To identify the advantages of modification treated poly (D, L-lactic and glycolic acid) with poly (ethylene glycol) (PLGA/mPEG, PELGA) block copolymer, blood compatibility was evaluated in vitro. Three different proportional block copolymers (LA/GA80: 20, 70: 30, 50: 50) with 15% mPEG were synthesized. According to the international standard organization (ISO10993) and National Standards of P. R. China GB/T 16886, siliconized glass tube was used as a negative control sample, while non-siliconized glass tube as a positive one. Blood compatibility of PELGA was evaluated by hemolytic ratio analysis, platelet adhesion investigation, dynamic clotting time, plasma recalcification time (PRT) measurements, plasma prothrombin time (PT) and clotting time (CT) test. The results revealed that blood compatibility of the synthesized materials was good. Nanoparticles made by this kind of materials might be promising for intravenous use.
Biocompatible Materials ; chemistry ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Lactic Acid ; chemistry ; Materials Testing ; Platelet Adhesiveness ; drug effects ; Polyethylene Glycols ; chemistry ; Polyglycolic Acid ; chemistry

Objective To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CESI) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH).Methods Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200∶ 273) after antituberculosis chemotherapy were analyzed by PCR-MassArray.Results In4 tags of CES1 single nucleotide polymorphism (SNP),the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group ( P =0.0236 ).The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 ( P =0.044,OR =0.649,95％ CI =0.426-0.989,AC/AA ) and rs1968753 ( P =0.048,OR =0.556,95％ CI =0.311-0.995,GG/AA).The diplotypes with ‘ CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P=0.048,OR=0.654,95％CI=0.430-0.996).Conclusions The genetic polymorphisms of CESI might have significant association with ATBDIH.SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.

In this study, we expressed and purified supercharged green fluorescent protein (+36GFP) that we used to study its combination with nucleic acid and its cell transduction efficiency as carrier of DNA. We transformed pET+36GFP-HA2 plasmid into Escherichia coli BL21 (DE3), then expressed and purified the target protein. We used the protein to transduce a variety of mammalian cell lines including B16 cells, 293 cells, A549 cells and HepG2 cells at specified protein concentrations. Transduction efficiency of the protein was analyzed by flow cytometry. Under laser scanning confocal microscope, we observed visually transduction efficiency of +36GFP protein (100 nmol/L) to A549 cells. We incubated +36GFP with plasmid DNA and analyzed their binding ability with gel mobility shift assay. Then we transduced cells with the mixture of plasmid DNA/+36GFP protein at various ratio and detected the expression of reporter gene by using laser scanning confocal microscope and flow cytometry. The experimental results demonstrate that +36GFP had high transduction efficiency, and as the concentration increased, the efficiency improved in a dose-dependent manner. Gel mobility shift assay indicates that +36GFP could bind to plasmid DNA, blocking the migration of DNA in the gel in a concentration-dependent manner. After the plasmid wrapped by +36GFP penetrated into cells, the cells could express target protein efficiently, proving that +36GFP had the ability to carry nucleic acids into cells. Sucussful expression and purification of +36GFP protein confirms its high efficiency of cell transduction and its ability as carrier to deliver exogenous nucleic acids into cells.
Cell Line, Tumor ; DNA ; genetics ; metabolism ; Escherichia coli ; genetics ; metabolism ; Green Fluorescent Proteins ; biosynthesis ; genetics ; pharmacology ; Humans ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; pharmacology ; Transduction, Genetic ; methods ; Transfection

Objective To study the therapeutic effects of Ag85A plasmid DNA vaccines in a mouse model of multi-drug resistant-(MDR-) Mycobacterium tuberculosis infection. Methods BALB/c mice were infected with Mycobacterium tuberculosis clinical strain HB361 with isoniazid and rifampin resist-ance by intratail-vein injection and were subsequently divided into 6 groups. At the third day after infection, the mice were treated with saline (group A), vector pVAX1 (greup B), rifampin (group C), vaccae (group D), Ag85A plasmid DNA vaccines (group E),rifampin and Ag85A plasmid DNA vaccines (group F) for 60 d. The lungs and spleens from the mice were taken and their pathological changes, weight and number of myeobacterial colony were examined at the third week after the end of treatment. Results At third week af-ter the end of treatment, the gross pathological observation and histopathological examination in lung showed that the lung lesions were limited, the profile of the alveoli was relatively clear, and normal structure could be seen in 2/3 areas of the lung sections in group D, E and F. The extent of lung lesion was 50% in group D,20% in group E and F. The pathological changes in group A, B, and C were more severer than those in group D, E and F. Compared with group A, the colony-forming units (CFU) in the lungs from mice in group D,E and F decreased 52%, 68%, 78%, respectively. The CFU in the spleens from mice in group D,E and F decreased 48%, 65%, 79%, respectively. Conclusion Ag85A plasmid DNA vaccines alone or Ag85A plasmid DNA vaccines along with chemotherapy have significant therapeutic effects on the mouse model of MDR-Mycobacterium tuberculosis infection.

Objective:To review the experience of closure of the left-main-bronchial stump fistula using endoscopic liner cutter staplers through the right thoracic approach and I stage or staged treatment for the left pyothorax.Methods:6 patients with the left-main-bronchial stump fistula after left pneumonectomy combined with pyothorax were treated by closing the left-main-bronchial stump using endoscopic liner cutter staplers through the right thoracic approach, and pleura was used to cover the distal and proximal incisional margin of the stump respectively. The thoracic T-tube drainage was used in the I stage or staged treatment for the left pyothorax.Results:All patients were survived without recurrence of the bronchopleural fistula. 4 patients were observed to have no recurrence of pyothorax when 1 patient had recurrence of pyothorax and was treated with intermittent T-tube drainage.1 patient operated with left-thoracic fenestration in the past was treated with drainage waiting for secondary operation.Conclusion:The right thoracic approach seemed to be a safer and more effective method than the transsternal transpericardial approach in cases with the left-main-bronchial stump fistula combined with pyothorax. The use of endoscopic liner cutter staplers reduced the risk of bleeding, infection and recurrence of fistula. The T-tube drainage in the I stage or staged treatment for the left pyothorax was considered to be an easier way for treatment.

Background::To perform anatomical anterior cruciate ligament reconstruction (ACLR), tunnels should be placed relatively higher in the femoral anterior cruciate ligament (ACL) footprint based on the findings of direct and indirect femoral insertion. But the clinical results of higher femoral tunnels (HFT) in double-bundle ACLR (DB-ACLR) remain unclear. The purpose was to investigate the clinical results of HFT and lower femoral tunnels (LFT) in DB-ACLR.Methods::From September 2014 to February 2016, 83 patients who underwent DB-ACLR and met the inclusion and exclusion criteria were divided into HFT-ACLR (group 1, n = 37) and LFT-ACLR (group 2, n = 46) according to the position of femoral tunnels. Preoperatively and at the final follow-up, clinical scores were evaluated with International Knee Documentation Committee (IKDC), Tegner activity, and Lysholm score. The stability of the knee was evaluated with KT-2000, Lachman test, and pivot-shift test. Cartilage degeneration grades of the International Cartilage Repair Society (ICRS) were evaluated on magnetic resonance imaging (MRI). Graft tension, continuity, and synovialization were evaluated by second-look arthroscopy. Return-to-sports was assessed at the final follow-up. Results::Significantly better improvement were found for KT-2000, Lachman test, and pivot-shift test postoperatively in group 1 ( P >0.05). Posterolateral bundles (PL) showed significantly better results in second-look arthroscopy regarding graft tension, continuity, and synovialization ( P <0.05), but not in anteromedial bundles in group 1. At the final follow-up, cartilage worsening was observed in groups 1 and 2, but it did not reach a stastistically significant difference ( P >0.05). No statistically significant differences were found in IKDC subjective score, Tegner activity, and Lysholm score between the two groups. Higher return-to-sports rate was found in group 1 with 86.8% (32/37) vs. 65.2% (30/46) in group 2 ( P = 0.027). Conclusion::The HFT-ACLR group showed better stability results, better PL, and higher return-to-sports rate compared to the LFT-ACLR group.

Objective:To investigate the clinical value of emergent endoscopic intervention at different times of acute esophageal and gastric fundal varices bleeding.Methods:From July 2020 to December 2022, data of 207 cases of liver cirrhosis with esophageal and gastric fundal variceal bleeding diagnosed by gastroscopy were retrospectively analyzed, including 74 cases from the Second Affiliated Hospital, Zhejiang University School of Medicine, 41 cases from Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 36 cases from Lanxi People's Hospital, 31 cases from Yongkang First People's Hospital and 25 cases from Pujiang People's Hospital. Patients were divided into 3 groups according to the time of endoscopic intervention and treatment. Patients who received endoscopic treatment within 6 h of hemorrhage were included in group A ( n=68); patients within 6-24 hours were in group B ( n=72). A total of 67 patients selected for conservative drug treatment were included in group C, who did not undergo endoscopic therapy. The prognosis (success rate of hemostasis, early rebleeding rate, mortality rate) and treatment benefit (open diet time, blood transfusion volume, hospital stay, hospital cost) of the 3 groups were compared. Results:The success rates of hemostasis were 100.00% (68/68), 97.22% (70/72), 86.57% (58/67) in group A, B and C respectively with significant difference ( χ2=13.51, P<0.001). The mortalities of the three groups were 0.00% (0/68) in group A, 2.78% (2/72) in group B and 13.43% (9/67) in in group C respectively with significant difference ( χ2 =15.61, P<0.001). The early rebleeding rates of the three groups were 0.00% (0/68) in group A, 2.86% (2/70) in group B, and 13.43% (5/58) in group C respectively with significant difference ( χ2 =3.41, P=0.182). There were significant differences in open diet time (group A: 28.32 ±2.52 h, group B: 37.25±2.45 h, group C: 66.62±2.65 h, F=58.69, P<0.001), blood transfusion volume (group A: 3.62 ± 0.30 U, group B: 5.46 ± 0.37 U, group C: 6.25 ± 0.39 U, F=11.35, P<0.001), hospital stay (group A: 6.58 ± 0.23 d, group B: 7.83 ± 0.34 d, group C: 8.24 ± 0.45 d, F=5.75, P=0.004) and cost (group A: 10 152±821 yuan, group B: 13 568 ± 1 017 yuan, group C: 15 306 ± 1 186 yuan, F=4.96, P=0.008) among the three groups. There was significant difference in Child-Pugh grading among hemostasis-success patients and those who failed ( χ2 =15.63, P<0.001). Conclusion:Early endoscopic diagnosis and treatment in the early 24 hours of acute esophageal and gastric fundal variceal hemorrhage can improve the prognosis and reduce the economic burden of patients with high clinical application value.

Objective:To summarize the experience of surgical methods without repairing the fistula for 92 cases with gastrointestinal intrathoracic fistula.Methods:The surgical methods without repairing the fistula were performed through VATS, small incision assisted with VATS or thoracotomy. The focus of the surgery was to promote lung expansion, eliminate the residual cavity of chest cavity and keep effective drainage. After entering the chest cavity from the affected side, wash chest cavity with a large amount of warm normal saline and sterilize intermittently with iodophor to ensure the sterile environment in the pus cavity. Then completely remove the pleural cellulose or fiberboard on visceral pleura to promote lung expansion, eliminate the residual cavity of the chest cavity. The fistula was covered tightly and supported firmly by the visceral pleura on the lung. Multiple T-tubes were placed in thoracic cavity and fistula to keep effective postoperative drainage.Results:Among 92 cases, 85 cases were cured and the cure rate was 92.4% (85/92).7 cases died and the mortality rate was 7.61% (7/92). The 7 dead cases include 5 cases with esophagogastric anastomotic fistula (the death of 3 cases was cause by aortic esophagogastric fistula, the death of 1 case was cause by thoracic gastric tracheal fistula and 1 case was dead because of pulmonary infection and respiratory failure), 1 case with esophageal rupture (the cause of death was septic shock ), and 1 case with esophageal perforation(the cause of death was pulmonary infection and respiratory failure).Conclusion:Most of the surgeries without repairing gastrointestinal intrathoracic fistula are conducted simply through VATS or small incision assisted with VATS., which is safe and effective.

Humans ; Arthroplasty, Replacement, Knee ; Follow-Up Studies ; Cohort Studies ; Treatment Outcome ; Minimally Invasive Surgical Procedures ; Knee Joint/surgery* ; Knee Prosthesis ; Osteoarthritis, Knee/surgery*