Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.

Objective:To evaluate the relationship between methyltransferase-like 3(METTL3)-mediated RNA N6-Methyladenosine (m6A) methylation modification and silent information regulator factor 1 (SIRT1) during sevoflurane post-conditioning-induced mitigation of cognitive impairments in a mouse model of hemorrhagic shock and resuscitation(HSR).Methods:Forty clean-grade healthy male C57BL/6 mice, aged 8-10 weeks, with a body weight ranging from 22-26 g, were assigned into 5 groups ( n=8 each) using a random number table method: sham operation group, HSR group, sevoflurane post-conditioning + HSR group (SP+ HSR group), over-expression of METTL3 gene rAAV + sevoflurane post-conditioning + HSR group (METTL3+ SP+ HSR group), and over-expression of METTL3 gene rAAV negative control + sevoflurane post-conditioning + HSR group (NC+ SP+ HSR group). The HSR model was established by withdrawing 40% of the total blood volume from mice through the right carotid artery within 30 min, followed by reinfusion of the withdrawn blood over 30 min 1 h later. The SP+ HSR group underwent HSR modeling first and then inhaled sevoflurane (end-tidal concentration 2.4%) for 30 min starting from the time point immediately after blood transfusion. The Sham group and HSR group inhaled a mixture of 70% O 2 and 30% CO 2 for 30 min at the corresponding time points. In METTL3+ SP+ HSR group and NC+ SP+ HSR group, the corresponding virus 450 nl was injected into bilateral hippocampus at 4 weeks before establishing the model.Morris water maze and novel object recognition tests were conducted at 72 h after developing the model to assess the learning and memory abilities. After the end of behavioral tests, the expression of METTL3 and SIRT1 in hippocampal tissues was detected using Western blot, the expression of SIRT1 mRNA was measured using qRT-PCR, and the methylation of RNA m6A was detected using Dot blot. Results:Compared to Sham group, the escape latency was significantly prolonged at 1-6 days, the time spent in the target quadrant was shortened, the number of crossing the original platform was decreased, the novel object recognition index was decreased, the expression of METTL3 was up-regulated, the expression of SIRT1 protein and mRNA was down-regulated, and the methylation of RNA m6A was increased in HSR group( P<0.05). Compared to HSR group, the escape latency was significantly shortened at 1-6 days, the time spent in the target quadrant was prolonged, the number of crossing the original platform was increased, the novel object recognition index was increased, the expression of METTL3 was up-regulated, the expression of SIRT1 protein and mRNA was down-regulated, and the methylation of RNA m6A was increased, the novel object recognition index was increased, the expression of METTL3 was down-regulated, the expression of SIRT1 protein and mRNA was up-regulated, and the methylation of RNA m6A was decreased in SP+ HSR group( P<0.05). Compared to SP+ HSR group, the escape latency was significantly prolonged at 2-6 days, the time spent in the target quadrant was shortened, the number of crossing the original platform was decreased, the novel object recognition index was decreased, the expression of METTL3 was up-regulated, the expression of SIRT1 protein and mRNA was down-regulated, and the methylation of RNA m6A was increased in METTL3+ SP+ HSR group( P<0.05), and no significant change was found in the aforementioned indicators in NC+ SP+ HSR group ( P>0.05). Conclusions:The mechanism by which sevoflurane post-conditioning alleviates cognitive dysfunction is associated with down-regulation of METTL3 expression, reduction of RNA m6A methylation, and up-regulation of SIRT1 expression in HSR mice.

Objective:To evaluate the role of silent information regulator-1 (SIRT1)/nucleotide-binding domain (NOD)-like receptor protein-3 (NLRP3) signaling pathway in sevoflurane postconditioning-induced attenuation of oxygen-glucose deprivation and restoration (OGD/R) injury in mouse hippocampal neuronal cell line (HT22) cells.Methods:The HT22 cells were seeded in a culture plate (96-well plate, 100 μl/well; 6-well plate, 2 ml/well) at the density of 5×10 4 cells/ml or in a culture dish (6 cm in diameter) and then divided into 4 groups ( n=24 each) using a random number table method: control group (Control group), OGD/R group, sevoflurane postconditioning group (SPC group), and SIRT1 small interfering RNA group (si-SIRT 1 group). In Control group, cells were cultured at 37 ℃ in normal culture atmosphere. In OGD/R group, the culture medium was replaced with glucose-free serum-free culture medium, and cells were exposed to 95% N 2+ 5% CO 2 for 4 h in an incubator at 37 ℃, and then the glucose-free serum-free culture medium was replaced with the primary culture medium, and cells were cultured for 24 h at 37 ℃ in normal culture atmosphere. In SPC group, the glucose-free serum-free culture medium was replaced with the primary cell culture medium after 4-h oxygen and glucose deprivation, the cells were put into the hypoxia incubator chamber which was filled with 2% sevoflurane immediately after start of reoxygenation, then the chamber was placed in an incubator and the cells were cultured for 1 h at 37 ℃ in normal culture atmosphere, and finally the cells were removed from the chamber and cultured for 23 h at 37 ℃ in normal culture atmosphere. In si-SIRT1 group, SIRT1 small interfering RNA 150 pmol was added at 24 h before surgery, cells were then incubated, and the other procedures were the same as those previously described in group SPC. The cell survival rate was determined using MTT assay. TUNEL assay was used to detect cell apoptosis, and the apoptosis rate was calculated. The expression of SIRT1, NLRP3, IL-1β and IL-18 mRNA was determined using polymerase chain reaction. The expression of SIRT1, NLRP3, interleukin-1beta (IL-1β) and IL-18 was detected using Western blot. Results:Compared with Control group, the cell survival rate was significantly decreased, the apoptosis rate was increased, the expression of SIRT1 protein and mRNA was down-regulated, and the expression of NLRP3, IL-1β and IL-18 protein and mRNA was up-regulated in OGD/R group ( P<0.05). Compared with OGD/R group, the cell survival rate was significantly increased, the apoptosis rate was decreased, the expression of SIRT1 protein and mRNA was up-regulated, and the expression of NLRP3, IL-1β and IL-18 protein and mRNA was down-regulated in SPC group ( P<0.05). Compared with SPC group, the cell survival rate was significantly decreased, the apoptosis rate was increased, the expression of SIRT1 protein and mRNA was down-regulated, and the expression of NLRP3, IL-1β and IL-18 protein and mRNA was up-regulated in si-SIRT1 group ( P<0.05). Conclusions:Activation of SIRT1-NLRP3 signaling pathway is involved in sevoflurane postconditioning-induced attenuation of OGD/R injury in HT22 cells.

OBJECTIVE To explore the effect and mechanisms of baicalein on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice.METHODS BALB/c mice were randomly placed into three groups (n=10):normal control group,TNBS group,and TNBS+baicalein (20 mg· kg-1,once per day) group.Mouse colitis was induced by intrarectal injection of TNBS.Baicalein was administered by oral gavage two days prior to TNBS treatment and until the end of the study (a total of 9 d).The colon length was measured before HE staining was performed for histological damage assessment.The remaining colon pieces were collected to measure the content of tumor necrosis factor-α(TNF-α).Lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage was used as a cell model to determine the content of nitric oxide (NO) in cell culture medium,the mRNA levels of TNF-α,interleukin-6(IL-6),IL-1β,inducible nitric oxide synthase(iNOS),cyclooxygenase 2(COX-2) and monocyte chemoattractant protein-1 (MCP-1),and the protein expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-κB (PI3K/AKT/NF-κB) pathway.RESULTS Baicalein significantly attenuated TNBS-induced colon shortening and histological injury (P＜0.05),which was correlated with the decline in the content of TNF-α in the colon.According to the jn vivo results,baicalein exposure down-regulated the secretion of NO and the mRNA expression of pro-inflammatory mediators (iNOS,COX-2,MCP-1,TNF-α,IL-1β and IL-6) in LPS-stimulated RAW264.7 cells (P＜0.05,P＜0.01).Additionally,the phosphorylation/activation of LPS-stimulated PI3K/AKT/NF-κB pathway was inhibited by baicalein treatment.CONCLUSION The beneficial effect of baicalein in TNBS-induced experimental colitis may be due to PI3K/AKT/NF-κB signaling inhibition.

BACKGROUND:Papain-induced rat knee osteoarthritis is a common modeling method, which can obtain a stable osteoarthritis model.
OBJECTIVE:To observe the change of ultrastructure of chondrocytes in the early process of papain-induced rat knee osteoarthritis under transmission electron microscope.
METHODS:A total of 18 Sprague-Dawley rats were randomly divided into three groups. Two rats were considered as a normal control group, without intervention. The mixture of papain and L-cysteine was injected in right knee joint cavity of 16 rats to induce osteoarthritis models (osteoarthritis model group). Physiological saline was injected in the left side (physiological saline control group). At 1, 2, 4 and 6 weeks after injection, samples were col ected. Transmission electron microscope was used to observe the change of cartilage ultrastructure of the medial femoral condyle joint.
RESULTS AND CONCLUSION:For the normal control group and physiological saline control group, their cytoplasm contained abundant rough endoplasmic reticulum and mitochondria. After 1 week of injection,
mitochondria vacuoles and light expanded rough endoplasmic reticulum were visible. Two weeks later, lipid droplets appeared, mitochondria degeneration was distinct, vacuolization was serious and its number was reduced, and rough endoplasmic reticulum expansion was obvious. Four weeks later, lipid droplets became increased, and the number of mitochondria decreased significantly. Most of the rough endoplasmic reticula were highly expanded, and part of the rough endoplasmic reticula were dissolved and fractured. Six weeks later, a number of lipid droplets were visible in cytoplasm, most of the mitochondria disappeared, only a smal number of mitochondria existed, and most of the rough endoplasmic reticula were dissolved and fractured. These results confirmed that cartilage ultrastructure changes gradual y in the early process of papain-induced rat knee osteoarthritis under transmission electron microscope.

OBJECTIVEHepatitis A immunization strategies were carried out in 2001 in Tianjin. We wanted to evaluate the effectiveness of the strategies related to hepatitis A control programs and to provide the basis for further modification of the strategies.

METHODSDescriptive epidemiology study was used to analyze the hepatitis A epidemic situation in 2000-2011 in Tianjin and to evaluate the disease reporting system. Hepatitis A vaccine coverage of target population and serum epidemiological study were carried out in 1999, 2005 and 2010 to check on the hepatitis A antibody levels so as to evaluate the immuno-barrier condition in the normal population. Cox-Stuart test was used to analyze the epidemic trend of hepatitis A and other intestinal infectious diseases in Tianjin.

RESULTSThe incidence rate of hepatitis A decreased from 2.89/100 000 in 2000 to 0.12/100 000 in 2011, and the percentage of hepatitis A in all types of viral hepatitis decreased from 8.02% in 2000 to 0.48% in 2011 in Tianjin. The positive rates of hepatitis A antibody also increased in the residents.

CONCLUSIONThe hepatitis A vaccination program was successful in the programs on prevention and control of hepatitis A in Tianjin, China.

China ; epidemiology ; Epidemics ; prevention & control ; Hepatitis A ; epidemiology ; prevention & control ; Hepatitis A Antibodies ; blood ; Hepatitis A Vaccines ; administration & dosage ; Humans

Health Personnel ; Humans ; Infection Control ; Infectious Disease Transmission, Patient-to-Professional ; Occupational Diseases ; prevention & control

Objective To study the effects of Jiangu tablet on articular chondrocyte apoptosis in T-2 toxin poisoning rats. Methods According to random number table, fifty weaning male SD rats were divided into two groups by body mass, i.e., 10 for normal control group and 40 for T-2 toxin group (intragastric administration of distilled water or T-2 toxin 200 ng·g-1·d-1) for 30 days. Then the T-2 toxin group was divided into T-2 toxin group, Jiangu tablet low-dose group, middle-dose group and high-dose group treating with 3 ml of T-2 toxin 200 ng or different concentration of Jiangu tablet (contain 1.562 5, 3.125 0 and 6.250 0 g Jiangu tablet active compound). Each group had 10 rats and was given T-2 toxin or different amount of Jiangu tablet for 30 days. Then the rats were killed. The articular cartilage was removed from rats and RNA was extracted from the articular cartilage by Trizol. The mRNA expressions of p53, Bax, Bcl-2 and cysteinyl aspartate specific proteinase(caspase)-3 were detected by real-time PCR. Results The mRNA expressions of p53, Bax, Bcl-2 and caspase-3 in normal control group, T-2 toxin group, Jiangu tablet low-dose group, middle-dose group and high-dose group were: 1.00 ± 0.98, 200.37 ± 30.39, 180.19 ± 28.14, 120.25 ± 15.35, 50.34 ± 10.12;1.00 ± 0.98, 185.37 ± 10.15, 152.59 ± 15.23, 108.46 ± 9.14, 57.18 ± 1.31; 1.00 ± 0.99,0.22 ± 0.03, 0.28 ± 0.06, 0.43 ± 0.08, 0.58 ± 0.04; 1.00 ± 0.97, 209.55 ± 25.64, 152.38 ± 15.46, 120.14 ± 11.52 and 49.24 ± 8.69, respectively. Compared with the normal control group, the mRNA expressions of p53, Bax and caspase-3 were up-regulated in T-2 toxin group, low-dose group, middle-dose group and high-dose group while the mRNA expression of Bc1-2 was down-regulated(all P < 0.05). The mRNA expressions of p53 and caspase-3 in Jiangu tablet high-dose group and middle-dose group were significantly decreased than those in T-2 toxin group (all P<0.05). The mRNA expressions of Bcl-2 in Jiangu tablet high-dose group and middle-dose group were significantly increased than that in T-2 toxin group(all P<0.05). The mRNA expression of Bax in Jiangu tablet high-dose group was significantly decreased than that in T-2 toxin group(P<0.05). Conclusion The Jiangu tablet can significantly inhibit the apoptosis of articular chondrocyte in T-2 toxin poisoning rats.

Objective Hepatitis A immunization strategies were carried out in 2001 in Tianjin. We wanted to evaluate the effectiveness of the strategies related to hepatitis A control programs and to provide the basis for further modification of the strategies. Methods Descriptive epidemiology study was used to analyze the hepatitis A epidemic situation in 2000-2011 in Tianjin and to evaluate the disease reporting system. Hepatitis A vaccine coverage of target population and serum epidemiological study were carried out in 1999,2005 and 2010 to check on the hepatitis A antibody levels so as to evaluate the immuno-barrier condition in the normal population. Cox-Stuart test was used to analyze the epidemic trend of hepatitis A and other intestinal infectious diseases in Tianjin. Results The incidence rate of hepatitis A decreased from 2.89/100 000 in 2000 to 0.12/100 000 in 2011,and the percentage of hepatitis A in all types of viral hepatitis decreased from 8.02%in 2000 to 0.48% in 2011 in Tianjin. The positive rates of hepatitis A antibody also increased in the residents. Conclusion The hepatitis A vaccination program was successful in the programs on prevention and control of hepatitis A in Tianjin,China.

Objective: To study the expression of Fas, Fas ligand (FasL) and IFN ? in gastric cancer and its possible significance. Methods: Fifty eight gastric paraffin wax embedded cancer tissues and fifty three normal tissues adjacent gastric cancer were tested for the expression of Fas and FasL protein by immunohistochemistry and IFN ? mRNA by in situ hubridisation respectively. Results: The positive rate of Fas in cancer cells of gastric cancer tissues was significantly lower than that in gastric epithelial cells of the tissues adjacent cancer(19.0% and 64.2%, respectively; ? 2=23.46, P = 0.00). The positive rate of FasL in cancer cells of gastric cancer tissues was significantly higher than that in gastric epithelial cells of the tissues adjacent cancer(63.8% and 45.3%,respectively; ? 2=3.83, P =0.05). The positive rate of IFN ? in cancer cells of gastric cancer tissues was significantly lower than that in gastric epithelial cells of the tissues adjacent cancer(0.0% and 49.1%,respectively; ? 2=37.16, P =0.00). Conclusion: The Fas-FasL system was unbalanced, and the expression of IFN ? was low in gastric cancer cells in this study. These may be related to the carcinogenesis of gastric epithelial cells and might be responsible for the immune escape of these cells.