Objective To study the relationship between the T helper cells (Th22)/interleukin (IL)-22 and rheumatoid arthritis (RA) with interstitial lung disease (ILD), and to define the clinical significance of Th22 cells for RA. Methods The quantity of Th22 cells in the peripheral blood from 40 patients with RA (20 RA with ILD, 20 RA without ILD) were examined by flow cytometry, the level of IL-22 in the sera was detected by enzyme-linked immunosorbent assay (ELISA). Comparisons between groups were analyzed by t-test, rank sum test, and the correlation of parameters were tested by linear correlation analysis. Results The quantities of CD4+IL-22+ cells (Th22) in RA patients [(0.15 ±0.07)%] were significantly higher than normal controls [(0.09 ±0.05)%] (t=4.097, P<0.01), and IL-22 levels in RA patients [(83 ±7) ng/L] were significantly higher than normal controls [(61±5) ng/L] (t=13.057, P<0.01). The quantities of Th22 cells in RA-ILD patients [(0.18±0.07)%] were significantly higher than RA-NILD patients [(0.13±0.05)%] (t=2.919, P=0.008), and IL-22 levels in RA-ILD patients [(87±6) ng/L] were significantly higher than RA-NILD patients [(80±6)ng/L] (t=3.624, P=0.001). The quantities of Th22 cells were positively correlated with erythrocyte sedimentation rate (ESR), rheumatoid factor(RF) and 1.4 disease activity score (DAS)28 (r=0.336, 0.377, 0.577, P<0.05),and the level of IL-22 were also positively correlated with ESR and DAS28 (r=0.406, 0.576, P<0.05). Conclusion The quantities of Th22 cells and IL-22 level are increased in RA patients, especially in RA-ILD patients. The quantities of Th22 cells and IL-22 level are positively correlated with ESR and DAS28. It may play a certain role in RA especially in RA with ILD.

The present study is to elucidate the mechanisms underlying Gleevec-induced apoptosis of chronic myeloid leukemia (CML) K562 cells in vitro. The apoptotic cell death and cell cycle distribution after Gleevec treatment and the effect of PDCD4 siRNA on Gleevec-induced apoptosis of K562 cells were analyzed by flow cytometry. The effect of Gleevec on p-Crkl, caspase-3, PARP and PDCD4 protein levels, and the knockdown efficacy of PDCD4 siRNA were detected by Western blotting. The results showed that Gleevec dramatically suppressed the phosphorylation level of Crkl in a dose-dependent manner and induced significant apoptosis and G0/G1 cell cycle arrest of K562 cells in time- and dose-dependent manners. In addition, Gleevec activated caspase-3 and its downstream substrates PARP, and the caspase pan inhibitor Z-VAD-FMK (50 micromol x L(-1)) markedly reduced Gleevec-induced apoptosis from 47.97% +/- 10.56% to 31.05% +/- 9.206% (P < 0.05). Moreover, Gleevec significantly increased the protein expression of programmed cell death 4 (PDCD4). PDCD4 knockdown by siRNA reduced Gleevec-induced apoptosis from 46.97% +/- 14.32% to 42.8% +/- 11.43%. In summary, Gleevec induced apoptosis in K562 cells via caspase-3 activation.

To analyse and compare the characteristics of the intestinal absorption of puerarin, baicalin, berberine and liquiritin in different combinations of Gegenqinlian decoction based on pharmacokinetic parameters, a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was applied for the quantification of four components in rat's plasma. And pharmacokinetic parameters were determined from the plasma concentration-time data with the DAS software package. The influence of different combinations on pharmacokinetics of four components was studied to analyse and compare the absorption difference of four components, together with the results of the in vitro everted gut model and the rat single pass intestinal perfusion model. The results showed that compared with other combinations, the AUC values of puerarin, baicalin and berberine were increased significantly in Gegenqinlian decoction group, while the AUC value of liquiritin was reduced. Moreover, the absorption of four components was increased significantly supported by the results from the in vitro everted gut model and the rat single pass intestinal perfusion model, which indicated that the Gegenqinlian decoction may promote the absorption of four components and accelerate the metabolism of liquiritin by the cytochrome P450.

Objective To evaluate the therapeutic effect of PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel interstitial chemotherapy for pancreatic cancer by using endoscopic ultrasonography.Methods PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel in vitro release experiments were performed in the following procedures:determination of lixivium drug concentration and calculation of its emission.Fifty nude mice with the pancreatic cancer cell line SW1990 were randomly divided into 5 groups,10 in each group.Group A was intratumorally injected with PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel at 4mg/kg ; group B with PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel at lmg/kg; Group C was intratumorally injected with 5-fluorouracil at 4 mg/kg ; Group D with PLGAPEG-PLGA matrix at 4mg/kg ;and group E was the control group.Tumor growth and audio-visual images of the nude mice tumor nodules were observed before administration,and 3,7,10,14 days after.Tumor growth curve was also drawn.Animals were sacrificed at 14 days Tumors were weighed to calculate the inhibitory rate and stained for pathological study.Results 1,3,5,8,10,and 14-day release of 5-fluorouracil temperature-sensitive hydrogel were 21.6％,33.8 ％,44.3％,63.6％,76.3％ and 91.8％.Tumor sizes of group A and group B were significantly different from those of other groups (P ＜ 0.05).Ultrasound endoscopic image characteristics were correlated with pathological findings.Conclusion PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel is able to release for 14 days in vitro,which constantly inhibits human pancreatic cancer cell line SW1990.Intratumoral injection of the agent can significantly inhibit the growth of pancreatic cancer of nude mice.Additionally,gelatinous preparations fixes better than liquid and is of clinical value.Therefore,monitoring temperature-sensitive 5-fluorouracil hydrogel interstitial chemotherapy for pancreatic cancer with endoscopic ultrasound is convenient and safe.

Objective To investigate the application value of Photoshop in grading invasive risk of gastric stromal tumors (GSTs). Methods EUS image of 97 cases of GSTs confirmed by pathological and immunohistochemical examination were collected. GSTs were divided into four groups (very low risk, low risk, intermediate risk, high risk) by tumor size, mitotic count and rupture of tumor. Mean gray value (intensity of echo) and gray value standard deviation (uniformity of echo) of EUS images of the lesions were determined by Photoshop and then the differences of each group were found by statistical analysis. Results It is difficult to differentiate EUS images of GSTs from each group by visual observation. The mean gray value of EUS image of very low risk group,low risk group, intermediate risk group and high risk group of GSTs respectively were (56.54 ± 6.10), (59.20 ± 7.51), (77.77 ± 10.90) and (83.43 ± 12.47). There was no significant difference between very low risk group and low risk group (P > 0.05). There was no significant difference between intermediate risk group and high risk group (P > 0.05). In addition, the others all had significantly different from that of each group (P < 0.05). The mean gray value standard deviation of EUS image of very low risk group, low risk group, intermediate risk group and high risk group of GSTs respectively were (8.46 ± 2.59), (12.57 ± 5.89), (12.84 ± 4.15) and (16.69 ± 4.69). There was no significant difference between low risk group and intermediate risk group (P > 0.05). In addition, the others all had significantly different from that of each group (P < 0.05). Conclusions The higher risk of GSTs, the higher of echo intensity and the worse of echo uniformity under EUS. Photoshop combined with EUS is helpful for differentiating different risk of GSTs by analyzing mean gray value and gray value standard deviation of the lesions.

OBJECTIVE:To optimize the hypoglycemic active parts from the leaves of Dimocarpus longan for type 2 diabetes mellitus mice,and to provide reference for material basis study of it. METHODS:Total extract was obtained from the leaves of D. longan with 95% ethanol percolation extraction. After confirming hypoglycemic effect of total extract,extract was suspended with water. Relevant extract was obtained by using petroleum ether,ethyl acetate and n-butanol in turn(respectively marked as ST,YT,ZT and WT). The model of type 2 diabetes mellitus mice was established by high glucose and high fat diet combined with STZ. Model mice were randomly divided into model group(distilled water),positive control group(metformin,0.1 g/kg), ST low-dose,medium-dose and high-dose groups(22.2,29.6,44 g/kg,calculated by crude drug,similarly hereinafter),YT low-dose,medium-dose and high-dose groups(10.7,16,32 g/kg),ZT low-dose,medium-dose and high-dose groups(10.5, 15.8,31.6 g/kg),WT low-dose,medium-dose and high-dose groups(18.5,24.6,37 g/kg),with 10 mice in each group. Other 10 normal mice were included in normal group(distilled water). Those groups were given relevant medicine intragastrically,once a day,for consecutive 28 d.The growth of mice and the change of body weight were observed and recorded. Fasting blood glucose(FBG)of mice was detected,and glucose tolerance test of mice was conducted. The contents of TC,TG,HDL-C and LDL-C in serum of mice were also determined. RESULTS:Compared with normal group,body weight and serum content of HDL-C in model group were decreased;FBG and the blood sugar after giving glucose for 0.5,1,2 h and area under glucose tolerance curve of mice were increased,and serum contents of TC,TG and LDL-C were alse increased,with statistical significance(P<0.01). compared with model group,body weight of mice in YT high-dose group after administration of 25 d was increased,FBG of mice in YT groups and ZT medium-dose,high-dose groups were decreased(P<0.05 or P<0.01);blood sugar of mice in YT medium-dose,high-dose groups and ZT high-dose group after giving glucose for 1 h as well as blood sugar of mice in YT high-dose group after giving glucose for 2 h were all decreased;area under glucose tolerance curve of mice and serum content of TC were decreased in YT groups and ZT high-dose group,while serum content of HDL-C was increased. Serum content of TG and LDL-C in YT high-dose group and ZT high-dose group as well as serum content of TG in YT medium-dose group were all decreased,serum content of HDL-C in ZT medium-dose group was increased,with statistical significance(P<0.05 or P<0.01). CONCLUSIONS:The ethyl acetate part and n-butanol part from the leaves of D. longan show good hypoglycemic effect on type 2 diabetes mellitus mice.

OBJECTIVE:To provide scientific reference for prescription comment. METHODS:Network questionnaire was de-signed to investigate the development of hospital prescription comment taking hospital pharmacists from Shanghai as the object. The surveyed data were analyzed statistically. RESULTS:A total of 51 effective questionnaires were collected with effective recovery rate of 100%,involving 51 hospitals. Second-level prescription comment mode was adopted in 51 hospitals;the mode of"initial clinical pharmacist comment,expert group re-comment"was mostly adopted in second-level hospitals,accounting for 23.53%. The mode of"outpatient pharmacist initial comment,clinical pharmacist re-comment"was mostly adopted in third-level hospitals and general hospitals,accounting for 23.53% and 21.57%,respectively. The method of"all prescriptions randomly selected at one stage"was mostly adopted in third-level hospital(accounting 23.53%). 45.10% of them did not adopt information system for pre-scription comment. 86.27% of surveyed hospitals carried out the review once a month. The limitation on the amount of drugs which were"less than 2 weeks"and"less than 1 month"took up the high proportion(41.18%,45.10%). Among irrational used common drugs,antibiotics accounted for the highest proportion (43.14%). In supernormal prescriptions,the most common problem was drug use without indication(accounting for 64.71%). Surveyed pharmacists from different types of hospital had different comments on same prescription. The effects of prescription comment on hospital rational drug use and pharmacist's ability had been widely recognized,but its effects on physician prescribing behavior was not satisfactory(only 5.88% respondents believed the great effects of prescription comment). Main ideas and suggestions of surveyed pharmacists for improving the role of prescription comment were"to improve the comment ability of pharmacists","to pay more attention by hospital leaders"and"to increase the degree of infor-mation management". CONCLUSIONS:During the process of prescription comment,it is necessary to improve the authority of prescription comment and the scientific sampling method,optimize the frequency of prescription comment and the consistency of comment results,and also pay attention to combination with administrative intervention.

Objective:To analyze the status of the construction and quality of scientific research ethics committee of medical institutions of Shanghai health and family planning system,and to provide the basis for promoting the standardization of ethic review of scientific research projects.Methods:Taking the training representative of ethics committee of Shanghai health and family planning system as participant,we obtained the relevant information of scientific research ethics committee using questionnaire survey method and carried on system analysis and evaluation.Results:Since the promulgation of local standard of Shanghai scientific research ethics review,scientific research ethics committees gradually standardly conducted the ethical review work of scientific research projects and carried out ethical training programs,but there were still some shortcomings and facing challenges in the aspect of the review quality management,specific ethical issues,discipline construction and personnel training.Conclusion:Scientific research ethics committee should enhance the quality of review,discipline construction and personnel training according to local standards.

Objective: To explore whether extracellular histones aggravate acute respiratory distress syndrome (ARDS) by inducing peripheral blood mononuclear cell (PBMC) pyroptosis. Methods: Twenty patients with ARDS admitted to Shanghai Pulmonary Hospital, Tongji University School of Medicine from April to September in 2019 were enrolled, and 20 healthy volunteers were enrolled as controls. In vivo experiment: peripheral blood samples of patients with ARDS within 24 hours after diagnosis and healthy volunteers were collected, and the levels of plasma extracellular histone, interleukins (IL-1β and IL-18) and lactic dehydrogenase (LDH) were determined by enzyme-linked immunosorbent assay (ELISA). PBMC were harvested, the expression levels of the pyroptosis associated N terminal-gasdermin-D (GSDMD-N) protein were determined by Western Blot. In vitro experiment: PBMC isolated from healthy volunteers were divided into four groups. Blank control group without any treatment; lipopolysaccharide (LPS) group was treated with 1 mg/L LPS for 4 hours; LPS+histones group was treated with 100 mg/L exogenous histones for 24 hours after LPS treatment; LPS+histone+heparin group was treated with 200 U heparin for 24 hours after LPS and exogenous histones treatment. The GSDMD-N protein expression was determined by Western Blot, and the levels of IL-1β, IL-18 and LDH in cell supernatant were determined by ELISA. Spearman test was used to test the correlation among the parameters. Results: In vivo experiment results: compared with healthy control group, the GSDMD-N protein expression in PBMC of patients with ARDS was significantly increased [GSDMD-N/GAPDH: 0.136 (0.062, 0.246) vs. 0.026 (0.018, 0.036), P < 0.01], as well as the plasma levels of IL-1β, IL-18, LDH and extracellular histones [IL-1β (ng/L): 120.0 (94.2, 213.0) vs. 88.5 (82.3, 105.3), IL-18 (ng/L): 164.5 (70.8, 236.3) vs. 60.5 (52.0, 89.0), LDH (U/L): 30.9 (24.7, 39.5) vs. 19.8 (17.2, 21.5), extracellular histones (mg/L): 73.0 (42.8, 112.9) vs. 12.2 (9.6, 16.9), all P < 0.01], indicating that the PBMC of ARDS patients had significant pyroptosis and release of a large number of inflammatory factors. The oxygenation index (PaO₂/FiO₂) of ARDS patients was 135.5 (94.5, 196.0) mmHg (1 mmHg = 0.133 kPa). Correlation analysis showed that the expression of GSDMD-N protein in patients with ARDS was negatively correlated with PaO₂/FiO₂ (r = -0.935, P < 0.01) and positively correlated with IL-1β, IL-18, LDH and extracellular histones (r value was 0.844, 0.843, 0.887, 0.899, respectively, all P < 0.01). In vitro experiment results: compared with blank control group, the expression of GSDMD-N protein in PBMC and the levels of inflammatory mediators in the supernatant of the LPS group were significantly increased [GSDMD-N/GAPDH: 0.035±0.006 vs. 0.028±0.006, IL-1β (ng/L): 39.8±5.5 vs. 22.6±4.7, IL-18 (ng/L): 31.2±4.4 vs. 20.0±2.2, LDH (U/L): 51.2±7.3 vs. 36.6±7.6, all P < 0.05], indicating that LPS stimulation could increase PBMC pyroptosis and the release of inflammatory mediators. Compared with LPS group, the expression of GSDMD-N protein and the levels of inflammatory mediators of the LPS+histones group were further increased [GSDMD-N/GAPDH: 0.114±0.009 vs. 0.035±0.006, IL-1β (ng/L): 119.0±18.7 vs. 39.8±5.5, IL-18 (ng/L): 49.2±8.5 vs. 31.2±4.4, LDH (U/L): 127.8±19.8 vs. 51.2±7.3, all P < 0.01], indicating that the stimulation of LPS on PBMC could be significantly amplified by exogenous histone treatment, GSDMD-N protein expression could be up-regulated and inflammatory factor release could be promoted to further induce PBMC pyroptosis. These adverse effects of exogenous histones on PBMC could be abrogated by heparin, the expression of GSDMD-N protein and the levels of inflammatory mediators were significantly lower than those of LPS+histones group [GSDMD-N/GAPDH: 0.063±0.004 vs. 0.114±0.009, IL-1β (ng/L): 46.8±8.6 vs. 119.0±18.7, IL-18 (ng/L): 33.0±5.1 vs. 49.2±8.5, LDH (U/L): 65.4±11.0 vs. 127.8±19.8, all P < 0.05]. Conclusion Extracellular histones in plasma may aggravate ARDS by mediating PBMC pyroptosis.

Objective:To investigate the surgical method and therapeutic effect on repairing soft tissue defects around ankle with lateral tarsal artery island flap.Methods:From July 2013 to December 2020, the lateral tarsal artery island flap were used to repair the soft tissue defects around ankle in 12 patients in Hand Surgery Department, Jiangnan Hospital Affiliated to Binjiang College. Of which, 6 patients had soft tissue defects complicated with bone or tendon exposure after injury and 6 had skin necrosis with internal fixation after fracture. The area of soft tissue defects was 6.0 cm×4.0 cm-9.0 cm×5.0 cm, and the size of the flaps was 7.0 cm×5.0 cm-10.0 cm×6.0 cm. After the flap was freed, the vascular pedicle was separated up to the origin of dorsalis pedis artery. As the pedicel was not long enough in 1 patient, the dorsal pedis artery was ligated and transected at the origin of the lateral tarsal artery. Full thickness skin graft was used to repair the donor sites. The patients were treated with anti-infection and anticoagulant therapies. The postoperative follow-ups were conducted by outpatient clinic visit, telephone or WeChat interviews or home visit to observe the recoveries in texture, appearance, sensation, donor site and function of ankle.Results:All the flaps and skin grafts survived. The wound healed well without occurrence of ulcer. The follow-up ranged 6-108 months (mean 17 months). Appearance of the flaps was good. It was not bloated and the sensation was restored to S 2-S 3. Conclusion:It is a good method to apply the lateral tarsal artery island flap in repair of the soft tissue defects around ankle. It features a hidden donor site, simple operation and the high level of safety. The texture and appearance of the flap are close to those of the recipient site.