ObjectiveTo investigate the effect and mechanism of caveolion-1 on the growth and proliferation of human pancreatic carcinoma cell Panc1, in vitro. MethodsThe plasmid pCI-neo-cav-1 and its corresponding empty vector (pCI-neo) were transfected into Panc1 cell line (study group and control group, respectively). Expressions of caveolin-1, Akt, and Aktphosphate (p-Akt) were determined in transfectants by Western blot analysis. The cell growth curve was drawn and the double time was calculated in each group, and the cell cycle was analyzed by flow cytometry. The colony formation ability of tumor cells was detected by anchorageindependent growth assay. ResultsCaveolin-1 expression was up-regulated (Plt;0.01) and the growth of Panc1 cell was inhibited significantly (Plt;0.01) in the study group comparing with the control group. Caveolin-1 overexpression inhibited proliferation of Panc1 cell by arresting the cell cycle in the G0/G1 phase (Plt;0.05), the rate of S phase in the study group was lower than that of the control group (Plt;0.01). Proliferation index of the study group was also lower than that of the control group (Plt;0.01). Caveolin-1 overexpression reduced the capacity of the cells to form colonies in soft agar (Plt;0.01). p-Akt protein was reduced in the study group as compared with the control group (Plt;0.05). ConclusionCaveolin-1 can function as a cancer suppressor through inhibiting the activation of PI3K/Akt signaling pathway in Panc1 cell.
Recently, many researchers paid more attentions to the association between air pollution and chronic obstructive pulmonary disease (COPD). Haze, a severe form of outdoor air pollution, affected most parts of northern and eastern China in the past winter. In China, studies have been performed to evaluate the impact of outdoor air pollution and biomass smoke exposure on COPD; and most studies have focused on the role of air pollution in acutely triggering symptoms and exacerbations. Few studies have examined the role of air pollution in inducing pathophysiological changes that characterise COPD. Evidence showed that outdoor air pollution affects lung function in both children and adults and triggers exacerbations of COPD symptoms. Hence outdoor air pollution may be considered a risk factor for COPD mortality. However, evidence to date has been suggestive (not conclusive) that chronic exposure to outdoor air pollution increases the prevalence and incidence of COPD. Cross-sectional studies showed biomass smoke exposure is a risk factor for COPD. A long-term retrospective study and a long-term prospective cohort study showed that biomass smoke exposure reductions were associated with a reduced decline in forced expiratory volume in 1 second (FEV1) and with a decreased risk of COPD. To fully understand the effect of air pollution on COPD, we recommend future studies with longer follow-up periods, more standardized definitions of COPD and more refined and source-specific exposure assessments.
ObjectiveTo screen and identify an ideal lead compound with potential inhibitory effects on N-methyl-D-aspartate receptor (NMDAR) from the ZINC15 drug database, promoting drug design and development to improve epilepsy treatment. Methods Potential NMDAR inhibitors were identified through a series of computer-aided structural and chemical virtual screening techniques (Discovery Studio). Structure-based virtual screening was used to predict and further filter candidate compounds based on physicochemical, pharmacological, and toxicological properties. The binding affinity and chemical bond distribution between selected compounds and NMDAR were then analyzed, and the stability of the ligand-NMDAR complex in a natural environment was evaluated. Results The study identified one novel natural compound from the ZINC15 database, with ZINC000096085903 showing low rodent carcinogenicity, no Ames mutagenicity, no developmental toxicity, and ideal physicochemical properties. This compound demonstrated high binding affinity and favorable interaction energy, with the ZINC000096085903-NMDAR complex exhibiting more favorable potential energy than the complex formed by NMDAR and the reference ligand ketamine. Furthermore, molecular dynamics simulation indicated that this complex remains stable in vivo and can inhibit NMDAR similarly to ketamine. Conclusion ZINC000096085903 is an ideal lead compound for NMDAR inhibition. With higher binding affinity and stability when bound to NMDAR, as well as slower metabolism, ZINC000096085903 showed significant potential for long-term epilepsy treatment.
To study the relationship between the level of serum thyrotropin receptor antibody (TRAb) and the severity of Crave′s disease. From August, 1996 to June, 1998, 156 outpatients with Crave′s disease were followed up. The level of serum TRAb were measured by radio-receptor-analysis (RRA). Results: ①The level of serum TRAb rose in 90.1% of the untreated group; ②The level of serum TRAb restored to normal after the antithyroid drugs were used and the thyroxine level in serum returned to normal; ③In recurrent patients with the treatment of131I, drugs or operation, the serum TRAb level increased. Conclusion: The level of serum TRAb has great significance in the diagnosis, treatment and follow up of the Crave′s disease.
Objective To develop a machine learning (ML) model to predict the risk of death in intensive care unit (ICU) patients with chronic obstructive pulmonary disease (COPD), explain the factors related to the risk of death in COPD patients, and solve the "black box" problem of ML model. Methods A total of 8088 patients with severe COPD were selected from the eICU Collaborative Research Database (eICU-CRD). Data within the initial 24 hours of each ICU stay were extracted and randomly divided, with 70% for model training and 30% for model validation. The LASSO regression was deployed for predictor variable selection to avoid overfitting. Five ML models were employed to predict in-hospital mortality. The prediction performance of the ML models was compared with alternative models using the area under curve (AUC), while SHAP (SHapley Additive exPlanations) method was used to explain this random forest (RF) model. Results The RF model performed best among the APACHE IVa scoring system and five ML models with the AUC of 0.830 (95%CI 0.806 - 0.855). The SHAP method detects the top 10 predictors according to the importance ranking and the minimum of non-invasive systolic blood pressure was recognized as the most significant predictor variable. Conclusion Leveraging ML model to capture risk factors and using the SHAP method to interpret the prediction outcome can predict the risk of death of patients early, which helps clinicians make accurate treatment plans and allocate medical resources rationally.
ObjectiveTo evaluate short-term effectiveness of revision total knee arthroplasty (TKA) with porous-coated metaphyseal Sleeve and MBT implant.MethodsA clinical data of 23 patients (24 knees) who underwent revision TKA by using porous-coated metaphyseal Sleeve combined with MBT implant between March 2015 and April 2017 was retrospectively analyzed. There were 8 males (8 knees) and 15 females (16 knees). The age ranged from 48 to 85 years (mean, 65.4 years). The cause of revision TKA included infection in 14 knees, aseptic loosening in 8 knees, instability in 1 knee, and stiff knee in 1 knee. Bone defects were classified according to the Anderson Orthopaedic Research Institute (AORI) bone defect classification. The femoral defect was rated as type ⅡA in 5 knees, type ⅡB in 17 knees, and type Ⅲ in 2 knees; the tibial defect was rated as type ⅡA in 2 knees, type ⅡB in 20 knees, and type Ⅲ in 2 knees. The mean time between primary TKA and revision TKA was 30.6 months (range, 6-86 months). The preoperative range of motion (ROM) was (56.0±24.9)°. The preoperative Hospital for Special Surgery (HSS) total score was 41.9±14.2; and the pain and function scores were 8.5±5.2 and 33.4±13.5, respectively.ResultsAll patients were followed up 12-39 months (mean, 25.6 months). The mean operation time was 2.2 hours (range, 1.6-2.9 hours). The mean intraoperative blood loss was 580 mL (range, 400-1 000 mL). There were 2 knees (8.3%) of intraoperative fracture associated with Sleeve insertion and 1 knee (4.2%) of acute postoperative infection at 25 days after revision TKA. All incisions healed by first intention. No deep venous thrombosis of lower extremity occurred. X-ray film showed that all implants were stable. At last follow-up, slight discomfort after exercise occurred in 4 knees (16.7%); end-of-stem pain in the tibia occurred in 1 knee (4.2%). The ROM was (114.6±5.1)°, which had significant improvement compared with the preoperative result (t=11.698, P=0.000). The HSS total score (89.0±10.9), pain score (26.9±6.6), and function score (62.1±5.8) also had significant improvement compared with the preoperative results (t=15.616, P=0.000; t=12.522, P=0.000; t=10.076, P=0.000).ConclusionThe porous-coated metaphyseal Sleeve combined with MBT implant in revision TKA has a significant improvement in short-term effectiveness and no signs of implant loosening.
ObjectiveTo explore the clinical value of modified Soave procedure with stapler for the treatment of Hirschsprung disease. MethodsThe clinical data of 26 patients with Hirschsprung disease adimitted in No.477 hospital from January 2002 to December 2010 were analyzed retrospectively. All the patients underwent modified Soave operation with rectal mucosa and proximal intestine stapled end-to-end. ResultsAll operations were successful without anastomotic leakage, aponeurosis of investment infection, and colonitis. Increased stool frequency presented in two cases, which were cured with astringents on day 15 and 30 after operation, respectively. Mild fecal contamination was in one case. All cases were followed up between 3 months to 60 months, with an average 32 months, without incontinence and constiptation. ConclusionModified Soave procedure with stapler is safe and effective for the treatment of Hirschsprung disease in elder children and adult.
Objective To summarize the early results and clinical experience of using the J-Valve for transcatheter valve-in-valve implantation in patients with degenerated bioprosthesis at different anatomic positions. Methods A retrospective analysis was conducted to evaluate the short-term outcomes of 39 consecutive patients who underwent transcatheter valve-in-valve implantation using the J-Valve System in the Department of Cardiac Surgery of Guangdong Provincial People’s Hospital from April 2020 to August 2021 due to bioprosthetic degeneration at different anatomic positions. Among them, 35 patients underwent transcatheter mitral valve-in-valve (TMViV) implantation, 1 transcatheter aortic valve-in-valve (TAViV) implantation, 1 transcatheter tricuspid valve-in-valve (TTViV) implantation, 1 TMViV implantation with simultaneous TAViV implantation, and another one TMViV implantation with simultaneous transcatheter aortic valve replacement (TAVR) and perivalvular leakage (PVL) closure. Results Among the 35 patients who underwent isolated TMViV implantation, 17 were male and 18 were female with a mean age of 72.6±10.8 years. Mean duration between two operations was 10.5±2.7 years. The mean Society of Thoracic Surgeons and EuroSCORE Ⅱ scores were 12.95%±9.61% and 13.91%±8.94%, respectively. The device success rate was 97.1% and no death occured during the operation. One patient was transferred to thoracotomy due to device displacement, 1 was re-opened for uncontrolled bleeding, and 1 presented left ventricular outflow tract obstruction. One patient underwent craniotomy due to intracranial hemorrhage within 30 days after surgery, and no other complications occurred including death, stroke, permanent pacemaker implantation, cardiac tamponade, or re-hospitalization. The mean follow-up time was 6.0±4.4 months, the mean mitral valve gradient was significantly improved (10.4±2.0 mm Hg vs. 5.5±1.2 mm Hg, P<0.05), and the New York Heart Association class≤Ⅱ in all the patients at the last follow-up. Among the other 4 patients who did not undergo isolated TMViV implantation, the transapical TAViV implantation and the trans-right atrium TTViV implantation were successful without intra- or post-operative complications. The patient who underwent TMViV and TAViV implantation simultaneously via transapical approach died of severe pulmonary hemorrhage and multiple organ failure 16 days after surgery. The other patient who underwent transapical TMViV combined with TAVR and PVL closure died of septic shock 10 days after the surgery. Conclusion Transcatheter valve-in-valve implantation using the J-Valve system is shown to be a safe and effective procedure to treat mitral, aortic and tricuspid bioprosthetic valve dysfunction in high-risk patients, providing a new alternative to surgical surgery for degenerated bioprosthesis at different anatomic positions. However, simultaneous different valves intervention should be very cautious.
ObjectiveTo review the research progress of different ways of stem cells generation and cells dedifferentiation induced by reversine. MethodsThe papers related to reversine inducing cells dedifferentiation and stem cells generation were reviewed. ResultsTo obtain stem cells, there are always some disadvantages via somatic cell nuclear transfer or gene transfection. However reversine, a small molecule, can induce cells dedifferentiation which has unique advantage. But its mechanism is still unclear. ConclusionThe chemical approach for generation of induced pluripotent stem cells by reversine may take the place of other methods.
ObjectiveTo explore the value of potaried technique with Trivex system in treatment for venous skin ulcer with deep venous thrombosis sequelae (DVTS) of lower limbs. MethodsTotal 166 patients with venous skin ulcer with DVTS of lower limbs were included in this study. The patients of operation group (94 patients involving 94 legs) were treated by using potaried technique with Trivex system. The patients of nonoperation group (72 patients involving 72 legs) were treated by using nonoperative method. The clinical indexes of skin infection rate, skin necrosis rate, shrinkage rate of wound area, skin depigmentation rate, ulcer healing rate and ulcer recurrence rate were used to assess the clinical curative effect between two groups on 5, 20, 120 and 360 d after operation or treatment, respectively. ResultsThere were no skin infection and skin necrosis in two groups on 5 d after operation or treatment. The rate of shrinkage of wound area and skin depigmentation of patients in operation group were significantly higher than those in nonoperation group on 20 d after operation or treatment 〔(95.8±2.138)% vs. (68.7±3.125)%，P=0.048; (87.6±1.263)% vs. (12.3±1.324)%， P=0.018〕. The rate of the ulcer healing of patients in operation group was significantly higher than that in nonoperation group on 120 d after operation or treatment (97.9%vs. 8.3%， P=0.014). The rate of the ulcer recurrence of patients in operation group was significantly lower than that in nonoperation group on 360 d after operation or treatment (5.3% vs. 97.2%， P=0.015). ConclusionThe potaried technique with Trivex system can be used as one of the surgical treatment methods for venous skin ulcer with DVTS of lower limbs.
