Objective To investigate the effects of spleen preservation on hepatic fibrosis and relevant cytokine in rabbits with advanced schistosomiasis. Methods After hepatic cirrhosis was induced by infecting Schistosoma japonicum cercariae in rabbits, total splenectomy (TSG), subtotal splenectomy (SSG) or sham operation (model control group, MCG) were performed respectively on these rabbits. Meanwhile,a normal control group (NCG) was established. The serum levels of tumor necrosis factor alpha (TNF-α) , interleukin-6 (IL-6) and interleukin-1 beta (IL-lβ) were detected respectively by radioimmunoassay(RIA) at the 8th, 15th and 21st week post-infection. The expressions of transforming growth factor betal (TGF-β1), type Ⅰ and type Ⅲ collagen in liver tissues were determined by immunohistochemistry before and after the operations. Results Compared with NCG, the serum levels of TNF-α, IL-6 and IL-1β of MCG rabbits increased significantly at the 8th week post-infection (P <0.01). However, the levels of them decreased to a lower level at the 15th week. At the 6th week after operation,no significant difference was found among the three model groups ( MCG, TSG, SSG) (P > 0.05). The expressions of TGF-β1, type Ⅰ and type Ⅲ collagen in liver tissue of MCG rabbits were significantly higher than those of NCG rabbits before the operation (P < 0. 01). No significant difference was found among the three model groups at the 6th week after the operation ( P > 0.05). Conclusion The residual splenic tissue after subtotal splenectomy does not aggravate the hepatic fibrosis at advanced schistosomiasis. The mechanism may be that the relevant cytokines of hepatic fibrosis (TGF-β1, TNF-a, IL-6, IL-1β) decreased to a lower level at this time,and splenectomy does not influence the levels of them.

In this study, indomethacin (IND) loaded solidified-polymeric micelles (IND-SPM) were prepared. Their in vitro characteristics were investigated. Methoxy-poly(ethylene glycol) poly(D, L-lactide) copolymer (mPEG-PDLLA) was used as IND carrier. The preparation of IND-SPM was conducted by solution-absorption method and evaporation by rotary evaporator. Polyplasdone XL-10 was used as adsorbent. The solution-absorption method was conducted by the following procedure; IND and mPEG-PDLLA were dissolved in acetone, followed by addition of polyplasdone XL-10 and stirred to obtain a suspension. The powder of IND-SPM was simply obtained after the organic solvent was completely evaporated. More than 90% (w/w) of IND (20 mg) in the powder was dissolved in 250 mL PBS within 30 min. DSC, 1H NMR and SEM results proved that IND was encapsulated within mPEG-PDLLA. The solubility of IND in the system increased 4.6 times with the highest amount of copolymer. The solidified particles were found to be suitable for the formulation of tablets or capsules.

This study is to prepare the in situ forming sustained-release injection which can perform sustained release behavior at the periodontal site for 7 days and to evaluate its in vitro and in vivo properties. After preparation of in situ forming sustained-release injection the in situ time was studied. And the surface of the solid injection was characterized by SEM. The rheological curve at 0 degrees C, 25 degrees C, 37 degrees C was determined and the impact of the temperature on the viscosity was examined. The in vitro release behavior was investigated. At last, rabbit periodontitis model was established to study its pharmacokinetics. The injection was stable, hard to stratify and decompose. The in situ forming time was about 6 seconds. It can easily adhere into periodontal pockets. There were lots of holes on the surface of the solid injection for the drug to diffuse. The drug releasing curves could be fit by Korsmeyer-Peppas equation. The drug smoothly released for 7 days at pH 7.4 PBS buffer with a very slight burst release and maintained a certain concentration. In vivo pharmacokinetics results indicated that after administration with the in situ forming injection, achievement of tinidazole (TNZ) concentration in gingival crevicular fluid (GCF) was more comparable and long-lasting than usual solution of TNZ management and relatively constant TNZ levels were attained until 168 h. All these results supported the prospect of tinidazole in situ forming sustained-release injection in clinical applications.

The aims of this research were to constitute and evaluate one targeting anticancer co-delivery system for both micro-molecularchemotherapeutic drugs(docetaxel, DTX)and small interfering RNA(siRNA)expressed by COX-2. The nanoparticles composed of poly(D, L-lactide-co-glycolide)(PLGA)bearing disulfide-linkaged reducible polyethyleneimine(PEIss)covered by hyaluronic acid(HA). Meanwhile, HA-PEI-PLGA nanoparticles were prepared as control. Firstly, the solvent evaporation was used to the particles which exhibited a core-shell structure with a uniform size of 150-200 nm. The cumulative drug release in two kinds of PBS media(pH 7. 4 and pH 5. 0)during 72 hours indicated that DTX-loaded nanoparticles had sustained-release effect within 24 hours. The cumulative release of DTX of HRPSP NPs in PBS pH 5. 0 was 10%-25% more than that in PBS pH 7. 4, which demonstrated that favored release of DTX from nanoparticles could be achieved in acidic tumor microenvironment. Then, the highest transfection efficiency was observed after 14-16 h incubation at N/P ratio of 40/1. Following the saturation of CD44 receptor, the mean fluorescence intensity of HRPSP NPs from the cells decreased drastically in the case of saturation with free HA before. However, there existed no significance in the fluorescence of RPSP NPs between the cells with and without saturation with free HA, which indicated the nanoparticles′ targeting potential toward tumor cells. In the Western blot, the relative silencing efficiency of Bcl-2, bax, capase-3 and COX-2 mRNAprotein was calculated. In comparison to the control group, the silence efficiencies of bax and capase-3 were both significantly increased while that of Bcl-2 was evidently reduced, particularly in siCOX-2/HRPSP NPs group(P< 0. 01). The similar results were obtained in the silence efficiency of COX-2 protein in which the COX-2 quantity on mRNA and protein decreased. The results suggest that the nanoparticles could achieve the synergistic effect on the combinatorial delivery of siRNA and lipophilic anti-tumor drugs.

Objective:To analyze the epidemiological characteristics and influencing factors of venous thrombosis in elderly patients with severe trauma.Methods:A retrospective study was conducted to collect and statistically analyze general information[sex, age, body mass index(BMI)], causes of trauma, injury severity score(ISS), Glasgow coma score(GCS), coagulation function[prothrombin time(PT), international normalized ratio(INR), D-dimer], B-type natriuretic peptide(BNP), liver function(alanine aminotransferase, aspartate aminotransferase), creatinine, Caprini score, surgical approach, immobilization mode, days of hospitalization, and treatment cost.Results:Totally 179 elderly patients with severe trauma were enrolled, including 130 men(72.6%), aged(67.6±6.4)years.The BMI, ISS and GCS scores of elderly patients with severe trauma were(22.9±3.4)kg/m 2, 28.4±10.5 and 10.2±4.6, respectively.The Caprini score was 11.7±4.0.Of these patients, 32(17.9%)had VTE events.Compared with the VTE negative group, the VTE positive group was older( t=-2.214, P=0.028), with a higher Caprini score( t=-2.684, P=0.008)and more lower limb fractures( P=0.008)and pelvic fractures( P=0.001). There were no significant differences in coagulation function, liver function, atrial natriuretic peptide levels, creatinine levels and surgical approaches between the VTE negative group and the VTE positive group(all P<0.05). No significant difference was found in the proportion of patients receiving surgical treatment between the two groups( P=0.563). In the VTE positive group, 18.8% had no fracture, 50.0% had one fracture, and 31.2% had two or more fractures, and the difference was statistically significant compared with the VTE negative group( P=0.029). However, VTE events had no significant effect on the average length of stay and hospitalization costs in elderly trauma patients(all P<0.05). Conclusions:For elderly patients with severe trauma, VTE is more likely to occur with increased age, a high Caprini score, multiple fracture sites and pelvic fracture.In addition, pelvic fracture is an independent risk factor for VTE in very old trauma patients.Attention should be paid to prevention and treatment to achieve steady improvement in the overall prognosis of trauma in these patients.

Objective:To explore the risk factors for early trauma-induced coagulopathy (TIC) following severe trauma in the elderly patients.Methods:A case-control study was used to analyze the clinical data of 317 elderly patients with severe trauma admitted to Second Affiliated Hospital of Zhejiang University School of Medicine between February 2015 and November 2020. There were 212 males and 105 females, aged 65-96 years [(72.6±6.8)years]. The patients were divided into TIC group ( n=32) and non-TIC group ( n=285) using the international normalised ratio (INR)>1.5 as the reference standard. Sex, age, trauma sites, injury severity score (ISS), Glasgow coma scale (GCS), first body temperature on admission, shock index(SI), first laboratory results of arterial blood gas, routine blood and coagulation, blood transfusion, usage of blood product, hospitalization days and clinical outcomes were compared between the two groups. Univariate and multivariate Logistic regression analysis were used to identify the risk factors for early TIC in patients with severe trauma. Results:Differences in sex, age, injuries to the face, chest and abdomen, GCS, first body temperature and hospitalization days were not statistically significant between the two groups (all P>0.05). The two groups showed statistical differences in the ratio of injuries to head, neck and extremities, ISS, SI, pH value, base excess (BE), lactate, hemoglobin (Hb), platelet (PLT) count (first detection, lowest level), activated partial thromboplastin time (APTT), thrombin time (TT), plasma fibrinogen (FIB), blood transfusion and usage of blood product and clinical outcomes (all P<0.05). According to the univariate analysis, injuries to the head, neck and extremities, ISS, first body temperature, SI, pH value, BE, lactate, Hb, PLT, APTT, TT and FIB were correlated with the occurrence of early TIC (all P<0.05). Multiple Logistic regressions analysis showed that SI ( OR=1.54, 95% CI 1.10-2.17, P<0.05), PLT ( OR=0.67, 95% CI 0.49-0.91, P<0.05) and FIB ( OR=0.56, 95% CI 0.40-0.78, P<0.01) were significantly correlated with the occurrence of early TIC. Conclusion:For elderly patients with severe trauma, higher SI, lower PLT count and lower concentration of FIB are independent risk factors for the incidence of early TIC.

Objective:To investigate the value of hypocalcaemia for predicting trauma-induced coagulopathy (TIC) in elderly trauma patients.Methods:The clinical data of elderly trauma patients in emergency ICU of the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to September 2020 were retrospectively analyzed, including age, sex, site of injury, injury severity score (ISS), Glasgow coma scale (GCS), admission arterial blood gas analysis (Ca 2+, K +), venous blood biochemical electrolyte (Ca 2+, K +, Na +); international normalized ratio (INR), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), use of blood products, length of stay, length of stay in ICU, total cost, and clinical prognosis. Receiver operating characteristic (ROC) curves and multivariate logistic regression analysis were performed to estimate the contribution of hypocalcaemia to triggering TIC in elderly trauma patients. Results:Totally 371 elderly trauma patients were included with a mean age of (72.5±6.8) years, and 248 (66.8%) were male. ISS score of the TIC group was higher than that of the non-TIC group [25(20, 34) vs. 21(16, 29)]. Compared with the non-TIC group, the incidence of chest injury, abdominal injury and limb injury were significantly higher , while the incidence of head and neck injury were significantly lower in the TIC group (all P<0.05). The biochemical blood calcium in the TIC group was significantly lower than that in the non-TIC group [(1.97±0.19) mmol/L vs. (2.15±0.16) mmol/L, P<0.001], but there was no significant difference in blood gas calcium between the two groups. The APTT value of the TIC group [(47.6±21.8) s vs. (33.8±4.1) s], PT value [(18.0±3.9) s vs. (13.7±0.8) s] were significantly higher than that of the non-TIC group, and FIB level was significantly lower than that of the non-TIC group[(1.7±0.8) g/L vs. (2.8±0.9) g/L] (all P<0.01). The utilization rate of blood products and the total cost in the TIC group were higher than that in the non-TIC group, while the recovery rate in the TIC group was lower than that in the non-TIC group (69.8% vs. 86.4%, P<0.001). Multivariate logistic regression analysis showed that hypocalcaemia was an independent risk factor for TIC in elderly trauma patients ( OR=5.830, 95% CI: 3.295-10.314). The area under ROC curve of correlation between biochemical calcium and TIC was 0.779 (95% CI: 0.728-0.831). The optimal diagnostic cut-off value was 2.06 mmol/L. Conclusions:The decrease of biochemical serum calcium level is an independent risk factor for TIC in elderly trauma patients. Positive correction of TIC in elderly trauma patients contributes to continuous improvement of clinical prognosis.