[Research progress on the effects of exposure to major persistent organic pollutants during pregnancy on the functional development of nervous system in children].

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.

[The effect of unexpected follicular development in artificial cycles on the clinical outcomes in frozen thawed embryo transfer based on propensity score matching].

Objective: To study the effect of unexpected follicular development in artificial cycles on the clinical outcomes in frozen thawed embryo transfer based on propensity score matching(PSM). Methods: The retrospective cohort study analyzed the clinical data of 7 064 cycles (5 716 patients) of artificial cycle frozen-thawed embryo transfer (AC-FET) in the Reproduction Center of the Third Affiliated Hospital of Zhengzhou University from January 1, 2016 to December 31, 2020. The clinical data were divided into three groups according to the degree of follicular development in AC-FET: no follicular growth group (group A, 6 349 cycles), small follicular growth group (group B, 248 cycles), and large follicular growth group (group C, 467 cycles). Differences in clinical outcomes between the small follicle growth group (Group B) and the large follicle growth group (Group C) were compared with the no follicle growth group (Group A) after PSM and logistic regression to adjust for confounding factors at baseline. A binary logistic regression model was used to analyze the factors related to the unanticipated follicular development in AC-FET. Results: Age [M(Q1,Q3)] was [31.0 (28.0, 36.0)] years in Group A, [34.5 (30.0, 40.0)] years in Group B, and [36.0 (31.0, 41.0)] years in Group C. After adjusting for confounders, the differences between Groups A and B in clinical pregnancy rate (P=0.169), live birth rate (P=0.318), early abortion rate (P=0.470), and miscarriage rate (P=0.783) were not statistically significant. The differences in clinical pregnancy rate (P=0.743), live birth rate (P=0.486) and miscarriage rate (P=0.080) between Groups A and C were not statistically significant, while early miscarriage rate (P=0.034) differences were statistically significant. The age, BMI, basal AFC, AMH and starting dose of estrogen were correlates of the emergence of non-expected small follicles in Groups B and A. The adjusted OR (AOR) values (95%CI) were 1.03 (1.01-1.06), 0.93 (0.90-0.98), 0.97 (0.95-0.99), 0.96 (0.95-0.97), and 0.59 (0.45-0.77), all P<0.05. Age, basal AFC, AMH and starting dose of estrogen were the associated factors of the appearance of non-expected large follicles in Groups C and A. The AOR values (95%CI) were 1.03 (1.01-1.05), 0.93 (0.91-0.95), 0.96 (0.95-0.97), and 0.52 (0.42-0.64), all P<0.05. Conclusions: In AC-FET, the clinical outcome of small follicular growth is similar to that of unfollicular growth; Compared with the growth without follicles, the growth and development of large follicles can reduce the early abortion rate; Patients with older age, less AFC, lower AMH, and lower initial dose of estrogen could be more likely to have unanticipated follicular development during endometrial preparation.

[Effect of preimplantation genetic testing for aneuploidies on pregnancy outcome in patients with unexplained recurrent spontaneous abortion].

Objective: To investigate the effect of preimplantation genetic testing for aneuploidies (PGT-A) on pregnancy outcome and perinatal outcome of single live birth in patients with unexplained recurrent spontaneous abortion (URSA). Methods: The clinical data of 351 cycles of the first transfer of a blastocyst through whole embryo freezing in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from 2019 to 2021 were retrospectively analyzed. According to whether PGT-A was performed before the transfer, the patients were divided into two groups: the PGT-A group (160 cycles) and the control group (191 cycles) were treated with in vitro fertilization/intracytoplasmic sperm microinjection (IVF/ICSI). To adjust for confounding factors, propensity score matching (PSM) was carried out in a 1∶1 ratio between the two groups of patients. After matching, 98 patients in the PGT-A group and 98 patients in the control group were compared for pregnancy outcome and perinatal outcome of singleton live births. Results: Before PSM, the female age in the PGT-A group was (33.6±4.0) years, lower than that in the control group (34.5±4.5) years (P=0.049). Male age in the PGT-A group was (33.6±4.1) years, lower than that in the control group (35.3±5.1) years (P<0.001). There were statistically significant differences between the two groups in infertility factors, female body mass index (BMI), years of infertility, number of spontaneous abortions, basal follicle stimulating hormone (FSH), endometrial thickness on the day of transfer and the percentage of high-quality blastocysts (all P values<0.05); After PSM, there was a statistically significant difference in fertilization methods and infertility factors between the two groups (P<0.05), while other differences were not statistically significant (all P values>0.05); There were statistically significant differences between the two groups in implant rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], clinical pregnancy rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], and live birth rate [42.9% (42 cycles) vs. 28.6% (28 cycles), P=0.037]. There was no statistically significant difference in perinatal outcomes between the PGT-A group and the control group in obtaining single birth live births (P>0.05). Conclusion: Compared with conventional IVF/ICSI assisted pregnancy, PGT-A assisted pregnancy significantly improves implantation rate, clinical pregnancy rate, and live birth rate in URSA patients. PGT-A improves the pregnancy outcomes in URSA patients but not perinatal outcomes in patients with singleton live births.

[Analysis for the breast cancer screening among urban population in Hebei province, 2018-2019].

From 2018 to 2019, 3 453 cases of high-risk population were screened by the Cancer Screening Program in Urban China (CanSPUC) in Hebei Province, with the age of (53.94±8.00). 147 and 686 cases of breast cancer positive and suspicious positive patients were found, with the positive rate and suspicious positive rate of 4.26% and 19.87% respectively. The suspicious positive rate of 45-49 years old age group was the highest (28.32%), and the positive rate of over 70 years old age group was the highest (7.32%). The positive detection rate of mammography combined with ultrasound was 5.16%, which was higher than that of ultrasound alone (2.46%) (χ²=30.28,P<0.001) or mammography alone (3.06%) (χ²=14.56,P<0.001).

[The distribution of peripheral anterior synechiae in patients with primary angle-closure glaucoma].

Objective: To describe the distribution and characteristics of peripheral anterior synechiae (PAS) in patients with primary angle-closure glaucoma (PACG). Methods: Retrospective case study. A total of 285 PACG patients (406 eyes) diagnosed in the Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University from January 2017 to August 2019 were included. They were 102 males and 183 females, with a median age of 67 years old (range, 21 to 95 years old). The PAS range was detected by gonioscopy examination, and the frequency distribution of PAS at 12 clock points was counted by clockwise. The PAS distribution at the middle point of PAS with continuous distribution and ≤6 clock points was assessed. Results: In all cases, PAS of the right eye was concentrated at 11:00 to 4:00 regions [range, 62.0% (129/208) to 78.8% (164/208)]. PAS of the left eye was concentrated at 7:00 to 1:00 regions [range, 50.0% (99/198) to 75.8% (150/198)]. When the PAS range of the atrial angle was ≤6 clock regions, it was mainly at 12:00 to 3:00 [range, 58.3% (74/127) to 67.7% (86/127)] in the right eye and at 10:00 to 12:00 [range, 54.8% (68/124) to 66.1% (82/124)] in the left eye. Among 121 cases (242 eyes) with both eyes involved, the PAS region was at 11:00 to 5:00 [range, 52.1% (63/121) to 79.3% (96/121)] in the right eye and at 8:00 to 1:00 [range, 50.4% (61/121) to 76.9% (93/121)] in the left eye. When the PAS range of the atrial angle was ≤6 clock regions, it was mainly at 12:00 to 4:00 [range, 53.2% (41/77) to 71.4% (55/77)] in the right eye and at 10:00 to 12:00 [range, 50.6% (39/77) to 64.9% (50/77)] in the left eye. In all cases, there were 171 cases of right eyes and 175 cases of left eyes with continuous angle PAS. The central PAS clock position of the right eye was mainly at 11:00 to 3:00 [range, 15.2% (26/171) to 24.0% (41/171)], and that of the left eye was mainly at 8:00 to 12:00 [range, 15.4% (27/175) to 20.6% (36/175)]. Among cases with both eyes involved, there were 98 cases of right eyes and 104 cases of left eyes with continuous angle PAS. The clock distribution of the middle position of the right eye angle PAS was concentrated at 11:00 to 3:00 [range, 17.3% (17/98) to 26.5% (26/98)], and that of the left eye was concentrated at 8:00 to 12:00 [range, 13.5% (14/104) to 20.2% (21/104)]. Conclusions: The PAS of PACG patients is mainly located in the upper and nasal sides, and the closer to the temporal side, the smaller the PAS frequency, showing a gradual downward trend. The PAS distribution of binocular angles is of obvious mirror symmetry. (Chin J Ophthalmol, 2021, 57: 666-671).

[Identification of Synthetic Cannabinoid New Psychoactive Substances 4F-MDMB-BUTINACA and MDMB-4en-PINACA].

ABSTRACT: Objective To establish a method that combines a series of techniques including Fourier transform infrared spectrum （FTIR）, gas chromatography-mass spectrometry （GC-MS）, high resolution mass spectrometry and nuclear magnetic resonance spectroscopy （NMR） for identification of unknown substances. Methods The unknown samples （off-white powder and yellow crystal） seized in the actual cases were detected by FTIR, GC-MS （methanol as solvent）, high resolution mass spectrometry （methanol as solvent） and NMR （deuterated methanol as solvent）. Results The mass spectrum characteristic ions m/z of the main components in the samples measured by GC-MS were 219 （base peak）, 363, 307, 304, 275, 145, 131 and 213 （base peak）, 357, 301, 298, 269, 185, 171, 145 and 131, respectively. The accurate mass numbers [M+H]+ measured by high resolution mass spectrometry were 364.203 61 and 358.212 34, respectively. The unknown samples were identified as synthetic cannabinoid new psychoactive substances 4F-MDMB-BUTINACA and MDMB-4en-PINACA after data consultation and database retrieval and comparison, combined with infrared analysis and mass spectrometry data analysis, and their structures were confirmed by 1H-NMR. Conclusion The established multi-technology joint identification method can be used to identify 4F-MDMB-BUTINACA and MDMB-4en-PINACA in unknown samples. This method is fast, convenient, accurate, reliable and practical, and can provide reference for the identification of cases involving such substances in the future.

Identification of the New Psychoactive Substance Dibutylone.

ABSTRACT: Objective To establish a method to identify unknown samples based on combined use of gas chromatography-mass spectrometry （GC-MS）, high resolution mass spectrometry （HRMS） and nuclear magnetic resonance spectrum （NMR） technique. Methods The unknown samples were dissolved in methanol solution containing internal standard SKF525A and detected by GC-MS and HRMS. The mixed samples were separated and purified by silica gel column chromatography, and then dissolved in methanol-d4 solution for structural analysis of 1H nuclear magnetic resonance spectroscopy （1H NMR）. Results The characteristic fragment ions （m/z） were 86.1 （base peak）, 71.2, 121.1, and 149.0, and the accurate mass number of molecular ion peak was measured by HRMS to be 236.128 89. By combined use of data analysis and database comparison, a new psychoactive substance of the cathinone class, Dibutylone, was detected in the sample, and the sample also contained a small amount of caffeine. The sample was purified, then identified using 1H NMR, and was further confirmed to be Dibutylone. In addition, the GC-MS retention time and characteristic fragment ions of the main components of the sample were consistent with those of Dibutylone reference material. Conclusion The method established in this study can be used for the identification of Dibutylone in mixed samples.

Long noncoding RNA LINC00313 modulates papillary thyroid cancer tumorigenesis via sponging miR-4429.

Mounting evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis. LncRNA LINC00313 has been found to be up-regulated and associated with poor prognosis in lung cancer. However, the potential role and clinical value of LINC00313 in human papillary thyroid cancer (PTC) remain elusive and therefore require examination. The aim of this study is to investigate the role of LINC00313 in papillary thyroid cancer (PTC). We found its expression was significantly up-regulated in PTC tissues and cell lines and that this up-regulation correlated with poor prognosis. In vitro experiments indicated that down-regulation of LINC00313 inhibited proliferation and the migratory and colony-forming abilities of PTC cells. Moreover, silencing LINC00313 induced cell cycle arrest and apoptosis in the PTC cells. In addition, mechanism studies showed that LINC00313 down-regulates miR-4429 expression, and that miR-4429 over-expression can abrogate the oncogenic role of LINC00313 in PTC cells. In summary, our data revealed that LINC00313 acts as an oncogene in PTC via sponging miR-4429, and this suggests that LINC00313 may be successfully applied as a therapeutic target in PTC.

[Prospective association between early adiposity rebound and adolescent development in girls].

Objective: To determine possible relations between early adiposity rebound and adolescent development. Methods: Prospective children cohort from 2 kindergartens selected through clustering convenience sampling method in Anhui Province was established since Sep. 2010. Participants were classified as Cohort 1 (2010), Cohort 2 (2011) and Cohort 3 (2012) according to the recruiting year. Till Sep. 2015, a toal of 802 girls were included in this study, and received follow-up till primary school. During kindergarten period, physical examination was carried out every 3 months, 8 times in total. In primary school, physical examination was carried out annually; till Sep.2015, the cohort 1, 2, 3 took physical examination for 12, 11, 10 times, respectively. Information on household economic status and child physical activity was acquired through parents questionnaire survey, and breast development were assessed through visual inspection and palpation. Adiposity rebound was determined according to Rolland-Cachera's method for each girl. Differences between early adiposity rebound and normal adiposity rebound groups were compared by using t test and χ(2) test. Multivariate regression analysis was applied to explore the association between early adiposity rebound and breast development. Results: The average age of participants was (8.90±0.87) years old and the BMI was (17.48±2.70) kg/m(2). The average age at adiposity rebound was (6.16±0.90) years old and the BMI was (15.33±1.82) kg/m(2). Premature breast development was found significantly higher in girls in early adiposity rebound group (27.8%, 54/802) than it in normal adiposity rebound group (13.7%) (P<0.001). After current adiposity, age, household economic status, childhood physical activity adjusted, the OR of premature beast development in early adiposity rebound group was 2.41(95%CI: 1.41-4.12). Conclusion: Early adiposity rebound increases the risk of premature puberty in girls.

[Association between hair cortisol concentration and overweight and obesity in 6-9 years old childhood].

Objective: To determine the possible relations between hair cortisol concentration (HCC) as a biomarker of chronic stress and childhood overweight and obesity. Methods: Children from grade 1 to 3 from 2 primary schools in Bengbu were invited to participate in the study; and those who suffer from mental disorders, endocrine diseases and those who took hormone drugs were excluded. Parental questionnaire was implemented to collect information on physical activity, screen time, sleep duration, sugar-beverage consumption, as well as socio-economic status. Height and weight were examined. Eligible hair samples from 1 263 children (598 boys and 665 girls) were obtained, and the cortisol content was determined. Multivariate logistic regression model analysis was recruited to examine the association between HCC quartiles and overweight and obesity among boys and girls, respectively. Results: HCC in P(50) (P(25)-P(75)) among girls and boys was separately 11.86 (10.57-13.15) and 11.71 (10.54-13.09) µg/kg (Z=-0.886, P=0.376); HCC in P(50) (P(25)-P(75)) among non-overweight, overweight and obesity boys was separately 11.62 (10.45-12.82), 12.24 (10.88-13.55) and 12.30 (10.99-13.53) µg/kg (χ(2)=8.24, P=0.016); HCC in P(50) (P(25)-P(75)) among non-overweight, overweight and obesity girls was separately 11.35 (10.06-12.62), 12.07 (11.04-13.21) and 12.59 (11.12-13.63) µg/kg (χ(2)=36.16, P<0.001). After age, physical activity, screen time, sleep duration, sugared beverages and socio-economic status adjusted, compared with HCC in Q1 level, girls whose HCC in Q2, Q3 Q4 level had higher rates in overweight, with OR (95%CI) at 1.10 (1.04-3.32), 2.59 (1.51-4.45) and 3.16 (1.79-5.57), respectively. Girls with HCC in Q3 and Q4 level had higher rates in obesity, with OR (95%CI) at 2.22 (1.16-4.26) and 5.62 (3.04-10.41). Among boys, highest quartiles in HCC was risk factor for overweight, OR (95%CI) was 2.14 (1.18-3.90). Conclusion: Hair cortisol had a significant relation with overweight and obesity in 6-9 years old childhood especially among girls.

Prognostic value of miR-141 downregulation in gastric cancer.

Previous research has shown that microRNA-141 (miR-141) expression levels are associated with survival in several types of cancer. In the present study, we investigated the clinical significance and prognostic value of miR-141 in gastric cancer. Paired tissue specimens (tumor and adjacent normal mucosa) from 95 patients with gastric cancer were obtained at the Department of General Surgery, Xiangya Hospital, Central South University from March 2009 to February 2014. The levels of miR-141 in cancerous and corresponding non-cancerous tissues were detected by quantitative reverse transcription-polymerase chain reaction. Associations between clinicopathological parameters and miR-141 expression were evaluated using chi-square tests. Overall survival was calculated and survival curves were plotted using the Kaplan-Meier method; differences between groups were compared using log-rank tests. Compared to the matched normal gastric mucosa, gastric cancer tissues had significantly lower miR-141 expression levels (P < 0.001). This decreased miR-141 expression was significantly associated with tumor differentiation (P = 0.044), positive lymph node metastasis (P = 0.010), distant metastasis (P < 0.001), and advanced tumor-node-metastasis (TNM) stage (P < 0.001). Furthermore, a significant relationship was found between miR-141 expression and overall survival (P = 0.012, log-rank test). Cox regression analysis revealed that lymph node metastasis (P = 0.003), distant metastasis (P = 0.001), TNM stage (P < 0.001), and miR- 141 expression (P = 0.007) were independent prognostic factors in patients with gastric cancer. Our data provide evidence that the downregulation of miR-141 may contribute to the aggressive progression and poor prognosis of human gastric cancer.

Genetic analysis of STR markers on chromosome 21 in a Han population from southeast China.

Short tandem repeats (STRs) are highly polymorphic sequences and have been extensively used as genetic markers in mapping studies, disease diagnosis, and human identity testing. In this study, 11 STR markers on chromosome 21, including D21S1432, D21S11, D21S1246, D21S1412, D21S1437, D21S1442, D21S2039, D21S1270, D21S1435, D21S1409, and D21S1446, were analyzed in 740 unrelated Han individuals from southeast China. A total of 132 alleles, ranging from 7-21 for each locus, were named according to the guidelines of the International Society for Forensic Haemogenetics. The distributions of allelic frequencies for the 11 STRs and population genetic parameters were determined. All 11 STR markers showed high polymorphism and heterogeneity in the southeast Han population, with polymorphism information content of 0.61-0.87, heterogeneity of 64.5-86.1%, and power of discrimination of 0.835-0.973. Among the 11 STR markers, D21S1412, D21S1270, D21S11, and D21S1442 showed relatively higher heterogeneity. Their combination was relatively informative and was used in a quantitative fluorescence-polymerase chain reaction assay to diagnose Down syndrome (trisomy 21) in a southeast Chinese Han population. The genetic information and population data for these 11 STRs may be used not only in quantitative fluorescence-polymerase chain reaction assays but also in forensic studies and other genetic tests.

Cohn process influences the functional anticoagulant activity of human protein C.

Cohn fraction IV (CFIV) is a byproduct of a plasma fractionation process known as the Cohn process. It is an inexpensive source of protein C, retaining about 90% of protein C (PC) in human plasma. We investigated whether PC is affected during the Cohn process and evaluated correlations among coagulant activity, amidolytic activity and PC antigen during the Cohn process. CFIV was redissolved with citrate-buffered saline for 5 h at 4°C, and then centrifuged at 3500 g for 40 min at 4°C. Functional anticoagulant activity was measured with a one-stage coagulation method based on activated partial thromboplastin time. The functional amidolytic activity of PC was determined using chromogenic substrate assay, and measurement of PC antigen was performed by ELISA. In CFIV, anticoagulant activity declined significantly, with a loss of >80%, while amidolytic activity was not significantly altered, compared to PC antigen. Prior to the Cohn process, high-rank correlations were observed in cryosupernatant, with rs = 0.921 for anticoagulant and amidolytic activities (P = 0.009), 0.896 for anticoagulant activity and antigen (P = 0.014) and 0.832 for amidolytic activity and antigen (P = 0.031). After the Cohn process in CFIV, there was also a high correlation between amidolytic activity and antigen (rs = 0.782, P = 0.038). There were no significant correlations between anticoagulant activity and antigen (rs = 0.223, P = 0.653), or anticoagulant and amidolytic activity (rs = 0.236, P = 0.675). We conclude that the Cohn process significantly influences the anticoagulant activity of PC. Compared to the antigen, PC lost greater than 80% of its anticoagulant activity, but retained its amidolytic activity, during the Cohn process.

Polymorphisms of the vitamin D receptor gene and the risk of inflammatory bowel disease: a meta-analysis.

The gene encoding vitamin D receptor (VDR) is recognized as a promising candidate for indicating the development of inflammatory bowel disease (IBD). Four genetic polymorphisms (ApaI, BsmI, FokI, TaqI) in VDR have been widely evaluated to determine their association with IBD, and the results of these evaluations are often inconsistent. Therefore, we conducted a meta-analysis to shed some light on this issue and explored the sources of the heterogeneity between studies. We identified six articles for ApaI (cases/controls: 1902/1468), eight for TaqI (3053/2145), and five each for BsmI (1512/1616) and FokI (2315/1676). Data were analyzed under the random-effects model, and heterogeneity was explored by subgroup analyses. Overall, except for TaqI in allelic comparison [odds ratio (OR) = 0.90, 95% confidence interval (CI): 0.83-0.98], ApaI, BsmI, and FokI polymorphisms showed no significant associations with IBD across different genetic models of inheritance. However, subgroup analyses indicated significance for the association of ApaI with Crohn's disease (CD) risk (AA versus aa: OR = 1.40; 95%CI = 1.05-1.88), for BsmI in East Asians (BB plus Bb versus bb: OR = 1.77, 95%CI = 1.14-2.74), for TaqI in Caucasians (TT plus Tt versus tt: OR = 0.79, 95%CI = 0.63- 1.00), and with ulcerative colitis (UC) risk (T versus t: OR = 0.89, 95%CI = 0.80-0.99). There was a low probability of publication bias for all studied polymorphisms. Pooling previous individual studies on IBD, our findings demonstrated that the ApaI polymorphism may increase the risk of CD, whereas the TaqI polymorphism may decrease the risk of UC, especially in Caucasians. Moreover, this study leaves open the question of divergent genetic profiles across different ethnic groups.

A case-control study indicates that the TRIB1 gene is associated with pancreatic cancer.

Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues that form the pancreas. To investigate whether the tribbles homolog 1 (Drosophila) gene (TRIB1) is associated with pancreatic cancer in the Chinese Han population, we conducted this case-control study and genotyped 3 single nucleotide polymorphisms (rs2980879, rs2980874, and rs2235108) of the TRIB1 gene in 182 patients and 359 normal controls of Chinese Han origin and analyzed their association. The results showed that the rs2980879 polymorphism was associated with pancreatic cancer [allele: P = 0.023434, genotype: P = 0.03005; odds ratio (OR) and 95% confidence interval (CI) = 0.727788 (0.552664-0.958404)], whereas the rs2980874 polymorphism had no association with pancreatic cancer [allele: P = 0.749885, genotype: P = 0.699533; OR and 95%CI = 1.041981 (0.809196-1.341734)], and the rs2235108 polymorphism was not associated with the disease [allele: P = 0.629475, genotype: P = 0.547534, OR and 95%CI = 1.128290 (0.690829-1.842770)]. Haplotype analyses and linkage disequilibrium tests were also conducted, and the results showed that these 3 loci are not in the same block. In conclusion, our study indicated that the TRIB1 gene is associated with pancreatic cancer. More studies with larger samples are needed in order to support this finding.

Pan-cancer analysis of heterogeneity of tumor mutational burden and genomic mutation under treatment pressure.

BACKGROUND: High tumor mutational burden (TMB) is one of the widely researched predictive biomarkers of immune checkpoint inhibitors and has been shown to be closely related with response to immunotherapy in multiple cancer types. However, for patients who have failed conventional therapy and are about to undergo immunotherapy, there is no consensus recommendation on the timing of tumor sampling for TMB analysis, and the effects of different therapies on TMB have not been clarified. This retrospective observational study aimed to investigate the heterogeneity of TMB and genomic mutation under the treatment pressure. PATIENTS AND METHODS: We retrospectively collected the available genomic and therapeutic information from 8051 samples across 15 tumor types (>50 samples/tumor) found in 30 published studies and investigated the distribution and heterogeneity of TMB under treatment across diverse cohorts. RESULTS: This integrated analysis has shown anticancer treatments increased TMB. Significant effects of treatment on TMB were more frequently observed in tumor types with lower treatment-naïve TMB, including breast, prostate, and pediatric cancers. For different cancer therapies, chemotherapy was prone to be correlated with an increased TMB in most cancer types. Meanwhile, the fraction of the TMB-high category of breast, prostate, and bladder cancers and glioma increased significantly after chemotherapy. Several actionable genes including ERS1 and NF1 in breast cancer, as well as some prognostic markers including TERT in bladder cancer and IDH1 in glioma, were significantly changed in post-chemotherapy tumors compared to treatment-naïve tumors. CONCLUSION: Our study reveals the heterogeneity of TMB under treatment across diverse cancer types and provides evidences that chemotherapy was associated with increases in TMB as well as the fraction of TMB-high category, suggesting that resampling tumor tissues for calculating post-chemotherapy TMB could be a better option for predicting the response to immunotherapy, especially for tumors with initially low TMB.

Lack of association between the interleukin 6 gene -174G>C polymorphism and colorectal cancer: evidence from a meta-analysis.

Interleukin 6 (IL6) is a pleiotropic cytokine involved in physiological processes and in a variety of human malignancies. It is thus a logical candidate for being a causative factor underlying colorectal cancer (CRC). The association between the IL6 -174G>C polymorphism and CRC has been widely evaluated; yet, there is a lack of agreement between studies on the role of this polymorphism in CRC. We performed a meta-analysis to evaluate this association signal. Articles published before May 10, 2012 were included in the meta-analysis. A total of 11 populations incorporating 6481 cases and 7935 controls were included in our analysis. A random-effect model was applied irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. Overall, the association of the -174G>C polymorphism with CRC was not significant in an allelic comparison model [odds ratio (OR) = 0.99; 95% confidence interval (95%CI) = 0.90-1.09; P = 0.827], a homozygote model (OR = 0.98; 95%CI = 0.83-1.15; P = 0.805), a dominant model (OR = 0.99; 95%CI = 0.87-1.13; P = 0.906), or a recessive model (OR = 0.97; 95%CI = 0.88-1.08; P = 0.610). Furthermore, the analyses of subgroups created based on common study design, genotyping methods, and ethnicity failed to find a significant association of this polymorphism with CRC. Therefore, our results collectively suggest that the IL6 -174G>C polymorphism might not be a potential candidate for CRC risk.

Meta-analysis demonstrates lack of an association of microsomal epoxide hydrolase 1 polymorphisms with esophageal cancer risk.

Epoxide hydrolases metabolize exogenous chemicals, including carcinogens such as polycyclic aromatic hydrocarbons. The relationship between microsomal epoxide hydrolase 1 (EPHX1) polymorphisms and esophageal cancer risk has been investigated in various ethnic populations, but the results have been contradictory. We investigated the association of EPHX1 Tyr113His and His139Arg polymorphisms with esophageal cancer via a comprehensive meta-analysis. Publications before August 20, 2012 were included. Eight studies concerning Tyr113His polymorphism associated with 1158 esophageal cancer cases and 1868 controls were identified; 7 studies concerning association of His139Arg with 901 esophageal cancer cases and 1615 controls were also included. A random-effect model was applied, irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. No significant association was found in either the allele or genotype models for Tyr113His or His139Arg polymorphism with risk for esophageal cancer. Lack of association was also identified in stratified analyses by ethnicity. No publication bias was observed. We conclude that current evidence does not demonstrate association of EPHX1 Tyr113His or His139Arg polymorphisms with risk for development of esophageal cancer.

Quantifying the contributions of natural and anthropogenic dust sources in Shanxi Province, northern China.

Dust storms have direct or indirect impacts on climate change and human health. Identifying and quantifying natural/anthropogenic dust sources can facilitate effective prevention and control of dust events. Based on surface real-time PM10 monitoring data, satellite remote sensing and the HYSPLIT model, this study determined the specific timing, coverage and sources of dust events in Shanxi Province, Northern China. Thus, a composite fingerprinting technique was established to quantify potential dust sources and dust contributions of single dust events. The dust oxidation model was validated, indicating that the composite fingerprinting technique was well suited to the study region. The results show that natural dust sources (67%) contributed more to the study region than anthropogenic dust sources. They were mainly from the northwest and north of the study region. Particularly, the contributions of Taiyuan (TY) and Linfen (LF) accounted for the largest (82%) and smallest (55%) proportions, respectively, both exceeding 50%. Anthropogenic dust sources contributed 33%, mainly from the east and south of the study region. The contribution of anthropogenic dust sources increased in the study region from north to south. In terms of potential dust sources, the Tengger Desert and Badain Jaran Desert (TDBD) contributed the most (26%), followed by the Otindag Sandy Land (OL) (22%). The Taklimakan Desert (TD) contributed the least (2%). The Middle Farmland region of the Hexi Corridor (HMF) in the west (15%) had the largest proportion of anthropogenic dust sources. Differences in the regional contribution of potential dust sources mainly resulted from winter winds, surface drought severity and particle size. At an insignificant distance from the study region, the contribution of potential dust sources was larger in the west than in the east and increased from south to north overall. These methods and findings can contribute to improving the ecological environment in Northern China.

[Progress in research of etiology of childhood obesity based on interaction between genes and environment].

Childhood obesity is a global public health problem, which can not only endangers children's health, but also might be an important cause of chronic diseases in adulthood. In recent years, with the in-depth development of precision medicine research, more and more research evidences have shown that there are interactions between environmental factors, such as early intrauterine environment, children's diet, physical activity and children's gene factor on the incidence of childhood obesity, which can result in or inhibit the incidence and development of childhood obesity. This paper summarizes the progress in research in this field to reveal the effects and potential mechanisms of genetic factors and environmental factors on the incidence of childhood obesity in order to provide reference for the precise prevention and control of childhood obesity under different genetic backgrounds.