Hepatitis B or C viral infection and risk of pancreatic cancer: A meta-analysis of observational studies

AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found. CONCLUSION: Chronic HBV and HCV infection increases pancreatic cancer risk. Our findings underscore the need for more studies to confirm this potential relationship.

Association of Lifestyle Factors and Sperm Motility in Adults from an Ethnic Minority Region of Southwest China

Objectives: To understand sperm motility in adults and its association with lifestyle in an ethnic minority area in Southwest China. Methods: A hospital-based cross-sectional study to assess sperm motility in male adults was conducted at the Reproductive Health Center from January 2018 to May 2019. The data was collected with a questionnaire and semen quality was analyzed with Computer-Aided Sperm Analysis system (CASA). Analysis of covariance (ANCOVA) was used to measure the relationship between lifestyle factors and sperm motility. Results: A total of 349 people were recruited. Dietary celery intake was significantly related to the increase of sperm progressive motility and total motility (β = 7.00, 95% CI: 1.59, 12.42 and β = 7.26, 95% CI: 1.45, 13.07, respectively). Cola consumption was associated with increased sperm progressive motility (β = 9.71, 95% CI: 1.46, 17.96). Frequent use of plastic bags for meat food storage (β = -5.56, 95% CI: -10.61, -0.51), industry work (β = -5.64, 95% CI: -11.21, -0.07), organic disease (β = -6.14, 95% CI: -11.00, -1.28) and sedentary lifestyle (β = -5.92, 95% CI: -10.66, -1.17 for 3-5 h/d and β = -6.04, 95% CI: -11.60, -0.47 for ≥5 h/d, respectively) were related with the decreased sperm progressive motility. Meanwhile, using plastic bags for meat food storage (β = -6.37, 95% CI: -11.79, -0.95), industry work (β = -7.96, 95% CI: -13.94, -1.98) and sedentary lifestyle (β = -5.51, 95% CI: -10.60, -0.42 for 3-5 h/d and β = -6.03, 95% CI: -12.01, -0.06 for ≥5 h/d, respectively) were also risk factors for total motility. Conclusions: Some modifiable lifestyle factors such as job title, cola consumption, dietary celery intake, plastic bags for meat food storage, and sedentary hours were linked to male sperm motility, indicating that changing these lifestyles may improve it.

Study on the mechanism of effect of Daodi Tongguan Decoction on rats with premature ovarian failure

Objective:To investigate the mechanism of the effect of Daodi Tongguan Decoction on ovarian function in rats with premature ovarian failure.Methods:Forty SD female rats with regular estrous cycle were randomly divided into the blank group,the model group,the positive group(Bujiale 0.099 mg/kg),the Daodigitongguan decoction high-dose group(1.4 g/100 g)and the Daodigitongguan decoction medium-dose group(0.7 g/100 g).The model group,positive group,Daodi Tongguan Decoction high-dose group and Daodi Tongguan decoction medium-dose group were given Tripterygium wilfordii polyglycoside tablets suspension(50 mg/kg)by continuous gavage for 14 days to establish a rat model of premature ovarian failure.After the modeling,each group was given the corresponding intervention agent for 28 consecutive days.After the intervention,serum and ovarian tissue were collected from rats in each group.The morphological structure of rat ovarian tissue was observed after HE staining.Serum AMH level was determined by ELISA.The expressions of Bcl-2,Bax and VEGF in ovarian tissue were detected by IHC.The apoptosis of granulosa cells in ovary was observed by TUNEL.Results:Compared to the normal group,the growth follicles in the model group were reduced and the atretic follicles were increased.Serum AMH level was significantly decreased(P<0.01).The expression of Bax protein in ovarian tissue was increased(P<0.01).The protein expressions of Bcl-2 and VEGF were decreased(P<0.01,P<0.05),and the apoptosis rate of follicular granulosa cells in ovarian tissue was increased(P<0.01).Compared to the molding group,the serum AMH level in the TCM dose groups was increased to varying degrees,and the change of the AMH in high-dose group was the most significant(P<0.05).The expression of Bax protein in ovarian tissue decreased(P<0.05),while the expression of Bcl-2 and VEGF protein increased(P<0.05,P<0.05).The apoptosis rate of follicular granulosa cells in ovarian tissue was decreased in the high dose group(P<0.05).Conclusion:Daodi Tongguan Decoction can improve the histological morphology of ovary and relieve ovarian injury,and its mechanism may be related to improving the sex hormone level of POF model rats,reducing the expression level of Bax protein in ovarian tissue,increasing the expression level of Bcl-2 and VEGF protein in ovarian tissue,and reducing the apoptosis rate of follicular granulosa cells in ovarian tissue.

Newborn screening with targeted sequencing:a multicenter investigation and a pilot clinical study in China

Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.

Rare inherited missense variants of POGZ associate with autism risk and disrupt neuronal development

Excess de novo likely gene-disruptive and missense variants within dozens of genes have been identified in autism spectrum disorder(ASD)and other neurodevelopmental disorders.However,many rare inherited missense variants of these high-risk genes have not been thoroughly evaluated.In this study,we analyzed the rare missense variant burden of POGZ in a large cohort of ASD patients from the Autism Clinical and Genetic Resources in China(ACGC)and further dissected the functional effect of diseaseassociated missense variants on neuronal development.Our results showed a significant burden of rare missense variants in ASD patients compared to the control population(P=4.6×10-5,OR=3.96),and missense variants in ASD patients showed more severe predicted functional outcomes than those in controls.Furthermore,by leveraging published large-scale sequencing data of neurodevelopmental disorders(NDDs)and sporadic case reports,we identified 8 de novo missense variants of POGZ in NDD patients.Functional analysis revealed that two inherited,but not de novo,missense variants influenced the cellular localization of POGZ and failed to rescue the defects in neurite and dendritic spine development caused by Pogz knockdown in cultured mouse primary cortical neurons.Significantly,L1CAM,an autism candidate risk gene,is differentially expressed in POGZ deficient cell lines.Reduced expression of L1cam was able to partially rescue the neurite length defects caused by Pogz knockdown.Our study showed the important roles of rare inherited missense variants of POGZ in ASD risk and neuronal development and identified the potential downstream targets of POGZ,which are important for further molecular mechanism studies.

Effects of changing the control ovarian stimulation protocol in patients without a transplantable embryo in the previous in vitro fertilization/intracytoplasmic sperm injection cycle

Objective:Some patients fail to obtain an embryo for transplantation during previousin vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI)cycles,and require multiple reproductive treatments.This study aimed to evaluate whether changing the control ovarian stimulation(COS)protocol during the subsequent stimulation cycle could improve laboratory and clinical outcomes in these patients.Methods:Patients without a transplantable embryo(TE)in the previous IVF/ICSI cycles were recruited during their second cycles.They were classified into two groups according to their first cycle protocol:Group A,patients treated with a gonadotropinreleasing hormone agonist(GnRH-a),and Group B,patients treated with a gonadotropin-releasing hormone antagonist(GnRH-ant).The study group included patients whose stimulation protocols were changed,whereas the control group consisted of patients who used the same stimulation protocol in the second cycle.We then compared the numbers of oocytes collected(OC)and TE,the incidence of non-TE,the pregnancy rate(PR),and the live birth rate(LBR).Results:In Group A,the numbers of OC and TE were significantly lower(6.0±4.7vs.9.4±6.4,2.3±2.2vs.4.5±3.8,P<0.05)in the study group compared with those in the control group.In Group B,the numbers of OC and TE were higher(7.0±5.5vs.4.0±4.3,3.5±3.4vs.1.8±2.1,P<0.05)in the study group.There was a significant increase in the incidence of non-TE(adjusted odds ratio(AOR)=2.12,95%CI:1.04–4.69)of the study group in Group A but not in Group B.No significant differences in the PR or LBR were found between the study and control groups in either Group A or B.Conclusion:Changing the COS protocol from GnRH-ant to GnRH-a or continuing the GnRH-a protocol can improve laboratory outcomes in patients with no TE in the previous IVF/ICSI cycle.