Characterization of an IDS pathogenic variant in a family with mucopolysaccharidosis type Ⅱ / 中华内分泌代谢杂志

Objective:To identify the genetic variation in a mucopolysaccharidosis type Ⅱ(MPS Ⅱ)family, and conduct a functional study of iduronate-2-sulfatase(IDS): c.323A>C.Methods:A five-generation MPS Ⅱ family of 83 individuals including 4 patients from northern China was collected. Urine mucopolysaccharide and Alder-Reilly body were tested to assist the clinical diagnosis of MPS Ⅱ. IDS enzyme activity was detected on core family members. By the whole exome sequencing of a MPS Ⅱ patient in this family and bioinformatics analysis, the variant was screened and further identified by PCR-Sanger sequencing. Finally, to validate the function of the variant in vitro, the wild-type IDS overexpression plasmid(pCMV-hIDS-WT)and the IDS overexpression plasmid carrying the mutation site(pCMV-hIDS-c.323A>C)were transfected into COS-7 cells and the IDS activity was detected. Results:The proband(Ⅳ3)and Ⅳ4 were diagnosed as MPS Ⅱ by urine mucopolysaccharide, Alder-Reilly body, and IDS enzyme activity tests. Ⅳ3, Ⅳ4, Ⅲ19, and Ⅲ32 were determined to carry IDS: c.323A>C missense variant through the whole-exome sequencing, and diagnosed as MPS Ⅱ. Meanwhile, Ⅱ2, Ⅱ4, Ⅱ8, Ⅱ12, Ⅱ14, Ⅲ5, Ⅲ7, Ⅳ14 in the MPS Ⅱ family carried IDS: c.323A>C missense variant, and were excluded as MPS Ⅱ. The in vitro experiment in COS-7 cells showed that the missense mutation led to a significant decrease in IDS enzyme activity. Conclusion:The variant IDS: c.323A>C: p.Y108S significantly decreases the activity of IDS enzyme in vivo and in vitro, and it is identified as a pathogenic variant for MPS Ⅱ.

Glutamyl transpeptidase trajectories and new-onset metabolic syndrome: A cohort study / 中华内分泌代谢杂志

Objective:To explore the association between glutamyl transpeptidase (GGT) trajectories and new-onset metabolic syndrome to provide insights for the prevention and treatment of metabolic syndrome.Methods:A total of 3 209 subjects who met the inclusion criteria were enrolled in the study cohort of physical examination population. The GGT levels before follow-up were classified by R LCTMtools program into 3 GGT trajectory groups: low-stable group, medium-stable group and high-stable group. Cox proportional hazards regression model was used to analyze the correlation between different GGT trajectories and new-onset metabolic syndrome.Results:At the end of follow-up in 2020, the cumulative incidence of metabolic syndrome was 7.0%, and the incidence of metabolic syndrome in the low-stable group, medium-stable group and high-stable group were 3.9%, 11.4%, and 15.0%, respectively, showing a growth trend ( P<0.001). After adjusting for multiple confounding factors by Cox proportional hazards regression model, the risk of metabolic syndrome in medium-stable group and high-stable group increased in the total population. The hazard ratios (95% CI)for the high stable group in males and the medium-stable group in females were 1.67(1.07-2.60) and 3.29(1.14-9.53), respectively, compared with their respective low-stable group. Conclusion:Elevated longitudinal trajectory of GGT is a risk factor for new-onset metabolic syndrome, the risk of metabolic syndrome in the total population increased with the increase of long-term GGT level. It is recommended to maintain the long-term level of GGT at about 28 U/L in males and 14 U/L in females, respectively, to achieve the goal of early prevention of metabolic syndrome.

Genetic background of idiopathic neurodevelopmental delay patients with significant brain deviation volume / 中华医学杂志(英文版)

BACKGROUND@#Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV).@*METHODS@#We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.@*RESULTS@#We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.@*CONCLUSION@#Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.

Value of atherogenic index of plasma in predicting metabolic associated fatty liver disease in patients with type 2 diabetes mellitus / 临床肝胆病杂志

Objective To investigate the association between atherogenic index of plasma (AIP) and metabolic associated fatty liver (MAFLD) in type 2 diabetes mellitus (T2DM). Methods A total of 375 patients with T2DM who were hospitalized and treated in Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, from September 2021 to September 2022 were enrolled, and according to the presence or absence of MAFLD, they were divided into T2DM+MAFLD group with 245 patients and T2DM group with 130 patients. Related clinical data were recorded, and AIP was calculated. According to the quartiles of AIP, the patients were divided into Q1 group (AIP≤0.20), Q2 group (0.20 0.48). The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups; the trend chi-square test was used for the trend analysis of categorical data. The multivariate logistic regression analysis was used to investigate the effect of AIP on MAFLD, and the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to assess the value of the indicators such as AIP, body mass index (BMI), and alanine aminotransferase (ALT) in predicting T2DM with MAFLD. Results Compared with the T2DM group, the T2DM+MAFLD group had significant increases in BMI, systolic pressure, uric acid, fasting blood glucose, glycosylated hemoglobin, ALT, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, triglyceride, low-density lipoprotein, and AIP and a significant reduction in high-density lipoprotein (all P < 0.05). The trend chi-square test showed that the prevalence rate of MAFLD in T2DM patients tended to increase with the increase in AIP level ( χ trend 2 =20.338, P < 0.05). The multivariate logistic regression analysis showed that compared with the Q1 group, the Q4 group had a significant increase in the risk of MAFLD (odds ratio =2.396, 95% confidence interval: 1.018-5.640, P =0.045). The ROC curve analysis showed that the diagnostic model of AIP combined with BMI and ALT had the best diagnostic performance (AUC=0.816), with a sensitivity of 70.2% and a specificity of 78.5% at the optimal cut-off value of 0.670. Conclusion AIP is an independent risk factor for MAFLD in T2DM patients, and AIP combined with BMI and ALT has a good predictive value for T2DM with MAFLD.

A cohort study on the correlation between alanine aminotransferase trajectories and new-onset metabolic fatty liver disease / 中华流行病学杂志

Objective: To explore the correlation between alanine aminotransferase (ALT) trajectories and new-onset metabolic fatty liver disease (MAFLD) to provide a scientific basis for the prevention and treatment of MAFLD. Methods: The study cohort was composed of 3 553 subjects who met the inclusion criteria in the cohort study of the Henan physical examination population. According to the ALT levels of the subjects' physical examination from 2017-2019, three different ALT trajectory groups were determined by R LCTMtools, namely low-stable group, medium-stable group, and high-stable group. The incidence of MAFLD during physical examination in 2020 was followed up, the cumulative incidence rate in each group was calculated by product-limit method, and Cox proportional hazards regression model analyzed the correlation between different ALT trajectories and new-onset MAFLD. Results: The incidence rate of MAFLD parallelly increased with the increase of ALT locus, which was 6.93%, 15.42%, and 19.05%, respectively, and the difference was statistically significant (P<0.001). After adjusting for multiple confounding factors, such as gender, waist circumference, blood pressure, BMI, fasting blood sugar, and blood lipid by Cox proportional hazards regression model, the risks of MAFLD in ALT medium-stable and the high-stable group were still 1.422 times (95%CI:1.115-1.813) and 1.483 times (95%CI:1.040-2.114) of low-stable ALT group (P<0.05). Conclusions: The risk of MAFLD parallelly increases with the increase of ALT level in the normal long-term range. it is necessary to carry out the intervention for MAFLD with long-term average high value to avoid the progress of MAFLD disease to achieve the early prevention on MAFLD.

Epidemiological characteristics of newly reported HIV-infected adolescents aged 15-17 years outside school in China, 2011-2019 / 中华流行病学杂志

Objective: To understand the epidemiological characteristics of HIV-infected adolescents outside school in China and provide reference to targeted prevention and control of HIV infection in this population. Methods: All the HIV-infected adolescents aged 15-17 years outside school reported during 2011-2019 were included this study. The information about their demographics, transmission routes and migration were collected from HIV/AIDS Comprehensive Response Information Management System. The χ2 test was done for comparison among groups. The Joinpoint 4.9.0 software was applied to the annual percent change (APC) for time trends analysis using the Joinpoint regression model. The Excel 2019 and SPSS 22.0 software were used for data cleaning and statistical analysis. Results: A total of 4 919 HIV-infected adolescents aged 15-17 years outside school were reported accumulatively in China between 2011 and 2019, accounting for 63.4% (4 919/7 757) of total reported HIV-infected cases in this age group. Analysis on trend revealed that the new HIV infection diagnosis rate has become stable since 2016 (APC=2.5%, P=0.173) after the increase between 2011 and 2015 (APC=36.4%, P<0.001). The migration across provinces was discovered in 13.9% (684/4 919) of the HIV-infected adolescents outside school. Males, workers, and those diagnosed in detention centers or transmitted by injecting drugs or homosexual contacts accounted for a larger proportion in migrated cases compared with non-migrated cases. The adolescents outside school mainly got HIV infected by sexual contacts route, in which 66.5% (280/421) of the males were infected by homosexual contacts, while 97.8% (182/186) of the females were infected by heterosexual contacts in 2019. Conclusions: HIV-infected adolescents aged 15-17 years outside school were mainly infected by sexual contacts. However, adolescents outside school have low awareness of sexual health and high mobility, to whom close attention should be paid to improve their awareness of sexual health and to provide them with appropriate HIV infection prevention and treatment service.

Relationship between preoperative inflammatory indexes and prognosis of patients with rectal cancer and establishment of prognostic nomogram prediction model / 中华肿瘤杂志

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.

A cohort study on the correlation between fasting plasma glucose trajectories and new-onset carotid plaque / 中华健康管理学杂志

Objective:To investigate the correlation between fasting plasma glucose (FPG) and new-onset carotid plaque through latent class trajectory models.Methods:A total of 953 observation objects came from the first affiliated hospital of Zhengzhou University in accordance with the inclusion criteria. According to the FPG values of the observed subjects during the annual physical examination from January 2017 to December 2019, the following four different FPG trajectories groups were determined by latent class trajectory modelling tools: the low-stable group, the medium stable group, the medium-high stable group, and the high stable group. Carotid plaque incidence in each group was followed up in 2020 to compare the differences of the cumulative incidences of the four groups. The Cox proportional risk regression model was used to analyze the correlation between different FPG trajectories and new-onset carotid plaque.Results:The incidence of carotid plaque increased with the increase of FPG trajectories by 11.13%, 19.70%, 23.44%, 23.81%, respectively, with significance ( P<0.001). After adjusting gender, age, BMI and other confounding factors with the cox proportional risk regression model, the risk of carotid plaque in the FPG medium stable group, medium and high stable group, high-stable group was still 1.895 (95% CI: 1.296-2.769), 2.273 (95% CI: 1.241-4.161), 2.527 (95% CI: 1.219-5.241) times of the low stable group (all P<0.05). Conclusion:The long-term high FPG levels are independent risk factors for the incidence of carotid plaque, and controlling FPG at a low level steadily can reduce the risk of carotid plaque.

Gasdermin E and neoplasms / 国际肿瘤学杂志

Gasdermin E is closely related to neoplasms, which is involved in the occurrence and development of neoplasms through gene methylation, gene mutation or other ways. Pyroptosis mediated by gasdermin E is involved in drug therapy of various neoplasms, which provides a new theoretical basis for drug therapy of neoplasms. The study of gasdermin E aims to deepen the understanding of neoplasms and provide a new perspective for the prevention and treatment of neoplasms.

Effects of shift work on adipokines, inflammatory factors, and insulin sensitivity in non-overweight/obese women / 中华内分泌代谢杂志

Objective:To observe the effect of shift work on the stability of the circadian clock and insulin sensitivity in non-overweight/obese individuals with normal blood glucose, and explore underlying connection.Methods:Female shift working nurses in the Department of Blood Transplantation and non-shift working nurses in the Health Management Center in the First Affiliated Hospital of Zhengzhou University were divided into shift worker group (SW group) and non-shift worker group (NSW group). Serum inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α)], adipokines (adiponectin, leptin, chemerin, visfatin), and melatonin levels were measured using enzyme linked immunosorbent assay (ELISA). Realtime fluorescence quantitative PCR was performed to detect peripheral blood circadian clock genes circadian locomotor output cycles protein kaput(Clock) and brain and muscle ARNT-like protein 1(Bmal1). Cortisol and fasting insulin were measured by chemiluminescent microparticle immunoassay, and HbA 1C was measured by capillary electrophoresis. In addition, visceral fat area (VFA) was assessed with bioelectrical impedance analyzer, and mid-sleep time composite phase deviations (CPD) was calculated based on the International Physical Activity Short Questionnaire. Results:SW group had lower serum level of melatonin ( P=0.023) and higher cortisol ( P=0.001) than the NSW group, and altered mRNA expression of Clock and Bmal1 ( P=0.034, P=0.047). Fasting blood glucose and HbA 1C in the SW group, although in the normal range, had been higher than in the NSW group ( P=0.011, P=0.033). Although body mass index was normal in SW group, VFA had been higher than that of the NSW group ( P=0.010). And homeostasis model assessment for insulin resistance (HOMA-IR), IL-6, TNF-α, leptin, chemerin, and visfatin were significantly higher in the SW group than NSW group ( P=0.033, P=0.012, P=0.001, P=0.011, P=0.021, P=0.007). In addition, adjusting for body mass index and activity factors revealed a significant positive correlation between CPD and VFA ( r=0.434, P=0.049), inflammatory factors IL-6 ( r=0.514, P=0.017) and TNF-α ( r=0.700, P<0.001) and pro-inflammatory adipokines leptin ( r=0.473, P=0.030), chemerin ( r=0.439, P=0.047), visfatin ( r=0.521, P=0.015). Conclusion:Shift work can affect circadian clock, with increased visceral adiposity, pro-inflammatory adipokines, inflammatory factors and decreased insulin sensitivity in women without overweight/obese.

Establishment of HPLC fingerprint and content determination of differential components in Ligusticum sinense / 中国药房

OBJECTIVE To establish the fingerprints of Ligusticum sinense from different habitats ，screen differential components and determine their contents. METHODS Using Z-ligustilide as reference ，HPLC fingerprints of 12 batches of L. sinense were established by using Similarity Evaluation System of Chromatographic Fingerprints of TCM （2012 edition）；common peaks were identified and their similarities were evaluated. Cluster analysis （CA），principal component analysis （PCA）and orthogonal partial least squares-discriminant analysis （OPLS-DA）were performed to screen differential components with variable importance in the projection （VIP）＞1 as standard ；meanwhile，the contents of above differential components were determined by the same HPLC method. RESULTS There were 17 common peaks in the fingerprints of 12 batches of L. sinense ，and their similarities ranged 0.989-1.000. A total of 9 common peaks were identified ，i.e. chlorogenic acid （peak 1），ferulic acid （peak 2）， senkyunolide Ⅰ（peak 7），coniferyl ferulate （peak 9），E-ligustilide（peak 13），senkyunolide A （peak 14），Z-ligustilide（peak 17）. CA results showed that 12 batches of L. sinense were divided into 3 categories，S1-S5（Wuning）were clustered into one category，S6-S8（Ruichang）were clustered into one category ，S9-S12（De’an）were clustered into one category ；the VIP values of peaks 2，13，14 and 17（corresponding to ferulic acid ，E-ligustilide，senkyunolide A ，and Z-ligustilide respectively ）were all greater than 1，respectively. In S 1-S5，S6-S8 and S 9-S12 samples，the contents of ferulic acid were 0.488-0.533，0.603-0.658 and 0.415-0.433 mg/g，respectively；senkyunolide A were 1.184-1.295，1.450-1.588 and 1.307-1.377 mg/g，respectively；E-ligustilide were 0.118-0.125，0.130-0.135 and 0.223-0.229 mg/g，respectively；Z-ligustilide were 7.200-7.681，8.076-8.643 and 4.508-4.996 mg/g， respectively；the differences between two groups were statisti-cally significant （P＜0.05）. CONCLUSIONS Established ARS-11）；fingerprint is simple and accurate ，and can be used for overall quality evaluation of L. sinense from different habitats by combining with multivariate statistical analysis. Ferulic acid ， senkyunolide A ，Z-ligustilide and E-ligustilide may be the differential components that affect the quality of L. sinense from different habitats ，the contents of the first 3 components in L. sinense from Ruichang are the highest ，and the content of E-ligustilide in samples from De’an is the highest.

Effects of continuous light exposure on muscle fiber remodeling and lipid metabolism in mice / 中华内分泌代谢杂志

Objective:To observe the effects of continuous light exposure on skeletal muscle fiber type transformation and lipid metabolism, and to explore its internal relationship.Methods:Mice were randomly divided into normal light group and 24-hour continuous light group by random number table. The serum and skeletal muscle lipid content and urine 6-sulfatoxymelatonin(6-SML)level were detected by ELISA. The expression of circadian clock and lipid metabolism related genes mRNA were observed by realtime PCR. The muscle fiber type and lipid deposition were evaluated by tissue immunofluorescence as well as oil red O staining.Results:Compared with the normal light group, the level of 6-SML in urine at night decreased( P<0.05), and the expression level and rhythm of brain and muscle ARNT-like protein 1(Bmal1), circadian locomotor output cycles protein kaput(Clock), and period 2(Per2)mRNA in the skeletal muscle changed in continuous light group. In addition, the body weight, blood lipid, free fatty acid, and triglyceride contents of skeletal muscle in continuous light group increased significantly( P<0.05 or P<0.01), the expression of carnitine palmitoyltransferase 1b (Cpt1b)mRNA, the key enzyme of fatty acid oxidation, decreased significantly( P<0.05), while the expression of stearoyl-CoA desaturase(Scd1)mRNA, a lipid synthesis related gene, increased significantly( P<0.01). Further immunofluorescence analysis showed that the proportion of slow muscle fibers decreased and that of fast muscle fibers increased in continuous light group(both P<0.05). Conclusion:The process of ectopic deposition of lipid in skeletal muscle in mice induced by continuous light exposure may be related to the remodeling of skeletal muscle fibers.

Genetic Diagnosis of Thalassemia in Baise, Guangxi Zhuang Autonomous Region / 中国实验血液学杂志

OBJECTIVE@#To understand the genotypes and distribution characteristics of thalassemia in Baise, Guangxi Zhuang Autonomous Region, to provide references for the prevention and diagnosis of thalassemia in the region and improve the quality of eugenics.@*METHODS@#3 482 pregnant women and their spouses from January 2019 to August 2019 in Baise Maternal and Child Health Hospital for prenatal genetic diagnosis were selected, α, β- thalassemia genes were detected by Gap-PCR, PCR and DNA reverse dot hybridization, cases carrying thalassemia gene were confirmed and statistical analyzed.@*RESULTS@#2 260 samples (64.90%) carrying thalassemia gene were found, among which 1 459 cases (64.56%) were diagnosed as α- thalassemia, 617 cases (27.30%) as β- thalassemia, 184 cases (8.14%) as α complex β- thalassemia. Among 1 459 α- thalassemia genes, --SEA /αα(637 cases, 43.66%), -α3.7 /αα (306 cases, 20.97%), -αCS /αα(143 cases, 9.80%), -α4.2 /αα(124 cases, 8.50%) and -αWS /αα(77 cases, 5.27%) were the most common, while among 617 β- thalassemia genes, CD17 (229 cases, 37.12%), CD41-42 (213 cases, 34.52%), IVS-I-1 (41 cases, 6.65%), βE (38 cases, 6.16%) and CD71-72 (34 cases, 5.51%) were the most common. And --SEA /αα/ CD17 (24 cases, 13.04%), -α4.2 /αα/ CD17 (13 cases, 7.07%), -α3.7 /αα/ CD41-42 (12 cases, 6.52% ) and --SEA /αα/ CD41-42 (12 cases, 6.52%) were mainly found in 184 cases of α complex β - thalassemia.@*CONCLUSION@#Genotyes of thalassemia in Baise, Guangxi Zhuang Autonomous Region are complex and diverse. The prenatal screening and diagnosis of thalassemia in the region should be strengthened in accordance with the characteristics of genetypes in the region, in order to reduce birth defects and improve eugenics quality.

Effect of Competitive Antagonist of Transmembrane Glutamine Flux V-9302 on Apoptosis of Acute Myeloid Leukemia Cell Lines HL-60 and KG-1 / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of V-9302 (an antagonist of transmembrane glutamine flux) on the proliferation and apoptosis of acute myeloid leukemia cells HL-60 and KG-1.@*METHODS@#HL-60 and KG-1 cells at logarithmic phase were treated by different concentrations of V-9302. CCK-8 assay was used to detect the proliferation of the cells. Annexin V-FITC / PI double staining flow cytometry was used to detect the apoptosis of HL-60 and KG-1 cells. The expressions of BAX, BCL-2 and Caspase3 were detected by RT-qPCR and Western blot.@*RESULTS@#V-9302 could significantly inhibit the growth of HL-60 and KG-1 cells. The concentration of V-9302 at 10, 20 μmol/L could significantly promote the apoptosis of HL-60 and KG-1 cells(P<0.05). The results of apoptosis related gene detection showed that when V-9302 was applied to HL-60 and KG-1 cell lines at 10 and 20 μmol/L, the expression levels of Pro-apoptotic protein genes BAX and Caspase3 in HL-60 and KG-1 were significantly higher than those in control group (P<0.05), while the expression level of anti-apoptotic protein gene BCL-2 was significantly lower than that in the control group (P<0.05). The results of Western blot were basically consistent with that of RT-qPCR.@*CONCLUSION@#Competitive antagonist of transmembrane glutamine flux V-9302 can significantly promote the apoptosis of acute myeloid leukemia cell lines HL-60 and KG-1.

Mechanism of Traditional Chinese Medicine and Its Compound on Liver Fibrosis / 中国实验方剂学杂志

Hepatic fibrosis refers to the pathological process of abnormal proliferation of intrahepatic connective tissue caused by various pathogenic factors, resulting in the excessive accumulation of extracellular matrix (ECM) in the liver and the formation of fibrous scar. Its continuous deterioration will gradually develop into liver cirrhosis, liver failure, liver cancer and other serious liver diseases. Because liver fibrosis and early liver cirrhosis can be reversed, it is very important to control the reversible process of liver fibrosis for the prevention and treatment of liver cirrhosis and liver cancer. In recent years, it has been found that traditional Chinese medicine(TCM) has the characteristics of multi-target, less toxic and side effects and good effect in the treatment of liver fibrosis. In this paper, the mechanism of anti-hepatic fibrosis of TCM and its compound was summarized. TCM can regulate transforming growth factor-β (TGF-β), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and other growth factors to inhibit the activation of (HSCs) and induce the apoptosis of activated HSCs, promote the expression of adiponectin and inhibit the secretion of leptin, inhibit the inflammatory reaction of liver, resist oxidant stress, inhibit the capillarization of hepatic sinusoidal endothelial cells, so as to effectively prevent the progress of liver fibrosis. Therefore, TCM can inhibit the development of liver fibrosis through multi-mechanism and multi-level, and is one of the important means to treat liver fibrosis.

Rat model construction and evaluation of pelvic inflammatory disease / 上海交通大学学报（医学版）

Pelvic inflammatory disease is one of the most common infections in women of childbearing age, and its pathogenesis is not clear. In order to explore its pathological pathogenesis and find prevention and treatment measures, it is necessary to establish an animal model similar to human pelvic inflammatory disease. Considering the biological characteristics, availability, safety, repeatability and economy of experimental animals, rats are the most suitable for pelvic inflammation model animals. According to the inducing factors of pelvic inflammation, the rat models of pelvic inflammation can be divided into biological modeling, physical modeling, chemical modeling and so on. According to the experimental purpose, experimental cycle, experimental technology and other factors, the selection of appropriate model animals and modeling methods is the key to success. In this paper, the pathogenesis, drug dose, modeling time, applicable scope, advantages and disadvantages of rodent pelvic inflammation animal model are reviewed in order to provide a reference for the selection of rodent pelvic inflammatory disease model.

Robotic and endoscopic cooperative surgery in the third space for the resection of gastric submucosal tumors / 中华普通外科杂志

Objective To evaluate combined robotic and endoscopic surgery in the third space for gastric submucosal tumors (SMTs).Methods Combined surgery in 4 patients were compared with 19 patients who underwent laparoscopic wedge resection between Aug 2017 and Feb 2018.Results R0 resection was achieved in all combined surgery patients.The operation time was longer (112 ±29)min vs.(93 ±11) min (t =2.338,P＜0.05),but less blood loss,(11 ±6)ml vs.(59 ±6)ml (t =15.102,P＜ 0.01).In combined surgery group,there was a larger tumor over resected tissue percentage,65.4％ ± 28.2％ vs.22.8％ ± 19.6％ (t =3.680,P ＜ 0.05).Combined surgery group patients were with earlier first breaking wind (3 ± 1.4) d vs.(4.1 ± 0.9) d (t =2.026,P ＞ 0.05),and shorter hospital stay (6.5 ± 1.3) d vs.(8.5 ±0.6) d (t =4.902,P＜0.01),but a little higher hospitalization costs(57 651 ± 10 097) rmb vs.(42 620 ± 5 086) rmb (t =4.508,P ＜ 0.01).There were no major postoperative complications occurred in neither groups,nor tumor recurrences after 3-month follow-up.Conclusion Combined robotic and endoscopic surgery in the third space for submucosal gastric tumors is a novel operation with short operation time,less blood loss and good result.

Robotic and endoscopic cooperative surgery in the third space for the resection of gastric submucosal tumors / 中华普通外科杂志

Objective@#To evaluate combined robotic and endoscopic surgery in the third space for gastric submucosal tumors(SMTs).@*Methods@#Combined surgery in 4 patients were compared with 19 patients who underwent laparoscopic wedge resection between Aug 2017 and Feb 2018.@*Results@#R0 resection was achieved in all combined surgery patients. The operation time was longer (112±29 )min vs. (93±11 ) min (t=2.338, P<0.05), but less blood loss, (11±6)ml vs.(59±6)ml (t=15.102, P<0.01). In combined surgery group, there was a larger tumor over resected tissue percentage, 65.4%±28.2% vs.22.8%±19.6% ( t=3.680, P<0.05). Combined surgery group patients were with earlier first breaking wind (3±1.4) d vs.(4.1±0.9) d (t=2.026, P>0.05), and shorter hospital stay (6.5±1.3) d vs.( 8.5±0.6) d (t=4.902, P<0.01), but a little higher hospitalization costs(57 651±10 097)rmb vs.(42 620±5 086)rmb (t=4.508, P<0.01). There were no major postoperative complications occurred in neither groups, nor tumor recurrences after 3-month follow-up.@*Conclusion@#Combined robotic and endoscopic surgery in the third space for submucosal gastric tumors is a novel operation with short operation time, less blood loss and good result.

Learning curve of Da Vinci robot-assisted radical gastrectomy for gastric cancer / 中华消化外科杂志

Objective To investigate the learning curve of Da Vinci robot-assisted laparoscopic radical gastrectomy for gastric cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 42 patients who underwent Da Vinci robot-assisted radical gastrectomy for gastric cancer in the First Affiliated Hospital of Xi'an Jiaotong University from October 2017 to August 2018 were collected.There were 30 males and 12 females,aged from 36 to 84 years,with an average age of 59 years.The learning curve was evaluated using the cumulative sum (CUSUM) analysis and the best fitting curve method.According to the minimum number of surgeries required to cross the learning curve,the patients were divided into learning stage group and mastery stage group.Then general data and surgical efficacy of the two groups were compared.Observation indicators:(1) surgical situations;(2) results of CUSUM analysis;(3) comparison of general data between the two groups;(4) comparison of surgical efficacy between the two groups;(5) follow-up.Patients were followed up by outpatient examination or telephone interview to detect the postoperative complications,tumor recurrence and metastasis up to February 2019.Measurement data with normal distribution were presented as Mean±SD,and comparison between groups was done using the independent sample t test.Count data were represented as absolute number,and comparison between groups was analyzed using the chi-square test or Fisher exact propability.Comparison of ordinal data between groups was analyzed using the Mann-Whitney U test.Results (1) Surgical situations:all the 42 patients underwent Da Vinci robot-assisted radical gastrectomy for gastric cancer successfully,without conversion to open surgery or perioperative death.Fourteen out of 42 patients underwent Da Vinci robot-assisted total radical gastrectomy and 28 underwent Da Vinci robot-assisted distal radical gastrectomy.The operation time and docking time were (213±31)minutes and (26± 11)minutes.The operation time and docking time had a tendency to decreasing as the surgical cases increasing.(2) Results of CUSUM analysis.The CUSUM learning curve were best modeled as a polynomial with equation:CUSUM (operation time)=0.016 9X3-1.913 3X2+ 50.985X-16.595,CUSUM (docking time) =0.012 8X3-1.070 7X2 + 22.189X-23.097 respectively (X means the surgical case).The P value of fitting test of models was ＜ 0.05,with goodness-of-fit (R2) as 0.960 and 0.985.The CUSUM learning curve of operation time reached its peak when the number of surgical cases accumulated to the 19th case.Nineteen cases were the minimum number of surgeries required to cross the learning curve.Similarly,The CUSUM learning curve of docking time reached its peak when the number of surgical cases accumulated to the 14th case,and 14 cases were the minimum number of surgeries required to skillfully master robot installation across the learning curve.(3) Comparison of general data between the two groups:patients were divided into learning stage group and mastery stage group with 19 cases as the cut-off point.Males,females,age,body mass index (BMI),cases in grade 1,2,3 of American society of anesthesiologists (ASA),cases with previous abdominal surgery history,cases with basic diseases,cases in T1,T2,T3,T4 stages of preoperative ultrasonic gastroscopic tumor T staging,maximum tumor diameter,cases in Ⅰ,Ⅱ,Ⅲ stages of postoperative clinical staging,cases with total gastrectomy and distal gastrectomy (surgical method) were 14,5,(60± 13)years,(23.7±2.9)kg/m2,1,16,2,3,8,5,3,3,8,(4.1±3.5)cm,6,7,6,10,9 in the learning stage group,and 16,7,(58±10)years,(23.7±1.3)kg/m2,1,17,5,2,14,3,6,9,5,(4.7±2.7)cm,8,9,6,18,5 in the mastery stage group,respectively.There was no significant difference in the sex,age,BMI,ASA score,basic diseases,preoperative ultrasonic gastroscopic tumor T staging,maximum tumor diameter,postoperative clinical staging,and surgical method between the two groups (x2 =0.086,t =0.475,-0.007,Z =-0.884,x2 =1.469,Z =-0.301,t =-0.651,Z =-0.079,-0.236,x2 =3.076,P ＞ 0.05).There was no significant difference in the previous abdominal surgery history between the two groups (P ＞ 0.05).(4) Comparison of surgical efficacy between the two groups:operation time,volume of intraoperative blood loss,number of lymph nodes harvested,time to first liquid food intake,cases with postoperative complications and duration of postoperative hospital stay were (230±25) minutes,(176± 103) mL,21±7,(5.1 ± 2.0) days,2,(9.3± 2.5)days in the learning stage group,and (191±18) minutes,(95±41)mL,21±6,(4.7±1.7)days,3,(8.4± 2.1)days in the mastery stage group,respectively.There were statistically significant differences in the operation time and volume of intraoperative blood loss between the two groups (t =5.951,-3.359,P＜0.05).There was no statistically significant difference in number of lymph nodes harvested,time to first liquid food intake,and duration of postoperative hospital stay between the two groups (t =-0.120,0.538,1.303,P＞0.05).There was no significant difference in the cases with postoperative complications between the two groups (P＞0.05).(5) Follow-up:all the 42 patients were followed up for 6-16 months,with a median time of 11 months.No serious long-term complications,tumor recurrence and metastasis or death occurred during the follow-up.Conclusions The CUSUM learning curve of Da Vinci robot-assisted radical gastrectomy for gastric cancer can be divided into the learning stage and the mastery stage.It is suggested that the surgeons need to finish 19 cases or more to master Da Vinci robot-assisted radical gastrectomy for gastric cancer.

Effects of neoadjuvant chemotherapy on the expression of ER, PR,HER-2 and Ki67 in breast cancer patients / 西安交通大学学报(医学版)

Objective To investigate the effect of neoadjuvant chemotherapy on the expression of four molecular markers ER,PR,HER-2 and Ki6 7 ,so as to provide the basis for accurate individualized treatment of breast cancer patients.Methods We enrolled 165 breast cancer patients who underwent radical surgery in the First Affiliated Hospital of Xi'an Jiaotong University from January 1,2013 to December 31,2015.Among them,62 patients received preoperative neoadjuvant chemotherapy (NAC group),and 103 received no adjuvant (control group).We collected all the patients'preoperative and postoperative pathological specimens;we detected the expression levels of ER,PR,HER-2 and Ki67 by immunohistochemical method.Results Compared with that in control group patients,in NAC group the change rate of ER expression was 12.1% (7/58)and 7.8% (8/103) before and after chemotherapy,respectively,with no significant difference (P=0.3 78);the change rate of PR expression was 10.3% (3/58)and 10.7% (11/103),with no significant difference (P=0.227);the change rate of HER-2 expression was 8.6% (5/58)and 22.3 (23/103),with significant difference (P=0.026);the change rate of Ki67 expression was 39.7% (23/58)and 19.4% (20/103),with significant difference (P=0.006).In addition,the effective rate of neoadjuvant chemotherapy for breast cancer patients with high Ki67 expression was 63.8% (30/47), that of neoadjuvant chemotherapy in patients with low Ki6 7 expression was 3 3 .3 % (5/15),with significant differences between the two groups (P=0.038).Conclusion Neoadjuvant chemotherapy can change the status of HER-2 and Ki6 7 in breast cancer patients,in which the high Ki6 7 expression level predicts better effect of chemo-therapy.