OBJECTIVE To establish a method for simultaneous determination of plasma concentration of lamotrigine（LTG）， levetiracetam（LEV） and perampanel（PER） in children with epilepsy and apply this method in clinical practice. METHODS Plasma proteins were precipitated with acetonitrile. Using PER-D 5 as internal standard， ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method was adopted. The determination was performed on ACQUITY UPLC HSS T3 C 18 column with mobile phase consisted of 0.1% formic acid with 5 mmol/L ammonium acetate-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and sample size was 5 μL. The analysis time was 5 min. The electrospray ionization source and multiple reaction monitoring mode were used for positive ion scanning. The ion pairs used for quantitative analysis of LTG， LEV， PER and internal standard were m / z 255.9→144.9， m / z 171.1→126.1， m / z 350.1→219.0 and m / z 354.9→220.2， respectively. The steady-state trough concentrations of the aforementioned drugs in the plasma of 14 pediatric epilepsy patients receiving combination therapy were determined using the same UPLC-MS/MS method as above. RESULTS The linear ranges of LTG， LEV and PER were 0.15-24 μg/mL （ R 2 ＞0.993）， 0.312 5-50 μg/mL （ R 2 ＞0.997） and 6.25-1 000 ng/mL （ R 2 ＞0.997）， respectively. The lower limits of quantification were 0.15 μg/mL， 0.312 5 μg/mL and 6.25 ng/mL， respectively. RSDs of intraday and interday precision tests of the three drugs were no more than 9.83%， and the accuracies （relative errors） were between －9.33% and 13.72%（ n ＝6 or n ＝18）； the average extraction recovery rates were 86.4%-97.9%， and the average matrix effects were 86.9%-110.0% （ n ＝6）. The absolute values of the relative errors in the stability tests were all below 15%. The steady-state trough concentrations of LTG， LEV and PER were （5.64±4.03）μg/mL， （10.67±8.78）μg/mL and（450.20±251.27）ng/mL， respectively； the rates of achieving target trough concentrations were 71.4%， 37.5% and 84.6%， respectively. CONCLUSIONS The established UPLC-MS/MS method is specific， rapid and suitable for the plasma concentration monitoring in epileptic children receiving combination therapy.

Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

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.

Autism spectrum disorder（ASD）is a multifactorial，pervasive neurodevelopmental disorder.As the morbidity rate of ASD in children increases year by year，feeding and eating behaviors，as an important and common clinical problem in children with ASD，are gaining more and more attention.Many children with ASD often have food selection issues，chewing problems，food allergy and related gastrointestinal symptoms，and even serious diseases such as eating disorders，which negatively impact on their growth and development.There are many factors affecting feeding and eating behavior problems in children with ASD，such as sensory processing，ritualistic eating behavior，gastrointestinal symptoms，age，and parenting pressure.There are also a variety of interventions that can help to improve feeding and eating behavior problems in children with ASD.Strengthening the understanding of these influencing factors and intervention treatment methods is beneficial for improving the quality of life in children with ASD.

Objective:To develop a scale to measure the sense of gain of the elderly, and to evaluate its reliability and validity.Methods:According to the content of the sense of gain, combined with the literature research method and interview method, the scale entry pool was established.After the expert consistency evaluation and the optimal test assembly method (OTA) analysis, the formal version of the scale was formed.The stratified sampling method was used to select 1 043 community-dwelling elders for the survey, and the reliability and validity of the scale were evaluated by methods based on classical test theory.Results:The scale of elderly sense of gain, which was screened by OTA method, included four dimensions: health status, relationship and communication, social security, and ideal expectation, with a total of 17 items. The Cronbach's α value of the formal version of the scale was 0. 850, and the Cronbach's α coefficients of the four dimensions were 0.721, 0.772, 0.779, and 0.930, respectively. The CR values of the combined reliabilities of each dimension were all above 0.7. In terms of AVE values, except for the health status dimension was acceptable, the other three dimensions were all above 0.36. The correlation coefficient between the sense of health acquisition and life satisfaction of the elderly was 0.531 ( P<0.01). Conclusion:The developed scale for measuring the sense of gain of the elderly has good reliability and validity, which can be used as an effective tool for measuring the sense of gain of the elderly.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

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.

Neoplasms characterized by the expression of markers of neuroendocrine differentiation in neoplastic cells are defined as neuroendocrine neoplasms. A case of neuroendocrine carcinomas (NECs) with a small amount of papillary adenocarcinoma and significantly vacuolar nucleus at the esophagogastric junction was reported in this article. A 77-year-old male had dysphagia for one week. Endoscopy revealed early-stage esophagogastric junction carcinoma, and biopsy was diagnosed as poorly differentiated carcinoma. Endoscopic submucosal dissection was performed. Histologically, the papillary adenocarcinoma progresses from typically branching papillary structures (well-differentiated) to hyperplasia of the lining epithelium of the papilla to form a cribriform structure (moderately differentiated), to solid area lacking papillary structures (poorly differentiated). There was a continuous process, and during this process, the vacuoles in the nuclei of tumor cells showed progressive changes from mild to obvious and finally to significant vacuoles. The tumor was mainly composed of solid areas (about 95%), with single cell, large cell, round or oval to irregular nuclei, and significantly vacuolar nuclei, nuclei with larger vacuoles appeared in a loop, a few thin weakly basophilic or weakly eosinophilic fine particles could be seen in the vacuoles, and the vacuoles had rough edges. The nucleus chromatin at the outer edge of the vacuoles was fine particles, and mitosis was common (20-30/mm²), atypical mitosis could be seen, and nucleoli could be seen easily, the cytoplasm was weakly eosinophilic, and the boundaries of cells were unclear. The cells were arranged in a nested, trabecular, or diffuse sheet shape, with some arranged in a glandular tube shape. Tumor thrombus was found in the vein of submucosa; the interstitial tissue rich in capillaries within the tumor was accompanied by a large number of neutrophil infiltration. Immunohistochemical staining showed that the solid area of the tumor was positive for synaptophysin (Syn) and chromogranin A (CgA), while papillary adenocarcinoma was negative. Mucin 5AC (MUC5AC) was diffusely positive in papillary adenocarcinoma, while the proportion of positive cells in the solid area of the tumor was about 10% to 15%. In a word, this case showed the extreme situation of the vacuolar nuclear characteristics of NECs, extremely rare, in a sense, this case expanded the boundary of the morphological spectrum of NECs. Understanding the extreme vacuolar features of this nucleus is helpful to make a correct pathological diagnosis.
Humans ; Male ; Esophagogastric Junction/pathology* ; Aged ; Carcinoma, Neuroendocrine/pathology* ; Vacuoles/pathology* ; Esophageal Neoplasms/pathology* ; Cell Nucleus/pathology* ; Adenocarcinoma, Papillary/pathology* ; Stomach Neoplasms/pathology*