Background Pyrethroid pesticides (PYRs) can cross the placental barrier to cause intrauterine fetal exposure, which may lead to developmental immunotoxicity (DIT). However, the specific effect of maternal PYR exposure during pregnancy on the cellular immune function of 1-year-old children remains unclear. Objective To explore the effect of PYRs exposure throughout the entire pregnancy on peripheral blood lymphocytes in 1-year-old children and potential sensitive window period of PYRs exposure. Methods A birth cohort was established by enrolling pregnant women in their first trimester and following them and their infants until one year of age. Ultra-high performance liquid chromatography-tandem mass spectrometry was used to detect the levels of PYRs metabolites, including 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid (cis-DBCA), in the urine of pregnant women during the first trimester (gestational weeks 6-12), the second trimester (gestational weeks 21-24), and the third trimester (gestational weeks 33-36). Peripheral blood leukocyte and lymphocyte counts were measured in children at 12 months of age using the Coulter principle combined with flow cytometry. Exposure levels of PYRs metabolites in each trimester were divided into low, moderate, and high exposure groups based on the 25th (P₂₅) and 75th (P₇₅) percentiles. Meanwhile, participants were classified as having repeated high or low exposure if their metabolite levels were > P₇₅ or <P₂₅ in at least two trimesters, respectively, while all others were categorized as having repeated moderate exposure. Generalized linear models were used to analyze the associations between trimester-specific and repeated PYRs metabolite exposure levels and the peripheral blood white blood cell (WBC) and lymphocyte counts in children aged 1 year. Results A total of 336 mother-child pairs were included in this study. For the pregnant women, the total detection rates of maternal urinary 3PBA, 4F3PBA, and cis-DBCA across the three trimesters of pregnancy were 80.5%, 100.0%, and 81.3%, respectively; and median creatinine-corrected concentrations were 0.24, 0.36, and 0.42 μg·g⁻¹, respectively. In children aged 1 year, the mean WBC and lymphocyte counts in peripheral blood were (8.9±2.0)×10⁹·L⁻¹ and (5.7±1.6)×10⁹·L⁻¹, respectively. The results of the generalized linear model analysis indicated that compared to the low exposure group, the high cis-DBCA exposure group during the third trimester of pregnancy had significantly lower peripheral blood WBC count (β=−0.87, 95%CI: −1.51, −0.23) and lymphocyte count (β=−0.64, 95%CI: −1.15, −0.13); and the repeated high-exposure group of cis-DBCA had significantly lower peripheral blood WBC count (β=−1.34, 95%CI: −2.34, −0.34) and lymphocyte count (β=−0.80, 95%CI: −1.60, −0.01) than the repeated low exposure group. Similarly, the repeated moderate-exposure group of cis-DBCA had a significantly lower peripheral blood WBC count (β=−0.83, 95%CI: −1.59, −0.07) than the repeated low exposure group. Conclusion High maternal exposure to PYRs with cis-DBCA as the major metabolite exposure is associated with decreased peripheral leukocyte and lymphocyte counts in children aged 1 year, and repeated high-level exposure throughout gestation appears to exacerbate DIT in offspring. The third trimester of pregnancy maybe a sensitive window for children's DIT induced by exposure to PYRs during pregnancy.

Objective:To evaluate the potential of IgG N-glycans as diagnostic biomarker for ankylosing spondylitis (AS) by comparing and analyzing the IgG N-glycan profiles with AS and healthy controls.Methods:A 1∶1 matched case-control study design was adopted, 81 AS patients who visited the Department of Rheumatology and Immunology at Taian City Central Hospital and the Second Affiliated Hospital of Shandong First Medical University between July 2020 and June 2021 were recruited. These patients were matched with 81 healthy individuals undergoing routine physical checkup. The levels of IgG N-glycosylation in human plasma were quantitatively measured using ultrahigh-performance liquid chromatography. Binomial logistic regression analysis was performed to identify IgG N-glycan biomarkers associated with AS.Results:A total of 14 primary glycans and 13 derived traits showed statistically significant differences between the AS case group and the control group. Binomial logistic regression analysis showed that glycan peak 4, agalactosylated glycans, fucosylated glycans, and fucosylated agalactosylated glycans were positively associated with AS[ OR(95% CI)=1.12(1.01, 1.42), 1.21(1.03, 1.43), 1.48(1.08, 2.03), and 1.27(1.04, 1.55); P=0.036, 0.022, 0.039, 0.020, respectively]. In terms of diagnostic performance, the single glycan GP4 exhibited the largest area under the ROC curve, with an AUC (95% CI) 0.751 (0.677, 0.826), while the combined glycan indicators (GP4+G0+F+FG0) achieved an AUC (95% CI) 0.768(0.697, 0.840). Conclusion:IgG N-glycans have the potentials to serve as candidate biomarkers for AS, and warrants further investigation.

Objective:To analyze the selection of internal fixation methods, surgical outcomes, and complications in patients with Neurofibromatosis Type 1 (NF1) accompanied by dystrophic lumbosacral deformities, and to evaluate the indications for pelvic fixation.Methods:A retrospective analysis was conducted on 21 patients with NF1 and associated dystrophic lumbosacral malformations (L 4 to sacrum) who underwent spinal deformity correction surgery at Nanjing Drum Tower Hospital from January 2009 to November 2022. The cohort included 11 males and 10 females, with a mean surgical age of 15.4±4.7 years (range, 7-24 years). Patients were divided into two groups based on whether pelvic fixation was performed: 10 patients in the non-pelvic fixation group (NP group) and 11 in the pelvic fixation group (P group), where fixation involved second sacral alar-iliac (S 2AI) screws or iliac screws. Radiographic parameters, including the Cobb angle of the lumbosacral fractional curve, main curve, and focal kyphosis, were compared preoperatively, postoperatively, and at the last follow-up. Results:The NP group had a significantly lower mean age (13.2±4.9 years) compared to the P group (17.5±3.5 years; t=2.287, P=0.034). Spinal instability (rotational subluxation or spondylolisthesis) due to dystrophic changes was observed in 2 patients in the NP group and 8 in the P group, a statistically significant difference (χ 2=5.838, P=0.030). In the P group, five patients underwent unilateral fixation and six underwent bilateral fixation. Implant types included 2 cases with iliac screws, 1 case with iliac screws plus S 2AI, and 8 cases with S 2AI screws alone. The utilization rate of hooks was significantly higher in the NP group (12.6%±11.5%) compared to the P group (3.5%±6.9%; t=2.230, P=0.038). The preoperative Cobb angle of the lumbosacral fractional curve was significantly smaller in the NP group (13.8°±9.0°) than in the P group (25.5°±13.9°; t=2.228, P=0.039). Postoperatively, the angles were corrected to 6.3°±6.1° and 6.4°±5.3°, respectively ( t=0.901, P=0.969), with correction rates of 57.3%±13.6% and 74.1%±17.8% ( t=2.369, P=0.029). At final follow-up, the angles remained stable (6.6°±6.6° vs. 6.3°±4.8°; t=0.116, P=0.909). For the main curve, preoperative Cobb angles were 52.5°±15.1° (NP) and 61.1°±16.9° (P; t=1.200, P=0.246), corrected to 31.3°±13.8° and 28.0°±8.4°, respectively ( t=0.646, P=0.526). Correction rates were 41.3%±13.0% in the NP group and 53.2%±11.6% in the P group ( t=2.206, P=0.037). At the final follow-up, these values were 32.4°±14.2° and 31.7°±10.3° ( t=0.133, P=0.896). Focal kyphosis, seen in 9 patients, was corrected from 19.7°±10.9° preoperatively to -13.6°±9.5° postoperatively, and remained at -14.1°±9.6° at the final follow-up ( F=33.547, P<0.001). Multi-rod systems were used in 6 cases (NP group) and 7 cases (P group), with no significant difference (χ 2=0.153, P=0.926). Two patients in the NP group developed coronal decompensation three years postoperatively, and one required revision surgery. In the P group, rod breakage occurred in 3 patients, two of whom underwent revision. Conclusions:Dystrophic rotational subluxation or spondylolisthesis of the lumbosacral spine is a primary indication for pelvic fixation in patients with NF1-associated deformities. However, complications related to internal fixation remain common. The combined use of a multi-rod screw-hook hybrid system, particularly when extending across the lumbosacral region, may reduce the risk of instrumentation failure.

Objective:To analyze the selection of internal fixation methods, surgical outcomes, and complications in patients with Neurofibromatosis Type 1 (NF1) accompanied by dystrophic lumbosacral deformities, and to evaluate the indications for pelvic fixation.Methods:A retrospective analysis was conducted on 21 patients with NF1 and associated dystrophic lumbosacral malformations (L 4 to sacrum) who underwent spinal deformity correction surgery at Nanjing Drum Tower Hospital from January 2009 to November 2022. The cohort included 11 males and 10 females, with a mean surgical age of 15.4±4.7 years (range, 7-24 years). Patients were divided into two groups based on whether pelvic fixation was performed: 10 patients in the non-pelvic fixation group (NP group) and 11 in the pelvic fixation group (P group), where fixation involved second sacral alar-iliac (S 2AI) screws or iliac screws. Radiographic parameters, including the Cobb angle of the lumbosacral fractional curve, main curve, and focal kyphosis, were compared preoperatively, postoperatively, and at the last follow-up. Results:The NP group had a significantly lower mean age (13.2±4.9 years) compared to the P group (17.5±3.5 years; t=2.287, P=0.034). Spinal instability (rotational subluxation or spondylolisthesis) due to dystrophic changes was observed in 2 patients in the NP group and 8 in the P group, a statistically significant difference (χ 2=5.838, P=0.030). In the P group, five patients underwent unilateral fixation and six underwent bilateral fixation. Implant types included 2 cases with iliac screws, 1 case with iliac screws plus S 2AI, and 8 cases with S 2AI screws alone. The utilization rate of hooks was significantly higher in the NP group (12.6%±11.5%) compared to the P group (3.5%±6.9%; t=2.230, P=0.038). The preoperative Cobb angle of the lumbosacral fractional curve was significantly smaller in the NP group (13.8°±9.0°) than in the P group (25.5°±13.9°; t=2.228, P=0.039). Postoperatively, the angles were corrected to 6.3°±6.1° and 6.4°±5.3°, respectively ( t=0.901, P=0.969), with correction rates of 57.3%±13.6% and 74.1%±17.8% ( t=2.369, P=0.029). At final follow-up, the angles remained stable (6.6°±6.6° vs. 6.3°±4.8°; t=0.116, P=0.909). For the main curve, preoperative Cobb angles were 52.5°±15.1° (NP) and 61.1°±16.9° (P; t=1.200, P=0.246), corrected to 31.3°±13.8° and 28.0°±8.4°, respectively ( t=0.646, P=0.526). Correction rates were 41.3%±13.0% in the NP group and 53.2%±11.6% in the P group ( t=2.206, P=0.037). At the final follow-up, these values were 32.4°±14.2° and 31.7°±10.3° ( t=0.133, P=0.896). Focal kyphosis, seen in 9 patients, was corrected from 19.7°±10.9° preoperatively to -13.6°±9.5° postoperatively, and remained at -14.1°±9.6° at the final follow-up ( F=33.547, P<0.001). Multi-rod systems were used in 6 cases (NP group) and 7 cases (P group), with no significant difference (χ 2=0.153, P=0.926). Two patients in the NP group developed coronal decompensation three years postoperatively, and one required revision surgery. In the P group, rod breakage occurred in 3 patients, two of whom underwent revision. Conclusions:Dystrophic rotational subluxation or spondylolisthesis of the lumbosacral spine is a primary indication for pelvic fixation in patients with NF1-associated deformities. However, complications related to internal fixation remain common. The combined use of a multi-rod screw-hook hybrid system, particularly when extending across the lumbosacral region, may reduce the risk of instrumentation failure.

Objective:To evaluate the potential of IgG N-glycans as diagnostic biomarker for ankylosing spondylitis (AS) by comparing and analyzing the IgG N-glycan profiles with AS and healthy controls.Methods:A 1∶1 matched case-control study design was adopted, 81 AS patients who visited the Department of Rheumatology and Immunology at Taian City Central Hospital and the Second Affiliated Hospital of Shandong First Medical University between July 2020 and June 2021 were recruited. These patients were matched with 81 healthy individuals undergoing routine physical checkup. The levels of IgG N-glycosylation in human plasma were quantitatively measured using ultrahigh-performance liquid chromatography. Binomial logistic regression analysis was performed to identify IgG N-glycan biomarkers associated with AS.Results:A total of 14 primary glycans and 13 derived traits showed statistically significant differences between the AS case group and the control group. Binomial logistic regression analysis showed that glycan peak 4, agalactosylated glycans, fucosylated glycans, and fucosylated agalactosylated glycans were positively associated with AS[ OR(95% CI)=1.12(1.01, 1.42), 1.21(1.03, 1.43), 1.48(1.08, 2.03), and 1.27(1.04, 1.55); P=0.036, 0.022, 0.039, 0.020, respectively]. In terms of diagnostic performance, the single glycan GP4 exhibited the largest area under the ROC curve, with an AUC (95% CI) 0.751 (0.677, 0.826), while the combined glycan indicators (GP4+G0+F+FG0) achieved an AUC (95% CI) 0.768(0.697, 0.840). Conclusion:IgG N-glycans have the potentials to serve as candidate biomarkers for AS, and warrants further investigation.

Objective To summarize the liver biopsy and clinical features of patients with liver injury of unknown origin,and to investigate the value of ultrasound-guided percutaneous liver biopsy in the diagnosis of liver injury of unknown origin.Methods A retrospective analysis was performed for the clinical data and ultrasound-guided percutaneous liver biopsy results of 94 patients with liver injury of unknown origin who were admitted to Zhongshan Hospital,Xiamen University,from January 2018 to February 2023.According to the proportion of the patients with different final diagnoses,the patients were divided into autoimmune liver disease(AILD)group,metabolic associated fatty liver disease(MAFLD)group,drug-induced liver injury(DILI)group,alcoholic liver disease(ALD)group,and unknown group.An analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the Bonferroni analysis or the Dunnett'T3 test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups;the Fisher's exact test was used for comparison of categorical data between multiple groups.Results All 94 patients with liver injury of unknown origin underwent ultrasound-guided percutaneous liver biopsy after admission,among whom 90 patients(95.7%)had a confirmed diagnosis based on liver biopsy and clinical features.There were 43 patients(45.7%)with AILD,21(22.3%)with MAFLD,15(16.0%)with DILI,6(6.4%)with ALD,1(1.1%)with AILD and MAFLD,1(1.1%)with hemochromatosis,1(1.1%)with Budd-Chiari syndrome,1(1.1%)with congenital hepatic fibrosis,and 1(1.1%)with idiopathic portal hypertension,while 4 patients(4.3%)still had an unknown etiology after liver biopsy.There were significant differences between the patients with top five diagnoses in age(F=4.457,P<0.05),body mass index(BMI)(F=3.245,P<0.05),aspartate aminotransferase(AST)(H=11.128,P<0.05),gamma-glutamyl transpeptidase(GGT)(H=24.789,P<0.05),alkaline phosphatase(ALP)(H=26.013,P<0.05),IgG(H=19.099,P<0.05),IgM(H=21.263,P<0.05),AMA-M2 positive rate(P<0.05),and ANA positive rate(P<0.05).Compared with the MAFLD group,the AILD group had significantly higher age,AST,GGT,and ALP and a significantly lower BMI;compared with the MAFLD group and the DILI group,the AILD group had significant increases in IgG and IgM;the AILD group had significant increases in the positive rates of AMA-M2 and ANA compared with the other four groups.Conclusion AILD,MAFLD,and DILI are the most common causes in patients with liver injury of unknown origin.Ultrasound-guided percutaneous liver biopsy plays an important role in determining the cause of liver injury of unknown origin,but it is still needed to make a comprehensive analysis based on clinical history,different types of liver injury,laboratory markers,and imaging data.

Objective:To evaluate the effect of losartan on acute kidney injury (AKI) and the relationship with mitochondrial fusion-fission in septic mice.Methods:One hundred and twenty-eight SPF male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (Sham group), sham operation+ losartan group (Sham+ LOS group), sepsis-associated AKI group (SA-AKI group), and sepsis-associated AKI+ losartan group (SA-AKI+ LOS group). Sepsis was induced by cecal ligation and puncture in anesthetized mice. Sham+ LOS group and SA-AKI+ LOS group received intraperitoneal injection of losartan 5 mg/kg, once a day, for 3 consecutive days, starting from 3 days before sham operation or developing the model. The equal volume of solvent was given instead in Sham group and SA-AKI group. Twenty mice were randomly selected to observe the survival 7 days after surgery. At 24 h after sham operation or establishing the model, serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were determined by the colorimetric method, and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high-mobility group box 1 protein (HMGB1) were measured using enzyme-linked immunosorbent assay. Renal tissues were obtained for microscopic examination of pathological changes which were scored and for determination of mitochondrial membrane potential (using JC-1 method) and expression of dynamin-related protein 1 (Drp1) and mitofusin-2 (Mfn2) (using Western blot). Results:Compared with Sham group, the survival rate was significantly decreased, the serum BUN, Cr, TNF-α, IL-6 and HMGB1 concentrations and renal tubular injury score were increased, the ATP content and MMP were decreased, the expression of Drp1 was up-regulated, the expression of Mfn2 was down-regulated ( P<0.05), and pathological changes were found in renal tissues in SA-AKI group and SA-AKI+ LOS group. Compared with SA-AKI group, the survival rate was significantly increased, serum concentrations of BUN, Cr, TNF-α, IL-6 and HMGB1 and renal tubular injury score were decreased, the ATP content and MMP were increased, the expression of Drp1 was down-regulated, the expression of Mfn2 was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in SA-AKI+ LOS group. Conclusions:Losartan can alleviate AKI in septic mice, and the mechanism may be related to promoting mitochondrial fusion and inhibiting mitochondrial fission.

Arsenic, a naturally occurring metal-like chemical element, is one of the 10 chemicals of major public concerns listed by the World Health Organization as harmful to the environment and human health. It can enter the human body through breathing, intaking food, drinking water, skin exposure, and other ways, and long-term exposure to arsenic can cause cancer of multiple organs and impaired function of multiple systems. Epigenetic mechanisms play an important role in arsenic-induced health effects, and research suggested that the carcinogenicity of arsenic may be associated with epigenetic changes. Previous studies focused on the effects of arsenic on DNA methylation modification. In recent years, research showed that 5-hydroxymethylcytosine (5-hmC), an intermediate of active demethylation of DNA, can act as a sensitive epigenetic mark and play a crucial role as a "bridge" between arsenic exposure and health effects. Based on the latest research progress on the role of DNA hydroxymethylation in the health effects associated with arsenic exposure, this article briefly described the relationship between the health effects of arsenic exposure and DNA hydroxymethylation, summarized the possible mechanisms of DNA hydroxymethylation in the health effects associated with arsenic exposure, and provided a scientific basis for preventing and treating the health effects associated with arsenic exposure.

Objective:To explore the genotype and clinical phenotype characteristics of patients with pancreatic agenesis caused by GATA6 gene mutations and to improve the clinical understanding of pancreatic agenesis.Methods:The clinical data of a newborn with pancreatic agenesis admitted to the Second Hospital of Shandong University were retrospectively analyzed. Relevant literature published until October 31, 2022, were retrieved from China National Knowledge Infrastructure, Wanfang Database, VIP Database, Chinese Medical Journal Full Text Database, PubMed, Embase and SCI Database with the terms of "pancreatic agenesis", "GATA6", "pancreatic agenesis/hypoplasia" and "GATA6 Translation Factor". The characteristics of gene variants and clinical manifestations of patients diagnosed with pancreatic agenesis caused by GATA6 gene mutation were retrieved and summarized.Results:This case was a full-term male infant who developed insulin dependent hyperglycemia and fatty diarrhea 2 d after birth, accompanied by intrauterine growth restriction, congenital heart disease, and cryptorchidism. Genetic testing showed a novel heterozygous mutation of GATA6 (c.1366C>T) which was consistent with the autosomal dominant inheritance pattern. The phenotype and genotype between the proband and his parents were consistent with the cosegregation. The ACMG mutation was rated as pathogenic variant. Intravenous infusion of insulin, subcutaneous injection of insulin, or long-acting insulin were not effective. After continuous subcutaneous pumping of aspartic insulin combined with oral pancreatic enzyme replacement therapy, the infant's condition was improved and discharged. Follow up to age of 15 months, the patient still relied on continuously subcutaneous pump to control blood glucose, pancreatic exocrine function was back to normal, and the development was generally normal. A total of 59 cases were reported in 22 articles, with the case from our hospital, there were 60 patients in total. Among them, 47 were probands and 13 were family members, about 61.7% (29/47) of which were de novo mutations. There were 39 variants, of which 28.2% (11/39) were missense mutations and 71.8% (28/39) were functional deletion variations. Mutations of GATA6 gene had a broad phenotype spectrum. The phenotypes mainly included neonatal diabetes mellitus ( n=39) and pancreatic exocrine insufficiency ( n=39). Other extra-pancreatic features included different types of congenital heart disease ( n=54), congenital biliary abnormalities ( n=23), intestinal developmental disorders ( n=16), neurocognitive disorders ( n=18) and endocrine abnormalities ( n=15). Conclusions:The heterozygous variations of GATA6 gene lead to pancreatic hypoplasia and a broad phenotype spectrum. The pancreatic phenotypes mainly include neonatal diabetes mellitus and pancreatic exocrine insufficiency, and extra-pancreatic phenotypes include congenital heart disease and other developmental abnormalities.

Objective:To explore the association between polymorphism of Histone Deacetylase 2 (HDAC2) gene and alcohol use disorder (AUD) in male people of Han nationality for seeking suitable single nucleotide loci(SNP), and provide reference for early diagnosis and intervention of alcohol use disorder(AUD).Methods:A total of 194 male AUD patients of Han nationality (case group) and 310 normal men of Han nationality (control group) were selected for the study. The genomic DNA of peripheral blood of the subjects in the two groups was extracted, and 13 SNP loci of HDAC2 gene were obtained from HapMap database. The subjects in the two groups were genotyped by Agena MassARRAY SNP genotyping method.SPSS 25.0 was used to statistically analyze the differences of genotype frequency and allele frequency between the two groups, and Haploview 4.2 software was used for linkage disequilibrium and haploid analysis. The multiple test correction was carried out by the replacement test with 50 000 replacement times.Results:The genotype frequency of the 3 SNP loci(rs9481408, rs6568819, rs9488289) of HDAC2 gene were statistically significant different between the case group and the control group (all P<0.05). Further analysis found that the three loci were significantly correlated with AUD in the recessive genetic model between case group and control group(T/T vs C/C-C/T: OR=1.78, 95% CI: 1.05-3.03, P=0.033; T/T vs C/C-C/T: OR=1.79, 95% CI: 1.05-3.03, P=0.032; G/G vs C/C-C/G: OR=1.85, 95% CI: 1.09-3.13, P=0.022). Seven SNP haplotypes were constructed and the association odds ratio of GATCTGCAATAA between the case group and control group was 2.44, and the difference was statistically significant ( P<0.05). Conclusion:The SNP loci rs9481408, rs6568819, rs9488289 in the HDAC2 gene and haplotype GATCTGCCAATAA are associate with AUD in male people of Han nationality. These results indicated that the HDAC2 gene is one of the susceptibility genes of AUD.