An injectable hydrogel/staple fiber composite for sustained release of CA4P and doxorubicin for combined chemotherapy of xenografted breast tumor in mice / 南方医科大学学报

OBJECTIVE@#To prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection.@*METHODS@#DOX-loaded PELA staple fibers (FDOX) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of FDOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (GCA4P/FDOX). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of GCA4P/FDOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments.@*RESULTS@#The average length of FDOX was 4.0±1.3 μm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 ℃, the composite rapidly solidified to form a gel in vitro. Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with GCA4P/FDOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm3 in GCA4P/FDOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G4A4P/FDOX.@*CONCLUSION@#As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.

Risk factors for the occurrence and treatment failure of peritoneal dialysis-associated E. coli peritonitis / 中华临床感染病杂志

Objective:To investigate the clinical characteristics of E. coli peritoneal dialysis-associated peritonitis (PDAP) and the risk factors for its occurrence and treatment failure.Methods:The clinical data of patients with episodes of PDAP in four general hospitals in Jilin Province from 2013 to 2019 were retrospectively reviewed. According to the pathogenic bacteria, the patients were divided into E. coli and non- E. coli groups. The incidence of E. coli PDAP in the last seven years was calculated and the clinical characteristics were compared between two PDAP groups. Logistic regression was used to analyze the risk factors for the occurrence and treatment failure of E. coli PDAP. Results:A total of 693 PDAP episodes/cases were enrolled in this study, including 100 episodes/cases in the E. coli group and 593 episodes/cases in the non- E. coli group. The incidence rate of E. coli PDAP in the four hospitals showed a decreasing trend during 2013 to 2019. Compared with the non-E.coli group, the proportion of diabetic patients and the average blood albumin levels in the E. coli group were lower ( χ2=5.006, Z=-2.992, P<0.05), while the proportion of refractory peritonitis was higher, and the duration of antibiotic therapy was longer ( χ2=6.350, Z=-2.779, P<0.05). Multivariate Logistic regression analysis showed that history of PDAP ( OR=1.577, 95% CI: 1.015-2.448) and low baseline serum albumin level ( OR=0.958, 95% CI: 0.923-0.995) were independent risk factors for the development of E. coli PDAP, while concomitant diabetes was an independent protective factor for E. coli PDAP ( OR=0.538, 95% CI: 0.330-0.876). Moreover, long-term dialysis was an independent risk factor for treatment failure of E. coli PDAP ( OR=1.047, 95% CI: 1.018-1.076). Conclusion:The incidence rate of E. coli PDAP in study institutions has declined in the past 7 years, but the rate of refractory PDAP is still high. The history of PDAP and low blood albumin level are independent risk factors for the occurrence of E. coli PDAP, while concomitant diabetes is an independent protective factor for the occurrence of E. coli PDAP. Long-term dialysis is an independent risk factor for treatment failure of E. coli PDAP.

Application and development of healthy life expectancy index / 公共卫生与预防医学

As the life expectancy of the population increases and traditional indexes are flawed in reflecting the health level, the concept of the healthy life expectancy has emerged, which integrates the length of the life and quality, more comprehensively reflects the health level of the population. This article has summarized the emergence and development of health life expectancy, classification of indexes, and commonly used measurement methods, as well as domestic and international application examples, and domestic research status. It proposes to establish a unified national measurement method, and make full use of big data resources in health care to comprehensively assess the health life expectancy of the population.

The value analysis of shear wave velocity combined with thyroid stimulating hormone in diagnosis of hyperthyroidism / 中国医师进修杂志

Objective:To analyze the value of shear wave velocity (SWV) combined with thyroid stimulating hormone (TSH) in the diagnosis of hyperthyroidism.Methods:Thirty-five patients with hyperthyroidism who were treated and confirmed in the Fuyang Affiliated Hospital of Anhui Medical University from December 2017 to September 2019 were selected as hyperthyroidism group, and 30 cases of normal health check-up patients in the outpatient department were selected as control group. All of the patients and medical persons were checked by conventional two-dimensional ultrasound and SWV, and the SWV and serum TSH, thyrotrophin receptor antibody(TRAb), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) expression levels of two groups were tested and compared. The correlation relationship in SWV value and serum TSH, TRAb, TGAb, TPOAb levels of hyperthyroidism patients was analyzed by Pearson methods. The receiver operating characteristic curve (ROC curve) method was used to analyze the value of SWV, serum TSH and SWV combined with serum in diagnosis of hyperthyroidism.Results:The SWV values of upper pole, middle pole and lower pole in the hyperthyroidism group had no significant differences ( P>0.05). The SWV values of upper hole, middle pole and lower pole of the left and right lobe of thyroid in the hyperthyroidism group were significantly higher than those in the control group [left lobe: (2.41 ± 0.34) m/s vs. (2.07 ± 0.28) m/s, (2.44 ± 0.39) m/s vs. (2.08 ± 0.25) m/s, (2.46 ± 0.43) m/s vs. (2.04 ± 0.30) m/s; right lobe: (2.47 ± 0.42) m/s vs.(2.01 ± 0.25) m/s, (2.41 ± 0.40) m/s vs. (1.95 ± 0.23) m/s, (2.43 ± 0.35) m/s vs. (2.06 ± 0.24) m/s] ( P<0.01). The serum TSH level in the hyperthyroidism group were significantly lower than that in the control group [(0.05 ± 0.03) kU/L vs. (2.74 ± 1.17) kU/L], while serum TRAb, TGAb and TPOAb levels were significantly higher than those in the control group [(15.82 ± 5.54) U/L vs. (0.55 ± 0.13) U/L, (290.63 ± 145.03) kU/L vs. (25.63 ± 7.12) kU/L, (627.17 ± 250.33) kU/L vs. (34.32 ± 5.95) kU/L], and the differences were statistically significant ( P<0.01). In the hyperthyroidism group, the SWV was negatively correlated with serum TSH ( r=- 0.862, P<0.05), but positively correlated with serum TRAb, TGAb and TPOAb ( r=0.763, 0.837, 0.804, P<0.05). The area under curve(AUC), sensitivity and specificity of combined diagnosis of hyperthyroidism with SWV value and serum TSH were 0.936, 94.29% and 91.43%, which was better than that of SWV (0.803, 80.00%, 74.29%) and serum TSH (0.842, 82.86%, 77.14%). Conclusions:SWV combined with TSH has a high clinical value in the diagnosis of hyperthyroidism.