Objective:To study the methylation level of miR-5194 promoter in bladder cancer tissues, and explore the effects of miR-5194 on the proliferation and migration of bladder cancer cells by targeting p21-activated protein kinase 2 (PAK2).Methods:The methylation level of miR-5194 promoter in bladder cancer tissues was analyzed using MethHC database. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-5194 in bladder cancer MGH-U3, EJ, J82, and UMUC3 cells. 5-aza-2′-deoxycytidine (5-Aza-CdR) was used to treat bladder cancer cell lines, and RT-qPCR was used to detect the changes in the expression of miR-5194 in bladder cancer cell lines after 5-Aza-CdR treatment. UMUC3 cells were divided into miR-5194 group and NC group, and miR-5194 or miR-NC were transfected into UMUC3 cells, respectively. Colony formation assay and scratch assay were used to detect the effect of overexpression of miR-5194 on the proliferation and migration of UMUC3 cells. The bioinformatics tool miRGator and dual-luciferase reporter gene experiments verified the targeting relationship between miR-5194 and PAK2. The effect of overexpression of miR-5194 on the expression of PAK2 mRNA in UMUC3 cells was detected by RT-qPCR. The effect of overexpression of miR-5194 on the expression of PAK2 protein, proliferation-related proteins (CDK1, Cyclin B) and migration-related proteins (FOXC2, E47) in UMUC3 cells was detected by Western blotting. The measurement data were expressed as mean ± standard deviation ( ± s), the independent sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison among multiple groups. Results:The methylation level of miR-5194 promoter in bladder cancer tissues was significantly higher than that in adjacent tissues ( P<0.01). Compared with the immortalized bladder epithelial cells SV-HUC-1, the expression of miR-5194 in bladder cancer cells was significantly down-regulated ( P<0.01). After 5-Aza-CdR treatment, the expression of miR-5194 in bladder cancer cells was significantly increased ( P<0.01). The number of colonies in miR-5194 group and NC group were 31.30 ± 8.09 and 99.98 ± 10.53, respectively, and the proliferation ability of UMUC3 cells in miR-5194 group was weakened ( P<0.01). The migration rates of UMUC3 cells in miR-5194 group and NC group were (31.50 ± 7.17)% and (76.06 ± 4.86)%, respectively, and the migration ability of UMUC3 cells in miR-5194 group was weakened ( P<0.01). miR-5194 can target bind PAK2 gene ( P<0.01). The relative expression of PAK2 mRNA in UMUC3 cells of miR-5194 group and NC group were 1.02 ± 0.34 and 5.43 ± 0.76, respectively, and miR-5194 could negatively regulate the expression of PAK2 mRNA ( P<0.01). Compared with the NC group, the expression of PAK2 protein, the expression of proliferation-related proteins CDK1 and Cyclin B, and the expression of migration-related proteins FOXC2 and E47 were down-regulated in UMUC3 cells with miR-5194 overexpression. Conclusion:The methylation level of miR-5194 promoter in bladder cancer tissue was significantly increased, and miR-5194 inhibited the proliferation and migration of bladder cancer cells by targeting down-regulation of PAK2 expression in bladder cancer UMUC3 cells.

Humans ; COVID-19 Vaccines/therapeutic use* ; COVID-19/prevention & control* ; SARS-CoV-2 ; China ; Antibodies, Viral

Objective To compare the pharmaceutics and drug interactions of noiiglutide injection,INS068 injection,HR17031 Injection,and noiiglutide+INS068 injection in healthy subjects Methods This was a single center,randomized,open-label,4-cycle,4-cohort trial.Healthy subjects were allocated to 4 groups randomly.HR17031(17 U/0.04 mg),INS068(17 U),noliglycopeptide(0.04 mg),and INS068(17 U)combined with noiiglutide(0.04 mg)were injected subcutaneously into the abdomenon on day 1,8,15 and 22 respectively.Venous blood was collected at different timing before and after administration,and the concentrations of noiiglutide in plasma and INS068 in serum were measured by HPLC-MS/MS method.Relevant pharmacokinetic parameters were calculated using the WinNonlin non compartment model.Results In HR17031,INS068,and INS068 combined with noiiglutide groups,the main pharmacokinetic parameters of INS068 in serum were calculated and listed as follows:Cmax were(19.50±4.06),(18.10±4.56)and(18.40±5.81)ng·mL-1,tmax was 12,10 and 8 h,t1/2 was(9.27±1.70),(11.00±2.81)and(11.0±3.18)h,AUC0-twere(505.00±62.20),(498.00±70.50)and(491.00±74.20)ng·mL-1·h.In HR17031,noiiglutide,and INS068 combined with noiiglutide groups,the main pharmacokinetic parameters of noiiglutide in plasma were calculated and listed as follows:Cmax were(3.61±0.82),(4.63±0.87)and(4.54±0.86)ng·mL-1,tmax was all 8.00 h,t1/2 was(10.50±1.61),(9.49±1.40)and(9.55±1.61)h,AUC0-twere(94.30±20.10),(106.00±20.20)and(105.00±19.00)ng·mL-1·h.Conclusion There was no significant difference in bioavailability of INS068 and noiiglutide in HR17031 compared with INS068 and noiiglutide whether combined or used alone.

Objective:To investigate the difference in the efficacy of extended trochanteric osteotomy (ETO) and subtrochanteric shortening osteotomy (SSO) in total hip arthroplasty (THA) for Crowe type IV developmental dysplasia of the hip (DDH).Methods:Forty patients (51 hips) who underwent primary THA for Crowe type IV DDH from April 2012 to August 2020 at the First Affiliated Hospital of Soochow University and the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The patients were classified into ETO (extended greater trochanteric osteotomy) group and SSO(subtrochanteric shortening osteotomy) group. There were 12 patients (14 hips) in the ETO group, with 3 males and 9 females, aged 49.9±16.7 years old (range, 22-75 years old) and 28 patients (37 hips) in the SSO group, with 7 males and 21 females, aged 50.3±14.0 years (range, 22-76 years). In both groups, Harris hip score (HHS), leg length discrepancy, limp, Trendelenburg sign were used to evaluate the functional results and anteroposterior radiographs of the pelvis were taken at each follow-up to assess bone healing at the osteotomy site, periprosthetic osteolysis, bone ingrowth and periprosthetic loosening. Complications were recorded and analyzed.Results:All 51 hips were followed up for at least 24 months. The operative time and total blood loss was 116.8±14.2 vs. 128.3±19.2 min and 650.8±191.4 vs. 808.3±151.3 ml in the ETO group and the SSO group with significant difference ( t=2.04, P=0.047; t=3.08, P=0.003) respectively. At the follow-up of 24 months the HHS of ETO and SSO groups were 94.8±6.3 vs. 93.9±4.9 points and the leg length discrepancy was 4.6±2.2 vs. 5.2±3.0 mm. The positive rate of Trendelenburg's sign was 7% vs. 16% and the incidence of limp was 17% vs. 29% in the ETO group and the SSO group with no significant difference ( t=0.54, P=0.591; t=0.68, P=0.499; P=0.657; P=0.693). The length of femoral shortening in the ETO group and SSO group was 30.8±4.1 vs 35.3±7.9 mm with significant difference ( t=2.02, P=0.049). Time for bone healing at the osteotomy site was 5.8±1.5 vs. 6.0±1.4 months and the incidence of intraoperative femoral fractures was 36% and vs. 65% with no significant difference ( t=0.45, P=0.657; χ 2=3.52, P=0.061). Bone in-growth (or bone on-growth) fixation was obtained for all acetabular and femoral prostheses, with no hips of prosthesis displacement, periprosthetic osteolysis, or dislocation. Conclusion:Total hip arthroplasty for Crowe type IV DDH can achieve satisfactory clinical efficacy with similar functional recovery and rate of complication in extended trochanteric osteotomy and subtrochanteric shortening osteotomy. However, the extended greater trochanter osteotomy can reduce the operation time, blood loss and length of femoral shortening.

Stenotrophomonas maltophilia is a gram-negative bacillus which widely exists in natural and hospital environment, and it is also one of the common opportunistic pathogens in clinical settings. The virulence and pathogenicity of Stenotrophomonas maltophilia are weak, however, due to resistance to a variety of antibacterial drugs, it can cause bloodstream infections or pneumonia in immunocompromised or critically ill patients, leading to poor prognosis. Moreover, the inherent drug resistance and increasing acquired drug resistance may make the treatment of the first line antibiotics, like trimethoprim-sulfamethoxazole or quinolone ineffective. Therefore, it is important to understand the drug resistance mechanism and the main countermeasures for it. In this article, the research progress on drug resistance mechanism and treatment for Stenotrophomonas maltophilia are reviewed.

Developing tumor-specific drug delivery systems with minimized off-target cargo leakage remains an enduring challenge. In this study, inspired from the natural cryptobiosis explored by certain organisms and stimuli-responsive polyphenol‒metal coordination chemistry, doxorubicin (DOX)-conjugated gelatin nanoparticles with protective shells formed by complex of tannic acid and Fe

OBJECTIVE: To compare activity, function and postoperative ulnar nerve function of elbow joint by anterior transposition of ulnar nerve or not during open reduction and internal fixation for intercondylar humerus fractures. METHODS: From January 2013 to May 2017, 168 patients with intercondylar humerus fractures were treated surgically with open reduction and internal fixation (ORIF). The patients were divided into anterior subcutaneous transposition group and simple decompression group according to handling method of ulnar nerve. There were 48 patients in transposition group, including 23 males and 25 females with an average age of (42.5±15.7) years old ranging from 14 to 77 years old, and ulnar nerve treated enough free and anterior subcutaneous transpostion after reduction of intercondylar humerus fractures; while there were 120 patients in simple decompression group, including 62 males and 58 females with an average age of (43.4±17.3) years old ranging from 14 to 81 years old, ulnar nerve returned to sulci nervi ulnaris. Activity of flexion and extension of elbow joint, range of rotation of forearm were recorded at the latest following-up, Mayo score of elbow joint was used to evaluate clinical effect, McGowan grading was used to assess dysfunction of unlnar nerve. RESULTS: There was 1 patient delayed union, and 2 patients occurred joint stiffness in transposition group; while 1 patient suffered from incision infection, 1 fracture nonunion, and 4 joint stiffness in simple decompression group; and there was no statistical difference between two groups(>0.05). Forty-eight patients in transposition group were followed-up from 12 to 59 months with an average of (32.2±14.2) months, activity of flexion and extension of elbow joint was (116±28)°, range of rotation of forearm was (152±12)°, MEPS score was 88.6±11.6; and 28 patients got excellent results, 16 good, 3 moderate and 1 poor. There were 17 patients occurred injury of ulnar nerve, and 7 patients still occurred dysfunction of ulnar nerve, and 6 patients were grade I, 1 patient was grade II according to McGowan grading. In simple decompression group, there were 120 patients were followed-up from 13 to 61 months with an average of (32.0±14.9) months, activity of flexion and extension of elbow joint was (119±27)°, range of rotation of forearm was (154±16)°, MEPS score was 88.9±12.5; and 67 patients got excellent results, 44 good, 7 moderate and 2 poor. There were 42 patients occurred injury of ulnar nerve, and 22 patients still occurred dysfunction of ulnar nerve, and 18 patients were grade I, 4 patients were grade II according to McGowan grading. There were no statistical differences in following time, activity of flexion and extension of elbow joint, range of rotation of forearm, MEPS score and dysfunction of ulnar nerve. CONCLUSIONS Whether anterior transposition of ulnar nerve or not has no clarified effects for open reduction and internal fixation for intercondylar humerus fractures.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Elbow Joint ; Female ; Fracture Fixation, Internal ; Humans ; Humeral Fractures ; Humerus ; Male ; Middle Aged ; Range of Motion, Articular ; Treatment Outcome ; Ulnar Nerve ; Young Adult

OBJECTIVETo evaluate the effects of polyethylene oxide (PEO) on blood perfusion in hind limb skeletal muscles in a rat model of chronic hind limb ischemia.

METHDOSTwelve rat models of chronic hind limb ischemia established by unilateral femoral artery ligation were randomized into PEO and control groups (n=6) and treated with intravenous infusion of PEO and saline through the internal jugular vein every other day for 2 weeks. Contrast-enhanced ultrasonography was performed after the treatments to evaluate the blood flow in the skeletal muscles at different time points and blood flow reserve in the ischemic hind limbs on day 28.

RESULTSStarting from 7 days after femoral artery ligation, blood flow in the ischemic hind limb skeletal muscles was significantly higher in PEO group than in the control group (P<0.05). On day 28, blood flow reserve in the ischemic hind limb was significantly higher (P=0.012), and blood volume was significantly increased in PEO group as compared that in the control group (P=0.024).

CONCLUSIONSPEO can increase blood flow, blood flow reserve and vascular volume in the hind limb skeletal muscles in rats with chronic hind limb ischemia, suggesting that PEO can promote angiogenesis and arterial formation by increasing blood flow shear stress to improve blood supply of ischemic hind limbs.

The experiment was aimed to investigate the difference of plasma concentration and pharmacokinetic parameters between liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats, such as ginsenosides Rg₁, Re, Rf, Rb₁, Rg₂, Rc, Rb₂, Rb₃, Rd. After intravenous injection of liposome and aqueous solution in rats, the blood was taken from the femoral vein to detect the plasma concentration of the above 9 ginsenoside monomers in different time points by using HPLC. The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters. After the intravenous injection of ginsenosides to rats, nine ginsenosides were detected in plasma. In general, among these ginsenosides, the peak time of the aqueous solution was between 0.05 to 0.083 3 h, and the serum concentration peak of liposome usually appeared after 0.5 h. After software fitting, the aqueous solution of ginsenoside monomers Rg₁, Re, Rf, Rg₂, Rc, Rd, Rb₃ was two-compartment model, and the liposomes were one-compartment model; aqueous solution and liposome of ginsenoside monomers Rb₁ were three-compartment model; aqueous solution of ginsenoside monomers Rb₂ was three-compartment model, and its liposome was one-compartment model. Area under the drug time curve (AUC) of these 9 kinds of saponin liposomes was larger than that of aqueous solution, and the retention time of the liposomes was longer than that of the aqueous solution; the removal rate was slower than that of the aqueous solution, and the half-life was longer than that of the water solution. The results from the experiment showed that by intravenous administration, the pharmacokinetic parameters of two formulations were significantly different from each other; the liposomes could not only remain the drug for a longer time in vivo, but also reduce the elimination rate and increase the treatment efficacy. As compared with the traditional dosage forms, the total ginsenoside of ginseng stems and leaves can improve the sustained release of the drug, which is of great significance for the research and development of new dosage forms of ginsenosides in the future.

Purpose To investigate the relationship between ultrasonic manifestations in prostate cancer (PCa) and Gleason score,and improve the clinical value of transrectal ultrasound (TRUS) examination of PCa.Materials and Methods 362 patients with PCa treated in the First Affiliated Hospital of Soochow University from September 2009 to January 2015 were analyzed retrospectively,according to TRUS examination,the ultrasonic manifestations of PCa were divided into the localized type,diffuse type and negative type.Gleason score of pathological tissue divided the risk factor of PCa into low risk (＜7 points),medium risk (=7 points),and high risk (＞7 points).The relationship between ultrasonic manifestations of PCa and risk factor was analyzed.Results Ultrasonic results showed that,for the 362 patients with PCa,patients with ultrasonic negative manifestations accounted for 32.9％ (119/362) and those with ultrasonic positive manifestations accounted for 67.1％ (243/362),including 38.7％ (140/362) localized type and 28.4％ (103/362) diffuse type.In localized and diffuse PCa,the number of patients in high risk group was significantly more than the low risk group,and the difference among the high risk,medium risk and low risk groups was statistically significant (P＜0.05);in the low risk group,the ultrasonic negative manifestations were more than the positive manifestations,and the difference was statistically significant (P＜0.05);in high risk group,the localized and diffuse manifestations were more than the negative manifestations and the difference was statistically significant (P＜0.05).Conclusion TRUS shows more clinical values in the diagnosis and treatment of PCa,and the ultrasonic positive manifestations can preliminarily evaluate the risk factor of PCa.