Background: Abnormal DNA methylation has been detected in breast cancer (BC). Downregulation of F-box protein 31 (FBXO31) in BC and its upregulated methylation level have been initially confirmed via bioinformatic analyses. Likewise, DNA methyltransferase 3 beta (DNMT3B) is highly expressed in BC. Accordingly, this study is engineered to fathom out whether DNMT3B can affect the progression of BC (Luminal A type) by regulating FBXO31 methylation. Methods: DNMT3B/FBXO31 expression and FBXO31 methylation level in BC were predicted by the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database. 5-methylcytosine (5mC) site of FBXO31 was analyzed with RMBase database. After human BC cells were collected and transfected, viability, apoptosis and migration/invasion were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry, and Transwell assay, respectively. FBXO31 methylation level was determined by methylation-specific polymerase chain reaction (MSP). Expression levels of FBXO31, DNMT3B, and apoptosis/proliferation-associated proteins were evaluated using quantitative real-time reverse transcription polymerase chain reaction or Western blotting. Results: DNMT3B expression was upregulated while FBXO31 expression was downregulated (p = 1.62 x 10-12), and FBXO31 methylation level was elevated in breast invasive carcinoma (p G 1 x 10-12). DNMT3B was highly expressed in MCF-7, MDAMB-231 and MDA-MB-453 cells (p G 0.001). DNMT3B silencing inhibited viability, migration and invasion (p G 0.05), enhanced apoptosis (p G 0.001), upregulated expression levels of Bax and FBXO31 (p G 0.001), downregulated expression levels of B cell leukemia/lymphoma 2 (Bcl-2), Ki67 and proliferating cell nuclear antigen (PCNA) (p G 0.001), and diminished FBXO31 methylation level in MCF-7 cells. FBXO31 silencing showed the opposite effects in MCF-7 cells (p G 0.001), whereas DNMT3B silencing reversed the effects of FBXO31 silencing in MCF-7 cells (p G 0.01). Conclusions: DNMT3B silencing alleviates malignant behaviors in Luminal A BC cells by suppressing FBXO31 methylation, indicating a novel mechanism of DNA methylation in Luminal A type BC.

OBJECTIVES:Stress urinary incontinence (SUI) is a common condition among women that severely impairs quality of life. Pelvic floor proprioceptive training (PFPT) has attracted increasing attention for its potential to enhance pelvic floor muscle function and alleviate SUI symptoms. This study aims to observe and compare the clinical efficacy of PFPT combined with electroacupuncture, electrical stimulation, and biofeedback therapy versus conventional therapy consisting of electroacupuncture, electrical stimulation, and biofeedback alone in women with SUI, and to explore the role of PFPT in improving symptom and functional outcomes. METHODS:In this randomized controlled trial, 72 women with mild to moderate SUI were recruited from the Department of Rehabilitation Medicine at Third Xiangya Hospital, Central South University, between December 2021 and October 2023. Participants were randomly assigned to an experimental group (n=36) or a control group (n=36). Both groups received health education. The control group underwent electroacupuncture combined with electrical stimulation and biofeedback therapy, while the experimental group additionally received PFPT 3 times per week for 4 weeks. The primary outcome was assessed using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Secondary outcomes included pelvic floor muscle strength, bladder neck mobility, and balance ability. The ICIQ-SF was reassessed at 1, 3, 6, and 12 months post-treatment. RESULTS:Both groups showed statistically significant improvements in all parameters after treatment (all P<0.05). However, there were no statistically significant differences between groups in most measures (all P>0.05). The experimental group demonstrated longer single-leg stance duration with eyes closed than the control group (left leg: P=0.026; right leg: P=0.006), with a significant increase from baseline (P<0.001). At 6 months post-treatment, the cure rate in the experimental group was significantly higher than that in the control group (P=0.037). CONCLUSIONS:Conventional therapy effectively improves SUI symptoms, but adding PFPT provides notable additional benefits, including enhanced balance ability and sustained mid-term cure rates. These findings suggest that PFPT is a valuable adjunct to standard SUI management strategies.

OBJECTIVES:Near vision loss (NVL) is one of the leading causes of visual impairment worldwide, exerting a profound impact on individual quality of life and socio-economic development. This study aims to analyze the burden of NVL in China by sex and age groups from 1990 to 2021 and to project trends over the next 15 years. METHODS:Using data from the Global Burden of Disease (GBD) 2021 database, we conducted descriptive analyses of NVL prevalence in China, calculated age-standardized prevalence rates (ASPR) and age-standardized disability-adjusted life years rates (ASDR) to compare burden differences between sexes and age groups, and applied an autoregressive integrated moving average (ARIMA) model to predict NVL trends for the next 15 years. The model selection was based on best-fit criteria to ensure reliable projections. RESULTS:From 1990 to 2021, China's ASPR of NVL rose from 10 096.24/100 000 to 15 624.54/100 000, and ASDR increased from 101.75/100 000 to 158.75/100 000. In 2021, ASPR (16 551.70/100 000) and ASDR (167.69/100 000) were higher among females than males (14 686.21/100 000 and 149.76/100 000, respectively). China ranked highest globally in both NVL cases and disability-adjusted life years (DALYs), with female burden significantly exceeding male burden. Projections indicated this trend and sex gap will persist until 2036. Compared with 1990, the prevalence cases and DALYs increased by 239.20% and 238.82%, respectively in 2021, with the highest burden among females and the 55-59 age group. The ARIMA model predicted continued increases in prevalence and DALYs by 2036, with females maintaining a higher burden than males. CONCLUSIONS:This study reveals a marked increase in the NVL burden in China and predicts continued growth in the coming years. Public health policies should prioritize NVL prevention and control, with special attention to women and middle-aged populations to mitigate long-term societal and health impacts.

OBJECTIVES:Tiletamine, a veterinary anesthetic, has emerged as a novel psychoactive substance and has been abused in many parts of the world, causing great harm to public health. However, the sensitivity of existing detection methods cannot meet the needs of forensic practice. This study aims to establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of tiletamine and its metabolite desethyltiletamine in human biological samples, and to verify its applicability in forensic practice. METHODS:SKF525A was used as the internal standard. Biological samples were extracted with acetonitrile containing 1 ng/mL SKF525A, vortexed for 10 min, ultrasonicated for 20 min, centrifuged at 10 000 r/min for 10 min, and 500 μL of the supernatant was filtered through a 0.22 μm membrane. Analyses were performed using an ACQUITY UPLC H-Class PLUS system and an XEVO TQ-S Micro triple quadrupole mass spectrometer. An ACQUITY UPLC® BEH C18 (1.7 µm, 2.1 mm×100 mm) column at a flow rate of 0.3 mL/min was used, and four mobile phase systems were tested to optimize separation. Detection used positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, with quantifier ion transitions of mass to charge 224.043→179.016 for tiletamine and mass to charge 196.08→151.06 for desethyltiletamine. Calibration curves were established over 0.1-200 ng/mL in spiked blood samples. The linear range, limit of detection (LOD), and limit of quantification (LOQ) were determined. Low (5 ng/mL), medium (20 ng/mL), and high (100 ng/mL) concentrations of tiletamine were spiked into blood, liver, and kidney to evaluate precision, accuracy, matrix effect, recovery, and stability. Finally, actual forensic case samples were tested to validate applicability. RESULTS:The established UPLC-MS/MS method achieved simultaneous detection of tiletamine and desethyltiletamine in human biological samples, with retention times of 3.42 min and 2.82 min, respectively. Using mobile phase A (20 mmol/L ammonium acetate and 0.1% formic acid in water) and mobile phase B (acetonitrile) produced the best separation. In blood, tiletamine showed good linearity from 0.1-200 ng/mL (r=0.992, R2=0.983), LOD 0.03 ng/mL, LOQ 0.1 ng/mL, recovery 92%-107%, and matrix effect 71%-99%. In liver and kidney, recoveries were 91%-98% and 93%-104%, and matrix effects were 69%-96% and 72%-100%, respectively. Intra- and inter-day precision [expressed as relative standard deviation (RSD)] and accuracy [expressed as relative error (RE)] were within 15%, and samples were stable at -20 ℃. Tiletamine was detected in actual case samples at 0.37 μg/mL (blood), 0.15 μg/g (liver), 0.11 μg/g (kidney) in case 1, and 8.75 ng/mL (blood) in case 2; desethyltiletamine was also detected in blood. CONCLUSIONS:The UPLC-MS/MS method is efficient, accurate, and sensitive, and is suitable for detecting tiletamine and desethyltiletamine in human biological samples.

Pelvic floor dysfunction(PFD)is a common clinical problem that can lead to bladder and bowel dysfunction such as urinary incontinence,urinary retention,fecal incontinence,pelvic organ prolapse,and sexual dysfunction.Pelvic floor rehabilitation aids are essential tools in the treatment of PFD.However,there is limited understanding of the efficacy and mechanisms of these aids,and there is a lack of standardized guidelines for selecting appropriate aids for different types of PFD.To assist patients in choosing suitable pelvic floor rehabilitation aids to their needs,it is necessary to summarize the existing types,mechanisms,and applications of these aids.Based on their mechanisms and target functions,pelvic floor rehabilitation aids can be mainly categorized into 3 main types.The first type includes aids that improve pelvic floor function,such as vaginal dumbbells,vaginal tampons,and vaginal dilators,which aim to strengthen pelvic floor muscles and enhance the contractility of the urethral,vaginal,and anal sphincters,thereby improving incontinence symptoms.The second type consists of aids that mechanically block the outlet,such as pessaries,urethral plugs,incontinence pads,incontinence pants,anal plugs,and vaginal bowel control systems,which directly or indirectly prevent incontinence leakage.The third type includes aids that assist in outlet drainage,such as catheters and anal excreta collection devices,which help patients effectively expel urine,feces,and other waste materials,preventing incontinence leakage.By summarizing the existing pelvic floor rehabilitation aids,personalized guidance can be provided to patients with PFD,helping them select the appropriate aids for their rehabilitation needs.

OBJECTIVES:Pelvic floor sensory training is commonly used in clinical practice for the treatment of stress urinary incontinence (SUI); however, there is a lack of comparative studies evaluating pelvic floor sensation between women with SUI and healthy controls. Additionally, normative data for two-point discrimination thresholds in the female pelvic floor region remain scarce. This study aims to compare the results of 4 sensory tests in the pelvic floor region between women with mild SUI and healthy women, in order to provide reference values for two-point discrimination thresholds in this area. METHODS:From April 1 to October 30, 2023, 108 healthy women [(32.5±3.6) years] and 90 women with mild SUI [(32.9±3.3) years] were recruited from the Third Xiangya Hospital, Central South University. Participants underwent 4 sensory tests in the pelvic floor region: Two-dot discrimination, weight perception, shape recognition, and 9-grid localization. The results were compared between the 2 groups. RESULTS:Compared with healthy women, those with mild SUI had lower sensitivity and higher thresholds in 2-dot discrimination tests in the pelvic floor region (all P<0.001). No significant differences were found between groups in weight perception, shape recognition, or grid localization tests (P>0.05). CONCLUSIONS:Women with mild stress urinary incontinence have impaired two-point discrimination ability in the pelvic floor region.

Background Postpartum women often experience stress urinary incontinence (SUI) and vaginal microbial dysbiosis, which seriously affect women's physical and mental health. Understanding the relationship between SUI and vaginal microbiota composition may help to prevent vaginal diseases, but research on the potential association between these conditions is limited.Results This study employed 16S rRNA gene sequencing to explore the association between SUI and vaginal dysbiosis. In terms of the vaginal microbiota, both species richness and evenness were significantly higher in the SUI group. Additionally, the results of NMDS and species composition indicated that there were differences in the composition of the vaginal microbiota between the two groups. Specifically, compared to postpartum women without SUI (Non-SUI), the relative abundance of bacteria associated with bacterial dysbiosis, such as Streptococcus, Prevotella, Dialister, and Veillonella, showed an increase, while the relative abundance of Lactobacillus decreased in SUI patients. Furthermore, the vaginal microbial co-occurrence network of SUI patients displayed higher connectivity, complexity, and clustering.Conclusion The study highlights the role of Lactobacillus in maintaining vaginal microbial homeostasis. It found a correlation between SUI and vaginal microbiota, indicating an increased risk of vaginal dysbiosis. The findings could enhance our understanding of the relationship between SUI and vaginal dysbiosis in postpartum women, providing valuable insights for preventing bacterial vaginal diseases and improving women's health.

OBJECTIVES:Pelvic organ prolapse (POP) is a common condition in postmenopausal women, with an increasing prevalence due to aging. Some women experience POP recurrence after surgical treatment, significantly affecting their physical and mental health. The uterosacral ligament is a critical pelvic support structure. This study aims to investigate the molecular pathological changes in the uterosacral ligament of postmenopausal women with recurrent POP using transcriptomic analysis. METHODS:Transcriptomic data of uterosacral ligament tissues were obtained from the public dataset GSE28660, which includes samples from 4 postmenopausal women with recurrent POP, 4 with primary POP, and 4 without POP. Differentially expressed genes (DEGs) were identified between recurrent POP and both primary and non-POP groups. Further analysis included intersection analysis of DEGs, gene ontology enrichment, protein-protein interaction (PPI) network construction, gene set enrichment analysis (GSEA), single-sample GSEA, and xCell immune cell infiltration analysis to explore molecular pathological changes in recurrent POP. Additionally, histological and molecular differences in the uterosacral ligament were compared between simulated vaginal delivery (SVD) rat models with and without ovariectomy. RESULTS:Compared with primary POP and non-POP groups, recurrent POP exhibited activation of adipogenesis and inflammation-related pathways, while pathways related to muscle proliferation and contraction were downregulated in the uterosacral ligament. Nine key DEGs (ADIPOQ, FABP4, IL-6, LIPE, LPL, PCK1, PLIN1, PPARG, and CD36) were identified, with most enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. These genes were significantly correlated with lipid accumulation, monocyte infiltration, and neutrophil infiltration in the uterosacral ligament. Urodynamic testing revealed that the bladder leak point pressure was significantly higher in ovariectomized SVD rats, both of which had higher values than the sham group. Masson staining showed pronounced adipogenesis in the uterosacral ligament of ovariectomized SVD rats, along with reduced collagen and muscle fibers compared to the sham and non-ovariectomized SVD groups. Furthermore, real-time RT-PCR confirmed significantly elevated expression of key DEGs, including ADIPOQ, IL-6, PCK1, and PLIN1, in the uterosacral ligaments of ovariectomized SVD rats. CONCLUSIONS:Adipogenesis and inflammation in the uterosacral ligament may contribute to its reduced supportive function, potentially leading to recurrence POP in postmenopausal women.

Background: PLAU is known as a selected serine protease converting plasminogen to plasmin. The role of PLAU in the development of pan-cancer, especially bladder urothelial carcinoma (BLCA) remains unclear.Method: A variety of online tools and cancer databases, including TCGA, GETx, HPA database, GSCALite, UALCAN, ESTIMATE, CIBERSORT, ssGSEA algorithms and SangerBox website, were applied to investigate the associations between PLAU expression and prognosis, genetic alterations, pathway activation, and tumor immunity in pan-cancer. Through cBioPortal and STITCH platforms, the oncogenic role of PLAU and related targeting medicines in BLCA were also explored. We verified the expression of PLAU in pan-cancer cells and its function in bladder cancer cell lines using wet-lab experiments.Results: PLAU expression levels were significantly higher in most cancer tissues. PLAU had a certain accuracy in the diagnosis of various types of cancers (90 % AUC > 0.700). In BLCA, PLAU has abundant methylated sites and showed statistical differences in clinical features. PLAU was involved in tumor immune infiltration, and especially positively correlated with neutrophil infiltration. High-expressed PLAU indicated poorer prognosis in the BLCA patients receiving Atezolizumab. A high mRNA and protein expression levels of PLAU were observed in pan-cancer cell lines, especially BLCA cells. Knockdown of PLAU inhibited the invasive, proliferative, and aggressive phenotypes of bladder cancer cells. Immunohistochemical staining validated PLAU's higher expression in BLCA tissues than in adjacent non-cancerous tissues. And overexpression of PLAU was associated with more advanced TNM stage, and high infiltrating depth.Conclusion: Our study revealed that PLAU can serve as a potential therapeutic target and prognostic marker for various malignancies, especially BLCA.

Background: Triple-negative breast cancer (TNBC) is a subtype of BC with high rates of mortality. The mechanism of PTPRG-AS1 in ferroptosis of TNBC was investigated. Methods: Chromatin immunoprecipitation and dual-luciferase reporter assays were used to measure intermolecular relationships. MTT and colony formation assays detected cell viability and proliferation. Kits detected Fe2+ and reactive oxygen species levels. The role of PTPRG-AS1 in tumor growth was analyzed in vivo. Results: PTPRG-AS1 was increased in TNBC tissues and cells. PTPRG-AS1 silencing increased the reduction of glutathione and GPX4, increased Fe2+ and reactive oxygen species in erastin-treated cells and inhibited proliferation. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11. PTPRG-AS1 knockdown suppressed tumor growth in vivo. Conclusion: POU2F2 transcriptionally activates PTPRG-AS1 to modulate ferroptosis and proliferation by miR-376c-3p/SLC7A11, promoting TNBC.

OBJECTIVES:Stress urinary incontinence is a common disease with many therapeutic ways, but it lacks long-term follow-up. This study aims to conduct a retrospective study on the long-term efficacy of women with mild and moderate stress urinary incontinence after pelvic floor rehabilitation treatment for 3-years so as to provide a more effective treatment plan for this disease. METHODS:Data were collected from 279 female patients, who were diagnosed with stress urinary incontinence at the Pelvic Floor Rehabilitation Center of the Third Xiangya Hospital of Central South University from January 2017 to January 2019. All patients received health education and were instructed to perform Kegel exercises for 20 min daily at home. According to the treatment pattern, patients were divided into 3 groups as A, B, and C. Group A (n=94) received pelvic floor biofeedback, electrical stimulation and electroacupuncture; Group B (n=99) received pelvic floor biofeedback and electrical stimulation; Group C (n=86) only got pelvic floor function examinations and did not receive any pelvic floor treatment. The pelvic floor functional examinations included a pelvic floor electrophysiological test, pelvic organ prolapse quantitive examination (POP-Q), and stress urinary incontinence severity assessment. All patients were followed up with questionnaire consisting of the International Committee on Urinary Incontinence Questionnaire-Short Form (ICI-Q-SF) and the Quality of Life questionnaire of Urinary Incontinence (I-QOL) before and after the treatment, as well as at 1-, 2-, and 3-years after the treatment (5 times in total). Among the patients who received the treatment, 43 returned to the hospital, including 21 in group A (Group Areturn) and 22 in group B (Group Breturn). Pelvic floor electrophysiological test and POP-Q were performed on the 2 groups. RESULTS:For the leakage rate at the end of the treatment and the following 1-, 2-, and 3-years: Group A0.05), but the I-QOL scores of Group A and Group B were much higher than that in Group C (both P<0.05). On the other hand, the I-QOL scores at 1-, 2-, and 3-years after the treatment were Group A>Group B>Group C (all P<0.05). In addition, the ICI-Q-SF scores at the end of the treatment and 1-, 2-, and 3-years after the treatment were Group A0.05). While the pelvic floor muscle strength in Group Areturn was much higher than that in Group Breturn (P<0.05) after 3 years of the treatment. What's more, the pelvic floor muscle potential in Group Areturn was much higher than that in Group Breturn (both P<0.05) at the end of the treatment and after 3 years of the treatment. CONCLUSIONS:Compared with pelvic floor biofeedback and electrical stimulation for stress urinary incontinence, electroacupuncture combined with pelvic floor electrical stimulation and biofeedback reveal more remarkable short-term efficacy and more stable long-term efficacy, which can significantly improve the quality of life in female patients.

Abstract Background Stress urinary incontinence and vaginal microbial dysbiosis frequently occur in postpartum women. A better understanding of the relationship between SUI and the composition of vaginal microbiota may help to prevent the emergence of vaginal diseases. However, limited research has been conducted to investigate the potential association between vaginal microbial dysbiosis and stress urinary incontinence. Results The present study revealed a strong correlation between changes in the composition of vaginal microbiota and stress urinary incontinence, with stress urinary incontinence being more likely to lead to dysbiosis of vaginal microbiota. In terms of the vaginal microbiota, both alpha diversity and evenness were significantly higher in the stress urinary incontinence group compared to the group without stress urinary incontinence. Additionally, there were notable differences in the composition of the vaginal microbiota between two groups. Specifically, among stress urinary incontinence patients, the abundance of bacteria associated with bacterial vaginosis, such as Streptococcus, Prevotella, Dialister, and Veillonella, showed an increase, while the abundance of Lactobacillus decreased. Furthermore, the vaginal microbial co-occurrence network of stress urinary incontinence patients displayed higher connectivity, complexity, and clustering. Conclusions As a result, our study emphasizes the significant role of Lactobacillus in maintaining homeostasis within the vaginal microbial community. A correlation between stress urinary incontinence and the vaginal microbiota was observed, indicating an increased risk of vaginal microbial disorders and bacterial vaginosis for individuals with stress urinary incontinence. Consequently, we anticipate that our findings will contribute novel insights into the prevention of bacterial vaginal diseases associated with stress urinary incontinence.

Background: Docetaxel is an important chemotherapy-agent for breast cancer treatment. One of its side-effects is weight gain, which increases the all-cause mortality rate. Considering gut microbiota is one important factor for weight regulation, we hypothesized that probiotics could be potentially used to reduce the docetaxel-related weight gain in breast cancer patients. Methods: From 10/8/2018 to 10/17/2019, 100 breast cancer (Stage I-III) patients underwent four cycles of docetaxel-based chemotherapy were enrolled and randomly assigned to receive probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) or placebo (supplementary material of the probiotics capsule) treatment for 84 days with three capsules per time, twice/day. The primary outcome: the changes in body weight and body-fat percentage of the patients were measured by a designated physician using a fat analyzer, and the secondary outcomes: the fasting insulin, plasma glucose, and lipids were directly obtained from the Hospital Information System (HIS); The metabolites were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); The fecal microbiome was analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequence. All indicators were measured 1 day before the first cycle of docetaxel-based chemotherapy and 21 days after the last cycle of docetaxel-based chemotherapy. Results: Compared with the placebo group, the probiotic group showed significantly smaller changes in body weight (Mean [SD] 0.77 [2.58] vs. 2.70 [3.08], P = 0.03), body-fat percentage (Mean [SD] 0.04 [1.14] vs. 3.86 [11.09], P = 0.02), and low density lipoprotein (LDL) (Mean [SD]−0.05[0.68] vs. 0.39 [0.58], P = 0.002). Moreover, five of the 340 detected plasma metabolites showed significant differences between the two groups. The change of biliverdin dihydrochloride (B = −0.724, P = 0.02) was inverse correlated with weight gain. One strain of the phylum and three strains of the genus were detected to be significantly different between the two groups. Also, the changes of Bacteroides (B = −0.917, P < 0.001) and Anaerostipes (B = −0.894, P < 0.001) were inverse correlated with the change of LDL. Conclusions: Probiotics supplement during docetaxel-based chemotherapy for breast cancer treatment may help to reduce the increase in body weight, body-fat percentage, plasma LDL, and minimize the metabolic changes and gut dysbacteriosis. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=24294, ChiCTR-INQ-17014181.

Objective:Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke.Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury.However,plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke.This study aims to explore the role of delayed recanalization on blood-brain barrier(BBB)in the penumbra(surrounding ischemic core)and neurological outcomes after middle cerebral artery occlusion(MCAO).Methods:Recanalization was performed on the 3rd day after MCAO.BBB disruption was tested by Western blotting,Evans blue dye,and immunofluorescence staining.Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO.The expression of fibroblast growth factor 21(FGF21),fibroblast growth factor receptor 1(FGFR1),phosphatidylinositol-3-kinase(PI3K),and serine/threonine kinase(Akt)in the penumbra were observed by immunofluorescence staining and/or Western blotting.Results:The extraversion of Evans blue,IgG,and albumin increased surrounding ischemic core after MCAO,but significantly decreased after recanalization.The expression of Claudin-5,Occludin,and zona occludens 1(ZO-1)decreased surrounding ischemic core after MCAO,but significantly increased after recanalization.Infarct volume reduced and neurological outcomes improved following recanalization(on the 7th day after MCAO).The expressions of Claudin-5,Occludin,and ZO-1 decreased surrounding ischemic core following MCAO,which were up-regulated corresponding to the increases of FGF21,p-FGFR1,PI3K,and p-Akt after recanalization.Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K,p-Akt,Occludin,Claudin-5,and ZO-1 in the penumbra,which weakened the beneficial effects of recanalization on neurological outcomes after MCAO.Conclusion:Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway,which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.

OBJECTIVES:The efficacy of using a single electrical or magnetic stimulation for treating pelvic floor dysfunction is limited. This study aims to investigate the efficacy of radiofrequency combined with magnetic stimulation treatment for mild to moderate pelvic organ prolapse.METHODS:Patients who completed the treatment in the Third Xiangya Hospital, Central South University were screened, and were divided into 2 groups based on different treatment plans. There were 28 patients who completed magnetic stimulation therapy (the magnetic stimulation therapy group) and 21 patients who completed radiofrequency combined with magnetic stimulation therapy (the combined treatment group). The pelvic organ prolapse quantitation (POP-Q), pelvic floor muscle strength, and pelvic floor ultrasound results were analyzed to assess the efficacy before and after the treatment in both groups, and the POP-Q results of 3 months after the treatment were used to evaluate the maintenance effect of the treatment mode.RESULTS:The POP-Q evaluation results of Aa, Ap, and C points after the treatment in both groups were better than those before the treatment, with statistical significance (all P<0.05). The Aa point POP-Q result of the combined treatment group was better than that of the magnetic stimulation therapy group, with statistical significance (P<0.05). Pelvic floor ultrasound evaluation showed that the bladder neck position during the valsalva maneuver in the combined treatment group was higher than that in the magnetic stimulation treatment group, with statistical significance (P<0.05). The persistence effect of the combined treatment group was long better than that of the magnetic stimulation treatment group, with significant statistical significance (P<0.01).CONCLUSIONS:The combined treatment is more effective and has a longer lasting effect than single magnetic stimulation treatment.

OBJECTIVE:To evaluate the role of hormone receptor expression on endocrine therapy in patients with breast cancer.METHODS:The databases were used to collect the effect of high expression and low expression of hormone receptors on the efficacy of endocrine therapy in breast cancer. Two evaluators independently screened the literature based on preset inclusion and exclusion criteria. The quality of the article was evaluated using a modified Newcastle-Ottawa Scale (NOS) system. The survival data included in the literature were extracted and the ln(hazard ratio (HR)) and se[ln(HR)] of the overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) rates were calculated according to different level of hormone receptors. The RevMan 5.3 software was used to evaluate the meta-analysis.RESULTS:A total of 13 relevant literature were included in the study. There were 8318 estrogen receptor (ER)-positive and 7926 progesterone receptor (PR)-positive patients. Overall survival, DFS, and RFS rates in high expression of ER(+) patients were significantly higher in low expression of ER(+) patients (OS HR = .59, 95% confidence interval (CI): .46-.76, P < .0001; DFS HR = .62, 95%CI: .50-.76, P < .00001; RFS HR = .44, 95% CI: .33-.58, P < .00001). In patients with high expression of PR(+), OS, DFS, and RFS rates were significantly higher than those with low expression of PR(+) (OS HR = .66, 95% CI: .57-.78, P < .00001; DFS HR = .52, 95% CI: .42-.65, P < .00001; RFS HR = .24, 95% CI: .11-.53, P = .0004).CONCLUSION:The expression of ER and PR are powerful predictors of adjuvant endocrine therapy response. Breast cancer patients with high expression of hormone receptors benefit more from endocrine therapy and have better prognosis.

Abstract Background: Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology, characterized by monoclonal proliferation and organ infiltration of Langerhans cells. The clinical manifestations are various, and may involve single or multiple organs. A case of LCH is introduced and the diagnosis and treatment are discussed. Case presentation: A 23-year-old woman presented with a huge mass in the left lower abdomen. Computed tomography (CT) of the lung revealed multiple diffuse nodules of different sizes in the right lung. The left thorax was collapsed, the left pleura was thickened and adhered, and a small, encapsulated effusion was observed in the thoracic cavity. Enhanced CT of the whole abdomen showed a huge cystic low-density focus on the left lower abdomen, multiple nodules in the spleen, and multiple osteolytic bone destruction in the spine, thorax, and pelvis. The possibility of LCH was considered based on the presence of diffuse reticulum nodules in the lungs observed in CT imaging. The patient was performed ultrasound-guided abdominal puncture, drainage, and chemotherapy with "vinorelbine and cisplatin". Follow-up is ongoing. Conclusion: LCH involving the serosal membrane is rare. The final diagnosis requires histopathological examination of the involved tissue. But in most cases, it’s enough to diagnose through the typical imaging changes in the lung, as observed by high-resolution computed tomography (HRCT), combined with certain clinical observations. Currently, there are no clearly established treatment guidelines for LCH. At present, systemic chemotherapy is the main treatment method that has been shown to improve patient’s prognosis.

Background Contralateral neck lymph node metastasis is rare in primary breast cancer. Its clinical staging and treatment principles lack authoritative guidelines. A case of a 30-year-old breast cancer patient with contralateral neck lymph node metastasis is presented. The clinical treatment is discussed in combination with current research. Case presentation A 30-year-old woman presented with a right breast mass for 5 months and left neck lymph node enlargement for 5 days. Mammography showed a 33 mm*14.3 mm mass in the inner quadrant of the right breast. The ultrasound showed several hypoechoic nodules on the left side of the neck. Rapid intraoperative pathological examination diagnosed a right breast malignant tumor and poorly differentiated carcinoma of the left cervical lymph nodes. Then, right mastectomy was performed immediately. The patient was scheduled to undergo chemotherapy, molecular targeted therapy, radiotherapy and endocrine therapy after the operation. The long-term efficacy remains to be seen. Conclusion The infrequent presentation of breast cancer with metastasis to the contralateral neck lymph node can be challenging for standard therapies.

OBJECTIVES:Cerebrovascular disease can be roughly divided into 2 subtypes: Cerebral ischemia (CI) and cerebral hemorrhage (CH). No scale currently exist that can predict the subtypes of cerebrovascular diseases. This study aims to establish a prediction scale for the subtypes of cerebrovascular diseases. METHODS:A total of 1 200 cerebrovascular disease patients were included in this study, data from 1 081 (90%) patients were used to establish the CI-CH risk scale, and data from 119 (10%) patients were used to test it. Risk factors for the CI-CH risk scale were identified by 2 screens, with two-tailed student's t-test and two-tailed Fisher's exact test preliminarily and with logistic regression analysis further. The scores of each risk factor for CI-CH risk scale were determined according to the odds rate, and the cut-off point was determined by Youden index. RESULTS:Nine risk factors were ultimately selected for score system, including age (≥75 years old was -1, <75 years old was 0), BMI (<24 kg/m2 was 0, 24-28 kg/m2 was -1, >28 kg/m2 was -2), hypertension grade (grade 1 was 1, grade 2 was 2, and grade 3 was 3), diabetes status (no was 0, yes was -1), antihypertensive drug use (no was 0, yes was -2), alcohol consumption (<60 g/d was 1, ≥60 g/d was 2), uric acid (less than normal was 0, normal was -1, high than normal was -2), LDL cholesterol (<2 mmol/L was 0, 2-4 mmol/L was -1, and >4 mmol/L was -2), and HDL cholesterol (<1.55 mmol/L was 0, ≥1.55 mmol/L was 2). Patients with a score more than 0 were classified as the CH group, Conversely, they were assigned to the CI group; its sensitivity, specificity, and accuracy were 74.5%, 77.9%, and 76.4%, respectively. CONCLUSIONS:The CI-CH risk scale can help the clinician predict the subtypes of cerebrovascular diseases.

OBJECTIVES:Pelvic floor tendons, fascia, and ligaments are rich in proprioceptors. Proprioceptive training can stimulate local proprioceptors to increase neuromuscular responses and promote the recovery of muscle and fascial ligament functions. This study aims to observe the therapeutic effect of proprioception training combined with pelvic floor electrical stimulation biofeedback on postpartum pelvic floor dysfunction (PFD), and to provide evidence for the treatment of postpartum PFD. METHODS:A total of 108 puerpera with postpartum PFD were selected and divided into a control group ( n =50) and an experimental group ( n =58). Puerpera in the control group received pelvic floor electrical stimulation biofeedback treatment. Puerpera in the experimental group received proprioception training combined with pelvic floor electrical stimulation biofeedback treatment. After one course of treatment, the pelvic floor muscle strength, muscle endurance, repetitive contraction ability, rapid contraction ability, percentage of normal vaginal posterior wall elevation, percentage of normal lower abdominal muscle synergistic contraction, percentage of normal reflex contraction during coughing, incidence of stress urinary incontinence (SUI), and staging of pelvic organ prolapse (POP) were compared before and after treatment between the 2 groups. RESULTS:After treatment, all indexes of the 2 groups were better than those before treatment; the pelvic floor muscle strength, muscular endurance, repetitive contraction ability, and rapid contraction ability of the experimental group were better than those of the control group (all P <0.05); the percentage of normal lower abdominal muscle synergistic contraction and percentage of normal reflex contraction during coughing of the experimental group were higher than those of the control group (both P <0.05); the incidence of SUI in the experimental group was lower than that in the control group ( P <0.05); the percentage of POP staging II in the experimental group was significantly lower than that in the control group ( P <0.05). There was no significant difference in the percentage of normal posterior vaginal wall elevation after treatment between the 2 groups ( P >0.05). CONCLUSIONS:Proprioception training combined with pelvic floor electrical stimulation biofeedback could improve the rehabilitation effect of postpartum pelvic floor dysfunction and promote the recovery of pelvic floor function, which possesses important clinical application value.