COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

Melanoma is characterized by high malignancy, ranking the third among skin malignancies, and is associated with lack of specific treatment options and poor prognosis. Therefore, the development of effective therapies for melanoma is imperative. A critical challenge in addressing subcutaneous disease lies in overcoming the skin barrier. In this study, we engineered a microneedle (MN) system that integrates chemotherapy, photothermal therapy (PTT), and targeted therapy to enhance anti-tumor efficacy while effectively penetrating the skin barrier. In vitro studies have demonstrated that the MN drug delivery system (DDS) can effectively penetrate the stratum corneum of the skin, deliver therapeutics to subcutaneous tumor sites, and establish a drug reservoir at these locations to exert anti-tumor effects. Cellular experiments indicated that the engineered PTT chemotherapy-targeted MNs can be internalized by tumor cells, exhibiting enhanced cytotoxicity against them. In vivo pharmacological investigations revealed that the combination of PTT and chemotherapy delivered via this MN DDS produced synergistic anti-tumor effects, achieving a tumor inhibition rate of up to 98.15%. This in situ DDS minimizes involvement with other organs, significantly reducing chemotherapy-related side effects. In summary, the PTT chemotherapy-targeted MNs developed in this study demonstrate promising application potential by enhancing anti-tumor efficacy while minimizing adverse effects.

Background::Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level.Methods::Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis.Results::The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010-2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45-54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking.Conclusion::With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

Objective:To investigate the correlation between overweight or obesity defined by body mass index (BMI) and functional outcome in patients with hypertensive intracerebral hemorrhage (HICH).Methods:Patients with HICH admitted to the Department of Neurosurgery, the First People's Hospital of Lianyungang from October 2020 to February 2022 were included retrospectively. According to BMI, they were divided into underweight or normal group (<24 kg/m 2) and overweight or obese group (≥24 kg/m 2). At one year after onset, the functional outcome were evaluated using the modified Rankin Scale. 0-2 was defined as good outcome, while >2 were defined as poor outcome. Cox proportional hazards regression model was used to analyze the correlation between BMI and the outcome of patients. Results:A total of 394 patients with HICH were enrolled, including 263 males (66.8%), aged 60.2±12.0 years. At one year after onset, 145 patients (36.8%) had poor outcome and 54 (13.7%) died. Compared with the underweight or normal group, the overweight or obese group had a higher proportion of previous type 2 diabetes history, as well as higher baseline diastolic blood pressure, low-density lipoprotein cholesterol and liver enzyme levels, better early outcome after discharge, and lower mortality at 1 year (all P<0.05). Multivariate analysis showed that the overweight or obese group had significantly better functional outcome compared to the underweight or normal group (hazard ratio 0.598, 95% confidence interval 0.419-0.854; P=0.005), but there was no statistically significant difference in all-cause mortality risk (hazard ratio 1.201, 95% confidence interval, 0.462-3.126; P=0.707). Conclusion:The overweight or obese patients with HICH have significantly better functional outcome at one year after onset, indicating that the obesity paradox also exists in patients with HICH.

Objective: To prospectively compare single-shot (SS) echo-planar imaging (EPI) and field-of-view optimized and constrained undistorted single-shot multiplexed sensitivity-encoding (FOCUS MUSE) for diffusion-weighted imaging (DWI) in evaluating thyroid-associated ophthalmopathy (TAO). Materials and Methods: SS EPI and FOCUS MUSE DWIs were obtained from 39 patients with TAO (18 male; mean ± standard deviation: 48.3 ± 13.3 years) and 26 healthy controls (9 male; mean ± standard deviation: 43.0 ± 18.5 years). Two radiologists scored the visual image quality using a 4-point Likert scale. The image quality score, signal-to-noise ratio (SNR), contrast-tonoise ratio (CNR), and apparent diffusion coefficient (ADC) of extraocular muscles (EOMs) were compared between the two DWIs. Differences in the ADC of EOMs were also evaluated. The performance of discriminating active from inactive TAO was assessed using receiver operating characteristic curves. The correlation between ADC and clinical activity score (CAS) was analyzed using Spearman correlation. Results: Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated significantly higher image quality scores (P < 0.001), a higher SNR and CNR on the lateral rectus muscle (LRM) and medial rectus muscle (MRM) (P < 0.05), and a non-significant difference in the ADC of the LRM and MRM. Active TAO showed higher ADC than inactive TAO and healthy controls with both SS EPI and FOCUS MUSE DWIs (P < 0.001). Inactive TAO and healthy controls did not show a significant ADC difference with both DWIs. Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated better discrimination of active from inactive TAO (AUC:0.925 vs. 0.779; P = 0.007). The ADC was significantly correlated with CAS in SS EPI DWI (r = 0.391, P < 0.001) and FOCUS MUSE DWI (r = 0.645, P < 0.001). Conclusion FOCUS MUSE DWI provides better images for evaluating EOMs and better performance in diagnosing active TAO than SS EPI DWI. The application of FOCUS MUSE will facilitate the DWI evaluation of TAO.

Objective: The aim of the study was to investigate the association of outdoor physical activity and insomnia symptoms with depressive symptoms in college students, so as to provide a theoretical basis for preventing and improving depression of the college students. Methods: A sample survey of 9 349 college students from 4 colleges and universities in 3 provinces in Hubei, Jiangxi and Chongqing were conducted from November to December 2021. The Patient Health Questionnaire, Insomnia Severity Index and outdoor physical activity questionnaire were used to evaluate the depressive symptoms, insomnia symptoms and outdoor activities of college students, respectively. The χ 2 test was used to compare the difference of the positive rate of depressive symptoms in college students. Logistic regression analysis was used to analyze the association between outdoor physical activity, insomnia symptoms and depressive symptoms. Generalized linear model was used to analyze the association of interaction effect of outdoor activity and insomnia symptoms with depressive symptoms. Results: The detection rate of depressive symptoms in college students was 37.4%. Significant differences in the detection rate of depressive symptoms were observed among college students with different majors, nationalities,educational backgrounds, family residence, family type, family economic conditions, study burden, number of friends, father s education level,mother s education level( P <0.05). Logistic regression analysis showed that outdoor physical activity ( OR=0.51-0.69, P <0.01) and insomnia symptoms ( OR=6.15-21.30, P <0.01) were associated with depressive symptoms( P <0.01). Generalized linear model showed that insomnia symptoms( B =0.57), outdoor physical activity ( B =-0.15) and their interaction terms ( B =-0.02) were associated with college students depression( P <0.05). Conclusion This study suggests that insufficient time for outdoor physical activity and insomnia symptoms may increase the risk of depressive symptoms in college students. College students with insufficient time for outdoor physical activity and insomnia have a higher risk of developing depressive symptoms.

Pharmaceutical analysis is a discipline based on chemical, physical, biological, and information technologies. At present, biotechnological analysis is a short branch in pharmaceutical analysis; however, bioanalysis is the basis and an important part of medicine. Biotechnological approaches can provide information on biological activity and even clinical efficacy and safety, which are important characteristics of drug quality. Because of their advantages in reflecting the overall biological effects or functions of drugs and providing visual and intuitive results, some biotechnological analysis methods have been gradually applied to pharmaceutical analysis from raw material to manufacturing and final product analysis, including DNA super-barcoding, DNA-based rapid detection, multiplex ligation-dependent probe amplification, hyperspectral imaging combined with artificial intelligence, 3D biologically printed organoids, omics-based artificial intelligence, microfluidic chips, organ-on-a-chip, signal transduction pathway-related reporter gene assays, and the zebrafish thrombosis model. The applications of these emerging biotechniques in pharmaceutical analysis have been discussed in this review.

Background::Contrast-enhanced ultrasound (CEUS) can detect lesions hidden in inflammatory regions and find necrosis or areas of severe fibrosis within the lesion. This retrospective study aimed to compare the diagnostic accuracy of solid pancreatic lesions using percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) with or without CEUS assessment.Methods::Clinical, imaging, and pathologic data of 181 patients from January 2014 to December 2018 in Pecking Union Medical College Hospital, with solid pancreatic masses who underwent percutaneous US-FNA and ThinPrep cytologic test were retrospectively evaluated. Patients were divided into CEUS and US groups according to whether CEUS was performed before the biopsy. According to FNA cytology diagnoses, we combined non-diagnostic, neoplastic, and negative cases into a negative category. The positive category included malignant, suspicious, and atypical cases. The final diagnosis was confirmed by pathology or clinical and radiological follow-up for at least 12 months. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of US-FNA were evaluated between the two groups.Results::This study enrolled 107 male and 74 female patients (average age: 60 years). There were 58 cases in the US group and 123 cases in the CEUS group. No statistically significant differences in age, gender, or lesion size were found between the two groups. The diagnostic accuracy of the CEUS group was 95.1% (117/123), which was higher than the 86.2% (50/58) observed in the US group ( P = 0.036). The sensitivity, specificity, PPV, and NPV of the CEUS group were increased by 7.5%, 16.7%, 3.4%, and 18.8%, respectively, compared with the US group. However, the differences of the two groups were not statistically significant. Conclusions::Compared with the conventional US, the use of CEUS could improve the biopsy accuracy and avoid the need for a repeat biopsy, especially for some complicated FNA cases.

Objective:To study the clinical characteristics of cornual pregnancy and compare the effects of various surgical methods on the outcomes.Methods:This was a single-center retrospective study. The clinical records of patients with cornual pregnancy who underwent surgery in Peking Union Medical College Hospital from June 2012 to December 2020 were collected. Surgical interventions included curettage (guided by ultrasound or monitored by laparoscope), and cornuostomy/cornectomy (the surgical approach by laparoscopy or laparotomy). The baseline data, perioperative treatment and whether persistent ectopic pregnancy (PEP) occurred after surgery were collected and analyzed statistically.Results:A total of 109 patients with cornual pregnancy diagnosed by surgical treatment were included in this study, whose average age was (32.9±4.8) years. Among them, the incidence of postoperative PEP was 16.5% (18/109). The risk of PEP in multipara was significantly higher than that in nulliparous women ( OR=7.639, 95% CI: 2.063-28.279, P=0.001). The risk of PEP in patients with the maximum diameter of lesion<1.5 cm was significantly higher than that in patients with the maximum diameter of lesion≥1.5 cm ( OR=8.600, 95% CI: 2.271-32.571, P=0.002). Among all surgical approaches for cornual pregnancy, the proportion of PEP in curettage under ultrasound monitoring was the highest (56.0%, 14/25), which was higher than that in curettage under laparoscope monitoring (1/10; χ2=6.172， P=0.013); the proportion of PEP in curettage group (42.9%, 15/35) was higher than that in cornuostomy/cornectomy group (4.1%, 3/74; χ2=25.950， P<0.01). Neither salpingectomy in the operation nor the routine use of methotrexate (MTX) in perioperative period could significantly reduce the incidence of PEP (all P>0.05). Conclusions:Among the patients with cornual pregnancy, multipara, the maximum diameter of lesion<1.5 cm and ultrasound-guided curettage are the risk factors of PEP after operation. Cornuostomy or cornectomy is recommended for patients with cornual pregnancy. If the patients would perform the curettage operation, laparoscopic monitoring is recommended. For patients with possible satisfactory operation outcome, it is not recommended to use MTX as a routine preventing measure.