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Background: Human T-cell leukemia virus type 1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATLL), a lymphoproliferative malignancy with a dismal prognosis and limited therapeutic options. Recent evidence shows that HTLV-1-transformed cells present defects in both DNA replication and DNA repair, suggesting that these cells might be particularly sensitive to treatment with a small helicase inhibitor. Because the "Werner syndrome ATP-dependent helicase" encoded by the WRN gene plays important roles in both cellular proliferation and DNA repair, we hypothesized that inhibition of WRN activity could be used as a new strategy to target ATLL cells. Methods: Our analysis demonstrates an apoptotic effect induced by the WRN helicase inhibitor in HTLV-1-transformed cells in vitro and ATL-derived cell lines. Inhibition of cellular proliferation and induction of apoptosis were demonstrated with cell cycle analysis, XTT proliferation assay, clonogenic assay, annexin V staining, and measurement of mitochondrial transmembrane potential. Results: Targeted inhibition of the WRN helicase induced cell cycle arrest and apoptosis in HTLV-1-transformed leukemia cells. Treatment with NSC 19630 (WRN inhibitor) induces S-phase cell cycle arrest, disruption of the mitochondrial membrane potential, and decreased expression of anti-apoptotic factor Bcl-2. These events were associated with activation of caspase-3-dependent apoptosis in ATL cells. We identified some ATL cells, ATL-55T and LMY1, less sensitive to NSC 19630 but sensitive to another WRN inhibitor, NSC 617145. Conclusions: WRN is essential for survival of ATL cells. Our studies suggest that targeting the WRN helicase with small inhibitors is a novel promising strategy to target HTLV-1-transformed ATL cells. [ABSTRACT FROM AUTHOR]

Peritoneal metastasis (PM) is a common metastasis site and death cause of gastric cancer, which is a complex biological process, but there is currently a lack of effective prediction and treatment targets. In this study, we first analyzed the differential gene expression of gastric cancer patients with or without peritoneal metastasis, and identified the HECT domain E3 ubiquitin protein ligase 2 (HECTD2) as the core gene of PM in gastric cancer. The current study shows that the role of HECTD2 in tumor is contradictory. In this study, our results show that the low expression of HECTD2 indicates that the survival rate of overall survival (OS), progression-free survival (PFS), disease-specific survival (DSS), and disease-free survival (DFS) are better, and can be used as an important component of prognostic indicators. In addition, through pathway enrichment analysis, we found that HECTD2 was mainly involved in metastasis related pathways such as extracellular matrix remodeling and cell adhesion in gastric cancer, and high expression of HECTD2 could activate epithelial-mesenchymal transition (EMT) metastasis related pathways in gastric cancer. In regulating the metastasis of gastric cancer cells, HECTD2 can also change the surrounding microenvironment, induce the enrichment of interstitial components and build an immune microenvironment conducive to tumor progression, while patients with low expression of HECTD2 may be more likely to benefit from immunotherapy. In conclusion, HECTD2 may be a novel biomarker for the diagnosis and prognosis of peritoneal metastasis of gastric cancer, providing basis for the mechanism of peritoneal metastasis of cancer and clinical medication., Competing Interests: Declarations Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of Changzhou No.2 People's Hospital. Competing interest The authors declare no competing interests., (© 2024. The Author(s).)

Background: Some research indicates that unsaturated fatty acids (UFAs) in the diet could enhance reproductive outcomes in infertile women. However, other research holds different views, possibly due to differences in the conversion rates of UFAs from various foods and bioavailability in the body. Therefore, this research examined the link between serum UFAs and infertility issues., Methods: This research included reproductive-age women participating in the 2013-2014 American National Health and Nutrition Examination Survey (NHANES). Serum levels of four UFAs, including palmitoleic acid (16:1n-7), vaccenic acid (18:1n-7), oleic acid (18:1n-9), and linoleic acid (18:2n-6) were measured through gas chromatography-mass spectrometry. Infertility data was collected by affirmative responses to targeted questionnaire items. Associations between serum UFA levels and infertility were evaluated utilizing Poisson regression models and smooth curve fitting methods. Sensitivity analysis was also conducted., Results: This study included 535 women, aged between 18 and 45. Poisson regression analysis, both adjusted and unadjusted for confounders, revealed no associations between palmitoleic acid, vaccenic acid, oleic acid, or linoleic acid and female infertility (all P > 0.05). However, four UFAs all showed non-linear relationships with infertility in smooth curve fitting analysis. Sensitivity analysis confirmed the stability of the findings., Conclusion: This research established non-linear associations between serum UFAs and infertility in American women. Specifically, maintaining appropriate serum levels of these UFAs may lower infertility risk. These findings offer new insights and practical dietary recommendations for improving female fertility., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Compared to traditional lower-limb prostheses (LLPs), intelligent LLPs are more versatile devices with emerging technologies, such as microcontrollers and user-controlled interfaces (UCIs). As emerging technologies allow a higher level of automation and more involvement from wearers in the LLP setting adjustments, the previous framework established to study human factors elements that affect wearer-LLP interaction may not be sufficient to understand the new elements (e.g., transparency) and dynamics in this interaction. In addition, the increased complexity of interaction amplifies the limitations of the traditional evaluation approaches of wearer-LLP interaction. Therefore, to ensure wearer acceptance and adoption, from a human factors perspective, we propose a new framework to introduce elements and usability requirements for the wearer-LLP interaction. This paper organizes human factors elements that appear with the development of intelligent LLP technologies into three aspects: wearer, device, and task by using a classic model of the human-machine systems. By adopting Nielsen's five usability requirements, we introduce learnability, efficiency, memorability, use error, and satisfaction into the evaluation of wearer-LLP interaction. We identify two types of wearer-LLP interaction. The first type, direct interaction, occurs when the wearer continuously interacts with the intelligent LLP (primarily when the LLP is in action); the second type, indirect interaction, occurs when the wearer initiates communication with the LLP usually through a UCI to address the current or foreseeable challenges. For each type of interaction, we highlight new elements, such as device transparency and prior knowledge of the wearer with the UCI. In addition, we redefine the usability goals of two types of wearer-LLP interaction with Nelson's five usability requirements and review methods to evaluate the interaction. Researchers and designers for intelligent LLPs should consider the new device elements that may additionally influence wearers' acceptance and the need to interpret findings within the constraints of the specific wearer and task characteristics. The proposed framework can also be used to organize literature and identify gaps for future directions. By adopting the holistic usability requirements, findings across empirical studies can be more comparable. At the end of this paper, we discuss research trends and future directions in the human factors design of intelligent LLPs., (© 2024. The Author(s).)

Background: To assess the prevalence and epidemic pattern of multidrug-resistant tuberculosis in Hangzhou City, Zhejiang Province, China during 2012-2022., Methods: All the tuberculosis cases undergoing drug susceptibility testing during 2012-2022 were included in this study. De-identified information was extracted from the electronic database Tuberculosis Information Management System for analysis of drug resistance prevalence in Hangzhou and ecdemic multidrug-resistant tuberculosis which originated from other regions. Chi-square tests were used to compare drug resistance rates between different groups, while Chi-square tests for trend were used to evaluate the change of drug resistance rates over the years of 2012-2022. The sources and destinations of ecdemic multidrug-resistant tuberculosis were illustrated using a Sankey diagram., Results: Of 21,127 cases included in this study, 1119 (5.3%) were multidrug-resistant tuberculosis. A significant decline in multidrug-resistant tuberculosis rates was observed during 2012-2022. There was a significant difference in multidrug-resistant tuberculosis rates among immigrant population and local residents in Hangzhou City. Of 1119 multidrug-resistant tuberculosis cases, 515(46%) were ecdemic multidrug-resistant tuberculosis cases, of which 277(53.8%) were from other parts of Zhejiang Province and 238(46.2%) were from other provinces in China. Anhui, Jiangxi and Sichuan were among top three provinces which were the source of ecdemic multidrug-resistant tuberculosis cases. Three districts including Xiaoshan, Shangcheng and Linping districts had the most cases in Hangzhou. The proportion of ecdemic multidrug-resistant tuberculosis cases in Binjiang, Xiaoshan, Qiantang and Linping districtalso exceeded 30% of total cases., Conclusions: Multidrug-resistant tuberculosis prevalence has been declining in Hangzhou. Migrant population contributed to a significant potion of cases in Hangzhou. Interventions should be tailed to local and migrant residents., (© 2024. The Author(s).)

Background: The aim was to assess the knowledge, attitudes, and practices (KAPs) of endoscopy among gastroenterologists in the diagnosis and management of IBD in China., Methods: A multicenter cross-sectional KAP study was performed. The questionnaire was developed and improved using feedback and opinions from a team of experienced IBD specialist professors and then distributed and collected online. In addition, eight fellow gastroenterologists participated in an IBD endoscopy training program were asked to review endoscopic images, and the consistency of the endoscopic scores before and after training was calculated., Results: A total of 193 participants from 12 provincial-level administrative regions encompassing both the Northern and Southern parts of China completed the study questionnaire. The median age of the participants was 40 (36, 45) years, with the majority being female (70.5%). The median professional experience as gastroenterologists was 11 (7, 17) years, while the median experience as endoscopists was 8 (3, 15) years. The median knowledge score was 8 out of 10 points for single-choice questions; however, most gastroenterologists believed that some concepts in these endoscopic indices were vague, including those regarding deep ulcerations, ulcerated surfaces, affected surfaces and narrowing in open-answer questions. The UCEIS and SES-CD were considered most consistent with clinical activity score in the evaluation of UC and CD, respectively. IBD subspecialists and gastroenterologists who had previously received IBD endoscopy screening training were more likely to use endoscopic indices (p<0.001, p = 0.029, respectively). The Rutgeerts score demonstrated the most significant improvement in consistency before and after training, from 0.407 (95% CI: 0.025-0.999) to 0.909 (95% CI: 0.530-1.000)., Conclusions: We propose the elucidation of ambiguous definitions in endoscopic indices, enhancement of training, and the application of innovative technology to enhance the application of endoscopic evaluation and endoscopic indices in clinical practice., (© 2024. The Author(s).)

Background: Chronic subdural hematoma (CSDH) is one of the most common diseases in neurosurgery. It is the result of chronic intracranial hemorrhage that converges between the dura mater and arachnoid three weeks after externally injuring the head. Chronic subdural hematomas are a common complication in neurosurgery. With the gradual increase in the amount of hematoma, the surrounding brain tissue is pushed and compressed, resulting in corresponding clinical symptoms and signs. It is reported that the overall incidence rate of CSDH is 1.72 to 20.6 per 100,000 people every year, and the incidence rate of the elderly is particularly high., Methods: The computer retrieves eight databases to obtain controlled trials at home and abroad on the effects of neuroendoscopy-assisted surgery in patients with chronic subdural hematoma. After a rigorous literature quality evaluation, data analysis was performed using RevMan 5.3 software., Results: Twenty studies were ultimately included in this meta-analysis. Seventeen studies reported the Recurrence rate of the test group and the control group, which was significantly lower (OR 0.27; 95% Cl 0.18, 0.38; P < 0.01) than the control group, Recovery rate (OR 1.18; 95% Cl 1.01, 1.38; P = 0.03), Total effective rate (OR 1.11; 95% Cl 1.04, 1.17; P < 0.01), Operative time (SMD 15.78; 95% Cl 9.69, 21.86; P < 0.01), Hospital stay (SMD - 1.66; 95% Cl - 2.17, - 1.14; P < 0.01) and Complications (OR 0.48; 95% Cl 0.30, 0.78; P < 0.01)., Conclusion: The results of this study suggest that neuroendoscopy-assisted surgery may be effective in patients with chronic subdural hematoma, as evidenced by recurrence rate, recovery rate, total effective rate, operative time, hospital stay, complications, and the above conclusions need to be verified by more high-quality studies., (© 2024. The Author(s).)

Background: Up to 17% of cancer survivors have been reported to develop second primary cancers (SPC), which cause significant physical and economic distress and often complicate clinical decision-making. However, understanding of SPC remains limited and superficial. Human leukocyte antigen (HLA) is characterized by its polymorphism and has been associated with various diseases. This study aims to explore the role of HLA diversity in SPC incidence., Methods: We analyzed a cohort of 47,550 cancer patients from the UK Biobank. SNP-derived HLA alleles were used and SPC-related HLA alleles were identified using logistic regression, followed by stepwise filtering based on the Akaike information criterion (AIC) and permutation tests. Additionally, we examined the association between extragenetic factors and the risk of SPC in patients carrying hazardous HLA alleles., Results: During a median follow-up of 3.11 years, a total of 2894 (6.09%) participants developed SPC. We identified three protective HLA alleles (DRB1*04:03 and DPA1*02:02 for males and DRB5*01:01 for females) and two hazardous alleles (A*26:01 for males and DPB1*11:01 for females) about SPC. The presence of the protective alleles was associated with a reduced SPC risk (males: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.59-0.89; females: HR 0.81, 95% CI 0.70-0.93), while the hazardous alleles were linked to an increased risk (males: HR 1.27, 95% CI 1.03-1.56; females: HR 1.35, 95% CI 1.07-1.70). The hazardous allele A*26:01 indicated skin-lung organ-specific SPC occurrence in males. Animal fat and vitamin C were associated with SPC risk in males carrying the hazardous alleles, while free sugar and vegetable fat were linked to SPC risk in females., Conclusions: These results suggest that HLA alleles may serve as biomarkers for the susceptibility and organ-specific occurrence of SPC, while dietary modulation may mitigate hazardous alleles-related SPC risk, potentially aiding in the early prediction and prevention of SPC., (© 2024. The Author(s).)

Backgrounds: The incidence of extramedullary diseases (EMDs) in patients diagnosed with acute myeloid leukemia (AML) is approximately 10-20%. These patients exhibit a significantly distinct etiology, therapeutic response, and prognosis compared to patients without EMDs. CLL1 CAR-T therapy has been demonstrated satisfactory efficacy and safety in the treatment of refractory and relapsed AML patients. However, concerns have been raised regarding the potential impact of extramedullary niduses on the effectiveness of CLL1 CAR-T therapy., Methods: A total of 47 patients were enrolled in this study, including 27 patients with isolated AML tumor bone marrow infiltration and 20 patients with both extramedullary and bone marrow infiltration of AML. CLL1 CAR-T cells were manufactured and subjected to rigorous quality control in the hematology laboratory of Tianjin First Central Hospital. The efficacy and adverse reactions were assessed following CAR-T cell infusion, while expansion of CAR-T cells, levels of cytokines releasing, and other indicators were closely monitored., Results: Among the 20 patients with EMDs and the 27 individuals without EMDs, complete remission in bone marrow was achieved by 65.00% and 81.48% of patients, respectively. Meanwhile, among the patients with EMDs, 55.00% achieved complete remission while 10.00% achieved partial remission when assessing the efficacy of CLL1 CAR-T cells against extramedullary niduses. Although the overall survival, progression-free survival, and duration of remission period appeared to be shorter for patients with EMDs compared to those without EMDs, this difference did not reach statistical significance. The incidence rates of complications were comparable between both groups. Meanwhile, there were no significant differences observed in the levels of CAR-T cell expansion and accompanying cytokines release between patients with and without EMDs., Conclusions: Our study findings have demonstrated the efficacy of CLL1 CAR-T therapy in the treatment of AML patients with EMDs, while also indicating manageable occurrence rates of complications within a tolerable range. The CLL1 CAR-T therapy, serving as an ideal strategy for AML patients irrespective of the presence of EMDs, effectively ameliorates the conditions of AML patients and provides them with an opportunity to undergo curative hematopoietic stem cell transplantation while significantly enhancing their prognosis., (© 2024. The Author(s).)

Background: Mammographic density has been associated with breast cancer risk, and is modulated by established breast cancer risk factors, such as reproductive and hormonal history, as well as lifestyle. Recent epidemiological and biological findings underscore the recognized benefits of breastfeeding in reducing breast cancer risk, especially for aggressive subtypes. Current research exploring the association among mammographic density, breastfeeding, and breast cancer is sparse., Main Findings: Changes occur in the breasts during pregnancy in preparation for lactation, characterized by the proliferation of mammary gland tissues and the development of mammary alveoli. During lactation, the alveoli fill with milk, and subsequent weaning triggers the involution and remodeling of these tissues. Breastfeeding influences the breast microenvironment, potentially altering mammographic density. When breastfeeding is not initiated after birth, or is abruptly discontinued shortly after, the breast tissue undergoes forced and abrupt involution. Conversely, when breastfeeding is sustained over an extended period and concludes gradually, the breast tissue undergoes slow remodeling process known as gradual involution. Breast tissue undergoing abrupt involution displays denser stroma, altered collagen composition, heightened inflammation and proliferation, along with increased expression of estrogen receptor α (ERα) and progesterone receptor. Furthermore, elevated levels of pregnancy-associated plasma protein-A (PAPP-A) surpass those of its inhibitors during abrupt involution, enhancing insulin-like growth factor (IGF) signaling and collagen deposition. Prolactin and small molecules in breast milk may also modulate DNA methylation levels. Drawing insights from contemporary epidemiological and molecular biology studies, our review sheds light on how breastfeeding impacts mammographic density and explores its role in influencing breast cancer., Conclusion: This review highlights a clear protective link between breastfeeding and reduced breast cancer risk via changes in mammographic density. Future research should investigate the effects of breastfeeding on mammographic density and breast cancer risk among various ethnic groups and elucidate the molecular mechanisms underlying these associations. Such comprehensive research will enhance our understanding and facilitate the development of targeted breast cancer prevention and treatment strategies., (© 2024. The Author(s).)

Background: Fournier's Gangrene is a severe surgical infectious disease, and various risk factors can increase its mortality rate. The purpose of this study is to retrospectively analyze the clinical characteristics and laboratory data of Fournier's Gangrene patients, followed by an analysis of mortality-related risk factors. This study has no secondary objectives., Methods: This study included 46 hospitalized patients diagnosed with Fournier's Gangrene at Suzhou Traditional Chinese Medicine Hospital from December 2013 to March 2024. Clinical data for all patients were extracted from the electronic medical records system. The collected data included gender, age, duration of illness, length of hospital stay, sites of infection involvement, comorbidities, white blood cell count, hematocrit, albumin, blood glucose, creatinine, serum sodium, serum potassium upon admission, microbial culture results, and patient outcomes (survival/death). The Simplified Fournier Gangrene Severe Index (SFGSI) was used to score all patients. Patients were categorized into survival and death groups based on clinical outcomes. Differences between categorical variables were compared using the χ² test or Fisher's exact test. Differences between numerical variables were compared using Student's t-test or the Mann-Whitney U test. Binary logistic regression was employed to analyze the risk factors for mortality in Fournier's Gangrene., Results: Among the 46 Fournier's Gangrene patients, 39 were male (84.8%) and 7 were female (15.2%). The age ranged from 17 to 86 years, with a median age of 61 years. Fourteen cases (30.4%) were confined to the perianal area, 26 cases (56.5%) had fascial necrosis involving the perianal, perineal, and genital regions, while 6 cases (13.0%) extended to the abdominal wall. At a 3-month postoperative follow-up, 43 patients (93.5%) survived, while 3 patients (6.5%) died shortly after admission due to severe illness. Based on the outcome, patients were divided into survival and death groups with 43 and 3 cases, respectively. Significant differences were observed between the two groups in terms of age (P<0.05), extension to the abdominal wall (P<0.01), hematocrit (P<0.01), albumin (P<0.01), SFGSI (P<0.01), and SFGSI>2 (P<0.01). Binary logistic regression analysis indicated that decreased hematocrit was an independent risk factor for mortality in Fournier's Gangrene patients., Conclusion: This study provides a detailed analysis of the clinical characteristics and risk factors for mortality in Fournier's Gangrene patients. The primary outcome of this study is that a decreased hematocrit is an independent risk factor for predicting mortality in FG patients. These findings offer valuable prognostic insights for clinicians, underscoring the importance of early identification and correction of reduced hematocrit to improve patient outcomes and survival rates., (© 2024. The Author(s).)

Background: Chemotherapy remains the standard first-line treatment for pancreatic adenocarcinoma, but with limited efficacy. We aimed to explore the feasibility of adding the PARP inhibitor fuzuloparib to mFOLFIRINOX in the locally advanced/metastatic (LA/M) setting., Methods: This was the dose-escalation and -expansion, phase 1b portion of a phase 1b/2 study. Patients were given oral fuzuloparib at escalating doses starting at 30 mg twice daily (BID) plus intravenous mFOLFIRINOX q2w for 8-12 cycles, followed by maintenance fuzuloparib at 150 mg BID. Cohorts at the maximal tolerated dose (MTD) and lower dose of fuzuloparib were expanded. Primary endpoints were dose-limiting toxicity (DLT), MTD, and recommended phase 2 dose (RP2D)., Results: As of data cutoff on Jan 15, 2023, 39 patients were recruited. 12 patients were enrolled during dose escalation (30 mg [n = 4]; 60 mg [n = 6]; 100 mg [n = 2]). DLT occurred in 1 patient in 60 mg cohort and 1 patient in 100 mg cohort. 60 mg BID was determined to be the MTD, and then 60 and 30 mg cohorts were expanded to 22 and 15 patients, respectively. The most common grade ≥ 3 treatment-related adverse events were hematologic toxicities. Efficacy in 60 mg cohort seemed to be most favorable, with an objective response rate of 50.0% (95% CI, 26.0-74.0) and disease control rate of 94.4% (95% CI, 72.7-99.9)., Conclusions: First-line fuzuloparib plus mFOLFIRINOX followed by maintenance fuzuloparib was generally safe and showed encouraging anti-tumor activity in patients with LA/M pancreatic adenocarcinoma. The RP2D of fuzuloparib combination was 60 mg BID., Trial Registration: ClinicalTrials.gov, NCT04228601., (© 2024. The Author(s).)

Context: Polycystic ovary syndrome (PCOS), a common endocrine disorder in women of reproductive age, is closely associated with chronic low-grade inflammation and metabolic disturbances. In PCOS mice, dietary inulin has been demonstrated to regulate intestinal flora and inflammation. However, the efficacy of dietary inulin in clinical PCOS remains unclear., Objective: The intestinal flora and related metabolic indexes of obese patients with polycystic ovary syndrome (PCOS) after 3 months of inulin treatment were analyzed., Setting and Design: To analyze the intestinal flora and related metabolic indexes in healthy controls and obese patients with polycystic ovary syndrome after 3 months of inulin treatment., Results: The results showed that dietary inulin improved sex hormone disorders, reduced BMI and WHR levels in obese women with PCOS. In addition, the inulin intervention reduced plasma TNF-α, IL-1β, IL-6, and MCP-1levels. Inulin intervention increased the abundance of Actinobacteria, Fusobacteria, Lachnospira, and Bifidobacterium, as well as decreased the ratio of F/B and the abundance of proteobacteria, Sutterella, and Enterobacter. Correlation analyses showed a strong relationship among plasma inflammatory factors, sex steroid hormones, and the intestinal flora of patients., Conclusions: Dietary inulin may improve obese PCOS women disease through the gut flora-inflammation-steroid hormone pathway., The Clinical Trial Registration Number: ChiCTR-IOR-17012281., (© 2024. The Author(s).)

Background: Lung cancer is the most common cause of cancer death worldwide and poses an immediate health threat. Despite decades of basic and clinical research, the 5-year survival rate for lung cancer patients is less than 10%.The most important drawbacks in efficient treatment of lung cancer are delayed diagnosis and absence of effective screening. Detection and study of precancerous lesions of the bronchial mucosa might be one of the turning points in understanding of neoplastic transformation. Therefore, it would be the most effective prevention and early treatment modality. We report a case of high-grade intraepithelial neoplasia of the bronchial mucosa in which a neoplastic growth in the lumen of intrinsic segment in the upper lobe of the left lung was detected on electronic bronchoscopy, and biopsy confirmed squamous papillary hyperplasia with high-grade intraepithelial neoplasia., Case Presentation: A 74-year-old male was admitted to the hospital due to a mass lesion in his left lung. After admission, computed tomography scan of the chest showed an intraluminal mass in the intrinsic segment of the upper lobe of the left lung and an enlarged left hilum., Conclusions: High-grade intraepithelial neoplasia of the bronchial mucosa is rare in the respiratory system. We report a case that can provide useful information for early diagnosis and treatment of the disease., (© 2024. The Author(s).)

Background: Magnetic resonance spectroscopy (MRS) studies have indicated that the imbalance between gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels was the potential cause of migraine development. However, the changes in the GABA and Glx levels in patients with New daily persistent headache (NDPH) remain unclear. This study aimed to investigate the changes in GABA and Glx levels in the periaqueductal gray (PAG) and dentate nucleus (DN) in patients with NDPH using the MEGA-PRESS sequence., Methods: Twenty-one NDPH patients and 22 age- and sex-matched healthy controls (HCs) were included and underwent a 3.0T MRI examination, using the MEGA-PRESS sequence to analyze GABA and Glx levels of PAG and DN. The correlations between these neurotransmitter levels and clinical characteristics were also analyzed., Results: There were no significant differences in the GABA+/Water, GABA+/Cr, Glx/Water, and Glx/Cr levels in both PAG and DN between the two groups (all p > 0.05). Moderate-severe NDPH patients had lower levels of Glx/Water (p = 0.034) and Glx/Cr (p = 0.012) in DN than minimal-mild NDPH patients. In patients with NDPH, higher Glx/Water levels in the PAG (r=-0.471, p = 0.031, n = 21) and DN (r=-0.501, p = 0.021, n = 21) and higher Glx/Cr levels in DN (r=-0.483, p = 0.026, n = 21) were found to be correlated with lower Visual Analogue Scale scores. Additionally, a positive correlation was observed between the GABA+/Cr levels in the DN and the Generalized Anxiety Disorder-7 scores (r = 0.519, p = 0.039, n = 16)., Conclusions: The results of this study indicated that the GABA and Glx levels in the PAG and DN may not be the primary contributor to the development of NDPH. The correlations between certain clinical scales and the neurotransmitter levels may be derived from the NDPH related symptoms., (© 2024. The Author(s).)

Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 F‑FDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice., (© 2024. The Author(s).)

Background: Ulcerative colitis (UC) is a chronic intestinal inflammation, resulting in a global healthcare challenge with no real specific medicine. Natural medicines are recognized as a potential clinical alternative therapy, but their applications are limited by poor solubility and low bioavailability., Results: In this work, inspired by the natural medicines of ancient China, novel functional carbon dots derived from Magnetite and Medicated Leaven (MML-CDs) were synthesized by hydrothermal method, and confirmed their ultrasmall nano-size (3.2 ± 0.6 nm) and Fe doped surface structure, thereby with excellent gastrointestinal stability, remarkable capabilities in eliminating ROS, and highly biocompatibility. With no external stimuli, the oral administration of MML-CDs demonstrated obvious alleviation to UC. Further experiments pointed that MML-CDs could improve hemostasis capability, suppress inflammation reactions and oxidative stress, and up-regulate the expression of tight junction proteins. Furthermore, MML-CDs also showed well regulation in the dysbiosis of intestinal flora., Conclusion: Overall, above evidence reveals that green-synthesized MML-CDs can significantly alleviate intestinal bleeding, inhibit colon inflammation, and repair colonic barrier damage, further regulating intestinal flora and intestinal inflammation microenvironment. Our findings provide an efficient oral administration of MML-CDs as a novel therapy strategy for ulcerative colitis., (© 2024. The Author(s).)

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Osteocalcin plays an important role in energy metabolism. In this study, we investigated the mechanism of action of chemically synthesized osteocalcin (csOCN) in ameliorating NAFLD. We demonstrated for the first time that csOCN attenuates lipid accumulation in the liver and hepatocytes by modulating CD36 protein expression. In addition, we found that the expression of p-AMPK, FOXO1 and BCL6 decreased and the expression of CD36 increased after OA/PA induction compared to the control group, and these effects were reversed by the addition of csOCN. In contrast, the therapeutic effect of csOCN was inhibited by the addition of AMPK inhibitors and BCL6 inhibitors. This finding suggested that csOCN regulates CD36 expression via the AMPK-FOXO1/BCL6 axis. In NAFLD mice, oral administration of csOCN also activated the AMPK pathway and reduced CD36 expression. Molecular docking revealed that osteocalcin has a docking site with CD36. Compared to oleic acid and palmitic acid, osteocalcin bound more strongly to CD36. Laser confocal microscopy results showed that osteocalcin colocalized with CD36 at the cell membrane. In conclusion, we demonstrated the regulatory role of csOCN in fatty acid uptake pathways for the first time; it regulates CD36 expression via the AMPK-FOXO1/BCL6 axis to reduce fatty acid uptake, and it affects fatty acid transport by may directly binding to CD36. There are indications that csOCN has potential as a CD36-targeted drug for the treatment of NAFLD., (© 2024. The Author(s).)

Background: The health effects of different weight loss strategies vary greatly, and the relationship between weight loss strategies, especially the combination of multiple strategies, and death is still unclear. We aimed to examine the associations of various numbers and combinations of weight loss strategies with all-cause and specific-cause mortality and to further evaluate the associations of different total weight loss volumes with mortality., Methods: Using data from NHANES (1999-2018) with 48,430 participants aged 20 and above, we collected fourteen self-reported weight loss strategies and identified five clusters using latent class analysis. Cox proportional hazards models were used to examine the association between the amounts and clusters of weight loss strategies and mortality., Results: During a median follow-up of 9.1 years of 48,430 participants, 7,539 deaths were recorded (including 1,941 CVDs and 1,714 cancer). Participants who adopted 2, 3-4, and ≥ 5 weight loss strategies had a lower risk of all-cause mortality, with HRs of 0.88 (95% CI, 0.81 to 0.97), 0.89 (95% CI, 0.81 to 0.96) and 0.71 (95% CI, 0.61 to 0.82). Regardless of weight loss or weight gain categories, there was a significant trend toward reduced mortality as the number of weight loss strategies increased (P trend < 0.05). Participants who adopted cluster-1 (four strategies), cluster-2 (five strategies) and cluster-3 (three strategies) had a significantly lower risk of all-cause mortality, with HRs of 0.71 (95% CI, 0.60 to 0.84), 0.70 (95% CI, 0.55 to 0.89) and 0.81 (95% CI, 0.70 to 0.94). Among them, cluster-1 and cluster-2 are both characterized by eating less food, exercising, drinking plenty of water, lowering calories and eating less fat. Conversely, cluster-4 (five strategies) and cluster-5 (four strategies) had marginally significant effects, and they both had actual higher total energy intakes. Similar associations were observed for CVDs and cancer mortality., Conclusions: Employing two or more weight loss strategies was associated with a lower risk of death, even among those who gained weight. Eating less food, exercising, drinking plenty of water, lowering calories and eating less fat is a better combination of strategies. On this basis, limiting the actual intake of total energy is necessary., (© 2024. The Author(s).)

Background: Advance care planning (ACP) can contribute to individuals making decisions about their healthcare preferences in advance of serious illness. Up to now, the acceptance level and associated factors of ACP among the public in China remain unclear. This study aims to investigate the acceptance level of ACP in China and identify factors associated with it based on the socioecological model., Methods: A total of 19,738 participants were included in this survey. We employed a random forest regression analysis to select factors derived from the socioecological model. Multivariate generalized linear model analysis was then conducted to explore the factors that were associated with the acceptance level of ACP., Results: On a scale ranging from 0 to 100, the median score for acceptance level of ACP was 64.00 (IQR: 48.00-83.00) points. The results of the multivariate generalized linear model analysis revealed that participants who scored higher on measures of openness and neuroticism personality traits, as well as those who had greater perceptions of social support, higher levels of health literacy, better neighborly relationships, family health, and family social status, were more likely to accept ACP. Conversely, participants who reported higher levels of subjective well-being and greater family communication levels demonstrated a lower likelihood of accepting ACP., Conclusions: This study identified multiple factors associated with the acceptance level of ACP. The findings offer valuable insights that can inform the design and implementation of targeted interventions aimed at facilitating a good death and may have significant implications for the formulation of end-of-life care policies and practices in other countries facing similar challenges., (© 2024. The Author(s).)

Background: The reactive aggressive behavior in individuals typically shows a rapid growth trend as individuals enter adolescence, and peaks during middle-school period. According to the Comprehensive Cognitive Model of Trait Anger, trait anger and hostile attribution bias play important roles in the development of reactive aggressive behavior. Based on this, current study explored the relationship between trait anger and reactive aggressive behavior in middle school students, as well as the mediating role of hostile attribution bias and interventions., Methods: The current study consisted of three sub-studies. Study 1 recruited 87 middle school students with an average age of 12.367 ± 0.889 years, investigated the relationship between trait anger and reactive aggressive behavior, as well as the mediating role of trait hostile attribution bias. Study 2 recruited 62 middle school students with an average age of 13.376 ± 0.963 years, investigated the relationship between trait anger and reactive aggressive behavior, as well as the mediating role of state hostile attribution bias. Study 3 recruited 80 middle school students with an average age of 13.392 ± 0.977 years, implemented an intervention targeting trait hostile attribution bias in middle school students with high trait anger to reduce their reactive aggressive behavior. In current study, data management was performed using SPSS 22.0. Descriptive statistics, independent samples t-test, paired samples t-test, repeated measures analysis of variance (ANOVA), and path analysis were used for statistical analysis., Findings: The results of Study 1 showed that trait anger predicted reactive aggressive behavior through trait hostile attribution bias. The results of Study 2 indicated that trait and state hostile attribution bias played mediating role intermediary, and trait hostile attribution bias had a stronger mediating effect than state hostile attribution bias. The results of Study 3 suggested that the intervention effectively decreased trait hostile attribution bias and reactive aggressive behavior., Conclusions: Trait anger can predict the reactive aggressive behavior of junior high school students, with trait hostility attribution bias and state hostility attribution bias mediating this relationship. Intervening in the hostility attribution bias of high-anger junior high school students can effectively reduce their reactive aggressive behavior., (© 2024. The Author(s).)

Background: Photo-thermo-sensitive male sterility (PTMS), which refers to the male sterility triggered by variations in photoperiod and temperature, is a crucial element in the wheat two-line hybrid system. The development of safe production and efficient propagation for male sterile lines holds utmost importance in two-line hybrid wheat. Under the stable photoperiod condition, PTMS is mainly induced by high or low temperatures in wheat, but the effect of daily temperature difference (DTD) on the fertility conversion of PTMS lines has not been reported. Here, three BS type PTMS lines including BS108, BS138, and BS366, as well as a control wheat variety J411 were used to analyze the correlation between fertility and DTD using differentially sowing tests, photo-thermo-control experiments, and transcriptome sequencing., Results: The differentially sowing tests suggested that the optimal sowing time for safe seed production of the three PTMS lines was from October 5th to 25th in Dengzhou, China. Under the condition of 12 h 12 °C, the PTMS lines were greatly affected by DTD and exhibited complete male sterility at a temperature difference of 15 °C. Furthermore, under different temperature difference conditions, a total of 20,677 differentially expressed genes (DEGs) were obtained using RNA sequencing. Moreover, through weighted gene co-expression network analysis (WGCNA) and KEGG enrichment analysis, the identified DEGs had a close association with "starch and sucrose metabolism", "phenylpropanoid biosynthesis", "MAPK signaling pathway-plant", "flavonoid biosynthesis", and "cutin, and suberine and wax biosynthesis". qRT-PCR analysis showed the expression levels of core genes related to KEGG pathways significantly decreased at a temperature difference of 15 ° C. Finally, we constructed a transcriptome mediated network of temperature difference affecting male sterility., Conclusions: The findings provide important theoretical insights into the correlation between temperature difference and male sterility, providing guidance for the identification and selection of more secure and effective PTMS lines., (© 2024. The Author(s).)

Background: Renal cell carcinoma (RCC) is presently recognized as the most prevalent kidney tumor. However, the role and underlying mechanism of action of the conversion factor-inducible protein (TGFBI), an extracellular matrix protein, in RCC remain poorly understood., Methods: In this study, we employed Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry techniques to assess the expression of TGFBI in RCC tissues or cells. Furthermore, we analyzed the proliferation and migration of RCC cells using CCK8, cloning, scratching, and migration assays. Additionally, we examined apoptosis and cell cycle progression through flow cytometry, analysis. Lastly, we employed gene set enrichment analysis (GSEA) to investigate the biological processes associated with TGFBI, which were subsequently validated., Results: The findings indicate that TGFBI exhibits significantly elevated expression levels in both renal cell carcinoma (RCC) tissues and cells. Furthermore, the knockdown of TGFBI in SiRNA transfected cells resulted in the inhibition of RCC cell proliferation, migration, invasiveness, apoptosis, and alteration of the cell cycle. Additionally, TGFBI was found to impede the epithelial-mesenchymal transition (EMT) process in RCC cells. Bioinformatics analysis suggests that TGFBI may exert its influence on various biological processes in RCC through the tumor immune microenvironment. Moreover, our study demonstrates that TGFBI promotes RCC progression by activating the PI3K/AKT/mTOR/HIF-1α., Conclusions: Our research indicates that TGFBI exhibits high expression in RCC and facilitate RCC progression and metastasis through various molecular mechanisms. Hence, TGFBI has the potential to be a novel therapeutic target for the diagnosis and treatment of RCC in the future., (© 2024. The Author(s).)

Background: Triple negative breast cancer (TNBC) is a type of breast cancer that is negative for oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, is highly malignant and aggressive, lacks of corresponding targeted therapy, and has a relatively poor prognosis. Therefore, understanding the mechanism of TNBC development and formulating effective treatment strategies for inducing cell death are still urgent tasks in the treatment of TNBC. Research has shown that uncarboxylated osteocalcin can promote the proliferation of prostate cancer, lung adenocarcinoma and TNBC cells, but the mechanism by which GluOC affects TNBC growth and metastasis needs further study., Methods: MDA-MB-231 breast cancer cells were used for in vitro cell analysis. Key target molecules or pathways were identified by RNA sequencing, and migration ability was detected by scratch assays, Transwell assays, cell adhesion assays and western blot analysis. Fluorescence staining, colony detection, qRT‒PCR and flow cytometry were used to detect apoptosis, oxidative stress, the cell cycle and the stemness of cancer cells, and a xenotransplantation model in BALB/C nude mice was used for in vivo analysis., Results: This study demonstrated that GluOC facilitates the migration of MDA-MB-231 breast cancer cells through the ROCK1/MYPT1/MLC2 signalling pathway and promotes the proliferation of TNBC cells via the ROCK1/JAK2/PIK3CA/AKT signalling pathway. Experiments in nude mice demonstrated that GluOC promoted tumour cell proliferation and metastasis in tumour-bearing mice, which further clarified the molecular mechanism of TNBC growth and invasion., Conclusion: Our findings highlight the importance of GluOC in driving TNBC progression and its association with poor patient outcomes. This study clarifies the functional effects of GluOC on TNBC growth, providing insight into the molecular basis of TNBC and potentially providing new ideas for developing targeted therapies to improve patient outcomes., (© 2024. The Author(s).)

Aims: Dipeptidyl peptidase-4 inhibitors (DPP-4i) served as oral antidiabetic agents for treatment of type 2 diabetes mellitus (T2DM). Although an action on glucose homeostasis was identified, no well-rounded illustration had been established on the changes of tumor necrosis factor alpha (TNF-alpha) levels during DPP-4i treatment. This study aimed to explore the anti-inflammatory effect of DPP-4i on TNF-alpha in patients with T2DM., Methods: PubMed, Embase and Cochrane Library were systematically searched from inception to May 31, 2024. Randomized controlled trials exploring the impact of DPP-4i on TNF-alpha levels were identified. Risk of bias was assessed according to the Cochrane criteria. A fixed or random-effects model was selected to pool estimate on whether the heterogeneity was present. Subgroup analysis were performed to explore the potential factors that influenced heterogeneity. Related meta-analysis was conducted with the software of Revman 5.3 and STATA 12.0., Results: Eleven trials involving 884 participants with T2DM were included. Pooled estimates suggested that DPP-4i did not significantly modulate TNF-alpha levels (WMD, - 0.70, 95% CI - 1.94 to 0.53, P = 0.26) in T2DM. DPP-4i produced a significant effect on TNF-alpha (WMD, - 4.50 pg/mL, 95% CI - 4.68 to - 4.32, P < 0.00001) when compared to placebo, and a comparable effect was demonstrated on TNF-alpha (WMD, 0.10 pg/mL, 95% CI - 0.11 to 0.30, P = 0.35) in comparison with active agents. Estimate was stable according to the sensitivity test. Subgroup analysis revealed that heterogeneity might not correlate with baseline glycated hemoglobin (HbA1c), age or treatment duration., Conclusions: A significant effect of DPP-4i on TNF-alpha levels was present in T2DM when compared to placebo. Administration of DPP-4i produced no significant effect on TNF-alpha in comparison with active comparators. Further studies with large samples should be performed to illustrate the impact of DPP-4i on TNF-alpha levels in T2DM. Trial registration International Prospective Register for Systematic Review (PROSPERO) number: CRD42020185479., (© 2024. The Author(s).)

Background: The energy/protein imbalance in a low-protein diet induces lipid metabolism disorders in late-phase laying hens. Reducing energy levels in the low-protein diet to adjust the energy-to-protein ratio may improve fat deposition, but this also decreases the laying performance of hens. This study investigated the mechanism by which different energy levels in the low-protein diet influences liver lipid metabolism in late-phase laying hens through the enterohepatic axis to guide feed optimization and nutrition strategies. A total of 288 laying hens were randomly allocated to the normal-energy and normal-protein diet group (positive control: CK) or 1 of 3 groups: low-energy and low-protein diet (LL), normal-energy and low-protein diet (NL), and high-energy and low-protein diet (HL) groups. The energy-to-protein ratios of the CK, LL, NL, and HL diets were 0.67, 0.74, 0.77, and 0.80, respectively., Results: Compared with the CK group, egg quality deteriorated with increasing energy intake in late-phase laying hens fed low-protein diet. Hens fed LL, NL, and HL diets had significantly higher triglyceride, total cholesterol, acetyl-CoA carboxylase, and fatty acid synthase levels, but significantly lower hepatic lipase levels compared with the CK group. Liver transcriptome sequencing revealed that genes involved in fatty acid beta-oxidation (ACOX1, HADHA, EHHADH, and ACAA1) were downregulated, whereas genes related to fatty acid synthesis (SCD, FASN, and ACACA) were upregulated in LL group compared with the CK group. Comparison of the cecal microbiome showed that in hens fed an LL diet, Lactobacillus and Desulfovibrio were enriched, whereas riboflavin metabolism was suppressed. Cecal metabolites that were most significantly affected by the LL diet included several vitamins, such as riboflavin (vitamin B 2 ), pantethine (vitamin B 5 derivative), pyridoxine (vitamin B 6 ), and 4-pyridoxic acid., Conclusion: A lipid metabolism disorder due to deficiencies of vitamin B 2 and pantethine originating from the metabolism of the cecal microbiome may be the underlying reason for fat accumulation in the liver of late-phase laying hens fed an LL diet. Based on the present study, we propose that targeting vitamin B 2 and pantethine (vitamin B 5 derivative) might be an effective strategy for improving lipid metabolism in late-phase laying hens fed a low-protein diet., (© 2024. The Author(s).)

Background: Given the critical importance of medication adherence in HIV/AIDS treatment, this study aims to compare medication adherence measured by self-report (SR) and indirect measurement among antiretroviral therapy (ART) patients, exploring the differences of adherence results measured by different tools., Methods: We systematically searched PubMed, Embase, and the Cochrane Library to identify all relevant literature published up to November 22, 2023, without language restrictions, reporting adherence to ART measured by both SR and indirect measurement methods, while also analyzing individual and group adherence separately. Discrepancies between SR and indirect measurement results were assessed using the Mann-Whitney U test or Wilcoxon signed-rank test, with correlations evaluated using the Pearson correlation coefficient. Following one-to-one comparisons, meta-epidemiological one-step analysis was conducted, and network meta-analysis techniques were applied to compare results obtained through specific adherence assessment tools reported in the identified articles., Results: The analysis encompassed 65 original studies involving 13,667 HIV/AIDS patients, leading to 112 one-to-one comparisons between SR and indirect measurement tools. Statistically significant differences were observed between SR and indirect measurement tools regarding both individual and group adherence (P < 0.05), with Pearson correlation coefficients of 0.843 for individual adherence and 0.684 for group adherence. During meta-epidemiological one-step analysis, SR-measured adherence was determined to be 3.94% (95% CI: -4.48-13.44%) higher for individual adherence and 16.14% (95% CI: 0.81-18.84%) higher for group adherence compared to indirectly measured results. Subgroup analysis indicated that factors such as the year of reporting and geographic region appeared to influence the discrepancies between SR and indirect measurements. Furthermore, network meta-analysis revealed that for both individual and group adherence, the results obtained from most SR and indirect measurement tools were higher than those from electronic monitoring devices, with some demonstrating statistical significance (P < 0.05)., Conclusions: The findings underscored the complexity of accurately measuring medication adherence among ART patients. Significant variability was observed across studies, with self-report methods showing a significant tendency towards overestimation. Year of reporting, geographic region, and adherence measurement tools appeared to influence the differences between SR and indirect measurements. Future research should focus on developing and validating integrated adherence measurements that can combine SR data with indirect measures to achieve a more comprehensive understanding of adherence behaviors., (© 2024. The Author(s).)

Background: Previous studies, including Mendelian randomization (MR), have demonstrated type 2 diabetes (T2D) and glycemic traits are associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). However, few studies have explored the underlying pathway, such as the role of iron homeostasis., Methods: We used a two-step MR approach to investigate the associations of genetic liability to T2D, glycemic traits, iron biomarkers, and liver diseases. We analyzed summary statistics from various genome-wide association studies of T2D (n = 933,970), glycemic traits (n ≤ 209,605), iron biomarkers (n ≤ 246,139), MASLD (n ≤ 972,707), and related biomarkers (alanine aminotransferase (ALT) and proton density fat fraction (PDFF)). Our primary analysis was based on inverse-variance weighting, followed by several sensitivity analyses. We also conducted mediation analyses and explored the role of liver iron in post hoc analysis., Results: Genetic liability to T2D and elevated fasting insulin (FI) likely increased risk of liver steatosis (OR liability to T2D : 1.14 per doubling in the prevalence, 95% CI: 1.10, 1.19; OR FI : 3.31 per log pmol/l, 95% CI: 1.92, 5.72) and related biomarkers. Liability to T2D also likely increased the risk of developing liver cirrhosis. Genetically elevated ferritin, serum iron, and liver iron were associated with higher risk of liver steatosis (OR ferritin : 1.25 per SD, 95% CI 1.07, 1.46; OR liver iron : 1.15 per SD, 95% CI: 1.05, 1.26) and liver cirrhosis (OR serum iron : 1.31, 95% CI: 1.06, 1.63; OR liver iron : 1.34, 95% CI: 1.07, 1.68). Ferritin partially mediated the association between FI and liver steatosis (proportion mediated: 7%, 95% CI: 2-12%)., Conclusions: Our study provides credible evidence on the causal role of T2D and elevated insulin in liver steatosis and cirrhosis risk and indicates ferritin may play a mediating role in this association., (© 2024. The Author(s).)

Background: Childhood adversities may lead to decreased activity participation in later life, impacting memory health in ageing adults. Childhood adversities related to deprivation and threat, as conceptualized by the Dimensional Model of Adversity, can exhibit distinct impacts on cognitive and emotional outcomes in children and younger adults. This study examined the potential influence of childhood deprivation and threat on memory function in later life and the mediating role of activity participation in these relationships., Methods: This study used data from the first wave of Panel Study of Active Ageing and Society (PAAS), a representative survey of Hong Kong residents aged 50 or above (N = 1,005). Key variables included late-life memory function measured by delayed recall test, deprivation- and threat-related childhood adversities, and the frequency of participation in informal and formal types of activities. Mediation tests were used for analysis., Results: Childhood deprivation was associated with a lower late-life memory function, whereas threat was not. The negative effects of childhood deprivation and its subdomain, economic hardship, on memory function were mediated by activity participation. Total participation scores presented the strongest mediating effect (17.3-20.6%), with formal activities playing a more substantial mediating role than informal activities in mitigating the effect of childhood deprivation., Conclusions: These findings expand the applicability of the Dimensional Model of Adversity to ageing populations, highlighting the influence of deprivation on life-long cognitive development. Furthermore, this study revealed an indirect mechanism by which childhood deprivation affects memory health in old age through diverse activity participation., (© 2024. The Author(s).)

Introduction: The correlation between radiation exposure before pregnancy and abnormal birth weight has been previously proven. However, for large-for-gestational-age (LGA) babies in women exposed to radiation before becoming pregnant, there is no prediction model yet., Material and Methods: The data were collected from the National Free Preconception Health Examination Project in China. A sum of 455 neonates (42 SGA births and 423 non-LGA births) were included. A training set (n = 319) and a test set (n = 136) were created from the dataset at random. To develop prediction models for LGA neonates, conventional logistic regression (LR) method and six machine learning methods were used in this study. Recursive feature elimination approach was performed by choosing 10 features which made a big contribution to the prediction models. And the Shapley Additive Explanation model was applied to interpret the most important characteristics that affected forecast outputs., Results: The random forest (RF) model had the highest average area under the receiver-operating-characteristic curve (AUC) for predicting LGA in the test set (0.843, 95% confidence interval [CI]: 0.714-0.974). Except for the logistic regression model (AUC: 0.603, 95%CI: 0.440-0.767), other models' AUCs displayed well. Thereinto, the RF algorithm's final prediction model using 10 characteristics achieved an average AUC of 0.821 (95% CI: 0.693-0.949)., Conclusion: The prediction model based on machine learning might be a promising tool for the prenatal prediction of LGA births in women with radiation exposure before pregnancy., (© 2024. The Author(s).)

Apalutamide, a novel endocrine therapy agent, has been shown to significantly improve the prognosis of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, resistance to apalutamide has also been reported, and the underlying mechanism for this response has yet to be clearly elucidated. First, this study established apalutamide-resistant prostate cancer (PCa) cells, and confirmed that apalutamide activated the release of calcium ions (Ca 2+ ) and endoplasmic reticulum stress (ERS) to enhance autophagy. Second, RNA sequencing, western blotting, and immunohistochemistry revealed significantly decreased Calpain 2 (CAPN2) expression in the apalutamide-resistant PCa cells and tissues. Furthermore, immunofluorescence and transmission electron microscopy (TEM) showed that CAPN2 promoted apalutamide resistance by activating protective autophagy. CAPN2 promoted autophagy by reducing Forkhead Box O1 (FOXO1) degradation while increasing nuclear translocation via nucleoplasmic protein isolation and immunofluorescence. In addition, FOXO1 promoted protective autophagy through the transcriptional regulation of autophagy-related gene 5 (ATG5). Furthermore, a dual-fluorescence assay confirmed that transcription factor 3 (ATF3) stimulation promoted CAPN2-mediated autophagy activation via transcriptional regulation. In summary, CAPN2 activated protective autophagy by inhibiting FOXO1 degradation and promoting its nuclear translocation via transcriptional ATG5 regulation. ATF3 activation and transcriptional CAPN2 regulation jointly promoted this bioeffect. Thus, our findings have not only revealed the mechanism underlying apalutamide resistance, but also provided a promising new target for the treatment of metastatic PCa., (© 2024. The Author(s).)

Background: The incidence of mental health problems among medical graduate students is much higher than among students of other disciplines. This can have adverse consequences for the medical students themselves as well as their future patients. This study aims to understand the pressures faced by Chinese medical students and the current status of mental health education. It also propose recommendations for the current situation and prospects for the future., Method: The authors conducted in-depth semi-structured interviews with 22 master's students from five medical schools during November 2023. All interview sessions were recorded and transcribed verbatim. The transcriptions were analyzed using the Colaizzi's seven-step method., Result: Three main themes were extracted from the students' statements: sources of psychological stress, ways to cope with stress, and perspectives on mental health education. The study showed that current mental health education in China is mostly in the form of printed mental health education manuals and mental health lectures, and there is no active tiered intervention for students at different levels. It is suggested that reforms should be made to shift to a model where the school proactively identifies problems and intervenes based on feedback., Conclusion: This study reveals the widespread psychological stress and shortcomings in current education methods. To address these challenges, institutions should develop tailored interventions, including tiered support systems, open dialogue promotion, and resilience training. Future research should focus on evaluating innovative interventions' effectiveness, ultimately fostering a supportive environment that enhances students' success and contributes to a healthier healthcare workforce., (© 2024. The Author(s).)

Aims: About 20-40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM., Methods: A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I 2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively., Results: A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m 2 , 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg's and Egger's tests., Conclusions: Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. INTERNATIONAL PROSPECTIVE REGISTER FOR SYSTEMATIC REVIEW (PROSPERO) NUMBER: CRD.42020144642., (© 2024. The Author(s).)

Objectives: Epidemiological studies of stroke and its risk factors can help develop strategies to prevent stroke. We aimed to explore the current gender-specific prevalence of stroke and associated risk factors., Methods: Data were collected using a structured precoded questionnaire designed by the Stroke Screening and Prevention Programme of the National Health and Wellness Commission Stroke Prevention and Control Project Committee, between June 2020 and November 2021. A total of 7394 residents took part in the study, 187 of whom had a stroke. The baseline information of each participant was obtained and included in this study. The chi-square test and Kruskal-Wallis tests were used to examine the relationship between these indicators and stroke, and then multivariate logistic regression was used to construct the prediction scale between different genders., Results: of 7394 participants,4571 (61.82%) were female. The overall prevalence of stroke patients in the study population was 2.53%, Multivariate analysis found that residence status (OR = 0.43, p = 0.002) 、HCY (OR = 0.962, p = 0.000)、Previous TIA (OR = 0.200, p = 0.002) 、Hypertension (OR = 0.33, p = 0.000) and Dyslipidemia (OR = 0.668, p = 0.028) were significant predictors of stroke. there are gender differences in the traditional risk factors for stroke, and women have more risk factors. ROC analysis confirmed the accuracy of the stroke risk model, and the AUC of the stroke risk model for the general population was 0.79 with p < 0.05. In the gender model, the female AUC was 0.796 (p < 0.05). and the male AUC was 0.786 with p < 0.05., Conclusion: The prevalence of stroke in adults aged 40 years and above is high in eastern China were high. management of risk factors can effectively prevent the occurrence of most strokes. more attention should be paid to gender differences associated with stroke., (© 2024. The Author(s).)

Background: The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC., Methods: Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM)., Results: Of the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6-16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn't. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC., Conclusion: Adjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort., (© 2024. The Author(s).)

Background: The World Health Organization (WHO) published the Integrated Care for Older People (ICOPE) framework to help healthcare providers cope with the population aging crisis. However, the relevant evidence on the demands of older people and the compensatory capacity of the environment is limited. This study reports for the first time the level of the ICOPE demand in Western China that includes the impact of geographic accessibility of medical resources (GAMR) on ICOPE demand and the potential mechanism of health status., Methods: A cross-sectional questionnaire survey was conducted among 1200 adults aged 60 years and older selected through multi-stage stratified cluster sampling to obtain relevant data, including ICOPE demand, health status, and GAMR. Propensity score matching (PSM) was used to analyze the impact of GAMR on ICOPE demand among older people and those with different health statuses., Results: Among the prospective research participants, 1043 were eligible for the study. The mean score of ICOPE demand among all participants was 3.68 (standard deviation [SD] = 0.78). After adjusting for covariates between high and low GAMR groups (1:1 match), ICOPE demand was significantly higher in the low GAMR group than in the high GAMR group (average treatment effect on the treated [ATT] = 0.270, p < 0.05). For both good and poor self-rated health status, the ICOPE demand of the low GAMR group was significantly higher than that in the high GAMR group (ATT = 0.345, p < 0.05; ATT = 0.190, p < 0.05). For chronic diseases, the ICOPE demand of older people with multimorbidity in the low GAMR group was significantly higher than that in the high GAMR group (ATT = 0.318, p < 0.01)., Conclusions: The older population in Western China has a relatively high demand for ICOPE. Low GAMR is a key factor in ICOPE demand growth in this region. It accelerates demand release for both older people with multimorbidity and self-perceptions of health., (© 2024. The Author(s).)

Background: HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors., Methods: We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW)., Results: The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings., Conclusions: HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment., (© 2024. The Author(s).)

Objective: This study synthesizes evidence from the Loughborough Passing Test to evaluate the short-passing ability of soccer players and summarizes the reported variables that affect this ability to provide support for the development and improvement of short-passing abilities in soccer players., Methods: In this systematic review using the PRISMA guidelines, a comprehensive search was conducted in Web of Science, PubMed, and EBSCOhost from inception to July 2023 to identify relevant articles from the accessible literature. Only studies that used the Loughborough test to assess athletes' short-passing ability were included. The quality of the included studies was independently assessed by two reviewers using the PEDro scale, and two authors independently completed the data extraction., Results: Based on the type of intervention or influencing factor, ten studies investigated training, nine studies investigated fatigue, nine studies investigated supplement intake, and five studies investigated other factors., Conclusion: Evidence indicates that fitness training, small-sided games training, and warm-up training have positive effects on athletes' short-passing ability, high-intensity special-position training and water intake have no discernible impact, mental and muscular exhaustion have a significantly negative effect, and the effect of nutritional ergogenic aid intake is not yet clear. Future research should examine more elements that can affect soccer players' short-passing ability., Trial Registration: https://inplasy.com/ ., identifier: INPLASY20237., (© 2024. The Author(s).)

C57BL/6 mice are frequently utilized as murine models with the desired genetic background for altertion in multiple research contexts. So far, there is still a lack of comprehensive kidney morphology and single-cell transcriptome atlas at all stages of growth of C57BL/6 mice. To provide an interactive set of reference standards for the scientific community, we performed the current study to investigate the kidney's development throughout the capillary-loop stage until senescence. Eight groups, with five to six mice each, represented embryonic stage (embryos 18.5 days), suckling period (1 day after birth), juvenile stage (1 month old), adulthood (containing 3 months old, 6 months old and 10 months old), reproductive senescence stage (20 months old), and post-senescence stage (30 months old), respectively. With age, the thickness of the glomerular basement membrane (GBM) was increased. Notably, GBM knobs appeared at three months and became frequent with age. Using single-cell transcriptome data, we evaluated how various biological process appear in particular cell types and investigated the potential mechanism of formation of GBM konbs. In conclusion, having access to detailed kidney morphology and single-cell transcriptome maps from C57BL/6 mice at various developmental stages of C57BL/6 mice would be a novel and major resource for biological research and testing of prospective therapeutic approaches., (© 2024. The Author(s).)

Objective: The present study aims to explore the influencing factors of the scientific fitness literacy of nurses and provide a strategic basis for literacy improvement., Methods: A questionnaire on the influencing factors of scientific fitness literacy of nurses was designed by the group conducting the present study; the questionnaire was based on the socioecology model and the questionnaire preparation method. The general data questionnaire and the questionnaire on the influencing factors of scientific fitness literacy of nurses were adopted to investigate nurses in tertiary hospitals in order to analyze and discuss the influencing factors of their scientific fitness literacy., Results: (1) The questionnaire on the influencing factors of the scientific fitness literacy of nurses comprised five dimensions and 36 items. The overall item-content validity index was 0.833-1.000, the scale-content validity index was 0.974, and the overall Cronbach's α coefficient was 0.955; (2) the results of the pairwise Pearson correlation analysis showed that all five dimensions were positively correlated with the scientific fitness literacy of nurses; and (3) the results of the multiple linear regression analysis revealed that five dimensions, as well as the existence of exercise habits in daily life, had a significant impact on the scientific fitness literacy of nurses (P < 0.001)., Conclusion: The factors influencing the scientific fitness literacy of nurses involved all levels of the socioecological system. The methods of improving the awareness of the scientific fitness of nurses and providing opportunities for scientific fitness activities via the hospital played a critical role in literacy improvement. However, the lack of professional guidance and an atmosphere promoting scientific fitness might hinder literacy improvement., (© 2024. The Author(s).)

Background: Evidence indicates that the Sport Education Model (SEM) has demonstrated effectiveness in enhancing students' athletic capabilities and fostering their enthusiasm for sports. Nevertheless, there remains a dearth of comprehensive reviews examining the impact of the SEM on students' attitudes toward physical education learning., Purpose: The purpose of this review is to elucidate the influence of the SEM on students' attitudes toward physical education learning., Methods: Employing the preferred reporting items of the Systematic Review and Meta-analysis (PRISMA) statement guidelines, a systematic search of PubMed, SCOPUS, EBSCOhost (SPORTDiscus and CINAHL Plus), and Web of Science databases was conducted in mid-January 2023. A set of keywords associated with the SEM, attitudes toward physical education learning, and students were employed to identify relevant studies. Out of 477 studies, only 13 articles fulfilled all the eligibility criteria and were consequently incorporated into this systematic review. The validated checklist of Downs and Black (1998) was employed for the assessment, and the included studies achieved quality scores ranging from 11 to 13. The ROBINS-I tool was utilized to evaluate the risk of bias in the literature, whereby only one paper exhibited a moderate risk of bias, while the remainder were deemed to have a high risk., Results: The findings unveiled significant disparities in cognitive aspects (n = 8) and affective components (n = 12) between the SEM intervention and the Traditional Teaching (TT) comparison. Existing evidence suggests that the majority of scholars concur that the SEM yields significantly superior effects in terms of students' affective and cognitive aspects compared to the TT., Conclusions: Nonetheless, several issues persist, including a lack of data regarding junior high school students and gender differences, insufficient frequency of weekly interventions, inadequate control of inter-group atmosphere disparities resulting from the same teaching setting, lack of reasonable testing, model fidelity check and consideration for regulating variables, of course, learning content, and unsuitable tools for measuring learning attitudes. In contrast, the SEM proves more effective than the TT in enhancing students' attitudes toward physical learning., Systematic Review Registration: ( https://inplasy.com/ ) (INPLASY2022100040)., (© 2024. The Author(s).)

Fungal non-ribosomal peptide synthetase (NRPS)-encoding products play a paramount role in new drug discovery. Fusarium, one of the most common filamentous fungi, is well-known for its biosynthetic potential of NRPS-type compounds with diverse structural motifs and various biological properties. With the continuous improvement and extensive application of bioinformatic tools (e.g., anti-SMASH, NCBI, UniProt), more and more biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) have been identified in Fusarium strains. However, the biosynthetic logics of these SMs have not yet been well investigated till now. With the aim to increase our knowledge of the biosynthetic logics of NPRS-encoding products in Fusarium, this review firstly provides an overview of research advances in elucidating their biosynthetic pathways., (© 2024. The Author(s).)

Background: Congenital stationary night blindness (CSNB) is an inherited retinal disorder. Most of patients have myopia. This study aims to describe the clinical and genetic characteristics of fifty-nine patients with CSNB and investigate myopic progression under genetic cause., Results: Sixty-five variants were detected in the 59 CSNB patients, including 32 novel and 33 reported variants. The most frequently involved genes were NYX, CACNA1F, and TRPM1. Myopia (96.61%, 57/59) was the most common clinical finding, followed by nystagmus (62.71%, 37/59), strabismus (52.54%, 31/59), and nyctalopia (49.15%, 29/59). An average SE of -7.73 ± 3.37 D progressed to -9.14 ± 2.09 D in NYX patients with myopia, from - 2.24 ± 1.53 D to -4.42 ± 1.43 D in those with CACNA1F, and from - 5.21 ± 2.89 D to -9.24 ± 3.16 D in those with TRPM1 during the 3-year follow-up; the TRPM1 group showed the most rapid progression., Conclusions: High myopia and strabismus are distinct clinical features of CSNB that are helpful for diagnosis. The novel variants identified in this study will further expand the knowledge of variants in CSNB and help explore the molecular mechanisms of CSNB., (© 2024. The Author(s).)

Background: Alfalfa (Medicago sativa. L) is one of the best leguminous herbage in China and even in the world, with high nutritional and ecological value. However, one of the drawbacks of alfalfa is its sensitivity to dry conditions, which is a global agricultural problem. The objective of this study was to investigate the regulatory effects of endogenous nitric oxide (NO) on endogenous hormones and related miRNAs in alfalfa seedling leaves under drought stress. The effects of endogenous NO on endogenous hormones such as ABA, GA3, SA, and IAA in alfalfa leaves under drought stress were studied. In addition, high-throughput sequencing technology was used to identify drought-related miRNAs and endogenous NO-responsive miRNAs in alfalfa seedling leaves under drought stress., Result: By measuring the contents of four endogenous hormones in alfalfa leaves, it was found that endogenous NO could regulate plant growth and stress resistance by inducing the metabolism levels of IAA, ABA, GA3, and SA in alfalfa, especially ABA and SA in alfalfa. In addition, small RNA sequencing technology and bioinformatics methods were used to analyze endogenous NO-responsive miRNAs under drought stress. It was found that most miRNAs were enriched in biological pathways and molecular functions related to hormones (ABA, ETH, and JA), phenylpropane metabolism, and plant stress tolerance., Conclusion: In this study, the analysis of endogenous hormone signals and miRNAs in alfalfa leaves under PEG and PEG + cPTIO conditions provided an important basis for endogenous NO to improve the drought resistance of alfalfa at the physiological and molecular levels. It has important scientific value and practical significance for endogenous NO to improve plant drought resistance., (© 2024. The Author(s).)

Background: Calcium (Ca) is a nutritional factor that associated with dental caries. A recent study showed that in the case of adequate Ca intake, a higher level of physical activity may contribute to bone mass accumulation. However, the combined effect between Ca intake and physical activity on caries experience is unclear. Herein, we aimed to explore the above combined effect on dental caries in children and adolescents., Methods: Data of 5,917 children and adolescents were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2015-2020 in this cross-sectional study. The NHANES assessed the dietary Ca intake through the 24-hour dietary recalls, and the physical activity level was self-reported using the questionnaires. Also, the dental caries was diagnosed according to the Decayed, Missing and Filled Teeth/Surfaces (DMFT/S) index. Weighted univariate and multivariate logistic regression analyses were utilized to screen the covariates and to investigate the associations of dietary Ca intake and physical activity with dental caries, respectively, and assess the combined effect between dietary Ca intake and physical activity on dental caries. The evaluation indexes were odd ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age, obesity, and total sugar intake were also performed., Results: Among the eligible participants, 2,687 had caries experience. After adjusting for the covariates, we found that children and adolescents who not reach the recommendation level of Ca intake combined with physical activity less than 7 time in 1 week seemed to have higher odds of dental caries [OR = 1.77, 95%CI: (1.38-2.27)], compared with those who reached the standards. In addition, this potential combined effect was also found in age < 12 years old [OR = 1.62, 95%CI: (1.23-2.14)], non-obesity [OR = 1.88, 95%CI: (1.49-2.35)], and total sugar intake (all P < 0.05) subgroups., Conclusions: Ca intake and physical activity had a potential combined effect on dental caries in children and adolescents, but the causal relationships between them needed further clarification., (© 2024. The Author(s).)

Background: In the background of an aging population, the risk of cognitive impairment in the older population is prominent. Exposure to complex neighborhood built environments may be beneficial to the cognitive health of older adults, and the purpose of this study was to systematically review the scientific evidence on the effects of neighborhood built environments on cognitive function in older adults., Methods: Keywords and references were searched in Web of Science, Pubmed, PsycINFO, and MEDLINE. Studies examining the relationship between the built environment and cognitive function in older adults were included. The neighborhood built environment as an independent variable was classified according to seven aspects: density, design, diversity, destination accessibility, public transportation distance, blue/green space, and built environment quality. The cognitive function as the dependent variable was classified according to overall cognitive function, domain-specific cognitive function, and incidence of dementia. The quality of the included literature was assessed using the National Institutes of Health's Observational Cohort and Cross-Sectional Study Quality Assessment Tool., Results: A total of 56 studies were included that met the inclusion criteria, including 31 cross-sectional studies, 23 longitudinal studies, 1 cross-sectional study design combined with a case-control design, and 1 longitudinal study design combined with a case-control design. Most of the studies reviewed indicate that the built environment factors that were positively associated with cognitive function in older adults were population density, street connectivity, walkability, number of public transportation stops around the residence, land use mix, neighborhood resources, green space, and quality of the neighborhood built environment. Built environment factors that were negatively associated with cognitive function in older adults were street integration, distance from residence to main road. The relationship between residential density, destination accessibility, and blue space with cognitive function in older adults needs to be further explored., Conclusion: Preliminary evidence suggests an association between the neighborhood built environment and cognitive function in older adults. The causal relationship between the built environment and cognitive function can be further explored in the future using standardized and combined subjective and objective assessment methods, and longitudinal or quasi-experimental study designs. For public health interventions on the cognitive health of older adults, it is recommended that relevant authorities include the neighborhood built environment in their intervention programs., (© 2024. The Author(s).)

Background: The Yi people are a sociolinguistic group living in Mile City, which is their typical settlement in southeastern Yunnan, China. Over the long history of using medicinal plants, the Yi people have accumulated and developed a wealth of traditional medicinal knowledge, which has played a vital role in their health care. However, only a few studies have been performed to systematically document the medicinal plants commonly used by the Yi people. This study provides fundamental data for the development and application of ethnomedicine as well as supports the conservation of the traditional medical knowledge of the Yi people., Methods: This study was conducted from May 2020 to August 2022 and involved five townships in Mile. Information regarding medicinal plants was obtained through semistructured interviews, key informant interviews, and participatory observation. The collected voucher specimens were identified using the botanical taxonomy method and deposited in the herbarium. Ethnobotanical data were analyzed using informant consensus factor, relative frequency of citation, and fidelity level., Results: In total, 114 informants distributed in five townships of Mile were interviewed. The Yi people used 267 medicinal plant species belonging to 232 genera and 104 families to treat various diseases. Asteraceae, Lamiaceae, and Fabaceae were the most commonly used plant families by the Yi people. In addition, herbs were most commonly used by the Yi people. Whole plants and roots were the preferred medicinal parts. Decoctions were the most common method of herbal medicine preparation. There are 49 different recorded diseases treated by Yi medicinal plants, and among them, respiratory diseases, rheumatism, traumatic injury, fractures, and digestive system diseases have the largest number of species used. A quantitative analysis demonstrated that plants such as Zingiber officinale, Lycopodium japonicum, Aconitum carmichaelii, Panax notoginseng, Cyathula officinalis, and Leonurus japonicus played crucial roles in disease prevention and treatment., Conclusion: Traditional knowledge of medicinal plants is closely associated with the social culture of the local Yi people. The medicinal plants used for health care in the study area were diverse. Local healers were skilled at using medicinal plants to treat various diseases. Their treatment methods were convenient and unique, exhibiting distinctive regional characteristics. However, the inheritance of their traditional medicinal knowledge and protection of wild medicinal plant resources are facing serious challenges, including the decreasing number of local healers, aging of healers, lack of successors, and excessive harvesting of medicinal plant resources. This ethnobotanical survey provides a useful reference for the sustainable utilization and protection of medicinal plant resources in Mile and the inheritance of traditional medicinal knowledge of the Yi people., (© 2024. The Author(s).)

The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation., (© 2024. The Author(s).)

Background: Previous observational studies have suggested a notably elevated prevalence of delirium in individuals diagnosed with Parkinson's disease (PD), thereby implying a potential increased susceptibility to delirium among PD patients. However, it is imperative to acknowledge that observational studies inherently possess limitations, rendering it arduous to establish a definitive causal or reverse causal association between delirium and PD., Methods: To explore the relationship between delirium and PD, a bidirectional two-sample Mendelian randomization (MR) was conducted using summary statistics obtained from genome-wide association studies. The main analysis was performed using the inverse-variance weighted (IVW) method, with further analyses conducted using MR Egger, weighted median, and weighted mode to ensure accuracy of findings. Additionally, Cochran's Q statistics and MR Egger intercept were utilized to assess heterogeneity and horizontal pleiotropy, respectively., Results: According to the results obtained from the IVW model, no compelling evidence was found to support a potential causal association between delirium and PD (IVW: odds ratio [OR]: 0.996, 95% confidence interval CI 0.949-1.043, P = 0.845). Additionally, in the reverse direction, based on the results obtained from the IVW model, no significant evidence was found to support a causal association between PD and delirium (IVW: OR: 1.078, 95%CI  0.960-1.204, P = 0.225). A sensitivity analysis verified the reliability of the results., Conclusion: According to the MR findings, a bidirectional causal relationship between delirium and PD is not observed. It is crucial to conduct further research in clinical practice to investigate the association between delirium and the risk of PD., (© 2024. The Author(s).)