Induction of apoptosis by artemisinin relieving the severity of inflammation in caerulein-induced acute pancreatitis

AIM:To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis(AP),and the influences of artemisinin on them.METHODS:AP was induced by 4 intraperitoneal injections of caerulein at 1 h intervals.To induce apoptosis,solution of artemisinin(50 mg/kg)was given intraperitoneally 1,12,24 and 36 h after the last caerulein injection.Histological examination of impairment of pancreatic tissue and detection of serum amylase were performed to evaluate the severity of acute pancreatitis.Apoptosis and oncosis were detected with acridine orange(AO)and ethylene dibromide(EB)staining.Caspase-3 and myeloperoxidase(MPO)activity were measured by colorimetric assay.Nuclear factor-kappa B(NF-κB)activation was detected by flow cytometry.Macrophage inflammatory protein-1α(MIP-1α)protein was measured by Western blot.Interleukin-1β(IL-1β)mRNA was detected by RT-PCR.RESULTS:Addition of artemisinin increased the number of apoptotic cells(11.7% ± 1.4% vs 6.3% ± 0.7%,P < 0.05),while reduced the number of oncotic cells(13.0% ± 2.4% vs 17.5% ± 2.2%,P < 0.05).The activity of caspase-3 speeded up(1.52 ± 0.21 vs 1.03 ± 0.08,P < 0.05),the pancreas pathological impairment was relieved(3.0 ± 0.5 vs 4.0 ± 0.5,P < 0.05)and the level of serum amylase decreased(5642 ± 721 U/dL vs 7821 ± 653 U/dL,P < 0.05).The activation of NF-κB(29% ± 4.1% vs 42% ± 5.8%),MIP-1α protein(3.7 ± 0.5 vs 5.8 ± 0.7),MPO(0.52 ± 0.06 U/g vs 0.68 ± 0.09 U/g),IL-1β mRNA(1.7 ± 0.3 vs 2.4 ± 0.4)in the apoptosis inducing group was obviously decreased(P < 0.05).CONCLUSION:Inducing apoptosis can relieve pathological impairment and inflammatory reaction in AP rats.

UPF1在肺腺癌中的表达及其临床意义的研究

目的:探索上游移码突变体(up-frameshift mutant 1,UPF1)在肺腺癌(adenocarcinoma,ADC)中的表达及其与各临床病理指标的关系,探讨其在临床预后判断中的作用及意义。方法:应用免疫组织化学方法测定2011年1月至2011年12月150例就诊于天津医科大学肿瘤医院ADC患者的UPF1表达情况。Kaplane-Meier分析UPF1的表达与无复发生存期(recurrence-free survival,RFS)以及总生存期(overall survival,OS)之间的关系。结果:UPF1表达水平随ADC恶性程度的增大而降低(P<0.01),也与TNM分期(P=0.014)、是否有淋巴结转移(P=0.016)及远处转移(P=0.035)相关。UPF1的表达水平显著影响ADC的患者RFS和OS,UPF1表达低患者的RFS和OS较短(P<0.05)。结论:UPF1在ADC中可能起到抑瘤的作用,可以作为ADC治疗及预后评估的参考指标,并且UPF1有可能成为新的ADC药物治疗靶点。

Modeling, Optimization, and Control of Solution Purification Process in Zinc Hydrometallurgy

The solution purification process is an essential step in zinc hydrometallurgy. The performance of solution purification directly affects the normal functioning and economical benefits of zinc hydrometallurgy. This paper summarizes the authors' recent work on the modeling, optimization, and control of solution purification process. The online measurable property of the oxidation reduction potential(ORP) and the multiple reactors, multiple running statuses characteristic of the solution purification process are extensively utilized in this research. The absence of reliable online equipment for detecting the impurity ion concentration is circumvented by introducing the oxidationreduction potential into the kinetic model. A steady-state multiple reactors gradient optimization, unsteady-state operationalpattern adjustment strategy, and a process evaluation strategy based on the oxidation-reduction potential are proposed. The effectiveness of the proposed research is demonstrated by its industrial experiment.

Risk factors of infected pancreatic necrosis secondary to severe acute pancreatitis

BACKGROUND： Severe acute pancreatitis（SAP） remains a clinical challenge with considerable morbidity and mortality.An early identification of infected pancreatic necrosis（IPN）, a life-threatening evolution secondary to SAP, is obliged for a more preferable prognosis. Thus, the present study was conducted to identify the risk factors of IPN secondary to SAP. METHODS： The clinical data of patients with SAP were retrospectively analyzed. Univariate and multivariate logistic regression analyses were sequentially performed to assess the associations between the variables and the development of IPN secondary to SAP. A receiver operating characteristic（ROC） curve was created for each of the qualified independent risk factors. RESULTS： Of the 115 eligible patients, 39（33.9%） progressed to IPN, and the overall in-hospital mortality was 11.3%（13/115）.The early enteral nutrition（EEN）（P=0.0092, OR=0.264）, maximum intra-abdominal pressure（IAP）（P=0.0398, OR=1.131）and maximum D-dimer level（P=0.0001, OR=1.006） in the first three consecutive days were independent risk factors associated with IPN secondary to SAP. The area under ROC curve（AUC） was 0.774 for the maximum D-dimer level in the first three consecutive days and the sensitivity was 90% and the specificity was 58% at a cut-off value of 933.5 μg/L; the AUC was 0.831 for the maximum IAP in the first three consecutive days and the sensitivity was 95% and specificity was 58%at a cut-off value of 13.5 mm Hg. CONCLUSIONS： The present study suggested that the maximum D-dimer level and/or maximum IAP in the first three consecutive days after admission were risk factors of IPN secondary to SAP; an EEN might be helpful to prevent the progression of IPN secondary to SAP.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer:Results from 24 hospitals in China

BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients with T1b GBC.METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China.The logrank test and Cox proportional hazards model were used to compare the overall survival(OS)of patients who underwent cholecystectomy(Ch)+RL and those who underwent Ch only.To investigate whether combined hepatectomy(Hep)improved OS in T1b patients,we studied patients who underwent Ch+RL to compare the OS of patients who underwent combined Hep and patients who did not.RESULTS Of the 121 patients(aged 61.9±10.1 years),77(63.6%)underwent Ch+RL,and 44(36.4%)underwent Ch only.Seven(9.1%)patients in the Ch+RL group had lymph node metastasis.The 5-year OS rate was significantly higher in the Ch+RL group than in the Ch group(76.3%vs 56.8%,P=0.036).Multivariate analysis showed that Ch+RL was significantly associated with improved OS(hazard ratio:0.51;95%confidence interval:0.26-0.99).Among the 77 patients who underwent Ch+RL,no survival improvement was found in patients who underwent combined Hep(5-year OS rate:79.5%for combined Hep and 76.1%for no Hep;P=0.50).CONCLUSION T1b GBC patients who underwent Ch+RL had a better prognosis than those who underwent Ch.Hep+Ch showed no improvement in prognosis in T1b GBC patients.Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines,RL was only performed in 63.6%of T1b GBC patients.Routine Ch+RL should be advised in T1b GBC.

Oncoprotein HBXIP promotes tumorigenesis through MAPK/ERK pathway activation in non-small cell lung cancer

Objective:The oncoprotein,hepatitis B X-interacting protein(HBXIP),has been reported to play an important role in human malignancies.However,its functions in non-small cell lung cancer(NSCLC)are poorly understood.The goal of the present study was to identify the role of HBXIP in the regulation of NSCLC development.Methods:The level of HBXIP expression in NSCLC tissue was assessed by immunohistochemical and Western blot analyses,and its relationships with clinicopathological features and outcomes were statistically evaluated.The effects of HBXIP on NSCLC cell progression were assessed through cell viability,colony formation,and flow cytometry analyses in vitro.The mechanism by which HBXIP regulated the MAPK pathway was studied by Western blot,immunofluorescence,and immunoprecipitation assays.In addition,in vivo experiments were performed to evaluate the progression of NSCLC and ERK signaling pathway activation after HBXIP knockdown.Results:HBXIP was overexpressed in human NSCLC and was correlated with the invasiveness of NSCLC.The high expression of HBXIP in NSCLC was significantly correlated with gender(P=0.033),N stage(P=0.002),and tumor-node-metastasis stage(P=0.008).In vitro experiments using an NSCLC cell line revealed that HBXIP knockdown resulted in the suppression of cell proliferation and colony formation,which was consistent with the enhanced cell cycle arrest in G1 phase.The results of a mechanistic investigation suggested that binding of HBXIP to MEK1 protein promoted MAPK/ERK signaling pathway activation in NSCLC by preventing the proteasome-mediated degradation of MEK1.In addition,the results obtained using in vivo subcutaneous tumor xenografts confirmed that HBXIP deficiency decreased MEK1 protein levels and NSCLC tumor growth.Conclusions:Taken together,our results showed that the HBXIP-MEK interaction promoted oncogenesis via the MAPK/ERK pathway,which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant feature.

Antidepressant effect of bioactive compounds from Paecilomyces tenuipes in mice and rats

A bioactive compound from Paecilomyces tenuipes（BCPT）has an inhibitory effect on monoamine oxidase A（MAO-A）in vitro.Researchers have thought that BCPT may be a potential antidepressant.The MAO-A suppressor moclobemide served as a control,and this study investigated the mechanisms of BCPT as an antidepressant.Results demonstrated that BCPT induced significantly increased sucrose intake in chronic unpredictable stressed rats,shortened immobility time in forced swimming mice,improved the scores of blepharoptosis and akinesia in reserpine-treated mice,increased the number of 5-hydroxy tryptophan-induced head-twitches,remarkably enhanced the expression of hippocampus mineralcorticoid receptor and glucocorticoid receptor mRNA,decreased the ratio of mineralcorticoid receptor to glucocorticoid receptor and raised the levels of dopamine,norepinephrine and 5-hydroxytryptamine,while decreasing hydroxyindole acetic acid levels or dihydroxy-phenyl acetic acid in chronic unpredictable stressed rats.Behavioral test results suggested that BCPT potentially had antidepressant-like activity.Meanwhile,BCPT increased the levels of neurotransmitters,and mineralcorticoid receptor and glucocorticoid receptor mRNA in the hippocampus,which may be an important mechanism of its antidepressant effect.

Smart manufacturing of nonferrous metallurgical processes:Review and perspectives

The nonferrous metallurgical(NFM)industry is a cornerstone industry for a nation’s economy.With the development of artificial technologies and high requirements on environment protection,product quality,and production efficiency,the importance of applying smart manufacturing technologies to comprehensively percept production states and intelligently optimize process operations is becoming widely recognized by the industry.As a brief summary of the smart and optimal manufacturing of the NFM industry,this paper first reviews the research progress on some key facets of the operational optimization of NFM processes,including production and management,blending optimization,modeling,process monitoring,optimization,and control.Then,it illustrates the perspectives of smart and optimal manufacturing of the NFM industry.Finally,it discusses the major research directions and challenges of smart and optimal manufacturing for the NFM industry.This paper will lay a foundation for the realization of smart and optimal manufacturing in nonferrous metallurgy in the future.

外伤后以囊内出血为首发症状的胃囊肿一例及文献回顾

背景胃囊肿(gastric duplication cysts,GDCs)是一种特殊的消化道囊肿,多发于婴幼儿时期,囊肿壁与胃壁相似,主要含有胃黏膜和平滑肌组织.病例概述本文报道1例GDCs囊内出血病例.本例患者外伤后突发腹部剧烈疼痛,结合其病史及相关检查术前曾误诊为肝囊肿囊内出血,术中探查发现囊肿基底部位于胃大弯侧.结论GDCs临床症状不典型,易误诊,其术前诊断主要依据影像学检查,以手术治疗为主.

Analysis of 300 consecutive cases of pancreatic adenocarcinoma in a single-center in China

BACKGROUND： Most of the reports on the prognostic indicators of patients with pancreatic adenocarcinoma are from developed countries. The present study focused on the prognostic indicators of Chinese patients with pancreatic adenocarcinoma. METHODS： A total of 300 patients with pancreatic adenocarcinoma who had undergone curative resection were included. The resection and R0/R1 resection rates for adenocarcinomas from different parts of the pancreas were calculated and clinical characteristics were analyzed.RESULTS： In 3427 patients diagnosed with pancreatic adenocarcinomas, only 300（8.8%） were eligible for radical resection. The total median survival of these patients was 19 months, and their 1-, 3-, and 5-year survival rates were 72.5%, 28.0% and 23.4%, respectively. The prognostic factors included socioeconomic status, smoking history, symptoms, high blood glucose, and various tumor characteristics, including perineural and vascular invasion, lymph node metastases, and CA19-9 levels before and after operation. Operation-associated prognostic indicators included operation time, blood loss and transfusions, pancreatic fistula, and complications. Independent predictors of mortality included poor socioeconomic status, smoking history, symptoms, CA19-9, perineural invasion and lymph node metastasis, grade of fistula and complications. Patient survival was not correlated with either resection margin or adjuvant chemotherapy in multivariate analysis.CONCLUSIONS： The survival rates of patients with curative resection for pancreatic adenocarcinoma in China are close to those in developed countries, but curative resection rate is far below. Socioeconomic status, symptoms, and CA19-9 are the three most prominent prognostic factors, which are helpful in patient selection and perioperative care.

Operative timing and indications for patients with severe acute pancreatitis: report of 172 cases

Objective: To investigate the operative timing and indi-cations for severe acute pancreatitis(SAP).Methods: Data collected from 172 patients with SAPtreated in our hospital since 1980 were analyzed retro-spectively.Results: In the 94 patients who had undergone early op-eration before June 1992, 57 (62.8%) healed, 35 (37.2%)died, and 16 (17.0%) had no postoperative compli-cations. In the 78 patients who had been treated after July1992 according to the principle of individualization, 66(84.6%) healed, 12 (15.4%) died, and 37 (47.4%)had no postoperative complications. In the 78 patients32 received non-operative treatment but 30 (93.8%)cured, 12 early operation but 7(58.3%)cured, 18 lateoperation but 13 (72.2%) cured, and 16 selected timeoperation but all cured.Conclusions: It is concluded that individualized thera-py is effective and reasonable for treating SAP. Theindications for early, late and selected time operationshould be emphasized.

One-step synthesis of inherently chiral p-tert-butylcalix[4]azacrown

A one-step procedure is developed to synthesize inherently chiral p-tert-butylcalix[4]azacrown 1 through etherification between p-tert-butylcalix[4]arene and compound 3, which can be amplifed to efficiently prepare more inherently cbiral calix[4]arenes in ABHH substitution pattern.

Analysis and prevention of factors predisposing to infections associated with severe acute pancreatitis

OBJECTIVE: To analyze factors predisposing to the infections associated with severe acute pancreatitis (SAP) and work out ways for their prevention. METHODS: 208 patients with SAP treated at our hospital from January 1986 to December 2001 were retrospectively analyzed. RESULTS: Statistical difference in the incidence of the infections was found between the following pairs: the groups of bloody or non-bloody ascites, paralytic ileus lasting shorter or longer than 5 days, Ranson's scores lower or higher than 5, hematocrit lower or higher than 45%, CT Balthazar scores lower or higher than 7, and between January 1986-June 1992 or July 1992-December 2001 admissions (x^2>7.58, P<0.05), while no statistical difference established between the groups of biliogenic and non-biliogenic pancreatitis, serum amylase<200 U/L and ≥200 U/L, serum calcium<2 mmol/L and≥2 mmol/L or groups of total parenteral nutrition shorter or longer than 7 days (x^2<1.61, P>0.05). CONCLUSIONS: Occurrence of infection in patients with SAP is closely related with bloody ascites, paralytic ileus (≥5 days), Ranson's scores (≥5), hematocrit (≥45%) and CT Balthazar scores (≥7), but not with pathogenesis, serum calium or total parenteral nutrition. Comprehensive prevention of pancreatic infection and individualized therapy may reduce the incidence of infection.

胆管内乳头状肿瘤的诊治策略

胆管内乳头状肿瘤(IPNB)是一种少见的胆系肿瘤,其特征为导管内肿瘤乳头状增生,伴有胆道系统扩张,及可能出现的导管内黏液分泌。IPNB的临床表现缺乏特异性,根据肿瘤不同的生长部位及发展程度可表现为腹痛及梗阻性黄疸,部分合并胆道感染患者可出现发热、寒战等急性胆管炎症状。血液化验可有肝功能异常、胆红素升高等改变。影像学检查包括腹部超声、平扫或增强CT、MRI、内镜超声等。现有影像学诊断方法尚无法在术前对IPNB进行高特异性的有效鉴别诊断。治疗方式目前推荐以手术切除作为首选。具体术式选择包括胰十二指肠切除术、胆总管切除胆肠吻合术、肝门胆管癌根治术联合肝脏部分切除术等。目前尚无明确证据证明手术切除后辅助放化疗的必要性。

Chinese expert consensus on multidisciplinary diagnosis and treatment of pancreatic neuroendocrine liver metastases

Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases.However,a lack of biological,molecular,and genomic information and an absence of data from rigorous trials limit the validity of these strategies.This review presents the viewpoints from an international conference consisting of several expert working groups.The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature,evaluating the evidence on which management decisions were based,developing internationally acceptable recommendations for clinical practice,and making recommendations for clinical and research endeavors.The review for each question will be followed by recommendations from the panel.

microRNA-218 Inhibits Oxygen-induced Retinal Neovascularization via Reducing the Expression of Roundabout I

Background： The mechanisms of pathological retinal neovascularization （RNV） remain unknown. Several microRNAs were reported to be involved in the process of RNV. Oxygen-induced retinopathy （O1R） is a useful model to investigate RNV. Our present work explored the expression and the role of microRNA-128 （miR-218） in oxygen-induced RNV. Methods： OIR was used to establish RNV model. The expression level ofmiR-218 in the retina from OIR mice was assessed by quantitative real-time reverse transcriptase polymerase chain reaction. Fluorescein angiography was performed in retinae of OIR mice, and RNV was quantified by hematoxylin and eosin staining to evaluate the effect of pCDH-CMV-miR-218 intravitreal injection on RNV in OIR mice. Roundabout 1 （Robol） expression was detected by Western blotting in mouse retinal vascular endothelial cells expressing a high or low level of miR-218 and retinal tissues from OIR mice. Cell migration was evaluated by scratch wound assay. Results： In OIR mice, the expression level of miR-218 was significantly down-regulated （P = 0.006）. Retinal Robol expression was significantly increased at both mRNA and protein levels （P = 0.001, 0.008： respectively）, miR-218 intravitreal injection inhibited retinal angiogenesis in OIR mice, and the restoration of miR-218 in retina led to down-regulation of Robol. Conelusions： Our experiments showed that restoration ofmiR-218 inhibited retinal angiogenesis via targeting Robo 1. MiR-218 contributed to the inhibition of retinal angiogenesis and miR-218 might be a new therapeutic target for preventing RNV.

Guidelines for the diagnosis and treatment of acute pancreatitis in China (2021)

Acute pancreatitis(AP)is a common acute abdominal condition of the digestive system.In recent years,treatment concepts,methods,and strategies for the diagnosis of AP have advanced,and this has played an important role in promoting the standardization of AP diagnosis and treatment and improving the treatment quality of AP patients.On the basis of previous guidelines and expert consensus,this guideline adopts an evidence-based,problem-based expression;synthesizes important clinical research data at home and abroad in the most recent 5 years;and forms 29 recommendations through multidisciplinary expert discussion,including diagnosis,treatment,and follow-up.It is expected to provide evidence support for the treatment of AP in the clinical setting in China.

Guidelines for the diagnosis and treatment of pancreatic cancer in China (2021)

The incidence of pancreatic cancer has been rising worldwide,and its clinical diagnosis and treatment remain a great challenge.To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years,Chinese Pancreatic Association,the Chinese Society of Surgery,Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China(2014)after reviewing evidence-based and problem-oriented literature published during 2015-2021,mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer,conversion strategies for locally advanced pancreatic cancer,treatment of pancreatic cancer with oligo metastasis,adjuvant and neoadjuvant therapy,standardized processing of surgical specimens and evaluation of surgical margin status,systemic treatment for unresectable pancreatic cancer,genetic testing,as well as postoperative follow up of patients with pancreatic cancer.Forty recommendation items were finally proposed based on the above issues,and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation,Assessment,Development,and Evaluation system.This guideline aims to standardize the clinical diagnosis and therapy,especially surgical treatment of pancreatic cancer in China,and further improve the prognosis of patients with pancreatic cancer.

The current surgical treatment of pancreatic cancer in China: a national wide cross-sectional study

Objective: The aim of this study is to investigate the current status of pancreatic cancer patients undoing surgical treatment in China and to find ways to improve the survival of these patients in the future. Methods: This study is a national, multicenter, cross-sectional study in China. Information regarding pancreatic cancer patients undergoing surgical treatment from 34 high-volume tertiary IIIA level hospitals was collected and analyzed from the March 1, 2016 to the February 28, 2017. Results: In total, 2200 pancreatic cancer patients were enrolled from 34 tertiary IIIA level hospitals in 16 provinces across China. The male-to-female ratio was 1.5. More than 80% of the patients were between 50 and 70 years old. The top 4 symptoms were epigastric discomfort, abdominal pain, jaundice, and weight loss. Carbohydrate antigen 19-9 and carcinoembryonic antigen were elevated in 70.9% and 27.1% of patients, respectively. A multidisciplinary team (MDT) discussion was carried out for 35.0% of patients before surgery. The proportion of minimally invasive pancreatic surgeries was approximately 20%. A total of 83.4% of the operations achieved R0 resection, and the incidence of grade 3/4 postoperative complications was 7.7%. Only 13.4% of the patients received postoperative adjuvant chemotherapy. The percentage of pathological stage I tumors was only 24.5%. Conclusion: The majority of pancreatic cancer patients undergoing surgical resection in China are in an advanced stage. The MDT consultations for pancreatic cancer have not been widely carried out. R0 resection has been achieved in most cases, with relatively low incidence of serious complications, but minimally invasive pancreatic surgery should be further promoted. The application of postoperative chemotherapy remains low. This national, multicentre, cross-sectional study comprehensively presents the current status of pancreatic cancer patients undergoing surgical treatment and shows the road to improve survival of these patients in the future.

A Chinese consensus statement on the diagnosis and treatment of pancreatic exocrine insufficiency after pancreatic surgery(2018)

A consensus statement on the diagnosis and treatment of pancreatic exocrine insufficiency(PEI)after pancreatic surgery was developed based on the latest references,combined with China’s actual situation.More than 20 Chinese excellent experts participated in this work and contributed many thorough discussions.This consensus discusses the definition,epidemiology,diagnosis,treatment,and follow-up of PEI after pancreatic surgery.The authors hope this consensus will promote the standard procedure of diagnosis and treatment of PEI in China.