Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

To study the prevalence of depression, anxiety, and insomnia among social workers during the prolonged battle against the COVID-19 pandemic and explore the associated risk factors.

ObjectiveTo investigate the current status of secondary prevention of stable angina in patients with coronary heart disease in three regions of China， namely Henan Province， Xinjiang Uygur Autonomous Region， and Tianjin City， and analyze the the influencing factors. MethodsA cross-sectional study was conducted to include patients with stable angina with coronary heart disease in Henan， Tianjin and Xinjiang from August 10， 2020 to March 14， 2021. General information， traditional Chinese medicine （TCM） syndrome elements， prescriptions and other data of patients were collected， and clinical characteristics， blood pressure， blood lipid and blood glucose of patients were analyzed； the patients were divided into groups according to whether their blood pressure， blood lipid and blood glucose were up to standard. With the most common syndrome element as the main variable， region， age and gender as covariables， Logistic regression equation was incorporated to analyze the influencing factors for the patients' blood pressure， blood lipid and blood glucose being up to standard. ResultsA total of 1061 coronary heart disease patients with stable angina were included， including 658 in Henan， 210 in Xinjiang， and 193 in Tianjin. The clinical characteristics of patients in the three regions showed statistical different in age， sex， disease course， complication， blood pressure， blood lipid， blood glucose， smoking， drinking， living habits， and medication treatment （P＜0.05 or P＜0.01）. For the included patients， qi deficiency （79.55%， 844/1061） and blood stasis （39.96%， 424/1061） were the main syndrome elements. The overall compliance rate of blood pressure was 48.89% （506/1035）， blood lipids 12.68% （133/1049） and blood glucose 48.18% （504/1046）. Qi deficiency was the independent factor affecting the blood pressure of coronary heart disease patients with stable angina combined with hypertension （P = 0.029，95%CI ［1.048， 2.369］）， and the independent factors influencing the blood lipid standard of coronary heart disease patients with stable angina （P = 0.011， 95%CI ［1.133， 2.646］）， but not the independent factors affecting blood glucose standard in coronary heart disease patients with diabetes （P＞0.05）. ConclusionCoronary artery disease patients with stable angina have geographical variability in clinical characteristics and distribution of TCM syndrome elements， and the overall control of blood pressure， blood lipids， and blood glucose is poor， and qi deficiency syndrome is an independent risk factor affecting the control of blood pressure and blood lipids.

Objective To explore the application of painless diagnosis and treatment technology in children's peripherally inserted central catheter(PICC)guided by ultrasound.Methods Totally 82 children who planned to undergo PICC in the hospital from January 2021 to January 2023 were selected and randomly divided into a control group and an observation group using a random number table method,with 41 cases in each group;The control group underwent conventional ultrasound guided PICC catheterization,while the observation group underwent painless diagnostic and therapeutic techniques using ultrasound guided PICC catheterization;Compare the success rate of catheterization,completion time of catheterization,degree of pain in the child pain[children's pain behavior scale(FLACC)],tolerance[Houpt behavior scale(HBS)],compliance[Frankl scale(FCS)],and family satisfaction between the two groups.Results The success rate of catheterization in the observation group was higher than that in the control group,and the catheterization time was shorter than that in the control group,with a statistically significant difference(P<0.05).The FLACC score of the observation group was lower than that of the control group,while the HBS score and FCS score were higher than those of the control group,with a statistically significant difference(P<0.05);The total satisfaction of family members in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion The use of painless diagnosis and treatment technology in ultrasound-guided PICC catheterization in children can improve the success rate of catheterization,shorten the catheterization time,reduce the degree of pain in children,enhance tolerance and compliance,and improve family satisfaction.

Objective:To investigate the risk factors of brain metastases in patients with limited-stage small cell lung cancer (SCLC) undergoing preventive brain radiotherapy after remission and to construct prediction model.Methods:A total of 231 patients with limited-stage SCLC who received chemoradiotherapy and achieved remission in 3201 Hospital from January 2015 to January 2023 were selected as the study objects. Logistic regression was used to analyze the influencing factors on the occurrence of brain metastases after remission in patients with limited-stage SCLC who received preventive brain radiotherapy. Binary logistic regression was used to construct a prediction model. Receiver operator characteristic (ROC) curve was used to evaluate the diagnostic efficacy of each indicator and the prediction model on the occurrence of brain metastases in patients.Results:The median follow-up time of the whole group was 73 months, and 42 cases of brain metastases occurred, with an incidence rate of 18.18%. There were statistically significant differences in the incidence of brain metastases among patients with different T stage ( Z=-4.97, P<0.001), clinical stage ( Z=-8.17, P<0.001), and time from initial treatment to thoracic radiotherapy ( χ2=21.38, P<0.001). Multivariate analysis showed that T stage (stage T 3: OR=6.29, 95% CI: 1.58-25.06, P=0.009; stage T 4: OR=12.91, 95% CI: 3.74-44.57, P<0.001), clinical stage (stageⅡ, OR=8.75, 95% CI: 2.89-26.51, P<0.001; stage Ⅲ, OR=18.43, 95% CI: 7.24-46.92, P<0.001), and time from initial treatment to thoracic radiotherapy ( OR=0.25, 95% CI: 0.11-0.56, P=0.001) were independent influencing factors on the occurrence of brain metastases after remission in patients with limited-stage SCLC who received preventive brain radiotherapy. The diagnostic prediction model based on the above indicators was logit ( P) =-19.91+1.84× stage T 3 +2.56× stage T 4+2.17× stage Ⅱ+2.91× stage Ⅲ-1.38× time from initial treatment to thoracic radiotherapy. ROC curve analysis showed that the area under the curve of T stage, clinical stage, time from initial treatment to thoracic radiotherapy, and the diagnostic prediction model for predicting the occurrence of brain metastasis after remission in patients with limited-stage SCLC who received preventive brain radiotherapy were 0.728, 0.660, 0.687, and 0.846, respectively, and the area under the curve of the diagnostic prediction model was significantly larger than those of the other indicators (all P<0.05) . Conclusion:T stage, clinical stage and the time from initial treatment to thoracic radiotherapy are all influential factors for the occurrence of brain metastases after remission in patients with limited-stage SCLC who received preventive brain radiotherapy. The diagnostic prediction model based on the above indicators can help to guide clinicians to accurately screen patients at high risk of brain metastases in the early stage.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

ObjectiveTo explore the mechanism of Danggui Niantongtang （DGNTT） against adjuvant-induced arthritis （AA） in rats with wind-dampness-heat arthralgia （FSR） based on the variation of intestinal flora. MethodA total of 60 SD rats were randomized into normal （control） group， FSR group， low-， medium-， and high-dose DGNTT （5.67， 11.34， 22.68 g·kg^-1） groups， and methotrexate （MTX） group （1.35 mg·kg^-1）， with 10 rats in each group. The rats， except the control group， were injected with Mtb adjuvant and then exposed to artificial climatic chamber （hot and humid with wind） for 64 h for modeling. The rats were treated with water， DGNTT or MTX for 28 days from the day of injection. Arthritis index （AI） of rats was measured and paw volume was determined with a volume meter. The morphology of synovial tissues of the knees was observed based on hematoxylin-eosin （HE） staining and the changes of intestinal flora were analyzed based on 16S rRNA sequencing. ResultDGNTT can alleviate the hyperplasia of synovial tissue and inflammation of AA rats with FSR and inhibit the formation of pannus. The results of 16S rRNA sequencing showed that the relative abundance of Firmicutes， Lactobacillus， Prevotella 9， and Alloprevotella decreased （P<0.05， P<0.01） and the relative abundance of Bacteroidetes and Bacteroides increased （P<0.01） in FSR group compared those in the control group. Compared with the FSR group， all DGNTT groups and MTX group had high relative abundance of Lactobacillus （P<0.05， P<0.01） and low relative abundance of Bacteroidetes （P<0.01） and medium-dose and high-dose DGNTT groups and MTX group showed high abundance of Firmicutes， Prevotella 9， and Alloprevotella and low abundance of Bacteroides （P<0.05， P<0.01）. Spearman's correlation analysis suggested that the abundance of Bacteroides and Helicobacter was in positive correlation with AI （P<0.05）， while the abundance of Prevotella 9 and Candidatus Saccharimonas was in negative correlation with AI （P<0.01， P<0.05）. There was a negative correlation between the abundance of Prevotella 9 and paw volume （P<0.01）， and the abundance of Ruminococcaceae NK4A214 group， Christensenellaceae R-7 group， and Bacteroides was in negative correlation with spleen index （P<0.05）. The abundance of Prevotella 9 was in negative correlation with spleen index （P<0.01）. ConclusionDGNTT is effective for arthritis with FSR， as it can regulate the composition of intestinal flora in AA rats by increasing the abundance of probiotics and inhibiting the growth of pathogenic bacteria. The mechanism is the likelihood that it improves intestinal immune metabolism to ensure intestinal homeostasis.

Objective To investigate the relationship between the genotypes of XRCC1 gene C26304T , G27466A, G28152A and the efficacy and prognosis of hepatocellular carcinoma in Nantong area. Methods The Genomic DNA was extracted from 252 newly diagnosed liver cancer patients admitted to the Department of Interventional Radiology, Affiliated Hospital of Nantong University from January 1, 2018 to December 31, 2018, and relevant clinical data and abdominal enhanced CT/MRI data were collected. Genotyping was performed using Panel high-throughput data analysis. All patients received TACE treatment, and abdominal enhanced CT/MRI was reexamined 4-6 weeks after treatment, and the efficacy was evaluated according to the efficacy of RECIST solid tumor. Survival of participants was followed up by telephone after 15 months. The frequency distribution differences of different genotypes in the efficacy and prognosis of different TACE treatments were compared, and the strength of association between related genotypes and the efficacy and prognosis of HCC TACE was indicated by odds ratio (OR) and its 95% confidence interval (CI). Results 1. The efficacy of TACE was better in AG patients with XRCC1 G28152A heterozygous mutation (OR=0.294, 95%CI:0.053-0.987), while there was no significant difference between patients with homozygous AA and patients with wild-type GG (OR=1.334, 95%CI:0.123-8.545). There was no significant difference in the efficacy of TACE between C26304T and G27466A genotypes. 2. Compared with the patients with wild-type GG, patients with G28152A heterozygous mutation AG were more likely to survive for 15 months and had a better prognosis after TACE (OR=0.262, 95%CI:0.051-0.988), but there was no significant difference in survival time between patients with homozygous mutation AA and patients with wild-type GG (OR=2.180, 95％CI:0.312-12.743）.There was no significant difference in survival time between the genotypes of C26304T and G27466A. Conclusion The patients with liver cancer in Nantong who carried heterozygous mutation AG at G27466A site of XRCC1 gene had better curative effect and prognosis of TACE. SNPs at C26304T and G28152A sites had no significant correlation with curative effect and prognosis of TACE.

Objective: To explore the function and molecular mechanism of Timeless in promoting hepatocellular carcinoma (HCC) growth. Methods: The expression of Timeless in HCC and paracancer tissues were analyzed by using the public data of HCC. Timeless was overexpressed in MHCC97L cells and silenced in MHCC97H cells, respectively, and the expression of Timeless and its downstream molecules were detected by real-time PCR and western blot. The effects of Timeless on cell glycolysis, oxidative phosphorylation and proliferation were detected by the glucose uptake experiment, lactic acid detection experiment, the extracellular fluid pH detection experiment, cell oxygen consumption test and cell viability assay, respectively. Results: The level of Timeless in HCC tissue was significantly higher than that of paracancer tissue (P<0.05). The relative cellular glucose uptake levels in the groups of Timeless knockdown, including siTimeless-1 and siTimeless-2 group were 0.510±0.119 and 0.508±0.099, respectively, significantly different from that of control group (P<0.05); The relative cellular uptake level of Timeless overexpressed group was 1.953±0.324, significantly different from that of vector transfected group (P<0.05). The relative levels of lactic acid production in the siTimeless-1 and siTimeless-2 group were 0.579±0.096 and 0.550±0.120, respectively, significantly different from that of control group (P<0.05); The relative production level of lactic acid in the Timeless overexpressed group was 1.463±0.179, significantly different that of vector transfected group (P<0.05). The extracellular pH values of siTimeless-1 and siTimeless-2 group were 7.390±0.035 and 7.370±0.060, respectively, significantly different from that of control group (P<0.05); the extracellular pH value of Timeless overexpressed group was 7.130±0.031, significantly different than vector transfected group (P<0.05). Oxygen consumption rate of siTimeless-1 and siTimeless-2 group were 3.686±0.389 and 3.955±0.431, respectively, significantly higher than 1.690±0.297 of control group (P<0.05); Oxygen consumption rate of Timeless overexpressed group was 1.302±0.336, significantly lower than 3.185±0.262 of vector transfected group (P<0.05) Timeless inhibited the expression of p53. The cell glucose uptake, lactic acid production, the pH of extracellular culture medium and cell oxygen consumption of control group were not significantly different from that of Timeless and p53 co-silenced group [(si-Timeless+sip53) group] (P>0.05); the glucose uptake, the production of lactic acid, the pH of the extracellular culture medium and the oxygen consumption of Timeless co-transfected with p53 (Timeless+p53) group were not significantly different from those of vector transfected group (P>0.05). Timeless promoted the proliferation of HCC cells through inhibiting the expression of p53. Conclusion Timeless promotes reprogramming of glucose metabolism and proliferation of HCC cells by inhibiting the p53-dependent signaling pathway.

Objective To analyze the correlation between functional single nucleotide polymorphisms (SNPs)in TYMS gene and the prognosis of hepatocellular carcinoma (HCC)patients treated with transcatheter arterial chemoembolization (TACE).Methods Five functional SNPs in TYMS gene were genotyped in a cohort of 41 9 unresectable Chinese HCC patients treated with TACE and prognosis analysis was performed.Results No SNP significantly associated with OS of HCC,but in patients with only TACE treat-ment,SNPs rs523230 exhibited significant associations with death risk in HCC patients under the additive model.Patients over 60 years old,SNP rs9967368 exhibited significant associations with death risk in HCC patients under the recessive model.Conclusion Genetic variations in TYMS gene may be a potential biomarker for predicting clinical outcome of HCC patients treated with TACE.