Objective To investigate the relationship between the expression of BRCA1,β-tubulin III (TUBB3) and their efficacies with platinum-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods The expression levels of BRCA1 and TUBB3 were detected by immunohistochemistry. The relationship between BRCA1 and TUBB3 expressions and their efficacies were analyzed. Results The high expression rate of BRCA1 was 34.8%, and the efficacy of platinum-based chemotherapy in patients with BRCA1-lower expression is obviously better than that in patients with BRCA1-higher expression. There was a significant difference between these two groups (30.4%vs 67.4%, P=0.004). The effective rate of platinum-based chemotherapy in TUBB3-higher expression group and TUBB3-lower expression group were illustrated no significance (59.4% vs 50.0%, P=0.445). Conclusion Platinum-based chemotherapy is more suitable for the advanced NSCLC patients with lower expression of BRCA1. The expression level of BRCA1 could be used to predict the efficacy of platinum-based chemotherapy in advanced NSCLC patients.

Purpose:To evaluate the effect, tolerabilily and toxic-side reactions of combined carboplatin and cisplatin with etopside in advanced non-small-cell lung cancer.Methods:From Oct. 1998 to Mar. 2000, 23 cases with advanced non-small-cell lung cancer were treated by combined carboplatin [200 mg/m 2intravenously (IV) on day 1]and Cisplatin ( 30 mg/m 2 IV on day 3～5) and etopside (100mg/m 2 IV on day 1～5) . The treatment was repeated every 3～4 weeks.Results:86 cycles were completed in the whole group. Median cycles was 4. The overall response rate was 43.48%(10/23,PR), the median survival time was 8.2 months, the 1-year survival rate was 32%. Myelosuppression was the main toxicity, The overall response rate was 86.96%(20/23). Conclusions:Our results indicate that combined carboplatin and cisplatin with etopside regimen is effective for advanced non-small-cell lung cancer.

Objective:To investigate the relationship of the mRNA expression of BRCA1 andβ-tubulinⅢwith docetaxel-resistance in esophageal cancer. Methods:The genes BRCA1 andβ-tubulinⅢwere determined at the mRNA level using RT-qPCR in 36 esophageal carcinoma specimens. Results:The mRNA expression of BRCA1 andβ-tubulinⅢwas determined in the 36 tumor samples using RT-qPCR. The median BRCA1 mRNA expression level in relation to that ofβ-actin was 6.27. The medianβ-tubulinⅢmRNA expression level in relation to that ofβ-actin was 4.44. The patients were divided into two groups using these cutoff values. The BRCA1 mRNA expression level was not correlated with the sensitivity of esophageal cancer patients to docetaxel (P=0.733). The response rate of the tumors with highβ-tubulinⅢexpression was (38.9%), which is significantly lower than in patients with lowβ-tubulinⅢexpression (83.3%) (P=0.015). Conclusion:Theβ-tubulinⅢexpression levels in the tumor tissues were probably an important biomarker for the efficacy of docetaxel chemotherapy in esophageal cancer patients. Our study may provide new insights into taxane chemotherapy for advanced esophageal cancer patients.

Objective To explore the mechanism of tripterygium wilfordii polyglycoside tablets for elderly patients with relapsing refractory immune thrombocytopenic purpura (ITP),and to seek the theoretical basis for Chinese medicine treatment of this disease.Methods The clinical data of 79 patients with relapsing refractory ITP were retrospectively analyzed.According to whether the combined use of tripterygium wilfordii polyglycoside,they were divided into the control group (35 cases) and the observation group (44 cases).The control group was treated with platelet and tranexamic acid,sulfasalazine,sulforaphane sodium,hemagglutinin and other symptomatic hemostasis treatment.The observation group in symptomatic hemostasis support on the basis of treatment with tripterygium wilfordii polyglycoside tablets.The CD4+/CD8+ ratio and CD4+ CD25+ Treg expression were compared between the two groups.Results The CD4+/CD8+ ratio,CD4+ CD25+ Treg and platelet count in the control group before treatmentwere (0.96 ± 0.36),(1.21 ± 0.67) ％,(13.14 ± 6.92) × 109/L,respectively,which of the observation group were (0.92 ± 0.37),(1.19 ± 0.59) ％,(11.51 ± 6.21) × 109/L,respectively,there were no statistically significant differences between the two groups (all P ＞ 0.05).The CD4+/CD8+ ratios in peripheral blood of the observation group at 2 weeks,3 weeks and 4 weeks after treatmentwere (1.04 ±0.56),(1.55 ±0.34),(1.59 ±0.41),respectively,there were statistically significant differences between the two groups (t =9.994,9.797,all P ＜ 0.05).The CD4+ CD25+ Treg proportions in the observation group at 2 weeks,3 weeks and 4 weeks after treatmentwere (1.01 ± 0.61) ％,(1.06:±:0.57) ％,(5.92 ± 0.65) ％,respectively,there was statistically significant difference between the 4 weeks after treatment and before treatment(t =5.378,P ＜ 0.05).The CD4+/CD8+ ratios in the peripheral blood of the control group were (1.01 ±0.60),(0.89 ±0.50) and (0.96 ±0.51),respectively,and the CD4+ CD25+ Treg in control group at 2 weeks,3 weeks and 4 weeks after treatment proportions were (0.99 ±0.72)％,(1.15 ±0.66)％,(1.22 ±0.56)％,respectively,there were no statistically significant differences between before and after treatment (all P ＞0.05).There were statistically significant differences in the CD4+/CD8+ ratio and CD4+ CD25+ Treg expression between the observation group and control group at 4 weeks after treatment (t =8.589,P ＜ 0.01;t =2.369,P ＜ 0.05).There was no statistically significant difference in the platelet count between the two groups(P ＞ 0.05),but the symptoms of bleeding of the observation group was lighter at 3 weeks after treatment.Conclusion Tripterygium wilfordii polyglycoside improves the expression of CD4+/CD8+ and CD4+ CD25+ Treg in peripheral blood of elderly patients with relapsed or refractory ITP.It is an ideal drug for the treatment of relapsed and refractory ITP in the elderly,it is worth further study.

Objective To investigate the antibiotic resistance trend of commonly used antibiotics of Helicobacter pylori (H.pylori) in Huzhou district,and to summarize the efficacy of eradication in related digestive diseases.Methods In year 2009,2013,2014 and 2015,8 139 gastric mucosa samples of patients undergoing gastroendoscopy examination were collected and H.pylori strains were isolated and cultured.The situation of resistance to levofloxacin,clarithromycin,metronidazole,amoxicillin,tetracycline and furazolidone was analyzed.The infection and antibiotics resistance of H.pylori were analyzed in 11 digestive diseases including functional dyspepsia,chronic gastritis,acute gastritis,duodenitis,gastric ulcer,duodenal ulcer,gastrointestinal dysfunction,gastric cancer,residual gastritis,reflux esophagitis and gastric lymphoma.The eradication schemes and eradication rate of H.pylori was reviewed in six digestive diseases including functional dyspepsia,chronic gastritis,duodenitis,gastric ulcer,duodenal ulcer and reflux esophagitis.Fisher's exact test was performed to compare the differences among the groups.Results A total of 3 263 H.pylori strains were obtained and the infection rate of H.pylori was 40.09％ (3 263/8 139).The H.pylori infection rates of 11 digestive diseases were from 0 to 57.89％,and which was high in duodenal ulcer,gastric ulcer,duodenitis,chronic gastritis and functional dyspepsia (57.89％,726/1 254;49.83％,301/604;42.91％,118/275;37.45％,1 518/4 053 and 36.78％,146/397;respectively).The results of single antibiotic resistance analysis in six digestive diseases needed or planed for H.pylori eradication indicated that resistance rate of H.pylori to levofloxacin and clarithromycin reached 23.09％ (663/2 871) and 17.87％ (513/2 871),respectively.The resistance rate tolevofloxacin dramatically increased from 5.03％ (8/159) in 2009 to 28.24％ (586/2 075) in 2015;the resistance rate to clarithromycin increased from 12.58％ (20/159) in 2009 to 21.78％ (452/2 075) in 2015;meanwhile,the resistance rate of H.pylori to metronidazole was nearly 100.00％.However,the resistance rates to amoxicillin,tetracycline and tetracycline were all zero.The results of double antibiotic resistance analysis in six digestive diseases needed or planed for H.pylori eradication indicated that the rate of both levofloxacin and clarithromycin resistance was 7.73 ％ (222/2 871).The double antibiotic resistance rate of levofloxacin and clarithromycin in different diseases fluctuated between 4.82 ％ and 10.96 ％.Totally 1 479patients of six digestive diseases were treated with quadruple therapy,and 1 363 patients were followed up after eradication therapy,with the eradication rate of 85.99％ (1 172/1 363).Conclusions In Huzhou district,for six common digestive diseases needed or planed for H.pylori eradication,any combination of two drugs in all three drugs including amoxicillin,tetracycline and furazolidone is the first choice for treatment.Only when patients are allergic to penicillin or furazolidone and tetracycline can not be obtained,will levofloxacin and clarithromycin be chosen.A high eradication rate can be achieved by choosing eradication schemes according to the results of H.pylori drug sensitivity test in local region.

Objective:To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy.Methods:Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary micro-bubble SonoVue by biotin-avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time intensity curve was used to analyse rat kidney perfusion characteristics in different groups. Results:Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased(P<0.05); the peak intensity of medulla increased (P<0.05), and the total area under the curve of medulla increased (P<0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P<0.05). The peak intensity of the curve increased (P<0.05), and the total area under the curve increased (P<0.05). Compared with the ordinary angiography group, the peak of GK rat medullacurve in targeted angiography group intensity increased (P<0.05), and the total area under the curve increased (P<0.05).Conclusions:Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

Objective:To explore differences in clinical characteristics and hemoglobin levels between different age groups in patients with metabolic-associated fatty liver disease (MAFLD) at high and low altitude areas, so as to provide a basis for further research on the effect of chronic hypoxia on MAFLD.Methods:Liver function indexes, non-invasive fibrosis indexes, metabolic indexes, and routine blood test of 1 458 (Xining area of Qinghai province) and 1 633 cases (Huzhou area, Zhejiang province) with MAFLD who underwent physical examination were retrospectively analyzed. The total population of the two places were compared and analyzed with the hemoglobin reference limit of 180 g/L. The population of Xining was divided into high and low hemoglobin groups for comparative analysis. The population of the two places was divided into five groups according to age stratification (≤30 years old, 31-40 years old, 41-50 years old, 51-60 years old, ≥61 years old). After multivariate adjustment, the characteristics of high and low hemoglobin groups and MAFLD were compared between the two groups. Statistical analysis was performed with t-test or χ2 test. Results:The detected indexes values observed were higher in Xining than Huzhou area population [fibrosis indexes (FIB4, 1.08±0.02 vs. 1.19±0.02), erythrocyte (5.14±0.13 vs. 5.30±0.13), hemoglobin (156.82±0.37 vs. 164.19± 0.39), alanine aminotransferase (ALT, 33.70±0.66 vs. 43.68±0.70), aspartate aminotransferase (AST, 24.34±0.28 vs. 29.23±0.30), γ-glutamyltransferase (42.40±1.02 vs. 51.82±1.53), alkaline phosphatase (77.92±0.56 vs. 84.63±0.85), triglyceride (TG, 2.07±0.04 vs. 2.74±0.05), uric acid (UA, 383.42±2.15 vs. 406.44±2.36)]. The detected indexes values observed were higher in Huzhou than Xining area population [platelet count (220.54±1.32 vs. 181.62±1.40), total cholesterol (TC, 5.10±0.02 vs. 5.04±0.03), fasting blood glucose (FBG, 5.67±0.04 vs. 5.29±0.04)]. The differences were statistically significant ( P<0.01). Xining population UA and body mass index were increased in high hemoglobin group than low hemoglobin group, and the other parameters difference were not statistically significant. After the population in Xining was grouped by age, high and low FIB4, ALT, and AST and UA levels were detected in the age group of 31-40 and 51-60 years old, >61 years old, 31-40 years old, and the difference between hemoglobin groups were statistically significant ( P<0.01). Conclusion:Patients with MAFLD are more likely to develop fibrosis, liver function impairment, metabolic disorders and so on under high-altitude hypoxic environment. Additionally, there is certain correlation with disease severity and age changes, suggesting that chronic hypoxia can accelerate MAFLD progression.

【Objective】 To analyze the dynamics of specific SARS-CoV-2 IgG antibodies in blood donors in Fuzhou area after receiving booster doses of inactivated COVID-19 vaccine and breakthrough infections, and to provide evidence for the timing of the collection of specific immune plasma or convalescent plasma and the subsequent vaccine doses. 【Methods】 A total of 109 volunteers who received the first booster dose of inactivated COVID-19 vaccine and 102 volunteers who experienced breakthrough infections were recruited at Fujian Blood Center from October to November 2021. Blood samples were collected at eight time points: 14 (11, 20) days before the booster dose (Time0), 14 (10, 23) days after the booster dose (Time1), 53 (45.5, 61) days after the booster dose (Time2), 88 (78, 101.5) days after the booster dose (Time3), 124 (112.5, 138.5) days after the booster dose (Time4), 158 (146, 174) days after the booster dose (Time5), 194 (179.5, 214) days after the booster dose (Time6) and within one month after the breakthrough infection (Time7). Serum SARS-CoV-2 IgG antibodies were detected using a chemiluminescence immunoassay. The dynamics of antibody levels were analyzed and the effects of age, gender, weight, BMI, blood type and smoking on antibody levels were also analyzed. 【Results】 The positive rate of SARS-CoV-2 IgG antibodies was 53.2% (58/109) at Time0, 100% (109/109) at Time1, and 95.4% (104/109) at Time6. The antibody levels were significantly higher at Time1 and Time6 than at Time0 (P<0.001). The highest level was observed at Time1, followed by a gradual decrease until Time2-Time6, which were 89.9% (9.74/10.84), 77.7% (8.42/10.84), 68.3% (7.4/10.84), 59.4% (6.44/10.84), and 53.9% (5.84/10.84) of the peak value at Time1 (P<0.001). There were no significant differences in IgG antibody levels among different gender, weight, BMI, age, blood type and smoker or non-smoker at the same time points (P values all >0.05). The IgG antibody level at Time7 was 2.07 times than that at Time1 (P<0.001). There were no significant differences in IgG antibody levels between asymptomatic groups and symptomatic groups and also between fever-free groups and fever groups (P values all >0.05). The IgG antibody level in breakthrough infection group was significantly higher than that in non-breakthrough infection group (P<0.001). 【Conclusion】 Booster doses of inactivated COVID-19 vaccine and breakthrough infections can stimulate stronger immune responses in the body. It is recommended to collect specific immune plasma or convalescent plasma within one month after breakthrough infections or booster doses of COVID-19 vaccine for special purposes. The timing of subsequent vaccine doses should be based on the dynamics of antibody levels. It is necessary to continuously monitor antibody levels to provide evidence for subsequent vaccine doses.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.