[Venetoclax Combined with CACAG Regimen in the Treatment of Patients with Refractory/Relapse Acute Myeloid Leukemia: A Prospective Clinical Study].

OBJECTIVE: To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML). METHODS: The study was a singlecenter prospective clinical trial. The enrolled patients met the criteria for R/R AML. Treatment included Azacidine(75 mg/m2，d 1-7), Ara-C (75-100 mg/m2, q12h, d 1-5), Aclacinomycin(20 mg d1,d3,d5), Chidamide(30 mg d1,d4), Venetoclax(100 mg d1, 200 mg d2, 400 mg d3-d14, in combination with Triazole Drug, reduced to 100 mg/d), and granulocyte colony-stimulating factor (300 µg /d until neutrophil recovery). The primary endpoint of observation was overall response rate after 1 course of treatment. RESULTS: A total of 19 patients were enrolled from January 2022 to April 2023. After 1 course of treatmen, the overall response rate was 81.3%(13/16), the CR rate was 68.8%(11/16), and the PR was 12.5%(2/16). Among the 11 patients who got CR/CRi, 8 cases achieved CRm (minimal residual disease negative CR) and 3 cases did not. As of March 27, 2023, the median follow-up time was 111(19-406) days. The six-month overall survival and progression-free survival rates were both 55.7%, the 1-year overall survival and progression-free survival rates were 46.4% and 47.7%, respectively. In addition, compared with the non-CRm group, CRm patients had a better PFS (377 days vs 111 days, P =0.046). Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression, complicated by various degrees of infection(n=12), hypokalemia(n=12) and hypocalcemia (n=10) and elevated liver enzymes (n=8), of which 3/4 degrees accounted for 47.4%(9/19). CONCLUSION: The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML, with high remission rate and safety profile.

Optimal choice of stapler and digestive tract reconstruction method after distal gastrectomy for gastric cancer: A prospective case-control study.

BACKGROUND: Gastric cancer is the most common cause of cancer-related deaths, and is classified according to its location in the proximal, middle, or distal stomach. Surgical resection is the primary approach for treating gastric cancer. This prospective study aimed to determine the best reconstruction method after distal gastrectomy for gastric cancer. AIM: To explore the efficacy of different staplers and digestive tract reconstruction (DTR) methods after radical gastrectomy and their influence on prognosis. METHODS: Eighty-seven patients who underwent radical gastrectomy for distal gastric cancer at our institution between April 2017 and April 2020 were included in this study, with a follow-up period of 12-26 mo. The patients were assigned to four groups based on the stapler and DTR plan as follows: Billroth Ⅰ (B-I) reconstruction + linear stapler group (group A, 22 cases), B-I reconstruction + circular stapler group (group B, 22 cases), Billroth II (B-II) reconstruction + linear stapler group (group C, 22 cases), and B-II reconstruction + circular stapler group (group D, 21 cases). The pathological parameters, postoperative gastrointestinal function recovery, postoperative complications, and quality of life (QOL) were compared among the four groups. RESULTS: No significant differences in the maximum diameter of the gastric tumors, total number of lymph nodes dissected, drainage tube removal time, QLQ (QOL questionnaire)-C30 and QLQ-STO22 scores at 1 year postoperatively, and incidence of complications were observed among the four groups (P > 0.05). However, groups A and C (linear stapler) had significantly lower intraoperative blood loss and significantly shorter anastomosis time, operation time, first fluid diet intake time, first exhaust time, and length of postoperative hospital stay (P < 0.05) than groups B and D (circular stapler). CONCLUSION: Linear staplers offer several advantages for postoperative recovery. B-I and B-II reconstruction methods had similar effects on QOL. The optimal solution can be selected according to individual conditions and postoperative convenience.

A novel scoring system for the quantitative prediction of prognosis in acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy. Patient prognosis cannot be accurately assessed in National Comprehensive Cancer Network (NCCN) risk stratification subgroups based on the current criteria. This study aimed to develop a novel prognostic score model for the quantitative prediction of prognosis in AML. Results: We developed a prognostic risk scoring model of AML using differentially expressed genes to predict prognosis in patients with AML. Furthermore, we evaluated the effectiveness and clinical significance of this prognostic model in 4 AML cohorts and 905 patients with AML. A prognostic risk scoring model of AML containing eight prognosis-related genes was constructed using a multivariate Cox regression model. The model had a higher predictive value for the prognosis of AML in the training and validation sets. In addition, patients with lower scores had significantly better overall survival (OS) and even-free survival (EFS) than those with higher scores among patients with intermediate-risk AML according to the NCCN guidelines, indicating that the model could be used to further predict the prognosis of the intermediate-risk AML populations. Similarly, patients with high scores had remarkably poor OS and EFS in the normal-karyotype populations, indicating that the scoring model had an excellent predictive performance for patients with AML having normal karyotype. Conclusions: Our study provided an individualized prognostic risk score model that could predict the prognosis of patients with AML.

Symptomatic and Asymptomatic SARS-CoV-2 Infection and Follow-up of Neutralizing Antibody Levels.

Objective: To investigate neutralizing antibody levels in symptomatic and asymptomatic patients with coronavirus disease 2019 (COVID-19) at 6 and 10 months after disease onset. Methods: Blood samples were collected at three different time points from 27 asymptomatic individuals and 69 symptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Virus-neutralizing antibody titers against SARS-CoV-2 in both groups were measured and statistically analyzed. Results: The symptomatic and asymptomatic groups had higher neutralizing antibodies at 3 months and 1-2 months post polymerase chain reaction confirmation, respectively. However, neutralizing antibodies in both groups dropped significantly to lower levels at 6 months post-PCR confirmation. Conclusion: Continued monitoring of symptomatic and asymptomatic individuals with COVID-19 is key to controlling the infection.

Differences and Correlation Analysis of Birth Weight and Overweight/Obesity in Shanghai Twin Cohort.

The objective of this study was to analyze differences in birth weight and overweight/obesity in a Shanghai twin cohort. We also wanted to study their association and explore possible risk factors for the discordance of overweight/obesity within twins. This was an internal case-control study designed for twins. The 2012 Shanghai Twin Registration System baseline survey data of a total of 3417 twin pairs were statistically analyzed using SPSS22 software. Results show that the body mass index (BMI) of the Shanghai twin population increased with age. Twins with a high birth weight had a higher BMI and a higher rate of overweight and obesity; 0- to 6-year-old twins, male twins and dizygotic (DZ) twins had higher rates of overweight/obesity than other groups. The greater the discordant birth weight rate of twins, the more obvious the difference in BMI (p < .05). There was a significant difference in overweight/obesity between twins with a relative difference of birth weight ≥15% in DZ twins (p < .05). DZ twins, male twins and 0- to 6-year-old twins were more likely to be discordant in overweight/obese than others. The discordant birth weight within twins was not a risk factor for discordant overweight/obesity. However, attention should be paid to childhood obesity, and appropriate interventions should be made at the appropriate time. Genetics may play an important role in the occurrence and development of overweight/obesity. In conclusion, discordant growth and development in the uterus early in life may not lead to discordant weight development in the future.

Mitigation of membrane biofouling by d-amino acids: Effect of bacterial cell-wall property and d-amino acid type.

Development of novel approaches for biofouling mitigation is of crucial importance for membrane-based technologies. d-amino acids (d-AAs) have been proposed as a potential strategy to mitigate biofouling. However, the effect of bacterial cell-wall properties and d-AAs type on biofouling mitigation remains unclear. This study assesses the effect of d-AAs type on membrane biofouling control, towards Gram positive (G+) and Gram negative (G-) bacteria. Three kinds of d-AAs were found to inhibit both G+ and G- bacterial attachment in short-term attachment and dead-end filtration experiments. The existence of d-AAs reduces extracellular polysaccharides and proteins on the membrane, which may decrease membrane biofouling. Cross-flow filtration tests further indicated that d-AAs could effectively reduce membrane biofouling. The permeate flux recovery post chemical cleaning, improved for both P. aeruginosa and B. subtilis treated with d-AAs. The results obtained from this study enable better understanding of the role of d-AAs species on bacterial adhesion and biofilm formation. This may provide a new way to regulate biofilm formation by manipulating the species of d-AAs membrane systems.

Design and synthesis of novel PEG-conjugated 20(S)-camptothecin sulfonylamidine derivatives with potent in vitro antitumor activity via Cu-catalyzed three-component reaction.

In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel structurally diverse PEG-based 20(S)-CPT sulfonylamidine derivatives were designed, synthesized via a Cu-multicomponent reaction (MCR), and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, and were more potent than irinotecan. Significantly, these derivatives exhibited comparable cytotoxicity against KBvin, while irinotecan was less active against this cell line. With a concise efficient synthesis and potent cytotoxic profiles, especially significant activity towards KBvin, these compounds merit further development as a new generation of CPT-derived PEG-conjugated drug candidates.

[Relationship between the clustering of risk factors and the prevalence of hypertension in the community residents living in Shanghai].

OBJECTIVE: To study the association between the clustering manifestation of factors as overweight and central obesity, family heredity, immoderate alcohol drinking, tobacco smoking, hyperlipidemia, hyperglycemia and the prevalence of hypertension. METHODS: Data was from a program related to the comprehensive prevention and control strategies on cardiac-cerebral vascular disease carried out in the communities of Shanghai, to describe the relationship between the clustering of risk factors and hypertension. This program included 15 158 people with complete data at the age of 35 - 74, from 2008 - 2011. Both single factor and multi-factor analysis were used and longitudinal study was performed to further explore the causal relationship. RESULTS: The overall prevalence of hypertension at the baseline survey was 41.9%. The associated ORs (age-adjusted) of hypertension parallelly increased with the number of risk factors under clustering. The associated OR of the males with 1, 2, 3, 4 as well as 5 and above risk factors were 3.157 [95% confidence interval (CI): 2.152 - 4.630], 6.428 (95%CI: 4.435 - 9.319), 11.797 (95%CI: 8.135 - 17.105), 19.723 (95%CI: 13.414 - 29.000), 33.051 (95%CI: 21.449 - 50.930) respectively. In females with 1, 2, 3 as well as 4 risk factors, the associated ORs were 2.917 (95%CI: 2.374 - 3.585), 6.499 (95%CI: 5.307 - 7.959), 15.717 (95%CI: 12.609 - 19.591) and 31.719 (95%CI: 21.744 - 46.270), respectively. For longitudinal study, the 2-year incidence of hypertension in males and females were 1.9% and 1.6%, respectively. Compared to those people without risk factors, the incidence was higher in the people with a larger number of clustering. When the clustering number reaching 2 or 3 in females, the relative risk (RR) were 2.111 (95%CI: 1.024 - 4.350) and 3.000 (95%CI: 1.287 - 6.995) respectively, with statistically significant difference. CONCLUSION: The risk of hypertension parallelly increased with the clustering number of relevant risk factors. Comprehensive prevention and control on related risk factors was required.

[A comparative study on blood pressure, obesity, smoking and alcohol drinking behavior in Chinese twins reared apart and together].

OBJECTIVE: To test the potential feasibility for studies conducted in twins reared apart and together from the Chinese National Twin Registry (CNTR) and to answer the question whether the rearing environment affects chronic disease risk factors. METHODS: The samples were composed of twins from two sub-registries, which included 503 twin pairs in Lishui and 505 twin pairs in Qingdao. RESULTS: There was a big difference in the rates of twins reared apart in different areas (from 0.6% in Qingdao to 5.4% in Lishui). Only nine pairs of dizygotic twins reared apart in Lishui were recruited. The intraclass correlation coefficients for many indices were not significant. Rearing environment might affect diastolic blood pressure and smoking behavior, but it was hard to interpret its impacts in systolic blood pressure, body mass index, waist-hip ratio and drinking behavior. CONCLUSION: The design of twins reared apart is a valuable study and can be conducted in the CNTR, but the current sample size is still a big issue which requires the registry to recruit more twins to support it.

[Study of twin-birth on genetic or environmental determinants of male Chinese smoking initiation].

OBJECTIVE: To determine the role of genetic and environmental factors in the onset of smoking in Chinese male twins. METHODS: Retrospective data on initiation and age at onset of smoking, reported by 1,006 adult twin pairs [aged 18 year-old or more, 638 pairs of monozygotic (MZ) twins and 368 pairs of dizygotic (DZ) twins] were analyzed to calculate the heritability of smoking behavior and smoking initiation. RESULTS: Different from western culture, 66.8% of males in this Chinese sample are smokers or have the experience of smoking, but only 0.2% of females do so. In the MZ twins, 88.7% (566/638 pairs) of them are both smokers or have smoking experience or both non-smokers, while the number is 63.6% (234/368 pairs) in the DZ twins. The heritability of smoking in this Chinese twin sample is 69.0%+/-4.1%. The smokers usually started their smoking at the age of 20.4+/-5.3 years old. The correlation coefficient for age at onset of smoking in male MZ twin smokers is 0.393, compared to correlation coefficient 0.860 in male DZ twin smokers. CONCLUSION: The moderate level of heritability shows that genetic factors have influence on smoking choice; when the smokers start their smoking, however, this depends more on individual environmental variation in our Chinese twin sample.

[Value of tumor markers series of hydrothorax in differential diagnosis of pleural effusion].

OBJECTIVE: To investigate the clinical value of pleural effusion lung ProGRP, neuron specific enolase (NSE), cytokeratin fragment 19 (CYFRA21-1), carcino-embryonic antigen (CEA), carbohydrate antigen 153 (CA153), carbohydrate antigen 19 - 9 (CA19-9) in differential diagnosis and histological typing of malignant pleural effusion caused by lung cancer. METHODS: All the 171 patients with malignant hydrothorax caused by lung cancer were from coal-mine area of Kailuan. They were divided into the small cell lung cancer (SCLC) group (n = 39), the adenocarcinoma group (n = 99) and the squamous cell carcinoma group (n = 37). The patients with benign pleural effusion served as the controls (n = 30). The diagnostic value of pleural effusion ProGRP, NSE, CYFRA21-1, CEA, CA153 and CA19-9 was compared for each group. RESULTS: Youden index and the accurate rate of pleural effusion ProGRP + NSE (sequence test) were the highest in the diagnosis of malignant hydrothorax caused by SCLC. CEA + CA153 + CA19-9 (sequence test) was the highest in the diagnosis of malignant hydrothorax caused by adenocarcinoma. CYFRA21-1 + CEA + CA153 (on parallel test) were the highest in the diagnosis of malignant hydrothorax caused by squamous cell carcinoma. The Yonden index and the accurate rate were the highest by the single detection of CYFRA21 (0.5514 and 0.6878), and by the combined detection of ProGRP + CYFRA21-1 + CEA (on parallel test) (0.7029 and 0.8878). CONCLUSION: The first pleural effusion tumor markers of malignant hydrothorax caused by the SCLC, adenocarcinoma of lung, and lung squamous cell carcinoma are ProGRP, CEA and CYFRA21-1, respectively. The best combinations of pleural effusion tumor marker in diagnosis of malignant hydrothorax caused by the SCLC, adenocarcinoma of lung, lung squamous cell carcinoma and lung cancer are the combined detection of ProGRP + NSE (sequence test), combined detection of CEA + CA153 + CA19-9 (sequence test), the combined detection of CYFRA21-1 + CEA + CA153 (on parallel test) and ProGRP + CYFRA21-1 + CEA (on parallel test), respectively.

[Level and heritability analysis of serum apoA I and apoB100 in twins].

OBJECTIVE: To describe the serum level of apoA I and apoB100 in twins, and study the contribution of genetic and environmental effects to them. METHODS: The researchers used immunoturbidimetric assay (ITA) for quantification of the serum apoA I and apoB100 in 329 monozygotic (MZ) and 173 dizygotic (DZ) twins identified by genotyping. Mx was used to fit a variety of genetic models covering age and sex for the variation of apoA I and apoB100. RESULTS: The serum levels were (1.33+/-0.23) g/L for apoA I and (0.75+/-0.19) g/L for apoB100. Model AES fitted apoA I data best and scalar effects sex-limitation model AE fitted apoB100 best. 60% of the variance in apoA I was due to additive effects and 69% in apoB100. CONCLUSION: The heritability of apoA I and apoB100 in this twin study was 60% and 69%.