Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

Objective: To explore the association between warning signs of psychological and behavioral development problems with emotional and behavioral problems in preschool children in Bao an District, Shenzhen, so as to provide an empirical basis for optimizing psychological screening strategies in kindergartens. Methods: From September 2023 to August 2024, a total of 49 804 preschool children aged 4-6 years from all 401 kindergartens in Bao an District were enrolled as study subjects. The Warning Signs Checklist for Screening Psychological, Behavioral and Developmental Problems of Children and the parent version of the Strengths and Difficulties Questionnaire (SDQ) were used to assess children s developmental status and emotional and behavioral problems, respectively. Multivariable Logistic regression analysis was used to examine the association between warning signs and emotional and behavioral problems, stratified by sex. Results: The overall positive screening rate for developmental warning signs was 1.5%, and the detection rate for high risk in the SDQ total difficulties score was 6.3%. Multivariable Logistic regression analysis revealed that after adjusting for age, children who screened positive for warning signs exhibited a significantly higher risk of elevated SDQ total difficulties and subscale scores compared to those who screened negative, across both sexes (a OR boys =1.66-13.42, a OR girls =2.04-22.15, all P <0.01). The only exceptions were gross motor skills and conduct problems in boys, and personal social skills and conduct problems in girls. Notably, abnormalities in the personal social domain demonstrated the strongest association with emotional/behavioral problems (a OR boys =7.72-13.42, a OR girls =3.88-22.15), followed by the language domain (a OR boys =4.63-9.23, a OR girls =3.78-14.41) (all P <0.01). Conclusion A positive screening result for warning signs, particularly in the personal social and language domains, serves as a strong indicator of emotional and behavioral problems in preschool children.

Objective:To investigate the impact of early invasive arterial blood pressure (IBP) monitoring on survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).Methods:This retrospective cohort study analyzed 44 OHCA patients receiving ECPR between January 2021 and January 2023. Patients were divided into: Early intervention group : IBP established within 3 min of ECMO initiation; Late intervention group : IBP established after ICU admission. Baseline characteristics, ECMO parameters, and clinical outcomes were compared. Multivariable logistic regression (adjusted for age, initial rhythm, etc.) and Spearman's correlation were used.Results:This study included a total of 44 patients treated with OHCA and ECPR, divided into an early intervention group of 23 cases and a late intervention group of 21 cases. The early intervention group showed significantly higher: Survival to discharge (43.5% vs. 9.5%, P<0.05), Good neurological recovery (CPC 1-2: 34.8% vs. 9.5%, P<0.05).Early intervention independently predicted survival (adjusted OR=18.84, 95% CI:1.97-179.98, P=0.01). Stratified analysis by pH (cutoff 7.0) demonstrated consistent benefits in both pH>7.0 ( aOR=0.392, 95% CI:0.106-0.678) and pH≤7.0 subgroups ( aOR=0.385, 95% CI: 0.075-0.695; interaction P=0.183). Early IBP positively correlated with CPC scores ( ρ=0.40, P=0.007). Conclusions:Early IBP monitoring significantly improves survival and neurological outcomes in OHCA-ECPR patients, supporting its integration into standardized protocols.

One of the technical bottlenecks limiting the high yield of 1,4-butanediamine is the insufficient tolerance of strains to 1,4-butanediamine. Enhancing the tolerance of strains to 1,4-butanediamine is therefore a primary challenge that needs to be addressed for the construction of strains with high yields of 1,4-butanediamine. Staphylococcus pasteuri 326180 exhibits exceptional tolerance to high-concentration 1,4-butanediamine, serving as both an ideal model for studying the mechanism underlying the 1,4-butanediamine tolerance and a novel host for constructing strains capable of efficiently producing 1,4-butanediamine. However, for both the research on the tolerance mechanism and the modification of chassis strains, gene editing of S. pasteuri needs to be carried out at the molecular level. The research objective of this paper is to establish a genetic manipulation system for S. pasteuri, laying foundation for subsequent studies on tolerance mechanism and the modification of chassis strains. This study systematically optimized the electroporation conditions, including key parameters such as the growth phase of cells, electric field strength, electroporation buffer, and recovery medium, successfully establishing an electroporation method for S. pasteuri. Additionally, we constructed the gene editing plasmid pCpfOA by replacing the resistance expression cassette, optimized the selection markers for gene editing, and finally established a CRISPR/Cpf1-based gene editing technology for S. pasteuri, achieving an editing efficiency of 90%. The genetic manipulation system of S. pasteuri established in this study provides technical support for research into the tolerance mechanism of this bacterium and the genetic modification of chassis strains.
Staphylococcus/drug effects* ; Gene Editing/methods* ; Electroporation/methods* ; Plasmids/genetics* ; CRISPR-Cas Systems ; Genetic Engineering/methods*

ObjectiveTo sum up the clinical features of 5α-reductase type 2 deficiency （5α-RD2） complicated by central precocious puberty （CPP）， and provide experience for clinicians. MethodsA retrospective review was conducted of child patients with 5α-RD2 followed up to puberty at a single tertiary pediatric center， in whom 6 cases developed CRP. Clinical characteristics and treatment history of them were analyzed. A literature review was also performed to investigate possible mechanisms underlying the co-occurrence of 5α-RD2 and CPP. ResultsThe median age at initial presentation was 5.55 years （IQR 3.50-7.20）. Common clinical features included micropenis and hypospadias. Median stretched penile length （SPL） was 2.25 cm （IQR 1.8-2.8）， with an SPL-SDS of -4.5 （IQR -3.1 to -5.8）. Median external masculinization score （EMS） and Prader scores were 8.5 （IQR 5.0-9.0） and 4.5 （IQR 3.0-5.0）， respectively. Pubertal onset occurred at a median age of 8.70 years （IQR 7.80-9.00）. Three patients were overweight or obese. Five had received 2.5% dihydrotestosterone （DHT） gel prior to pubertal onset， with a median cumulative dose of 205.5 mg/kg （IQR 72.0-660.3 mg/kg） with DHT gel therapy. Notably， one patient with normal body mass index （BMI） and no history of androgen or gonadotropin therapy also exhibited early pubertal onset at 8.4 years. ConclusionCPP in children with 5α-RD2 may be associated with prior dihydrotestosterone （DHT） gel therapy and elevated BMI； however， a potential intrinsic link to the underlying disorder cannot be excluded. Further studies are needed to elucidate the pathophysiological mechanisms.

Objective:To analyze the factors associated with non-radiographic bone erosion in gout pa-tients,to improve the understanding of bone erosion in gout,and to promote the early detection of bone erosion.Methods:A retrospective analysis was conducted on the medical records of gout patients treated at Beijing Jishuitan Hospital from January 2018 to January 2022.Bone erosion was detectable by ultra-sound but not detected by X-ray as non-radiographic bone erosion;no bone erosion was detected by both ultrasound and joint X-ray as undetected bone erosion.A case-control study was used,and the two groups were matched 1∶2 according to age and sex.The differences between the two groups were com-pared in terms of general information,joint involvement characteristics,laboratory indicators and compli-cations.In the univariate analysis,P＜0.1 was included in the multivariate analysis,and the conditional Logistic regression was used for the multivariate analysis.P＜0.05 was considered to have statistically significant differences.Results:Among the 41 patients with non-radiographic bone erosion,the top three joints with bone erosion before its occurrence were metatarsophalangeal joint(12 cases),ankle(10 ca-ses),and knee(7 cases).There were 82 patients undetected with bone erosion.There were no signifi-cant differences in general information between the two groups(P＞0.05),including age,gender,body mass index,and alcohol consumption history.The characteristics of affected joints in the non-radio-graphic bone erosion group were compared with those in the no bone erosion detected,and the former had more affected joints(P=0.02),and a higher proportion of patients with at least 3 attacks of gout per year(P＜0.001).There were no significant differences in serum uric acid,fasting blood glucose,cholesterol,triglycerides,low-density lipoprotein,high-density lipoprotein,creatinine,homocysteine,white blood cell count,and urine pH between the two groups(P＞0.05).The results of multivariate analysis showed that at least 3 flares of gout per year was an independent risk factor for radiologically negative bone erosion in patients with gout,with an OR(95％CI)of 5.139(1.529-17.271).Conclusion:At least 3 flares of gout per year predicts the occurrence of radiologically negative bone erosion,and these patients should be given more attention to achieving treatment targets.

Objective:To investigate the clinical manifestations and genetic characteristics of a Chinese Han family with Axenfeld-Rieger syndrome (ARS).Methods:A pedigree study was conducted.Three people from a Chinese Han family with ARS who visited Henan Eye Hospital in January 2024 were included, including 1 patient.Clinical data of the proband and her parents were collected.Comprehensive ophthalmic examination and general physical examination were performed on the proband and her parents.Peripheral blood samples were obtained from family members for DNA extraction.Whole exome sequencing was performed on the proband, and the copy number of the ZBED1P1, ENPEP, PITX2, and FAM241A genes in family members were validated using the real-time fluorescent quantitative PCR.Axenfeld-Rieger syndrome, Axenfeld-Rieger Syndrome, and PITX2 were used as keywords to search across databases such as OMIM, ClinVar, PubMed, CNKI, Wanfang, VIP, DECIPHER, and Google Scholar.The clinical manifestations and microdeletion types of different patients in ARS literature related to PITX2 microdeletions in China population were summarized, and the relationship between genotype and clinical phenotype was analyzed.The study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2024[34]).All subjects understood the purpose of the study and voluntarily signed the informed consent form. Results:The proband was a 25-year-old female, exhibiting diminutive cornea in both eyes, polycoria, deformation and displacement of pupils, a flat mid-face, maxillary dysplasia, tooth loss, and a protruding umbilicus, among other symptoms.Parents of the proband were phenotypically normal.DNA sequencing identified a 1.06 MB microdeletion on chromosome 4q25 in the proband.Real-time quantitative PCR confirmed that this microdeletion encompassed the PITX2 and ENPEP genes, and it was absent in the proband's parents.The ClinGen CNV pathogenicity scoring indicated that the deletion involving the PITX2 gene represented a novel pathogenic copy number variation (CNV).Five studies related to 4q25 microdeletion in Chinese families with Axenfeld-Rieger syndrome was screened, including 13 patients.Clinical manefestations of the 13 patients included corneal disorders (accounting for 100%), umbilical hernia and dental anomalies (accounting for 92%), irregular intraocular pressure (accounting for 62%), iris atrophy (accounting for 46%), and posterior corneal embryotoxon (accounting for 31%). Conclusions:For this Chinese family diagnosed with ARS, a novel pathogenic 4q25 microdeletion variant encompassing the PITX2 gene was found in the proband, which is associated with characteristic phenotypes including microcornea, congenital iris dysplasia, polycoria, tooth loss, and a protruding umbilicus.

The global aging population has intensified the incidence of degenerative bone diseases and the therapeutic demand for traumatic bone injuries, thereby making bone regenerative medicine a research focus. There is a close connection and interaction between the skeletal system and the nervous system, and innervation plays an indispensable regulatory role in the process of bone regeneration: the sympathetic nervous system exerts a negative regulatory effect during bone regeneration, while the parasympathetic nervous system plays a positive regulatory role in this process. Nerve fibers within bones are distributed alongside blood vessels, with their density decreasing from the periosteum to the cancellous bone. Nerve signals regulate bone regeneration either by directly acting on target cell receptors or indirectly modulating the metabolism of the local microenvironment (such as the levels of inflammatory factors and the supply of nutrients). A variety of neuropeptides (e.g., calcitonin gene-related peptide, substance P, neuropeptide Y, vasoactive intestinal peptide, etc.) play a crucial role in bone tissue, constructing a "neuro-osseous" regulatory axis, which in turn regulates the osteoblast-osteoclast balance, angiogenesis, and the homeostasis of the local microenvironment. This review focuses on the neural regulatory mechanisms in bone regeneration, with an emphasis on sorting out the functions of key neuropeptides and related neurotransmitters. Neuropeptides are the core mediators of neuro-osseous interaction; however, the interaction network among neuropeptides remains to be further clarified, which requires the application of advanced in vitro models such as three-dimensional bioprinted bone models and organoid technology, as well as cutting-edge techniques like single-cell sequencing for analysis. In the future, the integration of neural regulation strategies with traditional bone regeneration technologies, along with the expansion into interdisciplinary fields such as neuro-vascular and neuro-muscular fields, is expected to provide new directions for the treatment of bone defects and large maxillofacial tissue defects, and promote the transformation of regenerative medicine from prosthetic treatment to functional and neurotized tissue regeneration.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.