Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

ObjectiveTo investigate the value of MELD 3.0， MELD， and MELD-Na scores in assessing the 90-day prognosis of patients with acute-on-chronic liver failure （ACLF） through a comparative study. MethodsA retrospective analysis was performed for the clinical data of 605 patients with ACLF who were treated in Tianjin Third Central Hospital， The Fifth Medical Center of Chinese PLA General Hospital， and Beijing YouAn Hospital from November 2012 to June 2019， and according to the 90-day follow-up results after admission， they were divided into survival group with 392 patients and death group with 213 patients. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， net reclassification improvement （NRI）， integrated discrimination improvement （IDI）， and decision curve analysis （DCA） curve were used to investigate the value of MELD 3.0， MELD， and MELD-Na scores at baseline， day 3， week 1， and week 2 in predicting the prognosis of the disease. ResultsAt day 3 and week 1， MELD 3.0 score had an AUC of 0.775 and 0.808， respectively， with a better AUC than MELD score （P<0.05）. At day 3， week 1， and week 2， MELD 3.0 score showed an NRI of 0.125， 0.100， and 0.081， respectively， compared with MELD in predicting the prognosis of ACLF patients， as well as an NRI of 0.093， 0.140， and 0.204， respectively， compared with MELD-Na score in predicting prognosis. At baseline， day 3， week 1， and week 2， MELD 3.0 showed an IDI of 0.011， 0.025， 0.017， and 0.013， respectively， compared with MELD in predicting the prognosis of ACLF patients. At day 3 and week 2， MELD 3.0 showed an IDI of 0.027 and 0.038， respectively， compared with MELD-Na in predicting the prognosis of ACLF patients. All the above NRIs and IDIs were >0， indicating a positive improvement （all P<0.05）. DCA curves showed that MELD 3.0 was superior to MELD at day 3 and was significantly superior to MELD-Na at week 2. There was no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with different types， and there was also no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with the etiology of HBV infection， alcohol， or HBV infection combined with alcohol， while MELD 3.0 was superior to MELD for ACLF patients with other etiologies （P<0.05）. ConclusionMELD 3.0 score is better than MELD and MELD-Na scores in predicting the 90-day survival of patients with ACLF， but with limited superiority.

Objective:To investigate the effect of neoadjuvant chemotherapy on the safety of laparoscopic D 2 radical resection and prognosis of patients with locally advanced gastric cancer. Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 351 patients with locally advanced gastric cancer who underwent laparos-copic D 2 radical resection in the Second Affiliated Hospital of Air Force Medical University from December 2016 to December 2021 were collected. There were 256 males and 95 females, aged (58±9)years. Of the 351 patients, 124 cases undergoing neoadjuvant chemotherapy were divided into the neoadjuvant chemotherapy group, 227 patients undergoing postoperative adjuvant chemotherapy were divided into the adjuvant chemotherapy group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) effect evaluation of neoadjuvant chemotherapy; (3) intraoperative and postoperative situations; (4) postoperative histopathological examinations; (5) follow-up. Propensity score matching was done by the 1∶1 nearest neighbor matching method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measure-ment data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curves, and the Log-Rank test was used for survival analysis. Results:(1) Propensity score matching conditions and comparison of general data of patients between the two groups of patients after matching. Of 351 patients, 154 cases were successfully matched, including 77 cases in the neoadjuvant chemotherapy group and 77 cases in the adjuvant chemotherapy group. The elimination of gender, age, preoperative body mass index, clinical T staging and clinical N staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Effect evaluation of neoadjuvant chemotherapy. Of the 77 patients receiving neoadjuvant chemotherapy, none of patient achieved complete response, 26 patients achieved partial response, 46 patients showed stable disease, 5 patients had progression of disease, showing the objective response rate as 33.8%(26/77) and the disease control rate as 93.5%(72/77). There were 15 males and 11 females sensitive to neoadjuvant chemotherapy, while 46 males and 5 females not sensitive, showing a significant difference between them ( χ2=11.05, P<0.05). (3) Intra-operative and postoperative situations. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, time to postoperative first flatus, time to postoperative first liquid food intake, duration of postoperative hospital stay, cases with postoperative immediate complications, cost of hospital stay were (308±71)minutes, 100(range, 20?600)mL, 5, 3.0(range, 2.0?10.0)days, 4.0(range, 2.0?12.0)days, 9.0(range, 4.0?31.0)days, 7, 7.96(7.37,8.58) ten thousand yuan in patients of the neoadjuvant chemotherapy group, versus (296±67)minutes, 100(range, 20?500)mL, 4, 3.5(range, 1.0?14.0)days, 4.0(range, 2.0?15.0)days, 8.0(range, 5.0?45.0)days, 11, 8.18(7.52,9.19) ten thousand yuan in patients of the adjuvant chemotherapy group, showing no signifi-cant difference in the above indicators between the two groups ( t=1.13, Z=?0.37, χ2=0.12, Z=?1.26, ?0.33, ?0.70, χ2=1.01, Z=?1.04, P>0.05). (4) Postoperative histopathological examinations. Results of postoperative histopatho-logical examinations showed that all 154 patients achieving R 0 resection. Cases with pathological T staging as stage T1, stage T2, stage T3, stage T4, cases with pathological N staging as stage N0, stage N1, stage N2, stage N3, number of positive lymph nodes, cases with human epidermal growth factor receptor 2 (negative, positive) were 3, 7, 5, 62, 27, 19, 19, 12, 1(range, 0?28), 59, 18 in patients of the neoadjuvant chemotherapy group, versus 0, 0, 2, 75, 17, 15, 21, 24, 3(range, 0?31), 44, 33 in patients of the adjuvant chemotherapy group, showing significant differences in the above indicators between the two groups ( Z=?3.39, ?2.55, ?3.12, χ2=6.60, P<0.05). (5) Follow-up. Of the 154 patients, 143 patients were followed up for 37(range, 5?69)months. The 3-year overall survival rate and 3-year disease-free survival rate was 72.1% and 70.0%, respectively, in patients of the neoadjuvant chemotherapy group, versus 74.8% and 76.6% in patients of the adjuvant chemo-therapy group, showing no significant difference in the above indicators between the two groups ( χ2=0.14, 0.60, P>0.05). Conclusions:Compared to postoperative adjuvant chemotherapy, neoadjuvant chemotherapy does not bring additional surgical risks, but can reduce the tumor stage of patients who underwent laparoscopic D 2 radical resection for locally advanced gastric cancer. However, it does not show any advantage in improving survival of patients.

Objective:To study the learning curve in laparoscopic left lateral hepatic sectionectomy.Methods:The clinical data of 62 consecutive patients who underwent left lateral hepatic sectionectomy by a single operator from February 2015 to May 2022 in General Hospital of Northern Theater Command were retrospectively analyzed. There were 22 males and 40 females, with mean ±s.d. of (50.7±11.7) years. The learning curve was depicted and evaluated by using the cumulative summation test. The general information, operation and postoperative indicators of the growth level group and the master level group were compared.Results:The average operation time of the 62 consecutive subjects was (172.9±70.1) minutes. Intraoperative blood loss was 100 (50, 200) ml. Two patients were converted to open hepatectomy. Clavien-Dindo grade I postoperative complications occurred in 20 patients (32.3%), with grade Ⅱ in 1 patient (1.6%) and grade Ⅲb in another patient (1.6%). The learning curve reached its highest point on the 20th patient by using the cumulative summation test. The study subjects were then assigned into the growth level group (patient 1-20) and the master level group (patient 21-62). The master level group had a significantly wider spread of patient age [(52.9±11.0) years vs (46.1±11.9) years], decreased operation time [(146.8±55.6) min vs (227.9±66.7) min], shortened drainage tube removal time [4(3, 5) d vs 6(4, 7) d] and decreased postoperative hospital stay [5(5, 7) d vs 6.5(4, 9) d] (all P<0.05) when compared with the growth level group. Conclusion:Left lateral hepatic sectionectomy was safe and feasible, and a single operator went through a learning curve of 20 patients before he/she could master the operation more proficiently.

Objective:To investigate the effectiveness and safety of the VA regimen, which combines venetoclax with azacitidine in the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are not suitable candidates for conventional chemotherapy.Methods:In the Department of Hematology at the Second Hospital of Hebei Medical University, 66 AML patients who received venetoclax and azacitidine treatment from May 2020 to March 2022 were the subject of a retrospective study. The complete remission (CR) rate, cCR rate, ORR rate, MRD negative rate, the incidence of adverse events,1-year EFS, and OS were retrospectively analyzed. Patients subgroups with varying ages, ECOG scores, primary and secondary, risk stratifications, and gene mutation were compared for differences in efficacy and survival.Results:The median follow-up was 4.25 (0.9-19.9) months, and the median number of treatment courses was 2 (1–8) cycles. After the first cycle, the cCR rate was 78.8% , and the MRD negative rate was 51.9% . After prolonged treatment, the cCR rate was 81.8% and MRD negative rate was 66.7% . The median EFS and OS, respectively, were13.2 and 15.3 months. Secondary AML showed inferior efficacy and prognosis. IDH1/2 or NPM1 mutation groups had a significantly higher rate of CR than the control group ( P<0.05) . The CR rate and MRD negative rate of patients with rebound thrombocytosis were significantly higher than those without rebound thrombocytosis ( P<0.05) . Those who had epigenetic modification mutations (DNMT3, ASXL1, TET2) were more likely to benefit from ongoing therapy. The most common grade 3 and 4 adverse reactions were neutropenia, thrombocytopenia, and anemia. Conclusions:In real-world patients with newly diagnosed AML who are not candidates for standard chemotherapy, the VA regimen produces rapid deep remission. Primary AML patients, rebound thrombocytosis, IDH1/2, and NPM1 gene mutations are favorable factors for treatment benefit, and adverse reactions were tolerable.

Objective:To explore the associations between perceived built environment attributes and adults’ leisure-time physical activity in four cities of China.Methods:Multistage cluster random sampling method was used to select adults aged 25 to 64 in Hangzhou, Suzhou, Chengdu, and Qingdao. Data were collected from June 2017 to July 2018. The perception of the urban built environment was assessed by the neighborhood environment walkability scale-abbreviated (NEWS-A), and the physical activity was assessed by the International Physical Activity Questionnaire. Generalized linear mixed models were used to explore the relationship between the perceived built environment and leisure-time physical activities.Results:A total of 3 789 participants were included in the analysis. After adjusting for potential confounders, better access to public services ( OR=1.34, 95% CI: 1.02-1.75) and higher aesthetic quality ( OR=1.37, 95% CI: 1.09-1.73) were positively associated with the possibility of engaging in leisure-time physical activity in the past week. Similarly, these two attributes were positively associated with leisure-time walking. Higher scores on the perception of street connectivity were positively associated with leisure-time walking [ exp( β)=1.09, 95% CI: 1.00-1.19]. Higher residential density [ exp( β)=1.000 4, 95% CI:1.000 0-1.000 8], better access to physical activity destinations[ exp( β)=1.09, 95% CI: 1.00-1.19], and better aesthetics [ exp( β)=1.11, 95% CI:1.00-1.22] were associated with higher leisure-time physical activity. Similarly, these three attributes were positively associated with the possibility of meeting the WHO recommendations. Conclusion:Changing some urban built environment attributes may increase leisure-time physical activity.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Objective To investigate the correlation of moesin and E-cadherin with biological behavior of breast cancer and its mechanism by comparing expression of moesin and E-cadherin in breast invasive carcinoma of no specific type (BIC-NST),breast ductal carcinoma in situ (BDCIS) and normal breast tissues adjacent to carcinoma.Methods Breast cancer cases of the Huizhou Municipal Center People Hospital were collected between Jan 2008 and Dec 2010,expression of moesin and E-cadherin in 104 cases of BIC-NST,84 cases of BDCIS and 53 cases of normal breast tissues adjacent to carcinoma were detected by tissue-microarray and SP immunohistochemical staining.Western blot was used to detect moesin expression of 16 BIC-NST fresh tissues.Results Expression rate of moesin in BIC-NST and BDCIS were significantly higher than normal tissues(P ＜ 0.01),but the expression rate of E-cadherin in BIC-NST and BDCIS were significantly lower than those of normal tissues(P ＜ 0.01).Expression rate of moesin in BIC-NST grade Ⅲ group was significantly higher than that of the grade Ⅰ group.There was a significantly positive correlation between histological grade and moesin expression(P ＜ 0.05).However,E-cadherin expression rate in BICNST grade Ⅲ group was significantly lower than that in grade Ⅰ group,and there was a significantly negative correlation between histological grade and E-cadherin expression (P ＜ 0.05).Moreover,no significant correlation was observed between moesin and E-cadherin expression in BDCIS tissues.Expression of moesin in clinical stage Ⅱ + Ⅲ BIC-NST was significantly higher than that in stage Ⅰ (P ＜ 0.01).Expression of moesin was significantly associated with lymph node metastasis (P ＜ 0.01).But no significant correlation was observed between moesin expression and age,tumor size and vascular invasion.However,expression of E-cadherin in clinical stage Ⅱ + Ⅲ BIC-NST was significantly lower than that in stage Ⅰ (P ＜ 0.01).Expression of E-cadherin was significantly associated with lymph node metastasis and vascular invasion (P ＜ 0.01).But no significant correlation was observed between E-cadherin expression,age and tumor size.There was a negative correlation between expression of moesin and E-cadherin in BIC-NST(P =0.021)and BDCIS(P =O.032).Conclusion Higher moesin and lower E-cadherin signal transduction is closely related to the recurrence and development of breast carcinoma,therefore moesin and E-cadherin might provide new targets for gene therapy in breast carcinoma.

OBJECTIVETo investigate trend of dietary nutrient intake among adult females in China.

METHODSThe changes of dietary energy and major nutrient intake among females aged 25 to 55 years in 9 provinces were analyzed by using the data from Chinese Health and Nutrition Survey, 2000-2011 (CHNS) and indicators of Chinese Dietary Reference Intakes (DRIs) 2013.

RESULTSDuring the past decade, the proportion of females with the intake of energy and protein meeting the requirement of recommendation decreased, while the proportion of females with low carbohydrate (< 50% energy) and high fat (> 30% energy) intakes increased. Meanwhile, the vitamin and mineral intakes among the females were also unsatisfactory, only small proportion of the females met the requirement for micronutrient intake, and this proportion continued to decline. In 2011, the proportion of the females who met the requirements for energy and protein intakes were 43.0% and 54.4%, respectively; the proportion of the females with low carbohydrate and high fat intakes were 40.2% and 63.8%, respectively; the proportion of females who met the requirements for vitamin A, thiamine, riboflavin, niacin, vitamin C and vitamin E intakes were 25.2%, 10.7%, 6.9%, 54.9%, 24.3% and 88.5% respectively and the proportion of females who met the requirements for calcium, magnesium, iron, zinc and selenium intakes were 3.3%, 23.6%, 50.9%, 75.7% and 13.3% respectively.

CONCLUSIONFurther nutritional education and intervention is needed to improve nutrition status among Chinese females.

Adult ; Ascorbic Acid ; administration & dosage ; Calcium, Dietary ; administration & dosage ; China ; Diet ; trends ; Energy Intake ; Female ; Humans ; Iron ; administration & dosage ; Micronutrients ; administration & dosage ; Middle Aged ; Nutrition Surveys ; Nutritional Requirements ; Nutritional Status ; Vitamins ; administration & dosage

Objective To investigate trend of dietary nutrient intake among adult females in China. Methods The changes of dietary energy and major nutrient intake among females aged 25 to 55 years in 9 provinces were analyzed by using the data from Chinese Health and Nutrition Survey,2000-2011 (CHNS) and indicators of Chinese Dietary Reference Intakes (DRIs) 2013. Results During the past decade,the proportion of females with the intake of energy and protein meeting the requirement of recommendation decreased,while the proportion of females with low carbohydrate(<50%energy)and high fat(>30%energy)intakes increased. Meanwhile,the vitamin and mineral intakes among the females were also unsatisfactory,only small proportion of the females met the requirement for micronutrient intake,and this proportion continued to decline. In 2011,the proportion of the females who met the requirements for energy and protein intakes were 43.0% and 54.4%,respectively;the proportion of the females with low carbohydrate and high fat intakes were 40.2%and 63.8%,respectively;the proportion of females who met the requirements for vitamin A, thiamine,riboflavin,niacin,vitamin C and vitamin E intakes were 25.2%,10.7%,6.9%,54.9%,24.3%and 88.5% respectively and the proportion of females who met the requirements for calcium, magnesium,iron,zinc and selenium intakes were 3.3%,23.6%,50.9%,75.7%and 13.3%respectively. Conclusion Further nutritional education and intervention is needed to improve nutrition status among Chinese females.