A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

The reconstruction of the temporomandibular joint presents a multifaceted clinical challenge in the realm of head and neck surgery, underscored by its relatively infrequent occurrence and the lack of comprehensive clinical guidelines. This review aims to elucidate the available approaches for TMJ reconstruction, with a particular emphasis on recent groundbreaking advancements. The current spectrum of TMJ reconstruction integrates diverse surgical techniques, such as costochondral grafting, coronoid process grafting, revascularized fibula transfer, transport distraction osteogenesis, and alloplastic TMJ replacement. Despite the available options, a singular, universally accepted 'gold standard' for reconstructive techniques or materials remains elusive in this field. Our review comprehensively summarizes the current available methods of TMJ reconstruction, focusing on both autologous and alloplastic prostheses. It delves into the differences of each surgical technique and outlines the implications of recent technological advances, such as 3D printing, which hold the promise of enhancing surgical precision and patient outcomes. This evolutionary progress aims not only to improve the immediate results of reconstruction but also to ensure the long-term health and functionality of the TMJ, thereby improving the quality of life for patients with end-stage TMJ disorders.
Humans ; Temporomandibular Joint/surgery* ; Temporomandibular Joint Disorders/surgery* ; Transplantation, Autologous ; Arthroplasty, Replacement/methods* ; Joint Prosthesis ; Plastic Surgery Procedures/methods*

Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Objective:To investigate the value and clinical significance of fasting plasma glucose (FPG) in early pregnancy (8-12 gestational weeks) as a predictor of gestational diabetes mellitus (GDM) among women with different pre-pregnancy body mass index (pre-BMI) categories.Methods:A retrospective study was conducted including 9 710 singleton pregnant women (FPG levels in early pregnancy ≤5.6 mmol/L) who underwent prenatal screening and delivery in Yuyao People's Hospital from January 2020 to December 2022. Participants were stratified based on their pre-BMI as follows: <18.5 ( n=1 406), ≥18.5 to <25.0 ( n=7 162), ≥25.0 to <30.0 ( n=978), and ≥30.0 kg/m 2 ( n=164). Within each pre-BMI category, women were further divided into four groups based on FPG levels in early pregnancy (<4.5, ≥4.5 to <4.8, ≥4.8 to <5.1, and ≥5.1 mmol/L). Univariate and multivariate logistic regression analysis were used to identify risk factors for GDM, and receiver operating characteristic (ROC) curve was applied to evaluate the efficacy of FPG in early pregnancy based on different pre-BMI in predicting GDM. Results:The overall incidence of GDM in the singleton pregnancy women with FPG levels in early pregnancy ≤5.6 mmol/L was 12.3% (1 197/9 710). For a pre-BMI of <18.5 kg/m 2, the ORs with 95% CIs for GDM within the different FPG categories (<4.5, ≥4.5 to <4.8, ≥4.8 to <5.1, and ≥5.1 mmol/L) were 0.041 (95% CI: 0.015-0.409), 1.834 (95% CI: 1.089-3.088), 6.779 (95% CI: 4.041-11.371), and 13.723 (95% CI: 5.560-33.871), respectively. For pre-BMI of ≥18.5 to <25.0 kg/m 2, the respective the ORs with 95% CIs were 0.048 (95% CI: 0.012-0.203), 2.573 (95% CI: 2.091-3.168), 9.023 (95% CI: 7.240-11.245), and 9.158 (95% CI: 6.484-12.937). For pre-BMI of ≥25.0 to <30.0 kg/m 2, the ORs with 95% CIs were 0.108 (95% CI: 0.053-0.446), 1.698 (95% CI: 1.064-2.654), 7.537 (95% CI: 5.285-13.080), and 9.994 (95% CI: 5.613-18.218). For pre-BMI of ≥30.0 kg/m 2, the ORs with 95% CIs were 0.098 (95% CI: 0.072-1.015), 2.888 (95% CI: 0.911-9.157), 13.674 (95% CI: 3.480-53.736), and 20.509 (95% CI: 6.674-63.019). The optimal cutoff value of FPG in early pregnancy for GDM prediction was 4.7 mmol/L with an area under the curve of 0.752, the risk of GDM significantly increased with FPG levels ≥4.7 mmol/L in early pregnancy across all pregnant women ( OR=17.356, 95% CI: 13.757-21.896, P<0.001). Conclusions:In the singleton pregnancy women with FPG levels in early pregnancy ≤5.6 mmol/L, FPG in early pregnancy is an independent risk factor for the occurrence of GDM; for pregnant women stratified by the same pre-BMI, the risk of developing GDM increases progressively with the rise of FPG in early pregnancy. FPG in early pregnancy has a certain value in predicting the occurrence of GDM.

Objective To investigate the population characteristics,distribution of traditional Chinese medicine(TCM)syndromes and influencing factors of long-term prognosis of diarrhea-predominant irritable bowel syndrome(IBS-D),and to provide evidence for the formulation of intervention program for IBS-D patients.Methods A total of 124 patients with IBS-D admitted to the medical institutions of the project team members from July 2020 to August 2022 were selected.According to the scoring results of IBS Quality of Life Measure(IBS-QOL),the patients were divided into the good prognosis group(81 cases)and the poor prognosis group(43 cases).The distribution of TCM syndromes in patients with IBS-D was explored,and the difference of IBS-QOL scores of the patients between good prognosis group and poor prognosis group was compared.Univariate logistic regression analysis and multivariate logistic regression analysis were used to determine the main risk factors for poor prognosis in patients with IBS-D.Results(1)The analysis of population characteristics showed that there was no significant difference in the proportion of male and female patients with IBS-D.The patients with IBS-D were usually middle-aged,and had a large interval span of the course of disease.The severity of their symptoms was mostly moderate.All of the patients with IBS-D had various degrees of anxiety and depression,and had nutritional imbalance.(2)The distribution of TCM syndromes in the patients with IBS-D were shown as the following:78 cases were identified as liver depression and spleen deficiency type,accounting for 62.90％;26 cases were identified as spleen-qi deficiency type,accounting for 20.97％;20 cases were identified as spleen and kidney yang deficiency type,accounting for 16.13％.(3)Analysis of IBS-QOL score showed that compared with the good prognosis group,the items scores of negative emotion,physical function,behavioral disorder,health status,being fastidious about food,social function,sexual behavior and interpersonal relationship of IBS-QOL in the poor prognosis group were significantly lowered(P＜0.01).(4)The univariate analysis showed that the risk of poor prognosis in patients with IBS-D would be increased by the factors of age,education level,course of disease,severity of symptoms,anxiety state,depression state,TCM syndrome types,Acute Physiology and Chronic Health Evaluation scoring system Ⅱ(APACHE 11)score,complication of neurological diseases,hemoglobin level,albumin level and total protein level(P＜0.01).(5)The multivariate Logistic regression analysis showed that the risk factors for poor prognosis of IBS-D patients involved age,education level below junior high school,the severity of symptoms being severe,Self-Rating Anxiety Scale(SAS)score,Self-Rating Depression Scale(SDS)score,TCM syndrome being liver depression and spleen deficiency type,hemoglobin level,albumin level and total protein level(P＜0.01).Conclusion Most of IBS-D patients exert long-term poor prognosis,and their long-term prognosis is affected by the factors of age,education level,severity of symptoms,anxiety and depression state,nutritional imbalance and TCM syndrome being liver depression and spleen deficiency type.The identification of the risk factors of poor prognosis will provide evidence for the formulation and adjustment of clinical intervention programs.