Abnormal circulating steroids refine risk of progression to heart failure in ischemic heart disease.

BACKGROUND: Patients with ischemic heart disease (IHD) experience a high incidence of progression to heart failure (HF) despite current therapies. We speculated that steroid hormone metabolic disorders distinct adverse phenotypes and contribute to HF. METHODS: We measured 18 steroids using liquid chromatography with tandem mass spectrometry in 2023 patients from the Registry Study of Biomarkers in Ischemic Heart Disease (BIOMS-IHD), including 1091 patients with IHD in a retrospective discovery set and 932 patients with IHD in a multicentre validation set. Our outcomes included incident HF after a median follow-up of 4 years. RESULTS: We demonstrated steroid-based signatures of inflammation, coronary microvascular dysfunction and left ventricular hypertrophy that were associated with subsequent HF events in patients with IHD. In both cohorts, patients with a high steroid-heart failure score (SHFS) (>1) exhibited a greater risk of incident HF than patients with a low SHFS (≤1). The SHFS further improved the prognostic accuracy beyond clinical variables (net reclassification improvement of 0.628 in the discovery set and 0.299 in the validation set) and demonstrated the maximal effect of steroid signatures in patients with IHD who had lower B-type natriuretic peptide levels (pinteraction = 0.038). CONCLUSIONS: A steroid-based strategy can simply and effectively identify individuals at higher HF risk who may derive benefit from more intensive follow-ups.

Design, synthesis and biological evaluation of sulfonylurea derivatives as NLRP3 inflammasome inhibitors.

The NLRP3 inflammasome has been extensively studied in recent years and its aberrant activation can exacerbate inflammatory responses, contributing to various diseases. MCC950, a sulfonylurea drug, is a potent selective inhibitor of the NLRP3 inflammasome. However, its clinical development was halted due to hepatotoxicity, and studies have indicated significant reduction in activity among its metabolites. Building upon MCC950, we referenced substitution sites of NP3-146 for structural modifications aimed at addressing potential metabolism-related issues. Consequently, we synthesized a series of sulfonylurea derivatives. Ultimately, the optimized compound C4 exhibited a remarkable 80.39 % inhibition of IL-1ß at 2 µM, with an IC50 value of 0.805 µM. In conclusion, compound C4 shows potential as a lead compound and warrants further development as an anti-inflammatory NLRP3 inhibitor.

Design and synthesis of indol-2-one derivatives as potential RET inhibitors.

We synthesized and assessed five series of indol-2-one derivatives for their potential as RET kinase inhibitors. Notably, compounds B3, B6, D1, D2, D3, and D5 demonstrated significant inhibitory activity. Among these, D5 exhibited the best activity of inhibiting RET kinase, which provided reference for the subsequent development of RET kinase inhibitors as anti-thyroid cancer chemical.

Design and synthesis of Osthole-based compounds as potential Nrf2 agonists.

A total of 23 compounds based on Osthole skeleton were designed and synthesized. Their agonistic activity for Nrf2 were evaluated by Dual-luciferase Reporter Gene Assay. Most of the compounds showed better activities compared with Osthole, especially O15 and O21. And the median effective concerntration (EC50) values was calculated accordingly, both of which showed remarkable activity for Nrf2. The structure activity relationship study indicated that introduction of the structure of stilbene might be beneficial for enhancement of agonistic properties of Osthole, and the position of the substituent may have a greater effect on the activity than the electron-donating/withdrawing ability of the substituent. Mechanism of the action of selected compound O15 was investigated by molecular docking, cellular thermal shift assay and ubiquitination assay, which suggested the reason why O15 exhibited relatively stronger agonistic activity for Nrf2. Compound O15 and O21 both provided novel methods to investigate Osthole-based compounds as Nrf2 agonists.

Association of ADAM17 Expression Levels in Patients with Interstitial Lung Disease.

A disintegrin and metalloproteinases (ADAMs) are believed to be involved in the pathogenesis of many fibrosis-related diseases. However, little is known regarding the significance of ADAM17 as a biomarker for interstitial lung disease (ILD). In this study, by using the RT-PCR, western blotting and ELISA, we detected the expression level of ADAM17 in peripheral blood mononuclear cells and serum from idiopathic pulmonary fibrosis (IPF) patients, connective tissue disease associated ILD (CTD-ILD) patients and healthy controls, and correlations between clinical and laboratory parameters were also analyzed. We found that IPF patients and CTD-ILD patients showed higher levels of ADAM17 than healthy controls. Moreover, ADAM17 in IPF patients with acute exacerbation (AE-IPF) was significantly higher than that in stable IPF (S-IPF) patients. Expression of ADAM17 was positively correlated with disease duration and CRP but negatively correlated with diffusing capacity of carbon monoxide (DLCO) and total lung capacity (TLC). Among the CTD-ILD patients, SSc-ILD patients had the highest serum levels of ADAM17 compared with the RA-ILD, SS-ILD and IIM-ILD groups and ADAM17 expression levels were correlated with image grading. In conclusion, this study showed that ADAM17 is highly expressed in ILD patients and is associated with disease activity and severity. Additionally, ADAM17 expression is not only related to the primary CTDs, but also to image grading. ADAM17 may serve as a new biomarker for ILD.

Ring and Gellhorn pessaries used in patients with pelvic organ prolapse: a retrospective study of 8 years.

AIM: The aim of this study was to identify factors associated with pessary fitting, continued use of pessary and satisfaction of patients with pelvic organ prolapse. METHODS: A retrospective study was conducted in patients who received an initial pessary fitting. The clinical characteristics of these patients were recorded. The Pelvic Floor Disability Index PFDI-20 and PFIQ-7 were used to assess pelvic floor dysfunction and quality of life. Complications, satisfaction degree, and reasons for abandonment were recorded during the follow-up. T test and Chi square test in SPSS version 20 were used to analyze the data. RESULTS: Three hundred women with symptomatic prolapse were selected for pessary fitting, whose average age was 67.8 ± 10.7 years. For two hundred and forty-nine (83%) women, the fitting was successful, of whom 162 used ring pessaries and 87 used Gellhorn pessaries. Forty-seven patients abandoned using a pessary at the end of our study. Most clinical characteristics were not significantly different between the successful and unsuccessful fitting groups (P > 0.05). The average score of CRADI-8 was lower in successful fitting group (11.9 ± 15.9) than that in unsuccessful fitting group (18.8 ± 19.9) (P < 0.05). 162 patients with successful pessary fitting completed the satisfaction survey, 79% of whom were satisfied or very satisfied. Erosions (24.4%) were the most common complication. Difficulty in inserting or removing (30.4%) and erosions (22.8%) were the main factors, which affected the satisfaction degree. CONCLUSIONS: Patients with obvious symptoms of posterior pelvic prolapse are more likely to fit failure. Difficulty in inserting or removing and erosions are the main factors, which lead to the discontinuation of pessary use and decrease in the satisfaction degree.

Thermodynamic Analysis of an Irreversible Maisotsenko Reciprocating Brayton Cycle.

An irreversible Maisotsenko reciprocating Brayton cycle (MRBC) model is established using the finite time thermodynamic (FTT) theory and taking the heat transfer loss (HTL), piston friction loss (PFL), and internal irreversible losses (IILs) into consideration in this paper. A calculation flowchart of the power output (P) and efficiency (η) of the cycle is provided, and the effects of the mass flow rate (MFR) of the injection of water to the cycle and some other design parameters on the performance of cycle are analyzed by detailed numerical examples. Furthermore, the superiority of irreversible MRBC is verified as the cycle and is compared with the traditional irreversible reciprocating Brayton cycle (RBC). The results can provide certain theoretical guiding significance for the optimal design of practical Maisotsenko reciprocating gas turbine plants.

Safety and Efficacy of Using a Single Transradial MAC Guiding Catheter for Coronary Angiography and Intervention in Patients with ST Elevation Myocardial Infarction.

BACKGROUND: There are limited data on the impact of using a single dedicated radial guiding catheter in primary percutaneous coronary intervention (PCI) via radial access. OBJECTIVES: To investigate the effect of using a single guiding catheter (MAC 3.5) for left and right coronary angiography and intervention on catheterization laboratory door to balloon (C2B) time in patients with ST elevation myocardial infarction (STEMI). METHODS: Three hundred and sixty patients were randomized (1:1) to using a single MAC3.5 guiding catheter (MAC group) or diagnostic Tiger catheter first for coronary angiography followed by guiding catheter selection (control group) for intervention. The primary outcomes were C2B. The secondary outcomes were major adverse cardiac events (MACE) at 30 days and 6 months. RESULTS: Median C2B time (16.6 min, interquartile range [IQR] 14.3-20.2 min vs 19.0 min, IQR 14.3-23.1 min; P < 0.001), total procedure time (31.0 min, IQR 26.4-37.7 min vs 34.8 min, IQR 29.7-42.5 min, P < 0.001), and overall fluoroscopy time (8.0 min, IQR 6.4-10.4 min vs 8.8 min, IQR 6.5-12.2, P = 0.04) were significantly reduced in MAC Group. Contrast consumption were similar among both groups (103 ± 37 ml vs 110 ± 41 ml, P = 0.16). The MACE rate in MAC group and control group was 3.3 versus 4.4% (P = 0.586) at 30 days and 3.3 versus 5.0% (P = 0.429) at 6 months, respectively. CONCLUSIONS: A single MAC3.5 guiding catheter for coronary angiography and intervention can shorten C2B time, procedure time, and fluoroscopy time. (RAPID study; NCT01759043).

Tissue Reactions to Heterogenic and Allogeneic Acellular Dermal Matrix Mesh Placed in the Vesicovaginal Space in a Rabbit Model.

BACKGROUND AND AIM: This study is aimed at investigating the tissue reactions of heterogenic and allogeneic acellular dermal matrix (ADM) mesh implanted in the vesicovaginal space in a rabbit model. METHODS: Twenty eight rabbits were implanted with heterogenic or allogeneic mesh, respectively, in the vesicovaginal space, and 4 served as the no-implantation control group. Rabbits were sacrificed at 7, 30, and 90 days after implantation. Histopathological study and immunohistochemical examination for collagen were performed. RESULTS: Heterogenic but not allogeneic mesh was identifiable at 90 days. In the allogeneic group, neovascularization was observed from day 7 after implantation. A chronic inflammatory reaction was noted in the heterogenic group at 30 days that decreased at 90 days. Inflammation was less in the allogeneic group, but giant cells and fibroblasts were present. With respect to collagen, the heterogenic mesh remained structurally unchanged at 90 days, while new collagen fibers were observed in the allogeneic group from day 7. CONCLUSION: The immunological outcomes of heterogenic and allogeneic ADM mesh are different. Heterogenic mesh induces a chronic inflammatory reaction at day 30 after implantation, and maintains its original form longer. Allogeneic mesh is associated with new collagen generation, but degrades earlier.

An atresia cervix removal, lower uterine segment substitute for cervix and uterovaginal anastomosis: a case report and literature review.

PURPOSE: The management of cervical dysgenesis is still a big challenge, mostly due to the complexity of the malformation and the difficulty to conserve the patient's fertility during the surgery. The objective of this article is to report a new successful approach for treating cervical dysgenesis as well as conserving patients' fertility. MATERIALS AND METHODS: We presented a case of a 22-year-old girl with vaginal agenesis and cervical dysgenesis, who after an initial failure at reconstructive surgery was successfully treated by removing a cord-like cervix and a central muscular cylinder of her lower uterine segment and lining the channel with peritoneum as the reconstructed cervix. RESULTS: The patient has had normal menstruation without dysmenorrhea for one and a half years since the surgery. CONCLUSIONS: Several steps should be followed in managing patients with congenital cervical atresia: (1) a sufficient imaging evaluation before operation is necessary; (2) a falling-off-proof cervical catheter such as a mushroom catheter (also referred to as pezzers self-retaining catheter), and a proper vaginoplasty are key to a successful cervical canalization; (3) smooth grafted tissues such as peritoneum can be used to line the cervical canal to avoid adhesions.

[Relevance between expectations before treatment, new symptoms and satisfaction after treatment in patients with pelvic organ prolapse].

OBJECTIVE: To investigate the relevance between expectations before treatment, new symptoms and satisfaction after treatment of the pelvic organ prolapse (POP) patients. METHODS: Made a collection of 75 cases of POP patients at Peking University Third Hospital, who were affected by the POP symptoms and came to our clinic for treatment from January to December in 2013. Prospectively investigate the patients' expectations before treatment, which were the most troubling symptoms to be solved. According to treatment we divided the patients into surgery and pessary groups. Two groups were followed up with the degree to achieve the desired goals using patient global impression of improvement (PGI-I), new symptoms and satisfaction after treatment, try to find the relevance between expectations before treatment, new symptoms and satisfaction after treatment. RESULTS: There were 47 (63%, 47/75) patients in the surgical group and 28 (37%, 28/75) patients in the pessary group. The top three problems for patients were friction when walking (25%, 19/75), dysuria (23%, 17/75) and the feeling of vaginal prolapse (19%, 14/75). The follow-up rate was of 93% (70/75), follow-up time was (5 ± 4) months. Satisfaction score after treatment of surgical group was higher than that of pessary group [(4.9 ± 0.4) versus (4.0 ± 1.3) scores, P < 0.01]. There was no statistically significant difference between two groups of PGI-I score [(6.7 ± 0.6) versus (6.6 ± 0.9) scores, P = 0.886]. The top three new symptoms after treatment were increased secretion, urinary incontinence and dysuria. PGI-I and satisfaction scores was relevant (P = 0.021). The availability of new symptoms and satisfaction scores was relevant (P = 0.001). CONCLUSION: When achieving higher expectations to the treatment and no more new symptoms, the satisfaction score after treatment is higher.

[Factors influencing therapy decision in patients with severe pelvic organ prolapse].

OBJECTIVE: To investigate the factors influencing therapy decision of surgery or pessary in patients with severe pelvic organ prolapse (POP). METHODS: Totally 419 cases of III to IV degree POP patients were studied retrospectively. Patients were divided into surgery and pessary groups according to their own choice. Clinical characters were compared such as age, body mass index (BMI), age of onset and disease duration, POP stage, complications. RESULTS: 67.5% (283/419) patients were in the surgical group and 32.5% (136/419) patients in the pessary group. Patients in surgical group had higher BMI [(25.1 ± 3.5) versus (23.8 ± 2.6) kg/m²], elder age of onset [(62 ± 12) versus (57 ± 11) years old], longer disease duration [(5 ± 8) versus (11 ± 11) years] and higher POP staging of middle compartment and less cardiac disease [20.1% (57/283) versus 30.9% (42/136)] than those in pessary group, all had significant difference (P < 0.05). Logistic regression analysis on the above factors showed a statistically significant difference between two groups, BMI, disease duration and POP staging of middle compartment were independent factors (OR = 1.141, 0.932, 1.389; all P < 0.01). CONCLUSIONS: Patients with higher BMI, higher POP staging of middle compartment and less cardiac disease tended to choose surgery. Patients with younger age of onset and longer disease duration tended to choose pessary. Factors as age, POP staging of anterior and posterior compartment, history of POP surgery, complicated with hypertension and diabetes, showed no influence on treatment choice.

[Clinical value of MRI in cesarean scar pregnancy].

OBJECTIVE: To explore the clinical value of MRI in diagnosing and treating cesarean scar pregnancy (CSP). METHODS: A retrospective analysis was conducted on the clinical manifestations of 54 patients diagnosed with CSP between January 2009 to January 2013 in Peking University Third Hospital. Based on the patients' MRI image and other clinical datas, we did transvaginal operation on patients with CSP1, and transvaginal combined with abdominal operations on patients with CSP2. The intraoperative blood loss, operation time, postoperative hospital stay, and the length of time required for of serum hCG dropping to normal of the patients were analyzed. RESULTS: The average age of the 54 patients was (34±5) years and the average duration of gestation was (56±16) days, all patients' vital sign were stable, the hCG level was 23-142 962 U/L before treatment. Twelve patients were diagnosed with CSP1 by MRI, and 5 of them had focus of 1-2 cm in diameter, the 5 patients' serum hCG level was 436-1 159 U/L and 23-32 days after drug administration, their hCG level returned to normal; the other 7 patients had focus of 2.0-4.4 cm in diameter, and their hCG level was 2 218-63 446 U/L, lesion resection was done on the 7 patients by hysteroscope or under B-ultrasound monitor. Forty-two patients were diagnosed with CSP2, and their focus were 1.0-7.1 cm in diameter, and serum hCG level were 23-142 962 U/L. We did bilateral uterine artery occlusion by laparoscope or laparotomy during operation for 22 patients or bilateral uterine artery embolization (UAE) before operation for 20 patients, then we did lesion resections. The blood loss during operation of CSP1 or CSP 2 was 50.1, 267.2 ml; operation time was 30, 128 minutes; postoperative hospital stay was 4.6, 6.7 days; their serum hCG returned to normal 13-30 days after the surgery. All the 54 patients' uterus were and the patients undergoing operations were all cured without the second operation. CONCLUSION: MRI is an effective method to conduct clinical treatment in CSP.

Taurine Regulates the Expression of Interleukin -17/10 and Intestinal Flora and Protects the Liver and Intestinal Mucosa in a Nonalcoholic Fatty Liver Disease Rat Model.

Purpose: To investigate the intestinal inflammatory response and the abundance of intestinal bacteria in rats with high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and assess the intervention effects of taurine (TAU). Methods: Forty male Sprague-Dawley rats were randomly divided into five groups: group I, normal diet and normal saline gavage; group II, normal diet and TAU gavage; group III, HFD and normal saline gavage; group IV, HFD and TAU gavage (from the 1st week); group V, HFD and TAU gavage (from the 10th week). At the end of the 16th week, all the animals were sacrificed. Body weight, liver weight, liver function, and serum lipid levels were measured. The histopathologies of the liver and ileum were observed. The mRNA and protein expression levels of interleukin 17 (IL-17) and IL-10 in the ileum were detected by reverse transcription quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Three types of bacteria were detected in intestinal feces using the 16S rDNA qPCR method. Results: The ileal IL-17 level in group III was significantly higher than those in the other four groups (P < 0.01). The ileal IL-10 mRNA levels in group IV was significantly higher than those in groups III and V (P < 0.05), and IL-10 protein MOD levels in group III was significantly lower than those in the other four groups (P < 0.01). The numbers of Lactobacillus in group III were significantly lower than those in the other four groups (P < 0.01 or P < 0.05). The numbers of Bifidobacteria in groups IV and V were significantly increased compared with that in group III (P < 0.05). Conclusion: TAU may down-regulate the expression of IL-17, up-regulate the expression of IL-10 and regulate the intestinal flora, and alleviate the liver and intestinal damage in rats with HFD-induced NAFLD.

The efficacy and safety of Bazi Bushen Capsule in treating premature aging: A randomized, double blind, multicenter, placebo-controlled clinical trial.

PURPOSE: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. STUDY DESIGN AND METHODS: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. RESULTS: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. CONCLUSIONS: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. TRIAL REGISTRY: https://www.chictr.org.cn/showproj.html?proj=166181.

[Analysis of mesh related complications after trans-vaginal mesh-augmented pelvic floor reconstruction surgery].

OBJECTIVE: To evaluate the complications after trans-vaginal mesh-augmented pelvic floor reconstruction in treatment of pelvic organ prolapse (POP). METHODS: From February 2007 to October 2009, vaginal mesh procedures were performed on 91 women with POP stage III-IV in Peking University Third Hospital. The operative complications were studied. RESULTS: Ninety patients underwent successful surgery among 91 patients. Follow-up rate was 94% (85/90) at a median follow-up of 28.4 (15 - 44) months. One patient underwent intraoperative organ injuries, and 10 patients had postoperation mesh-related complications. The rate of mesh-related complications was 2% (2/85), 2% (2/85), 4% (3/85), 4% (3/85) on 6, 6 - 12, 12 - 24 and more than 24 months following up, respectively. Seven patients underwent conservative treatment and the symptoms were improved. Three patients underwent the second surgery, and the symptoms were cured or relieved. CONCLUSION: The incidence of mesh-related complications was low, and interventions were effective in vaginal mesh procedure.

[Clinical study on silicone pessary in the treatment of pelvic organ prolapse].

OBJECTIVE: To evaluate the therapeutic effect and influence factors of silicone pessary in treatment of pelvic organ prolapse (POP). METHODS: From October 2005 to October 2010, 132 with symptomatic POP managed by pessary were enrolled in this retrospective study. Validated prolapse quality of life questionnaire (pelvic floor distress inventory short form 20, PFDI-20), pelvic floor impact questionnaire short form 7 (PFIQ-7) and the patients' satisfaction degree were used to evaluate the therapeutic effect. Clinical characteristic of the patients with successful using for more than 6 months (successful fitting group), giving up within 6 months (giving up group), unsuccessful fitting (unsuccessful fitting group) were compared. Factors influencing satisfaction degree and causing discontinuation were investigated. RESULTS: One hundred and six among 132 (106/132, 80.3%) patients were in successful fitting group, 26 (26/132, 19.7%) patients were in the unsuccessful fitting group. In the successful fitting group, 86.8% (92/106) patients were followed up, the median follow-up time was 12.5 months. And 78.3% (72/92) patients continued to use pessary with the wearing time ranged 3 - 69 months; 21.7% (20/92) patients discontinued with the wearing time ranged 1 - 38 month, 14 patients (14/20) gave up in the initial 6 months. The median scores of PFDI-20 and PFIQ-7 questionnaires before pessary use were 50.0 and 47.6, which decreased to 8.9 and 0.0 after pessary use (P < 0.05). And 87.1% (61/70) patients were satisfied. There was no significantly difference among 3 groups on clinical characteristics, such as age, body mass index (BMI), pelvic surgery and so on (P > 0.05). The main factor influencing satisfaction degree and causing discontinuation was difficulties in placing and removing. CONCLUSIONS: Silicone pessary is effective for patients with POP. It could relieve discomfort symptoms and improve quality of life. The main factor influencing pessary use is difficulties in placing and removing. Thus, More suggestions are needed for patients in the initial 6 months.

Seaweed polysaccharide relieves hexavalent chromium-induced gut microbial homeostasis.

Heavy metals released in the environment pose a huge threat to soil and water quality, food safety and public health. Additionally, humans and other mammals may also be directly exposed to heavy metals or exposed to heavy metals through the food chain, which seriously threatens the health of animals and humans. Chromium, especially hexavalent chromium [Cr (VI)], as a common heavy metal, has been shown to cause serious environmental pollution as well as intestinal damage. Thus, increasing research is devoted to finding drugs to mitigate the negative health effects of hexavalent chromium exposure. Seaweed polysaccharides have been demonstrated to have many pharmacological effects, but whether it can alleviate gut microbial dysbiosis caused by hexavalent chromium exposure has not been well characterized. Here, we hypothesized that seaweed polysaccharides could alleviate hexavalent chromium exposure-induced poor health in mice. Mice in Cr and seaweed polysaccharide treatment group was compulsively receive K2Cr2O7. At the end of the experiment, all mice were euthanized, and colon contents were collected for DNA sequencing analysis. Results showed that seaweed polysaccharide administration can restore the gut microbial dysbiosis and the reduction of gut microbial diversity caused by hexavalent chromium exposure in mice. Hexavalent chromium exposure also caused significant changes in the gut microbial composition of mice, including an increase in some pathogenic bacteria and a decrease in beneficial bacteria. However, seaweed polysaccharides administration could ameliorate the composition of gut microbiota. In conclusion, this study showed that seaweed polysaccharides can restore the negative effects of hexavalent chromium exposure in mice, including gut microbial dysbiosis. Meanwhile, this research also lays the foundation for the application of seaweed polysaccharides.

[Study on mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapse].

OBJECTIVE: To evaluate clinical outcome and complications of mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapse. METHODS: From Feb 2007 to Jan 2009, mesh-augmented vaginal reconstructive surgery were performed on 66 women with pelvic organ prolapse stage III-IV. Pre and postoperative symptoms, pelvic organ prolapse quantitation (POP-Q) stage and pelvic floor distress inventory-short form 20 (PFDI-20) measurements were studied to assess anatomic and quality-of-life outcome. Operative complications were also analyzed. RESULTS: Totally 65 patients underwent successful surgeries. The rate of follow-up was 97% (63/65) with a median follow-up of 17.2 months. Subjective cure rate and objective cure rate were both 97% (61/63) at 6 and 12 months after surgeries, 51 women completed PFDI-20 measurements and scores were 102 ± 50 before surgery, 16 ± 21 at 6 months and 15 ± 20 at 12 months. It reached statistical difference when scores were compared before and after surgeries (P < 0.05). Among 66 patients, 2 patients underwent organ injuries, 2 had recurrent prolapse, 4 had mesh-related complications and 1 had severe de novo stress urinary incontinence. Six patients underwent second surgery. CONCLUSIONS: Mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapsed brought satisfied clinical outcome. The incidence of mesh-related complications was low and secondary operative interventions were effective.

Design, synthesis, and biological evaluation of diosgenin-indole derivatives as dual-functional agents for the treatment of Alzheimer's disease.

The complex pathogenesis of Alzheimer's disease (AD) has become a major obstacle in its treatment. An effective approach is to develop multifunctional agents that simultaneously target multiple pathological processes. Here, a series of diosgenin-indole compounds were designed, synthesized and evaluated for their neuroprotective effects against H2O2 (hydrogen peroxide), 6-OHDA (6-hydroxydopamine) and Aß (beta amyloid) damages. Preliminary structure-activities relationship revealed that the introduction of indole fragment and electron-donating group at C-5 on ring indole could be beneficial for neuroprotective activities. Results indicated that compound 5b was the most promising candidate against cellular damage induced by H2O2 (52.9 ± 1.9%), 6-OHDA (38.4 ± 2.4%) and Aß1-42 (54.4 ± 2.7%). Molecular docking study suggested the affinity for 5b bound to Aß1-42 was -40.59 kcal/mol, which revealed the strong binding affinity of 5b to Aß1-42. The predicted values of brain/blood partition coefficient (-0.733) and polar surface area (85.118 Å2) indicated the favorable abilities of BBB permeation and absorption of 5b. In addition, 5b significantly decreased ROS (reactive oxygen species) production induced by H2O2. In the following in vivo experiment, 5b obviously attenuated memory and learning impairments of Aß-injected mice. In summary, compound 5b could be considered as a promising dual-functional neuroprotective agent against AD.