Random allocation is essential in randomized controlled trials (RCTs) to ensure impartial treatment allocation and minimize selection bias. Despite permuted block design (PBD) is used in approximately 75

Background:The Sustainable Development Goals (SDGs) aim to reduce the global maternal mortality ratio (MMR) to below 70 deaths per 100 000 live births by 2030. However, progress has been uneven, with regional disparities and new challenges. We aimed to report global trends in maternal disorder burdens from 1990 to 2021. Methods:Using the Global Burden of Disease (GBD) 2021 database, we systematically analysed trends in incidence, mortality, and disability-adjusted life-years (DALYs) associated with maternal disorders from 1990 to 2021 and employed age-period-cohort (APC) models to assess changes in these indicators. For selected age-specific analyses, we additionally expressed incidence and DALY rates per 100 000 live births using age-specific fertility rates. We used the Bayesian APC model to forecast trends in maternal disorder incidence and mortality from 2022 to 2036. Results:From 1990 to 2021, there was a decrease in global incidence (38.5%), mortality (43.2%), and DALYs (61.4%) of maternal disorders. However, significant regional disparities persist. The burden was considerably lower in higher-sociodemographic-index regions than in sub-Saharan Africa. Maternal haemorrhage and hypertensive disorders continue to represent the primary causes of mortality, with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)-related deaths increasing, particularly among women aged 30-34 years and older. The APC model revealed that the age effect on maternal disorders initially decreased and then increased. The projected MMR of 136.5 (95% confidence interval = 100.2-172.7) per 100 000 live births by 2030 falls short of the SDG target of 70 maternal deaths per 100 000 live births, indicating a markedly insufficient annual reduction rate. Conclusions:Despite a decrease in the global burden of maternal disorders, regional disparities persist. Major challenges include haemorrhage, hypertensive disorders, and increasing HIV/AIDS-related deaths. Achieving SDG targets by 2030 requires universal access to quality maternal care.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, interstitial lung disease lacking an efficient drug to reverse it. Thus, there is an urgent need to elucidate the complex pathogenesis of IPF and identify new therapeutic targets. It has been revealed that the pathophysiology of IPF is a highly orchestrated process that includes multiple cell types in which the contribution of endothelial cells (ECs) has attracted researchers' attention. However, although the involvement of ECs in fibrosis has been recognized, the underlying key molecules driving these changes are not well defined. In this study, we revealed that von Willebrand factor (VWF), a marker of damaged ECs, and endothelial dysfunction are positively correlated with IPF progression on the basis of reanalysis of gene expression profiles of patients with IPF. Next, we discovered that VWF deficiency attenuated fibrosis in experimental models, including human cell lines (in vitro) and mice (in vivo). Mechanistically, VWF deficiency inhibited endothelial-to-mesenchymal transition, regulated vascular abnormalities, and limited M2 macrophage infiltration, which were achieved, at least in part, by the inhibition of Wnt signaling. Our findings provided evidence for the pivotal role of ECs in IPF and revealed that VWF might be a driving factor of endothelial-to-mesenchymal transition, suggesting that VWF can be developed as a potential therapeutic target against IPF.

The metabolic score for insulin resistance (METS-IR) is a novel indicator used to assess insulin resistance. Previous studies have shown that it is associated with an increased risk of hypertension. However, its relationship with preeclampsia (PE) remains unclear. This study aims to investigate the association between METS-IR and PE. A total of 39,693 singleton pregnant women from three hospitals in China between January 2018 and June 2024 were included in the study. Data were collected through the hospital information system, and METS-IR was calculated using the following formula: ln([HDL-C (mg/dL)] × [2 × fasting glucose (mg/dL)] + TG (mg/dL) × BMI (kg/m2)). ROC curve analysis was used to evaluate the predictive performance of METS-IR and identify an optimal threshold. Participants were grouped based on METS-IR quartiles and this threshold value. Smooth curve fitting, multivariable logistic regression models, and subgroup analyses were conducted to evaluate the association between METS-IR and PE. The results showed a nonlinear dose–response relationship between METS-IR and PE. The area under the ROC curve (AUC) was 0.649, with an optimal cutoff value of 38.644. After adjusting for potential confounders, higher METS-IR levels were significantly associated with increased risk of PE. Compared with the lowest quartile (Q1), the odds ratios (ORs) for PE in the Q2, Q3, and Q4 groups were 1.19 (95

3589 Background: Single-incision laparoscopic surgery (SILS) is increasingly being embraced in the medical community due to its potential to offer less-invasiveness and quick recovery. This multi-center randomized controlled trial compared the short-term and long-term outcomes of single-incision laparoscopic surgery (SILS) with conventional laparoscopic surgery (CLS) for colorectal cancer, which might be the first of its kind that involved both colon and rectal cancer. Study recruitment has completed, and the follow-up is ongoing. Here we report the short-term outcomes of this trial. Methods: The trial was conducted across 11 hospitals in 6 provinces of China. Participants included patients with histologically confirmed colorectal carcinoma that situated above the peritoneal reflection, clinically staged as I-III. Patients were randomly assigned in a 1:1 ratio to SILS or CLS group. Comprehensive perioperative data were meticulously gathered, and follow-up assessments were scheduled postoperatively. The primary endpoint was 3-year disease-free survival (DFS), secondary endpoints included overall survival (OS), oncological efficacy, and postoperative outcomes. Results: Between May 2021 and April 2023, a total of 712 patients were randomly assigned to either the Single-incision Laparoscopic Surgery (SILS) group (n = 354) or the Conventional Laparoscopic Surgery (CLS) group (n = 358). The distribution of surgical procedures included 162 (22.8%) right hemicolectomies, 326 (45.8%) left hemicolectomies, and 224 (31.4%) proctectomies. The pathological TNM stages I, II, and III of the mITT population were 10.7%, 36.9%, and 52.4%, respectively. In the SILS group, 92.9% (n = 329) of the cases were completed entirely with a single incision. An additional trocar was used to assist the surgical procedure in 5.6% (n = 20) of the cases, and 0.8% (n = 3) were converted to conventional laparoscopic surgery. Two patients in the SILS group required conversion to open surgery, compared to 10 patients in the CLS group. The incidence of postoperative complications and oncological efficacy were statistically equivalent between the two groups. Moreover, patients in the SILS group reported significantly less postoperative pain (p = 0.02). There were no significant differences in short-term overall survival (OS) and disease-free survival (DFS) between the two arms. Conclusions: Single-incision laparoscopic surgery (SILS) for colorectal cancer has demonstrated with feasibility, safety, and efficacy. The less painful postoperative experience was aligned with the principles of Enhanced Recovery After Surgery (ERAS). This surgical approach extended the concept of minimally invasiveness and represents a logical progression towards Natural Orifice Transluminal Endoscopic Surgery (NOTES) or single-incision robotic surgery. Clinical trial information: NCT04527861 .

Background and aims:Despite progress made under the United Nations Millennium Development Goals (MDGs) and the Sustainable Development Goals (SDGs), inequalities in global health persist, particularly in the maternal health. Public health emergencies also affect health equity. This research examined long-term disease burden trends (1990-2021) of maternal hypertensive disorders (MHD), with a focus on the influence of age and socio-demographic index (SDI) differences, as well as short-term disruptions during the COVID-19 pandemic, to inform more equitable maternal health policies. Methods:Using the Global Burden of Disease database (2021), this study conducted a systematic examination of indicators of MHD: incidence, maternal mortality ratio (MMR), and disability-adjusted life years (DALYs). All analyses were standardized for age-specific fertility rates (ASFR). Analyses included frontier analysis to identify achievable health outcomes, decomposition analysis to identify key factors, and age-period-cohort (APC) model to assess independent effects. Health inequalities were measured using the slope index of inequality (SII) and concentration curve. The secular trends were characterized using the average annual percentage change (AAPC), while the impact of the COVID-19 pandemic was assessed through the estimated annual percentage change (EAPC). Results:The APC model revealed elevated risks for adolescent and older pregnancies, with incidence fluctuating over 32 years but MMR steadily declining. Disease burden generally decreased with higher SDI levels. Decomposition analysis suggested that demographic factors increased the burden, while epidemiology mitigated it. Frontier analysis indicated effective maternal health control in Canada but Cameroon required progress. While the SII in 2021 declined [-2003.35 (95% CI: -2184.75 to -1821.96)], concentration curves revealed increased relative inequality in lower-SDI populations. Over 32 years, the global MHD burden declined, with a reduction in low-SDI regions [AAPC: -29.46 (95% CI: -30.06 to -28.85)] approximately 24 times that of high-SDI regions. However, the pandemic significantly slowed the decline in low- and low-middle SDI regions. Conclusion:This study highlights marked disparities in the disease burden among age groups across diverse SDI regions. Public health emergencies have intensified existing health inequalities and exposed gaps in healthcare resource distribution. Implementing targeted interventions and reinforcing maternal care during emergencies are critical for enhancing maternal health and advancing health equity.

Background Colorectal cancer (CRC) is one of the leading causes of death among the elderly worldwide. Due to population aging, the burden of CRC among older adults is continuously increasing. However, the epidemiological characteristics, sex differences, and sociodemographic associations of colorectal cancer in adults aged 65 years and older have not been fully elucidated. Methods Leveraging data from the Global Burden of Disease 2021 study, we analyzed CRC burden trends—including incidence, mortality, and disability-adjusted life years (DALYs)—from 1990 to 2021 in individuals aged 65 and above. Temporal trends were assessed using the estimated annual percentage change. Health inequalities were evaluated using the slope index of inequality and the relative concentration index. Frontier analysis was employed to identify potential areas for reducing the CRC burden. Results In 2021, the number of newly diagnosed CRC cases among the elderly was approximately 2.5 times higher than in 1990, with deaths and DALYs roughly doubling over the same period. From 1990 to 2021, the global age-standardized incidence rate of CRC in adults aged 65 and older increased, while the age-standardized mortality and DALY rates declined. The CRC burden escalated with advancing age, and men experienced a higher burden compared to women. Health inequality analysis revealed that the disparity in DALY rates across different Socio-demographic Index (SDI) groups slightly narrowed by 2021 compared to 1990. Frontier analysis demonstrated an inverse correlation between the age-standardized DALY rate and the SDI. Conclusion This study highlights the increasing burden of CRC among adults aged 65 years and older. The findings provide a robust foundation for revising screening guidelines and implementing more effective, region-specific interventions to mitigate the CRC burden.

Background Mandibular distraction osteogenesis (MDO) is a major part of the treatment for hemifacial microsomia patients. Due to the narrow surgical field of the intraoral approach, osteotomy accuracy is highly dependent on the surgeons’ experience. Electromagnetic (EM) tracking systems can achieve satisfying accuracy to provide helpful real-time surgical navigation. Our research team developed an EM navigation system based on artificial intelligence, which has been justified in improving the accuracy of osteotomy in the MDO in animal experiments. This study aims to clarify the effect of the EM navigation system in improving the MDO accuracy for hemifacial microsomia patients. Methods This study is designed as a single-centered and randomized controlled trial. Altogether, 22 hemifacial microsomia patients are randomly assigned to the experiment and control groups. All patients receive three-dimensional CT scans and preoperative surgical plans. The EM navigation system will be set up for those in the experiment group, and the control group will undergo traditional surgery. The primary outcome is the surgical precision by comparing the osteotomy position of pre- and postoperative CT scan images through the Geomagic Control software. The secondary outcomes include mandibular symmetry (occlusal plane deviation angle, mandibular ramus height, and body length), pain scale, and complications. Other indications, such as the adverse events of the system and the satisfactory score from patients and their families, will be recorded. Discussion This small sample randomized controlled trial intends to explore the application of an EM navigation system in MDO for patients, which has been adopted in other surgeries such as orthognathic procedures. Because of the delicate structures of children and the narrow surgical view, accurate osteotomy and protection of nearby tissue from injury are essential for successful treatment. The EM navigation system based on artificial intelligence adopted in this trial is hypothesized to provide precise real-time navigation for surgeons and optimally improve patient outcomes, including function and aesthetic results. The results of this trial will extend the application of new navigation technology in pediatric plastic surgery. Trial registration Chinese Clinical Trial Registry ChiCTR2200061565. Registered on 29 June 2022.

OBJECTIVE:To investigate the contribution of longitudinal mean arterial pressure (MAP) measurement during the first, second, and third trimesters of twin pregnancies to the prediction of pre-eclampsia. METHODS:A retrospective cohort study was conducted on women with twin pregnancies. Historical data between 2019 and 2021 were analyzed, including maternal characteristics and mean artery pressure measurements were obtained at 11-13, 22-24, and 28-33 weeks of gestation. The outcome measures included pre-eclampsia with delivery <34 and ≥34 weeks of gestation. Models were developed using logistic regression, and predictive performance was evaluated using the area under the curve, detection rate at a given false-positive rate of 10%, and calibration plots. Internal validation was conducted via bootstrapping. RESULTS:A total of 943 twin pregnancies, including 36 (3.82%) women who experienced early-onset pre-eclampsia and 93 (9.86%) who developed late-onset pre-eclampsia, were included in this study. To forecast pre-eclampsia during the third trimester, the most accurate prediction for early-onset pre-eclampsia resulted from a combination of maternal factors and MAP measured during this trimester. The optimal predictive model for late-onset pre-eclampsia includes maternal factors and MAP data collected during the second and third trimesters. The areas under the curve were 0.937 (95% confidence interval [CI] 0.894-0.981) and 0.887 (95% CI 0.852-0.921), respectively. The corresponding detection rates were 83.33% (95% CI 66.53%-93.04%) for early-onset pre-eclampsia and 68.82% (95% CI 58.26%-77.80%) for late-onset pre-eclampsia. CONCLUSION:Repeated measurements of MAP during pregnancy significantly improved the accuracy of late-onset pre-eclampsia prediction in twin pregnancies. The integration of longitudinal data into pre-eclampsia screening may be an effective and valuable strategy.

This consensus specifies the terms, definitions, requirements, and test methods for auxiliary surgical devices and auxiliary surgical systems using robotic technology under high-stress conditions. This expert consensus applies to auxiliary surgical devices and auxiliary surgical systems using robotic technology under high-stress conditions.

Background Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. Methods A total of 35 patients received 6 × 107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. Findings No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. Interpretation hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. Funding National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

Figure S17. External validation of the GSE6891 cohort. (A) The upper panel shows the expression patterns of 9 APL9-related genes from eight GSE6891 patients with APL. The bottom panel shows the bar plot of the APL9 score in ascending order. (B) Kaplan-Meier estimates of overall survival according to the APL9 score groups in GSE6891 cohort. P-value is calculated using the log-rank test.

Figure S10. The outcomes of different APL9 score groups. (A) Sankey plot for reclassification from the Sanz risk to the APL9 score groups in the training cohort. (B) Kaplan-Meier estimates of OS, EFS, and DFS in accordance with the APL9 score groups of the training cohort. (C) Sankey plot for reclassification from the Sanz risk to the APL9 score groups in the validation cohort. (D) Kaplan-Meier estimates of OS, EFS, and DFS in accordance with the APL9 score groups of the validation cohort. (E) Area under the curve (AUC) for APL9 score to assess patients' molecular risk status as subcohorts (SC) 1 and 2 in the training (n = 158) and validation (n = 104) cohort. P-value is calculated using the log-rank test. OS, overall survival; EFS, event-free survival; DFS, disease-free survival; CI, confidence interval.

Figure S1. Kaplan-Meier plot of clinical outcomes in consolidation arms with or without ATO. Kaplan-Meier estimates of overall survival (A), event-free survival (B), and disease-free survival (C) in accordance with the consolidation arms with or without ATO. P-value is calculated using the log-rank test.

Figure S9. The ROC curves for the establishing process of the APL9 score. The ROCs of the randomized 10 models in each training set (A) and validation set (B). The shadow indicates the 500-bootstrap confidence intervals of APL9 score. ROC, receiver operating characteristic.

Figure S4. Functional gene categories among different Sanz risk groups and pairwise co-occurrence and mutual exclusivity analysis. (A) Different distributions of mutations of known functional gene groups among the Sanz risk groups. (B) Co-occuring and mutually exclusive mutations in genes with a mutational frequency > 2%. P-value is calculated using the Fisher's exact test. *P < 0.05, **P < 0.01, ***P < 0.001.

Background: Some patients with cervical low-grade squamous intraepithelial lesions (LSIL) undergo invasive laser ablation or loop electrosurgical excision procedures. Photodynamic therapy (PDT) is a photosensitizer 5-aminolevulinic acid (5-ALA)-based minimally invasive technique that causes minimal normal tissue and cell damage. We investigated 5-ALA-mediated PDT efficacy for cervical LSIL complicated by human papillomavirus (HPV). Methods: This prospective cohort study was conducted on patients with cervical LSIL, who were divided into treatment (20 % 5-ALA PDT thrice every 7-14 days; n = 216) and control (observation; n = 220) groups. The treatment group underwent cervical cytology and HPV genotyping 3 months after treatment; both groups underwent cervical cytology, HPV genotyping, colposcopy biopsy, and histopathological examination 6 and 12 months post-treatment. Results: The 3-, 6-, and 12-month follow-ups revealed gradually improved cervical cytology findings: no intraepithelial lesions or malignant tumor (NILM) rates (approximately 80 %). The HPV clearance rate (baseline subtype) was approximately 68 %: approximately 60 % for HPV16/18 and 71 % for non-HPV16/18 baseline subtypes. By months 6 and 12 after PDT, the LSIL regression rate of cervical histopathology increased (75.46 %- 82.08 %). The 6- and 12-month follow-ups revealed significantly increased cervical LSIL regression rates in the treatment group. Compared with the control group, the number of HPV subtypes in the treatment group decreased significantly by 6 and 12 months. Conclusions: 5-ALA PDT effectively eliminated cervical LSIL and HPV, with sustained effects for up to 12 months post-treatment. Therefore, 5-ALA PDT is an effective and safe treatment for cervical LSIL with HPV that promotes cervical LSIL regression to normal cervical tissue.

Figure S8. Spearman's correlation between the gene expression (x axis) and methylation level (y axis) at different regions of GATA1 in patients with APL from the The Cancer Genome Atlas (TCGA) dataset (n = 15). P-values are indicated on each panel. The line shown is a y~x regression line, and the shaded regions are the 95% confidence intervals for the slope of the line.

Figure S3. Genes newly found in APL and pairwise comparison among Sanz risk groups. (A) Schematic representation of three genes newly found in APL. (B) Genes with significant differences in the pairwise comparison among Sanz risk groups. P-value is calculated using the Fisher's exact test

Since our team reported the application of robot-assisted surgery in facial contouring surgery in 2020, further clinical trials with large samples have been conducted. This paper will report the interim results of a single-center, large-sample randomized controlled trial of the first robot developed by our team for facial contouring surgery. Meanwhile, this research field will be systematically reviewed and prospected.