Background Per- and polyfluoroalkyl substances (PFAS), a group of persistent organic pollutants associated with adverse health effects including hepatotoxicity, immunosuppression, and carcinogenicity, have undergone risk assessments by multiple international organizations, with dietary exposure being the primary pathway. Objective To characterize the exposure to PFAS from food and drinking water sources of elderly residents in Songjiang District of Shanghai and to evaluate associated health risk and health effects. Methods A cross-sectional study was conducted from May to July 2024 in Songjiang District based on the Shanghai Suburban Adult Cohort and Biobank (SSACB) cohort. Dietary surveys were administered via face-to-face interviews among older adults aged 65 years and above, yielding 4 583 valid questionnaires. The estimated daily intake (EDI) of PFAS was calculated by integrating data from the Sixth National Dietary Survey and recent literature on PFAS concentrations in food and drinking water in Shanghai. Health risk assessment was performed using health-based guideline values (HBGV) proposed by various institutions and studies. Additionally, correlation analysis and linear regression modeling of EDI and biochemical indicators in the elderly were conducted to evaluate potential adverse health effects. Results The elderly population in Songjiang District exhibited dietary characteristics consistent with the Eastern Healthy Diet Pattern. Among PFAS compounds, PFOA showed the highest level of oral exposure [mean: 1.495 ng·(kg·d⁻¹)], followed by PFOS [mean: 0.637 ng·(kg·d⁻¹)], PFHxS [mean: 0.636 ng·(kg·d⁻¹)], and PFBS [mean: 0.273 ng·(kg·d⁻¹)]. Specifically, drinking water was the primary source of PFOA [1.415 ng·(kg·d⁻¹), accounting for 94.60%], while aquatic products were the major source of PFOS [0.278 ng·(kg·d⁻¹), accounting for 43.66%]. Using the HBGV derived by China's epidemiological studies, the mean hazard index (HI) for PFAS exposure was 1.39, indicating 54.35% of the population had potential health risks (HI>1). Following the 2024 standard established by the Food Safety Commission of Japan (FSCJ), the HI value dropped to 0.11, suggesting negligible risk. PFAS exposure was negatively associated with triglyceride levels and the indicators of liver and kidney function, but positively associated with low-density lipoprotein cholesterol (LDL-C) and lung cancer markers in the elderly residents. Conclusion PFAS exposure among the elderly residents in Songjiang District is predominantly attributed to PFOA, PFOS, PFHxS, and PFBS, with drinking water and aquatic products identified as primary exposure sources. Current exposure levels demonstrate significant associations with biomarkers of lipid metabolism and lung cancer markers, suggesting potential population health risks. These findings underscore the urgent need to establish HBGV for PFAS compounds based on Chinese population-specific metabolic characteristics.

Background Water serves as an indispensable resource for human survival and constitutes one of the primary means through which humans are exposed to environmental chemicals. Consequently, the safety of drinking water is critical to safeguarding public health. Objective To analyze the levels of the 10 metal/metalloid indicators [Al, Fe, Mn, Cu, Zn, As, Cd, Cr(VI), Pb, and Hg] in drinking water from a region of the Fuchun River Basin, and to evaluate the health risks in drinking water through oral ingestion. Methods In accordance with the national Standard Examination Method for Drinking Water – Part 2: Collection and Preservation of Water Samples (GB/T 5750-2006 and GB/T 5750-2023), a total of 2016 drinking water samples were collected from urban and rural water supply systems in a region of the Fuchun Basin from 2017 to 2024. Two batches of water samples were collected annually during the dry and wet seasons, with each batch comprising 72 samples from the urban water supply system and 54 samples from the rural water supply system. These samples were analyzed according to the Standard Examination Method for Drinking Water – Part 6: Metal and Metalloid Indicators (GB/T 5750-2006 and GB/T 5750-2023) and the results were compared with the limits specified in the Standards for Drinking Water Quality (GB 5749-2022). Health risks were evaluated using the U.S. Environmental Protection Agency (EPA) health risk assessment model. Results All tested metal/metalloid elements in the drinking water samples of the area met the national standards. The results of risk assessment showed that the non-carcinogenic risks associated with oral intake of drinking water, ranked from highest to lowest, were as follows: As>Cr(VI)>Pb>Cd>Hg>Mn>Cu>Zn>Fe>Al, with values of 4.55×10⁻², 2.79×10⁻², 2.06×10⁻², 1.20×10⁻², 4.95×10⁻³, 4.58×10⁻³, 2.85×10⁻³, 1.95×10⁻³, 1.52×10⁻³, and 9.21×10⁻⁴, respectively. The non-carcinogenic risk of each indicator was less than 1, which suggested no potential risk to population health. The carcinogenic risks ranked as Cr(VI)>As>Cd>Pb, with values of 4.18×10⁻⁵, 2.05×10⁻⁵, 3.85×10⁻⁶, and 2.45×10⁻⁷, respectively. The carcinogenic risks of Cr(VI), As, and Cd were between 10⁻⁶ and 10⁻⁴, which suggested an acceptable carcinogenic risk, while the carcinogenic risk of Pb was relatively negligible. Children's total non-carcinogenic/total carcinogenic risks were comparable to those of adult males, both higher than those of adult females. Additionally, rural areas exhibited higher non-carcinogenic/carcinogenic risks for Cr(VI), while those risks for As and Pb were lower than those in urban water samples, and those risks for Cd were comparable between the two. Conclusion The concentrations of the 10 metal/metalloid indicators in drinking water from the studied region in the Fuchun River Basin comply with the national standards from 2017 to 2024. There is a certain carcinogenic risk associated with oral intake of drinking water, but it is still within the acceptable range. In terms of non-carcinogenic risk, no potential threat to population health is anticipated.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the characteristics of SMN1 gene variants and carry out functional verification for two children with Spinal muscular atrophy (SMA). Methods:Two male children with complicated SMA diagnosed at the Children′s Hospital Affiliated to Capital Institute of Pediatrics respectively in July 2021 and April 2022 due to delayed or retrograde motor development were selected as the study subjects. Clinical data of the children were collected. Primary culture of skin fibroblasts was carried out, and peripheral blood samples were collected from both children and their parents. Multiplex ligation-dependent probe amplification, combined long-range PCR and nested PCR, and Sanger sequencing were carried out to detect the copy number and variants of the SMN1 gene. Absolute quantitative real-time PCR, Western blotting and immunofluorescence were used to determine the transcriptional level of the SMN gene, expression of the SMN protein, and the number of functional SMN protein complexes (gems body), respectively. This study was approved by Medical Ethics Committee of the Children′s Hospital Affiliated to Capital Institute of Pediatrics (Ethics No. SHERLLM2021009). Results:Child 1, a 1-year-old boy, was clinically diagnosed with type 1 SMA. Child 2, a 2-and-a-half-year-old boy, was clinically diagnosed with type 3 SMA. Both children were found to harbor a paternally derived SMN1 deletion and a maternally derived SMN1 gene variant, namely c. 824G>T (p.Gly275Val) and c. 884A>T (p.*295Leu). Compared with the normal controls and carriers, the levels of full-length SMN1 transcripts in their peripheral blood and skin fibroblast cell lines were significantly decreased ( P<0.05), and the levels of SMN protein normalized to that of β-actin, and the numbers of gems bodies in the primary fibroblast cells were also significantly lower ( P<0.05). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were classified as likely pathogenic (PS3+ PM3+ PM5+ PP3; PS3+ PM3+ PM4+ PP3). Following the diagnosis, both children had received nusinersen treatment. Although their motor function was improved, child 1 still died at the age of 2 due to severe pulmonary infection. The walking ability of child 2 was significantly improved, and his prognosis appeared to be good. Conclusion:Two cases of clinically complicated SMA have been confirmed by genetic testing and experimental studies, which has provided a reference for their accurate treatment.

The endoplasmic reticulum is a key site for protein production and quality control.More than one-third of proteins are synthesized and folded into the correct three-dimensional conformation in the endoplasmic reticulum.However,during protein folding,unfolded and/or misfolded proteins are prone to occur,which may lead to endoplasmic reticulum stress.Organisms can monitor the quality of the proteins produced by endoplasmic reticulum quality control(ERQC)and endoplasmic reticulum-associated degradation(ERAD),which maintain endoplasmic reticulum protein homeostasis by degrading abnormally folded proteins.The underlying mechanisms of protein folding and ERAD in mammals have not yet been fully explored.Therefore,this paper reviews the process and function of protein folding and ERAD in mammalian cells,in order to help clinicians better understand the mechanism of ERAD and to provide a scientific reference for the treatment of diseases caused by abnormal ERAD.

Objective:To clarify the transitional components in the blood of compound Banlangen Granules; To explore the mechanism of drugs in the treatment of epidemic encephalitis B, hepatitis and parotitis.Methods:The transitional components in blood of compound Banlangen Granules were analyzed by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The regulatory targets and pathways of compound Banlangen Granules in the treatment of epidemic encephalitis B, hepatitis and parotitis were analyzed based on UPLC-MS/MS and network pharmacology.Results:A total of 9 blood components were identified, of which 8 were prototype components, including sucrose, o-aminobenzoic acid, uridine, adenosine, guanosine, indole-3-acetonitrile-2 murine-S-β-D-glucopyranoside and salicylic acid. Through network pharmacological analysis, it was concluded that compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.Conclusion:The 9 blood components of compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.

Flubromazolam(Flub)is a novel psychoactive substance of benzodiazepines and the mechanism underlying its addiction still remains elusive.This study investigated the reward effect of Flub using conditioned place preference(CPP)mouse model.The neuronal activity was evaluated by c-Fos expression,and the neural circuit was tracked by virus tracing.This study also investigated the regulatory effect of neural circuits on Flub-induced reward effects through chemogenetic approach.The results showed that,at the dose of 3 mg/kg,Flub significantly increased CPP score and c-Fos expression in dopaminergic(DA)neurons of ventral tegmental area(VTA).Inhibition of VTA dopaminergic neuron activity dramatically decreased Flub-induced CPP score.Virus tracing verified GABAergic neuronal projection of medial rostrum tegmental nucleus(RMTg)to VTA dopaminergic neurons.Activation of RMTgGABA→VTADA circuit or blockade of benzodiazepine receptors(BZR)in RMTg significantly decreased Flub-induced CPP score.These results indicate that Flub produced reward effect via BZR-mediated RMTgGABA→VTADA circuit.

Objective:To discuss the clinical efficacy and plausible mechanism of Tiao Yang Qu Xie(regulating Yang to eliminate pathogenic factors)needling method plus paroxetine in treating mild-to-moderate depression. Methods:Sixty-six patients with mild-to-moderate depression were divided into an observation group and a control group using the random number table method,each consisting of 33 cases.Another 25 healthy subjects were recruited as a healthy group.The control group took oral paroxetine tablets for treatment,and the observation group received additional acupuncture treatment 3 times weekly.Both groups underwent 4-week treatment.Before treatment,after 2-week and 4-week treatment,and 2 weeks after treatment(follow-up),the patients were assessed using the Hamilton depression scale-17-item(HAMD-17),self-rating depression scale(SDS),self-rating anxiety scale(SAS),and traditional Chinese medicine(TCM)pattern element identification scale for depression.The two groups each randomly contributed 25 cases to detect the protein content of brain-derived neurotrophic factor(BDNF)before treatment and after 4-week treatment,and compared with the healthy group. Results:After 2-week treatment,the markedly effective and total effective rates were significantly higher in the observation group than in the control group(P<0.05);after 4-week treatment,the observation group significantly surpassed the control group in comparing the markedly effective rate(P<0.05).After 2 and 4 weeks of treatment and at the follow-up,the HAMD-17 total score and sleep disorder factor score were lower in the observation group than in the control group(P<0.05);the anxiety-somatic score was lower in the observation group than in the control group after 2-week treatment(P<0.05).After 2 and 4 weeks of treatment and at the follow-up,the observation group was lower than the control group in comparing the scores of SDS,SAS,and TCM pattern element identification scale for depression(P<0.05).After 4-week treatment,the observation group had an increased serum BDNF protein content,higher than that in the control group(P<0.05)and had no significant difference compared to the healthy group(P>0.05). Conclusion:Compared to the use of oral paroxetine alone,acupuncture plus paroxetine can produce more significant efficacy in treating mild-to-moderate depression and act faster in improving sleep disorder and anxiety-somatic symptoms;increasing the serum BDNF protein content may be a part of the mechanism underlying its antidepressant actions.

OBJECTIVE: To explore the clinical phenotype and genetic basis of a neonate with Au-Kline syndrome (AKS). METHODS: Clinical data and result of genetic testing of a neonate with AKS who was admitted to the Affiliated Provincial Children's Hospital of Anhui Medical University in January 2021 were retrospectively analyzed. Relevant literature was searched from the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed databases using key words "Au Kline syndrome", "Au-Kline syndrome", "HNRNPK" and "AKS". The research period was set as from January 1, 2000 to December 31, 2020. RESULTS: The male newborn has manifested feeding difficulties, hypotonia, absence of the upper jaw to the uvula and facial dysmorphism. Trio-whole exome sequencing revealed that he has harbored a frameshift c.478dupA (p.Ile160AsnfsTer7) variant of the HNRNPK gene, which was varified by Sanger sequencing to have a de novo origin. The variant has not been included in the databases. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). Literature retrieval has identified 14 children with AKS and de novo mutations of the HNRNPK gene. Their clinical manifestations have included growth and motor retardation, various degree of mental retardation, facial dysmorphism and a high frequency of congenital heart malformations. CONCLUSION The AKS in this child may be attributed to the c478dupA frameshifting variant of the HNRNPK gene. Diagnosis of AKS should be suspected for children with mental retardation and multiple congenital malformation syndromes including Kabuki syndrome.
Humans ; Male ; Abnormalities, Multiple/genetics* ; Genetic Testing ; Heterogeneous-Nuclear Ribonucleoprotein K/genetics* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Infant, Newborn