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 investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

Shengyutang is a famous classical formula of tonic， which is made from Siwutang with Ginseng Radix et Rhizoma and Astragali Radix. It is included in the Catalogue of Ancient Famous Classical Formulas（The First Batch）. Based on the Principles of Key Information Research of Ancient Famous Classical Formulas， this paper used bibliometrics to sort out and research the key information of Shengyutang in the aspects of history， composition， origin and processing， dosage， decocting method， efficacy and indications. After research， it has been found that this formula was first recorded in Lanshi Micang written by LI Dongyuan during the Jin dynasty， composed of Rehmanniae Radix， Rehmanniae Radix Praeparata， Chuanxiong Rhizoma， Ginseng Radix et Rhizoma， Astragali Radix and Angelicae Sinensis taproot. The name of the formula passed down through generations was relatively unified， with clear origins and veins. In later generations， this formula was the mainstream， and adjustments were made to the dosage and composition according to the indication. In the formula， Astragalus membranaceus var. mongholicus was selected as the origin of Astragali Radix， and the origins of other medicinal materials were consistent with the 2020 edition of Chinese Pharmacopoeia. Except for Rehmanniae Radix Praeparata， the other medicinal materials were made from raw products， and the dosage form was boiled powder. According to the measurement standard in the Jin dynasty， the recommended usage and dosage were 1.24 g of Rehmanniae Radix， Rehmanniae Radix Praeparata， Chuanxiong Rhizoma， Ginseng Radix et Rhizoma each， 2.07 g of Astragali Radix and Angelicae Sinensis taproot each， crushed into coarse particles that pass through the 4 mesh sieve but can't pass through the 10 mesh sieve， added 1 200 mL of water and boiled to 300 mL， and removed the residue. Shengyutang has the functions of tonifying Qi and blood， and blood intake， treating various sores， and restlessness and insomnia caused by excessive blood flow. In ancient times， this formula was widely used in the treatment of surgical sores， gynecological diseases， deficiency syndrome， etc. In modern clinical practice， it is mostly used to treat gynecological， neurological， musculoskeletal， hematological diseases caused by Qi and blood deficiency. In this paper， the key information of Shengyutang was researched by reviewing relevant ancient literature， in order to provide reference for the modern application and development of this formula.

Objective: To explore the association between mental health and muscle strength among Chinese adolescents aged 13- 18, providing a theoretical foundation and intervention strategies for mental health promotion. Methods: Data were obtained from the 2019 Chinese National Survey on Students Constitution and Health, including 98 631 Chinese adolescents aged 13- 18. Psychological distress was assessed by using the Kessler Psychological Distress Scale (K10), and mental well being was measured with the Warwick-Edinburgh Mental Well being Scale (WEMWBS). Based on the gender and age specific Z scores of various test items [grip strength, standing long jump, pull ups (for males), and sit ups (for females)], muscle strength index (MSI) was constructed to evaluate the comprehensive level of muscle strength in adolescents. According to the Dual factor Model (DFM) of mental health, participants were categorized into four groups:troubled, symptomatic but content, vulnerable, and complete mental health. Gender differences were analyzed by using Chi-square tests, trends were tested with Cochran-Armitage tests, and multinomial Logistic regression models were applied to assess associations between muscle strength and mental health among adolescents. Results: In 2019, 37.4% of Chinese adolescents aged 13-18 were reported of high mental distress, and 59.9% were reported of low mental well being. Boys had significantly lower rates of high mental distress (35.3%) and low mental well being (55.6%) compared to girls (39.4%, 64.3%), and the differences were of statistical significance ( χ 2=176.13, 780.42, both P <0.05). In 2019, the rate of complete mental health among adolescents showed a downward trend with increasing age ( χ 2 trend = 258.47) and a gradual upward trend with increasing muscle strength levels ( χ 2 trend =123.14)，and both boys and girls exhibited similar trends ( χ 2 trend =103.83, 168.46; 57.00 , 67.34) (all P <0.05). The results of the unordered multiclass Logistic regression model showed that after controlling for confounding factors such as age and gender, when the completely pathological group as a reference, for every 1 unit increase in MSI in adolescents, the likelihood of being in a completely mental health state increased by 29% ( OR = 1.29); for every unit increase in the Z-score for pull ups, the likelihood of being in a completely mental health state increased by 6% ( OR =1.06) among boys; for every 1 unit increase in sit up Z score, the likelihood of being in a completely mental health state increased by 19% ( OR =1.19) among girls (all P <0.05). Conclusions The mental health status of Chinese adolescents is not good enough. Muscle strength is positively associated with mental health.

Parkinson′s disease (PD) is a neurodegenerative disorder prevalent among the elderly, characterized by the degeneration of dopaminergic neurons in the substantia nigra. The motor symptoms of PD include resting tremor, bradykinesia, rigidity, and postural gait disturbances. Additionally, non-motor symptoms such as depression, pain, cognitive impairment, sleep disorders, and autonomic dysfunction are gaining increasing attention. Among these, bladder and urethral dysfunction is one of the most common manifestations of autonomic dysfunction and significantly impacts patients′ quality of life in the later stages of the disease. This article provides a review of recent research on the epidemiology, pathogenesis, and treatment of bladder and urethral dysfunction in PD, aiming to enhance the understanding and management of urinary symptoms associated with PD.

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.

Objective:To determine the diagnosis of microtia-associated syndrome through genetic testing.Methods:Peripheral venous blood samples were collected from members of a two-generation family with a syndrome associated with ear malformations (3 patients and 1 normal control). Pathogenic mutations were identified using whole exome sequencing analysis, Sanger sequencing validation, and bioinformatics analysis. Based on the genetic diagnosis and a review of the literatures, the patients′ clinical phenotypes were thoroughly evaluated to confirm the clinical diagnosis.Results:All three patients carried a novel heterozygous insertion mutation (c.1171_1172insGGCC: p.Pro391fs) in the paired box 1 ( PAX1) gene. This mutation showed genotype-phenotype co-segregation within the family and was predicted to be pathogenic. Consequently, the family was diagnosed with autosomal dominant otofaciocervical syndrome 2. The clinical phenotypes of the patients included not only ear malformations and conductive hearing loss but also branchial cleft fistula, preauricular fistula, bilateral facial asymmetry, spinal deformities, and short stature, which were major symptoms of otofaciocervical syndrome 2. Imaging also revealed previously unreported phenotypes, including parotid gland malformation and facial nerve dysplasia. Conclusion:The heterozygous insertion in PAX1 (c.1171_1172insGGCC: p.Pro391fs) found in this family causes otomandibular-cervical syndrome type 2 in an autosomal dominant manner, leading to congenital anomalies affecting external and middle ear, craniofacial region, and spine.

Objective:To assess the predictive value of the percentage of Gleason pattern 4 (G4%) in prostate biopsy for adverse pathology and biochemical recurrence.Methods:We retrospectively analyzed consecutive patients who underwent radical prostatectomy in our institution between January 2019 and December 2023, and included those who were diagnosed with ISUP 2-3 cancer at biopsy. A total of 109 patients were included in this study. The average age of patients was (67.40±6.11) years, and the average BMI of patients was (25.36±2.97) kg/m 2. 49 Cases (45.0%) had a PI-RADS score of 5, and the median prostate volume was 32.60 (24.57, 45.63) ml. The median of most recent tPSA before biopsy was 9.76 (6.89, 12.95) ng/ml, the median PSAD was 0.28 (0.17, 0.44) ng/ml 2, and the median f/tPSA was 0.11 (0.08, 0.16). Clinical T 2b or higher stage was found in 84 cases (77.1%). The total biopsy core length was (22.91±5.18) cm, with a median of 24 (20, 24) biopsy cores and a median of 6 (4, 9) positive cores. Gleason score 3+ 4 was found in 52 cases (47.7%), and Gleason score 4+ 3 in 57 cases (52.3%). Cribriform was present in 30 cases (27.5%). G4% was calculated based on the proportion of Gleason grade 4 tumor relative to total tumor, tumor proportion relative to total tissue, and tissue length. Patients were divided into high-G4% (≥2.45%) and low-G4% (<2.45%) groups based on the median G4% value, with 55 and 54 cases, respectively. No significant differences were observed in baseline characteristics between the two groups ( P>0.05). The main risk factor of adverse pathology was analyzed by logistic regression, and receiver operating characteristic (ROC) curve and area under curve (AUC) were performed. Patients were further stratified by the G4% cutoff value from ROC, and Kaplan-Meier survival curves were plotted to compare biochemical recurrence free survival (BCRFS) between groups. The main risk factor affecting BCRFS was analyzed by Cox regression. Adverse pathology was defined as postoperative Gleason score ≥4+ 3 or pathological stage ≥T 3a. Results:Adverse pathology occurred in 44 (80.0%) high-G4% and 16 (29.6%) low-G4% patients ( P<0.01). Multivariate analysis identified G4% as an independent risk factor for adverse pathology ( OR=1.23, 95% CI 1.02-1.50, P=0.033). The highest ROC AUC value was seen for G4% (0.799), significantly outperforming Gleason score (0.799 vs. 0.641, P=0.003), tPSA (0.799 vs. 0.615, P=0.003), PSAD (0.799 vs. 0.679, P=0.038), positive cores (0.799 vs. 0.677, P=0.009), clinical T stage (0.799 vs. 0.607, P=0.001) and cribriform (0.799 vs. 0.639, P=0.001). The G4% cutoff value for predicting biochemical recurrence was 10.97%. The median BCRFS was significantly higher in the low G4% (<10.97%) group than that in the high G4% (≥10.97%) group (55 vs. 28 months, P=0.002). Cumulative recurrence free survival rates at 1 and 3 years were 94.6% vs. 74.1% and 78.0% vs. 47.6%, respectively. Multivariate Cox regression analysis indicates that G4% was an independent risk factor affecting BCRFS ( HR=1.11, 95% CI 1.00-1.23, P=0.041). Conclusions:For patients with ISUP 2-3 nmPCa, a higher G4% in biopsy specimens demonstrates strong predictive ability for adverse pathology and biochemical recurrence, outperforming traditional clinical indicators such as Gleason score and PSA.

OBJECTIVE:To systematically evaluate the correlation between phase angle and sarcopenia and its diagnostic indexes.METHODS:The PubMed,EMbase,Cochrane Library,Web of Science,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect studies on the correlation between phase angle and sarcopenia and its diagnostic indexes from database inception to May 8,2024. Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.3 and Stata 14.0 software. RESULTS:A total of 50 eligible articles were included. Meta-analysis results showed that compared with the non-sarcopenic population,the phase angle was significantly reduced in sarcopenic patients[standardized mean difference (SMD)=-0.99,95％ confidence interval (CI) (-1.09,-0.90),P<0.00001]. The results of subgroup analysis indicated that the difference of phase angle was more significant in patients with severe sarcopenia and Asian sarcopenia. Moreover,reduction in the phase angle was more obvious in patients with malignant tumors and respiratory diseases with sarcopenia. And skeletal muscle mass index (Pearson's r=0.565,P<0.00001),grip strength (Pearson's r=0.446,P<0.00001),and gait speed (Pearson's r=0.405,P<0.00001) all showed a moderate positive correlation with phase angle. However,appendicular skeletal muscle mass index showed a very weak positive correlation with phase angle (Pearson's r=0.139,P=0.02). CONCLUSION:Phase angle has a significant difference between sarcopenia and non-sarcopenia population,and it is correlated with the diagnostic indexes of sarcopenia to different extents. It suggests that phase angle has some clinical values in the objective diagnosis of sarcopenia. However,the results may be influenced by some factors such as sarcopenia severity and detection instruments of phase angle. Due to the limited quality and quantity of the included studies,more high-quality studies are needed to verify the above conclusion.

BACKGROUND:Ligament rupture and defect of the lateral or medial malleolus caused by high-energy injuries are common challenges in foot and ankle surgery.Their neighboring core tendons are often used as grafts to reconstruct the deficient ligaments.It is of paramount importance to investigate the mechanical properties of such tendons in the context of ligament defects to provide a suitable donor tendon.OBJECTIVE:To investigate the interactive dynamics and biomechanical alterations among their core tendons during ankle joint motions under varying degrees of lateral or medial malleolar ligament defect.METHODS:Based on CT imaging data of the left foot of a 50-year-old healthy male,a surface stereolithography model was extracted and constructed using MIMICS software.After Geomagic Wrap software was employed to fit the surfaces,a bone-cartilage-ligament-tendon ankle complex model incorporating varying degrees of ligament deficiencies was created within SOLIDWORKS software.Finite element analysis was then conducted using Ansys Workbench software,and the model's validity was verified through a simulated anterior drawer test.Following validation,the mechanical response of the ankle under the conditions of internal and external rotation,as well as inversion and eversion,was simulated.The variation and distribution patterns of the maximum Von-Mises stress in the peroneus brevis and longus tendons,as well as the anterior and posterior tibial tendons,were observed.RESULTS AND CONCLUSION:(1)In the anterior drawer test,the maximum talar displacement reached 5.208 5 mm,which was similar to the data in the previous literature,thereby the effectiveness of the model was validated.(2)Under four loading conditions,the defect of unilateral single-bundle ligaments exerted minimal influence on the maximum stress of adjacent core tendons,whereas the defect of unilateral multi-bundle ligament significantly increased the maximum tendon stress.Except for the consistently high stress across segments of the anterior tibial tendon,the high-stress regions in the long and short peroneal tendons and posterior tibial tendon were concentrated at their distal ends near the insertions.(3)Regarding the defect of the lateral malleolar ligament,the maximum stress and its variation in the peroneus brevis tendon during inversion and internal rotation were higher than those in the peroneus longus tendon.During inversion under the condition of the defect of the anterior talofibular ligament,the maximum stress in the short peroneal tendon increased by 0.951 2 MPa compared to that of normal condition,while that in the long peroneal tendon decreased by 0.065 1 MPa.Under the condition of the defect of the calcaneofibular ligament during internal rotation,the maximum stress in the short peroneal tendon increased by 2.352 9 MPa,while the maximum stress in the long peroneal tendon decreased by 0.269 2 MPa.(4)During eversion and external rotation under the defect of medial malleolar ligament,the variations in the maximum stress of the anterior and posterior tibial tendons were complex and depended on the type of ligament defect.Notably,full-thickness ligament defect significantly augmented the maximum stress in both tendons.