Purpose: Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods: In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results: The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Objective:To study the value of sound touch elastography (STE) linear combined with ultrasound score (US) in the diagnosis of chronic hepatitis B (CHB) liver fibrosis, and to investigate whether their combination can improve the diagnostic efficiency of subdividing the degree of CHB liver fibrosis. Furthermore, a comparison with STE linear combined with the serological model was performed to seek the optimal linear combination model.Methods:A total of 313 subjects were enrolled from September 2018 to December 2021 in Shenzhen Third People′s Hospital Affiliated to Guangdong Medical University, including 259 patients with CHB who had completed liver biopsy and 54 healthy volunteers. CHB patients were divided into liver fibrosis group (F1-F4 group) according to METAVIR classification standard, and healthy volunteers were used as the control group. All subjects underwent liver ultrasound examination, STE and blood biochemical indexes of liver function. The US was performed according to the liver ultrasound examination, and the liver stiffness measurement (LSM) was measured by STE, aspartate aminotransferase and platelet ratio index (APRI) was calculated by blood biochemical index. Fisher discriminant analysis was used to establish the linear combination (LC) diagnostic marker of US and LSM, and the linear combination (LC2) diagnostic marker of LSM and APRI, successively. Spearman rank correlation coefficient was used to analyze the correlations between US, LSM, APRI, LC2, LC and pathological results. The ROC curves of US, LSM, APRI, LC2 and LC for diagnosing CHB liver fibrosis were plotted, and the diagnostic efficiency of above diagnostic markers was evaluated according to the accuracy, sensitivity, specificity and area under the ROC curve (AUC).Results:The formula for the linear combination of US and LSM was LC=0.986 0×US+ 0.166 7×LSM, and LC was highly positively correlated with pathological findings ( rs=0.851, P<0.001), higher than US, LSM, LC2 and APRI ( rs=0.825, 0.775, 0.802, 0.586, all P<0.001). LC showed the best diagnostic efficiency. The AUCs for diagnosing ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis were 0.945, 0.911, 0.954, 0.955, respectively, which superior to the AUCs of US (0.913, 0.879, 0.934 and 0.916, respectively), the AUCs of LSM (0.860, 0.871, 0.934 and 0.952, respectively) and the AUCs of LC2(0.899, 0.883, 0.941, 0.946, respectively). Compared with US, the AUC of LC diagnosis of ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis increased by 3.2%, 3.2%, 2.0% and 3.9%, respectively, with all significant differences ( P<0.05). Compared with LSM, the AUC of LC increased by 8.5%, 4.0%, 2.0% and 0.3%, respectively, with significant difference ( P<0.05) except for stage =F4 cirrhosis.Compared with LC2, the AUC of LC increased by 4.6%, 2.8%, 1.3% and 0.9%, respectively, and there were significant differences in the diagnosis of ≥F1 and ≥F2 liver fibrosis ( P<0.05). Moreover, the overall efficiency of LC2 was not significantly improved than LSM, the difference was not significant ( P>0.05). Conclusions:US, LSM, LC2 and LC can be used to diagnose the degree of CHB liver fibrosis, but LC is better than US or LSM and LC2 alone, especially in the subdivision of mild liver fibrosis, which is a promising new diagnostic marker to subdivide the degree of CHB liver fibrosis.

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 optimize the spray drying process of Banlangen(Isatidis Radix)formula granules based on quality by design(QbD)concept.Methods Using powder yield and the contents of uridine,adenosine,guanosine,and(R,S)-goitron as the critical quality attributes(CQAs),Plackett-Burman design was used to screen out critical process parameters(CPPs)for inlet temperature,spray pressure,liquid temperature,pump speed,and liquid relative density.The central-composite design(CCD)test was used to optimize the CPPs,which were screened.Based on the quadratic polynomial regression model,the design space of spray drying process of Banlangen(Isatidis Radix)formula granules was established,and further validated by experiments.Results Plackett-burman test results show that liquid relative density and inlet velocity are the key parameters for the study.The variance analysis results of CCD test showed that the constructed model in a good prediction ability,since the P-values of model was less than 0.01 and P-values of items lack of fit was more than 0.05.The optimized design space of CPPs was the liquid relative density 1.05-1.08,and pump speed 30%-40%.Conclusion Based on the QbD concept,the design space for the spray drying process of Banlangen(Isatidis Radix)formula granules can improve the stability of its process and help ensure the consistency of product quality.

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.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by poor differentiation, high malignancy and rapid growth fast, short double time, early and extensive metastatic malignancy. In clinical, chemotherapy is the main treatment method, while resistance to multiple chemotherapy drugs in six to nine months has been a major clinical challenge in SCLC treatment. Therefore, It has important clinical value to building SCLC aninimal model which is similar to patients with SCLC. Animal model of xenotransplantation (PDX) from the patients with small cell lung cancer can well retain the characteristics of primary tumor and is an ideal preclinical animal model. The study is aimed to establish SCLC PDX animal model and induce the chemoresistance model to help to study the mechanism of chemoresistance and individual treatment. METHODS: Fresh surgical excision or puncture specimens from SCLC patients were transplanted into B-NSGTM mice subcutaneous tissues with severe immunodeficiency in one hour after operation the B-NSGTM mice subcutaneous in 1 hour, and inject chemotherapy drugs intraperitoneally after its tumor growed to 400 mm³ with EP which is cisplatin 8 mg/kg eight days and etoposide 5 mg/kg every two days until 8 cycles. Measure the tumor volum and mice weights regularly, then re-engrafted the largest tumor and continue chemotherapy. RESULTS: Nine cases were conducted for B-NSG mice modeling. Three of nine cases could be engrafted to new B-NSG mice at least two generation. The SCLC PDX animal models have been established successfully. After adopting chemotherapy drugs, the chemoresistance PDX models have been established. High homogeneity was found between xenograft tumor and patient's tumor in histopathology, immunohistochemical phenotype (Syn, CD56, Ki67). CONCLUSIONS The SCLC PDX animal model and the chemoresistance PDX animal model have been successfully constructed, the success rate is 33%, which provides a platform for the clinical research, seeking for biological markers and choosing individual treatment methods of SCLC.
Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cisplatin ; administration & dosage ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Etoposide ; administration & dosage ; Female ; Humans ; Interleukin Receptor Common gamma Subunit ; deficiency ; genetics ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Small Cell Lung Carcinoma ; drug therapy ; metabolism ; pathology ; Transplantation, Heterologous ; methods ; Xenograft Model Antitumor Assays