Objective:To explore the clinical and genetic characteristics of a child with autosomal recessive primary microcephaly (MCPH).Methods:A case study has been carried out on a boy who had presented at the Inner Mongolia Maternity and Child Health Care Hospital for microcephaly and mental deficiency in September 2022. Prenatal ultrasound images were retrospectively analyzed, and whole exome sequencing and Sanger sequencing were carried out for his family. A literature review was also carried out using keywords such as " ASPM gene", "microcephaly", "prenatal diagnosis", "primary microcephaly", " ASPM", "MCPH5", "MCPH", "autosomal recessive microcephaly", and "prenatal diagnosis on ultrasonography" on the PubMed database, Wanfang Data and China National Knowledge until September 2023. This study was approved by Medical Ethics Committee of the Inner Mongolia Maternity and Child Health Care Hospital (Ethics No. 2021-093-1). Results:The proband had shown progressive reduction in biparietal diameter (BPD) and head circumference (HC) during the fetal period. He was found to harbor compound heterozygous variants of the ASPM gene, which included a paternally derived c. 8044C>T (p.R2682X) and a maternally derived c.8652dup (p.A2885Sfs*35). Both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4; PVS1+ PM2_Supporting+ PM3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). For other fetuses in his family, prenatal ultrasound and genetic testing were all normal. Literature research has identified 11 relevant articles, which included 14 MCPH cases. All of the MCPH5 cases had shown various degrees of reduced BPD/HC on fetal imaging (100%, 15/15). Developmental delay, intellectual disability, and attention deficits were noted in all survived cases, with one case having seizures (12.5%, 1/8). Their genotypes had included homozygotes (46.2%, 6/13) and compound heterozygotes (53.8%, 7/13) for nonsense variants (45%, 9/20) and frameshifting variants (55%, 11/20). Conclusion:The compound heterozygous variants c. 8044C>T (p.R2682X) and c. 8652dup (p.A2885Sfs*35) of the ASPM gene probably underlay the reduced BPD and HC in this proband with MCPH.

Objective To investigate the effects of sulforaphane(SFN)in regulating the macrophage glycolysis via the arachidonate 5-lipoxygenase(ALOX5)/nuclear factor kappa B(NF-κB)signaling pathway on the progression of diabetic nephropathy(DN).Methods Bioinformatics analysis was used to identify the target genes of SFN in the treatment of DN.Human proximal tubular epithelial cell line(HK-2 cells)was induced with 30 mmol/L high glucose(HG)to create an in vitro model of DN.HK-2 cells were divided into the following groups:normal glucose(NG)group,HG group,HG+SFN(3 mmol/L)group,HG+ALOX5 group,HG+SFN(3 mmol/L)+ALOX5 group,HG-treated macrophages+HK-2 group,HG+SFN(3 mmol/L)treated macrophages s+HK-2 group,HG+ALOX5 transfection treated macrophages+HK-2 group,HG+SFN(3 mmol/L)+ALOX5 transfection treated macrophages+HK-2 group.CCK-8 assay was used to detect cell viability,Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)method was used to detect cell apoptosis;glucose and lactate levels in the cells were measured using assay kits;Western blot was performed to detect the expression of ALOX5,NF-κB,and glycolysis-related proteins hexokinase-2(HK2),pyruvate kinase M2(PKM2),glucose transporter 1(GLUT1)in each group.Diabetic nephropathy(DN)mouse models were established using streptozotocin(STZ)and treated with SFN(0.5 mg/kg).Various biochemical parameters were measured in the mice,and kidney tissue pathology was examined using H&E staining.Western blot was used to detect the expression of glycolysis-related proteins(HK2,PKM2,GLUT1)in kidney macrophages.Results Bioinformatics analysis revealed ALOX5 as the target gene of SFN in treating DN.Compared to the HG group,SFN treatment enhanced HK-2 cell viability and in-hibited apoptosis(P<0.05);concurrently,SFN treatment suppressed HG-induced macrophage glycolysis-related protein and attenuated macrophage-mediated HK-2 cellular injury(P<0.05).Western blot results showed that SFN inhibited the expression of ALOX5 and NF-κB(P<0.05).The mouse experiment results showed that SFN treatment improved kidney function and pathological changes in the kidney of DN mice,and inhibited the related protein expression of acrophage glycolysis in kidney tissue(P<0.05).Conclusion SFN improves the progression of DN by inhibiting the expression of macrophage glycolysis-related protein through the ALOX5/NF-κB signaling pathway.

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

OBJECTIVE：To establish the quality standards of Mongolian medicine Cynanchum thesioides. METHODS ：TLC was used for the qualitative identification of C. thesioides . According to 2015 edition of Chinese Pharmacopeia （part Ⅳ），the moisture，total ash and ethanol-soluble extract were determined. HPLC method was used to determine the content of thesioideoside in C. thesioides . RESULTS ：TLC spots were clear ，there were same yellow green fluorescent spots on the corresponding position of the sample （C. thesioides ）and control （thesioideoside）. In 22 batches of samples ，contents of moisture were 6.18％-12.97％，total ash were 4.64％-7.95％，ethanol-soluble extract were 12.46％-32.70％. The linear range of thesioideoside were 0.048-3.050 μg（R2＝ 0.999 9）. RSDs of precision ， stability， repeatability and durability tests were all less than 1％ . The recoveries were 104.03％-106.36％（RSD＝0.96％，n＝6）. The contents of thesioideoside in 22 batches of C. thesioides were 0.006 2％-0.130 5％. CONCLUSIONS：It is suggested that the moisture and total ash should not exceed 11.50％ and 7.50％，respectively；the contents of ethanol-soluble extract and the sioideoside are no less than 17.00％ and 0.05％，respectively. The established quality standards can be used for quality control of Mongolian medicine C. thesioides .

Objective:To analyze the trend of smoking prevalence and its risk factors among adults in Shaanxi province from 2007 to 2015.Methods:We used data from China Chronic Disease and Risk Factor Surveillance in 2007, 2010, 2013 and 2015. The current smoking prevalence and trends of the four surveys were calculated. Its risk factors were analyzed by multivariate logistic regression from each survey and then from all pooled data of the three surveys.Results:The number of participants in 2007, 2010, 2013 and 2015 was 1 542, 3 000, 10 166 and 6 330, respectively. The current smoking prevalence dropped from 34.34 % in 2007 to 26.22 % in 2013, but increased to 28.33 % in 2015 (trend χ2 test: Z=2.53, P=0.01). The results from four pooled data showed that the current smoking prevalence of men was higher than that of women ( OR=75.03, 95 %CI: 63.57-88.55). The current smoking prevalence of people aged 45-59 was higher than that of people aged 18-44 ( OR=1.28, 95 %CI: 1.15-1.41). In addition, the current smoking prevalence of those who were educated for 7-9 years and more than 9 years were higher than those who were educated for less than 6 years (people with education for 7-9 years OR=1.44, 95 %CI: 1.29-1.61; people with education >9 years OR=1.43, 95 %CI: 1.26-1.63). The current smoking prevalence of the single was lower than those of married/cohabitants ( OR=0.54, 95 %CI: 0.37-0.77). The current smoking prevalence of retirees were lower than those of employees ( OR=0.46, 95 %CI: 0.38-0.57) and smoking prevalence of alcohol drinkers were higher than those of non-drinkers ( OR=2.92, 95 %CI: 2.67-3.19). Conclusion:From 2007 to 2015, the current smoking prevalence of Shaanxi population was high and the trends remained stable. It is necessary to strengthen smoking control and health education for men, people over 45 years old, people with education level 7 years and above, and working personnel in Shaanxi province.

Objective: To explore the prevalence of chronic diseases and related risk factors in Shaanxi province. Methods: Multi-stage stratified cluster random sampling was used to collect the sample from permanent residents in 10 national surveillance points in Shaanxi province in 2015. Behavioral risk factors (smoking, drinking, diet and physical activity) were investigated by face-to-face interviews and biological risk factors (BMI, blood pressure, blood glucose and blood lipid) were collected by physical measurements and laboratory tests. Designed weight, no response weight and post hierarchical weight were taken into account in the data analysis. Binary logistic regression models were used to examine the pair-wise associations among 8 risk factors. Results: A total of 6 174 persons were included in the analysis. The following weighted prevalence were noticed in Shaanxi province in 2015, that including current smoking as 28.19%, harmful use of alcohol as 6.20%, inadequate intake of vegetables and fruits as 55.62%, physical inactivity as 19.56%, overweight and obesity as 46.82%, hypertension as 31.12%, raised fasting blood glucose as 4.27%, and raised total cholesterol as 20.96%. Eight risk factors were found to be associated with each other. The mean numbers of risk factors were 2.41 per male and 1.85 per female, 1.94 per urban resident and 2.28 per rural resident. Conclusions Risk factors for chronic diseases among adults aged 18 or older were more than the national levels in Shaanxi province in 2015. Male and rural residents presented more risk factors than their counterparts. Correlations between risk factors implied that a combined package of interventions was needed to reduce these risk factors.

BACKGROUNDPsoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population.

METHODSSeventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software.

RESULTSThe frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10-3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10-7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05).

CONCLUSIONSPolymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; DNA-Binding Proteins ; genetics ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Psoriasis ; epidemiology ; genetics ; Young Adult

Objective To investigate the association between endoplasmic reticulum aminopeptidase 1 (ERAP1)gene polymorphisms and psoriasis vulgaris (PsV)in a Chinese Han population. Methods Five milliliters of venous blood samples were collected from 289 patients with PsV and 292 human controls of Han nationality after informed consent. Three single nucleotide polymorphisms (SNPs)in the encoding area of the ERAP1 gene, including rs27044, rs30187 and rs26653, were genotyped by ligase detection reaction (LDR). With the PLINK 1.07 package, statistical analysis was carried out by using the chi-square test for comparisons of allele and genotype frequencies between the patient group and control group. The allelic odds ratio (OR)and its 95% confidence interval (CI)were calculated. In addition, haplotype analysis was conducted with the Haploview software. Results The frequencies of rs30187-C and rs26653-G alleles were significantly lower in the patient group (0.460 2 and 0.430 8 respectively), especially in patients with early-onset PsV(0.448 5 and 0.422 7 respectively), than in the control group(0.534 2 and 0.501 7 respectively, all P <0.05). The SNPs rs27044, rs30187 and rs26653 showed strong linkage disequilibrium with each other (r2 ≥ 0.717, D′ ≥0.962). Genotype analysis showed that the frequency of the rs30187 CC genotype was significantly lower in the patient group, especially in patients with early-onset PsV, than in the control group (P < 0.05 and 0.016 7 respectively)under a recessive mode of inheritance. Haplotype analysis revealed that the frequency of the haplotype H4: CTC was significantly increased in the patient group(0.050), especially in patients with early-onset PsV(0.052), compared with the control group (0.022, P < 0.05 and 0.016 7 respectively). Conclusions ERAP1 gene polymorphisms are associated with PsV, especially with early-onset PsV in Chinese Han population. The risk haplotype H4: CTC may be a susceptible factor for PsV.

Objective To investigate association between polymorphisms of the tumor necrosis factor α-induced protein 3 (TNFAIP3)interacting protein 1 (TNIP1)gene and systemic lupus erythematosus (SLE)in a Chinese Han population. Methods Blood samples were collected from 284 patients with SLE of Han nationality(SLE group)and 630 healthy controls of Han nationality (control group). Ligase detection reaction (LDR)was performed to determine the genotypes of 120 single nucleotide polymorphisms (SNPs)in the TNIP1 gene. Data were analyzed with the PLINK 1.07 package and Haploview software. Results After quality control, data on 105 SNPs underwent statistical analysis finally. Four SNPs including rs3805433, rs12516176, rs6869605 and rs4958882 in the TNIP1 gene were significantly associated with SLE (OR: 1.50 - 1.53, all P < 4.72 × 104), and there was a significant increase in the frequency of rs3805433 C, rs12516176 C, rs6869605 C and rs4958882 G alleles in the SLE group (0.301 - 0.306)compared with the control group (0.221 - 0.225). There was strong linkage disequilibrium between these 4 SNPs (r2 ≥ 0.871, D′ ≥ 0.938). In addition, moderate linkage disequilibrium was observed between these 4 SNPs and a previously reported SLE-related SNP rs10036748 (r2 ≥ 0.073, D′ ≥ 0.868). The frequency of the haplotype H2: CCCGT was significantly higher in the SLE group than in the control group(0.290 vs. 0.210, OR = 1.54, P < 4.72 × 10-4). Conclusion TNIP1 gene polymorphisms are associated with SLE in Chinese Han population.

Objective To investigate the association between polymorphisms in the tumor necrosis factor α-induced protein 3 (TNFAIP3)-interacting protein 1 (TNIP1) gene and psoriasis vulgaris in a Han population from north China.Methods Totally,465 patients with psoriasis vulgaris (PsV) and 476 healthy human controls were enrolled into the study.Five milliliters of venous blood samples were collected from these subjects after informed consent.Three single nucleotide polymorphisms (SNPs) in the TNIP1 gene,including rs17728338,rs3762999 and rs999556,were selected for genotyping with ligase detection reaction (LDR).With the PLINK 1.07 package,statistical analysis was carried out by using the chi-square test for comparisons of allele frequencies and genotype frequencies between the patient group and control group.The allelic odds ratio (OR) and its 95％ confidence interval (CI) were calculated.In addition,linkage disequilibrium analysis was performed for the three SNPs by calculating the r2 and D' values.Results There was a difference in the allele frequencies of the three SNPs between the patients with psoriasis vulgaris and controls,but the difference was statistically significant in only the allele frequencies of rs17728338,but not in those of the other two SNPs after Bonferroni correction.Under the dominant inheritance model,the genotype frequencies of the 3 SNPs all significantly differed between the patients and controls after Bonferroni correction (all P ＜ 0.016 7).Stratification analysis showed that there was a significant difference in the allele and genotype frequencies of the three SNPs between the patients with a family history and healthy controls (all P ＜ 0.016 7),and the frequency of A allele of rs17728338 was significantly lower in the controls than in the patients with psoriasis vulgaris,patients with early-onset psoriasis vulgaris (n =355),patients with late-onset psoriasis vulgaris (n =107),patients with a family history (n =68),and patients without a family history (n =394) (all P ＜ 0.0167).Strong linkage disequilibrium existed between rs3762999 and rs999556 (r2 =0.910,D' =0.982),and moderate linkage disequilibrium existed between rs17728338 and rs3762999 (r2 =0.371,D' =0.989) as well as rs999556 (r2 =0.353,D' =1).Conclusion The SNPs rs17728338,rs3762999 and rs999556 in the TNIP1 gene were associated with psoriasis vulgaris in the Chinese Han population.