bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRD7 facilitates ferroptosis via modulating clusterin promoter hypermethylation and suppressing AMPK signaling in diabetes-induced testicular damage
Authors: Xiao Yuehai , Liang Zongjian , Qiao Jun , Zhu Zhiqiang , Liu Bei , Tian Yuan 
Published: July 2024

Abstract
Background
Diabetes mellitus (DM)-induced testicular damage is associated with sexual dysfunction and male infertility in DM patients. However, the pathogenesis of DM-induced testicular damage remains largely undefined.

Methods
A streptozotocin (STZ)-induced diabetic model and high glucose (HG)-treated in vitro diabetic model were established. The histological changes of testes were assessed by H&E staining. Serum testosterone, iron, MDA and GSH levels were detected using commercial kits. Cell viability and lipid peroxidation was monitored by MTT assay and BODIPY 581/591 C11 staining, respectively. qRT-PCR, immunohistochemistry (IHC) or Western blotting were employed to detect the levels of BRD7, Clusterin, EZH2 and AMPK signaling molecules. The associations among BRD7, EZH2 and DNMT3a were detected by co-IP, and the transcriptional regulation of Clusterin was monitored by methylation-specific PCR (MSP) and ChIP assay.

Results
Ferroptosis was associated with DM-induced testicular damage in STZ mice and HG-treated GC-1spg cells, and this was accompanied with the upregulation of BRD7. Knockdown of BRD7 suppressed HG-induced ferroptosis, as well as HG-induced Clusterin promoter methylation and HG-inactivated AMPK signaling in GC-1spg cells. Mechanistical studies revealed that BRD7 directly bound to EZH2 and regulated Clusterin promoter methylation via recruiting DNMT3a. Knockdown of Clusterin or inactivation of AMPK signaling reverses BRD7 silencing-suppressed ferroptosis in GC-1spg cells. In vivo findings showed that lack of BRD7 protected against diabetes-induced testicular damage and ferroptosis via increasing Clusterin expression and activating AMPK signaling.

Conclusion
BRD7 suppressed Clusterin expression via modulating Clusterin promoter hypermethylation in an EZH2 dependent manner, thereby suppressing AMPK signaling to facilitate ferroptosis and induce diabetes-associated testicular damage.
Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway
Authors: Liu Hai-Hua , Wei Wei , Wu Fei-Fei , Cao Lu , Yang Bing-Jie , Fu Jia-Ning , Li Jing-Xia , Liang Xin-Yue , Dong Hao-Yu , Heng Yan-Yan , Zhang Peng-Fei 
Published: July 2024

Abstract
Background
Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia.

Methods
In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation.

Results
Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression.

Conclusions
These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
What determines informal care need among community-dwelling older adults in China? Results from a longitudinal study
Authors: Zhang Liangwen , Shen Shuyuan , Zhang Wenzheng , Fang Ya 
Published: July 2024

Abstract
Background
With an intensified aging population and an associated upsurge of informal care need in China, there is an ongoing discussion around what factors influence this need among older adults. Most existing studies are cross-sectional and do not focus on older people living in the community. Conversely, this study empirically explores the factors that affect informal care need of Chinese community-dwelling older individuals based on longitudinal data.

Methods
This study constructed panel data using the China Health and Retirement Longitudinal Research Study (CHARLS) from 2011 to 2018 for analysis. Generalized linear mixed models were used to analyze the factors affecting reception of informal care, and linear mixed models were used to analyze the factors affecting informal care sources and intensity.

Results
During the follow-up period, 7542, 6386, 5087, and 4052 older adults were included in 2011–2018, respectively. The proportion receiving informal care increased from 19.92 to 30.78%, and the proportion receiving high-intensity care increased from 6.42 to 8.42% during this period. Disability (estimate = 4.27, P < 0.001) and living arrangement (estimate = 0.42, P < 0.001) were the critical determinants of informal care need. The rural older adults reported a greater tendency to receive informal care (estimate = 0.14, P < 0.001). However, financial support from children did not affect informal care need (P > 0.05).

Conclusions
At present, there is a great demand for the manpower and intensity of informal care, and the cost of informal care is on the rise. There are differences in informal care needs of special older groups, such as the oldest-old, living alone and severely disabled. In the future, the region should promote the balance of urban and rural care service resources, rationally tilt economic support resources to rural areas, reduce the inequality of long-term care resources, improve the informal care support system, and provide a strong community guarantee for the local aging of the older adults.
Differences of anticholinergic drug burden between older hospitalized patients with and without delirium: a systematic review and meta-analysis based on prospective cohort studies
Authors: Ieong Chifong , Chen Tingjia , Chen Sai , Gao Xiang , Yan Kemin , He Wen , Hong Hua , Gu Yong , Chen Xiao , Yuan Gang 
Published: July 2024

Abstract
Objectives
This review aims to comprehensively summarize the differences in anticholinergic drug burden (ADB) scores between older hospitalized patients with and without delirium.

Methods
We searched PubMed, Embase, Web of Science, Cochrane Library and CINAHL EBSCOhost databases to identify prospective cohort studies exploring the relationship between ADB and the occurrence of delirium in older hospitalized patients. The primary outcome of the review was the mean ADB scores for the delirium and non-delirium groups, and the secondary outcome was the scores for the subsyndromal and non-delirium groups. The standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were incorporated using a fixed-effect method. Moreover, we performed subgroup analysis according to the admission type, age, the ADB scale type and the ADB classification.

Results
Nine prospective cohort studies involving 3791 older patients with a median age of 75.1 (71.6–83.9) were included. The ADB score was significantly higher in the delirium group than in the non-delirium group (SMD = 0.21, 95%CI 0.13–0.28). In subgroup analysis, the age subgroup was split into < 75 and ≥ 75 according to the median age of the older people. There were significant differences in ADB scores between older people with delirium and those without delirium in various subgroups: surgical (SMD = 0.20, 95%CI 0.12–0.28), internal medicine (SMD = 0.64, 95%CI 0.25–1.02), age < 75 (SMD = 0.17, 95%CI 0.08–0.26), age ≥ 75 (SMD = 0.27, 95%CI 0.15–0.39), ADS scale (SMD = 0.13, 95%CI 0.13–0.40), ARS scale (SMD = 0.15, 95%CI 0.03–0.26), ACB scale (SMD = 0.13, 95%CI 0.01–0.25), pre-admission ADB (SMD = 0.24, 95%CI 0.05–0.43) and ADB during hospitalization (SMD = 0.20, 95%CI 0.12–0.27).

Conclusions
We found a quantitative relationship between ADB and delirium in older patients admitted for internal medicine and surgery. And this relationship remained significant in different age, ADB scale type and ADB classification subgroups. However, the actual difference in ADB scores between patients with delirium and without delirium was small. More high-quality observational studies should be conducted to explore the impact of ADB on delirium and subsyndromal delirium.

Clinical Trial Registration
The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) [Ref: CRD42022353649].
Gastric bezoars secondary to mixed infection with Sarcina ventriculi and G + bacilli: a case report
Authors: Wang Tao , Xiang Dan 
Published: July 2024

AbstractSarcina ventriculi is a bacterium with a specific histological morphology and infection can present with symptoms such as abdominal pain, nausea, vomiting and occasionally fatal complications. Delayed gastric emptying is regarded as the most significant risk factor for infection. Its pathogenicity is currently unknown and treatment options are inconsistent. Here we report a case of gastric bezoars secondary to a mixed infection of Sarcina ventriculi and G + bacilli, which is diagnosed by a pathological biopsy.
Analyzing the molecular mechanism of Scutellaria Radix in the treatment of sepsis using RNA sequencing
Authors: Deng Yaxing , Leng Linghan , Wang Chenglin , Yang Qingqiang , Hu Yingchun 
Published: July 2024

Abstract
Background
Sepsis is a life-threatening organ dysfunction, which seriously threatens human health. The clinical and experimental results have confirmed that Traditional Chinese medicine (TCM), such as Scutellariae Radix, has anti-inflammatory effects. This provides a new idea for the treatment of sepsis. This study systematically analyzed the mechanism of Scutellariae Radix treatment in sepsis based on network pharmacology, RNA sequencing and molecular docking.

Methods
Gene expression analysis was performed using Bulk RNA sequencing on sepsis patients and healthy volunteers. After quality control of the results, the differentially expressed genes (DEGs) were analyzed. The active ingredients and targets of Scutellariae Radix were identified using The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Ontology (GO) and Protein-Protein Interaction (PPI) analysis were performed for disease-drug intersection targets. With the help of GEO database, Survival analysis and Meta-analysis was performed on the cross-targets to evaluate the prognostic value and screen the core targets. Subsequently, single-cell RNA sequencing was used to determine where the core targets are located within the cell. Finally, in this study, molecular docking experiments were performed to further clarify the interrelationship between the active components of Scutellariae Radix and the corresponding targets.

Results
There were 72 active ingredients of Scutellariae Radix, and 50 common targets of drug and disease. GO and PPI analysis showed that the intersection targets were mainly involved in response to chemical stress, response to oxygen levels, response to drug, regulation of immune system process. Survival analysis showed that PRKCD, EGLN1 and CFLAR were positively correlated with sepsis prognosis. Meta-analysis found that the three genes were highly expressed in sepsis survivor, while lowly in non-survivor. PRKCD was mostly found in Macrophages, while EGLN1 and CFLAR were widely expressed in immune cells. The active ingredient Apigenin regulates CFLAR expression, Baicalein regulates EGLN1 expression, and Wogonin regulates PRKCD expression. Molecular docking studies confrmed that the three active components of astragalus have good binding activities with their corresponding targets.

Conclusions
Apigenin, Baicalein and Wogonin, important active components of Scutellaria Radix, produce anti-sepsis effects by regulating the expression of their targets CFLAR, EGLN1 and PRKCD.
Hemodialysis patients have signs of a chronic thrombotic burden
Authors: Stegmayr Bernd G. , Lundberg Lennart D. 
Published: July 2024

AbstractBackgroundCardiovascular diseases are the dominant cause of morbidity in hemodialysis (HD) patients. Unless sufficient anticoagulation is used during HD, clotting may appear. The objective was to investigate if levels of fibrin degradation products (D-dimer) were increased before and during HD.MethodsThe combined observational study included 20 patients performing a total of 60 hemodialysis divided into three sessions of low-flux dialysis. None of the patients suffered from any clinically evident thromboembolic event before or during the study. Median bolus anticoagulation (mainly tinzaparin) doses were 84 Units/kg bow. Blood samples were drawn before HD (predialysis), and at 30min and 180min during HD with focus on analyzing D-dimer levels and its relation to interdialytic weight gain (IDWG) and speed of fluid elimination by HD (UF-rate).ResultsPredialysis, D-dimer levels (mean 0.767 ±0.821, min 0.136mg/L) were above the upper reference value in 95% of the sessions. D-dimer levels were lowered at 30min (p<0.001) and returned to predialysis levels at 180min. Predialysis D-dimer correlated with NT-pro-BNP, Troponin T, IDWG and UF-rate. Multiple regression analysis revealed that the D-dimer levels were significantly related to IDWG and the UF-rate.ConclusionsD-dimer levels were elevated in a high proportion predialysis and during HD and related to the IDWG and the UF-rate. Awareness of D-dimer levels and future studies will help clarify if optimization of those variables, besides anticoagulation and biocompatibility measures, will eradicate the repeated subclinical thromboembolic events related to each HD; one reason that may explain organ damage and shortened life span of these patients.
Nomogram for predicting the probability of rectal anastomotic re-leakage after stoma closure: a retrospective study
Authors: Li Yuegang , Hu Gang , Zhang Jinzhu , Qiu Wenlong , Mei Shiwen , Wang Xishan , Tang Jianqiang 
Published: July 2024

Abstract
Background
In this study, we aimed to identify the risk factors in patients with rectal anastomotic re-leakage and develop a prediction model to predict the probability of rectal anastomotic re-leakage after stoma closure.

Methods
This study was a single-center retrospective analysis of patients with rectal cancer who underwent surgery between January 2010 and December 2020. Among 3225 patients who underwent Total or Partial Mesorectal Excision (TME/PME) surgery for rectal cancer, 129 who experienced anastomotic leakage following stoma closure were enrolled. Risk factors for rectal anastomotic re-leakage were analyzed, and a prediction model was established for rectal anastomotic re-leakage.

Results
Anastomotic re-leakage after stoma closure developed in 13.2% (17/129) of patients. Multivariable analysis revealed that neoadjuvant chemoradiotherapy (odds ratio, 4.07; 95% confidence interval, 1.17–14.21; p = 0.03), blood loss > 50 ml (odds ratio, 4.52; 95% confidence interval, 1.31–15.63; p = 0.02), and intersphincteric resection (intersphincteric resection vs. low anterior resection: odds ratio, 6.85; 95% confidence interval, 2.01–23.36; p = 0.002) were independent risk factors for anastomotic re-leakage. A nomogram was constructed to predict the probability of anastomotic re-leakage, with an area under the receiver operating characteristic curve of 0.828 in the cohort. Predictive results correlated with the actual results according to the calibration curve.

Conclusions
Neoadjuvant chemoradiotherapy, blood loss > 50 ml, and intersphincteric resection are independent risk factors for anastomotic re-leakage following stoma closure. The nomogram can help surgeons identify patients at a higher risk of rectal anastomotic re-leakage.
Blepharoptosis and corneal epithelial thickness alterations, is there any relation?
Authors: Rafizadeh Seyed Mohsen , Sonbolestan Seyed Ali , Zeidabadinejad Haniyeh , Abtahi Mohammad-Ali 
Published: July 2024

Abstract
Background
To compare the epithelial thickness map of ptotic eyes of blepharoptosis patients with contralateral non- ptotic eyes.

Methods
Unilateral blepharoptosis patients were enrolled consecutively. Patients were underwent full ophthalmologic examination and their demographic data such as age and gender and specific ptosis findings e.g. the cause and duration, MRD-1, and levator palpebralis superioris function were registered. Anterior segment imaging for epithelial thickness measurements was done using the Avanti RTVue-XR platform. The corneal epithelial thickness maps of ptotic and non-ptotic eyes were compared.

Results
44 patients with unilateral blepharoptosis were included in the study. 27 (61.4%) of them were female and 17 (38.6%) cases were male. The mean of the patients’ ages was 24.40 ± 15.16 years. Ptotic eyes had significantly thinner superior (p = 0.000), superior-temporal (p = 0.000) and superior-nasal (p = 0.005) sectors of the cornea and slightly thicker corneal epithelium (CE) in the inferior-nasal sector. The correlation of difference of superior-inferior CE was evaluated with different parameters including patient’s age (p = 0.457), type of blepharoptosis (p = 0.786), duration of blepharoptosis (p = 0.477) and MRD1 (p = 0.248), but no correlation was found.

Conclusions
This study revealed that lid position in blepharoptosis may have effects on the corneal epithelial thickness map. Because of the lower position of upper eyelid, a thinning effect on superior corneal sectors may happen.
Temporal relationship between hepatic steatosis and fasting blood glucose elevation: a longitudinal analysis from China and UK
Authors: Liu Yujie , Liang Xian , Hu Yifan , Zhang Ning , Zhu Xingren , Feng Yuemei , Qin Zixiu , Wang Zihao , Kangzhuo Baima , Xiao Xiong , Zhao Xing 
Published: July 2024

Abstract
Background
The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect.

Methods
This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects.

Results
In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (βCMEC = 0.068, βUK−Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (βCMEC = 0.027, βUK−Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D.

Conclusions
Our findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well.
Metagenomic next-generation sequencing promotes diagnosis and treatment of Pneumocystis jirovecii pneumonia in non-HIV infected children: a retrospective study
Authors: Zhang Zhenyu , Liu Tingyan , Ming Meixiu , Shen Meili , Zhang Yi , Chen Hanlin , Chen Weiming , Tao Jinhao , Wang Yixue , Liu Jing , Zhou Jihua , Lu Guoping , Yan Gangfeng 
Published: July 2024

Abstract
Background
Metagenomic next-generation sequencing (mNGS) excels in diagnosis of infection pathogens. We aimed to evaluate the performance of mNGS for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV infected children.

Methods
Totally 36 PJP children and 61 non-PJP children admitted to the pediatric intensive care unit from March 2018 to December 2021 were retrospectively enrolled. Clinical features of PJP children were summarized. 1,3-β-D glucan (BDG) test and bronchoalveolar lavage fluid (BALF) mNGS were used for evaluation of PJP diagnostic performance. Antimicrobial management modifications for PJP children after the mNGS results were also reviewed.

Results
Pneumocystis jirovecii was detected in all PJP children by mNGS (36/36), and the sensitivity of mNGS was 100% (95% confidence interval [CI]: 90.26–100%). The sensitivity of BDG was 57.58% (95% CI: 39.22–74.52%). Of the 26 (72.2%) PJP patients with mixed infection, twenty-four (66.7%) were detected by BALF-mNGS. Thirteen patients (36.1%) had their antimicrobial management adjusted according to the mNGS results. Thirty-six PJP children included 17 (47.2%) primary immunodeficiency and 19 (52.8%) secondary immunodeficiency, of whom 19 (52.8%) survived and 17 (47.2%) died. Compared to survival subgroup, non-survival subgroup had a higher rate of primary immunodeficiency (64.7% vs. 31.6%, P = 0.047), younger age (7 months vs. 39 months, P = 0.011), lower body weight (8.0 kg vs. 12.0 kg, P = 0.022), and lower T lymphocyte counts.

Conclusions
The mortality rate of PJP in immunosuppressed children without HIV infection is high and early diagnosis is challenging. BALF-mNGS could help identify PJP and guide clinical management.
An elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with large cell neuroendocrine carcinoma of the lung
Authors: Naka Masamitsu , Inaba Atsushi , Miyasaka Hana , Suzue Keisuke , Ishigaki Junichi , Shibuya Hideki , Hara Kei , Ohishi Nobuya , Sugiyama Yusuke , Shiio Yasushi , Tajiri Ryosuke , Kishida Yukiko , Ishihara Tasuku , Yugeta Akihiro 
Published: July 2024

Abstract
Background
Recent studies have suggested that N-methyl-D-aspartate (NMDA) receptors are involved in the cell proliferation in several tumors. However, there have been no reports demonstrating the expression of NR1 subunit of the NMDA receptor in large cell neuroendocrine carcinoma (LCNEC).

Case presentation
Here, we report the first elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with LCNEC of the lung with NR1 expression. Of note, NR1 subunit expression in the tumor cells of the present case was confirmed by immunohistochemistry (IHC). Radiation therapy and immunotherapies, such as corticosteroids and intravenous immunoglobulin (IVIG), shrank the tumors and improved neurological symptoms in the present case. Additionally, we also confirmed the expression of NR1 in the tumor cells obtained from three other cases with LCNEC of the lung at our hospital by IHC.

Conclusion
Our IHC results indicate that LCNEC generally expresses NR1 subunit and NMDA receptor may be involved in the tumor development and growth.