Objective:To evaluate the current situation of the protective effect of hearing protection device (HPD) worn by manufacturing workers and discuss their possible influencing factors.Methods:A total of 3634 noisy workers were surveyed and tested. The study conducted surveys of workers on the use of HPD. The 3M TM E-A-R Fit TM binaural verification system was used to measure the personal attenuation device (PAR) of workers wearing HPD. Results:The M ( Q1, Q3) of baseline PAR obtained by 3634 workers was 12 (2, 19) dB. There was a statistically significant difference in baseline PAR among the three types of HPDs ( H=336.39, P<0.01) . After pairwise comparison, it was found that the baseline PAR of workers wearing foam earplugs and earmuffs was higher than that of pre-molded earplugs ( P<0.01) . There were differences in baseline PAR among workers in different industries ( Z=359.73, P<0.01) . Education level, age of using HPD, types of HPDs, noise exposure intensity, with or without knowledge of correct methods, and comfort evaluation were the main factors affecting baseline PAR ( P<0.05) . There were 1536 workers (43.4%) failed the baseline PAR test. After the intervention, the median PAR increased significantly from 1 (0, 6) dB (baseline) to 18 (14, 22) dB (after the intervention) ( P<0.01) . The follow-up test found that the follow-up PAR of 328 workers was higher than the baseline PAR of the initial test, and the follow-up PAR was higher than the post-intervention PAR of the initial test ( P<0.01) . Conclusion:Under the conditions of this study, the protective effect of HPD was affected by factors such as incorrect understanding of wearing methods, exposure to high-intensity noise, low education level, a short period of time of HPD use and low comfort of hearing protectors. The protective effect could be improved through training, optimizing the wearing of hearing protector models, and follow-up interventions. Enterprises should use suitability verification to ensure the correct selection and wearing of noisy workers.

Objective:To observe and analyze the pathogenic genes and clinical phenotype characteristics of retinitis pigmentosa sinepigmento(RPSP).Methods:A retrospective clinical study. Two patients (proband) and five family members from two RPSP families admitted to Xiamen Eye Center of Xiamen University in December 2022 and Shenzhen Eye Hospital in July 2023 were included in the study. Two families have no blood relationship and were both Han Chinese. Detailed ocular and systemic medical history and specialized examinations were performed for all members, including color fundus photography, fundus autofluorescence (FAF), and full field electroretinogram (ff-ERG) examination. The peripheral venous blood of all members was collected, and genomic DNA was extracted. Pathogenic genes and their loci were screened using whole exome high-throughput sequencing technology. Sanger sequencing was used to verify the pathogenic genes in the two pedigrees. The pathogenicity of candidate variants was evaluated according to the American Society for American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants.Results:The two probands were male, aged 9 and 7 years, respectively. The main complaint was poor binocular vision for 6 and 3 years and poor treatment effect of amblyopia. The proband (Ⅱ2) in family 1 had a pale red color on the optic disc, with leopard-like changes in the posterior pole and thinner retinal arteries. FAF showed mottled fluorescence attenuation outside the macular vascular arch. There was no significant waveform in both bright and dark visual responses of ff-ERG. He also had 6-toed deformity of both feet, renal cysts, and a slightly overweight body. The clinical diagnosis was non-pigmentary retinitis pigmentosa. The proband of family 2 (Ⅱ1) had poor binocular vision in a dark environment and had atrophy lesions on the nasal side of the optic disc and leopard print like changes in the fundus. FAF showed uneven enhancement in the fovea. ff-ERG showed severe abnormalities in dark and light response, with significant decrease and delay in b-wave amplitude and latency. He had no other systemic abnormalities. The clinical diagnosis was binocular RPSP. There were no abnormal ocular and systemic manifestations in the two family members. Gene sequencing revealed a homozygous mutation (c.534+1G>T) of BBS2 gene, which was inherited from the mother and father respectively. Based on clinical manifestations and genetic testing results, the final diagnosis was Bardet Biedl syndrome. The genetic sequencing results confirmed a novel compound heterozygous mutation (c.950T>G: p. Leu317Arg missense mutation and c.849+1G>C splicing mutation) of BBS7 gene. His father (Ⅰ1) and mother (Ⅰ2) carried M1 heterozygous variants. Combined with the clinical manifestations and genetic testing results, the final diagnosis was Bardet-Biedl syndrome (BBS). Family 2 proband (Ⅱ1) carried the BBS7 gene C.950T>G (p.Leu317Arg) (M2) missense variation and C.849 +1G>C (M3) splice site variation. His father (Ⅰ1) and mother (Ⅰ2) carried M3 shear site variation and M2 missense variation, respectively. The two families all fit the autosomal recessive inheritance pattern, and the genotype and clinical phenotype were coseparated. According to ACMG guidelines, M1, M2 and M3 were all identified as possible pathogenic variants. Conclusions:BBS2 gene M1 homozygous variation and BBS7 gene M2, M3 complex heterozygous variation are the possible pathogenic genes in family 1 and family 2, respectively. Two families are affected by BBS and RPSP, respectively.

Objective:To evaluate the current situation of the protective effect of hearing protection device (HPD) worn by manufacturing workers and discuss their possible influencing factors.Methods:A total of 3634 noisy workers were surveyed and tested. The study conducted surveys of workers on the use of HPD. The 3M TM E-A-R Fit TM binaural verification system was used to measure the personal attenuation device (PAR) of workers wearing HPD. Results:The M ( Q1, Q3) of baseline PAR obtained by 3634 workers was 12 (2, 19) dB. There was a statistically significant difference in baseline PAR among the three types of HPDs ( H=336.39, P<0.01) . After pairwise comparison, it was found that the baseline PAR of workers wearing foam earplugs and earmuffs was higher than that of pre-molded earplugs ( P<0.01) . There were differences in baseline PAR among workers in different industries ( Z=359.73, P<0.01) . Education level, age of using HPD, types of HPDs, noise exposure intensity, with or without knowledge of correct methods, and comfort evaluation were the main factors affecting baseline PAR ( P<0.05) . There were 1536 workers (43.4%) failed the baseline PAR test. After the intervention, the median PAR increased significantly from 1 (0, 6) dB (baseline) to 18 (14, 22) dB (after the intervention) ( P<0.01) . The follow-up test found that the follow-up PAR of 328 workers was higher than the baseline PAR of the initial test, and the follow-up PAR was higher than the post-intervention PAR of the initial test ( P<0.01) . Conclusion:Under the conditions of this study, the protective effect of HPD was affected by factors such as incorrect understanding of wearing methods, exposure to high-intensity noise, low education level, a short period of time of HPD use and low comfort of hearing protectors. The protective effect could be improved through training, optimizing the wearing of hearing protector models, and follow-up interventions. Enterprises should use suitability verification to ensure the correct selection and wearing of noisy workers.

Objective:To observe and analyze the pathogenic genes and clinical phenotype characteristics of retinitis pigmentosa sinepigmento(RPSP).Methods:A retrospective clinical study. Two patients (proband) and five family members from two RPSP families admitted to Xiamen Eye Center of Xiamen University in December 2022 and Shenzhen Eye Hospital in July 2023 were included in the study. Two families have no blood relationship and were both Han Chinese. Detailed ocular and systemic medical history and specialized examinations were performed for all members, including color fundus photography, fundus autofluorescence (FAF), and full field electroretinogram (ff-ERG) examination. The peripheral venous blood of all members was collected, and genomic DNA was extracted. Pathogenic genes and their loci were screened using whole exome high-throughput sequencing technology. Sanger sequencing was used to verify the pathogenic genes in the two pedigrees. The pathogenicity of candidate variants was evaluated according to the American Society for American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants.Results:The two probands were male, aged 9 and 7 years, respectively. The main complaint was poor binocular vision for 6 and 3 years and poor treatment effect of amblyopia. The proband (Ⅱ2) in family 1 had a pale red color on the optic disc, with leopard-like changes in the posterior pole and thinner retinal arteries. FAF showed mottled fluorescence attenuation outside the macular vascular arch. There was no significant waveform in both bright and dark visual responses of ff-ERG. He also had 6-toed deformity of both feet, renal cysts, and a slightly overweight body. The clinical diagnosis was non-pigmentary retinitis pigmentosa. The proband of family 2 (Ⅱ1) had poor binocular vision in a dark environment and had atrophy lesions on the nasal side of the optic disc and leopard print like changes in the fundus. FAF showed uneven enhancement in the fovea. ff-ERG showed severe abnormalities in dark and light response, with significant decrease and delay in b-wave amplitude and latency. He had no other systemic abnormalities. The clinical diagnosis was binocular RPSP. There were no abnormal ocular and systemic manifestations in the two family members. Gene sequencing revealed a homozygous mutation (c.534+1G>T) of BBS2 gene, which was inherited from the mother and father respectively. Based on clinical manifestations and genetic testing results, the final diagnosis was Bardet Biedl syndrome. The genetic sequencing results confirmed a novel compound heterozygous mutation (c.950T>G: p. Leu317Arg missense mutation and c.849+1G>C splicing mutation) of BBS7 gene. His father (Ⅰ1) and mother (Ⅰ2) carried M1 heterozygous variants. Combined with the clinical manifestations and genetic testing results, the final diagnosis was Bardet-Biedl syndrome (BBS). Family 2 proband (Ⅱ1) carried the BBS7 gene C.950T>G (p.Leu317Arg) (M2) missense variation and C.849 +1G>C (M3) splice site variation. His father (Ⅰ1) and mother (Ⅰ2) carried M3 shear site variation and M2 missense variation, respectively. The two families all fit the autosomal recessive inheritance pattern, and the genotype and clinical phenotype were coseparated. According to ACMG guidelines, M1, M2 and M3 were all identified as possible pathogenic variants. Conclusions:BBS2 gene M1 homozygous variation and BBS7 gene M2, M3 complex heterozygous variation are the possible pathogenic genes in family 1 and family 2, respectively. Two families are affected by BBS and RPSP, respectively.

Objective·To explore the association between gene-gene interaction of glutamate pathway and anhedonia.Methods·A total of 279 patients with schizophrenia(SZ)and 236 patients with major depression disorder(MDD)recruited in the outpatient department and ward of Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 236 healthy controls(HC)recruited in the community from January 2017 to August 2020 were included in the study.General demographic data and clinical characteristics of the three groups were collected and compared.The Chinese version of Temporal Experience of Pleasure Scale(TEPS)was used to evaluate the pleasure experience ability of the three groups.Generalized multifactor dimensionality reduction(GMDR)method was used to establish the interaction model of the single nucleotide polymorphism(SNP)in glutamate pathway genes(NOS1AP,GSK3β,DAOA,DISC1 and GRIN2A).According to the interaction model,SZ and MDD patients were divided into high-risk group and low-risk group,and the differences in pleasure experience ability were compared between the two groups,so as to analyze the effect of gene-gene interaction on anhedonia.Results·There were significant differences in age and years of education among the three groups,and in age of onset and duration of illness between SZ and MDD groups(all P=0.000).There were significant differences among the three groups of participants in terms of overall pleasure experience,anticipatory pleasure experience and consummatory pleasure experience(all P=0.000);the overall pleasure experience,anticipatory pleasure experience and consummatory pleasure experience in the SZ and MDD group were lower than those in the HC group(all Pcorr=0.000),and there was marginal statistical difference in anticipatory pleasure experience between the SZ and MDD groups(Pcorr=0.051).Through GMDR modeling,it was found that the 2-loci interaction model composed of DAOA-rs3916965 and DISC1-rs821577 had a predictive effect on the overall pleasure experience ability of SZ patients(P=0.003),and the 2-loci interaction model composed of NOS1AP-rs1858232 and GRIN2A-rs1014531 had a predictive effect on the anticipatory pleasure experience ability of MDD patients(P=0.037);moreover,the overall pleasure experience ability of patients in the SZ high-risk group and anticipatory pleasure experience ability of patients in MDD high-risk groups were lower than those in their low-risk groups(t=3.443,P=0.000;t=3.471,P=0.001).Conclusion·The interaction of glutamate pathway gene polymorphisms may be involved in the occurrence of anhedonia.

Objective:To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring′s birth weight and risk of small for gestational age (SGA) infant.Methods:The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1 st September 2016 to 11 th November 2022. A standardized questionnaire was used to collect the mothers′ demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B 12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results:A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B 12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight ( β=-2.30, 95% CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight ( β=-7.39, 95% CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring ( RR=1.05, 95% CI 1.01-1.08, P=0.002). Periconceptional vitamin B 12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions:Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Background and aims:Kehuang(KH)capsule is an herbal medical product approved for the treatment of liver diseases,including liver injury,in China.However,the mechanism is still unclear.This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride(CCl4)-induced acute liver injury(ALI)in a murine model.Methods:Mice were randomly divided into control,model(CCl4),CCl4+KH_Low and CCl4+KH_High group.Liver enzyme levels and histological changes were assessed to evaluate liver injury.Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured.Additionally,network pharmacology was employed to explore the potential mechanisms of KH capsule.Results:KH capsule significantly reduced serum alanine aminotransferase(ALT)and aspartate amino-transferase(AST)levels,as well as the necrotic area in liver tissue.KH capsule also decreased the infil-tration of macrophages and neutrophils,thereby inhibiting the expression of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β).Furthermore,KH capsule decreased liver malondialdehyde(MDA)levels and increased superoxide dismutase(SOD)activity.The number of ter-minal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive cells in liver tissue was also reduced.The expression of nuclear factor erythroid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins was significantly elevated,while the protein expression of cyto-chrome P450 2E1(CYP2E1)was significantly reduced.Mass spectrometry identified genistein,galangin,wogonin,skullcapflavone Ⅱ,and hispidulin as potential active ingredients of KH capsule.Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways.Western blot analysis confirmed that KH capsule suppressed AKT,extracellular signal-regulated kinase(ERK),and p38 signaling.Conclusions:These findings suggest that KH capsule could exert protective effects against CCl4-induced ALI,with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mecha-nism of action.

Objective:To explore the application effect of case-based learning (CBL), teaching mode combined with 3D printing in clinical teaching of sacral tumors.Methods:A total of 108 undergraduate interns and standardized residency training students who studied in our hospital from 2017 to 2018 were divided into the CBL teaching group ( n = 53) and the CBL combined with 3D printing teaching group ( n = 55) according to their study time. The combined teaching group used computer tomography (CT) data to reconstruct and print out a 3D model of sacral tumors based on CBL, and performed preoperative teaching on the invasion of the surrounding tissues of the tumor. The scores of the students in the two groups were evaluated respectively, and the students were surveyed by self-identification questionnaire (learning interest, self-learning ability, teamwork ability, comprehensive analysis ability and clinical thinking ability). The t-test (one-sided) was used for comparison between groups using stata 14.0. Results:The score of CBL teaching group (75.90±6.70) was lower than that of CBL combined with 3D printing teaching group (83.60±7.40). In terms of critical thinking ability evaluation, self-learning ability, learning interest, comprehensive analysis ability and clinical thinking ability, the CBL combined 3D printing teaching group was superior to the CBL teaching group, and the difference was statistically significant ( P<0.001). In terms of teamwork ability, there was no statistical difference between the two groups. Conclusion:The CBL teaching mode combined with 3D printing can improve academic performance, students' learning interest and clinical thinking ability of sacral tumors in the teaching of undergraduate interns and standardized residency training students.

Background and Objectives: Galectin-3 promotes fibroblast-to-myofibroblast differentiation and facilitates injury repair. Previous studies have shown that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) promote the differentiation of myocardial fibroblasts into myofibroblasts under inflammatory environment. Whether hucMSC-ex derived Galectin-3 (hucMSC-ex-Galectin-3) plays an important role in fibroblast-to-myofibroblast differentiation is the focus of this study. Methods: and Results: Galectin-3 was knocked-down by siRNA in hucMSCs, and then exosomes were extracted. Fibroblasts were treated with LPS, LPS＋hucMSC-ex, LPS＋negative control-siRNA-ex (NC-ex), or LPS＋ Galectin-3-siRNA-ex (si-ex) in vitro. The coronary artery of the left anterior descending (LAD) branch was permanently ligated, followed by intramyocardial injection with phosphate buffered saline(PBS), hucMSC-ex, hucMSC-NC-ex, or hucMSC-si-ex in vivo. Western blot, RT-PCR, and immunohistochemistry were used to detect the expression of markers related to fibroblast-to-myofibroblast differentiation and inflammatory factors. Migration and contraction functions of fibroblasts were evaluated using Transwell migration and collagen contraction assays, respectively. β-catenin expression was detected by western blot and immunofluorescence. The results showed that hucMSC-ex increased the protein expression of myofibroblast markers, anti-inflammatory factors, and β-catenin. HucMSC-ex also reduced the migration and promoted the contractility of fibroblasts. However, hucMSC-si-ex did not show these activities. Conclusions HucMSC-ex-Galectin-3 promoted the differentiation of cardiac fibroblasts into myofibroblasts in an inflammatory environment, which was associated with increased β-catenin levels.