimal critical values of LMR and LMR/LDH before treatment. The chi-square test was used to analyze the constituent ratio and rate of high and low LMR groups as well as high and low LMR/LDH groups. Kaplan-Meier method was used to calculate survival rate. Log rank method and Cox risk regression model were used for univariate and multivariate analyses, respectively. Results The optimal critical values of LMR and LMR/LDH were 2.97 and 1.56, respectively. The prognosis of patients in the high LMR group was significantly better than that in the low LMR group (P < 0.001). The prognosis of patients in the high LMR/LDH group was significantly better than that in the low LMR/LDH group (P < 0.001). Univariate analysis showed that age, B symptoms, clinical stage, treatment efficacy, IPI score, LDH level, LMR and LMR/LDH were important factors that influenced the prognosis of early-stage Waldeyer's Ring DLBCL. Multivariate analysis showed that the age, clinical stage and LMR/LDH were independent prognostic factors. Conclusion LMR and LMR/LDH before treatment may have certain value in predicting the prognosis of Waldeyer's Ring DLBCL patients.

Objective:To explore the influence of hypophosphatemia on weaning from mechanical ventilation.Methods:An observational study was conducted. The medical records of 30 mechanical ventilated patients with hypophosphatemia admitted to intensive care unit of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to August 2020 were analyzed; another 60 mechanical ventilated patients with normophosphatemia around the same time were enrolled as controls by 1∶2 case-control matching based on gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score. And then the duration of invasive mechanical ventilation, times of spontaneous breathing trial (SBT), the diaphragmatic ultrasonography movement indexes, and outcome of weaning and prognosis during hospitalization were compared between the two groups. Receiver operator characteristic curve (ROC curve) was plotted to calculate the areas under ROC curve (AUC) and cut-off values of serum phosphorus for successful weaning and hospital survival. The correlations between the diaphragmatic ultrasonography movement indexes and serum phosphorus were analyzed by Pearson partial correlation analysis.Results:Compared with normophosphatemic group, the duration of invasive mechanical ventilation in hypophosphatemia group was significantly longer [days: 13.0 (7.0, 22.0) vs. 10.0 (5.5, 14.0), P < 0.05], and SBT attempts were more often [times: 3 (0, 5) vs. 1 (1, 2), P < 0.01], while the rate of successful weaning was lower (53.3% vs. 91.7%, P < 0.01), and the hospital mortality was higher (20.0% vs. 1.7%, P < 0.01). ROC curve analysis showed that serum phosphorus could predict successful weaning of mechanical ventilated patients, the AUC was 0.795, and the optimum cut-off value of serum phosphorus was 0.85 mmol/L with sensitivity of 73.2% and specificity of 84.2%. Serum phosphorus could predict hospital survival of mechanical ventilated patients, the AUC was 0.782, and the optimum cut-off value of serum phosphorus was 0.48 mmol/L with sensitivity of 81.9% and specificity of 85.7%. Compared with normophosphatemic group, diaphragm thickness at the end of inspiration (DTei), diaphragm thickness at the end of expiration (DTee), diaphragm thickening fraction (DTF), diaphragm excursion (DE) in hypophosphatemia group were all significantly decreased [DTei (cm): 0.19±0.07 vs. 0.27±0.08, DTee (cm): 0.14±0.05 vs. 0.19±0.06, DTF: (33.55±16.17)% vs. (45.04±18.66)%, DE (cm): 1.17±0.49 vs. 2.28±0.69, all P < 0.01]. Pearson partial correlation analysis showed that linear correlations were found between serum phosphorus and DTei, DTee, DTF, DE ( r values were 0.442, 0.351, 0.293, 0.628 respectively, all P < 0.01). Conclusions:Serum phosphorus may have correlation with the diaphragmatic ultrasonography movement indexes. Hypophosphatemia may impair the contractile properties of diaphragm, induce more SBT attempts and longer duration of invasive mechanical ventilation, and affect outcome of weaning and prognosis.

Objective:To study the clinical prognosis and related factors affecting optimal medical therapy (OMT) compliance of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).Methods:A prospective study was conducted to select 3 818 patients who were diagnosed with CAD and successfully underwent PCI in TEDA International Cardiovascular Hospital from October 2016 to September 2017. The clinical information and application of OMT during hospitalization and 1 year later were collected for research.The patients were divided into OMT group and non OMT group according to whether they adhered to OMT during follow-up one year after discharge. After comparing the imbalance baseline data of hypertension,diabetes and hyperlipidemia with propensity score,demographic characteristics, coronary revascularization history, CAD, laboratory related laboratory examinations,and the use of OMT drugs were compared between the two groups. Cox regression model was used to analyze the relationship between long-term OMT and clinical prognosis in patients with CAD.Multivariate binary logistic regression was used to analyze the related factors affecting long-term OMT compliance.Results:A total of 3 818 cases of CAD patients were matched by propensity score and 2 596 patients were included in the study. There were 1 609 males and 987 females. The age was (62.51±9.56) years old.One year later,1298 patients (50%) insisted on OMT,including dual antiplatelet therapy(DAPT), statins, β-blockers and ACEI/ARB were 97.0% (2 517/2 596),94.5%(2 454/2 596),69.6% (1 806/2 596) and 64.2% (1 666/2 596), especially angiotensin converting enzyme inhibitors / angiotensin receptor blockers and β Receptor blockers decreased the most.Cox regression analysis showed that after adjusting for other factors, compared with non-adherence to OMT group,OMT after PCI was associated with better prognosis ( HR=0.416,95% CI 0.270-0.641, P<0.001). The prognosis of CAD patients with history of old myocardial infarction ( HR=1.804,95% CI 1.070-3.041, P=0.027),cardiac insufficiency ( HR=2.074,95% CI 1.161-3.702, P=0.014),multivessel coronary disease ( HR=2.211,95% CI 1.228-3.983, P=0.008) and BMI>24 ( HR=1.570,95% CI 1.037-2.377, P=0.033) were related to worse clinical outcomes. Multi-factor binary Logistic regression showed that OMT at hospitalization was a strong influencing factor of long-term adherence to OMT ( OR=41.278,95% CI 29.961-56.871, P<0.001). Patients with higher education,employee medical insurance and with history of PCI tend to persist in OMT. Conclusion:The medication compliance of patients with long-term OMT after PCI is still poor,while the high compliance of OMT is related to the lower incidence of adverse cardiovascular events,including death, nonfatal myocardial infarction and stroke. If there is no obvious contraindication,all patients after PCI should adhere to OMT.