Efficacy and safety of trifluridine/tipiracil (TAS-102) in patients with metastatic colorectal cancer: a systematic review and meta-analysis

Objectives The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. Methods The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs). Results There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events. Conclusion TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable (AU)

Efficacy and safety of trifluridine/tipiracil (TAS-102) in patients with metastatic colorectal cancer: a systematic review and meta-analysis.

OBJECTIVES: The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. METHODS: The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events. CONCLUSION: TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable.

Deoxythymidylate kinase (DTYMK) participates in cell cycle arrest to promote pancreatic adenocarcinoma progression regulated by miR-491-5p through TP53 and is associated with tumor immune infiltration.

Background: This study aimed to understand the mechanism of action of deoxythymidylate kinase (DTYMK) and its effect on the prognosis of patients with pancreatic cancer. So as to provide better reference value for improving the clinical management of pancreatic cancer patients. Methods: First, The Cancer Genome Atlas (TCGA) database was employed to identify DTYMK as a differentially expressed gene and to further confirm its expression and its association with the prognosis of pancreatic adenocarcinoma (PAAD) patients. Furthermore, Cox Law of Return is used for multi factor analysis. By constructing a multi factor regression model, a nomogram is constructed according to the contribution of each influencing factor in the model to the outcome variables, The GeneMania and STRING databases served as the basis for investigating the protein-gene interaction network. Moreover, to understand the correlation between DTYMK and immune cells, the TIMER and TCGA databases were explored. Then, Gene Set Enrichment Analysis (GSEA) was performed to investigate potential mechanisms of action. TargetScan was used to identify the miRNAs binding to the 3'UTR of DTYMK mRNA, and starBase was used to verify a possible link between candidate miRNAs and DTYMK. In parallel, the expression of these potential miRNAs in PAAD and their correlation with prognosis was validated through the TCGA database. Results: PAAD patients were observed to have high overall survival (OS), progression free interval (PFI), and disease-specific survival (DSS) with reduced DTYMK expression. Data from the TIMER database show that DTYMK expression inversely correlated with the infiltration levels of most immune cells. GSEA results suggested that DTYMK has a role in cell senescence, DNA repair, pyrimidine metabolism, MYC activation, TP53 control of cell cycle arrest, apoptosis, and the MAPK6/MAPK4 pathway, all of which might influence the biological processes of PAAD. Conclusions: Reduced DTYMK expression may be considered a novel prognostic biomarker for PAAD patients, associated with improved OS, DSS, and PFI. Immune escape may play an important facilitative role. Moreover, we found that miR-491-5p may negatively regulate DTYMK and participate in cell cycle arrest through TP53 to promote pancreatic cancer progression.

SOX combined with intraperitoneal perfusion of docetaxel compared with DOS regimen in the first-line therapy for advanced gastric cancer with malignant ascites: a prospective observation.

OBJECTIVE: This study aimed to verify the survival superiority of the combination of intraperitoneal perfusion and systemic chemotherapy over standard systemic chemotherapy. METHODS: A total of 78 advanced gastric cancer patients with malignant ascites were randomly divided into D-SOX group (intraperitoneal infusion of docetaxel 30 mg/m2 on d1 and d8, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14) and DOS group (intravenous docetaxel 60 mg/m2 on d1, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14). Efficacy of both groups was evaluated every 2 cycles with 21 days as a cycle. The primary endpoint was overall survival, and the secondary endpoints were objective response rate, ascites control rate, negative conversion rate of ascites cytology, and side effects. RESULTS: The median overall survival in D-SOX group was significantly higher than that in the DOS group (11.7 vs 10.3 months, HR 0.52, 95%CI 0.31-0.86, P = 0.005). The ascites control rate in the D-SOX group was 58.9% and 30.8% in DOS group (95%CI 42.8-75.1% vs 95%CI 15.6-45.9%, P = 0.012). Besides, the adverse reactions were tolerable in both groups, and patients in the D-SOX group had lower grade 3/4 blood toxicity than that in the DOS group (26% vs 54%, P = 0.01). CONCLUSION: Compared with traditional systemic chemotherapy, docetaxel intraperitoneal infusion combined with chemotherapy has better therapeutic effect on gastric cancer ascites, with better survival benefit and tolerance and less hematological toxicity, which is worthy of further research and clinical application.

Chidamide combined with traditional chemotherapy for primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma: A case report.

BACKGROUND: Traditional chemotherapy has benefited many patients with non-Hodgkin's lymphoma, but results in a very poor response in patients with rare lymphomas or refractory lymphomas. Previous studies have shown that chidamide has potential anti-lymphoma activity and reverses lymphoma cell chemoresistance to increase the chemosensitivity of lymphoma cells to traditional chemotherapy. CASE SUMMARY: A 14-year-old boy was admitted to our hospital with a 5-d history of generalized erythema, papules, and blisters. Initially, the disease was refractory to potent anti-allergic and anti-infective treatment, and his condition progressively worsened. Skin biopsy revealed primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Considering that the disease is extremely rare in clinical practice, existing case reports have shown poor efficacy with traditional chemotherapy alone. We recommend chidamide combined with traditional chemotherapy for treatment. The regimen was as follows: Chidamide 30 mg/biw, cyclophosphamide 1100 mg/d1, pirarubicin 70 mg/d1, vincristine 2 mg/d1, dexamethasone 20 mg/d1-5, etoposide 100 mg/d1-5, in a 21 d cycle. The treatment effect was considerable, and complete remission was achieved after 4 cycles of treatment, after which the patient completed a total of 6 cycles of treatment. Subsequently, the patient regularly took chidamide 20 mg/biw as maintenance therapy for 1 year. To date, the patient has been disease-free for 3 years. CONCLUSION: This case suggests that the combination of chidamide and traditional chemotherapy is effective in primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma.

The expression of Slit2 and Robo1 increased during retinoic acid syndrome in acute promyelocytic leukemia and impacted differentiated cell migration.

Retinoic acid syndrome (RAS) is a serious complication developed during the induction therapy of acute promyelocytic leukemia (APL). Cytokines and differentiated cells migration play important roles in the development of RAS. Slit guidance ligand 2 (Slit2) and roundabout 1 (Robo1) involve in cell migration. Our study aimed to investigate the expression of Slit2 and Robo1 in APL and check whether they affected promyelocytes migration. 62 cases of newly diagnosed APL patients were involved and received all-trans retinoic acid (ATRA) and arsenic trioxide as induction therapy. Bone marrow cells (BMCs) were obtained on days 0 and 28, and promyelocytes and plasma were collected from day 1 to day 21. The expression of Robo1 in promyelocytes, and that of Slit2 and cytokines, including IL-8,IL-1ß and others, in serum were monitored. 20 healthy individuals donated their cells as control. Of the 62 APL patients, 16 (25.81%) patients developed RAS. The expression of Robo1, Slit2 and IL-8 increased significantly with the development of RAS. In the 16 patients with RAS, levels of Slit2, Robo1 and IL-8 were higher during the development of RAS than before or after the RAS (P < 0.05). RhSlit2-N and rhIL-8 induced cells migration, and the migration induced by IL-8 was not inhibited by rhSlit2-N. Elevated Slit2 and Robo1 levels might be useful markers for the diagnosis and treatment of RAS. The levels of Slit2, Robo1 and IL-8 showed a positive correlation with the severity of RAS. Slit2 and IL-8 promoted the migration of differentiated cells.

Analysis of foodborne diseases outbreaks in schools from 2011 to 2020 in Henan Province / 中国学校卫生

Objective@#To analyze the epidemiological characteristics of school foodborne disease outbreaks in Henan Province from 2011 to 2020 and to provide the basis for effective prevention and control of school foodborne disease outbreaks.@*Methods@#The outbreaks of foodborne diseases in schools in Henan Province reported by the foodborne disease outbreak surveillance system from 2011 to 2020 were statistically analyzed.@*Results@#A total of 47 outbreaks of school foodborne diseases were reported in Henan province in the past 10 years, with a total of 1 258 cases, 701 hospitalizations and 1 death. Zhengzhou, Zhumadian, Xinyang and Xinxiang were the top 4 cities in Henan Province in terms of the number of school foodborne disease outbreaks reported. The peak of foodborne illness incidents in schools was in June and September. The largest number of incidents occurred in middle school canteens and primary school canteens(all 12). The number of reported incidents (12) and the number of cases of foodborne diseases (371) in schools caused by cereals and their products were the largest. Pathogenic bacteria and their toxins were the main pathogenic factors that caused the outbreaks of foodborne diseases in schools, accounting for 78.26% of the identified causes. Bacillus cereus was the top pathogens causing foodborne diseases outbreaks in schools. The pathogenic factor that caused the largest number of cases was Diarrheogenic Escherichia Coli, and the pathogenic factor that caused the death cases was poisonous mushrooms. Apart from unexplained incidents, improper processing was the main link leading to foodborne diseases outbreaks in schools.@*Conclusion@#The primary and middle school students are the group with high incidence of foodborne diseases in schools. The supervision and management of school canteen should be strengthened in summer to prevent the outbreak of bacterial foodborne diseases caused by improper processing and storage of grain food.

Effects of the COVID-19 Pandemic on Obsessive-Compulsive Symptoms Among University Students: Prospective Cohort Survey Study.

BACKGROUND: The COVID-19 pandemic is associated with common mental health problems. However, evidence for the association between fear of COVID-19 and obsessive-compulsive disorder (OCD) is limited. OBJECTIVE: This study aimed to examine if fear of negative events affects Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores in the context of a COVID-19-fear-invoking environment. METHODS: All participants were medical university students and voluntarily completed three surveys via smartphone or computer. Survey 1 was conducted on February 8, 2020, following a 2-week-long quarantine period without classes; survey 2 was conducted on March 25, 2020, when participants had been taking online courses for 2 weeks; and survey 3 was conducted on April 28, 2020, when no new cases had been reported for 2 weeks. The surveys comprised the Y-BOCS and the Zung Self-Rating Anxiety Scale (SAS); additional items included questions on demographics (age, gender, only child vs siblings, enrollment year, major), knowledge of COVID-19, and level of fear pertaining to COVID-19. RESULTS: In survey 1, 11.3% of participants (1519/13,478) scored ≥16 on the Y-BOCS (defined as possible OCD). In surveys 2 and 3, 3.6% (305/8162) and 3.5% (305/8511) of participants had scores indicative of possible OCD, respectively. The Y-BOCS score, anxiety level, quarantine level, and intensity of fear were significantly lower at surveys 2 and 3 than at survey 1 (P<.001 for all). Compared to those with a lower Y-BOCS score (<16), participants with possible OCD expressed greater intensity of fear and had higher SAS standard scores (P<.001). The regression linear analysis indicated that intensity of fear was positively correlated to the rate of possible OCD and the average total scores for the Y-BOCS in each survey (P<.001 for all). Multiple regressions showed that those with a higher intensity of fear, a higher anxiety level, of male gender, with sibling(s), and majoring in a nonmedicine discipline had a greater chance of having a higher Y-BOCS score in all surveys. These results were redemonstrated in the 5827 participants who completed both surveys 1 and 2 and in the 4006 participants who completed all three surveys. Furthermore, in matched participants, the Y-BOCS score was negatively correlated to changes in intensity of fear (r=0.74 for survey 2, P<.001; r=0.63 for survey 3, P=.006). CONCLUSIONS: Our findings indicate that fear of COVID-19 was associated with a greater Y-BOCS score, suggesting that an environment (COVID-19 pandemic) × psychology (fear and/or anxiety) interaction might be involved in OCD and that a fear of negative events might play a role in the etiology of OCD.

Double Burden of Malnutrition: Examining the Growth Profile and Coexistence of Undernutrition, Overweight, and Obesity among School-Aged Children and Adolescents in Urban and Rural Counties in Henan Province, China.

Objective: To examine the gender, age, and region of residence in the anthropometric and nutritional profiles of children and adolescents aged 6-18 in Henan Province, China's third most populous province. Design: This cross-sectional study of the China National Nutrition and Health survey (2010-2013) used a multistage cluster sampling technique. The sample included Chinese schoolchildren and adolescents aged 6 to 18 years (1,660 boys and 1,561 girls). Multiple logistic regression models were used to estimate the associations between sociodemographic correlates and overweight or obesity and stunting. Setting. Nine districts/counties in Henan Province. Participants. 3,221 subjects completed the questionnaire. Sociodemographic information was obtained. Body weight and height were measured. Results: There were statistically significant regional differences in average height and weight for boys in all age groups. Girls followed the same trends except for height when 15-18 years old. The urban-rural residence differences were found in relation to prevalence of stunting and weight status. Subjects in poor rural areas (15.43%) and ordinary rural areas (15.34%) had higher rates of stunting compared to their urban counterparts. Prevalence of overweight or obesity was highest in big city areas (15.71%) and lowest in ordinary rural areas (6.37%). Being a boy (OR = 1.69, 95% CI = 1.314-2.143), living in a big city (OR = 2.10, 95% CI = 1.431-3.073), or in a small-medium city (OR = 2.28, CI = 1.606-3.247), or being in a younger age group was associated with being overweight or obese. In addition, being a boy, living in a big city, or in a small-medium city, or being younger in age meant they were less likely to be stunted. Conclusions: A substantial dual burden of malnutrition among children and adolescents in Henan Province was revealed. The urban-rural differences in nutritional status were found. Stunting was more prevalent in rural areas than in urban. In contrast, while the rising problem of childhood and adolescent obesity still exists in the big city, we also found a great spike in obesity in small-medium cities. Evidence also indicated that boys were more likely to be overweight or obese. Our findings suggest that nutrition education, as well as environmental and policy interventions, is needed to target specific geographic regions.

[Growth and nutritional status of children and adolescents aged 6 to 17 years in Henan Province from 2010 to 2013].

OBJECTIVE: To analyze the height, weight and BMI of children and adolescents aged 6-17 in different sex, age and area in Henan Province from 2010 to2013. METHODS: Based on the monitoring of nutrition and health status of Chinese residents conducted in 9 urban and rural monitoring points in Henan Province from October 2010 to December 2013, 3221 aged 6-17 children and adolescents were selected by multi-stage stratification and population proportional random sampling method, including 1660 male students and 1561 female students; 420 in large cities, 628 in small and medium-sized cities, 1460 in rural areas, and 713 in poor rural areas. Family members basic information questionnaires were used to collect basic information, measured height, weight to obtain data, after weighted to analyze the height, weight, body mass index(BMI), stunting, wasting, overweight and obesity. RESULTS: In 2010-2013, the development of children and adolescents aged 6-17 in Henan Province were in line with the general principles. The height and weight development of urban students were generally better than those of rural students. The difference between urban and rural areas had been narrowed in BMI. The overall malnutrition rate in the province was 6. 89%. A total of 89 children and adolescents had stunting with a stunting rate of 2. 76%. In addition to stunting, there were 59 moderate-serve wasting(1. 83%) and 74 mild wasting(2. 30%). The malnutrition of rural students was more serious than that of cities. The overweight and obesity rates of children and adolescents in big cities, small and mediumsized cities, ordinary rural areas and poor rural areas were 10. 0%, 9. 69%, 5. 47%, 4. 56%, and 9. 02%, 9. 34%, 3. 40% and 4. 10%, respectively. The overweight and obese were more serious in urban than rural areas. Especially the obesity was epidemic in low-age primary school students. CONCLUSION: In view of the double burden coexists in stunting, wasting, overweight and obesity of children and adolescents in Henan Province, and meanwhile, the feature that malnutrition in rural students more serious, overweight and obese in urban students more critical, scientific and effective preventive measures should be carried out in time to ensure the healthy growth of children and adolescents, especially more attention on lower grade children in primary school.

A meta-analysis of the lymphatic microvessel density and survival in gastric cancer with 1809 cases.

Lymph node metastasis commonly occurs in gastric cancer. Previous studies have demonstrated that the overexpression of lymphatic microvessel density (LVD) is correlated with various malignancies. To evaluate the potential role of LVD in various malignancies, we conducted a systematic review and meta-analysis to thoroughly investigate the association of LVD expression with tumor progression and survival in gastric cancer. We performed a comprehensive search of common databases and selected studies demonstrating the relationship between LVD expression and gastric cancer prognosis. Hazard ratios (HR) were used to determine the value of LVD for predicting gastric cancer metastasis and prognosis. The data were extracted from the included studies and pooled with the appropriate effects model using STATA 12.0. The results showed that high LVD expression obviously impacted the prognosis of gastric cancer, based on an overall survival (OS) HR of 2.58 (95% CI: 1.91-3.48, P < 0.001) and a disease-free survival (DFS) HR of 2.51 (95% CI: 1.35-4.68, P = 0.004) in the univariate analysis. In addition, the results of the multivariate analysis indicated a remarkable relationship between high LVD expression and gastric neoplasm prognosis. The pooled OS HR was 4.12 (95% CI: 3.45-4.91, P < 0.001). The current meta-analysis shows that high LVD is closely related to tumor metastasis and poor prognosis in gastric malignancy. LVD could be a key factor in tumor lymphatic metastasis. Moreover, LVD is likely a potential index and an effective biomarker for the prediction of patient prognosis.

The essential role of MTDH in the progression of HCC: a study with immunohistochemistry, TCGA, meta-analysis and in vitro investigation.

Recent studies found that metadherin (MTDH) played an essential role in hepatocellular carcinoma (HCC). Nevertheless, the exact function of MTDH in the pathogenesis of HCC was unclarified. In the present study, we aimed to investigate the clinical significance of MTDH in HCC and its effect on HCC cells. Immunohistochemistry (IHC) was performed to detect MTDH expression in HCC tissues. Data from The Cancer Genome Atlas (TCGA) and ONCOMINE was obtained to examine MTDH expression in HCC and its clinical significance. Meta-analysis was conducted to assess the correlation between MTDH expression and both the prognosis (Overall Survival (OS) or Disease-free Survival (DFS)) and clinicopathological features of HCC via STATA 12.0. In vitro experiments were performed to investigate the role of MTDH in cell growth, caspase-3/7 activity and apoptosis in HCC cells. The MTDH staining was remarkably stronger in HCC tissues than in non-cancer tissues from IHC, TCGA and ONCOMINE data. Moreover, MTDH-positive expression was significantly correlated with pathological grade, distant metastasis and hepatitis B virus (HBV) infection by IHC. For meta-analysis, MTDH expression was indicative of poor OS without heterogeneity in HCC patients. Additionally, MTDH expression was correlated with high-grade histological differentiation, non-vascular invasion and metastasis in HCC. In vitro experiments revealed that MTDH could the inhibit cell growth and activate caspase-3/7 activity and apoptosis in the four HCC cell lines. In conclusion, MTDH expression may serve as a novel targeting strategy for HCC due to its clinical significance and oncogenic function in HCC cells.

[Investigation on the nutrition labels of prepackaged traditional foods of Henan Province].

OBJECTIVE: To understand the current status of nutrition labeling on Henan province local traditional prepackaged food product. METHODS: Purchasing the samplings according with the include criteria in the supermarket and retail stores within the scope of province, then taking photographs and logging nutrition labeling information to questionnaire, using Excel and SPSS 15.0 software to analyze. The .significance of difference rate was judged by chi-square test. RESULTS: The sum of meeting requirement samplings was 565 (including 5 major categories and 13 small classes) and the entire nutritional labeling signing rate was 91.9%. The signing rate of forced signing nutrients such as energy, protein, carbohydrates, fat and sodium was 98.8%. There were 7 kinds of mistakes of nutritional labeling signing. The nutrition labeling signing rate of optional nutrients was very low. The signing rate of nutrition claims and function claims was less than 4%. CONCLUSION: In the traditional local prepackaged food products made in Henan province, the forced signed nutrition labeling was well sighed but optional content was ignored.

[Analysis of phytosterol contents in food plant materials and Chinese traditional medicines].

OBJECTIVE: To analyze the phytosterol content in food plant materials and Chinese traditional herbal medicines commonly used in China. METHODS: 18 kinds of food plant materials and 32 kinds of Chinese traditional herbal medicines, which were commonly used in functional food, were chosen as samples. The contents of beta-sitosterol, campesterol, stigmasterol, beta-sitostanol were analyzed by GC methods and the percent of each ingredient were calculated. RESULTS: The contents of phytosterols in 18 kinds of food plant materials were from 14.8 mg/100 g to 208.3 mg/100 g, while the content of phytosterols in 32 Chinese traditional herbal medicines were from 9.4 mg/100 g to 280.3 mg/100 g. In most samples, beta-sitosterol is the largest part of total phytosterol. CONCLUSION: Phytosterols were existed in 50 kinds of food plant materials and Chinese traditional herbal medicines commonly used in functional food, maybe phytosterol is an important functional ingredient in some plant materials.

[Genotyping of hepatitis B virus and clinical investigation].

OBJECTIVE: To investigate the distribution of HBV genotypes in Changzhou area and to clarify the genotype-related difference in the liver function, the level of HBV DNA and the long-term effect of lamivudine in the pathogenicity of HBV. METHODS: Nested PCR and sequence analysis were conducted in 14 acute hepatitis (AH), 104 chronic hepatitis (CH), and 28 liver cirrhosis or hepatocellular carcinoma (LC/HCC) patients. RESULTS: One hundred and forty six samples were positive for HBV DNA, and 51 samples were classified as genotype B (34.9%), 95 samples were classified as genotype C, serum ALT value was 383.8 +/- 335.7 IU in patients with HBV genotypes B, and 364.3 +/- 333.7 IU in genotypes C, HBV DNA value was 10(7.795 +/- 1.22) copies/ml in genotypes B and 10(7.69 +/0- 1.19) copies/ml in genotypes C, and there were 36 and 64 HBeAg positive cases in patients with genotypes B and C; there were no significant difference on the level of ALT, HBV DNA and the expression of HBeAg (P>0.05), but genotype C in LC/HCC was higher than CH (P<0.01). Twenty three genotype B and forty five genotype C patients received lamivudine treatment, after 48 weeks, 18 genotype B and 14 genotype C patients had higher ALT or HBV DNA positive. CONCLUSIONS: These results indicate that genotype B and C existing Changzhou area; genotype C is associated with the development of severe liver disease and better therapeutic effect could be obtained in the patients with genotype C.