Precision medicine in the treatment of pancreatic ductal adenocarcinoma

Pancreatic cancer has a poor prognosis. Current therapies for pancreatic cancer have limited effects. In the past decade, precision medicine has shown great potential for clinical applications. In this review, different strategies for applying precision medicine to the treatment of pancreatic cancer are described.

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

International consensus statement on robotic hepatectomy surgery in 2018

The robotic surgical system has been applied in liver surgery. However,controversies concerns exist regarding a variety of factors including the safety,feasibility, efficacy, and cost-effectiveness of robotic surgery. To promote the development of robotic hepatectomy, this study aimed to evaluate the current status of robotic hepatectomy and provide sixty experts' consensus and recommendations to promote its development. Based on the World Health Organization Handbook for Guideline Development, a Consensus Steering Group and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 22 topics were prepared analyzed and widely discussed during the 4 meetings. Based on the published articles and expert panel opinion, 7 recommendations were generated by the GRADE method using an evidence-based method, which focused on the safety, feasibility, indication,techniques and cost-effectiveness of hepatectomy. Given that the current evidences were low to very low as evaluated by the GRADE method, further randomized-controlled trials are needed in the future to validate these recommendations.

Management of borderline and locally advanced pancreatic cancer:Where do we stand?

Many patients with pancreas cancer present with locally advanced pancreatic cancer(LAPC).The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound,axial imaging with computed tomography and magnetic resonance imaging,and diagnostic laparoscopy.The definition of resectability has historically been vague,as there is considerable debate and controversy as to the definition of LAPC.For the patient with LAPC,there is some level of involvement of the surrounding vascular structures,which include the superior mesenteric artery,celiac axis,hepatic artery,superior mesenteric vein,or portal vein.When feasible,most surgeons would recommend possible surgical resection for patients with borderline LAPC,with the goal of an R0 resection.For initially unresectable LAPC,neoadjuvant should be strongly considered.Specifically,these patients should be offered neoadjuvant therapy,and the tumor should be assessed for possible response and eventual resection.The efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad,ranging from 3%-79%.The different modalities of neoadjuvant therapy include sin-gle or multi-agent chemotherapy combined with radiation,chemotherapy alone,and chemotherapy followed by chemotherapy with radiation.This review focuses on patients with LAPC and addresses recent advances and controversies in the field.

Syndrome differentiation in traditional Chinese medicine and E-cadherin/ICAM-1 gene protein expression in gastric carcinoma

AIM： To explore the syndrome differentiation in traditional Chinese medicine （TCM） and gene protein expression in gastric carcinoma METHODS： Preoperative data of gastric cancer cases were collected from the General Surgery Department and classified according to the criteria for syndrome differentiation in TCM. E-cadherin （E-cad） and ICAM-1 gene protein expressions were detected in postoperative specimens from these cases by the immunohistochemical EnVision two-step method. RESULTS： The E-cad positive expression rate was 90% in 100 cases of gastric carcinoma. The difference in E-cad expression was significant between the different syndrome differentiation types in TCM （P 〈 0.01）. Further group-group comparison showed that there was a significant difference in E-cad expression between the stagnation of phlegm-damp type and the deficiency in both qi and blood and the deficiency-cold of stomach and spleen types, where E-cad expression was high. There was no significant difference between the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type, where E-cad expression was relatively low. The ICAM-1 positive expression rate was 58%, and there was no statistically significant difference between the two groups （x^2= 8.999, P 〉 0.05）. CONCLUSION： E-cad expression is relatively low in the internal obstruction of stagnant toxin type and the incoordination between liver and stomach type, where tumor development and metastasis may be associated with low E-cad expression, or with low homogeneous adhesiveness between tumor cells.

次髎穴埋线治疗对混合痔病人术后疼痛和营养状况的影响

目的:探讨次髎穴埋线用于混合痔术后镇痛治疗的效果以及对病人营养状况的影响。方法:2019年9月至2021年7月本院收治的混合痔手术病人90例,随机分为3组:埋线组、针刺组和药物组,每组30例。术后不同时间对病人进行疼痛评分,检测病人血清总蛋白、白蛋白和球蛋白水平,记录住院时间、住院费用和镇痛治疗费用。结果:术后12 h、24 h、3 d、5 d及7 d,次髎穴埋线组病人疼痛评分均明显低于针刺组和药物组(P<0.05)。术后7 d,埋线组病人血清总蛋白水平明显高于针刺组(P<0.05)。埋线组病人住院时间和住院费用均低于针刺组和药物组(P<0.01)。结论:次髎穴埋线具有良好的镇痛作用,有助于改善病人营养状况,缩短住院日,降低医疗费用,加快病人术后康复,具有较好的临床应用前景。

茯苓酸对小鼠黑色素瘤细胞增殖、迁移和侵袭的影响及机制研究

目的:研究茯苓酸(pachymic acid,PA)对小鼠黑色素瘤B16细胞增殖、迁移和侵袭的影响及其可能机制。方法:采用CCK8法和细胞克隆形成实验检测不同浓度(20、40、80μmol/L)PA对B16细胞增殖的影响;细胞划痕和Transwell小室实验观察PA对B16细胞迁移和侵袭能力的影响;Western Blot法和免疫荧光法检测PA对B16细胞的上皮-间质转化相关蛋白表达的变化。结果:PA可以明显抑制B16细胞增殖,并呈一定的浓度依赖性关系(P<0.01);PA干预24 h后可以显著抑制B16细胞的迁移和侵袭能力(P<0.01);40μmol/L的PA能上调B16细胞的E-cadherin蛋白表达(P<0.05)并下调Vimentin蛋白的表达(P<0.05);免疫荧光法检测显示40μmol/L的PA可明显降低B16细胞Vimentin蛋白的表达。结论:PA可以抑制B16细胞的增殖、迁移和侵袭,其机制可能与上调B16细胞的E-cadherin蛋白表达,降低Vimentin蛋白表达,从而抑制B16细胞的上皮-间质转化有关。

Clinical Analysis on the Effectiveness of Conservative Compression Suture Technique to Conserve Fertility on Pernicious Placenta Previa

Objective: To evaluate the effectiveness of conservative compression surgical suture techniques used for the management of pernicious placenta previa to conserve fertility in the subsequent pregnancies. Study Design: This was a non-comparative retrospective study of 188 patients diagnosed with pernicious placenta previa who underwent cesarean section in The First Hospital of Jilin University, China, from 1 January 2013 to 1 January 2018. Successful group was defined as those in which the intraoperative bleeding was managed by either modified CHO or by B-lynch suture technique and those who had further intervention including hysterectomy were designated as failure group. Results: Out of 217 patients, 188 met inclusion criteria and 29 patients were excluded. In 188 cases, 183 (97.34%) cases successes and 5 (2.65%) cases had hysterectomy. Among included group, 118 patients (62.76%) had undergone emergency cesarean section and 70 patients (37.23%) underwent elective cesarean section. The emergency group had significantly lesser gestation period of gestation at the time of cesarean section (P = 0.021) and lower neonatal weight (P = 0.001) than that of elective group. The estimated blood loss during surgery was 500 - 3200 ml (mean: 925 ml). Additionally, the amount of bleeding was found to be significantly more in patient with intraoperative complication (P = 0.007) and in patient with implanted placenta (P 0.001). Conclusion: The conservative compression suture technique including modified CHO and B-lynch suture technique during the cesarean delivery is a feasible, safe and effective alternative conservative surgical technique for the management of bleeding in case of pernicious placenta previa. Besides good surgical outcome and proper neonatal result this technique also reduces the rate of hysterectomy, thus conserving the fertility.

A pan-cancer analysis of the biological function and clinical value of BTLA in tumors

B and T-lymphocyte attenuator(BTLA)plays an immunosuppressive role by inhibiting T-and B-cell functions.BTLA is associated with a variety of diseases,especially cancer immunity.However,the function of BTLA in various cancers and its clinical prognostic value have still not been comprehensively analyzed.This study aimed to identify the relationship between BTLA and cancer from the perspectives of differences in BTLA expression,its clinical value,immune infiltration,and the correlation with immune-related genes in various cancers.Data regarding mRNA expression,miRNA expression,lncRNA expression,and clinical data of patients of 33 existing cancers were collected from the TCGA database.Target miRNA of BTLA and the lncRNA that interacts with the target miRNA were obtained from the StarBase database.Based on bioinformatics analysis methods,the relationship between various types of cancers and BTLA was thoroughly investigated,and a competing endogenous RNA network of BTLA,target miRNA,and interacting lncRNA was constructed.The Kaplan-Meier(KM)prognostic analysis of BTLA and target miRNA(has-miR-137)in various types of cancers was completed using the KM plotter.BTLA expression varied in different cancers,with statistical significance in nine cancer types.KM plotter to analyze the overall survival(OS)and regression-free survival prognosis of cancer patients revealed that the BTLA expression was statistically different in the OS of 11 types of cancers out of 21 types of cancers;the OS of 8 type of cancers was also statistically different.Correlation analysis of tumor immune genes revealed a positive correlation of BTLA expression with immunosuppressive gene(CTLA4 and PDCD1)expression.Gene Set Enrichment Analysis showed that BTLA and its co-expressed genes mainly act through biological processes and pathways,including immune response regulation,cell surface receptor signaling pathway,antigen binding,antigen receptor-mediated signaling pathway,and leukocyte migration.BTLA has the potential as a prognostic marker for CLL,COAD,NSCLC,and OV and a diagnostic marker for CLL,COAD,and KIRC.BTLA has a close and complex relationship with the occurrence and development of tumors,and cancer immunotherapy for BTLA is worthy of further analysis.

Blood neutrophil extracellular traps:a novel target for the assessment of mammary health in transition dairy cows

Background:Mammary health is important for transition dairy cows and has been well recognized to exert decisive effects on animal welfare.However,the factors influencing mammary health are still unclear.Differential somatic cell count(DSCC)could reflect the mastitis risk since it is the percentage of neutrophils plus lymphocytes in total somatic cells and could be reflective of mammary health of dairy cows.This work aimed to investigate the assessment and prognosis of the health of transition cows based on blood neutrophil extracellular traps(NETs).Results:Eighty-four transition Holstein dairy cows were selected.The serum was sampled in all the animals at week 1 pre-and postpartum,and milk was sampled at week 1 postpartum.Based on the DSCC in milk at week 1,cows with lower(7.4%±4.07%,n=15)and higher(83.3%±1.21%,n=15)DSCCs were selected.High DSCC cows had higher levels of red blood cell counts(P<0.05),hemoglobin(P=0.07),and hematocrit(P=0.05),higher concentrations of serum oxidative variables[reactive oxygen species(P<0.05),malondialdehyde(P<0.05),protein carbonyl(P<0.05),and 8-hydroxy-2-deoxyguanosine(P=0.07)],higher levels of serum and milk NETs(P<0.05)and blood-milk barrier indicators,including serumβ-casein(P=0.05)and milk immunoglobulin G2(P=0.09),than those of low DSCC cows.In addition,lower concentrations of serum nutrient metabolites(cholesterol and albumin)(P<0.05)and a lower level of serum deoxyribonuclease I(P=0.09)were observed in high DSCC cows than in low DSCC cows.Among the assessments performed using levels of the three prepartum serum parameters(NETs,deoxyribonuclease I andβ-casein),the area under the curve(0.973)of NETs was the highest.In addition,the sensitivity(1.00)and specificity(0.93)were observed for the discrimination of these cows using NETs levels with a critical value of 32.2 ng/mL(P<0.05).Conclusions:The formation of NETs in blood in transition dairy cows may damage the integrity of the blood-milk barrier and thereby increase the risk for mastitis in postpartum cows.

Research on Load Characteristic of Electrothermal Film Heating Community

In this paper, a case study of an electrothermal film heating community in Tianjin is carried out, in which the winter load characteristic and electricity use law are analyzed. In this community, every household installs two watt-hour meters, one of which is only used to measure the electrothermal heating power, so the interference factors are eliminated. The main factors influencing the residents’ power consumption are summarized, and a method for estimating the thermal load of the residents is given. The conclusions can provide important reference to generalize the electric heating technology.

Clinical Analysis on the Effectiveness of Transvaginal Cervical Cerclage in Singleton Pregnancies and Its Predictive Factors

Objective: To evaluate the effectiveness of transvaginal cervical cerclage in singleton pregnancies with cervical incompetence, determine the predictive factors of success and failure, and then compare elective and emergency cerclage. Study Design: This was a retrospective study of 62 patients who underwent cervical cerclage in The First Hospital of Jilin University, China, between May 2015 and January 2018. Successful group was defined as those who delivered live babies and failure group who experienced abortion or stillbirth. Results: Out of 104 patients, 62 met inclusion criteria. In 62 cases, 47 (75.8%) succeeded and 15 (24.2%) failed. In successful group, 21 (44.7%) women delivered pretermly and 26 (55.3%) termly. No severe complications occurred except cervical laceration (2, 3.23%), premature rupture of membranes (13, 20.97%). In 62 cases, 40 (64.5%) have ≤2 previous second-trimester losses and 22 (35.5%) have >2 previous second-trimester losses. No significant differences were found in neonatal outcomes. Analysis revealed that higher postoperative C-reactive protein and presence of premature rupture of membranes were the strongest predictors of cerclage failure. Among 62 cases, 48 (77.4%) were allocated in elective and 14 (22.6%) in emergency cerclage. Pregnancy prolongation was significantly more (P = 0.014) in elective group with no significant differences in premature rupture of membranes, neonatal outcomes (all P > 0.05) except Apgar score at 5 min (P = 0.042). Conclusion: Achieving 75.8% live births proves that transvaginal cervical cerclage is an effective and safe technique in prolonging the gestational age, improving the obstetric outcomes in singleton pregnancies with cervical incompetence under various cerclage indications. Postoperative C-reactive protein and premature rupture of membranes are the predictive factors related to success or failure. Elective cerclage is more effective in prolonging the pregnancy compared to emergency cerclage, no significant differences are seen regarding neonatal outcomes and complications.

Effects of astragalus injection on the skin lesion degree and Caspase-14,SOCS1 and STAT3 levels of psoriasis model in Balb/c nude mice

Objective: To investigate the effect of Astragalus Injection on the Skin Lesion Degree and Caspase-14, SOCS1 and STAT3 Levels of Psoriasis Model in Balb/c Nude Mice. Methods:Sixty Balb/c nude mice were randomly divided into groups A, B and C with 20 mice in each group. Group A mice were used as blank control, group B mice as model group and group C mice as treatment group. The PASI score of psoriasis, skin thickness, inflammatory factors, serum levels of Caspase-14, SOCS1 and STAT3 in three groups of mice were analyzed after 2 weeks of treatment. Result: After treatment, the P ASI score of group B was significantly higher than that of group C, with statistical significance (P < 0.05);there was statistical significance in the measurements of lesion skin of three groups of mice after treatment (P <0.05). Compared with the blank control group, the thickness of lesion skin in group B and C was significantly higher, and the thickness of lesion skin in treatment group was significantly lower than that in control group (P < 0.05). Compared with the blank control group, the inflammatory factors IL-17, IL-22 and IL-23 in the B and C groups were significantly increased, and the inflammatory factors IL-17, IL-22 and IL-23 in the treatment group were significantly lower than those in the model group. The levels of serum C aspase-14, SOCS1 and STAT3 in three groups of mice were significantly different after treatment (P < 0.05). Compared with the blank control group, the levels of serum C aspase-14 and SOCS1 in B and C groups were significantly lower and the levels of STAT3 were significantly higher, and the levels of inflammatory factors aspase-14 and SO in treatment group were significantly higher than those in control group. The level of CS1 was significantly lower than that of model group, and the level of STAT3 was significantly higher than that of model group (P <0.05). Conclusion: Astragalus membranaceus injection can effectively improve the degree of psoriasis in Balb/c nude mice. Its possible mechanism is that it can decrease the expression of Caspase-14 and SOCS1, reduce the degree of keratosis in the lesion site of mice, improve the local surface hyperplasia, increase the level of STAT3 and enhance the level of local cell proliferation, which is of positive significance for the rehabilitation of psoriasis.

公司治理水平与数字化转型:来自上市公司的证据

基于股东、董事和高管视角,构建了包含股东网络、股权集中度、董事会多样性和传统技术导向型高层管理团队在内的公司治理水平指标,以中国3040家沪深A股上市公司为样本,探讨公司治理水平对数字化转型的作用机制。研究发现:公司治理水平是企业进行数字化转型的关键驱动因素;另外,公司治理水平不同维度指标的影响机制表明,股东网络降低了企业的融资约束,股权集中度增加了企业的风险承担,董事会多样性增加了企业的创新能力,从而推动了企业的数字化转型;而传统技术导向型高层管理团队降低了企业的战略执行,阻碍了企业的数字化转型。

Epididymal tissue in the dilated portion of a dysgenetic kidney with an ipsilateral seminal vesicle cyst and ectopic ureteral insertion

Dear Editor： I am Dr Xiao-Mei Ma, from the Department of Pathology in Changzheng Hospital at the Second Military Medical University, Shanghai, China. We present here a case report of a seminal vesicle cyst （SVC） in a young man with epididymal tissue in a dysgenetic kidney and ectopic ureteral insertion. SVCs are usually found in the second to fourth decades of life. SVCs can be congenital or acquired. Congenital SVCs seem to be invariably associated with renal dysplasia, hypoplasia, agenesis and duplication abnormalities in the same side, with the exception of two cases .

控制性详细规划空间生产逻辑转变与编制管理响应

从空间生产理论出发,对控制性详细规划的空间生产调控特征进行深入认识,探讨控制性详细规划当前的空间生产困境以及新时期调控空间生产逻辑的转变。聚焦“前端评估—中端编制—后端实施”的全生命周期,从评估查底线、分层强弹性、功能重混合、设计更精细、实施保公益等方面探索新时期控制性详细规划编制管理的创新发展思路和趋势,希冀为各城市控制性详细规划编制管理提供借鉴。

白藜芦醇调控磷脂酰肌醇3-激酶/蛋白激酶B通路对结肠癌细胞增殖凋亡的影响

目的探究白藜芦醇调控磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)通路对结肠癌细胞增殖、凋亡的影响。方法体外培养人结肠癌SW480细胞,噻唑蓝(MTT)法检测人结肠癌SW480细胞增殖,将细胞分成对照组、低剂量白藜芦醇组(20μmol/L)、中剂量白藜芦醇组(40μmol/L)及高剂量白藜芦醇组(80μmol/L)。细胞划痕实验法测定人结肠癌SW480细胞迁移能力,Transwell小室检测人结肠癌SW480细胞侵袭能力,流式细胞仪检测人结肠癌SW480细胞凋亡,吖啶橙染色法检测人结肠癌SW480细胞自噬,实时定量聚合酶链反应(RT-PCR)法检测各组细胞B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关蛋白(Bax)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)mRNA水平,蛋白质免疫印迹法检测各组细胞PI3K-Akt信号通路。结果与对照组比较,20、40和80μmol/L白藜芦醇导致细胞存活率降低(P<0.05),且不同浓度白藜芦醇培养48 h最为适宜。与对照组对比,白藜芦醇不同剂量组中,细胞迁移能力减弱(P<0.05),且细胞的迁移率随着白藜芦醇浓度的提高逐渐减少。在对照组的基础上经白藜芦醇处理的实验组细胞凋亡率增加(P<0.05)。细胞凋亡率随白藜芦醇浓度增加而逐步提高(P<0.05)。在实验组中,与对照组比较,细胞在接受白藜芦醇处理后细胞自噬数量增加,且随着白藜芦醇浓度的提高,细胞自噬数量逐步增加(P<0.05)。相较于对照组,各剂量的白藜芦醇组Bcl-2下降、Bax与Caspase-3增加。相较于对照组,不同剂量白藜芦醇组显示出PI3K和p-Akt蛋白下降;不同剂量白藜芦醇组Akt蛋白差异无统计学意义(P>0.05)。结论白藜芦醇可通过介导PI3K/Akt信号通路促进结肠癌细胞凋亡,降低其增殖能力,减弱细胞迁移和侵袭能力,以控制结肠癌的侵袭和恶化。

倾斜摄影测量数据轻量化处理工具设计与实现

针对现有倾斜摄影测量数据轻量化软件处理功能单一、处理效果不佳等问题,设计并实现了一种轻量化处理工具,为用户提供模型简化、顶层合并、重置LOD参数和数据压缩等功能。利用无人机航拍数据进行实验,分别从轻量化处理前后的数据量、模型点平面高程精度和模型精细度进行分析。结果表明该工具处理后的倾斜摄影测量数据具有数据量小、加载速度快、渲染效率高、保真度较高等特点,说明该工具具有较好的处理能力,能够满足用户数据轻量化处理需求。

4-香豆酸辅酶A连接酶响应大豆孢囊线虫胁迫的潜在功能

大豆孢囊线虫是大豆产区病虫害防治策略的重要目标之一,大豆孢囊线虫的防控也一直是线虫领域研究热点之一。大豆孢囊线虫侵染不仅会造成大豆地下部分损伤,也使得地上部分受损从而影响其产量,因此需对大豆孢囊线虫的抗性机制进行分析以达到防控的目的。大豆孢囊线虫成功寄生宿主植物需对其细胞壁进行降解融合,形成为其生长发育提供唯一营养来源的合胞体。而阻碍大豆孢囊线虫移动和合胞体建立的细胞壁抗性是大豆抵御大豆孢囊线虫的关键,其中木质素是细胞壁发挥抗性的重要成分。木质素的生物合成主要包括莽草酸代谢途径、苯丙烷代谢途径和木质素合成的特异途径,4-香豆酸辅酶A连接酶(4-coumarate-Coenzyme A ligase,4CL)作为连接苯丙烷代谢途径和木质素特异合成途径的重要转折酶,决定了木质素的合成,其很可能是响应大豆孢囊线虫胁迫的重要调控因子。本文从线虫入侵需要细胞壁降解融合建立合胞体出发,围绕木质素导致的细胞壁抗性展开讨论,分析了4CL在细胞壁抗性中的响应机制,为进一步探索大豆孢囊线虫胁迫机制提供科学依据。

基于风电消纳评估的电力系统鲁棒低碳经济调度

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