ObjectiveTo investigate the temporal trend of weight-adjusted-waist index （WWI） and its association with the risk of incident cardiovascular diseases （CVD） among middle-aged and older Chinese adults. MethodsBased on the China Health and Retirement Longitudinal Study （CHARLS）， this research enrolled participants aged 45 and above with complete physical measurement data from the 2011， 2013， and 2015 waves. Complex sampling weights were applied to calculate the mean WWI， and the Mann-Kendall test was used to analyze its trend. From the 2011 baseline survey， individuals with a history of cardiovascular disease or missing key covariates were further excluded. New-onset cardiovascular outcome events were collected during follow-up until 2020. Participants were categorized into Q1–Q4 groups based on baseline WWI quartiles. Multivariable log-binomial regression models were constructed to assess the association between WWI and CVD， while restricted cubic splines were employed to evaluate potential nonlinear relationships. Sensitivity analyses were conducted to verify the robustness of the findings. ResultsFrom 2011 to 2015， the weighted mean WWI among Chinese middle-aged and older adults remained generally stable （2011： 11.17±1.68； 2013： 11.28±1.35； 2015： 11.24±1.59； P for trend <0.05）. During the longitudinal follow-up， 1 784 incident CVD cases were documented. After multivariable adjustment， each unit increase in WWI was associated with a 17% increased risk of CVD （RR： 1.17， 95%CI： 1.10-1.24）. Compared with the Q1 group， the risk of CVD in the Q2， Q3， and Q4 groups increased by 23% （RR： 1.23， 95% CI： 1.07-1.40）， 27% （RR： 1.27， 95% CI： 1.11-1.44）， and 40% （RR： 1.40， 95% CI： 1.22-1.60）， respectively. A significant linear trend was observed between the increasing WWI and elevated CVD risk （P for trend <0.001）. Subgroup analysis revealed a stronger association in participants aged 45-60 years （P for interaction <0.05）. The results of sensitivity analysis were consistent with the main research results. ConclusionsThe overall trend of WWI level in the middle-aged and elderly population in China is stable from 2011 to 2015. The higher level of WWI is associated with an increased risk of CVD， suggesting that WWI may be used as a simple and effective indicator to evaluate the risk of cardiovascular metabolism in middle-aged and elderly people.

ObjectiveTo enhance the genetic diagnostic yield for fetal short femur length （FL） and to evaluate the integration of whole exome sequencing （WES） with chromosomal abnormality detection in prenatal diagnosis. MethodsA total of 27 mid-to-late trimester fetuses diagnosed with short FL ［FL < 5th percentile for gestational age or < -2 SD （Standard Deviation）］ at the Prenatal Diagnosis And Medical Genetics Center，Shenshan Medical Center，Memorial Hospital of Sun Yat-Sen University between November 2023 and May 2025 were included. Amniotic fluid or umbilical cord blood samples were collected and subjected to chromosomal karyotyping （19cases）， chromosomal microarray analysis （CMA） or low-coverage whole genome copy number variation（CNV-Seq） （27 cases）， and trio-based whole exome sequencing （trio-WES） （27 cases）. The pathogenicity of genetic variants were interpreted according to the American College of Medical Genetics and Genomics （ACMG） guidelines. ResultsTwenty-six genomic variants were detected in 17 of the 26 fetuses， including numerical chromosomal abnormalities （mosaic type）， copy number variations （CNVs）， single nucleotide variants （SNVs） and insertions-deletions （INDELs）. Genomic variants detected in 11 cases could explain the short femur phenotype.The overall diagnostic rate was 11/27， with pathogenic/likely pathogenic variants explaining 9 cases and variants of uncertain significance （VUS） accounting for 1 cases. In addition Chromosomal karyotype analysis revealed chromosome mosaicism explaining 1 case. The diagnostic rate of CNV detection （CMA/CNV-seq） was 2/27， while WES achieved a diagnostic rate of 10/27， with an incremental yield of 8/27 in cases with negative or inconclusive CNV results. Pathogenic mutations involved genes such as FGFR3， SHOX， DUOX2， CLCN5， and HBA1/HBA2. ConclusionTrio-WES significantly improves the genetic diagnostic rate for fetal short femur length， particularly in cases where chromosomal analysis fails to identify a cause. Karyotyping remains valuable for detecting low-level mosaicism in large-scale chromosomal abnormalities， thereby complementing WES and CNV detection. A stepwise or parallel genetic testing strategy is recommended in prenatal diagnosis to optimize diagnostic efficiency and support clinical decision-making.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Background::The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate. Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome, who subjected to preimplantation genetic testing for aneuploidy (PGT-A) treatment. However, it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods::From February 2020 to May 2021, we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos, the clinical information of couples, and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment. Initially, we developed a novel deep learning model called the Attentive Multi-Focus Selection Network (AMSNet) to analyze time-lapse videos in real time and predict blastocyst formation. Building upon AMSNet, we integrated additional clinically predictive variables and created a second deep learning model, the Attentive Multi-Focus Video and Clinical Information Fusion Network (AMCFNet), to assess the euploidy status of embryos. The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements. The receiver operating characteristic curve (ROC) was used to evaluate the superiority of the model. Results::A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task, and 1422 qualified blastocysts received PGT-A ( n = 589) or PGT for chromosomal structural rearrangement (PGT-SR, n = 833) were enrolled for the euploidy assessment task in this study. The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy. The real-time accuracy for AMSNet to predict blastocyst formation reached above 70% on the day 2 of embryo culture, and then increased to 80% on the day 4 of embryo culture. Combing with 4 clinical features of couples, the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement. Conclusion::Integrating seven focal raw time-lapse images of embryos and parental clinical information, AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.
Humans ; COVID-19 ; Medicine, Chinese Traditional ; SARS-CoV-2 ; Critical Illness ; Treatment Outcome

Integration of sports and medicine focuses on using exercise to prevent chronic diseases and enhance physical health.Frailty, a common syndrome in the elderly, has significant impacts on various aspects of their well-being.China currently lacks clear and unified recommendations for physical and health integration interventions for frailty.This consensus aims to gather the latest evidence and clinical experiences, both domestically and internationally, to minimize functional impairments in the elderly, slow down frailty progression, and improve quality of life through integrated strategies.Ultimately, the goal is to ensure the health and well-being of the elderly population.

Integration of sports and medicine focuses on using exercise to prevent chronic diseases and enhance physical health.Frailty, a common syndrome in the elderly, has significant impacts on various aspects of their well-being.China currently lacks clear and unified recommendations for physical and health integration interventions for frailty.This consensus aims to gather the latest evidence and clinical experiences, both domestically and internationally, to minimize functional impairments in the elderly, slow down frailty progression, and improve quality of life through integrated strategies.Ultimately, the goal is to ensure the health and well-being of the elderly population.

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.
Female ; Humans ; Cervix Uteri/surgery* ; Prognosis ; Retrospective Studies ; Uterine Cervical Neoplasms/surgery* ; Carcinoma, Neuroendocrine/surgery* ; Recurrence

Aim To explore the signaling pathway of matrine derivative ZS10 in inhibiting proliferation and inducing apoptosis of BEL-7402 cells. Methods ZS10 was synthesized by organic synthesis. The inhibitory effect of ZS10 on the proliferation of BEL-7402 cells was analyzed by MTT method at the time of 24 h, 48 h and 72 h, respectively, and IC50 was calculated. DAPI staining was used to observe the state of BEL-7402 cells. Clone formation method was used to observe the colony formation of BEL-7402 cells, flow cytometry was used to observe the cell cycle arrest and apoptosis of BEL7402 cells, and Western blot was used to detect the expression level of PI3K/AKT pathway and related proteins. Results MTT results showed that the IC50 was(6.62±1.11)μmol·L-1; DAPI staining showed that the cell state changed significantly with the increase of drug concentration, and the results of colony formation showed that ZS10 significantly inhibited the colony formation of BEL-7402 cells. The results of flow cytometry showed that ZS10 induced S phase arrest and cycle apoptosis of BEL-7402 cells. Western blot showed that ZS10 at the concentration of 08 μ mol·L-1 could regulate the PI3K/AKT pathway and its related proteins in a dose-dependent manner. Compared with the control group, the expression of PI3K, AKT, P-AKT and anti-apoptotic protein Bcl-2 significantly decreased, the expression of pro-apoptotic protein Bax significantly increased, the expression of Cyclin D1 and CDK2 significantly decreased, and the expression of EGFR and N-cadherin, Vimentin significantly decreased in the treatment group. The expression of E-cadherin increased. Conclusions Matrine derivative ZS10 can inhibit the growth and proliferation of hepatocellular carcinoma cell line BEL-7402.