Objective To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage(HIBD)and to explore its mechanisms via the PI3K/AKT signaling pathway,aiming to provide a basis for the clinical application of melatonin.Methods Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group,an HIBD group,and a melatonin group(n=9 each).The neonatal rat HIBD model was established using the classic Rice-Vannucci method.Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining.Autophagy-related protein levels of microtubule-associated protein 1 light chain 3(LC3)and Beclin-1 were detected by immunofluorescence staining and Western blot analysis.Phosphorylated phosphoinositide 3-kinase(p-PI3K)and phosphorylated protein kinase B(p-AKT)protein expression levels were measured by immunohistochemistry and Western blot.The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis.Results Twenty-four hours post-modeling,neurons in the sham operation group displayed normal size and orderly arrangement.In contrast,neurons in the HIBD group showed swelling and disorderly arrangement,while those in the melatonin group had relatively normal morphology and more orderly arrangement.Nissl bodies were normal in the sham operation group but distorted in the HIBD group;however,they remained relatively intact in the melatonin group.The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group,but was reduced in the melatonin group compared to the HIBD group(P<0.05).The number of p-PI3K+and p-AKT+cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group(P<0.05).LC3 and Beclin-1 protein expression levels were higher,and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group(P<0.05);however,in the melatonin group,LC3 and Beclin-1 levels decreased,and p-PI3K and p-AKT increased compared to the HIBD group(P<0.05).The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+and p-AKT+cells between the two groups(P<0.05).Conclusions Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD,thereby alleviating HIBD.This mechanism is associated with the PI3K/AKT pathway.

Objective:To investigate the genotype,mutation type,and ethnic distribution characteristics of thalassemia in the population of Hechi area,Guangxi,and to provide a reference basis for prevention and control of thalassemia and eugenic counseling in the region.Methods:Gap-polymerase chain reaction(gap-PCR)and reverse dot blot(RDB)were used for genetic testing on suspected thalassemia persons,and the results were analyzed.Results:Among 29 136 samples,a total of 17 016(58.40％)positive samples for thalassemia genes were detected,with a higher detection rate in males than in females(X2=49.917,P＜0.001).The detection rates of thalassemia genes were significant different among Zhuang,Han,Yao,Mulao,and Maonan ethnic groups(x2=546.121,P＜0.001).The α-thalassemia genotypes were mainly--SEA/αα(16.67％),-α3.7/αα(8.90％),αCSα/αα(6.00％).Additionally,four rare genotypes were detected,including--THAI/αα(47 cases),HKαα/αα(2 cases),--SEA/-α21.9(2 cases),and--THAI/αcsα(1 case).The β-thalassemia genotypes were mainly βCD17/βN(7.49％),βCD41-42/βN(6.70％),βCD71-72/βN(0.44％).108 cases of moderate and severeβ-thalassemia were detected,of which 81 cases had a history of blood transfusion,the transfusion frequency of 60 cases was more than 10 times/year,and 10 cases received bone marrow transplantation.Conclusion:Thalassemia in Hechi area is predominantly deletion type--SEA/αα,the detection rate of thalassemia in ethnic minorities is higher than that in Han population.In this area,moderate and severe β-thalassemia have certain incidence,these patients mostly need regular blood transfusion and iron removal treatment,and very few patients have received bone marrow transplantation.This study provides a certain reference basis for prevention and control of thalassemia and eugenic counseling in the region.

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --^SEA, followed by 5.70% for -α^3.7, and 0.24% for --^Thai. Among 32 α-thalassemia genotypes, the most common five were --^SEA/αα, -α^3.7/αα, α^CSα/αα, -α^4.2/αα and α^WSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --^Thai/αα. A total carrying rate of 13 kinds of β-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 β-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining β-thalassemia genotypes, the most common were --^SEA/αα, -α^3.7/αα combining CD41-42/N and --^SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --^SEA/-α^3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α^3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of α^WSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --^SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --^SEA/αα in α-thalassemia and CD41-42/N in β-thalassemia, and deletion genotype --^Thai is not rare. There is a certain incidence of intermediate and severe β-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Dipeptidyl Peptidase 4/genetics* ; China/epidemiology* ; Genotype ; Mutation

OBJECTIVE: To investigate the detection rate and hematologic phenotype of HKαα thalassemia in south Guangxi, in order to provide reference for the prevention and control of thalassemia and prenatal and postnatal care consultation in this region. METHODS: Gene testing was performed on pre-marital medical examinations, pre-pregnancy eugenic health examinations, prenatal examinations and hospitalized thalassemia-positive persons in south of Guangxi, and the results were analyzed. RESULTS: A total of 183 190 thalassemia patients were included in this study, the age was mainly concentrated in 26-35 years old (101 709 cases, accounting for 55.521%), and 40 HKαα mutations were detected, detection rate was 0.022%, including 5 cases in Nanning, 22 cases in Qinzhou, 2 cases in Fangchenggang, 11 cases in Beihai. A total of 29 ethnic groups were included in the survey, but HKαα gene was observed only in Han nationality (0.0380%) and Zhuang nationality (0.0068%). A total of 8 genotypes carrying HKαα mutations were detected in this study ( HKαα/--^SEA, β^N/ β^N, HKαα/αα, β^-28/ β^N, HKαα/αα, β^-50/ β^N, HKαα/αα, β^CD17/ β^N, HKαα/αα, β^CD27/28/β ^N, HKαα/αα, β^CD41-42/ β^N, HKαα/αα, β^CD71-72/ β^N, and HKαα/αα, β^N/ β^N). Except for most cases with HKαα/αα, β^N/ β^N genotypes with no significant changes in the hematological indexes, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) of other genotypes were decreased, showing microcytic hypochromic performance, mild anemia or no anemia. CONCLUSION HKαα carrier is often misdiagnosed as -α^3.7 carrier, which easily leads to missed diagnosis or misdiagnosis. Therefore, it is necessary to continuously improve the diagnostic level of laboratory testing personnels and genetic counselors to avoid unnecessary interventional puncture operations and birth of children with moderate and severe thalassemia.
Child ; Female ; Pregnancy ; Humans ; Adult ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; China ; Genotype ; Phenotype ; Mutation

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths and has the third highest incidence in the world. Almost half of the patients with CRC have metastases at the time of diagnosis. However, the treatment for patients with metastatic CRC that progresses after approved conventional chemotherapy is still controversial. Chinese medicine (CM) has unique characteristics and advantages in treating metastatic CRC. OBJECTIVE: To assess the effectiveness and safety of CM in patients with metastatic CRC after failure of conventional chemotherapy. METHODS: The study is a multicenter prospective cohort study. A total of 384 patients with documented metastatic CRC after failure of conventional chemotherapy will be included from 9 hospitals among Beijing, Shanghai, Nanjing, and Guizhou, and assigned to three groups according to paitents' wishes: (1) integrated Chinese and Western medicine (ICM) group receiving CM herbal treatment combined with Western medicine (WM) anti-tumor therapy, (2) Chinese medicine (CM) group receiving only CM herbal treatment, and (3) WM group receiving only WM anti-tumor therapy. The primary endpoint is the overall survival (OS). Secondary endpoints include the progression free survival (PFS), quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire, tumor control, and CM symptom score. DISCUSSION This prospective study will assess the effectiveness and safety of CM in treating metastatic CRC after conventional chemotherapy failure. Patients in the ICM group will be compared with those in the WM group and CM group. If certified to be effective, national provision of CM treatment in metastatic CRC will probably be advised. (Registration No. NCT02923622 on ClinicalTrials.gov).

Objective: To analyze the epidemiological characteristics of hepatitis E Virus antibody (anti-HEV) in people aged 1-29 years in China in 2014. Methods: Based on database of the national serologic survey of hepatitis B in people aged 1-29 years in China, in 2014, the sample size was estimated. The serum samples of the people surveyed were randomly selected to detect anti-HEV IgG by using enzyme- linked immunosorbent assay (ELISA). Statistical software SAS 9.1.3 was used to calculate the positive rate of anti-HEV and 95% confidence interval (CI) in different age, gender groups, urban and rural areas and geographic areas by using the Taylor series linear method with sampling weight. The difference was determined by comparing 95%CI. Results: A total of 14 106 serum samples were detected from people aged 1-29 years, including 6 996 males (49.60%), 7 013 urban residents (49.72%). The positive rate of anti-HEV was 8.12%(95%CI: 7.19-9.15) in people aged 1-29 years. There was no statistical difference between the men and women, between urban area and rural area. The positive rates of anti-HEV in western area(11.36%, 95%CI: 9.45-13.62) was higher than those in eastern and central areas. The positive rates of anti-HEV were 2.46%, 2.24%, 4.50%, 7.58%, 11.89% and 17.27% in people aged 1-, 5-, 10-, 15-, 20- and 25-29 years, respectively. As the age increased, the positive rate of anti-HEV gradually increased. In different ethnic groups, the positive rate of anti-HEV was higher in Tibetan (18.32%, 95%CI: 12.02-26.90), Zhuang (9.54%, 95%CI: 4.33-19.73) ethnic groups. Conclusion The positive rate of anti-HEV declined slightly in China in 2014. It is still necessary to pay close attention to the HEV infection, morbidity of hepatitis E and risk factors in people aged 1-29 years.

Objective To analyze the genetic etiology of lateral ventriculomegaly fetal on the genome-wide level with chromosomal microarray analysis (CMA),and investigate the relationship between copy number variations (CNVs) and lateral ventriculomegaly and the application value of CMA in prenatal diagnosis of fetuses with lateral ventriculomegaly.Methods Seventy fetuses with lateral ventriculomegaly but normal or uncertain karyotype were selected and invasive prenatal diagnosis was performed in Xi Jing Hospital of the Fourth Military Medical University from Jan.2015 to Nov.2016.Microarray testing was performed using Affymetrix CytoScanTM 750k arrays and the results were analyzed according to biological information science database.The fetal development was regularly inspected,and follow up was conducted to find out the pregnancy outcome and fetal postnatal conditions.Results In 70 cases of lateral ventriculomegaly fetuses,there were 9 fetuses with pathogenic copy number variations (CNVs),3 fetuses with likely pathogenic CNVs and 1 fetus with likely pathogenic 1 oss of heterozygosity (LOH).During the 70 fetuses with lateral ventriculomegaly,2 pathogenic CNVs were detected in 6 fetuses with severe and non isolated lateral ventriculomegaly (33.3％).Pathogenic CNVs was not detected but 1 likely pathogenic CNV was detected in 3 fetuses with severe and isolated lateral ventriculomegaly (33.3％).Six pathogenic CNVs were detected in 31 mild and non isolated lateral ventriculomegaly (19.4％),and 2 likely pathogenic CNVs were also detected in these group (6.5％).One pathogenic CNV and 1 likely pathogenic CNV were detected in 30 fetuses with mild and isolated fetal lateral ventriculomegaly.Conclusions CMA can identify chromosome abnormality microdeletion/microduplication which was unrecognizable by conventional karyotyping analysis.The application of CMA may increase the detection rate of pathogenic CNVs in fetuses with lateral ventriculomegaly,and benefit evaluation of fetal prognosis in prenatal genetic counselling.

Objective: To evaluate the effect of hepatitis B prevention and control by comparative analysis on the results of HBsAg, anti-HBs and anti-HBc prevalence from national hepatitis B seroepidemiological surveys in 1992 and 2014 in different epidemic regions of China. Methods: Data was from the national seroepidemiological surveys of hepatitis B conducted in 1992 and 2014. The survey in 1992 was conducted in 145 disease surveillance points of 30 provinces (excluding Hong Kong, Macao Special Administrative Region and Taiwan province) in China. The survey in 2016 was conducted in 160 disease surveillance points of 31 provinces (excluding Hong Kong, Macao Special Administrative Region and Taiwan province) in China. In the two surveys, face-to-face interviews with the subject by door to door or on the investigation site were conducted by trained staff using standard questionnaires to obtain basic information including birth date, gender, ethnicity, resident place and so on. And then 5 ml venous blood was collected to test the sero-markers of HBsAg, anti-HBs and anti-HBc. We analyzed unweighted point prevalence and 95% CI of HBsAg, anti-HBs and anti-HBc in 1992 which had no design weighting, and analyzed weighted point prevalence and 95%CI of HBsAg, anti-HBs and anti-HBc in 2014 which had design weighting. Results: 34 291 and 31 713 people aged 1-29 years were involved in 1992 and 2014 national serosurveys of China, respectively. For the people aged 1-29 years, HBsAg prevalence was 2.64% (95%CI: 2.28%-3.06%) in 2014 and decreased by 73.92% as compared with the rate 10.13% (95% CI: 9.81%-10.45%) in 1992. Anti-HBc prevalence was 13.01% (95%CI: 12.09%-14.00%) in 2014 and decreased by 71.61% as compared with the rate 45.84% (95% CI: 45.31%-46.37%) in 1992. Anti-HBs prevalence was 57.79% (95%CI: 56.33%-59.25%) in 2014 and ascended by 127.41% as compared with the rate 25.41% (95% CI: 24.95%-25.87%) in 1992. In high, medium and low epidemic region, for the people who born during 1992-2001 when hepatitis B vaccine was introduced in routine immunization management, HBsAg prevalence was 4.74% (95%CI: 3.79%-5.69%), 1.59% (95%CI: 1.09%-2.10%) and 2.53% (95%CI: 1.66%-3.39%), respectively, and anti-HBs prevalence was 64.25% (95% CI: 62.11%-66.39%), 56.34% (95% CI: 54.50%-58.57%), 54.49% (95%CI: 51.75%-57.23%), respectively, and anti-HBc prevalence was 15.16% (95%CI: 13.56%-16.76%), 11.07% (95%CI: 9.80%-12.33%), 7.61% (95%CI: 6.15%-9.07%), respectively. In high, medium and low epidemic region, for the people who born during 2002-2013 the duration which hepatitis B vaccine was integrated in expanded immunization program born during when HBsAg prevalence was 0.88% (95%CI: 0.66%-1.11%), 0.37% (95%CI: 0.24%-0.49%)and 0.71% (95%CI: 0.48%-0.94%), respectively, and anti-HBs prevalence was 60.74% (95%CI: 59.57%-61.90%), 59.46% (95%CI: 58.44%-60.49%), 52.56% (95% CI: 51.20%-53.92%), respectively, and anti-HBc prevalence was 3.30% (95% CI: 2.87%-3.72%), 1.91% (95%CI: 1.63%-2.20%), 2.25% (95%CI: 1.85%-2.66%), respectively. Conclusion China had made great achievement in hepatitis B prevention and control. HBsAg prevalence among people aged 1-29 years old in 2014 decreased dramatically as compared with that in 1992. Since hepatitis B vaccine was integrated into expanded immunization program, China reduced HBsAg prevalence to less than 1% among people aged 1-12 years in 2014 in different epidemic region.

Objective To analyze the 18 F?FDG uptake features and the correlation between 18 F?FDG uptake and the prognosis in patients with pathologic stageⅠlung adenocarcinoma. Methods One hundred and seventeen patients with stageⅠlung adenocarcinoma proved by surgery, who underwent a preoperative 18 F?FDG PET?CT, were studied retrospectively. The tumors′ SUVmax in different groups of clinicopathologic factors were compared. The correlations between the SUVmax and clinicopathologic factors were analyzed using Spearman rank correlation. The ROC was plotted to estimate the most discriminative cut?off point for SUVmax in predicting the recurrence or progression of tumor. The progression?free survival ( PFS) in different clinicopathologic groups were estimated using the Kaplan?Meier method and Log?rank test. Results The SUVmax of pathologic stageⅠlung adenocarcinomas were significantly different in different groups of gender,tumor size, density, tumor differentiation grade and T staging, respectively ( P<0.05 for all) . Patients with a larger tumor size, a higher proportion of solid component, poorer grade of tumor differentiation had a higher SUVmax. The T1b group had a higher SUVmax than T1a and T2a groups. The male group had a higher SUVmax than the female group. The SUVmax was positively correlated with the size of the adenocarcinomas ( P<0. 01 ) , and was negatively correlated with both the density and tumor differentiation grade (P<0.01). But there was no correlation between SUVmax and the T stage (P>0.05). The patients with an SUVmax of<3.0 had a much better PFS (75.1±3.0 month)than those with an SUVmax of ≥3.0 (52.7±5.9 month)(P<0.01). The tumor with a poorer differentiation grade was associated with reduced PFS (45.7±5.4 months) compared with those with well differentiated tumor (76.7±4.2 month)(P<0.05) . The PFS showed no statistically significant differences in different gender, age, smoking history, tumor size, density and T staging groups (P>0.05). Conclusions 18F?FDG uptake is correlated with the tumor size, density, and differentiation grade, and has a prognostic value for predicting the PFS in the patients with pathologic stageⅠ lung?adenocarcinoma. Patients with an SUVmax of <3.0 have a much better PFS than those with an SUVmax of ≥3.0.

Objective To analyze the 18 F?FDG uptake features and the correlation between 18 F?FDG uptake and the prognosis in patients with pathologic stageⅠlung adenocarcinoma. Methods One hundred and seventeen patients with stageⅠlung adenocarcinoma proved by surgery, who underwent a preoperative 18 F?FDG PET?CT, were studied retrospectively. The tumors′ SUVmax in different groups of clinicopathologic factors were compared. The correlations between the SUVmax and clinicopathologic factors were analyzed using Spearman rank correlation. The ROC was plotted to estimate the most discriminative cut?off point for SUVmax in predicting the recurrence or progression of tumor. The progression?free survival ( PFS) in different clinicopathologic groups were estimated using the Kaplan?Meier method and Log?rank test. Results The SUVmax of pathologic stageⅠlung adenocarcinomas were significantly different in different groups of gender,tumor size, density, tumor differentiation grade and T staging, respectively ( P<0.05 for all) . Patients with a larger tumor size, a higher proportion of solid component, poorer grade of tumor differentiation had a higher SUVmax. The T1b group had a higher SUVmax than T1a and T2a groups. The male group had a higher SUVmax than the female group. The SUVmax was positively correlated with the size of the adenocarcinomas ( P<0. 01 ) , and was negatively correlated with both the density and tumor differentiation grade (P<0.01). But there was no correlation between SUVmax and the T stage (P>0.05). The patients with an SUVmax of<3.0 had a much better PFS (75.1±3.0 month)than those with an SUVmax of ≥3.0 (52.7±5.9 month)(P<0.01). The tumor with a poorer differentiation grade was associated with reduced PFS (45.7±5.4 months) compared with those with well differentiated tumor (76.7±4.2 month)(P<0.05) . The PFS showed no statistically significant differences in different gender, age, smoking history, tumor size, density and T staging groups (P>0.05). Conclusions 18F?FDG uptake is correlated with the tumor size, density, and differentiation grade, and has a prognostic value for predicting the PFS in the patients with pathologic stageⅠ lung?adenocarcinoma. Patients with an SUVmax of <3.0 have a much better PFS than those with an SUVmax of ≥3.0.