Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Background Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental and behavioral disorder in children, often diagnosed during school age. The etiology of ADHD remains unclear; however, existing studies suggest that environmental factors, such as exposure to triclosan (TCS), may be associated with the occurrence of ADHD-like symptoms in offspring. Nevertheless, relevant research in China remains limited. Objective To investigate the impact of early pregnancy TCS exposure on ADHD-like symptoms in 7-year-old children. Methods This study was based on the Shanghai Birth Cohort (SBC) and included 662 mother-child pairs. TCS concentrations in early pregnancy urine samples were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Demographic information was collected via questionnaires and medical record abstraction. ADHD-like symptoms in 7-year-old children were first assessed using the Strengths and Difficulties Questionnaire (SDQ). Further differentiation of ADHD-like symptom subtypes (inattentive and hyperactive/impulsive) was conducted using the SNAP-IV, a clinically validated ADHD screening tool. Negative binomial regression models were applied to evaluate the associations between prenatal TCS exposure and hyperactive behavior (SDQ assessment) as well as ADHD-like symptom subtypes (SNAP-IV assessment) in 7-year-old children. Results The positive rate of TCS in early pregnancy urine samples was 91.39%, with median concentrations of 0.69 μg·L⁻¹ and 0.63 μg·g⁻¹ before and after the creatinine adjustment, respectively. The modeling results indicated that prenatal TCS exposure was associated with an increased risk of hyperactive symptoms (SDQ assessment) in 7-year-old children (RR=1.04, 95%CI: 1.02, 1.06); the stratified analyses by children sex revealed similar effects for both boys (RR=1.04, 95%CI: 1.02, 1.07) and girls (RR=1.04, 95%CI: 1.01, 1.07). Further analysis of ADHD-like symptom subtypes showed that prenatal TCS exposure increased the risk of inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.05); the sex-stratified analyses indicated associations between TCS exposure and inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.07) as well as hyperactive/impulsive symptoms (RR=1.04, 95%CI: 1.01, 1.08) in girls. Conclusion Prenatal TCS exposure is associated with an increased risk of ADHD-like symptoms in 7-year-old children, primarily contributing to the risk of the inattention subtype. The impact is more pronounced in girls.

Kounis syndrome is an acute coronary syndrome triggered by an allergic reaction, which is clinically rare and frequently subject to misdiagnosis or missed diagnosis. This article presents a case report of a 70-year-old male patient who developed a rash, pruritus, and chest pain following colon polyp resection. Coronary angiography revealed occlusion of the left anterior descending artery, and blood flow was restored after stent implantation. However, the patient experienced recurrent symptoms accompanied by loss of consciousness. Drug skin tests confirmed positive reactions to chlorhexidine and fondaparinux sodium, leading to a diagnosis of type Ⅱ Kounis syndrome. By avoiding allergenic drugs and combining antihistamines with symptomatic treatment to correct myocardial ischemia, the patient′s clinical symptoms significantly improved, and he eventually recovered and was discharged from the hospital. This case underscores the importance of maintaining vigilance for this syndrome in patients with allergies accompanied by chest pain and promptly identifying and avoiding allergens.

OBJECTIVE: To evaluate the effectiveness of Poster Fusion Cage combined with xenogeneic bone graft augmentation for bone defect management in distal radius fractures. METHODS: A retrospective analysis was conducted on 20 patients with bone defects complicating distal radius fractures who met the selection criteria and were treated between June 2022 and June 2024. The cohort comprised 2 males and 18 females, aged 54-87 years (mean, 63.3 years). Etiologies included falls in 17 cases, traffic accidents in 2 cases, and crush injury in 1 case. According to AO classification, there were 5 cases of type A, 8 cases of type B, and 7 cases of type C. The interval from injury to operation ranged from 2 to 10 days (mean, 5.8 days). All patients underwent volar plate fixation augmented with Poster Fusion Cage and demineralized xenogeneic bone matrix grafting. The operation time, intraoperative blood loss, fracture healing time, and postoperative complications were recorded. Radiographic parameters, including radial height, volar tilt, and ulnar deviation, were measured on standardized X-ray films obtained immediately postoperatively and at last follow-up, and whether secondary reduction loss occurred was judged. At last follow-up, wrist range of motion (extension, flexion, radial deviation, ulnar deviation, pronation, and supination) and grip strength (expressed as a percentage of the contralateral side) were measured. Wrist function was assessed using the Disabilities of the Arm, Shoulder, and Hand (DASH) score and Patient-Rated Wrist Evaluation (PRWE) score. RESULTS: The operation time was 70-200 minutes (mean, 116.4 minutes), and the intraoperative blood loss was 10-80 mL (mean, 36.5 mL). All surgical incisions healed by first intention, with no neurovascular complications documented. All patients were followed up 9-12 months (mean, 11.6 months). All fractures healed normally, with a healing time of 8-14 weeks (mean, 9.95 weeks). No significant difference was observed in radial height, volar tilt, or ulnar deviation between immediate postoperatively and last follow-up ( P>0.05). All fractures achieved satisfactory reduction, with no secondary loss of reduction or implant failure occurring during follow-up. At last follow-up, the range of motion of the affected wrist joint was 60°-65° (mean, 62.5°) in extension, 67°-75° (mean, 71.1°) in flexion, 18°-23° (mean, 20.4°) in radial deviation, 28°-33° (mean, 30.1°) in ulnar deviation, 69°-80° (mean, 74.7°) in pronation, and 69°-82° (mean, 75.6°) in supination. Grip strength recovered to 75%-85% (mean, 80%) of the contralateral side. Functional scores showed a DASH score of 5-15 (mean, 9.4) and PRWE score of 8.0-12.5 (mean, 10.2). CONCLUSION The combination of Poster Fusion Cage and xenogeneic bone graft augmentation provides a safe and effective treatment for bone defects in distal radius fractures.
Retrospective Studies ; Humans ; Male ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Treatment Outcome ; Wrist Fractures/surgery* ; Heterografts ; Transplantation, Heterologous/methods* ; Bone Transplantation/methods* ; Operative Time ; Blood Loss, Surgical ; Radius/surgery* ; Fracture Healing ; Time Factors ; Postoperative Complications/etiology* ; Range of Motion, Articular ; Follow-Up Studies ; Internal Fixators ; Fracture Fixation, Internal/methods* ; Combined Modality Therapy

Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.
Receptors, Opioid, mu/genetics* ; Pruritus/chemically induced* ; Humans ; Analgesics, Opioid/administration & dosage* ; Female ; Male ; Animals ; Polymorphism, Single Nucleotide/genetics* ; Adult ; Mice ; Middle Aged

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.

Background Per- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. Objective To analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. Methods Based on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable. Results Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P <0.05). The results of multiple linear regression analysis showed that age at pregnancy and household income were associated with serum PFAS levels in both groups. The serum concentrations of PFOS were higher in pregnant women aged ≥35 years old who conceiving through ART (GM ratio=1.26, 95%CI: 1.04, 1.54) and conceiving naturally (GM ratio=1.24, 95%CI: 1.08, 1.42) than pregnant women aged <30 years old respectively. Pregnant women conceiving through ART and conceiving naturally whose household annual income >300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income <200000 CNY. Additionally, pregnant women conceiving naturally with a graduate education or above had lower serum 6∶2 Cl-PFESA concentrations than women with an education below college (GM ratio: 0.81), and multiparous pregnant women conceiving naturally had higher serum concentrations of PFOS, 6∶2 Cl-PFESA, and PFHxS than primiparous pregnant women (GM ratio: 1.14, 1.25, and 1.27 respectively). Conclusion Although differences in serum PFAS levels are found between pregnant women conceiving through ART and women conceiving naturally in this study, maternal age and household income are common determinants of PFAS exposure levels in both populations. We find no special sociodemographic factors to affect PFAS concentrations of pregnant women conceiving through ART compared to pregnant women conceiving naturally. Further research is required to explore other potential factors.

Critically ill patients are at high risk for hospital acquired infections, which can significantly increase the mortality rate and treatment costs for these patients. Therefore, in the process of treating the primary disease, strict prevention and control of new hospital infections is an essential component of the treatment for critically ill patients. The treatment of critically ill patients involves multiple steps and requires a concerted effort from various aspects such as theory, management, education, standards, and supervision to achieve effective prevention and control of hospital infections. However, there is currently a lack of unified understanding and standards for hospital infection prevention and control. To address this, in March 2024, a group of experts in critical care medicine, infectious diseases, and hospital infection from China discussed the current situation and issues of hospital infection control in the intensive care unit together. Based on a review of the latest evidence-based medical evidence from both domestic and international sources, 2024 Expert Consensus on Hospital Acquired Infection Control Principles in the Department of Critical Care Medicine was formed, aiming to provide a basis for the development of hospital infection prevention and control strategies in the field of critical care medicine.

Objective:To explore the relationship between blood urea nitrogen to creatinine ratio and frailty in the elderly aged ≥65 years in 8 longevity areas in China.Methods:Participants were recruited from the Healthy Aging and Biomarkers Cohort Study. Based on baseline information about blood urea nitrogen and risk for frailty obtained at follow-up of the participants, blood urea nitrogen to creatinine ratio was classified according to quintiles, Cox proportional hazard regression models were used to analyze the association between blood urea nitrogen to creatinine ratio and frailty.Results:A total of 1 562 participants aged (81.0±17.0) years were included, in whom 814 (52.1%) were men, and 258 frailty events occurred during a mean follow-up of (3.73±1.43) years. Cox proportional hazards model showed that after adjusting for relevant confounders, compared with the participants in the lowest quintile group ( Q1), the risk for frailty decreased by 36%, 44%, and 40% in the participants in the third quintile group ( Q3), the fourth quintile group ( Q4) and the highest quintile group ( Q5) respectively [hazard ratio ( HR)=0.64, 95% CI: 0.43-0.94; HR=0.56, 95% CI: 0.38-0.84; HR=0.60, 95% CI: 0.41-0.88]. The risk for frailty decreased by 20% for every unit standard deviation increase in blood urea nitrogen to creatinine ratio ( HR=0.80, 95% CI: 0.70-0.91). Moreover, blood urea nitrogen to creatinine ratio and the risk for frailty showed a nearly linear dose-response relationship. Conclusions:The increase in blood urea nitrogen to creatinine ratio was associated with higher risk for frailty. Maintaining high blood urea nitrogen to creatinine ratio is important for the prevention of frailty in the elderly.

The combined exposure to environmental pollutants can result in unanticipated adverse effects on human health,and how to compare and assess these effects has always been a matter of great concern for the international community.Currently,several prevalent methods for assessing combined exposure risks in the field of human health risk assessment primarily encompass the hazard index(HI)method,the point of departure index(PODI)method,the margin of exposure(MOE)method,and the relative potency factor(RPF)method.The review summarizes the application of these methods to the cumulative risk assessment of combined exposure to the same class of chemicals with the same toxic mechanism,primarily focusing on pesticides such as organophosphorus pesticides,pyrethroids,carbamates,and neonicotinoids,as well as typical compounds intimately related to human production and life,including organophosphorus flame retardants,per-and poly-fluoroalkyl substances,and bisphenols.Furthermore,progress in the application of physiologically based pharmacokinetics models to human health risk assessment has been introduced,which might provide more options for risk assessment of combined exposure to multiple chemicals,and help to provide insights for further exploration and establishment of more systematic and scientific approaches to human health risk assessment.