OBJECTIVE To conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

AIM: To explore the therapeutic effect and prognosis of intense pulsed light combined with pralprofen eye drops for meibomian gland cysts in children. METHODS: Children with meibomian gland cysts visited the hospital for treatment from April 2023 to October 2024 were selected as the research subjects. All subjects were grouped using the random number table methed. In the control group, patients were treated with hot compress. In the drug group, patients were treated with pralprofen eye drops combined with hot compress. In the laser group, patients were treated with intense pulsed light combined with hot compress. In the combination group, patients were treated with pralprofen eye drops combined with intense pulsed light and hot compress. The treatment effective rate, cyst surface area, ocular symptom score, and occurrence of adverse reactions of children in each group were compared. RESULTS: A total of 80 children(80 eyes)were enrolled in this study, with 20 cases(20 eyes)in each of the control group, drug group, laser group, and combination group. The mean age was 7.49±1.09 y in the control group(9 males and 11 females), 7.63±0.98 y in the drug group(11 males and 9 females), 7.39±0.59 y in the laser group(12 males and 8 females), and 7.63±1.21 y in the combination group(12 males and 8 females). The total effective rate was 70%(14/20)in the combination group, which was significantly higher than that in the control group, drug group, and laser group(all P<0.05). After treatment, the cyst surface area and ocular symptom scores decreased to varying degrees in all groups. Notably, at 21 d post-treatment, the cyst surface area and ocular symptom scores in the combination group were significantly lower than those in the control group, drug group, and laser group(all P<0.05). No adverse reactions occurred in the combination group, which was lower than that in the control group, drug group, and laser group, with no statistically significant difference among the four groups(P>0.05).CONCLUSION: Intense pulsed light combined with pralprofen eye drops can improve the ocular symptoms of children with meibomian gland cysts, reduce the surface area of meibomian gland cysts, increase the clinical cure rate, and this treatment method is highly safe.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

OBJECTIVE To conduct a systematic review concerning the safety of using glucagon-like peptide-1 receptor agonists （GLP-1RA） before gastrointestinal endoscopy. METHODS Chinese and English databases including CNKI， Wanfang Data， VIP， CBM， and PubMed were searched to collect systematic reviews and meta-analyses on the safety of using GLP-1RA before gastrointestinal endoscopy， with a search period from the inception to September 30， 2025. Report quality， methodological quality， risk of bias， and evidence quality were assessed using the PRISMA 2020 statement， AMSTAR 2 scale， ROBIS tool， and GRADE tool， respectively. Corrected covered area （CCA） was used to quantitatively evaluate the degree of outcome overlap， and a comprehensive quality analysis was performed on the quantitative results of systematic reviews/meta-analyses. RESULTS Ten studies were included. All 10 stu dies had some information deficiencies （15.5-19.5 points）， and were at high risk of bias； 9 studies were extremely low methodological quality， while 1 study was low. In terms of evidence quality， among 88 outcome indexes， there was 1 moderate-level index， 28 low-level indexes， and 59 extremely low-level indexes. The CCA values of the incidence of residual gastric contents， aspiration， endoscopy interruption， repeated endoscopy， inadequate bowel preparation and Boston Bowel Preparation Scale scores were 37.30%， 35.00%， 35.00%， 50.00%， 29.60% and 20.00%， respectively. Results of comprehensive quality analysis showed that compared with the control group， the incidence of residual gastric contents， endoscopy interruption and repeated endoscopy were increased significantly in the intervention group， along with a notably prolonged gastric emptying time and a significantly lower score of Boston Bowel Preparation Scale （ P ＜0.05）. However， the study results regarding the effects of GLP-1RA on the incidence of aspiration and inadequate bowel preparation were inconsistent. CONCLUSIONS The use of GLP-1RA before gastrointestinal endoscopy can increase certain safety risks， including residual gastric contents， endoscopy interruption and repeated endoscopy， prolong gastric emptying time， and reduce the quality of bowel preparation. However， the effects on aspiration and inadequate bowel preparation remain controversial. The reports included in systematic reviews/meta-analyses exhibited low quality in reporting， methodology and evidence， with high risk of bias. Therefore， conclusions should be interpreted with caution.

AIM:To evaluate the optimal timing of preoperative intravitreal anti vascular endothelial growth factor(VEGF)therapy in proliferative diabetic retinopathy(PDR)using intraoperative fluorescein angiography(IOFA).METHODS:A retrospective case series study was conducted on patients who underwent vitrectomy for PDR with vitreous hemorrhage(VH)at Sichuan Provincial People's Hospital from January 2023 to February 2025. Patients were divided into three groups according to the interval between intravitreal conbercept injection and surgery: Group A(3 d before surgery), Group B(7 d before surgery), and Group C(14 d before surgery). IOFA was used to assess the number and size of retinal neovascularization(NV). Additional data were collected including preoperative best corrected visual acuity(BCVA), vitreous hemorrhage grading, operative time, frequency of intraoperative endodiathermy, duration of high perfusion pressure, vitreoretinal adhesion grade, postoperative BCVA, and central macular thickness(CMT). Multidimensional analyses were performed.RESULTS:This study enrolled a total of 91 patients(94 eyes)with PDR accompanied by vitreous hemorrhage. Among them, Group A consisted of 31 patients(31 eyes; 18 males, 13 females; mean age 53.26±12.38 y), Group B consisted of 34 patients(37 eyes; 21 males, 13 females; mean age 51.61±14.16 y), and Group C consisted of 26 patients(26 eyes; 18 males, 8 females; mean age 51.00±12.02 y), with baseline characteristics comparable among the three groups(all P>0.05). Comparative analysis of NV visualized via IOFA revealed that both the number and size of NVs were significantly lower in Groups B and C than in Group A(all P<0.0167), while no statistically significant differences were observed between Groups B and C(both P>0.05). No significant differences were found among the three groups regarding other intraoperative parameters, including operation time, frequency of electrocoagulation application, duration of high perfusion pressure, or grading of vitreoretinal adhesion(all P>0.05).CONCLUSION:IOFA confirms that preoperative anti-VEGF therapy administered 7 or 14 d before surgery is more effective than a 3 d interval in suppressing retinal NV activity in PDR patients.

OBJECTIVE: To investigate the genetic mechanism for adverse pregnancies due to submicroscopic chromosomal structural variants in two cases, and to provide a precise guidance for preimplantation genetic testing. METHODS: Two families who had visited Chengdu Women's and Children's Central Hospital for reproduction guidance due to recurrent miscarriages, adverse pregnancy history and abnormal genetic testing of the offspring in June and December 2023 were selected as the study subjects. Chromosomal karyotyping and optical genome mapping (OGM) were carried out on peripheral blood samples from the two couples, and preimplantation genetic testing for structural rearrangement (PGT-SR) were performed on the blastocyst trophoblasts. This study was approved by the Medical Ethics Committee of the Hospital (Ethic No.: 2023-23). RESULTS: No abnormality was found on the G-banded karyotyping analysis for both couples. The OGM results revealed that the female partner of couple 1 had a translocation between 4pter-p16.3 (3.99 Mb) and 11pter-p15.4 (2.66 Mb), whilst no abnormality was found in the male partner. Similarly, the male partner of couple 2 had a translocation between 19q13.43-qter (1.90 Mb) and 22q13.31-qter (3.34 Mb). No abnormality was found in the female partner of couple 2. Neither breakpoints nor the adjacent region had involved an OMIM gene, except the formation of a fusion gene ZIM2-AS1-Z82186.1 (Both genes are non-coding, and the fusion gene was deemed as variant of unknown significance). PGT-SR of 11 blastocysts derived from couple 1 revealed that one embryo was suitable for priority transfer, three embryos were suitable for transfer, one embryo was recommended for genetic counselling, and six embryos were unsuitable for the transfer. For couple 2, six blastocysts were tested, of which only one embryo was deemed suitable for transfer. CONCLUSION When genetic testing of offspring indicates copy number variations such as deletions, duplications or mosaicism, the high-resolution OGM technique can be selected to screen parents for submicroscopic chromosomal structural variations. The result can facilitate accurate assessment for the risk of recurrence in offspring, selection of suitable method for reproduction, and identifying targets for PGT.
Humans ; Female ; Pregnancy ; Adult ; Male ; Karyotyping ; Chromosome Aberrations ; Abortion, Habitual/genetics* ; Preimplantation Diagnosis ; Genetic Testing

OBJECTIVE: To investigate the detection patterns, clinical phenotypic characteristics, and differences in diagnostic timeliness of Klinefelter syndrome (KS) across prenatal and postnatal stages, with an aim to provide a basis for optimizing strategies for early screening, diagnosis, and intervention. METHODS: A retrospective study was conducted to analyze data from two phases. The prenatal diagnosis group included 33,302 pregnant women who underwent amniocytic karyotyping due to advanced maternal age, abnormal ultrasound findings, or high-risk non-invasive prenatal testing (NIPT). The postnatal diagnosis group included 52,101 patients who underwent peripheral blood karyotyping due to primary infertility, abnormal external genitalia, or growth and developmental abnormalities. Additionally, medical histories of adult diagnosed patients were reviewed retrospectively to identify early occult symptoms. This study was approved by the Medical Ethics Committee of Chengdu Women's and Children's Central Hospital (Ethics No.: LCYJ-2025-030). RESULTS: In the prenatal group, 96 cases of KS were detected (detection rate 0.29%). The primary indications for referral were NIPT indicating sex chromosome abnormalities (45.83%), advanced maternal age (16.66%), and ultrasound abnormalities (17.70%). In the postnatal group, 128 cases of KS were detected (detection rate 0.25%). Clinical presentations were primarily primary infertility/azoospermia (77.34%), and the patients were predominantly adults (84.40%). Retrospective analysis revealed that adult patients presented with specific physical signs that had been overlooked during childhood. CONCLUSION As KS lacks typical early clinical manifestations, diagnosis is often delayed until adulthood when reproductive needs arise, showing a pattern of "passive detection" and resulting in missed opportunities for optimal intervention. By conducting a comparative analysis of prenatal diagnostic data and postnatal retrospective data, a risk association model linking prenatal screening indications with childhood-specific signs was developed. This study has provided empirical evidence for establishing a multidisciplinary, full life-cycle management system of "screening ~ diagnosis ~ monitoring ~ intervention" helping to shift from "passive detection in adulthood" to "proactive management across the entire life course," and laid a foundation for improving early diagnosis rate and long-term quality of life for patients.
Humans ; Klinefelter Syndrome/genetics* ; Female ; Adult ; Pregnancy ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Male ; Phenotype ; Karyotyping ; Young Adult ; Adolescent ; Middle Aged

The implantation of left ventricular assist device (LVAD) has significantly improved the quality of life for patients with end-stage heart failure. However, it is associated with the risk of complications, with unplanned readmissions gaining increasing attention. This article reviews the influencing factors, prediction methods and models, and intervention measures for unplanned readmissions in LVAD patients, aiming to provide scientific guidance for clinical practice, assist healthcare professionals in accurately assessing patients' conditions, and develop rational care plans.

Gliomas, especially high-grade gliomas such as glioblastoma multiforme (GBM), are primary malignant tumors of the central nervous system, characterized by high proliferative capacity, invasiveness, and therapeutic resistance. The development of GBM relies heavily on continuous metabolic reprogramming to adapt to the unique intracranial microenvironment, with nicotinamide adenine dinucleotide (NAD⁺) metabolic remodeling playing a pivotal role. Dysregulation of NAD⁺ and its associated metabolic pathways sustains increased intracellular NAD⁺ levels, which drive the malignant proliferation and invasive potential of GBM, correlating with worsened patient prognosis. This review systematically summarizes the current research landscape of NAD⁺ metabolic remodeling in GBM, elucidates the mechanisms by which NAD⁺ contributes to GBM pathogenesis and progression, and explores the clinical potential of NAD⁺-targeted diagnostic and therapeutic strategies to provide novel insights and directions for the clinical management of GBM.

Objective To explore the longitudinal associations of body roundness index (BRI), visceral adiposity index (VAI), and metabolic score for visceral fat (METS-VF) with the risk of new-onset atrial fibrillation (AF). Methods This study included participants from the UK Biobank who were free of AF or pregnancy at baseline and completed the first and second assessments of BRI, VAI, and METS-VF. The changes in BRI, VAI, and METS-VF were classified using K-means clustering analyses, and the cumulative adiposity indices were also calculated. The primary outcome was new-onset AF. Three Cox regression models were employed to investigate the longitudinal associations of the BRI, VAI, and METS-VF changes with the risk of incident new-onset AF. The results were presented as hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Restricted cubic spline analyses were performed to explore potential non-linear associations between baseline or cumulative adiposity indices and the risk of new-onset AF. C-index analyses were conducted to evaluate the predictive value of BRI, VAI, and METS-VF for new-onset AF. Subgroup analyses were performed according to age, gender, race, smoking status, alcohol consumption, and physical activity. Polygenic risk scores were applied to account for genetic susceptibility and investigate potential interactions between adiposity indices and genetic risk. Univariate linear regression analyses were performed to evaluate the relationships of cumulative adiposity indices and magnetic resonance imaging and dual X-ray absorptiometry parameters, including visceral adipose tissue (VAT) volume, VAT mass, trunk fat volume, and trunk fat mass. We further applied the eXtreme Gradient Boosting (XGBoost) algorithm, with the feature importance being measured to evaluate the predictive value of each adiposity index for imaging parameters. Mendelian randomization analysis was further conducted to investigate the potential causal relationship between trunk fat mass and AF. Results A total of 12 776 participants were included. Over a median follow-up of 9.60 years, 761 (5.96%) new-onset AF events were recorded. Participants were divided into four classes based on the changes in adiposity indices. In the fully adjusted model, compared to participants in Class 1 of BRI, those in Class 3 (HR＝1.30, 95%CI 1.04-1.63, P＝0.023) and Class 4 (HR＝2.17, 95%CI 1.61-2.93, P＜0.001) were associated with significantly higher risks of new-onset AF. Regarding METS-VF, participants in Class 4 of METS-VF also demonstrated a significantly higher risk of new-onset AF compared to those in Class 1 (HR＝1.66, 95%CI 1.15-2.39, P＝0.007). However, no significant association was observed between different classes of VAI and the risk of new-onset AF. For every 1 standard deviation increase in cumulative BRI, VAI, and METS-VF, the fully adjusted HRs of new-onset AF were 1.23 (95%CI 1.13-1.35), 1.02 (95%CI 0.94-1.10), and 1.23 (95%CI 1.12-1.35), respectively. Cumulative adiposity indices (BRI, VAI, and METS-VF) were divided into quartiles. Using the first quartile as reference, participants in the highest quartiles of BRI (HR＝1.40, 95%CI 1.10-1.79, P＝0.007) and METS-VF (HR＝1.44, 95%CI 1.13-1.83, P＝0.003) both exerted a significantly higher risk of new-onset AF. Regarding VAI, no significant association was observed (HR＝1.00, 95%CI 0.81-1.23, P＝0.988). Restricted cubic spline analyses revealed non-linear relationships between cumulative BRI, baseline/cumulative VAI, and baseline/cumulative METS-VF with new-onset AF risk (all P_overall＜0.05, P_non-linear＜0.05). In the C-index analysis, BRI demonstrated the highest predictive performance for new-onset AF, followed by METS-VF and VAI. Subgroup analysis indicated a stronger association between METS-VF and the risk of new-onset AF amongst participants younger than 60 years (P_interaction＝0.008). Polygenic risk score analysis stratified by genetic risk demonstrated a synergistic effect between BRI and genetic risk with new-onset AF, with the overall risk of new-onset AF increasing as both BRI and genetic risk increased. Linear regression analysis revealed a positive correlation between cumulative BRI with VAT volume, VAT mass, trunk fat volume, and trunk fat mass. The feature importance plot derived from the XGBoost algorithm indicated that cumulative BRI had the greatest predictive value on VAT volume, VAT mass, trunk fat volume, and trunk fat mass. Mendelian randomization analysis confirmed a significant causal relationship between trunk fat mass and AF. Conclusions There are significant non-linear associations between BRI, METS-VF, and VAI with new-onset AF. Higher BRI and METS-VF are significantly associated with a higher risk of new-onset AF, whereas no significant association is observed for the VAI. BRI exhibits a positive correlation with VAT and trunk fat, and demonstrates superior performance in predicting new-onset AF compared to VAI and METS-VF. Monitoring and managing BRI may be important in the early detection and intervention of AF.