Failure in syndromic management due to drug-resistant Mycoplasma genitalium in Florianópolis, South Brazil / Falha no manejo sindrômico devido a Mycoplasma genitalium resistente em Florianópolis, Sul do Brasil

Introduction: Mycoplasma genitalium is a bacterium associated with sexually transmitted infections that can cause urethritis in men and complications in women, including preterm birth. Increasing macrolide resistance in M. genitalium poses challenges to treatment efficacy. Objective: To present a case of treatment failure of urethritis caused by macrolide-resistant M. genitalium. Case report: This case report describes a 20-year-old man with persistent urethral symptoms despite azithromycin treatment, wherein M. genitalium harbored the A2058G mutation in the 23S rRNA. Subsequent treatment with moxifloxacin resolved symptoms and cleared M. genitalium. Conclusion: The study highlights the importance of resistance testing to guide antimicrobial therapy and emphasizes the need for updated treatment guidelines in Brazil. (AU)

Introdução:Mycoplasma genitalium é uma bactéria associada a infecções sexualmente transmissíveis, que pode causar uretrite em homens e complicações em mulheres, incluindo nascimento prematuro. O aumento da resistência aos macrolídeos em M. genitalium coloca desafios à eficácia do tratamento. Objetivo: Apresentar um caso de falha terapêutica de uretrite causada por M. genitalium resistente aos macrolídeos. Relato de caso: Este relato de caso descreve um homem de 20 anos com sintomas uretrais persistentes, apesar do tratamento com azitromicina, em que M. genitalium possuía a mutação A2058G no rRNA 23S. O tratamento subsequente com moxifloxacino resolveu os sintomas e eliminou M. genitalium. Conclusão: O estudo destacou a importância dos testes de resistência para orientar a terapia antimicrobiana e enfatizou a necessidade de atualizar as diretrizes de tratamento no Brasil. (AU)

Adiponectin gene polymorphism and postpartum type 2 diabetes in pregnant women with gestational diabetes mellitus / 中国医师杂志

Objective:To investigate the relationship between adiponectin (ADIPOQ) gene polymorphism and postpartum type 2 diabetes mellitus (T2DM) in pregnant women with gestational diabetes mellitus (GDM).Methods:A retrospective study was conducted on 236 GDM postpartum women admitted to the Affiliated Hospital of Jining Medical College from June 2020 to June 2021 as observation subjects. They were divided into a T2DM group and a non T2DM group based on the occurrence of T2DM after delivery. The clinical data of the two groups were compared. The double deoxygenation end termination method was used to detect the single nucleotide polymorphism (SNP) of the ADIPOQ gene, and the four loci rs17366568, rs822395, rs1501299, and rs2241766 were classified. The relationship between ADIPOQ genotype polymorphism and postpartum T2DM was analyzed using a logistic regression model.Results:The G allele carrying the rs2241766 locus in ADIPOQ gene was negatively correlated with the occurrence of T2DM ( OR=0.71, 0.68, P<0.05). Compared with T2DM patients with TT genotype, the GT+ GG genotype at the rs2241766 locus had a lower risk of occurrence for gestational age ≥2 and HbA 1c>85%. Similarly, T2DM patients with pre pregnancy body mass index (BMI)>25 kg/m 2 were more likely to be carriers of the rs2241766 TT genotype ( P=0.026). The (GT+ TT) genotype carrying the T allele at the rs1501299 locus was a protective factor for gestational age and HbA 1c in T2DM patients. Conclusions:The rs2241766 and rs1501299 polymorphisms of the ADIPOQ gene are associated with susceptibility to postpartum T2DM in GDM women. Individuals with rs2241766 and rs1501299 mutant genotypes belong to the high-risk population for T2DM.

ENAM gene polymorphisms associated with dental anomalies in individuals with cleft lip and palate

Aim: This study aimed to investigate the occurrence of enamelin gene (ENAM) single nucleotide polymorphisms (SNP) and ENAM polymorphism association with dental anomalies (DA) in individuals with unilateral or bilateral cleft lip and palate (CLP). Methods: Saliva samples were collected from 147 individuals aged between 6 and 15 years-old, both genders, and divided into 4 groups: Group 1 (G1) - CLP and DA; Group 2 (G2) - CLP without DA; Group 3 (G3) - without CLP with DA; Group 4 (G4) - without CLP and DA. The genomic DNA was extracted from saliva samples and the following ENAM SNPs markers were genotyped: rs3796703, rs3796704, rs3796705, rs7671281, rs2609428, and rs35951442. Fisher exact and Pearson's Chi-square tests statistically analyzed the results (α=5%). Results: Individuals without CLP with DA (Group 3 - 19.2%) showed statistically higher prevalence of SNP rs2609428 heterozygotes (p=0.006) than individuals with CLP and DA (Group 1 - 0%). Individuals without CLP (10%) exhibited statistically higher prevalence of mutated heterozygotes/homozygous (p=0.028) than in individuals with CLP (1.3%). Conclusion: SNP rs2609428 marker of ENAM gene may be associated with dental anomalies in individuals without cleft lip and palate

The COL5A1 Gene Allelic Combination and ACL Injury Risk in Team Sport: A Preliminary Report / Gene COL5A1 e o risco de lesões do LCA no esporte de equipe: Um relatório preliminar

Abstract Objective: The aim of this study was to examine the relationship between BstUI restriction fragment length polymorphisms (RFLP) C/T (rs 12722) and DpnII RFLP B1/B2 (rs 13946) COL5A1 polymorphisms and the anterior cruciate ligament (ACL) rupture in competitive team-sport athletes. Methods Sixty-eight team-sport players (n = 36 women and n = 32 men) with non-contact ACL rupture (ACLR) occurred during sport practices (ACLR Group) and 42 healthy players (n = 20 women and n = 22 men) (Control Group) participated in the study. Genomic DNA was extracted from buccal swab with salting out method. All samples were genotyped for the polymorphisms rs12722 and rs13946 by polymerase chain reaction (PCR) and restriction enzymes analysis. Results No significant difference has been found between ACRL and Control groups in age, height, weight body, mass index, sport practice (hours/week) and gender distribution among the different team sports. Control group had longer sport careers (p< 0.005). The frequency distributions of COL5A1 DpnII nucleotide polymorphisms were in Hardy-Weinberg equilibrium (HWE) in both groups (p of the Hardy-Weinberg (HW) -test > 0.005). Genotype frequencies of COL5A1 BstUI RFLP C/C was lower in the ACLR group compared to the Control group (p of the HW-test = 0.001). Combined CC, B1B1 genotypes showed a protective effect against ACL rupture (OR = 83.3 / 16.7 = 5). Conclusions The COL5A1 gene may be one of the genetic factors associated with ACLR in team sport.

Resumo Objetivo: O objetivo deste estudo foi examinar a relação entre os polimorfismos do comprimento do fragmento de restrição (RFLP) BstUI C/T (rs 12722) e RFLP DpnII B1/B2 (rs 13946) COL5A1 e a ruptura do ligamento cruzado anterior (LCA) em atletas de esportes coletivos. Métodos Sessenta e oito atletas de esportes coletivos (n = 36 mulheres e n = 32 homens) com ruptura do LCA (RLCA) sem contato ocorreram durante práticas esportivas (Grupo RLCA) e 42 jogadores saudáveis (n = 20 mulheres e n = 22 homens) (Grupo Controle) participaram do estudo. O DNA genômico foi extraído do swab bucal com o método salting out. Todas as amostras foram genotipadas para os polimorfismos rs12722 e rs13946 por reação em cadeia da polimerase (PCR) e análise de enzimas de restrição. Resultados Nenhuma diferença significativa foi encontrada entre os grupos RLCA e Controle em idade, altura, peso corporal, índice de massa, prática esportiva (horas/semana) e distribuição de gênero entre os diferentes esportes coletivos. O grupo controle teve carreiras esportivas mais longas (p< 0,005). As distribuições de frequência dos polimorfismos de nucleotídeos COL5A1 DpnII estavam em equilíbrio de Hardy-Weinberg (EHW) em ambos os grupos (p do teste de Hardy-Weinberg (HW) > 0,005). As frequências genotípicas de COL5A1 BstUI RFLP C/C foram menores no grupo RLCA em comparação com o grupo Controle (p do teste HW = 0,001). Os genótipos combinados CC, B1B1 mostraram um efeito protetor contra a ruptura do LCA (OR = 83,3 / 16,7 = 5). Conclusões O gene COL5A1 pode ser um dos fatores genéticos associados à RLCA em esportes coletivos.

Serotonin, ghrelin, and motilin gene/receptor/transporter polymorphisms in childhood functional constipation

SUMMARY OBJECTIVE: Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. There are a limited number of studies in the literature where hormone levels and gene polymorphisms of serotonin and motilin are examined. Our study aimed to investigate the role of motilin, ghrelin, and serotonin gene/receptor/transporter polymorphisms in constipation pathogenesis in patients diagnosed with functional constipation according to the Rome 4 criteria. METHODS: Sociodemographic data, symptom duration, accompanying findings, the presence of constipation in the family, Rome 4 criteria, and clinical findings according to Bristol scale of 200 cases (100 constipated patients and 100 healthy control) who applied to Istanbul Haseki Training and Research Hospital, Pediatric Gastroenterology Outpatient Clinic, between March and September 2019 (6-month period) were recorded. Polymorphisms of motilin-MLN (rs2281820), serotonin receptor-HTR3A (rs1062613), serotonin transporter-5-HTT (rs1042173), ghrelin-GHRL (rs27647), and ghrelin receptor-GHSR (rs572169) were detected by real-time PCR. RESULTS: There was no difference between the two groups in terms of sociodemographic characteristics. Notably, 40% of the constipated group had a family history of constipation. The number of patients who started to have constipation under 24 months was 78, and the number of patients who started to have constipation after 24 months was 22. There was no significant difference between constipation and control groups in terms of genotype and allele frequencies in MLN, HTR3A, 5-HTT, GHRL, and GHSR polymorphisms (p<0.05). Considering only the constipated group, the rates of gene polymorphism were similar among those with/without a positive family history of constipation, constipation onset age, those with/without fissures, those with/without skin tag, and those with type 1/type 2 stool types according to the Bristol stool scale. CONCLUSION: Our study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.

Influence of rs2587552 polymorphism of DRD2 gene on the effect of a childhood obesity intervention: A prospective, parallel-group controlled trial / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between rs2587552 polymorphism (has a strong lin-kage disequilibrium with rs1800497 which had been found in many studies to be related to obesity, r2=0.85) of DRD2 gene and the effect of a childhood obesity intervention in Chinese population, and provide a scientific basis for future personalized childhood obesity intervention based on genetic background.@*METHODS@#From a multi-center cluster randomized controlled trial studying the effect of a childhood obesity intervention, we enrolled 382 children from 8 primary schools (192 and 190 children from intervention and control groups, respectively) in Beijing as study subjects. Saliva was collected and DNA was extracted to detect the rs2587552 polymorphism of DRD2 gene, and the interactions between the gene and study arms on childhood obesity indicators [including body weight, body mass index (BMI), BMI Z-score, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, and body fat percentage] were analyzed.@*RESULTS@#No association was found between rs2587552 polymorphism and the changes in hip circumference or body fat percentage in the intervention group (P>0.05). However, in the control group, children carrying the A allele at DRD2 rs2587552 locus showed a greater increase in hip circumference and body fat percentage compared with those not carrying A allele (P < 0.001). There were interactions between rs2587552 polymorphism of DRD2 gene and study arms on the changes in hip circumference and body fat percentage (P=0.007 and 0.015, respectively). Compared with the control group, children in the intervention group carrying the A allele at DRD2 rs2587552 locus showed decrease in hip circumference by (-1.30 cm, 95%CI: -2.25 to -0.35, P=0.007) and decrease in body fat percentage by (-1.34%, 95%CI: -2.42 to -0.27, P=0.015) compared with those not carrying A allele. The results were consistent between the dominant model and the additive model (hip circumfe-rence: -0.66 cm, 95%CI: -1.28 to -0.03, P=0.041; body fat percentage: -0.69%, 95%CI: -1.40 to 0.02, P=0.056). No interaction was found between rs2587552 polymorphism and study arms on the changes in other childhood obesity-related indicators (P>0.05).@*CONCLUSION@#Children carrying the A allele at rs2587552 polymorphism of DRD2 gene are more sensitive to intervention and showed more improvement in hip circumference and body fat percentage after the intervention, suggesting that future personalized childhood obesity lifestyle intervention can be carried out based on the rs2587552 polymorphism of DRD2 gene.

Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Pathogenesis of brain arteriovenous malformations / 国际脑血管病杂志

Brain arteriovenous malformations (bAVMs) are a complex congenital cerebrovascular disease. The lack of common capillaries results in blood flowing directly from the arteries to the veins, forming abnormal vascular malformations between the arteries and veins. BAVMs are usually found due to "epilepsy, intracranial hemorrhage, and focal neurological dysfunction", with a low incidence rate but a high mortality and disability rate. However, the specific pathogenesis of bAVMs is not fully understood. This article reviews the signaling pathways, pathophysiological mechanisms, and non-coding RNAs related to the pathogenesis of bAVMs, with the aim of providing new diagnostic and therapeutic strategies for bAVMs.

Analysis of AHNAK2 gene polymorphism in Xinjiang patients with coronary heart disease / 心血管康复医学杂志

Objective:To explore the relationship between the polymorphisms of AHNAK2 gene rs12882641,rs28583515 and rs2582497 loci and coronary heart disease(CHD)in the population of Xinjiang.Materials:This study used a case-control method,a total of 602 patients who were hospitalized and underwent coronary angiogra-phy(CAG)at ourheart center from Jan 2019 to Dec 2021 were selected.According toCAG results,the patients were divided into CHD group(n=301)and non-CHD group(n=301).The AHNAK2 gene rs12882641,rs28583515 and rs2582497 loci were genotyped using the improved multiple ligase detection reaction(iMLDR)technique,and the relationship between AHNAK2 gene polymorphisms and CHD was analyzed.Results:Compared with non-CHD group,there was significant rise in the distribution frequencies of AC+CC genotypes(52.8%vs.61.1%,P= 0.040)at rs2582497 locus of the AHNAK2 gene under the dominant model;there was significant reduction in distri-bution frequency of the CC genotype(65.8%vs.53.8%)at the rs28583515 locus of the AHNAK2 gene,and signif-icant rise in distribution frequencies of CT+TT(34.2%vs.46.2%)under the dominant model,TT under the re-cessive model(0.7%vs.3.0%)and CT under the additive model(33.6%vs.43.2%)in CHD group,P＜0.05 or＜0.01.After adjusting for confounding factors,logistic regression analysis indicated that the dominant model of the rs28583515 locus remained an independent risk factor for CHD(OR=1.509,P=0.036).Conclusion:The AH-NAK2 gene rs28583515 locus is closely related to the occurrence and development of CHD in the Xinjiang popula-tion.The dominant model of the AHNAK2 gene rs28583515 locus is an independent risk factor for CHD.

Association of syndecan-2 gene polymorphism in colorectal cancer and genotype frequency analysis / 中华全科医师杂志

A total of 225 patients with colorectal cancer (CRC) admitted to the General Hospital of Shaoxing Second Hospital Medical community from May 5, 2020 to May 28, 2022 were enrolled (CRC group), and 101 healthy subjects underwent colorectal examination were selected as the control group. The tissue biopsy samples of all subjects were obtained by colonoscopy, and subjected to Sanger sequencing to determine the polymorphism sites of the syndecan-2 (SDC2) gene. The association between SDC single nucleotide polymorphism (SNP) and colorectal cancer in CRC patients was analyzed with logistic regression. The logistic regression analysis showed that the gene polymorphism of SDC2 rs2515127 was associated with colorectal cancer ( OR=1.643, 95% CI: 1.025-2.337, P=0.012). The frequency of GG, AG and AA the in genotypes of SDC2 rs2515127 was 60.7% (102/168), 30.4% (51/168) and 8.9% (15/168), respectively. The results showed that the gene polymorphism of SDC2 rs2515127 was associated with colorectal cancer, and the frequencies of GG and AG genotypes were higher in the genotypes of SDC2 rs2515127.

Genetic susceptibility of PLCE1 gene polymorphism and primary nephrotic syndrome in Guangxi Zhuang children / 中华肾脏病杂志

Objective:To investigate the relationship between single nucleotide polymorphic (SNP) loci of PLCE1 gene and primary nephrotic syndrome (PNS) and its response to glucocorticoid therapy in Guangxi Zhuang children. Methods:It was a retrospective cohort study. One hundred and fifty-five Guangxi Zhuang children with PNS in the Affiliated Hospital of Youjiang Ethnic Medical College from October 2020 to May 2022, and 100 healthy Zhuang children during the same period as controls were included. Four SNP loci including rs17109674, rs10786156, rs3740360 and rs2274224 of PLCE1 gene were selected and high-throughput sequencing was used to analyze the genotypes. Logistic regression analysis model was used to analyze the correlation between each SNP locus and onset of PNS and steroid-resistant nephrotic syndrome. The SHEsis online software was used to analyze the link disequilibrium of each SNP locus, and construct the haploid type. Results:(1) Logistic regression analysis results showed that AC+CC genotype (AA as reference, OR=0.449, 95% CI 0.256-0.786, P=0.005), AC genotype (AA as reference, OR=0.354, 95% CI 0.188-0.667, P=0.001) and C allele gene (A as reference, OR=0.615, 95% CI 0.390-0.971, P=0.037) of rs3740360 were correlated with the risk of PNS in children. The genotypes and allele genes of rs17109674, rs10786156, rs3740360 and rs2274224 were not associated with the risk of steroid-resistant nephrotic syndrome in children (all P>0.05). (2) Strong linkage disequilibrium existed between rs10786156 and rs2274224 ( D'=0.702, r2=0.484). rs17109674 and rs10786156 ( D'=0.128, r2=0.007), rs17109674 and rs3740360 ( D'=0.142, r2=0.007), rs17109674 and rs2274224 ( D'=0.045, r2=0.001), rs10786156 and rs3740360 ( D'=0.255, r2=0.023), and rs3740360 and rs2274224 ( D'=0.281, r2=0.028) all had weak linkage disequilibrium. (3) The haploid AGCG ( OR=0.282, 95% CI 0.079-1.008, P=0.038), GGCC ( OR=0.327, 95% CI 0.111-0.967, P=0.034) and GGAG ( OR=4.616, 95% CI 1.179-18.069, P=0.016) were all correlated with the risk of PNS in children. Conclusions:AC genotype, AC+CC genotype, and C allele gene of rs3740360 SNP locus may reduce the risk of PNS in Guangxi Zhuang children. Haploid AGCG and GGCC may be associated with decreased incidence of PNS, while GGAG may be associated with increased incidence of PNS in Guangxi Zhuang children. The genotypes and alleles of 4 SNP loci are not associated with the risk of steroid-resistant nephrotic syndrome.

Meta analysis of the relationship between DEPDC5 gene polymorphism and hepatocellular carcinoma susceptibility / 中国医师杂志

Objective:To systematically evaluate the relationship between rs1012068 and rs5998152 single nucleotide polymorphisms of DEPDC5 gene and susceptibility to hepatocellular carcinoma (HCC).Methods:Up to October 31, 2022, PubMed, Embase, Scopus, Web of Science and China National Knowledge Internet (CNKI) were used to search the relationship between rs1012068, rs5998152 and susceptibility to HCC. The odds ratio (OR) values and 95% CI of the five genetic models were calculated, and the RevMan5.3 software was used for meta analysis. Results:A total of 12 articles were included in this study, including 11 articles about rs1012068 locus, including 2 609 patients with HCC and 8 171 controls, and 3 articles about rs5998152 locus, including 411 patients with HCC and 1 448 controls. The results of meta analysis showed that among the five genetic models of rs1012068 locus, allele pattern (G vs T: P=0.02), dominant pattern (GG+ TG vs TT: P=0.01) and heterozygote pattern (TG vs TT: P=0.009) were significantly different between the case group and the control group. In homozygous mode (GG vs TT: P=0.05) and recessive mode (GG vs TG+ TT: P=0.08), there was no correlation between rs1012068 gene polymorphism and susceptibility to HCC. Among the five genetic models of rs5998152 locus, allele model (C vs T: P=0.03), dominant model (CC+ TC vs TT: P=0.001) and heterozygous model (TC vs TT: P<0.000 01) were significantly different between case group and control group. There was no correlation between rs5998152 gene polymorphism and susceptibility to HCC in recessive model (CC vs TC+ TT: P=0.31) and homozygous model (CC vs TT: P=0.09). Conclusions:There is a correlation between rs1012068 locus and susceptibility to HCC in allele model and dominant gene model, which is a genetic factor promoting tumorigenesis. The allele pattern, dominance pattern and heterozygote pattern of rs5998152 locus can increase the risk of liver cancer, but no correlation was found in other patterns.

The impact and interaction of TLR2 and IRF-5 gene polymorphisms on the susceptibility to neonatal sepsis / 中国医师杂志

Objective:To investigate the impact and interaction of Toll like receptor 2 (TLR2) and interferon regulatory factor 5 (IRF-5) gene polymorphisms on the susceptibility to neonatal sepsis.Methods:A total of 78 cases of neonatal septicemia patients admitted to Baoding Children′s Hospital from July 2018 to August 2021 were prospectively selected as the study group, and 78 cases of healthy newborns in the same period were selected as the control group. The TLR2 and IRF-5 gene polymorphisms and the levels of inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in different genotypes of infants were compared between the two groups. We evaluated the relationship between TLR2 and IRF-5 genotypes, inflammatory markers, and susceptibility to neonatal sepsis, and analyzed the interaction between their gene polymorphisms and susceptibility to neonatal sepsis.Results:There were significant differences in the distribution of TLR2 (rs3804099) and IRF-5 (rs2004640) loci genotype and Allele frequency between the two groups (all P<0.05); The serum CRP, TNF-α, and IL-6 levels in children with TLR2 (rs3804099) genotype TT genotype [(111.12±30.87)mg/L, (77.50±20.02)pg/ml, (40.27±11.31)pg/ml] were higher than those in children with CC/CT genotype [(72.46±24.51)mg/L, (54.18±17.65)pg/ml, (28.34±9.05)pg/ml], and the differences were statistically significant (all P<0.05). The serum CRP, TNF-α, and IL-6 levels [(113.90±28.94)mg/L, TNF-α (79.84±19.82)pg/ml, IL-6 (41.05±11.49)pg/ml] in children with the IRF-5 (rs2004640) TT genotype were higher than those in children with the GG/GT genotype [(70.88±22.16)mg/L, (52.27±16.73)pg/ml, (27.96±9.75)pg/ml], and the differences were statistically significant (all P<0.05). The TT genotypes at TLR2 (rs3804099) and IRF-5 (rs2004640) loci were positively correlated with serum CRP, TNF-α, and IL-6 levels (all P<0.05); The TT genotypes at TLR2 (rs3804099) and IRF-5 (rs2004640) loci were independent risk factors for susceptibility to neonatal sepsis (all P<0.05); The TT genotype at the TLR2 (rs3804099) locus and the TT genotype at the IRF-5 (rs2004640) locus exhibited a positive interaction in susceptibility to neonatal sepsis ( OR=7.467, γ=1.728). Conclusions:TLR2 (rs3804099) TT genotype and IRF-5 (rs2004640) TT genotype significantly increase the susceptibility to neonatal sepsis, and there is a positive interaction between the two.

Research progress on the correlation between genetic factors and sudden cardiac death in the elderly / 中华老年医学杂志

Sudden cardiac death(SCD)in the elderly is defined as a sudden accidental death in patients over 65 years of age within one hour of symptom onset or within 24 hours with no symptoms, possibly due to arrhythmia or abrupt hemodynamic changes.It is characterized by rapid onset, rapid progression, and high mortality.Sudden cardiac death in the elderly is the most serious clinical syndrome in elderly patients with heart disease.It accounts for more than 80% of all sudden death cases and is the cause of sudden death in the vast majority of elderly patients.Clinical methods for the detection of sudden cardiac death include mostly screening through family and personal history, physical examination, electrocardiogram analysis and echocardiography, but their drawbacks include lack specificity, low detection rates and relatively limited scenarios for their use.Genetic susceptibility is also responsible for sudden cardiac death.Genetic factors play an important role in the occurrence and development of sudden cardiac death.This review summarized the correlation between sudden death and genetic factors underlying different cardiovascular diseases, including the role of genetic polymorphisms in the occurrence of sudden cardiac death in older adults.

Prenatal diagnosis and genetic analysis of seven fetuses with 16p12.2 microdeletion or microduplication / 中华围产医学杂志

Objective:To investigate the prenatal ultrasonographic features and diagnosis of 16p12.2 copy number variation (CNV).Methods:This retrospective study recruited seven fetuses with 16p12.2 microdeletion/microduplication in the First Affiliated Hospital of Fujian Medical University from January 2017 to December 2021. Data, including the prenatal diagnostic indications, ultrasound findings, karyotypes, genetic testing and mutation tracing results, pregnancy outcomes, and postnatal follow-up data, were summarized with descriptive statistical analysis.Results:Prenatal ultrasound indicated three fetuses with structural abnormalities, including one case each of multiple malformations, interventricular septal defect, and cleft lip and palate. The other four cases were positive for ultrasonic soft markers involving the heart and kidney. The chromosome karyotypes of the seven fetuses were normal. Single nucleotide polymorphism array (SNP array) results showed that four cases had a 381.7-542.4 kb microdeletion containing three genes ( OTOA, METTL9, and IGSF6) in Online Mendelian Inheritance in Man (OMIM) at 16p12.2 (distal region) and three cases had a 484.0-701.7 kb microdeletion/microduplication containing four OMIM genes ( UQCRC2, CDR2, EEF2K, and POLR3E) at 16p12.2 (proximal region). Five (cases 1, 2, 4, 5, and 6) out of the seven fetuses inherited the variants from their phenotypically normal mother/father, and among them, three (cases 2, 4, and 5) were delivered at term and healthy. Two cases (cases 3 and 7) refused to undergo pedigree verification. Case 3, a full-term infant, underwent ventricular septal defect repair three months after birth, and no abnormality was found at 18 months of age. Conclusions:No specific phenotype presents in fetuses with 16p12.2 microdeletion/microduplication in prenatal diagnosis. OTOA gene is the key gene associated with abnormality in the distal region of 16p12.2. Pedigree analysis is conducive to preventing unnecessary termination of pregnancy.

Genetic analysis of unexplained neonatal encephalopathy / 中华围产医学杂志

Objective:To explore the potential genetic causes of unexplained neonatal encephalopathy.Methods:This retrospective study enrolled 113 infants diagnosed with unexplained neonatal encephalopathy and underwent genetic testing in the Children's Hospital of Hunan Province from January 2019 to May 2021. Perinatal data, clinical manifestations, electroencephalograph, brain MRI findings, genetic information, and prognosis of those patients were analyzed. T-test or Chi-square test were used for data analysis. Results:Of the 113 infants enrolled, 74 (65.5%) were males. The gestational age at birth was (38.6±1.5) weeks, and the birth weight was (2 957±561) g. The most common clinical manifestation was the disturbance of consciousness (83/113, 73.5%), followed by seizures (39/113, 34.5%). There were 38.2% (34/89) of the patients with abnormal brain MRI, and 80.4% (74/92) presented abnormal electroencephalography. Among the 113 infants, 60 (53.1%) had genetic abnormalities, including 48 with single nucleotide variations, eight with copy number variations, and four with chromosome abnormalities. Single nucleotide variations in the 48 patients were classified into syndromic ( n=18, 37.5%), metabolic ( n=16, 33.3%), epileptic ( n=11, 22.9%) and mitochondrial-related genes ( n=3, 6.3%), of which 14 were not included in any database. Among the 103 cases which were successfully followed up until December 31, 2021, 75 (72.8%) had a poor prognosis, including 52 (50.5%) death cases and 23 (22.3%) cases of development retardation. Birth weight and the incidence of seizures in the poor prognosis group were both lower than those in the non-poor prognosis group [(2 876±536) vs (3 254±554) g, t=3.15; 29.3% (22/75) vs 53.6% (15/28), χ2=5.20; both P<0.05], while the incidence of disturbance of consciousness was higher [80.0% (60/75) vs 53.6% (15/28), χ2=7.19, P<0.05]. The proportion of infants with genetic abnormalities in the poor prognosis group was higher than that in the non-poor prognosis group, but the difference was not statistically significant [53.3% (40/75) vs 46.4% (13/28), χ2=0.39, P=0.533]. Conclusions:Genetic abnormality is one of the leading causes of unexplained neonatal encephalopathy. Nucleotide variation is the most common genetic type. Syndromic, metabolic, and epileptic variants are frequently detected in these patients.

Endoplasmic reticulum aminopeptidase 1 and genetic susceptibility to pre-eclampsia / 中华围产医学杂志

Objective:To investigate whether endoplasmic reticulum aminopeptidase 1 ( ERAP1) is a susceptible gene for pre-eclampsia (PE) and the possible mechanism in the pathogenesis. Methods:This retrospective study included 990 PE patients (case group) and 1 240 healthy pregnant women (control group) in six prefecture-level tertiary hospitals in Shandong Province, including the Affiliated Hospital of Qingdao University and Zaozhuang Maternal and Child Health Hospital, from September 2018 to April 2021. Peripheral blood were collected for DNA extraction. Single-nucleotide polymorphisms in the ERAP1 gene (rs30187, rs27044, and rs469783 loci) were analyzed by Taqman probe polymerase chain reaction (PCR). Two missense mutant plasmids, rs30187(c.1583A>G) and rs27044(c.2188C>G), were constructed by point mutation induction based on wild-type plasmids. Six groups (knock-down control, knock-down, over-expression control, over-expression, variant 1 and 2 groups) were set up in this study. After transfecting Htr8 cells with different transfection molecules, the expression of ERAP1 at mRNA and protein levels were detected. Besides, the effects of different transfections on cell function were detected using Transwell migration assay, Transwell invasion assay, cell scratch assay, and CCK-8 assay. Statistical analysis was performed using two independent samples t-test, rank sum test, and Chi-square test. Results:(1) There were significant differences in the genetic distribution of rs30187 (Genotype: χ2=29.25, Allele: χ2=4.68) and rs469783 (Genotype: χ2=7.01, Allele: χ2=6.45) as well as the genotype distribution of rs27044 ( χ2=28.95) between the case group and the control group (all P<0.05). Statistical analysis of the genetic model revealed that rs30187 and rs27044, both recessive models, were statistically different between the two groups with a higher frequency of CC genotypes in the case group ( χ2=20.82 and 19.97, both P<0.05), but a lower frequency in CC dominant gene pattern for rs469783 ( χ2=5.82, P=0.016). (2) Compared with the knock-down control group, the knock-down group showed significantly inhibited expression of ERAP1 (mRNA: 0.5±0.1 vs 1.0±0.0, t=7.49; protein: 0.4±0.1 vs 0.7±0.1, t=2.81; both P<0.05), reduced cell migration rate after 48 h of scratching [(16.5%±1.8%) vs (23.8%±2.4%), t=3.33, P=0.031] and decreased number of cells crossing Transwell chambers after 24 h of culture (423.7±21.3 vs 499.0±24.6, t=3.29, P=0.031). Compared with the over-expression group, variant 1 group and variant 2 group showed significantly inhibited expression of ERAP1 at mRNA (both P<0.001) and protein ( P=0.003 and 0.006) levels after transfection, decreased number of cells crossing Transwell chambers ( P=0.001 and 0.032) and down-regulated cell migration rate after 48 h of scratching [variant 1: P=0.004; variant 2: (21.1±4.6)% vs (28.3±1.1)%, t=2.10, P=0.099]. ERAP1 expression at both mRNA ( P<0.001) and protein ( P=0.008) levels, as well as cell proliferation ( P<0.001) and invasion ability ( P<0.001), were all enhanced in the over-expression group than those in the over-expression control group. Moreover, the migration rate of cells after 48 h of scratching ( P=0.002) and the number of cells crossing Transwell chambers after 24 h of culture ( P=0.001) were also increased. Conclusions:The rs30187, rs27044, and rs46978 on ERAP1 gene were all associated with PE susceptibility, with more carriers of the CC genotype in PE patients at rs30187 and rs27044 loci and more carriers of the CC genotype in healthy gravida at rs469783 locus. ERAP1 may be involved in the pathogenesis of PE by affecting the migratory and invasive ability of trophoblast cells.

Relationship and interaction between tissue delta-like ligand 3 expression and xeroderma pigmentosum gene G gene polymorphism and sensitivity to platinum-based chemotherapy in advanced squamous lung cancer / 中国医师进修杂志

Objective:To analyze the interaction of tissue delta-like ligand 3 (DLL3) expression and xeroderma pigmentosum gene G (XPG) gene polymorphism on the sensitivity of advanced lung squamous cell carcinoma to platinum-based chemotherapy.Methods:One hundred and forty patients with advanced squamous lung cancer admitted to Yuechi County People′s Hospital from March 2019 to December 2021 were selected and all were given carboplatin and paclitaxel for injection (albumin-bound) in a fully informed manner, with one cycle every 3 weeks for a total of 4 cycles of treatment. The patients were divided into sensitive group (46 cases) and non-sensitive group (94 cases) according to their sensitivity to chemotherapy. Baseline information, tissue DLL3 expression and XPG gene polymorphism were compared between the two groups, and tissue DLL3 expression in patients with different XPG genotypes was compared. Multi-factor Logistic regression analysis was used to analyzed the factors associated with the sensitivity to chemotherapy, and interaction coefficient γ was used to analyze tissue DLL3 expression and XPG.Results:The tissue DLL3 expression score of the sensitive group was lower than that in the non-sensitive group: (3.28 ± 0.93) scores vs. (7.59 ± 1.22) scores, there was statistical difference ( P<0.01). The patients with CC genotype in the sensitive group were more than those in the non-sensitive group, and the patients with CT and TT genotypes were less than those in the non-sensitive group ( P<0.05). Tissue DLL3 expression score in patients with CC, CT, TT genotype were (3.51 ± 0.93), (6.76 ± 1.08), (10.09 ± 1.12) scores, there was statistical difference ( P<0.05); and tissue DLL3 expression score was CC<CT<TT genotype, there were significant differences between pairwise comparisons ( P<0.05). Multivariate Logistic regression analysis showed that the probability of insensitivity to platinum chemotherapy in patients with high tissue DLL3 expression was 8.368 times than that of patients with low expression, and the probability of insensitivity to platinum chemotherapy in patients with XPG genotype CT and TT was 5.349 and 9.517 times higher than that in CC genotype. The OR value caused by DLL3 alone was 6.222, the OR value caused by XPG gene polymorphism alone was 56.000, and the OR value caused by the coexistence of the two was 275.333, and the interaction coefficient γ = 1.396, indicated that the expression of tissue DLL3 was related to XPG gene polymorphism. The effect of sex had a positive interaction, and the OR value of the interaction between the two was less than the product of the OR value of the two independent factors. The model representing the interaction effect of tissue DLL3 expression and XPG gene polymorphism on chemotherapy sensitivity was a submultiplicative model. Conclusions:Patients with advanced squamous lung cancer of the CC genotype at the XPG C46T locus are more sensitive to platinum-based chemotherapy than patients of the CT and TT types, and are associated with platinum-based chemotherapy responsiveness. High tissue DLL3 expression has a positive interaction with the effect of the XPG gene polymorphism, and the two are consistent with a submultiplicative model, which may be a genetic mechanism for poor response to platinum-based chemotherapy.

Association between fasting blood glucose combined with gene polymorphisms of adiponectin, interleukin 6 and tumor necrosis factor-alpha in early pregnancy and insulin resistance in peri-pregnancy / 中国医师进修杂志

Objective:To study the relationship between fasting glucose (FPG) and gene polymorphisms of adiponectin (ADIPOQ), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in early pregnancy and insulin resistance in patients with gestational diabetes mellitus (GDM).Methods:Sixty patients diagnosed with GDM within 24 -28 weeks from January 2022 to August 2022 in the Affiliated Hospital of Jining Medical University were selected as the GDM group, and another 60 healthy pregnant women were taken as the normal control group. The fasting insulin (FINS), FPG levels and the homeostatic model assessment insulin resistance index (HOMA-IR) and other clinical data were detected at 8 -12 weeks of pregnancy. Meanwhile, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the polymorphisms of ADIPOQ gene at S0100622 locus, IL-6 gene at S01006318 locus, TNF- α gene at S01009718. Receiver operating characteristics(ROC) curve was used to evaluate the diagnostic performance of FPG combined with polymorphisms of ADIPOQ, IL6 and TNF-α in predicting GDM in early pregnancy.Results:The body mass index (BMI), early pregnancy FPG, mid pregnancy FPG, 75 g oral glucose tolerance test (OGTT) 1 h blood glucose, OGTT 2 h blood glucose, glycosylated hemoglobin (HbA 1c), FINS and HOMA-IR in the GDM group were higher than those in the normal control group: (27.1 ± 2.6) kg/m 2 vs. (25.6 ± 2.5) kg/m 2, (4.7 ± 1.3) mmol/L vs. (4.1 ± 1.5) mmol/L, (5.5 ± 1.3) mmol/L vs. (4.2 ± 1.2) mmol/L, (6.3 ± 1.5) mmol/L vs. (5.5 ± 1.7) mmol/L, (6.0 ± 1.5) mmol/L vs. (5.2 ± 1.4) mmol/L, (5.8 ± 0.7)% vs. (5.2 ± 0.6)%, (6.4 ± 1.1) mU/L vs. (5.2 ± 1.2) mU/L, 1.5 ± 0.6 vs. 1.0 ± 0.7, there were statistical differences ( P<0.05). According to the risk assessment of genotype, the high-risk rate in the GDM group was 88.33% (53/60), while the normal control group was 56.67% (34/60), there was statistical difference ( χ2 = 17.67, P<0.05). In GDM group, the HOMA-IR with ADIPOQ gene S0100622 locus TG genotype was higher than that with TT genotype: 6.58 ± 0.89 vs. 4.98 ± 0.58; the HOMA-IR with IL-6 gene S01006318 locus CG genotype was higher than CC and GG genotype: 8.13 ± 1.31 vs. 6.53 ± 0.81, 4.85 ± 0.54, the HOMA-IR with TNF-αgene S01009718 locus AG genotype was higher than GG genotype: 6.31 ± 1.04 vs. 5.16 ± 0.82, there were statistical differences ( P<0.05). Logistic regression analysis showed that age>35 years, previous diabetes history, BMI, TG genotype at S0100622 locus of ADIPOQ gene, CG genotype at S01006318 locus of IL-6 gene, AG genotype at S01009718 locus TNF- α gene were risk factors for the onset of GDM ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of FPG for predicting GDM onset was 0.737, with a specificity of 83.50%; FPG combined with ADIPOQ, IL-6, TNF- α genetic risk assessment predicted with AUC of 0.921 and a specificity of 86.80%. Conclusions:ADIPOQ gene TG genotype at S0100622 locus, IL-6 gene CG genotype at S01006318 locus, TNF- α gene AG genotype at the S01009718 locus has a certain correlation with the onset of GDM, which can predict the onset of GDM and is associated with perioperative insulin resistance in patients. Early FPG testing combined with genetic screening has practical clinical guiding significance in reducing adverse pregnancy outcomes for mothers and infants.

Implication of FSHB rs10835638 variant in endometriosis in Brazilian women

ABSTRACT Objective The follicle-stimulating hormone subunit beta gene rs10835638 variant (c.-211G>T) may have detrimental effects on fertility and protective effects against endometriosis. A case-control analysis was performed, aiming to investigate the possible relationship between this variant and the development and/or progression of endometriosis. Methods This study included 326 women with endometriosis and 482 controls without endometriosis, both confirmed by inspection of the pelvic cavity during surgery. Genotyping was performed using a TaqMan real-time polymerase chain reaction assay. Genotype and allele frequencies and genetic models were compared between the groups. Results The genotype and allele frequencies of the rs10835638 variant did not differ between women with and those without endometriosis. Subdividing the endometriosis group into fertile and infertile groups did not result in a significant difference in these frequencies. However, the subgroup with minimal/mild endometriosis had a higher frequency of the GT genotype than the Control Group, regardless of fertility. The T allele was significantly more common in women with minimal/mild endometriosis than in the Control Group in the recessive model. Conclusion The T allele is associated with the development of minimal/mild endometriosis in Brazilian women.