Objective To establish a highly efficient and sensitive technical system for the identification and analysis of platycodin-type saponins, systematically compare the differences in platycodin-type saponins among Platycodon grandiflorum from different producing areas, and provide scientific references for the screening of high-quality Platycodon grandiflorum resources, authenticity evaluation, and construction of standardized quality control systems. Methods A total of 45 batches of P. grandiflorum medicinal materials from 3 producing areas （Anhui, Henan, and Jilin, with 15 batches per area） were selected as research objects. Qualitative identification and semi-quantitative analysis of saponin components were performed based on ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UHPLC-Q-TOF/MS） technology. Meanwhile, two multivariate statistical methods, principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA）, were combined to analyze the differences in platycodin-type saponins of Platycodon grandiflorus from different producing areas. Results A total of 28 saponin components were identified from Platycodon grandiflorus of the three producing areas. PCA results showed that there were minor differences in platycodin-type saponins between Henan Platycodon grandiflorus and Jilin Platycodon grandiflorus, while Anhui P. grandiflorum exhibited significant differences from both. PLS-DA further screened 15 major differential compounds. Among them, the contents of 6 components including 3''-O-acetylpolygalacin D2 and platycodin H in Anhui Platycodon grandiflorus were higher than those in Henan and Jilin Platycodon grandiflorus; platycodigenic acid A had the highest content in Jilin Platycodon grandiflorus; the contents of platycodin D3, polygalacin J, and polygalacin D were relatively higher in Henan Platycodon grandiflorus. Conclusion This study clarified the characteristic differences in core components of Platycodon grandiflorus from the three major producing areas, which provided an important theoretical basis for the screening of high-quality Platycodon grandiflorus resources, elucidation of the mechanism underlying its authenticity, and construction of a standardized quality control system.

Background Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents. Current research suggests that environmental factors, such as per- and polyfluoroalkyl substances (PFAS), may be associated with an increased risk of ADHD in offspring. However, most epidemiological evidence originates from non-Chinese populations, with limited research investigating the association between prenatal PFAS and ADHD-like symptoms in Chinese school-aged children. Objective To examine the association between prenatal PFAS exposure and ADHD-like symptoms in 7-year-old children. Methods Based on the Shanghai Birth Cohort, this study included 488 mother-child pairs. PFAS were measured in maternal serum during the second trimester using ultra-performance liquid chromatography-tandem mass spectrometry. The analysis focused on eight specific compounds from three PFAS categories [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS)]. The hyperactivity subscale of the Strengths and Difficulties Questionnaire (SDQ) was used to assess ADHD-like symptoms in children at age 7. Basic demographic information was collected via questionnaires and medical records. Negative binomial regression models were used to evaluate the relationship between individual exposures to the three typical PFAS categories (PFOA, PFOS, and PFHxS) and children's ADHD-like symptoms, while the bayesian kernel machine regression (BKMR) mixture model was employed to assess the overall effect of PFAS mixture exposure on ADHD-like symptoms. Results The detection rates of the eight target PFAS in maternal second-trimester serum were all above 85%, with PFOA exhibiting the highest median concentration (10.21 ng·mL⁻¹). Overall, 14.75% of the children exhibited ADHD-like symptoms. Results from the negative binomial regression models showed that second-trimester exposures to PFOA (IRR=1.15, 95%CI: 1.05, 1.26), n-PFOS (IRR=1.08, 95%CI: 1.01, 1.15), 6m-PFOS (IRR=1.13, 95%CI: 1.05, 1.21), and 1m-PFOS (IRR=1.11, 95%CI: 1.03, 1.18) were associated with an increased risk of ADHD-like symptoms in 7-year-old children. Stratified analyses suggested potentially statistically significant associations in girls [e.g., for PFOA, boys vs. girls: 1.09 (0.96, 1.23) vs. 1.25 (1.09, 1.44), P-int=0.31]. The BKMR mixture model indicated that the risk of ADHD-like symptoms trended upward with increasing PFAS mixture concentrations, although this association was statistically significant only among girls (P < 0.05). Conclusion Prenatal PFAS exposure may be associated with an increased risk of ADHD-like symptoms in 7-year-old children, and this adverse association appears to be more prominent in girls.

Background Work-related musculoskeletal disorders (WMSDs) are common across industries. Workers in the hairdressing industry are frequently exposed to repetitive upper-limb movements and awkward working postures, which may increase their susceptibility to WMSDs. However, evidence on WMSDs among workers in this industry remains limited. Objective This study aimed to investigate the prevalence of self-reported WMSDs symptoms and associated factors among workers in the hairdressing industry in Hongkou District, Shanghai. Methods A cross-sectional survey was conducted using quota sampling in all eight subdistricts of Hongkou District, Shanghai. Hair salons in each subdistrict were ranked by the number of hairdressers and shampoo workers, and the 6 salons with the largest staff size in each subdistrict were selected, resulting in 48 survey sites. Hairdressers and shampoo workers who met the inclusion and exclusion criteria were surveyed using the Chinese version of the Musculoskeletal Disorders Questionnaire. Information on their individual characteristics, musculoskeletal symptoms, and work-related factors was collected. Chi-square tests and Firth logistic regression were used to estimate the prevalence of self-reported WMSDs symptoms and identify associated factors. Results The overall prevalence of self-reported WMSDs symptoms among workers in the hairdressing industry was 45.72%. Among hairdressers, the most commonly affected body regions were the neck (31.51%), shoulders (25.57%), lower back (15.98%), and feet (14.61%). Among shampoo workers, the most commonly affected regions were the neck (24.17%), lower back (24.17%), shoulders (20.83%), and upper back (10.83%). Firth logistic regression showed that fatigue in the corresponding body region after several hours of continuous work was positively associated with self-reported WMSDs symptoms in both types of workers (OR=6.544-52.838). Regarding individual characteristics, shorter height (female≤160 cm, male≤165 cm) was positively associated with self-reported neck and foot symptoms among hairdressers, and self-reported shoulder symptoms among shampoo workers (OR=16.324, 15.084, 9.680). Female shampoo workers had higher odds of self-reported neck symptoms than male shampoo workers (OR=4.924). Smoking was positively associated with self-reported upper-back and lower-back symptoms among shampoo workers (OR=10.544, 4.381). Among work-related factors, maintaining a fixed neck posture for long periods among hairdressers and prolonged standing among shampoo workers were positively associated with self-reported neck symptoms (OR=6.123, 3.080). Among shampoo workers, frequent overtime and maintaining a twisted posture were positively associated with self-reported upper-back symptoms (OR=11.710, 35.306). Sufficient rest time was negatively associated with self-reported foot symptoms among hairdressers (OR=0.238). Conclusion The prevalence of self-reported WMSDs symptoms was relatively high among workers in the hairdressing industry. Work-related fatigue and awkward working postures were strongly associated with WMSDs symptoms. Measures such as optimizing work-rest schedule, improving ergonomic workplace design, implementing fatigue monitoring and management, promoting work-break exercises, and providing training on appropriate working posture may help reduce the burden of WMSDs symptoms in this occupational group.

ObjectiveTo observe the clinical efficacy and safety of Tianmeng Lingjiao Formula（天礞羚角方， TLF） as an adjunctive therapy for paroxysmal atrial fibrillation （PAF） with phlegm-heat harassing the interior syndrome. MethodsNinety patients with PAF and phlegm-heat harassing the interior syndrome were enrolled and randomly assigned in a 2∶1 ratio to test group （60 cases） and control group （30 cases）. The control group received conventional western medicine， while the test group received TLF in addition to the conventional treatment， with one dose administered daily. The treatment course for both groups was 4 weeks. The efficacy of traditional Chinese medicine （TCM） syndrome and the rate of atrial fibrillation （AF） conversion were compared between groups. Assessments included AF burden， frequency and duration of AF episodes， TCM syndrome scores， and European Heart Rhythm Association （EHRA） AF symptom classification before and after treatment. Safety indicators such as blood routine， urine routine， stool routine， liver function， kidney function， and electrolytes were also monitored. Adverse events were recorded. ResultsA total of 82 patients completed the study （54 in the test group and 28 in the control group）. After treatment， AF burden， the frequency and duration of AF episodes， and TCM syndrome scores were significantly reduced in both groups， and the test group showed lower indicators than the control group （P＜0.01 or P＜0.05）. The AF conversion rate was 25.93% （14/54） in the test group， significantly higher than 3.57% （1/28） in the control group （P＜0.05）. The total effective rate for TCM syndrome efficacy was 83.33% （45/54） in the test group， which was significantly higher than 67.86% （19/28） in the control group （P＜0.05）. After treatment， the EHRA atrial fibrillation symptom severity in the test group showed significant improvement， and the improvement in atrial fibrillation symptoms was superior to that in the control group （P＜0.01or P＜0.05）. No significant abnormalities were observed in safety indicators， and no adverse events occurred during the trial. ConclusionTLF as an adjunctive therapy can reduce AF burden， enhance the conversion rate of AF， decrease the frequency and duration of episodes， and improve clinical symptoms in patients with paroxysmal atrial fibrillation presenting with phlegm-heat harassing the interior syndrome， with a favorable safety profile.

ObjectiveThis nested case-control study, based on the Shanghai Birth Cohort (SBC), aimed to explore the impact of early pregnancy exposure to organophosphorus flame retardants (OPFRs) on attention deficit hyperactive disorder (ADHD)-like symptoms in 4-year-old children, so as to provide epidemiological evidence regarding the health effects of emerging contaminant OPFRs in children. MethodsStrengths and Difficulties Questionnaire (SDQ) was used to assess ADHD like symptoms in 4-year-old children. Children with an SDQ hyperactivity subscale score ≥6 points were defined as cases, while those with a score <5 points were considered as controls. The case and control groups were matched at 1∶1 based on the child’s age (±6 months), sex, and parental or primary caregiver’s education level. A total of 105 cases and 112 controls were included eventually. Concentrations of eight OPFRs metabolites in early pregnancy urine samples were measured using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), including di-phenyl phosphate (DPHP), di-m-cresylphosphate (DmCP), di-o-cresylphosphate (DoCP), di-p-cresylphosphate (DpCP), di-n-butyl phosphate (DnBP), di-iso-butyl phosphate (DiBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(2-ethylhexyl) phosphate (BEHP). Basic demographic information of mothers and children were collected through questionnaire surveys and medical records extraction. Binary logistic regression models were used to analyze the effect of individual OPFRs exposure during early pregnancy on ADHD-like symptoms, while a quantile g-computation (Qgcomp) regression model was employed to assess the effects of mixed OPFRs exposure (with detection rates >75%) on ADHD-like symptoms in 4-year-old children. ResultsIn this study, the detection rates of DPHP, DoCP, and the DmCP&DpCP in the urine of early pregnancy women were higher than 75%, with DPHP having the highest detection rate (86.18%). The median concentrations of DPHP were highest in both the case and control groups (0.396 μg·L^-1 and 0.305 μg·L^-1, respectively). Binary logistic regression analyses revealed that exposure to DPHP during early pregnancy increased the risk of ADHD-like symptoms in 4-year-old children (OR=1.262, 95%CI: 1.017‒1.565). The mixed exposure model analyses showed that early pregnancy co-exposure to OPFRs increased the risk of ADHD-like symptoms (OR=1.508, 95%CI: 1.012‒2.258), with DPHP being the primary contributor to the association. ConclusionEarly pregnancy exposure to DPHP is positively associated with an increased risk of ADHD-like symptoms in 4-year-old children. Additionally, DPHP contributed the most to the adverse effects of mixed OPFRs exposure on ADHD-like symptoms. However, these findings require further validation through other large-scale prospective cohort studies.

Glucagon and insulin are the main regulatory factors for blood glucose and jointly maintain the homeostasis of energy me-tabolism in the body,but the internal mechanism of the mutual regulation and influence between them remains complex and unclear.The liver is one of the key target organs for both insulin and glucagon,playing a crucial role in maintaining the homeostasis of glucose and lipid metabolism.Insulin resistance is often accompanied by abnormal glucose and lipid metabolism in the liver,which may affect the functional activity of glucagon in the liver.There is a glucagon-related feedback loop between the liver and the pancreas,known as the"liver-α-cell axis",which may play a critical role in understanding the metabolic effect of glucagon in the state of insulin resis-tance.In addition to the regulation of glucose homeostasis,the physiological action of glucagon has been extended to lipid and amino acid metabolism.Therefore,abnormal regulation of glucagon metabolism may further lead to the imbalance of glucose,lipid,and amino acid metabolism.This article briefly reviews the regulatory mechanism of glucagon in liver glucose homeostasis,lipid metabolism,and amino acid metabolism in physiological condition and the state of insulin resistance.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

Objective To analyze the results of newborn screening for galactocerebrosidase(GALC)gene and enzyme activity and pro-vide a basis for the clinical diagnosis and genetic counseling of Krabbe disease.Methods The dried blood samples on filter paper from 12 744 newborns born at Nanjing Women and Children's Healthcare Hospital from March 18,2022 to December 31,2022 were collect-ed.The pathogenic variant sites of GALC gene were detected using the chip capture next-generation sequencing technology and Sanger sequencing was used for family validation.The tandem mass spectrometry was used to determine the enzyme activity of GALC in dried blood spots.The comparison of GALC enzyme activity between the carriers with GALC variants and negative group was conducted using the independent sample t-test.Results Among the 12 744 newborns,315 were identified as the carriers with GALC variants,with a carrier rate of 1/40.The most common variant was c.1901T＞C(269 cases,1/47),followed by c.1592G＞A(12 cases,1/1 062).Four newborns(P1-P4)were found to have two pathogenic variant sites and 2 cases were homozygous variants of c.1901T＞C.Family validation showed that the two variant sites in the four newborns were inherited from their parents,leading to a diagnosis of Krabbe dis-ease.Meanwhile,the family validation of the potential P2 patient's sister revealed that they had the same genotype,and the diagnosis of Krabbe disease was made.A preliminary threshold of 0.42 μmol/(L·h)for the enzyme activity of GALC detected by the tandem mass spectrometry was established based on 200 newborn samples.The GALC enzyme activities of 4 children with Krabbe disease were 0.74,0.21,0.17,and 0.29 μmol/(L·h),respectively.The GALC enzyme activity of the P2 patient's sister was 0.28 μmol/(L·h).Except for the P1 patient,the GALC enzyme activities of the P2,P3,and P4 patients and the P2 patient's sister were reduced,indica-ting a positive result.Conclusion The carrier rate of pathogenic variants in the GALC gene is relatively high,with the hotspot mutation being c.1901T＞C.The estimated prevalence of Krabbe disease is 1/3 186.The screening strategy using genetic testing as the primary screening and enzyme activity testing as the second screening can effectively improve the diagnostic efficiency of Krabbe disease,provi-ding a reference for the clinical diagnosis and genetic counseling of Krabbe disease.

Bisphenol A (BPA) is an environmental chemical that is widely exposed in human daily life. It has attracted much attention because of its estrogenic effect. Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disease in women of reproductive age. Its pathogenesis involves the interaction of genetic, environmental and endocrine disorders. In recent years, more and more studies have shown that BPA plays an important role in the occurrence and development of PCOS. BPA promotes the development of PCOS by interfering with insulin sensitivity, immune response and changing ovarian structure and function. In addition, BPA exposure levels are associated with hyperandrogenism, insulin resistance, obesity, dyslipidemia, and decreased ovarian reserve in PCOS patients. This review summarizes the effects of BPA on PCOS in terms of ovarian function, glucose and lipid metabolism, and inflammatory response, so as to provide theoretical basis for clinical intervention and prevention of BPA in the development of PCOS.