BackgroundMonitoring the blood concentrations of antipsychotic drugs and their metabolites can guide the adjustment of clinical treatment plans， improving therapeutic efficacy while reducing adverse effects. However， there is currently a lack of a method that can accurately and efficiently quantitatively detect multiple antipsychotic drugs and their metabolites. ObjectiveTo establish a ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the simultaneous identification and quantitation of 12 antipsychotic drugs and their main metabolites in human serum. MethodsUsing UPLC-MS/MS technology， protein precipitation method was employed for sample pretreatment. An Agela Technologies Durashell C₈ chromatographic column （50 mm×3.0 mm， 5 μm） was selected for chromatographic separation with gradient elution. The flow rate was 0.4 mL/min， and the total analysis time was 5 minutes. The column temperature was 40℃. The mass spectrometry detection was carried out in the multiple reaction monitoring （MRM） mode， and the isotope internal standard method was used for quantification. ResultsThe relative standard deviation （RSD） of the internal standard normalization matrix effect factor for 12 antipsychotic drugs and their main metabolites at low and high quality concentrations was all less than 15%. The extraction recovery rate was 85% to 115%. They showed good linear relationships within their respective standard curve ranges （r>0.995）. At low， medium， and high quality concentrations， the accuracy was 85.24% to 114.71%， and the RSD of intra-batch and inter-batch precision was all ≤14.15%， with good stability. ConclusionAll the analytical performance indicators of this method meet the verification requirements， providing an analytical means for the quantitative detection of antipsychotic drugs and their main metabolites in human serum. ［Funded by The Third Batch of Science and Technology Projects in Chaozhou City in 2023 （number， 202303GY02）］

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

46XY simple gonadal hypoplasia, also known as Sweyer syndrome, patients often due to primary amenorrhea or pubertal secondary sex characteristics do not develop the doctor, its combined gonadal tumor is more likely, in the treatment process is often recommended prophylactic removal of gonads, postoperative hormone replacement therapy. We describe two patients diagnosed with Sweyer syndrome, one with gonadowlastoma and mature teratoma, and one with nodular Leydig cell hyperplasia and ectopic adrenal tissue, and reviews the literature.

Objective:To predict the incidence, prevalence, and mortality of dementia in China from 2020 to 2040.Methods:The age-standardized incidence rate (ASIR), incidence number, age-standardized prevalence rate (ASPR), prevalence number, age-standardized mortality rate (ASMR), and death number of dementia in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease Study (GBD) database. We used the overall change rate and estimated annual percentage change (EAPC) to describe the epidemic situation of dementia and compared the trend of dementia between genders. A T-test was used to determine whether EAPC was statistically significant. Every five years, we divided the age into 17 groups to analyze the incidence, prevalence, and mortality of dementia. The prophet model predicted ASIR, ASPR, ASMR, incidence, prevalence, and death from dementia in China from 2020 to 2040.Results:The ASIR, ASPR, and ASMR of dementia showed an increasing trend from 1990 to 2019, with an average annual increase of 0.33%, 0.66%, and 0.15% ( t=10.13, 14.49 and 3.62, all P<0.05). The ASIR, ASPR, and ASMR in males increased faster annually than in females. In 2019, the number of incidence, prevalence, and death from dementia in groups aged≥80 years was the highest among all age groups (685 057 cases, 5 772 861 cases, and 217 827 cases). Prediction results of the prophet model showed that the ASIR, ASPR, and ASMR of dementia were further increased in China from 2020 to 2040, with an average annual increase of 0.55%, 0.78%, and 0.06% ( t=177.63, 161.21, and 7.91, all P<0.05). In 2040, the ASIR, ASPR, and ASMR will reach 117.72/10 5, 940.98/10 5, and 23.64/10 5, respectively. In addition, the number of incidence, prevalence, and death from dementia will show an upward trend from 2020 to 2040. In 2040, the incidence, prevalence, and death will reach 3 334 770 cases, 25 303 146 cases, and 590 138 cases, respectively. Conclusion:From 2020 to 2040, the ASIR, ASPR, ASMR, number of incident cases, number of prevalent cases, and number of deaths due to dementia in China will continue to grow.

Objective:To predict the incidence, prevalence, and mortality of dementia in China from 2020 to 2040.Methods:The age-standardized incidence rate (ASIR), incidence number, age-standardized prevalence rate (ASPR), prevalence number, age-standardized mortality rate (ASMR), and death number of dementia in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease Study (GBD) database. We used the overall change rate and estimated annual percentage change (EAPC) to describe the epidemic situation of dementia and compared the trend of dementia between genders. A T-test was used to determine whether EAPC was statistically significant. Every five years, we divided the age into 17 groups to analyze the incidence, prevalence, and mortality of dementia. The prophet model predicted ASIR, ASPR, ASMR, incidence, prevalence, and death from dementia in China from 2020 to 2040.Results:The ASIR, ASPR, and ASMR of dementia showed an increasing trend from 1990 to 2019, with an average annual increase of 0.33%, 0.66%, and 0.15% ( t=10.13, 14.49 and 3.62, all P<0.05). The ASIR, ASPR, and ASMR in males increased faster annually than in females. In 2019, the number of incidence, prevalence, and death from dementia in groups aged≥80 years was the highest among all age groups (685 057 cases, 5 772 861 cases, and 217 827 cases). Prediction results of the prophet model showed that the ASIR, ASPR, and ASMR of dementia were further increased in China from 2020 to 2040, with an average annual increase of 0.55%, 0.78%, and 0.06% ( t=177.63, 161.21, and 7.91, all P<0.05). In 2040, the ASIR, ASPR, and ASMR will reach 117.72/10 5, 940.98/10 5, and 23.64/10 5, respectively. In addition, the number of incidence, prevalence, and death from dementia will show an upward trend from 2020 to 2040. In 2040, the incidence, prevalence, and death will reach 3 334 770 cases, 25 303 146 cases, and 590 138 cases, respectively. Conclusion:From 2020 to 2040, the ASIR, ASPR, ASMR, number of incident cases, number of prevalent cases, and number of deaths due to dementia in China will continue to grow.

Objective:To investigate the differences in understanding and diagnosis of polycystic ovary syn-drome(PCOS)among obstetricians and gynecologists with different clinical experiences,in order to promote com-munication and improve medical quality.Methods:This was a multi-center cross-sectional survey.Information on participants'basic information and their knowledge of PCOS comorbidities and treatment management was col-lected online.Physicians were divided into two groups according to their experience:experienced(>200 consulta-tions/year)and inexperienced(≤200 consultations/year).The differences in the diagnosis and treatment of PCOS among different groups were compared.Logistic regression analysis was used to explore other factors that might influence the diagnosis and treatment of PCOS.Results:1689 questionnaires were finally included,among which 95 were experienced and 1594 were inexperienced.①In the comparison of basic conditions,the proportion of experienced persons in tertiary hospitals and reproductive endocrinology specialties was higher than that of in-experienced persons(P<0.05);The percentage of experienced persons who predicted patients with comorbid insulin resistance(proportion>30%)and predicted comorbid overweight/obesity(proportion 30%-50%)was higher than that of less experienced persons(P<0.05).②There was no significant difference in the evaluation of PCOS and its complications among different groups(P>0.05).Logistic regression suggested that different expe-riencers did not significantly affect the assessment of androgens,OGTT and lipid testing(P>0.05).③There was no statistical significance in the choice of treatment for those with no fertility need(P>0.05).For those with fertili-ty needs,metformin and letrozole were more actively selected by experienced group than inexperience(P<0.05).In terms of weight loss,experienced participants were more active in using metformin(P<0.05)and were more likely to choose1.0 or1.5 g/d(P<0.05)than those with inexperience.Conclusions:There was no signifi-cant difference in PCOS assessment among participants with different experience,but in treatment,experienced participants were better able to take into account the multi-system abnormalities brought by PCOS,and at the same time,they give more comprehensive and accurate treatment opinions on patients with or without fertility needs.

Objective:To investigate the factors affecting the accuracy of electronic portal imaging device (EPID)-based in vivo dose verification in radiotherapy for patients with lung and esophageal cancers, and to recommend the workflow and specifications for the application of the in vivo dose verification. Methods:This study randomly selected 32 patients who received radiotherapy for esophageal and lung cancers at the Department of Radiation Oncology, Jinhua Municipal Central Hospital from May to August 2022, including 14 lung cancer cases and 18 esophageal cancer cases. Using a uRT-linac 506c linear accelerator, these patients were treated according to the dynamic intensity-modulated radiotherapy (dIMRT) and EPID-based In vivo dose verification ( In vivo EPID) plans developed with the uRT-TPOIS planning system. The In vivo dose verification performed during the treatment included 238 fractions of In vivo EPID and 80 fractions of image-guided radiotherapy (IGRT) for the lung cancer cases, as well as 414 fractions of In vivo EPID and 105 fractions of IGRT for the esophageal cancer cases. The 2D γ passing rate for each irradiation field was obtained according to the set threshold value. Furthermore, fractioned irradiation fields with γ-passing rates below the threshold value were analyzed, and primary factors decreasing the γ-passing rate were further analyzed by combining the online CT images and 3D reconstruction-derived dose. Results:For lung and esophageal cancers, the mean γ-passing rates were 95.1% ± 5.7% and 96.5% ± 4.5%, respectively at 3 mm/5%; 91.5% ± 8.4% and 92.2% ± 4.9%, respectively at 3 mm/3%, and 79.1% ± 14.7% and 83.7% ± 8.2%, respectively at 2 mm/2%, indicating no statistically significant differences between two cancers ( P > 0.05). The average γ passing rate for beam orientations near 0°/180° (Group A) was higher than those near 90°/270° (Group B) 3 mm/5%: Z = -25.4, P < 0.05; 3 mm/3%: Z = -26.8, P < 0.05). The IGRT correction of setup errors significantly improved the γ passing rates (96.3% ± 5.1% and 96.4% ± 4.9%, respectively at 3 mm/5%, Z = -5.50, P < 0.05; 92.3% ± 8.0% and 91.3% ± 7.7%, respectively at 3 mm/3%, Z = -9.54, P < 0.05). The results of In vivo dose verification were affected by changes in the volumes and motion of tumors and normal tissues, radiotherapy positioning, and adequacy of pre-treatment preparation. Conclusions:EPID-based In vivo dose verification during radiotherapy can avoid incorrect irradiation. However, it is necessary to standardize the workflow of the EPID-based In vivo dose verification to avoid the decrease in the γ passing rate caused by artificial factors.

Objective:To explore the clinical and laboratory characteristics of acquired immunodeficiency syndrome (AIDS) patients complicated with disseminated nontuberculous mycobacterial (NTM) disease, in order to provide basis for clinical therapy.Methods:The clinical findings, imaging and etiological data of the 71 AIDS patients complicated with disseminated NTM disease admitted to Beijing You′an Hospital from June 2016 to June 2021 were retrospectively analyzed.Results:Among 71 patients with disseminated NTM disease, the most common initial symptom was fever, followed with cough, expectoration, fatigue, poor appetite, abdominal pain and diarrhea. Seventy point four percent (50/71) of these patients had at least two comorbidities, with oral candida infection, cytomegalovirus infection, syphilis, pneumocystis pneumonia and bacterial pneumonia being the most common. Hemoglobin ((87.8±24.2) g/L) and albumin ((27.3±7.0) g/L) levels significantly decreased, while erythrocyte sedimentation rate ((59.8±28.6) mm/1 h) and C-reactive protein ((74.7±50.8) mg/L) levels increased in most cases. The median CD4 + T lymphocyte count was 7×10 6/L. The median time of positive blood culture of NTM was 260 h. Among the 71 patients, 40 cases (56.3%) were infected with Mycobacterium avium, 15 cases (21.1%) with Mycobacterium intracellulare, 10 cases (14.1%) with Mycobacterium colombiense, three cases (4.2%) with Mycobacterium marseillense and three cases (4.2%) with Mycobacterium kansasii.The frequent imaging findings were patchy and nodular shadows in lungs, and most patients had mediastinal or hilar lymph node enlargement and splenomegaly. Conclusions:AIDS complicated with disseminated NTM disease is prevalently occurred in patients with severe immune deficiency, and most of the bacteria belong to the Mycobacterium avium- intracellulare complex. Early obtaining positive etiological results of NTM is essential to guide the correct clinical diagnosis and accurate treatment.

BACKGROUND: As one of the most common endocrinal disorders for women at childbearing age, the diagnostic criteria of polycystic ovary syndrome (PCOS) have been defined differently among different international health organizations. Phenotypic heterogeneity of PCOS also brings about difficulties for its diagnosis and management assessment. Therefore, more efficient biomarkers representing the progression of PCOS are expected to be integrated into the monitoring of management process using metabolomic approaches. METHODS: In this prospective randomized controlled trial, 117 PCOS patients were enrolled from December 2016 to September 2017. Classical diagnostic parameters, blood glucose, and metabolome were measured in these patients before and at 2 months and 3 months of different medical interventions. The receiver operating characteristic (ROC) curves were built based on multivariate statistical analysis using data at baseline and 3 months' management, and combinational biomarkers with appreciable sensitivity and specificity were selected, which then validated with data collected at 2 months. RESULTS: A set of metabolites including glutamic acid, aspartic acid, 1-methylnicotinamide, acetylcarnitine, glycerophosphocholine, and oleamide were filtered out with high performance in representing the improvement through 3-month management of PCOS with high sensitivity and specificity in ROC analysis and validation with other two groups showed an appreciable area under the curve over 0.96. CONCLUSIONS: The six metabolites were representative of the remission of PCOS through medical intervention, making them a set of potential biomarkers for assessing the outcome of PCOS management. TRIAL REGISTRATION ClinicalTrials.gov, NCT03264638.
Biomarkers ; Female ; Humans ; Metabolomics ; Polycystic Ovary Syndrome/diagnosis* ; Prospective Studies ; ROC Curve