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Abstract Background Limb-girdle muscular dystrophies (LGMDs) are a group of heterogeneous inherited diseases predominantly characterized by limb-girdle muscle weakness and dystrophic changes on histological analysis. The frequency of LGMD subtypes varies among regions in China and ethnic populations worldwide. Here, we analyzed the prevalence of LGMD subtypes, their corresponding clinical manifestations, and molecular data in a cohort of LGMD patients in Southeast China. Methods A total of 81 consecutive patients with clinically suspected LGMDs from 62 unrelated families across Southeast China were recruited for targeted next-generation sequencing and whole-exome sequencing from July 2017 to February 2020. Results Among 50 patients (41 families) with LGMDs, the most common subtypes were LGMD-R2/LGMD2B (36.6%) and LGMD-R1/LGMD2A (29.3%). Dystroglycanopathies (including LGMD-R9/LGMD2I, LGMD-R11/LGMD2K, LGMD-R14/LGMD2N and LGMD-R20/LGMD2U) were the most common childhood-onset subtypes and were found in 12.2% of the families. A total of 14.6% of the families had the LGMD-R7/LGMD2G subtype, and the mutation c.26_33dupAGGTGTCG in TCAP was the most frequent (83.3%). The only patient with the rare subtype LGMD-R18/LGMD2S had TRAPPC11 mutations; had a later onset than those previously reported, and presented with proximal‒distal muscle weakness, walking aid dependency, fatty liver disease and diabetes at 33 years of age. A total of 22.0% of the patients had cardiac abnormalities, and one patient with LMNA-related muscular dystrophy/LGMD1B experienced sudden cardiac death at 37 years of age. A total of 15.4% of the patients had restrictive respiratory insufficiency. Muscle imaging in patients with LGMD-R1/LGMD2A and LGMD-R2/LGMD2B showed subtle differences, including more severe fatty infiltration of the posterior thigh muscles in those with LGMD-R1/LGMD2A and edema in the lower leg muscles in those with LGMD-R2/LGMD2B. Conclusion We determined the prevalence of different LGMD subtypes in Southeast China, described the detailed clinical manifestations and distinct muscle MRI patterns of these LGMD subtypes and reported the frequent mutations and the cardiorespiratory involvement frequency in our cohort, all of which might facilitate the differential diagnosis of LGMDs, allowing more timely treatment and guiding future clinical trials.

Abstract Background Caregivers of elderly patients with multiple chronic conditions have heavy caregiver burden and poor sleep quality, which has an important impact on both caregivers and patients. This study aimed to examine among rural caregivers of elderly patients who have multiple chronic conditions in China, whether self-efficacy and well-being mediate the link between caregiver burden and sleep quality. Methods The study recruited 325 caregivers of elderly patients having multiple chronic conditions in rural China. Several measures including the Caregiver Burden Inventory (CBI), Athens Insomnia Scale (AIS), General Self-Efficacy Scale (GSES) and Index of Well-Being (IWB) were utilized to collect data. Structural equation modeling was employed to study the relationships among caregiver burden, sleep quality, self-efficacy, as well as well-being. Results Significant correlations were found between the measured variables (each p

The CoCrFeNiMn high-entropy alloy and TiB2p/CoCrFeNiMn high-entropy composite (HEC) were manufactured by Selective laser melting. For the CoCrFeNiMn, a coarse epitaxial columnar microstructure with strong crystallographic textures was generated. While in the TiB2p/CoCrFeNiMn, TiB2 particles are distributed in the significantly refined dendrites and nearly equiaxial grains, and phase transformation occurs to form σ phase. TiB2 and σ phase construct a strong interface relationship with the matrix. TiB2p/CoCrFeNiMn HEC has extremely high microhardness (329 ± 2 HV) and excellent wear resistance (coefficients of friction 0.31 ± 0.02). The wear mechanism of the HEC was studied refer to the microstructure, composition and hardness.IMPACT STATEMENTTiB2-reinforced CoCrFeNiMn-based high-entropy composite is successfully fabricated by Selective laser melting, which exhibits exceptional hardness and the best wear resistance.

Abstract Patients with chronic obstructive pulmonary disease (COPD) who exhibit elevated blood eosinophil levels often experience worsened lung function and more severe emphysema. This implies the potential involvement of eosinophils in the development of emphysema. However, the precise mechanisms underlying the development of eosinophil-mediated emphysema remain unclear. In this study, we employed single-cell RNA sequencing to identify eosinophil subgroups in mouse models of asthma and emphysema, followed by functional analyses of these subgroups. Assessment of accumulated eosinophils unveiled distinct transcriptomes in the lungs of mice with elastase-induced emphysema and ovalbumin-induced asthma. Depletion of eosinophils through the use of anti-interleukin-5 antibodies ameliorated elastase-induced emphysema. A particularly noteworthy discovery is that eosinophil-derived cathepsin L contributed to the degradation of the extracellular matrix, thereby leading to emphysema in pulmonary tissue. Inhibition of cathepsin L resulted in a reduction of elastase-induced emphysema in a mouse model. Importantly, eosinophil levels correlated positively with serum cathepsin L levels, which were higher in emphysema patients than those without emphysema. Expression of cathepsin L in eosinophils demonstrated a direct association with lung emphysema in COPD patients. Collectively, these findings underscore the significant role of eosinophil-derived cathepsin L in extracellular matrix degradation and remodeling, and its relevance to emphysema in COPD patients. Consequently, targeting eosinophil-derived cathepsin L could potentially offer a therapeutic avenue for emphysema patients. Further investigations are warranted to explore therapeutic strategies targeting cathepsin L in emphysema patients.

Introduction: Robot-assisted radical cystectomy (RARC) has gained momentum in the management of muscle invasive bladder cancer (MIBC). Predictors of RARC outcomes are not thoroughly studied. We aim to investigate the implications of preoperative hydronephrosis on oncological outcomes. Patients and Methods: This study analysed data from the Asian RARC consortium, a multicentre registry involving nine Asian centres. Cases were divided into two groups according to the presence or absence of pre-operative hydronephrosis. Background characteristics, operative details, perioperative outcomes, and oncological results were reviewed. Outcomes were (1) survival outcomes, including 10-year disease-free survival (DFS) and overall survival (OS), and (2) perioperative and pathological results. Multivariate regression analyses were performed on survival outcomes. Results: From 2007 to 2020, 536 non-metastatic MIBC patients receiving RARC were analysed. 429 had no hydronephrosis (80.0%), and 107 (20.0%) had hydronephrosis. Hydronephrosis was found to be predictive of inferior DFS (HR = 1.701, p = 0.003, 95% CI = 1.196–2.418) and OS (HR = 1.834, p = 0.008, 95% CI = 1.173–2.866). Subgroup analysis demonstrated differences in the T2-or-above subgroup (HR = 1.65; p = 0.004 in DFS and HR = 1.888; p = 0.008 in OS) and the T3-or-above subgroup (HR = 1.757; p = 0.017 in DFS and HR = 1.807; p = 0.034 in OS). Conclusions: The presence of preoperative hydronephrosis among MIBC patients carries additional prognostic implications on top of tumour staging. Its importance in case selection needs to be highlighted.

There is an urgent need for a thorough assessment of forest landscape fragmentation to inform forest protection and restoration, and reforestation policies. However, there is currently a lack of an effective comprehensive index for forest landscape fragmentation, and detailed knowledge of the forest landscape fragmentation dynamics remains insufficient. Here, taking Putian City of Fujian Province in Southeastern China as a case, we employed a forest fragmentation comprehensive index (FFCI) to capture key features of forest landscape fragmentation, such as patch size, number, and distribution. Then, bivariate spatial autocorrelation analysis was employed to identify the spatial associations between the static forest landscape fragmentation (FFCI) and the dynamic forest landscape fragmentation (ΔFFCI), and the spatial coupling modes among the three individual components of FFCI (mean patch area, MPA; aggregation index, AI; patch density, PD) were identified to explore the detail process of forest landscape fragmentation. Finally, the random forest model was applied to observe the impact factors of forest landscape fragmentation dynamics. The findings showed that forest landscapes with different degrees of fragmentation exhibited more noticeable changes at both ends (i.e., either high or lower-level fragmentation), with the intermediate level remaining consistent from 2000 to 2020. Around 18.3% of forest landscapes experienced a decrease in fragmentation, particularly in the northern part of the study area, while approximately 81.7% of forest landscapes exhibited an increasing trend in fragmentation. The bivariate spatial autocorrelation analysis indicated that the proportion of Low–High-type grids was the highest at 17.3%, followed by the High–High type at 7.0%. We also identified eight forest landscape fragmentation modes, which indicate the most significant forest landscape fragmentation pattern is a decrease in MPA and an increase in PD. Moreover, the anthropogenic factors (e.g., population density and night light intensity) were found to dominate the FFCI dynamics during 2000–2020. This study offers an efficient research paradigm for the dynamics of forest landscape fragmentation. The outcomes are conducive to an in-depth comprehension of the detailed dynamic information of forest landscape fragmentation, and supply a scientific foundation for enhancing the overall ecological service function of the forest.

Objectives To explore the impact of the triglyceride-glucose (TyG) index on the severity of coronary stenosis and the risk of in-hospital mortality in patients with acute ST segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).Design A multicentre retrospective cohort study.Setting Patients with STEMI undergoing PCI from three centres in China from 2015 to 2019.Participants A total of 1491 individuals presenting with STEMI were enrolled.Primary outcome measure The degree of coronary stenosis was quantified by the Gensini score (GS). The association between the TyG index and the severity of coronary stenosis was explored by using a logistic regression analysis. Cox proportional hazards regression analyses were used to investigate the associations between the variables and in-hospital mortality.Results We found a significant correlation between the TyG index and the degree of coronary stenosis in the present study. The TyG index was an independent risk factor for the severity of coronary stenosis (OR 2.003, p

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), is a benign histiocytosis with hyperreactive proliferation of the mononuclear phagocyte system caused by immune function abnormalities, which often occurs under the background of genetic mutations, inflammation, infection or tumors. Because the research on malignancy-associated HLH (M-HLH) is focused on hematological malignancies, reports on HLH secondary to solid tumors are rare. In this case, we report a 14-year-old girl who developed HLH during treatment for intracranial multifocal germinoma, and the disease was controlled after hormone combined with etoposide(VP-16) and other related treatments. To our knowledge, there have been no documented cases of HLH caused by intracranial multifocal germinoma.

As the physical and mental development of the young is not only influenced by the parent-child relationship (PR) and the student's academic performance, but also moderated by trait coping styles (TCS), the changes between these three during the online learning period in an epidemic need to be reconsidered. This study aims to explore the factors affecting online learning satisfaction (OLS) among students and their interaction with parent-child relationship and trait coping style. A web-based questionnaire was employed, encompassing general information, the Trait Coping Style Questionnaire (TCSQ), and queries related to OLS. A total of 1,287 valid questionnaires were collected, with 593 from junior high school students, 197 from high school students, and 497 from university students. Our findings indicate that parent-child relationship (PR), positive coping style (PCS), and learning status (LS) showed a positive correlation with OLS (r=0.110, P

The deployment of energy storage systems can play a role in peak and frequency regulation, solve the issue of limited flexibility in cleaner power systems in China, and ensure the stability and safety of the power grid. This paper presents a comprehensive environmental impact analysis of a lithium iron phosphate (LFP) battery system for the storage and delivery of 1 kW-hour of electricity. Quantities of copper, graphite, aluminum, lithium iron phosphate, and electricity consumption are set as uncertainty and sensitivity parameters with a variation of [90%, 110%]. The results show that global warming potential is 9.08E+01 kg CO2 eq. and fossil resource use is 1.21E+03 MJ, with uncertainty ranges of [8.54E+01, 9.23E+01] and [1.15E+03, 1.23E+03], respectively. Electricity consumption during the manufacture and installation process is the greatest contributor to climate change (CO2 eq. emissions), accounting for 39.71% and largely owing to non-renewable sources, followed by cathode materials at 27.85% and anode materials at 18.36%. The disposal and recycling process offers emission reductions but requires an additional 1.17% use of fossil resources. Sobol T indices for the quantity of electricity are the highest for acidification, climate change, fossil resource use, and ionizing radiation. By considering the pathway of China’s electricity mix from 2020 to 2050 under the Paris Agreement’s 2° target, the potential for environmental emission reduction in the system is evaluated. The results show that the greener electricity mix could lead to a 24.59% reduction in acidification impact, a 35.74% reduction in climate change impact, a 33.24% reduction in fossil resource use, and a 44.13% reduction in ionizing radiation impact. This study offers a comprehensive view of the environmental impact reductions associated with the lithium iron phosphate battery and its industry.

Leptospirosis is a zoonosis that is related to potential respiratory, renal, neurological, and cardiovascular failure. At present, antibiotics are the recommended treatment, but due to the underlying cause of the disease, they may induce the Jarisch-Herxheimer reaction (JHR) within 24 hours. At the same time, we speculate that JHR may aggravate the natural course of leptospirosis. Considering that there are few available reports on this event, we will share a case of pulmonary hemorrhagic leptospirosis, where antibiotic treatment is suspected to have triggered the JHR. This report is expected to improve clinical attention to the relationship between leptospirosis and JHR.

Resistance to chemotherapy is the main reason for treatment failure and poor prognosis in patients with triple-negative breast cancer (TNBC). Although the association of RNA N6-methyladenosine (m6A) modifications with therapy resistance is noticed, its role in the development of therapeutic resistance in TNBC is not well documented. This study aimed to investigate the potential mechanisms underlying reactive oxygen species (ROS) regulation in doxorubicin (DOX)-resistant TNBC. Here, we found that DOX-resistant TNBC cells displayed low ROS levels because of increased expression of superoxide dismutase (SOD2), thus maintaining cancer stem cells (CSCs) characteristics and DOX resistance. FOXO1 is a master regulator that reduces cellular ROS in DOX-resistant TNBC cells, and knockdown of FOXO1 significantly increased ROS levels by inhibiting SOD2 expression. Moreover, the m6A demethylase ALKBH5 promoted m6A demethylation of FOXO1 mRNA and increased FOXO1 mRNA stability in DOX-resistant TNBC cells. The analysis of clinical samples revealed that the increased expression levels of ALKBH5, FOXO1, and SOD2 were significantly positively correlated with chemoresistance and poor prognosis in patients with TNBC. To our knowledge, this is the first study to highlight that ALKBH5-mediated FOXO1 mRNA demethylation contributes to CSCs characteristics and DOX resistance in TNBC cells. Furthermore, pharmacological targeting of FOXO1 profoundly restored the response of DOX-resistant TNBC cells, both in vitro and in vivo. In conclusion, we demonstrated a critical function of ALKBH5-mediated m6A demethylation of FOXO1 mRNA in restoring redox balance, which in turn promoting CSCs characteristics and DOX resistance in TNBC, and suggested that targeting the ALKBH5/FOXO1 axis has therapeutic potential for patients with TNBC refractory to chemotherapy.

PurposeThis study comprises an investigation of the role of meteorin-like (Metrnl) in an experimental model of diabetic kidney disease (DKD).MethodsTwenty-four db/db mice were randomly assigned to one of the following groups: DKD, DKD + Metrnl-/-, and DKD + Metrnl+/+. Plasma Metrnl concentrations were measured using ELISA. Kidney tissues were examined via western blotting, qRT-PCR, and immunohistochemistry to determine the expression levels of inflammatory factors. Electron microscopy was employed to observe stained kidney sections.ResultsCompared with the NC group, FBG, BW, and UACR were elevated in the DKD and Metrnl-/- groups, with severe renal pathological injury, decreased serum Metrnl concentration, decreased renal Metrnl expression, and increased expression levels of TNF-α, TGF-β1, TGF-R1, pSmad2, pSmad3, and α-SMA. In contrast, the Metrnl+/+ group showed decreased FBG and UACR, BUN, TC and TG, increased HDL-C and serum Metrnl concentration, increased renal Metrnl expression, and decreased expression of TNF-α, TGF-β1, TGF-R1, pSmad2, pSmad3, and α-SMA, compared to the DKD and Metrnl-/- groups. A Pearson bivariate correlation analysis revealed a negative correlation between UACR and Metrnl, and a positive correlation between UACR and TGF-β1.ConclusionUpregulation of renal Metrnl expression can improve renal injury by downregulating the expression of molecules in the TGF-β1/Smads signaling pathway in the renal tissues of type 2 diabetic mice; and by reducing the production of fibrotic molecules such as α-SMA.

Objectives: The concept of possible sarcopenia (PS) was recently introduced to enable timely intervention in settings without the technologies required to make a full diagnosis of sarcopenia. This study aimed to investigate the association between PS and all-cause mortality in patients with solid cancer. Design: Retrospective observational study. Setting and participants: 13,736 patients with 16 types of solid cancer who were ≥18 years old. Measurements: The presence of both a low calf circumference (men

In this paper, we use the krill swarm optimization algorithm to optimize the optimization-seeking ability of the projection-seeking analysis model and construct the IKH-PP model. Evaluation indexes of ideological and political education strategies are built from seven dimensions, such as moral quality and political performance, and the index values are standardized using the extreme value normalization method. Create and enhance the projection indicator function, sort based on the projection value size, and determine the advantages and disadvantages of various samples. Taking psychology as the perspective, efforts were made to explore a collaborative educational path for psychological counseling and ideological education for medical students using the psychological perspective. The results showed that 50% of the 600 medical students at University Z chose “realization of ideal pursuit,” and they were generally more positive and progressive. However, only 48 of them expressed that they were very concerned about current affairs and that their political awareness still needed to be improved. Before and after the collaborative psychological counseling and political education interventions, there were statistically significant differences between Group I and Group II in the G3/F3 dimension (P=0.047, 0.008) and the G11/F11 dimension (P=0.022, 0.034), which were statistically significant or not. There were statistically significant differences in the overall access to Civics and all dimensions of Civics among medical students of different genders (P

Abstract Understanding how urbanization affects compound hot extremes (CHEs) is important for the sustainable development in urban agglomeration under global warming. In this study, we investigate the changes of CHEs in summer over the Beijing‐Tianjin‐Hebei region (BTH), Yangtze River Delta (YRD) and Pearl River Delta (PRD) in China, and assess the effects of urbanization on these changes. We find that the frequency and intensity of CHEs in summer show significantly increasing trends in these agglomerations in the recent five decades, particularly in megacities such as Beijing, Shanghai, Guangzhou and Tianjin. The urbanization contributions to CHEs in the YRD and PRD were estimated to 36 ∼ 58%, while relatively small in the BTH, ranging 16 ∼ 29%. They were bonded to the unban size, expansion speed and local climate. In addition to global warming and urbanization, the strengthening continental high and enhancing Western Pacific Subtropical High and its westward displacement were favor to the increased CHEs.

In the context of the new era, reforming “curriculum and political thinking” in the medical specialty of colleges and universities is a key path to realizing the fundamental task of cultivating moral integrity. The study adopts a blended teaching mode, combines online and offline resources, and focuses on analyzing the learning behavior of medical students. The correlation between learning behavior and performance was analyzed by DH-Kmeans cluster analysis algorithm and Pearson’s correlation coefficient. The experimental data came from the online learning behaviors of students in the 2022-2023 academic year of T Medical College, and a total of 2426 data were collected. The results showed that learning behaviors were highly correlated with grades, especially the number of tasks completed, course video progress, and the number of chapter studies. In addition, the comparative analysis of teaching experiments showed that students in the experimental class were better than the control class regarding ideological values, learning attitudes and grades. The conclusion shows that the blended teaching mode effectively improves medical students’ learning effect and the quality of ideological education.

Aims: Yin Yang 1 (YY1) is a multifunctional transcription factor that plays an important role in tumour development and progression, while its clinical significance in diffuse large B-cell lymphoma (DLBCL) remains largely unexplored. This study aimed to investigate the expression and clinical implications of YY1 in DLBCL. Methods: YY1 expression in 198 cases of DLBCL was determined using immunohistochemistry. The correlation between YY1 expression and clinicopathological parameters as well as the overall survival (OS) and progression-free survival (PFS) of patients was analyzed. Results: YY1 protein expression was observed in 121 out of 198 (61.1 %) DLBCL cases. YY1 expression was significantly more frequent in cases of the GCB subgroup than in the non-GCB subgroup (P = 0.005). YY1 was positively correlated with the expression of MUM1, BCL6, pAKT and MYC/BCL2 but was negatively associated with the expression of CXCR4. No significant relationships were identified between YY1 and clinical characteristics, including age, sex, stage, localization, and B symptoms. Univariate analysis showed that the OS (P = 0.003) and PFS (P = 0.005) of patients in the YY1-negative group were significantly worse than those in the YY1-positive group. Multivariate analysis indicated that negative YY1 was a risk factor for inferior OS (P