Objective To investigate the predictive value of the inflammation scoring system based on the blood routine for complicated acute pancreatitis(CAP).Methods The clinical data of 630 patients with a-cute pancreatitis(AP)receiving the treatment in the People's Hospital of Chongqing Liang Jiang New Area from January 2021 to January 2024 were retrospectively analyzed.The patients were divided into the mild a-cute pancreatitis(MAP)group and CAP group according to the disease severity degree.The propensity score matching was used to balance the baseline characteristics of the cases in the two groups,the differences be-tween the inflammatory scoring system based on the blood routine[neutrophile granulocyte/lymphocyte ratio(NLR),derived neutrophile granulocyte/lymphocyte ratio(dNLR),platelet/lymphocyte ratio(PLR),system-ic immune inflammatory index(SII)and systemic inflammatory response index(SIRI)]and the clinical out-come indexes within 24 h of admission were analyzed,and the logistic regression was used to analyze the risk factors of CAP.Results A total of 404 patients were included in the study by the propensity score matching,each 202 cases in the two groups.In the CAP group,there were 35 cases(16.7％)receiving intensive care unit(ICU)treatment and 4 cases(1.9％)of death.Compared with the MAP group,WBC,neutrophile granulo-cyte,CRP,BUN,amylase and lipase levels and NLR,dNLR,SII and SIRI scores in the CAP group were high-er,serum calcium and albumin levels were lower,and the differences were statistically significant(P＜0.05).The stepwise logistics regression analysis showed that CRP,albumin,lipase,serum calcium and SIRI were the independent influencing factors of CAP occurrence(P＜0.05).Conclusion The inflammation scoring system based on the blood routine could predict the CAP occurrence.

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC.Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

Objective:To review the clinical efficacy and safety of the FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, fluorouracil) regimen in treatment of pancreatic cancer.Methods:The clinical data of 31 patients with pancreatic cancer who were treated with the FOLFIRINOX regimen from July 2016 to December 2019 at the Department of General Surgery, China-Japan Friendship Hospital were retrospectively analyzed. For the 20 males and 11 females who were enrolled into this study, their age ranged from 29 to 80 years (mean 56.9 years). The FOLFIRINOX regimen was used as neoadjuvant therapy in 12 patients, postoperative therapy in 10 patients with liver-metastases, and postoperative adjuvant therapy in 9 patients (as second-line chemotherapy in 7 patients and as first-line chemotherapy in 2 patients). The clinical efficacy and adverse reactions of chemotherapy were evaluated.Results:In this study, 8 patients received the modified FOLFIRINOX regimen. Of the remaining 23 patients who received the standard FOLFIRINOX regimen, 10 (43.3%) were converted to the modified regimen because of adverse events. On clinical efficacy evaluation after neoadjuvant therapy: 5 patients achieved partial remission (PR), 3 stable disease (SD) and 4 progression disease (PD). The disease control rate (DCR) was 66.7% (8/12). For 10 patients got remission of abdominal pain, 5 patients underwent surgical resection. For the 10 patients with liver-metastases, 6 achieved PR, 1 SD, 3 PD. For 7 patients got disease control. For 8 patients had remission of abdominal pain, 1 patient underwent surgical resection. For the 7 patients who received second-line chemotherapy, 2 achieved PR and 5 PD. No tumor recurrence or metastases were found in the two patients after the first-line chemotherapy. Adverse events above grade three in all the patients included neutropenia in 12 patients (38.7%), leukopenia in 7 patients (22.6%) and thrombocytopenia in 1 patient (3.2%).Conclusions:The FOLFIRINOX regimen was efficacious with a high DCR rate and controllable adverse events. Balancing its efficacy and safety showed this regimen to be beneficial to patients with pancreatic cancer.

Mutants of proteins are the basis for studying their structure and function, this work aimed to establish an efficient and rapid method for constructing multi-site mutants. When four or more adjacent amino acid residues need to be mutated, firstly, two long and two short primers (long primers Ⅰ/Ⅰ, short primersⅡ/Ⅱ) were designed: the long primers contain mutated sites, and the number of mutant bases is ≤20 bp, the short primers do not contain mutated sites; GC contents of the long and short primers are ≤80%, and the difference of annealing temperature is ≤40 °C. Then two sets of reverse PCR amplifications were performed using primer pairs (Ⅰ/Ⅱand Ⅰ/Ⅱ) and templates, respectively. After amplification, each system can obtain non-methylated linear plasmids which contain mutated sites, and the breakpoints of the two sets of linear plasmids amplified by primers Ⅰ/Ⅱ and Ⅲ/Ⅳ were distributed on both sides of the mutated sites. Followed by digested by DpnⅠ to remove the methylated templates, the recovered PCR products, which were mixed in an equimolar ratio, were performed another round of denaturation and annealing: the two sets of linear plasmids were denatured at 95 °C and then annealed with each other's single-stranded DNA as templates to form open-loop plasmids, and then the transformants containing the mutations will be obtained after transformed the open-loop plasmids into Escherichia coli competent cells. Results showed that, this method can mutate 4 to 11 consecutive amino acid residues (8-20 bp) simultaneously, which will greatly simplify the construction of multi-site mutants, Thereby improve the efficiency of protein structure and function research further.
DNA Primers ; genetics ; Escherichia coli ; Mutagenesis, Site-Directed ; methods ; Plasmids ; genetics ; Polymerase Chain Reaction

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

Objective: To investigate the incidence of postoperative pancreatic fistula (POPF) and its risk factors after radical gastrectomy. Methods: The prospective study was conducted. The clinicopathological data of 2 089 patients who underwent radical gastrectomy in 22 medical centers between December 2017 and November 2018 were collected, including 380 in the Zhongshan Hospital of Fudan University, 351 in the Renji Hospital of Shanghai Jiaotong University School of Medicine, 130 in the Ruijin Hospital of Shanghai Jiaotong University School of Medicine, 139 in the Peking University Cancer Hospital, 128 in the Fujian Provincial Cancer Hospital, 114 in the First Hospital Affiliated to Army Medical University, 104 in the First Affiliated Hospital of Nanchang University, 104 in the Affiliated Hospital of Qinghai University, 103 in the Weifang People′s Hospital, 102 in the Fujian Medical University Union Hospital, 99 in the First Affiliated Hospital of Air Force Medical University, 97 in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, 60 in the Hangzhou First People′s Hospital Affiliated to Zhejiang University School of Medicine, 48 in the Fudan University Shanghai Cancer Center, 29 in the First Affiliated Hospital of Xi′an Jiaotong University, 26 in the Lishui Municipal Central Hospital, 26 in the Guangdong Provincial People′s Hospital, 23 in the Jiangsu Province Hospital, 13 in the First Affiliated Hospital of Sun Yat-Sen University, 7 in the Second Hospital of Jilin University, 4 in the First Affiliated Hospital of Xinjiang Medical University, 2 in the Beijing Chao-Yang Hospital of Capital Medical University. Observation indicators: (1) the incidence of POPF after radical gastrectomy; (2) treatment of grade B POPF after radical gastrectomy; (3) analysis of clinicopathological data; (4) analysis of surgical data; (5) risk factors for grade B POPF after radical gastrectomy. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using ANOVA. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the t test or chi-square test based on data excluding missing data of clinico-pathological and surgical data. Multivariate analysis was conducted using the Logistic regression model based on factors with P<0.20 in univariate analysis. Results: There were 2 089 patients screened for eligibility, including 1 512 males, 576 females and 1 without sex information, aged (62±11)years. The body mass index (BMI) was (23±3)kg/m². (1) The incidence of POPF after radical gastrectomy: the total incidence rate of POPF in the 2 089 patients was 20.728%(433/2 089). The incidence rates of biochemical fistula, grade B pancreatic fistula, and grade C pancreatic fistula were 19.627%(410/2 089), 1.101%(23/2 089), 0, respectively. (2) Treatment of grade B POPF after radical gastrectomy: 2 of 23 patients with grade B POPF after radical gastrectomy had drainage tube placed for more than 21 days and received anti-infective therapy. Four of 23 patients with grade B POPF after radical gastrectomy had ascites detected by imaging examination, of which 2 received peritoneal drainage guided by ultrasound, 1 received failed puncture drainage, 1 received no puncture drainage, and they were given anti-infective therapy. Eleven of 23 patients with grade B POPF after radical gastrectomy had no ascites detected by imaging examinations, and they were given anti-infective therapy and inhibitors of pancreas secretion for clinical manifestation as fever or elevated white blood cells. Six patients with no typical clinical manifestations were given somatostatin to inhibite pancreas secretion and prolonged duration of abdominal drainage tube placement (with a median time of 7 days). All the 23 patients recovered well after treatment, without reoperation. (3) Analysis of clinicopathological data: for the 2 089 patients, BMI, cases with or without neoadjuvant therapy were (23±3)kg/m^2, 1 487, 160 of patients without pancreatic fistula, (23±3)kg/m^2, 386, 22 of patients with biochemical fistula, and (24±3)kg/m^2, 22, 1 of patents with grade B pancreatic fistula, showing significant differences between the three groups (F=5.787, χ²=8.269, P<0.05). (4) Analysis of surgical data: for the 2 089 patients, cases with open surgery, laparoscopic assisted surgery, totally laparoscopic surgery (surgical method), cases with D₁ lymph lode dissection, D₂ lymph lode dissection, and other lymph lode dissection (range of lymph lode dissection), cases with no omentectomy, partial omentectomy, and total omentectomy (range of omentectomy), cases with no usage of energy facility, usage of CUSA, LigaSure, LigaSure+ CUSA as energy facility, cases with or without biological glue, the number of lymph node dissection were 737, 624, 292, 24, 1 580, 51, 418, 834, 381, 63, 1 530, 23, 16, 1 431, 201, 33±14 of patients without pancreatic fistula, 146, 189, 74, 11, 389, 9, 110, 171, 128, 35, 359, 6, 9, 378, 31, 31±14 of patients with biochemical fistula, and 14, 5, 4, 0, 20, 3, 6, 13, 4, 2, 18, 1, 2, 22, 1, 37±16 of patients with grade B pancreatic fistula, showing significant differences between the three groups (χ²=15.578, 9.397, 15.023, 28.245, 8.359, F=4.945, P<0.05). (5) Risk factors for grade B POPF after radical gastrectomy: results of univariate analysis showed that usage of energy facility was a related factor for grade B POPF after radical gastrectomy (χ²=9.914, P<0.05). Results of multivariate analysis showed that laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, the number of lymph lode dissection were independent factors for for grade B POPF after radical gastrectomy (odds ratio=0.168, 3.922, 9.250, 1.030, 95% confidence interval: 0.036-0.789, 1.031-14.919, 1.036-82.602, 1.001-1.059, P<0.05). Conclusions The incidence of grade B POPF after radical gastrectomy is relatively low. Laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, and the number of lymph lode dissection are independent risk factors for grade B POPF. Trial Registration: This study was registrated at ClinicalTrial.gov in United States with the registration number of NCT03391687.

Objective To investigate the feasibility,safety and efficacy of endovascular recanalization of the symptomatic occlusion of large intracranial artery in anterior circulation.Methods From October 2015 to December 2017,13 patients with symptomatic non-acute occlusion of large intracranial artery in anterior circulation were enrolled into this study and underwent endovascular recanalization.The initial procedural results,including the rate of successful recanalization and perioprocedural complications,and angiographic and clinical follow-up results were collected.The functional outcome was evaluated at discharge and 90 days.Results Recanalization was successful in 11 out of 13 patients.Perioperative complications occurred in 8 cases,including distal embolization in 7 cases (3 with symptom and 4 without),in which intracerebral hemorrhage associated with embolectomy was found in 1 case;and distal embolization concomitant with artery dissection in 1 case.At discharge,the symptoms of 10 out of 11 patients with successful recanalization were improved and 1 was unchanged;one of 2 patients with recanalization failure was aggravated and 1 was unchanged.After the procedure,1 patient with successful recanalization,but complicated with intracerebral hemorrhage associated with embolectomy was lost at follow-up,thus angiographic follow-up was available in the remaining 10 patients.Of the 10 patients,1 patient developed in-stent restenosis at 12 months and 9 patients had no hemodynamic stenosis/reocclusion.The clinical follow-up was available in 12 patients.No recurrence of TIA or stroke was found in 9 cases with successful recanalization except for 1 case who developed in-stent stenosis and suffered from TIA.At the follow-up of 90 days,l0 patients with successful recanalization showed good function (mRS∶0-2),2 patients with recanalization failure were deteriorated.Conclusions In strictly selected patients with symptomatic non-acute occlusion of large intracranial artery in anterior circulation,endovascular recanalization was feasible and safe,which may improve patients' symptoms in a short term and reduce the recurrence rate of stroke,but its definite efficacy needs to be confirmed by studies with larger sample and longer follow-up.

Objective To investigate the difference of hepatic microvessel density, neovasculariza-tion of regenerating liver tissue after ablation of two ways of irreversible electroporation and radiofrequency ablation in rats. Methods 90 male Sprague-Dawley rats were randomly divided into 3 groups, including the control group ( n =30), the irreversible electroporation group ( n =30 ) and the radiofrequency ablation group (n=30). 3,7 and 10 days were executed after the operation and draw material, expression of vascu-lar endothelial growth factor(VEGF) and CD34 in tissue was studied by immunohistochemistry, and the mi-crovascular density of tissue and VEGF positive cells were measured. Results The microvascular density of 3, 7 and 10 days in the control group was 50. 3 ± 12. 5, 54. 6 ± 11. 9 and 58. 2 ± 14. 7, the microvascular density of the radiofrequency ablation group was 18. 4 ± 4. 7, 17. 3 ± 5. 1 and 18. 1 ± 5. 9, respectively. The microvascular density of the irreversible electroporation group was 42. 8 ± 10. 4, 45. 6 ± 10. 2 and 49. 2 ± 13. 8, respectively. The positive cells of VEGF in control group was 50, 56 and 57 at 3, 7 and 10 days, and 32, 30 and 33 at 3, 7 and 10 days in radiofrequency ablation group, 44, 43 and 45 at 3, 7 and 10 days in irreversible electroporation group; expression of VEGF and CD34 in 3, 7, 10 d and the microvascular density of ablation area in radiofrequency ablation group was significantly lower than those in control group after irreversible electroporation and radiofrequency ablation. No significant differences were found between irreversible electroporation group and control group. Conclusion The irreversible electroporation can effectively protect the microvessels in the ablation area, ensure the tissue’s blood supply after the ablation, and provide a guarantee for the repair and regeneration of the tissue.