Objective To identify novel mutations in the GATA6 gene associated with congenital atrial septal defects (ASD).Methods This was a case-control study.A cohort of 220 unrelated Han-race patients with congenital ASD and 200 unrelated ethnically matched healthy individuals used as controls,who were admitted to Tongji University Affiliated Tongji Hospital from January,2007 to October,2011,were recruited.The peripheral venous blood samples from the participants were prepared.All the coding exons and their flanking sequences of the GATA6 gene were amplified by polymerase chain reaction and sequenced using the di-deoxynucleotide chain termination technique.The acquired sequences were aligned with the sequences derived from GenBank by BLAST to identify the sequence variations.The software ClustalW was used to analyze the conservation of the altered amino acids.Results Three novel heterozygous missense GATA6 mutations,c.250G ＞A (p.A84T),c.649G ＞C (p.G217R) and c.1270A ＞C (p.S424R),were identified in 3 of 220 ASD patients,respectively.None of the three mutations was detected in 200 healthy control individuals.A cross-species alignment of GATA6 encoded protein sequences showed that the mutated amino acids were relatively conserved evolutionarily.Conclusion The identification of novel GATA6 mutations associated with ASD contributes to the reveal of the mechanism involved in the pathogenesis of ASD.

Objective:In order to enhance the early dignosis level and strengthen the understanding of pathogeny、pathology by stage and prognosis of primary gallbladder car-cinoma(PGC). Methods : The results of 679 patients of PGC from 1956 to 1998 in first affiliated hospital of Xi'an medical university were retrospectively analyzed. Results: Most of the patients belong to advanced stage when dignosised. The PGC were usually found among the old women patients. The sex ratio(female/male) was 3:1. There is a intimate relatioship between gallstone and PGC. About sixty percents of PGC might be found gallstone.The dignostic accordance rate was low between preoperation and postopera-tion.Most patients with PGC were found unexpectedly in operation due to gallstone or a-cute cholecystitis. To worse more, many of patiens with PGC were missed the opportunities of dignosis and treatment because of only paying attention to gallstone. Most of the pathological types were adenocarcinoma. The development of imaging examination is hoped to find early stage cases and improve its prognosis. Conclusion : It is a basic way for early dignosis and improving prognosis to strengthen the understanding of pathogeny, pathology by stage and prognosis and rationalize application of all kinds of exzamination means in PGC.

OBJECTIVEA multi-center randomized phase III clinical trial was designed to evaluate the efficacy, clinical benefit response (CBR) and toxicity profile of germcitabine (GEM) or GEM plus cisplatin (CDDP) for locally advanced (LAPC) or metastatic pancreatic cancer (MPC).

METHODSFrom July 2000 to May 2001, 42 untreated patients with LAPC or MPC were collected and randomized into two groups: Arm A-GEM 20 patients and Arm B-GEM + CDDP 22 patients. Eligibility criteria were: cytologically and pathologically proven pancreatic carcinoma, Karnosky performance status (KPS) 60 - 80, age 18 - 75 yrs, adequate hematological, renal and liver function, measurable disease, and controllable pain. For Arm A patients, weekly dose of GEM 1 000 mg/m(2)/w for 7 times followed by a week rest. Then weekly GEM at the same dose for 3 times every 4 weeks. Arm B patients were given weekly dose of GEM 1 000 mg/m(2)/w for 3 times every 4 weeks combined with CDDP 60 mg/m(2) on D15 for 3 cycles.

RESULTSThirty-four patients were available for objective response (Arm A 16 and Arm B 18) and 36 (Arm A 16 and Arm B 20) for CBR evaluation. In Arm A and Arm B, PR 1 (6.3%) and 2 (11%), MR 4 (25%) and 3 (16.7%), SD 7 (43.8%) and 8 (44.4%), PD 4 (25%) and 5 (27.8%), PR + MR 31.3% and 27.8%, PR + MR + SD 75% and 72.2% were observed. Positive CBR was 14/16 (87.5%) in Arm A and 14/20 (70.0%) in Arm B. The negative results was 2/16 (12.5%) in Arm A and 6/20 (30.0%) in Arm B. The median time of disease progression was not yet available at present. The 3-month survival rate of both Arm A and B was 100%, the 6-month survival rates of Arm A and B were 81.3% and 61.6% and the 12-month survival rates of Arm A and B was 31.3% and 11.1%, with median survivals of 273 and 217 days. The incidence of hematological and non-hematological toxicity of Arm A was lower than that of Arm B without statistical significance. The toxicity ranging from being mild to moderate was manageable.

CONCLUSIONGEM or GEM plus CDDP is able to lead to a moderate objective response rate, also significantly improve the quality of life in patients with locally advanced or metastatic pancreatic cancer patients, prolonging the survival time with tolerable toxicity.

Adult ; Aged ; Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; CA-19-9 Antigen ; analysis ; Cisplatin ; adverse effects ; therapeutic use ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms ; drug therapy ; mortality ; Survival Rate ; Treatment Outcome

Objective: To compare the clinical effects of laparoscopic repair and open repair of gastroduodenal ulcer perforation. Methods: Retrospective analysis was performed on 117 patients with perforated gastroduodenal ulcer admitted to Sijing Hospital of Shanghai Songjiang District from October 2005 to February 2018, including 86 males and 31 females. The average age was 35.56 years with a range from 17 to 68 years. Patients were divided into two groups according to different surgical methods: laparoscopic group (n=56) and open group (n=61). Patients in the laparoscopic group were received laparoscopic repair for perforated gastroduodenal ulcer, while patients in the open group received open repair for perforated gastroduodenal ulcer. Comparison of two groups of patients with operation time, intraoperative blood loss, postoperative first anal exhaust time, analgesic utilization rate, length of hospital stay, the body′s inflammatory response [preoperative and 24 h, 72 h, 120 h of postoperative peripheral white blood cell (WBC)], C-reactive protein level (CRP), postoperative complications (postoperative incision infection, incision dehiscence, gastric duodenal fistula, abdominal abscess, adhesion intestinal obstruction and lung infection). Measurement data were expressed as mean±standard deviation (Mean±SD), and t-test was used for comparison between groups; count data were compared by Chi-square test. Results: All the patients in the two groups successfully completed the operation, and there were no cases transferred to laparotomy in the laparoscopic group. Intraoperative blood loss[(15.3±9.5) ml vs (30.5±11.3) ml, P<0.001], time of first anal exhaust[(56.5±9.8) h vs (83.8±15.6) h, P<0.001], analygesic utilization rate (10.71% vs 52.46%, P<0.005), and length of hospital stay [(7.5±1.5) d vs (10.0±3.4) d, P<0.001] of the laparoscopic group were significantly better in the open group, the differences were statistically significant. The WBC and CRP at 24 h, 72 h and 120 h after surgery of the laparoscopic group were also significantly better than in the open group [WBC: 24 h, (14.55±3.44) ×10⁹/L vs (16.02±4.12) ×10⁹/L, P=0.020; 72 h, (10.25±2.32) ×10⁹/L vs (14.22±3.29) ×10⁹/L, P<0.001; 120 h, (8.12±3.11)×10⁹/L vs (11.58±2.33) ×10⁹/L, P<0.001. CRP: 24 h, (50.35±13.73) mg/L vs (80.11±13.56) mg/L, P<0.001; 72 h, (29.37±7.81) mg/L vs (53.57±8.05) mg/L, P<0.001; 120 h, (17.71±7.01) mg/L vs (34.35±7.72) mg/L, P<0.001], the differences were statistically significant. There was no significant difference in operation time and postoperative complications between the two groups (P>0.05). Conclusion Compared with open gastroduodenal ulcer perforation repair, laparoscopic gastroduodenal ulcer perforation repair surgery trauma are smaller, and the body′s inflammatory response are lighter, postoperative complications is no statistical significance, but will look from actual data, the cases of complications is less, is now a better surgical treatment of gastroduodenal ulcer perforation.

Animal model of hydrocephalus is an important object to study the mechanism, pathological characteristics, and treatment of hydrocephalus. A stable and controllable animal model in accordance with clinical development of hydrocephalus can help to develope hydrocephalus related basic research and clinical translational application. According to the study purpose and genetic and physiological characteristics of experimental animals, a variety of animals have been used to establish different types of hydrocephalus animal models. The methods for congenital hydrocephalus models include gene edition and metabolic induction, while secondary hydrocephalus models can be induced by blocking the circulation of cerebrospinal fluid and interfering cerebrospinal fluid absorption. The hydrocephalus models constructed by different methods are also different in progression, neurofunctional changes, and histopathological characteristics. This paper reviews the construction methods and pathological characteristics of various hydrocephalus models in order to provide references for selection of animal models for hydrocephalus-related research.

ObjectiveTo investigate the expression and role of response gene to complement 32 （RGC32） in liver regeneration after partial hepatectomy （PH）. MethodsA total of 42 male C57BL/6 mice， aged 10 weeks， were randomly divided into control group， postoperative day 1 group （1－d group）， postoperative day 2 group （2－d group）， postoperative day 4 group （4－d group）， postoperative day 6 group （6－d group）， postoperative day 8 group （8－d group）， and postoperative day 10 group （10－d group）， with 6 mice in each group. In the control group， the complete liver of the mice was resected for weighing and photography as the normal control group （sham group）； further， the left and middle lobes of the liver were resected for weighing and photography as the surgical control group （0－day group）； the sham group and the 0－day group shared the same group of mice. After successful modeling by PH， the mice were sacrificed on days 1， 2， 4， 6， 8， and 10 after surgery， and the liver was collected to measure the change in size. HE staining and oil red O staining were used to evaluate liver histomorphological changes； serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured to evaluate the changes in liver function； immunohistochemical staining was used to measure the expression of proliferating cell nuclear antigen （PCNA） and Ki67 and analyze the change in cell proliferation during liver regeneration； quantitatie real－time PCR and immunohistochemical staining were uused to measure the expression and subcellular distribution of RGC32 during liver regeneration； EdU cell proliferation assay was used to analyze the effect of RGC32 overexpression or knocknout on hepatocyte proliferation in L02 cells. For continuous data， comparison between multiple groups was made by analysis of variance， and further pairwise comparisons were conducted using the LSD－t test. The independent samples t－test was used for comparison of continuous data between two groups. A Pearson correlation analysis was performed. ResultsThe liver gradually enlarged after PH， and the liver/body weight ratio rose to the peak from days 0 to 6， with significant differences between different time points （all P<0.05）， while there was no significant change in liver size from days 6 to 10. The number of liver lipid droplets significantly increased after PH surgery and gradually decreased with liver regeneration， with a significant difference between the portal vein region and the central vein region （all P<0.05）. Compared with the sham group， the 1d group had significant increases in the serum levels of ALT and AST （all P<0.05）， which gradually returned to the levels of the sham group on day 6 and day 2 after surgery， respectively （P>0.05）. Immunohistochemical staining showed that there were rapid increases in the numbers of PCNA－ and Ki67－positive liver parenchymal cells after PH surgery， with the highest numbers of 86±5 and 89±5， respectively， on day 2， which then gradually decreased； however， there were gradual increases in the numbers of PCNA－ and Ki67－positive nonparenchymal cells， with the peak numbers of 34±5 and 25±3， respectively， on day 6， which then gradually decreased. The total expression of RGC32 increased to the highest level on day 2 after PH surgery and then gradually decreased， and the changing trend of RGC32 expression in cytoplasm was consistent with that of total RGC32 expression； however， the expression of RGC32 in nucleus decreased to the lowest level on day 2 after PH surgery and then increased gradually. The correlation analysis showed that the expression of RGC32 in nucleus was negatively correlated with the proliferation of liver parenchymal cells （R²=0.308 3， P=0.016 7）， and the expression of RGC32 in cytoplasm was positively correlated with the proliferation of liver parenchymal cells （R²=0.808 6， P<0.000 1）. Cell experiments showed that compared with the control group， the EdU－positive rate was reduced by 15.6% after RGC32 overexpression （P<0.01） and was increased by 19.2% after RGC32 knockdown （P<0.01）. ConclusionLiver parenchymal cells and nonparenchymal cells show asynchronous proliferation and participate in liver regeneration together. During liver regeneration after hepatectomy， there are differences in the expression of RGC32 between nucleus and cytoplasm， and RGC32 in nucleus may inhibit hepatocyte proliferation.

ObjectiveTo evaluate the efficacy of TCM health management based on tertiary management system for patients with myocardial infarction （MI）. MethodsA total of 277 patients with non-acute MI were enrolled and given comprehensive TCM health management strategies including health education， lifestyle adjustment， risk factors control， medication and TCM appropriate techniques management through a tertiary management system with "the patient as the core， village/community physicians as the main executive body， and tertiary TCM hospital specialists as the leading body"， for a period of 12 months by using a prospective single-arm cohort study. Through patient reporting and medical records surveys， various indicators before and after 12-month management were collected and compared. The primary efficacy indicators were readmission rate and recurrent exacerbation rate， and the secondary efficacy indicators included disease awareness-related indicators， lifestyle behavior-related indicators， cardiovascular risk factor-related indicators and Canadian cardiovascular society （CCS） cardiac function classification. ResultsA total of 255 patients completed the study and were included in the final analysis. The recurrent exacerbation and readmission rates of patients after management were 23.14% （59 cases） and 20.25% （49 cases）， respectively， significantly lower than 36.08% （92 cases） and 53.72% （130 cases） before management （P＜0.05）. Except for knowledge on diabetes diagnostic criteria with no significant difference before and after management （P＞0.05）， awareness of other knowledge with regard to the prevention and treatment of cardiovascular and cerebrovascular diseases were improved after management （P＜0.01）， as well as the total score （P＜0.01）. In terms of daily life behaviors， the rates of salty diet， sweet diet and greasy diet were significantly lower than baseline， while the rate of moderate exercise was significantly higher （P＜0.05 or P＜0.01）； the rates of ongoing smoking and vigorous exercise were not significantly changed （P＞0.05）. For cardiovascular risk factors， patients' total cholesterol， low-density lipoprotein （LDL） cholesterol， triglycerides， fasting glucose， total depression assessment scale score， and total anxiety assessment scale score were significantly reduced after management （P＜0.01）. Systolic blood pressure and body mass index （BMI） were both higher after management （P＜0.05 or P＜0.01）， and there was no statistically significant difference in diastolic blood pressure （P＞0.05）. In terms of the cardiovascular disease risk factors reaching the standard levels， the rate of LDL cholesterol ＜1.8 mmol/L significantly increased （P＜0.01）， while the rate of BMI ＜24 kg/m² and the rate of systolic blood pressure ＜140 mmHg both decreased significantly （P＜0.05 or P＜0.01） from baseline； the diastolic blood pressure and rate of fasting glucose ＜7.0 mmol/L were not significantly changed （P＞0.05）. The patients' CCS cardiac function classification was significantly reduced （P＜0.05）. ConclusionTCM health management based on the tertiary management system can enhance MI patients' awareness of the disease， change poor lifestyle habits， reduce risk factors such as blood lipids and blood glucose， improve anxiety and depression， increase activity tolerance， and reduce their recurrence exacerbation and readmission rates， which is worthy of clinical promotion.

OBJECTIVE To evaluate the efficacy and safety of guideline-directed medical therapy （GDMT） combined with vericiguat in treating heart failure with reduced ejection fraction （HFrEF）. METHODS A retrospective study was conducted on 346 patients with HFrEF who received standardized diagnosis and treatment at the First People’s Hospital of Changzhou from January 2023 to May 2024. They were divided into standard treatment group （n＝215） and vericiguat group （n＝131）. Patients in the standard treatment group received GDMT， while patients in the vericiguat group received GDMT combined with vericiguat. Propensity score matching （PSM） was used to balance confounding factors between two groups， and the effectiveness （including outcome and prognostic indicators） and safety （occurrence of adverse events） of both groups were evaluated. Kaplan-Meier survival curves for primary and secondary outcome events were drawn， and the influential factors of primary outcome events were screened through univariate and multivariate Cox regression analysis. RESULTS After PSM， there were 100 patients in the standard treatment group and 100 patients in the vericiguat group， and there was no statistically significant differences in baseline data between two groups （P＞0.05）. During a 1-year follow-up， there were statistically significant differences in the cumulative incidence of major outcome events between the standard treatment group and the vericiguat group， cumulative incidence of hospitalization events due to heart failure， changes in N-terminal pro-B-type natriuretic peptide levels before and after treatment between the standard treatment group and the vericiguat group （P＜0.05）. There was no statistically significant difference in the incidence of adverse events between the two groups （P＞0.05）. Multivariate Cox regression analysis results showed that left ventricular ejection fraction ≤35% was a risk factor for the occurrence of major outcome events within 1 year [hazard ratio （HR）＝ 2.090， 95% confidence interval （CI）： 1.175-3.718， P＝0.012]， while the use of vericiguat was a protective factor for the occurrence of major outcome events within 1 year （HR＝0.505， 95%CI： 0.284-0.899， P＝0.020）. CONCLUSIONS Compared with GDMT， GDMT combined with vericiguat can improve the clinical symptoms and prognosis of HFrEF patients， and has good safety.

Objective: This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining for triage high risk HPV (HR-HPV) infected women. Method: Target objects were women who infected HR-HPV and received colposcopy examination between April and December of 2016 at the Second Affiliated Hospital of Zhengzhou University. Gynecologists collected the cervical exfoliated cells from eligible women for p16/Ki-67 dual staining, LBC testing and HPV DNA testing. Histology diagnosis were used as gold standard. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs) of p16/Ki-67 dual staining, LBC testing and HPV16/18 testing for triage of HR-HPV positive population were calculated and compared. Results: A total of 295 HR-HPV infected women were selected, and the mean age was (44.29±11.48) years old. Positive rates of p16/Ki-67 dual staining, HPV16/18 testing and LBC testing were 70.17% (207), 56.95% (168) and 85.76% (253), respectively. When CIN2+as the endpoint, among the three triage methods, sensitivity of p16/Ki-67 dual staining was 90.00% (95%CI: 85.06%-93.43%), higher than the value of HPV 16/18 testing, but lower than the value of LBC testing. Specificity, PPV and NPV of p16/Ki-67 dual staining were the highest [71.58% (95%CI: 61.81%-79.67%), 86.96% (95%CI:81.69%-90.88%) and 77.27% (95%CI: 67.49%-84.78%)]. When detection for CIN3+, sensitivity of p16/Ki-67 dual staining was 92.90% (95%CI: 87.74%-95.99%), lower than the value of LBC testing, but higher than the value of HPV16/18 testing. Specificity of p16/Ki-67 dual staining was 55.00% (95%CI: 46.74%-63.00%), lower than the value of HPV16/18 testing, but higher than the value of LBC testing. PPV of p16/Ki-67 dual staining was 69.57% (95%CI: 62.99%-75.43%), lower than the value of HPV 16/18 testing, but higher than the value of LBC testing. NPV of p16/Ki-67 dual staining was 87.50% (95%CI: 78.99%-92.87%), higher than value of HPV 16/18 testing, but lower than the value of LBC testing. Conclusion p16/Ki-67 dual staining has better clinical effects than HPV 16/18 testing and LBC testing for triage women with HR-HPV infection.