Objective To investigate the causal relationship between metabolic syndrome and breast cancer by using a bidirectional two-sample Mendelian randomization (MR) approach. Methods Genome-wide association study (GWAS) summary statistics for metabolic syndrome and breast cancer were acquired from the Integrative Epidemiology Unit GWAS database and the GWAS Catalog, with populations encompassing the United States and East Asia. A bidirectional causal design was employed: a forward analysis with metabolic syndrome as the exposure and breast cancer as the outcome, followed by a reverse analysis wherein their roles were interchanged. The inverse-variance weighting (IVW) method was primarily used for effect estimation, supplemented by MR-Egger regression, the weighted median method, the simple mode method, and the weighted mode method. Instrument variable strength was screened using the F-statistic (F>10). Robustness of the results was assessed through heterogeneity tests, horizontal pleiotropy tests, forest plots, and leave-one-out sensitivity analyses. Results The IVW analysis indicated no significant causal relationship between metabolic syndrome and breast cancer (OR=1.00, 95%CI: 0.97-1.03), P>0.05). Sensitivity analyses yielded consistent results, suggesting the good robustness of the study findings. Conclusion This study found no evidence to support a causal relationship, either positive or negative, between metabolic syndrome and breast cancer.

ObjectiveTo delineate imaging findings using an imaging platform and investigate the correlation between MRI characteristics of spinal cord atrophy and clinical diagnosis in children with spinal cord injury (SCI). MethodsImaging data of 150 children with SCI admitted to Beijing Bo'ai Hospital, China Rehabilitation Research Center, from January, 2002 to March, 2024 were collected and imported into the imaging platform. The anteroposterior and transverse diameters of the middle part of the spinal cord at the cross-section with the most severe atrophy were measured, and the relevant indicators of the previous normal spinal cord segment were measured as controls; the radiomic features were extracted. Clinical data of the children including gender, age, cause of injury, sensory level, motor level, spinal cord injury level, injury severity and disease course were collected. ResultsSpinal cord atrophy was identified in 81 cases (54%), among which 78 cases (96%) were American Spinal Injury Association Impairment Scale (AIS) grade A and 3 cases (4%) were AIS grade C. The upper boundary of the spinal cord atrophy site strongly correlated with the injury level, motor level and sensory level (r > 0.8, P < 0.001). ConclusionMore than half of children with SCI may develop secondary spinal cord atrophy, the vast majority of whom suffer from complete spinal cord injury; the upper boundary of spinal cord atrophy is correlated with the injury level.

Objective:To evaluate the clinical significance of morular metaplasia (MM) in fertility-preserving treatment for young patients with endometrial hyperplasia and grade 1 endometrial endometrioid carcinoma.Methods:Clinical data was retrospectively collected from patients diagnosed with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma under 40 years old who underwent progestin-based fertility-sparing treatmentat in Tianjin Medical University General Hospital between January 2018 and November 2022.Patients were divided into the MM group (37 cases) and the non-MM group (63 cases) based on pathological findings. Clinical characteristics, hysteroscopic features, treatment efficacy and fertility outcomes were compared between the two groups. The MM group was further stratified into three subgroups based on the timing of MM occurrence:(1) MM-Bef group ( n=10): MM was present in the initial endometrial curettage or hysteroscopic biopsy pathology before fertility-sparing treatment and disappeared after treatment; (2) MM-Sus group ( n=14): MM persisted consistently before and after therapy;(3) MM-Aft group ( n=13): MM was absent before therapy but appeared after treatment. The risk factors which had impact on the treatment outcomes of the patients were analyzed using univariate and multivariate Cox regression analysis. Results:The rate of polycystic ovary syndrome were higher in the MM group than the non-MM group [51% (19/37) vs 27% (17/63), P=0.014]. The complete response (CR) rate was significantly lower in the MM group than in the non-MM group [73% (27/37) vs 95% (60/63), P=0.006], and the median time to CR was significantly longer in the MM group (6.0 vs 5.0 months, P=0.005).Multivariate analysis identified that MM-Sus ( HR=0.355, 95% CI:0.174-0.723; P=0.004) and MM-Aft ( HR=0.314, 95% CI:0.145-0.681; P=0.003) were independent risk factors for delayed CR in fertility-sparing treatment. The patients in the MM group and non-MM group underwent hysteroscopic biopsy for 76 and 131 times. "Gravel-like change" was a more frequent hysteroscopic manifestation in the MM group than that in the non-MM group [18% (14/76) vs 2% (2/131), P<0.001]. Conclusions:Patients in the MM group have poorer treatment outcomes than patients in the non-MM group. MM-Sus and MM-Aft are risk factors for fertility-preserving treatment in young patients with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma. "Gravel-like change" is the characteristic hysteroscopic manifestations of MM.

Objective:To evaluate the changes of right atrial volume and function in patients with atrial septal defect（ASD）by four-dimensional ultrasound automatic quantitative technology，and to explore the predictive value and clinical significance for ASD with pulmonary arterial hypertension（PAH）.Methods:Sixty-one patients with ASD and 32 healthy volunteers（control group）who attended Central China Fuwai Hospital of Zhengzhou University，Fuwai Central China Cardiovascular Hospital from March 2023 to April 2024 were prospectively collected，and classified ASD patients into ASD without PAH group（non-PAH group， n=30）and ASD with PAH group（PAH group， n=31）according to whether or not they had PAH，and obtained right atrial reserve，ductal，systolic longitudinal and circumferential strains（RASr，RAScd，RASct，RASr-c，RAScd-c，RASct-c），right atrial minimal，maximal，and presystolic volumes（RAVmin，RAVmax，and RAVpreA），and calculated right atrial total，passive，and active ejection fraction（RAEF，RAPEF，RAAEF）. The ultrasound parameters and clinical data were compared between groups. Pearson's linear correlation was applied to analyse the correlation between the parameters（RASr，RAA，PASP，NT-proBNP）and mean pulmonary artery pressure（mPAP）. ROC curves were plotted and the area under the curve（AUC）was calculated to analyse the value of the four-dimensional strain parameters of the right atrium in independently and jointly predicting the combination of ASD with PAH. Results:①Compared with the control group，RAVmin，RAVmax，and RAVpreA were elevated in the non-PAH and PAH groups，and the absolute values of RAPEF and RAScd were decreased，whereas the absolute values of RAEF，RAAEF，RASr，RASct，RASr-c，and RASct-c were elevated in the non-PAH group，and decreased in the PAH group（all P<0.05）；compared with the non-PAH group，only RAVmin，RAVmax，and RAVpreA were elevated in the PAH group，and the rest of the above parameters were reduced，with statistically significant differences（all P<0.05）. ②The right atrial four-dimensional strain parameter RASr had the highest predictive value for ASD combined with PAH，with an AUC of 0.876，a specificity of 83.3%，and a sensitivity of 77.4%，respectively. ③RASr was negatively correlated with mPAP（ r=-0.591， P<0.001）and RAA，PASP and NT-proBNP were positively correlated with mPAP（ r=0.539，0.697，0.616；all P<0.001）. ④The predictive value of RASr combined with RAA，PASP，and NT-proBNP was superior for ASD combined with PAH（AUC=0.933）. Conclusions:Four-dimensional ultrasound automatic quantitative technology can effectively evaluate the changes of right atrial volume and function in patients with ASD. ASD patients without PAH have increased right atrial reserve and pump function，and decreased right atrial pipeline function. The right atrial function of ASD patients with PAH is significantly reduced，and the impairment is more severe. Among the right atrial four-dimensional strain parameters，RASr has the highest efficacy in predicting ASD combined with PAH. Moreover，the combination of RASr with RAA，PASP，and NT-proBNP has the best predictive efficacy for ASD combined with PAH，which holds significant clinical value.

Objective:To evaluate the clinical significance of morular metaplasia (MM) in fertility-preserving treatment for young patients with endometrial hyperplasia and grade 1 endometrial endometrioid carcinoma.Methods:Clinical data was retrospectively collected from patients diagnosed with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma under 40 years old who underwent progestin-based fertility-sparing treatmentat in Tianjin Medical University General Hospital between January 2018 and November 2022.Patients were divided into the MM group (37 cases) and the non-MM group (63 cases) based on pathological findings. Clinical characteristics, hysteroscopic features, treatment efficacy and fertility outcomes were compared between the two groups. The MM group was further stratified into three subgroups based on the timing of MM occurrence:(1) MM-Bef group ( n=10): MM was present in the initial endometrial curettage or hysteroscopic biopsy pathology before fertility-sparing treatment and disappeared after treatment; (2) MM-Sus group ( n=14): MM persisted consistently before and after therapy;(3) MM-Aft group ( n=13): MM was absent before therapy but appeared after treatment. The risk factors which had impact on the treatment outcomes of the patients were analyzed using univariate and multivariate Cox regression analysis. Results:The rate of polycystic ovary syndrome were higher in the MM group than the non-MM group [51% (19/37) vs 27% (17/63), P=0.014]. The complete response (CR) rate was significantly lower in the MM group than in the non-MM group [73% (27/37) vs 95% (60/63), P=0.006], and the median time to CR was significantly longer in the MM group (6.0 vs 5.0 months, P=0.005).Multivariate analysis identified that MM-Sus ( HR=0.355, 95% CI:0.174-0.723; P=0.004) and MM-Aft ( HR=0.314, 95% CI:0.145-0.681; P=0.003) were independent risk factors for delayed CR in fertility-sparing treatment. The patients in the MM group and non-MM group underwent hysteroscopic biopsy for 76 and 131 times. "Gravel-like change" was a more frequent hysteroscopic manifestation in the MM group than that in the non-MM group [18% (14/76) vs 2% (2/131), P<0.001]. Conclusions:Patients in the MM group have poorer treatment outcomes than patients in the non-MM group. MM-Sus and MM-Aft are risk factors for fertility-preserving treatment in young patients with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma. "Gravel-like change" is the characteristic hysteroscopic manifestations of MM.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

The PIF7 gene is a member of the bHLH family, playing a pivotal role in plant germination. However, its roles in tea plants (Camellia sinensis) remain largely unexplored. In this study, we cloned the phytochrome-interacting factor gene CsPIF7 to elucidate its role in the germination of tea plants. Subcellular localization analysis demonstrated that CsPIF7 was localized in the nucleus. Yeast one-hybrid and dual-luciferase reporter assays demonstrated that CsPIF7 directly bound to a specific region (7-321 bp) of the CsEXP promoter, thereby repressing the expression of CsEXP. These findings suggest that CsPIF7 may modulate the germination of tea plants by inhibiting the expression of CsEXP. Quantitative real-time PCR results showed that both CsPIF7 and CsEXP exhibited high expression levels in tea buds, with different expression patterns in response to abscisic acid (ABA) treatment. Furthermore, both CsPIF7 and CsEXP were upregulated under cold stress at 4 ℃, indicating their involvement in the cold response of tea plants. Taken together, these results suggest that CsPIF7 regulates CsEXP expression in an ABA-dependent manner, thereby influencing the germination of tea plants. This study provides both theoretical and experimental insights into the molecular mechanisms governing the germination of tea plants, laying the groundwork for further exploring the role of PIF7 in plant development and stress responses.
Camellia sinensis/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Abscisic Acid/pharmacology* ; Germination/genetics* ; Basic Helix-Loop-Helix Transcription Factors/metabolism* ; Promoter Regions, Genetic ; Cold Temperature

Objective:To evaluate the changes of right atrial volume and function in patients with atrial septal defect（ASD）by four-dimensional ultrasound automatic quantitative technology，and to explore the predictive value and clinical significance for ASD with pulmonary arterial hypertension（PAH）.Methods:Sixty-one patients with ASD and 32 healthy volunteers（control group）who attended Central China Fuwai Hospital of Zhengzhou University，Fuwai Central China Cardiovascular Hospital from March 2023 to April 2024 were prospectively collected，and classified ASD patients into ASD without PAH group（non-PAH group， n=30）and ASD with PAH group（PAH group， n=31）according to whether or not they had PAH，and obtained right atrial reserve，ductal，systolic longitudinal and circumferential strains（RASr，RAScd，RASct，RASr-c，RAScd-c，RASct-c），right atrial minimal，maximal，and presystolic volumes（RAVmin，RAVmax，and RAVpreA），and calculated right atrial total，passive，and active ejection fraction（RAEF，RAPEF，RAAEF）. The ultrasound parameters and clinical data were compared between groups. Pearson's linear correlation was applied to analyse the correlation between the parameters（RASr，RAA，PASP，NT-proBNP）and mean pulmonary artery pressure（mPAP）. ROC curves were plotted and the area under the curve（AUC）was calculated to analyse the value of the four-dimensional strain parameters of the right atrium in independently and jointly predicting the combination of ASD with PAH. Results:①Compared with the control group，RAVmin，RAVmax，and RAVpreA were elevated in the non-PAH and PAH groups，and the absolute values of RAPEF and RAScd were decreased，whereas the absolute values of RAEF，RAAEF，RASr，RASct，RASr-c，and RASct-c were elevated in the non-PAH group，and decreased in the PAH group（all P<0.05）；compared with the non-PAH group，only RAVmin，RAVmax，and RAVpreA were elevated in the PAH group，and the rest of the above parameters were reduced，with statistically significant differences（all P<0.05）. ②The right atrial four-dimensional strain parameter RASr had the highest predictive value for ASD combined with PAH，with an AUC of 0.876，a specificity of 83.3%，and a sensitivity of 77.4%，respectively. ③RASr was negatively correlated with mPAP（ r=-0.591， P<0.001）and RAA，PASP and NT-proBNP were positively correlated with mPAP（ r=0.539，0.697，0.616；all P<0.001）. ④The predictive value of RASr combined with RAA，PASP，and NT-proBNP was superior for ASD combined with PAH（AUC=0.933）. Conclusions:Four-dimensional ultrasound automatic quantitative technology can effectively evaluate the changes of right atrial volume and function in patients with ASD. ASD patients without PAH have increased right atrial reserve and pump function，and decreased right atrial pipeline function. The right atrial function of ASD patients with PAH is significantly reduced，and the impairment is more severe. Among the right atrial four-dimensional strain parameters，RASr has the highest efficacy in predicting ASD combined with PAH. Moreover，the combination of RASr with RAA，PASP，and NT-proBNP has the best predictive efficacy for ASD combined with PAH，which holds significant clinical value.

Objective:To understand the current situation of care needs for disabled elderly people, analyze the impact of the family environment and community services on the care needs and care pathways of older people with disabilities and to formulate effective interventions.Methods:A cross-sectional survey was conducted from August 2022 to March 2023 in five tertiary-level hospitals in Tangshan city. The survey included 332 elderly people who were disabled before hospitalization and their primary caregivers, who were selected using a convenience sampling method. The survey investigated their general information, degree of disability, family members′ support, children′s filial piety and old age ethical level, family relationships, and the care needs of the elderly people who were disabled. SPSS 22.0 was used for one-way and correlation analyses as well as multiple linear regression analyses, and AMOS 22.0 was used for the development of structural equations for path analysis.Results:Among 332 disabled elderly individuals, there were 166 males and 166 females each. The care needs score for elderly people with disabilities was 101.54 ± 16.38. The care needs of this population can be influenced by several factors, including the level of disability, number of chronic conditions, presence of chronic pain, filial piety and old age ethical level of caregivers, family relationships, and the availability of care services in the community or village. These factors had direct effects of 0.468, 0.155, -0.083, -0.350, -0.094, and 0.104, respectively.Chronic diseases and chronic pain indirectly affected the demand for care through the degree of incapacity (with respective indirect effect values of 0.065 and 0.049). Additionally, the demand for care was indirectly influenced by the level of filial piety and ethics of the caregiver through the degree of incapacity and the family relationships (an indirect effect value of -0.162).Conclusions:The care needs of the disabled elderly are high, and the personal physiology, family environment and community support of the disabled elderly will directly or indirectly affect their care needs. Therefore, many factors should be considered comprehensively considered to improve the quality of care of the disabled elderly.

Objective:To Explore the diagnosis, treatment and prognosis of FH-deficient renal cell carcinoma (FH-deficient RCC) with tumor thrombus, and share surgical experience.Methods:From August 2019 to October 2022, 6 cases of FH-deficient RCC with tumor thrombus were diagnosed and treated in our center, including 4 males and 2 females. The patients were aged 22 to 57 years, with 2 cases younger than 40 years, icluding 5 cases on the left and 1 case on the right. The median maximum diameter of the tumor is 8 (4.8, 14.0) cm. Operations were performed after complete examination (enhanced CT and other related examinations). One case underwent open surgery and palliative resection of the left kidney was performed because of severe adhesion of the inferior vena cava. Among the remaining 5 cases, 1 case underwent retroperitoneal laparoscopic right radical nephrectomy with inferior vena cava thrombectomy, 1 case underwent transabdominal laparoscopic left radical nephrectomy with inferior vena cava thrombectomy, and 3 cases underwent robot assisted laparoscopic left radical nephrectomy with inferior vena cava thrombectomy.Results:The median surgical time was 293 (185, 366) min, with blockage of the vena cava for 13 min and 28 min in 2 of 6 cases, respectively. The pathological report of renal tumor and tumor thrombus was FH-deficient renal carcinoma. The pathological features were as follows: the gross section of the specimen was gray yellow solid, often accompanied by necrosis, and the cystic cavity could be seen locally. Microscopically, the tumor extensively involved the renal parenchyma, with papillary, cribriform and tubular cystic structures. Immunohistochemistry showed FH (-), 2SC (+ ). The median postoperative hospital stay was 8 (4, 15) days. The median follow-up time was 13 (4, 27) months. One patient undergoing palliative resection of the left kidney underwent targeted therapy and radiotherapy after surgery (died 15 months after surgery due to gastrointestinal perforation). During the follow-up process, 4 cases experienced metastasis and received systematic treatment, with 1 death 27 months after surgery. Uterine leiomyomas were found in the remaining 1 case during follow-up.Conclusions:FH-deficient RCC with tumor thrombus is very rare. This disease is highly invasive, difficult to be diagnosed preoperatively and poor clinically prognostic. Operation combined with systemic therapy is an effective way to treat FH-deficient RCC with tumor thrombus.