OBJECTIVE:To explore the potential correlation between clinical efficacy of pemetrexed in the treatment of ad-vanced breast cancer and TS mRNA expression. METHODS:Patients with advanced breast cancer were recruited in our study. Three cycles of pemetrexed was given to these patients,TS mRNA expression of their tumor tissues were detected. The relationship of ther-apeutic efficacies of different chemotherapy with TS mRNA expression were observed and compared during the study period. RE-SULTS:58 patients received pemetrexed chemotherapy and therapeutic efficacies of them were evaluated. One patient (1.7%) had complete response,19 patients(32.8%)had partial response,31 patients(53.4%)had stable response and 7 patients(12.1%)has progressive disease. Objective response rate was 34.5%,and disease control rate was 87.9%. TS mRNA expression level of 55 pa-tients with completed TS mRNA expression analysis varied from 0.04 to 5.11,with a median of 0.62. Mann-Whitney rank test showed that,responders had lower TS mRNA expression than nonsponders at all visits,there was statistical significance (P<0.05). Chi-square test showed that patients with low expression level of baseline(before chemotherapy)TS mRNA had significantly higher objective response rate(63.3%)than those with high expression(36.7%),there was statistical significance(P<0.05). CON-CLUSIONS:TS mRNA expression level is related to therapeutic efficacy of pemetrexed,which may be useful for predicting thera-peutic efficacy of pemetrexed therapy in patients with advanced breast cancer.

Objective To explore the curative effect of percutaneous cavity injection for the treatment of drug resistant pulmonary tuberculosis guided by color Doppler ultrasound.Methods Ninety-six bacterial culture positive patients with drug resistant pulmonary tuberculosis were randomly divided into treatment group(n =48) and control group (n =48).Patients in both groupswere given systemic anti tuberculosis therapy,and those who in the treatment group were given extra percutaneous cavity injection guided by color Doppler ultrasound.Results After 3 months of treatment,the sputum negative conversation rate,X-ray absorption rate,cavity closure rate,and cavity efficiency rate of the treatment group were 56.3％ (27/48),81.3％ (39/48),58.3％ (28/48) and 75.0％ (36/48) respectively,higher than those of the control group 35.4％ (17/48),62.5％ (30/48),37.5％ (18/48) and 50.0％ (24/48) respectively),and the differences were statistically significant(x2 =4.20,P =0.02 4 ; x2 =4.17,P =0.041; x2 =9.58,P =0.004 ; x2 =6.40,P=0.020).After 12 months of treatment,the sputum negative conversation rate,cavity closure rate,cavity efficiency rate of the treatment group were 93.8％ (45/48),83.3％ (40/48),95.8％ (46/48) respectively,higher than those of control group(77.1％ (37/48),62.5％ (30/48) and 81.3％ (39/48)),and there were significant differences between two groups (x2 =5.35,5.27,5.03 ; P =0.040,0.038,0.025) ; the X-ray absorption rate of the treatment group was 93.8％ (45/48),higher than that of ciontrol group (83.3％ (40/48)),but there was no significant difference between two groups(x2 =2.56,P =0.199).Conclusion It is very effective to treat drug resistant pulmonary tuberculosis using percutaneous cavity injection guided by Color Doppler Ultrasound.No obvious complications or adverse reactions have been observed so far.

Objective To study the changes and significance of plasma atrial natriuretic peptide (ANP),endothehn-1 (ET-1),von Willebrand factor (vWF) levels in newborns with persistent pulmonary hypertension (PPHN) after the treatment of sildenafil.Methods Sixty-six cases with PPHN group and 40 cases with non-PPHN (control group) were enrolled.PPHN group was in the treatment of sildenafil.Collected the blood when before the treatment of sildenafil and 3,7 d after treatment,respectively.Arterial blood gas were done and pulmonary arterial systolic pressure (PASP) was measured before treatment and 3,7 d after treatment,and by the same time recording pulse oxygen saturation (SpO2).Plasma ANP,ET-1,vWF levels were measured by ELISA method.Results The levels of PASP,SpO2 arterial partial pressure of oxygen (PaO2),arterial partial pressure of carbon dioxide (PaCO2) and plasma ANP,ET-1,vWF in PPHN group before treatment [(66.5 ± 13.4)mm Hg (1 mm Hg =0.133 kPa),0.726 ±0.531,(46.3 ±7.2)mm Hg,(59.2 ± 7.4) mm Hg,(272.6 ± 20.3)ng/L,(221.3 ± 24.3) ng/L,(142.5 ± 20.3)％] compared with controlgroup [(25.0±6.2) mm Hg,0.896 ± 0.767,(88.3 ±7.6) mm Hg,(41.1 ±6.1) mm Hg,(68.4 ± 7.9) ng/L,(39.8 ± 6.5) ng/L,(95.3 ± 18.5)％] were statistically significant(P ＜ 0.05).Their levels in PPHN group 3 dafter treatment[(48.3 ± 3.2) mm Hg,0.841 ± 0.416,(73.6 ± 9.3)mm Hg,(50.5 ± 7.2) mm Hg,(102.6 ±20.3) ng/L,(79.6 ± 15.2) ng/L,(103.6 ± 14.1)％] were significantly improved,there was significantdifference compared with before treatment and control group(P ＜ 0.05).Their levels in PPHN group 7 d aftertreatment [(25.2 ± 3.6) mm Hg,0.882 ± 0.724,(85.4 ± 7.4) mm Hg,(40.2 ± 6.4) mm Hg,(64.4 ± 3.6)ng/L,(37.3 ± 5.4)ng/L,(92.9 ± 11.7)％] were significantly improved,there was significant difference compared with 3 d after treatment (P ＜ 0.05),the difference was no statistically significant compared with control group (P＞ 0.05).Linear correlation analysis showed that ANP,ET-1,vWF and PASP,PaCO2 were significantly positively correlated (P ＜ 0.01),ANP,ET-1,vWF and SpO2,PaO2 were significantly negatively correlated (P＜ 0.01).On the basis of cardiac ultrasound monitoring PASP,ANP evaluation of the efficacy of sildenafil sensitivity was 82.2％,specificity was 83.4％ ;ET-1 was 86.4％ and 87.6％; vWF was 85.1％ and 84.7％.Conclusion ANP,ET-1,vWF may play an important role in the mechanism of the treatment of PPHN by sildenafil,and could be used as an objective index to evaluate the effect of sildenafil on PPHN.

Objective To evaluate the efficacy and safety of short-term sensor-augmented insulin-pump (SAP) therapy for poorly controlled patients with type 1 diabetes mellitus (T1DM).Methods Sixty T1DM patients with glycosylated hemoglobin (HbA1c)>9.0% were randomly assigned to 2 groups treated with SAP or multiple daily insulin injection ( MDI) for 6 days, then all patients converted to MDI therapy. Results Compared with MDI group and before therapy, the mean blood glucose concentration ( MBG) , SD of blood glucose, mean amplitude of glycemic excursion ( MAGE) and 24-h area under curve at 10.0 ( AUC10.0 ) levels in SAP group significantly decreased after 6-day therapy ( compared with MDI group:t=1.761,P=0.028, t=2.569,P=0.037, t=2.712,P=0.020, t=2.985,P=0.014, compared with before therapy:t=3.128,P=0.006, t=2.689,P=0.024, t=2.966,P=0.013, t=3.076,P=0.009);while there was no difference in 24-h area under curve at 3.9 (AUC3.9) between groups (P>0.05).After 1 month follow-up HbA1c levels decreased in SAP group (t=2.344,P=0.023) and were significantly lower than those in MDI group (t=1.844, P=0.035).There was no difference in daily insulin dosage, fasting C peptide (FCP) and postprandial 2h C peptide (2hCP) between two groups (P>0.05).Age (t=2.125, P=0.012) and SAP therapy (t=3.376, P=0.009) were independently correlated with the HbA1c after 1 month.Conclusion Short-term SAP therapy is effective and safe for poorly controlled T1DM patients with rapid glucose lowering and glycemic excursions reduction.

Objective To evaluate the role of gliocytes in the spinal cord in the development of inflammatory pain (IP) in rats. Methods Adult male SD rats weighing 180-220 g were used in this experiment. A catheter was implanted in the subarachnoid space according to the method described by Yang. Animals with abnormal motor function of the hindlimb after intrathecal (IT) catheter implantation were excluded. IP was induced by subcutaneous (sc) injection of complete Freund's adjuvant (CFA) 50 μl at the lateral side of the ankle joint of the right hindpaw. Sixty-five rats were randomly divided into 5 groups ( n = 13 each): group I IP control normal saline (NS) 50μl was injected sc instead of CFA; group II IP; group IE PC (IT) + IP control fluorinated citric acid (FC, a gliocyte metabolism inhibitor) 1 nmol/10μl was injected IT at 15 min before NS 50 μl sc injection; group IV NS (IT) + IP and group V FC (IT) + IP. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured 2 d before induction of IP (T_0, baseline) .before and at 2, 4, 6, 8, 10, 12, 24 and 26 h (T_(1-9)) after sc NS or CFA injection. Five enimals in each group were killed at T_5 (8 h after sc NS/CFA injection) and the lumbar segment (L_(4,5)) was removed for determination of glial fibrillary acidic protein ( CFAP) and OX-42 expression by immuno-histochemistry. Results In group Ⅱ and Ⅳ sc CFA significantly decreased MWT and TWL. Mechanical and thermal hyperalgegia induced by sc CFA was significantly suppressed by intrathecal FC in group V . IP significantly increased GFAP and OX-42 expression in the spinal cord. Intrathecal FC significantly attenuated IP-induced up-regulation of GFAP and OX-42 expression in the spinal cord. Conclusion The activation of gliocytes in the spinal cord is involved in the development of CFA-induced hyperalgesia in rats.

Objective To investigate the impacts of phillyrin on exudates and lung injury in rats with acute pleurisy by regulating the NLRP3 inflammatory pathway.Methods Ninety rats were randomly divided into the control group,the model group,the low-dose phillyrin(PH-L,5 mg/kg)group,the medium-dose phillyrin(PH-M,10 mg/kg)group,the high-dose phillyrin(PH-H,20 mg/kg)group and the NLRP3 pathway inhibitor(PJ34,10 mg/kg)group.FVC,FEV 0.1 and FEV 0.3 were detected by lung function analyzer.Electronic balance was used to weigh the mass of chest exudate.The number of white blood cells in exudate was detected by Wright staining.Contents of prostaglandin E2(PGE2),monocyte chemoattractant protein-1(MCP-1),interleukin(IL)-6 and tumor necrosis factor-α(TNF-α)in exudate were detected by ELISA.Automatic blood gas analyzer was used to detect p(CO2)and p(O2)of rats.HE staining was used to observe pathological changes of lung tissue.The expression levels of NLRP3 and Caspase-1 protein were detected by immunohistochemistry.Western blot assay was used to detect the expression of NLRP3 pathway protein.Results Compared with the control group,the quality of pleural exudate and the number of white blood cells,the contents of PGE2,MCP-1,IL-6,TNF-α,the expression of p(CO2)and NLRP3 pathway proteins in exudate of the model group increased obviously,FVC,FEV 0.1,FEV 0.3 and p(O2)decreased obviously,and the lung tissue showed obvious pathological damage(P＜0.05).Compared with the model group,the quality of pleural exudate and the number of white blood cells,the contents of PGE2,MCP-1,IL-6,TNF-α,the expression of p(CO2),NLRP3 pathway proteins in the exudate of rats decreased obviously in the PH group and the PJ34 group,FVC,FEV 0.1,FEV 0.3 and p(O2)increased obviously,the pathological injury of lung tissue was obviously improved(P＜0.05).Compared with the PH-H group,there were no significant differences in the above indexes in the PJ34 group(P＞0.05).Conclusion PH can improve lung injury induced by acute pleurisy in rats by inhibiting the activation of NLRP3 pathway and inhibiting inflammatory reaction.

OBJECTIVETo explore the efficacy and prognostic factors of induction therapy combined with autogenetic peripheral blood stem cells transplantation (APBSCT)in patients with multiple myeloma (MM).

METHODSFrom January 1998 to May 2015, 201 patients with MM were enrolled. All patients received APBSCT after induction therapy. With the follow up to 20 June 2015, the overall survival (OS), progression free survival (PFS)and prognostic factor were analyzed.

RESULTS① With a media follow up of 36.67 months, the median PFS and OS were 22.87 (17.48- 28.26)and 69.63 (63.57- 75.69)months, 5-year PFS and OS were 17% and 49%, respectively. ②After APBSCT, when the subgroup (n= 112) achieved complete response (CR)compared with the subgroup (n=89) not achieved CR, the median PFS were 32.93 (21.03-44.83) and 18.13 (14.46-21.80) months (P<0.001), respectively; And the media OS were 96.77 (71.79- 121.75)and 54.70 (49.53- 59.87) months (P=0.004), respectively. The risks for disease progression and death declined in CR subgroup. ③ Two subgroups included or not included bortezomib/thalidomide at induction therapy (123 patientsvs 21 patients), the media PFS were 31.67 (24.36- 38.98)and 15.20 (10.11- 20.29) months (P=0.013), respectively; And the media OS were 76.30 (55.44- 97.15)and 52.03 (33.76- 70.30) months (P=0.014), respectively. ④According to the ISS stage, the media OS of stageⅠ, Ⅱ, Ⅲ were 99.47 (59.58-139.36), 66.77 (52.17-81.37), 53.97 (28.71-79.23) (P< 0.001), respectively. The risk for death of stage Ⅱ, Ⅲ were 2.16 and 3.04 times higher than stage Ⅰ, with no difference in terms of PFS. ⑤ The media PFS in IgD (n=22) and IgG (n=101) type MM were 11.17 (10.27- 13.13)and 35.43 (22.69- 48.17)months (P=0.007) , respectively; The media OS were 30.83 (0.24-61.42)and 70.70 (53.52-87.88) months (P=0.039), respectively. The risk for disease progression of IgD type was 2.47 times higher than IgG type. ⑥ Patients received 1 line induction therapy (n=132) compared with more than 1 line (n=69), the media PFS were 25.43 (16.09- 34.77)and 20.27 (15.04- 25.50) months (P=0.042). ⑦Cox analysis showed that CR after APBSCT and ISS stage were independent prognostic factors for OS. IgD type MM and CR after APBSCT were independent prognosis factor for PFS.

CONCLUSIONCR after APBSCT and ISS stage were independent prognostic factors for OS in MM. CR after APBSCT was independent prognostic factor for PFS in MM. However, disease progression more likely occurred in IgD type MM, which was independent negative prognostic factor for PFS in MM.

Antineoplastic Combined Chemotherapy Protocols ; Bortezomib ; therapeutic use ; Disease-Free Survival ; Humans ; Multiple Myeloma ; diagnosis ; therapy ; Neoadjuvant Therapy ; Peripheral Blood Stem Cell Transplantation ; Prognosis ; Remission Induction ; Survival Rate ; Thalidomide ; therapeutic use ; Transplantation, Autologous ; Treatment Outcome

To summarized the experiences from our basic experimental and clinical research on peritoneal dialysis. In the past 16 years, peritoneal fibrosis rat models and rabbit models of peritonitis were first established successfully in our laboratory in China. Peritoneal mesothelial cells were also separated and identificated. Besides, we assessed the biocompatibility of peritoneal dialysis fluid and analyzed the molecular mechanism of peritoneal mesothelial cell injury. We demonstrated the key role of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF) and peroxisome proliferative activated receptor-gamma (PPAR-gamma) in the pathogenesis of peritoneal fibrosis, as well as their regulation of molecular mechanism. Furthermore, we transfected the plasmids encoding TGF-beta1-shRNA or pCTGF-shRNA into peritoneal cells and tissues by nanocarrier technologies. In clinical research, the positioning of peritoneal dialysis catheters, peritoneal dialysis treatment modalities and the prevention and treatment of its complications were studied. The characteristics and mechanism of solute transport in peritoneal dialysis was also explored.
Animals ; Connective Tissue Growth Factor ; metabolism ; Fibrosis ; physiopathology ; prevention & control ; Humans ; Kidney Failure, Chronic ; metabolism ; therapy ; Peritoneal Dialysis ; methods ; Peritoneal Dialysis, Continuous Ambulatory ; adverse effects ; Peritoneum ; pathology ; Rabbits ; Rats ; Retrospective Studies ; Tissue Adhesions ; physiopathology ; prevention & control ; Transforming Growth Factor beta ; metabolism

AIM: To investigate the application of two-stage estimation (TSE) on adjustment for treatment switch in oncology trials. METHODS: The theory and implementation of TSE method was described, and was applied to adjust the data from a two-arm randomized controlled trial of anti-tumor drugs. The changes of survival curves and hazard ratio of two groups after adjustment for cross-over were evaluated. In addition, the results of two-stage estimation and rank preserving structural failure time model (RPSFT) were compared. RESULTS: After adjustment for cross-over using TSE methods, the results showed that the median survival time of control group was shorter than the original one, and the hazard ratio was lower than the observed value. Moreover, TSE method showed similar results to rank preserving structural failure time model. CONCLUSION: The TSE method is relatively simple to use, reliable and has a good practice property in cross-over analysis of oncology trials. At the same time, it is necessary to pay attention to its application scopes.

【Objective】 To analyze the hepatitis B virus (HBV) infection data of blood donors from 18 domestic blood stations, so as to investigate the HBV infection situation of blood donors. 【Methods】 The positive rate of HBV and its distribution characteristics of regions, the percentage of HBsAg+ ELISA in first-time vs repeated blood donors, and the percentage of HBsAg-/HBV DNA+ blood donors of 18 domestic blood stations during 2017 to 2020 were collected from the Working Platform for Practice Comparison of Blood Centers, and the HBV infection among blood donors were statistically analyzed. 【Results】 From 2017 to 2020, the positive rate of HBV in blood donors among 18 domestic blood stations was 13.48/10 000-144.02/10 000, with the average HBV positive rate in eastern, central and western region at 26.14/10 000, 51.98/10 000 and 41.00/10 000, respectively. The HBsAg+ rate by ELISA among first-time and repeated blood donors was 14.55/10 000-305.39/10 000 vs 1.04/10 000-87.43/10 000 The HBsAg-/HBV DNA+ yield was 1.80/10 000-35.31/10 000. 【Conclusion】 The distribution of HBV infection in blood donors has regional characteristics, and HBV prevalence was low in repeated blood donors. HBsAg ELISA combined with HBV DNA detection can better ensure blood safety.