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AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or ?at anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P

The pupose of this review was to explore the application of machine learning in the realm of flavor molecule research, particularly in the analysis of the flavor of Jasmine tea. The study of flavor molecules is fundamental to understand and optimize the taste and quality of food, especially tea. The introduction of machine learning technology has opened new horizons for the identification and analysis of flavor molecules. This paper firstly outlined the basic concepts and research methods of flavor molecules, and a detailed discussion on the application of machine learning in deciphering the relationships between molecular structures and flavor characteristics, as well as in the analysis, prediction and optimization of the flavor and intelligent processing of Jasmine tea and other applications, put forward the research prospect. Thereby, this review could enhance the quality of Jasmine tea and provide technical support for the further development of the tea industry.

Abstract Background The obesity paradigm has been a health concern globally for many years, its meaning is controversial. In this study, we assess the characteristics and causes of obesity paradigm and detail the mediation of obesity and inflammation on survival. Methods The original cohort included participants from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, a prospective cohort of a nationally representative sample of adult participants; the oncology validation cohort included patients from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) from 2013 to 2021, a prospective cohort of Chinese patients with cancer. Survival analysis was performed using weighted (NHANES) or unweighted (INSCOC) Cox survival analyses. The normal BMI group was used as a reference for all comparisons. Systemic inflammation was defined as neutrophil‐to‐lymphocyte ratio (NLR) > 3. Model‐based causal mediation analysis was used to identify the mediators. Results A total of 52 270 (weighted population: 528506229) participants of the NHANES [mean follow‐up times: 10.2 years; mean age (SD): 47 (19.16) years] were included in the original cohort; and a total of 17 418 patients with cancer of INSCOC [mean follow‐up times: 2.9 years; mean age (SD): 57.37 (11.66) years] were included in the validation cohort. In the subgroups of all the participants, the obesity paradigm was more apparent in older participants and participants with disease [HR (95% CI): age ≥ 65 years, 0.84 (0.76, 0.93); with cancer, 0.84 (0.71, 0.99); with CVD, 0.74 (0.65, 0.85)]. As aged, the protective effect of a high BMI on survival gradually increased and a high BMI showed the effect of a protective factor on older participants [for obese II, HR (95% CI): young adults, 1.91 (1.40, 2.62); middle age, 1.56 (1.28, 1.91); old adults, 0.85 (0.76, 0.96]). The aged‐related obesity paradigm in patients with cancer from the NHANES was verified in the INSCOC cohorts [for obese, HR (95%CI): 0.65 (0.52, 0.81)]. The NLR is an important mediator of the effect of BMI on survival (proportion of mediation = 15.4%). Conclusions The obesity paradigm has a strong correlation with age. Relative to normal weight, obese in young people was association with higher all‐cause mortality, and obese in elderly people was not association with higher mortality. The protection of obesity is association with systemic inflammation.

Objective: Bisphenol A (BPA) is a common environmental endocrine disruptor that negatively impairs male reproductive ability. This study aimed to explore the alterations in serum metabolomics that occur following BPA exposure and the mechanism via which BPA induces the death of testicular cells in a male mouse model. Methods: The mice were classified into two groups: BPA-exposed and control groups, and samples were collected for metabolomic determination, semen quality analysis, electron microscopy, enzyme-linked immunosorbent assay, quantitative real-time PCR, pathological staining, and Western blot analysis. Results: BPA exposure caused testicular damage and significantly decreased sperm quality in mice. Combined with non-target metabolomic analysis, this was closely related to ferroptosis induced by abnormal metabolites of arachidonic acid and phosphatidylcholine, and the expression of its related genes, acyl CoA synthetase 4, glutathione peroxidase 4, lysophosphatidylcholine acyltransferase 3, and phosphatidylethanolamine-binding protein 1 were altered. Conclusion: BPA induced ferroptosis, caused testicular damage, and reduced fertility by affecting lipid metabolism in male mice. Inhibiting ferroptosis may potentially function as a therapeutic strategy to mitigate the male reproductive toxicity induced by BPA.

Abstract Background Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. Methods Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). Results In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762–0.823), 0.904 (0.835–0.973), 0.759 (0.731–0.787), 0.221 (0.186–0.256), 0.974 (0.967–0.982), 0.353 (0.306–0.399), and 0.834 (0.696–0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753–0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. Conclusions This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

Abstract This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase‐5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual‐combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event‐free survival at 6 months and all‐cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low‐risk group, 35 in the intermediate‐low‐risk group, 91 in the intermediate‐high‐risk group, and 44 in the high‐risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT‐proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO‐FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low‐risk criteria (from 5.7% to 13.5%). Among the low‐risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate‐low‐risk group exhibited significant enhancements in WHO‐FC and tricuspid annular plane systolic excursion. For those in the intermediate‐high and high‐risk groups, there were marked improvements in activity tolerance, as reflected by WHO‐FC and 6MWD. The event‐free survival rate at 6 months stood at 88%. Over the long‐term follow‐up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

OBJECTIVES: To determine whether experiences of off-the-job training in domestic (DT) and overseas study (OS) settings are associated with work performance and work-family conflict in physicians. DESIGN, SETTING AND PARTICIPANTS: We conducted a national cross-sectional survey in 77 public hospitals across seven provinces in China between July 2014 and April 2015. Participants were 3182 physicians. EXPOSURE: Participants were categorised into four groups: none, DT only, OS only and DT and OS. PRIMARY OUTCOME MEASURES: Work performance was assessed by work engagement, career attrition and patient-centred care. Work-family conflict was assessed by affecting care for family, feeling guilty towards family and receiving complaints from family. RESULTS: A total of 25.89% participants had experienced DT only, 8.71% OS only and 8.47% DT and OS. After adjustment for potential confounders, participants who had experiences of DT and OS compared with those with no training were more likely to report positive work performance (pride in work: OR=2.11, 95% CI: 1.43 to 3.10; enjoyment of work: OR=1.67, 95% CI: 1.11 to 2.51; turnover intention: OR=0.54, 95% CI: 0.38 to 0.77; early retirement: OR=0.63, 95% CI: 0.45 to 0.89; and exhaustion: OR=0.66, 95% CI: 0.45 to 0.98) and less work-family conflicts (feeling guilty towards family: OR=0.51, 95% CI: 0.35 to 0.74; and complaints from family: OR=0.66, 95% CI: 0.47 to 0.91). We found no obvious association between DT/OS experience with patient-centred care. CONCLUSIONS: Physicians with DT and OS experiences are more likely to have better work performance and less work-family conflict than those without such experience. Physicians face increasing pressure to pursue continuing education and experience associated distress. Therefore, hospitals and government policy-makers should promote DT and OS.

BackgroundCOVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity.MethodsWe conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature.ResultsA total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3+ T cell (× 106, MD, - 413.87; 95%CI, - 611.39 to - 216.34), CD4+ T cell (× 106, MD, - 203.56; 95%CI, - 277.94 to - 129.18), CD8+ T cell (× 106, MD, - 128.88; 95%CI, - 163.97 to - 93.79), B cell (× 106/L; MD, - 23.87; 95%CI, - 43.97 to - 3.78) and NK cell (× 106/L; MD, - 57.12; 95%CI, - 81.18 to - 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 106, MD, - 0.13; 95%CI, - 1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, - 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, - 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, - 0.49 to 0.60), IL-4 (pg/ml; MD, - 0.03; 95%CI, - 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, - 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, - 2.88 to 4.75).ConclusionOur meta-analysis revealed significantly lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19 patients.

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are downloaded from the Gene Expression Database. Weighted gene co-expression network analysis is used to identify the co-expression modules related to PF and PH. We used the ClueGO software to enrich and analyze the common genes in PF and PH and obtained the protein–protein interaction (PPI) network. Then, the differential genes were screened out in another cohort of PF and PH, and the shared genes were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on the intersection genes. In the result, the positive correlation module with the highest correlation between PF and PH was determined, and it was found that lymphocyte activation is a common feature of the pathophysiology of PF and PH. Eight common characteristic genes (ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17 and SEL1L) were gained. Immune infiltration showed that compared with the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene IGF1 was obtained. Knocking down IGF1 could significantly reduce the proliferation and apoptosis resistance in pulmonary microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-β1 (TGF-β1), respectively. Our work identified the common biomarkers of PF and PH and provided a new candidate gene for the potential therapeutic targets of PF and PH in the future.

Summary: The mechanism of long-term depression (LTD), a cellular substrate for learning, memory, and behavioral flexibility, is extensively studied in Schaffer collateral (SC) synapses, with inhibition of autophagy identified as a key factor. SC inputs terminate at basal and proximal apical dendrites, whereas distal apical dendrites receive inputs from the temporoammonic pathway (TAP). Here, we demonstrate that TAP and SC synapses have a shared LTD mechanism reliant on NMDA receptors, caspase-3, and autophagy inhibition. Despite this shared LTD mechanism, proximal apical dendrites contain more autophagosomes than distal apical dendrites. Additionally, unlike SC LTD, which diminishes with age, TAP LTD persists into adulthood. Our previous study shows that the high autophagy in adulthood disallows SC LTD induction. The reduction of autophagosomes from proximal to distal dendrites, combined with distinct LTD inducibility at SC and TAP synapses, suggests a model where the differential distribution of autophagosomes in dendrites gates LTD inducibility at specific circuits.

Objective To investigate the clinical efficacy of combined gonadotropin-releasing hormone agonist(GnRH-a) therapy in patients with ovarian endometrioma after conservative surgery. Methods Using a retrospective cohort study analysis, 206 patients who underwent conservative surgery for ovarian endometriosis cysts at the Department of Gynecology, Affiliated Hospital of Nanjing University of Chinese Medicine from December 2014 to December 2018 were selected and divided into 138 cases in the observation group(postoperative combined GnRH-a use for 6 months) and 68 cases in the control group(postoperative with no drug). Recurrence between two groups and the scores of dysmenorrhea, pain during in tercouse（PDI）, and chronic pelvic pain were compared between two groups at different times in 2 years after surgery. Results In the 2 years follow-up, the observation group was superior with statistical significance in the comparison of chronic pelvic pain and dysmenorrhea scores between the two groups and time points(P＜0.05). There was no significant difference in intergroup effect and time effect of sexual intercourse pain (P>0.05). The recurrence rate of patients in the observation group was lower than that of the control group in the first year after surgery(3.62% vs 11.77%, P＜0.05), while no significant difference in recurrence rate of two groups was found in the second year after surgery (P>0.05), but the 2-year cumulative recurrence rate in the observation group was lower than that in the control group (13.24% vs 25.00%, PConclusion GnRH-a can be a choice for postoperative pain management and recurrence prevention in endometriosis.