This paper presents the general principles and usual problems involved in the development of Institutional Review Board in research institutions. And suggestions are made in this regard. Meanwhile, it discusses two common difficult issues involved in ethical review.

Objective To investigate the clinicopathological features,treatment and prognosis of leiomyomatosis peritonealis disseminata (LPD).Methods A total of 10 patients suffered from LPD after laparoscopic uterine myomectomy were collected in the First Affiliated Hospital of Zhengzhou University from September 2012 to September 2016,and all clinical database were retrospectively analyzed.Results (1)Clinical features:the age of 10 cases was 25-50 years old,and 8 cases of them were in child-bearing age,while 2 cases were in perimenopausal period.Of 10 cases,2 cases manifested as discontinuous lower abdominal pain,and the other cases were seen the doctor for the examinations found tumors of pelvis or abdomen.All 10 cases had a history of laparoscopic uterine myomectomy under went power morcellation with an average of (4.0±2.2) years (range 1.3 to 8.1 years),2 cases of them had a history of oral hormone treatment after the first myoma morcellation.(2) Treatment methods and postoperative pathologic diagnosis:during intraoperative exploration,LPD nodules were most distributed in Douglas pouch (10 cases),and next in mesentery (7 cases),abdominal peritoneum (6 cases) and omentum majus (4 cases),etc.Seven of the 8 cases of child-bearing age were performed laparoscopic LPD nodules removal,1 case gone combined with laparotomy and resecting LPD nodules;2 cases in perimenopausal period done laparotomy oophorotomy and resected all LPD nodules and omentum.(3) Postoperative relapse and reproductive outcomes:the follow-up time of all cases was 2.8 years,and no recurrence was found during the follow-up period;2 cases had natural conception and term vaginal birth during the follow-up period.Conclusions LPD is mainly related to iatrogenic planting and spreading,which is a benign disease and characterized by multiple smooth muscle nodules throughout abdominopelvic cavity,and the nodules of LPD is commonly located in Douglas pouch,mesenteric and omentaum majus,etc.The preferred method of LPD should be individual operative treatment according to different situations,and in which patients may be have better prognosis.

Objective: To investigate the factors influencing the development of gastric cancer in Chinese populations, so as provide insights into creating a model for predicting gastric cancer incidence among Chinese populations. Methods: The case-control and cohort studies pertaining to factors affecting the development of gastric cancer were retrieved in electronic Chinese and English databases, including CNKI, Wanfang Data, VIP, PubMed, Web of Science and Embase from their inception until September 30, 2021. A meta-analysis was performed using R package version 4.1.0. Sensitivity analysis was performed using the “leave-one-out” evaluation procedure, and the publication bias was evaluated using the Egger regression test and the trim-and-fill procedure. Results: A total of 5 301 publications were screened and 116 eligible studies were included in the final analysis, including 103 case-control studies and 13 cohort studies, which covered approximately 3.23 million study subjects. A total of 45 factors affecting the development of gastric cancer were collected, and there were less than 4 publications reporting 7 factors, which were only qualitatively described. There were 38 factors included in the final meta-analysis. A total of 21 factors were identified as risk factors of gastric cancer, including a history of gastrointestinal diseases (pooled OR=4.85, 95%CI: 3.74-6.29), H. pylori infection (pooled OR=3.18, 95%CI: 2.35-4.32), binge eating and drinking (pooled OR=2.88, 95%CI: 2.09-3.97) and a family history of tumors (pooled OR=2.78, 95%CI: 2.17-3.56), and 10 factors as protective factors, including vegetable intake (pooled OR=0.48, 95%CI: 0.38-0.61), tea consumption (pooled OR=0.55, 95%CI: 0.47-0.64), administration of aspirin (pooled OR=0.53, 95%CI: 0.31-0.92) and administration of statins (pooled OR=0.59, 95%CI: 0.44-0.80). Sensitivity analyses of eating moldy food frequently, white meat intake, favoring spicy food and administration of sulfonylureas were not robust. Following correction with the trim-and-fill procedure, there was still a publication bias pertaining to high income, diabetes, administration of stains, alcohol consumption, tea consumption and white meat intake. Conclusions The development of gastric cancer is associated with a medical history of gastrointestinal disease, H. pylori infection, family history of tumors and poor dietary habits. Risk and protective factors of gastric cancer are recommended to be included in models used to predict gastric cancer incidence among Chinese populations.

Objective To explore the best multiplicities of infection (MOI),the expression of the target gene and in vitro MR imaging of adenovirus vector-mediated transferrin receptor (TFRC) reporter gene transfection of human colorectal cancer Lovo cells.Methods Lovo cells were transfected with recombinant adenovirus (Ad-TFRC) at 5,10,50,100 MOI to determine the best MOI,and quantitative real-time PCR was performed to detect the eDNA of TFRC.The transfected cells were incubated in the culture medium including Tf-USPIO of various concentrations,and were observed by Prussian blue staining,then the cell viability was evaluated via Trypan blue staining.The labeled cells were scanned with 7.0T MR T2W,T2 map,T2* map sequences,and the signal intensities were analyzed.Results Ad-TFRC were successfully transfected into Lovo cells.The best MOI was 50,and the efficiency of infection was more than 90％.The relative expression amount of TFRC in transfected cells was higher than that in control Lovo cells by real-time quantitive PCR (P＜ 0.01).Prussian blue staining showed numerous blue iron particles in transfected cells when the best labeling concentration was 1.5 μg/ml.Trypan blue staining results of transfected Lovo cells and control Lovo cells was (93.80± 1.60)％ and (95.10±2.30) ％,respectively (P＞0.05).MR imaging in vitro showed that compared with control Lovo cells,the signal intensity decreased on T2WI,T2 map and T2* map sequences in transfected Lovo cells (P＜0.05).Conclusion TFRC reporter gene can be efficiently mediated by adenovirus for expression in Lovo cells.After magnetization labeling,7.0T MR imaging of Lovo cells can be successfully achieved in vitro.

Objective:To evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia.Methods:From January 2018 to March 2023, 689 patients who underwent total hysterectomy for adenomyosis in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. According to the preoperative medication, they were divided into study group (127 cases) and control group (562 cases). Patients in the study group underwent GnRH-a pretreatment for 3 cycles before surgery, and the control group received operation directly. SPSS 26.0 software was used to perform 1∶1 matching for the two groups of patients through the propensity score matching method. Matching variables included age, body mass index, gravidity, parity, history of pelvic and abdominal surgery, menstrual cycle, menstrual period, dysmenorrhea score, initial diagnosis of cancer antigen 125 (CA 125), uterine volume and hemoglobin value. The dysmenorrhea score, uterine volume, hemoglobin value and CA 125 level before and after GnRH-a pretreatment in the study group were compared. And the duration of operation, intraoperative blood loss, postoperative white blood cell count, perioperative blood transfusion cases, postoperative disease rate, duration of hospitalization, total hospitalization cost between the two groups were compared. Results:With propensity score matching, 119 patients in the study group and 119 patients in the control group were finally enrolled in this study. In the study group, before and after the treatment with GnRH-a, the dysmenorrhea score (7.4±1.7 vs 5.6±1.8), uterine volume [(362±160) vs (233±126) cm 3], hemoglobin value [(74.1±10.7) vs (102.5±13.5) g/L], and CA 125 level [(104±76) vs (64±51) kU/L] were statistically different (all P<0.05). There were statistical differences of operation time [(86±18) vs (116±31) minutes], intraoperative blood loss [(24±9) vs (43±22) ml], white blood cell count after 1 day of operation [(9.80±0.10)×10 9/L vs (9.90±0.10)×10 9/L], number of perioperative blood transfusion case [5.9% (7/119) vs 61.3% (73/119)], postoperative disease rate [5.0% (6/119) vs 16.0% (19/119)], hospitalization duration [(7.1±1.6) vs (7.9±1.6) days], and total hospitalization cost [(35 323±5 275) vs (37 159±5 640) yuan] between the study group and the control group (all P<0.05). Conclusion:The pretreatment of using GnRH-a before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia is not only conducive to improving dysmenorrhea, signs of anemia, reducing uterine volume, but also conducive to the implementation of surgery, reducing intraoperative and postoperative complications, and reducing hospital costs.

Objective:To summarize the best evidence related to intermittent catheterization in adult patients with neurogenic bladder, and provide reference for clinical practice and patient self-management.Methods:According to the "6S" pyramid model, the system searched UpToDate, Guidelines International Network, European Association of Urology, UK National Institute for Health and Clinical Excellence, Scottish Interhospital Guidelines Network, Cochrane Library, PubMed, Web of Science, EmBase, EBSCO, OVID, Scopus, SinoMed, CNKI, Wanfang, VIP, Yimaitong, literature on intermittent catheterization of neurogenic bladder in adults, including clinical decision, best practice, guidelines, expert consensus, etc. The retrieval period was from the database establishment to August 2023. The search time was established until August 2023. The literature was screened by two research members, and four research members evaluated the quality of the literature and extracted the evidence.Results:A total of 14 articles were included, including 1 clinical decision, 1 evidence summary, 4 systematic reviews, 5 guidelines, 2 expert consensus, and 1 best practice. Finally, 31 pieces of best evidence were summarized, involving 5 aspects such as intermittent catheterization (IC) indication, IC timing, IC implementation process, IC health education, extended care.Conclusions:The evidence summary strictly follows the evidence-based process and the content of the evidence is comprehensive. The incidence of neurogenic bladder complications can be reduced by comprehensive management of intermittent catheterization, ultimately improving the quality of care. The localization characteristics should be combined in the application of evidence to improve the quality of life of patients.

PURPOSE: Cancer-associated fibroblasts (CAFs) activated by cancer cells has a central role in development and malignant biological behavior in colorectal cancer (CRC). Adult fibroblasts do not express Snail, but Snail-positive fibroblasts are discovered in the stroma of malignant CRC and reported to be the key role to chemoresistance. However, the reciprocal effect of CAFs expressed Snail to chemoresistance on CRC cells and the underlying molecular mechanisms are not fully characterized. MATERIALS AND METHODS: Snail-overexpressed 3T3 stable cell lines were generated by lipidosome and CT26 mixed with 3T3-Snail subcutaneous transplanted CRC models were established by subcutaneous injection. Cell Counting Kit-8, flow cytometry and western blotting assays were performed, and immunohistochemistry staining was studied. The cytokines participated in chemoresistance was validated with reverse transcriptase-polymerase chain reaction and heatmap. RESULTS: Snail-expression fibroblasts are discovered in human and mouse spontaneous CRCs. Overexpression of Snail induces 3T3 fibroblasts transdifferentiation to CAFs. CT26 co-cultured with 3T3-Snail resisted the impairment from 5-fluorouracil and paclitaxel in vitro. The subcutaneous transplanted tumor models included 3T3-Snail cells develop without restrictions even after treating with 5-fluorouracil or paclitaxel. Moreover, these chemoresistant processes may be mediated by CCL1 secreted by Snail-expression fibroblasts via transforming growth factor β/nuclear factor-κB signaling pathways. CONCLUSION: Taken together, Snail-expressing 3T3 fibroblasts display CAFs properties that support 5-fluorouracil and paclitaxel chemoresistance in CRC via participation of CCL1 and suggest that inhibition of the Snail-expression fibroblasts in tumor may be a useful strategy to limit chemoresistance.
Adult ; Animals ; Blotting, Western ; Cell Count ; Cell Line ; Colorectal Neoplasms* ; Cytokines ; Drug Resistance, Multiple ; Fibroblasts* ; Flow Cytometry ; Fluorouracil ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Injections, Subcutaneous ; Mice ; Paclitaxel ; Snails ; Transforming Growth Factors

Objective:To investigate the mechanism of polygonatum and astragalus compound(PA)in inhibiting the progression of lung adenocarcinoma. Methods:CCK-8 assay was used to assess the inhibitory rate of proliferation in A549 and H1299 cells treated with PA at different concentrations and to calculate the half maximal inhibitory concentration(IC50).C57BL/6 mice(KRASG12D/+;TP53flox/flox)were treated with adenovirus carrying Cre enzyme via nasal inhalation to establish a mouse model of primary lung adenocarcinoma.The model mice were fed with PA-containing diet to directly observe the effect of PA on the lung adenocarcinoma tissue.Immunohistochemical staining was used to examine the pathological status of the lung tissue.Bioinformatics analysis indicated that PA affects the progression of lung adenocarcinoma through the apelin-peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1α)-mitochondrial brown fat uncoupling protein 1(UCP1).Real-time quantitative PCR and Western blotting analysis were used to study the effect of PA on the mRNA and protein expression levels of apelin-PGC1α-UCP1 signaling pathway related genes.An ATP detection kit and flow cytometry were used to evaluate the effect of PA on the ATP and mitochondrial ROS production,respectively,in A549 and H1299 cells.siUCP1 was used to silent the expression of UCP1 while Z160 was used to induce UCP1 overexpression in A549 and H1299 cells,and the changes in ATP and mitochondrial ROS production were examined to further investigate whether PA acts on apelin-PGC1α-UCP1 signaling pathway to affect the progression of lung adenocarcinoma. Results:PA could obviously inhibit the proliferation of A549 and H1299 cells with the IC50 values of 10.66 mg/mL for A549 cells and 9.66 mg/mL for H1299 cells.In the mouse primary lung adenocarcinoma model,PA could effectively inhibit the growth of tumor,downregulate apelin-PGC1α-UCP1 signaling pathway and inhibit the expression of lung adenocarcinoma-promoting gene UCP1.In A549 and H1299 cells,PA could significantly inhibit the expression of apelin,PGC1α and UCP1(P＜0.05),promote the production of ATP(P＜0.000 1)and ROS,restore mitochondrial oxidative phosphorylation,and inhibit aerobic glycolysis(P＜0.01).UCP1 silencing could increase the production of ATP(P＜0.01)and mitochondrial ROS and decrease the expression of key glycolysis enzymes hexokinase 2(HK2)and pyruvate kinase isozyme type M2(PKM2)(P＜0.05).Increasing the expression of UCP1 could reduce the ATP production(P＜0.01)and mitochondrial ROS generation in cells while increase the expression of HK2 and PKM2(P＜0.05).Treating cells with PA and Z160 simultaneously(PA+Z160)could reverse the inhibitory effect of PA on the ATP production and glycolysis of tumor cells(P＜0.05). Conclusion:PA can downregulate the apelin-PGC1α-UCP1 signaling pathway,inhibit mitochondrial uncoupling,restore mitochondrial oxidative phosphorylation,inhibit aerobic glycolysis,reverse the Warburg effect,and thus inhibit lung adenocarcinoma progression.

Epidemiology is one of main courses for undergraduate students majoring in preventive medicine.There are some limitations in the traditional epidemiology teaching,which is usually characterized in indoctrinated education:"lectured by the teachers and listened by the students." In Zhejiang University,staff of the epidemiology division tried to explore a new teaching mode as ‘student-centered,teacher-leading,question-based,and combining with literature discussion and course practice.'After practicing for two years,students were inspired in learning initiatives,with teaching effectiveness obviously improved.

Objective:To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS). Methods:The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively. Results:Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN) 7, (GCN) 13, (GCN) 14, (GCN) 15 and (GCN) 20. The frequency of the (GCN) 20 allele was the highest (94.79%). And five genotypes were identified, which included (GCN) 7/(GCN) 20, (GCN) 13/(GCN) 20, (GCN) 14/(GCN) 20, (GCN) 15/(GCN) 20, (GCN) 20/(GCN) 20. The homozygous genotypes were all (GCN) 20/(GCN) 20, and the carrier rate was 89.58%. Four GCN sequences of the (GCN) 20 homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the, Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN) 20/(GCN) 25 and (GCN) 20/(GCN) 30, respectively. Conclusion:It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.