Endothelial dysfunction is a key factor linking obstructive sleep apnea hypopnea syndrome (OSAHS) with cardiovascular diseases. In this study, we used advanced proteomics and metabolomics approaches to investigate the impact of extracellular vesicles (EVs) derived from the serum of OSAHS patients on endothelial function. Our multi-omics analysis identified dysregulated pathways related to fatty acid metabolism, apoptosis regulation, and inflammatory responses, highlighting fatty acid synthase (FASN) as a crucial player in OSAHS-induced endothelial dysfunction. Both in vitro and in vivo experiments demonstrated that FASN-enriched EVs impair endothelial cell viability and disrupt metabolic homeostasis, offering new insights for the development of targeted therapies for cardiovascular complications associated with OSAHS.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and a-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of b-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the b-catenin/cMyc/cyclin D1 pathway. CONCLUSION This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

Osteoporotic fracture is the most major complication of osteoporosis. It is a significant global public health problem which continues to bring serious family and social burden. In order to improve the prevention and treatment of osteoporotic fractures， many countries have carried out new ways of fracture prevention and management， and achieved some results. Prevention mainly aims at those at high risk of fracture， and includes new health education on fracture and the promotion of fall prevention measures. For management， the "Fracture liaison services" mode is mainly applied to the fracture patients， with refined patient management to deal with the fractures that have occurred. This article summarizes the global prevalence of osteoporotic fractures， risk factors， and the current research progress in fracture prevention and management in China and the West.

Objective To analyze the correlation between the concentration of serum and cerebrospinal fluid clusterin(CLU)and the severity of acute traumatic brain injury(TBI).Methods A total of 102 patients with acute moderate and severe TBI admitted to the Second Hospital of Jiaxing from September 2019 to October 2020 were included in the study,and were divided into two batches in chronological order.The first batch of 20 cases were tested for serum CLU content and its time expression map for 4 consecutive days after injury by Western blot;The second batch of 82 cases were divided into groups according to Glasgow coma score(GCS),Rotterdam-CT score and brain contusion and laceration volume,the CLU concentration in serum and cerebrospinal fluid was detected by enzyme linked immunosorbent assay(ELISA)at peak time according to the serum CLU time expression map,and the differences of CLU concentrations between the groups were compared;The correlation between CLU concentration and patients'general data,GCS score,Rotterdam CT score and brain contusion and laceration volume was analyzed by Spearman correlation coefficient;The factors affecting CLU concentration were analyzed by multiple linear regression.Results The serum CLU concentration gradually increases in patients after TBI,and reached the peak at 3 days after injury;There was no statistical difference in serum CLU concentration in two GCS groups,three Rotterdam-CT score groups and two brain contusion and laceration volume groups(P>0.05),but there was a statistical difference in cerebrospinal fluid CLU concentration(P<0.05);Cerebrospinal fluid CLU concentration was negatively correlated with GCS score(r=-0.542,P<0.05),and positively correlated with Rotterdam-CT score and brain contusion and laceration volume(r=0.414,0.738,P<0.05);There was statistical difference in the influence of brain contusion and laceration volume on cerebrospinal fluid CLU concentration(β=8.074,P<0.001).Conclusion The concentration of CLU in cerebrospinal fluid can reflect the severity of TBI,which is mainly related to the volume of brain contusion and laceration.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective To investigate the effect and psychological intervention of compound polyethylene glycol electrolyte powder in preoperative bowel preparation for gynecologic tumor patients. Methods According to the different drugs,nursing interventions will be January 2015 to March 2017 in third affiliated hospital of Tianjin medical university for surgical treatment of gynecological cancer patients 80 cases groups:control group with routine nursing intervention observation group with mannitol, psychological nursing and compound polyethylene glycol electrolyte with intervention;observation of two groups of patients improve psychological status and intestinal cleaning and the incidence of adverse reactions,the strict record related data and make comparative analysis. Results The psychological nursing and compound polyethylene glycol electrolyte powder(observation group)intervention in patients with gynecologic tumor significantly,the psychological state of patients with improvement than the control group,the bowel cleaning is better than the control group,the difference was statistically significant(P<0.05);two patients with adverse reaction rate comparison,the difference was not statistically significant. Conclusion The preparation of intestinal tract tumor patients before gynecologic selection of psychological nursing and intervention effect of polyethylene glycol electrolyte powder can significantly improve the psychological state,full bowel cleansing patients with high effective rate,and will not increase the adverse reactions,and is worthy of clinical application.

Objective To evaluate cerebrospinal fluid adenosine deaminase(CSF-ADA)activity in the diagnosis of tuberculous meningitis(TMB), and to observe its dynamic changes. Methods A total of 160 patients were included and were divided into two groups: 76 cases of TBM and 84 cases of non-TBM.Among the cases of non-TBM, there were 36 cases of bacterial meningitis, 30 cases of viral meningitis and 18 cases of cryptocoocal meningitis. All the patients were measured with their CSF-ADA activity by Enzymecoupled assay(Trinder method)and 47 patients of TBM were measured again after 2 weeks' and 6 weeks'antitubercular therapy. Results were expressed as(-x)± s. Mann-Whitney U test and paired-samples t test were used. Results CSF-ADA activity in TBM group was(12.9 ±6.4)U/L, while that in the non-TBM group was(6.0 ± 4.1)U/L, the difference was of statistical significance(U = 7.860, P ＜ 0.05). With the cutoff value of 9 U/L, the sensitivity and specificity to differentiate TBM from non-TBM was 84.21% and 83. 33%, respectively. CSF-ADA activity decreased in TBM patients after antitubercular treatment.Conclusions CSF-ADA activity can be an effective laboratory marker for early differential diagnosis of TMB with the cut-off value of 9 U/L. Dynamic changes of CSF-ADA activity may be a indicator for the effect of antitubercular treatment.

BACKGROUND: One of mechanisms involved in treating cerebral ischemia with bone marrow mesenchymal stem cells (BMMSCs) implantation is paracrine action. However, few studies have reported this mechanism.OBJECTIVE: To observe the inhibitory effect of BMMSCs paracrine action on apoptosis and its mechanism after cerebral ischemia. METHODS: BMMSCs were isolated from rats with adherent culture. Rat cerebral ischemia model was established by the middle cerebral artery occlusion. A total of 24 rats were divided into 4 groups, with 6 animals in each group. Cell implantation medication group: rats were received U0126 medication after BMMSCs implantation; Non-implantation medication group: rats were received U0126 medication after PBS injection; Cell implantation control group: received solvent medication after BMMSCs implantation; Non-implantation control group: received solvent medication after PBS injection. At 7 days after operation, the expressions of vascular endothelial cell growth factor (VEGF) and p-ERK1/2 protein were measured by Western blot analysis, and the apoptosis cells in the area of ischemic penumbra and cortex were examined by TUNEL. RESULTS AND CONCLUSION: The VEGF protein content in the brain tissue was significantly greater in the cell implantation groups than that of the non-implantation group, with increased p-ERK1/2 and decreased apoptosis cells. The expression of p-ERK1/2 was down-regulated in rats which were administrated U0126 while the number of the apoptosis cells was increased, but the VEGF protein expression had no statistical difference. It suggested that BMMSCs can paracrine VEGF in the striatum of brain and play an inhibitory effect on apoptosis in the ischemia area via activating ERK1/2.

This study examined the effect of GHRP-6,a known GHSs receptor agonist,on the phosphorylation of cAMP-responsive clement-binding protein(CREB)and the underly mechanism.GH3 cells were cultured and subjected to different treatments as follows: GHRP-6,GHRP-6 plus GHRH,phorbol ester(PMA),an activator of PKC,alone or in combination with GHRP-6,G(o)6983,a general inhibitor of PKCs,in the presence or absence of GHRP-6,rottlerin,an inhibitor of PKCs,alone or plus GHRP-6.The cells were transiently transfected with PKCσ-specific siRNA and then treated with GHRP-6.GH level was measured by enzyme-linked immunosorbent assay(ELISA).The expression of phosphor-CREB,PKCσ,PKCθ and phosphor-PKCσ was determined by Western blotting.The results showed that GHRP-6 stimulated GH secretion in both time-and dose-dependent manners and enhanced the effect of GHRH on GH secretion.GHRP-6 was also found to induce CREB phosphorylation.Moreover,GH secretion was enhanced by the PKC activator PMA and reduced by the PKC inhibitors(G(o)6983,rottlerin)and knockdown of PKCσ.PKCσ could be activated by GHRP-6.It is concluded that PKC,especially PKCσ,mediates CREB phosphorylation and GHRP-6-induced GH secretion.

This study examined the effect of GHRP-6, a known GHSs receptor agonist, on the phosphorylation of cAMP-responsive element-binding protein (CREB) and the underly mechanism. GH3 cells were cultured and subjected to different treatments as follows: GHRP-6, GHRP-6 plus GHRH, phorbol ester (PMA), an activator of PKC, alone or in combination with GHRP-6, Gö6983, a general inhibitor of PKCs, in the presence or absence of GHRP-6, rottlerin, an inhibitor of PKCs, alone or plus GHRP-6. The cells were transiently transfected with PKCsigma-specific siRNA and then treated with GHRP-6. GH level was measured by enzyme-linked immunosorbent assay (ELISA). The expression of phosphor-CREB, PKCsigma, PKCtheta and phosphor-PKCsigma was determined by Western blotting. The results showed that GHRP-6 stimulated GH secretion in both time- and dose-dependent manners and enhanced the effect of GHRH on GH secretion. GHRP-6 was also found to induce CREB phosphorylation. Moreover, GH secretion was enhanced by the PKC activator PMA and reduced by the PKC inhibitors (Gö6983, rottlerin) and knockdown of PKCsigma. PKCsigma could be activated by GHRP-6. It is concluded that PKC, especially PKCsigma, mediates CREB phosphorylation and GHRP-6-induced GH secretion.