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 investigate the situation of iodized salt consumption of the households in Bazhong City from 2008 to 2018, and to discuss the change trend of the consumption rate of qualified iodized salt, so as to provide a scientific basis for prevention and control of iodine deficiency disorders in the next stage.Methods:Monitoring of iodized salt for households was carried out in 4 counties (districts) of Bazhong City from 2008 to 2012, and in 5 counties (districts) of Bazhong City from 2013 to 2018. According to the requirements of different monitoring programs in each year, 288 salt samples were collected from each county (district) from 2008 to 2011, and 300 salt samples were collected from each county (district) from 2012 to 2018, salt iodine was determined. Determination methods of salt iodine: the arbitration method was adopted from 2008 to 2013, and the redox titration method was adopted from 2014 to 2018. Decision criteria: 20 - 50 mg/kg was qualified iodized salt from 2008 to 2014; 21 - 39 mg/kg was qualified iodized salt from 2015 to 2018. Bazhong City achieved the goal of eliminating iodine deficiency disorders in 2010, lowered the iodization standard of salt in 2012, and the consumption rates of qualified iodized salt in each year were compared with those in 2010 and 2012.Results:In 2008 - 2011, 1 152 salt samples were collected; in 2012, 1 200 salt samples were collected; in 2013 - 2018, 1 500 salt samples were collected in Bazhong City. The coverage rate of iodized salt ranged from 98.09% to 100.00%, the qualified rate of iodized salt ranged from 91.69% to 98.35%, and the consumption rate of qualified iodized salt ranged from 91.27% to 98.26%. The consumption rates of qualified iodized salt in Bazhong City in 2008 - 2018 were compared, the difference was statistically significant (χ 2 = 133.953, P < 0.01). The consumption rates of qualified iodized salt in 2011 and 2014 - 2018 [95.40% (1 099/1 152), 95.00% (1 425/1 500), 92.93% (1 394/1 500), 93.67%(1 405/1 500), 91.27% (1 369/1 500), 92.73% (1 391/1 500)] were significantly lower than that in 2010 [98.26% (1 132/1 152)], the differences were statistically significant (χ 2 = 15.406, 20.097, 40.913, 33.196, 59.413, 43.067, P < 0.01). The consumption rates of qualified iodized salt in 2014 - 2018 were significantly lower than that in 2012 [97.50% (1 170/1 200)], the differences were statistically significant (χ 2 = 11.148, 29.066, 22.187, 46.194, 31.020, P < 0.01). Conclusions:From 2008 to 2018, the widespread situation of iodized salt in Bazhong City is generally good; the consumption rate of qualified iodized salt has reached the elimination standard of iodine deficiency disorders (> 90%). After the elimination target of iodine deficiency disorders has achieved in 2010 and the standard of qualified iodized salt has lowered in 2012, the consumption rate of qualified iodized salt in Bazhong City has decreased. It is suggested to continue to strengthen the supervision of salt market, health education and iodized salt monitoring, improve the quality of iodized salt production, maintain a high level of consumption rate of qualified iodized salt, and to ensure the continuous elimination of iodine deficiency disorders.

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.

The Kashin-Beck disease is a kind of unknown cause disabling arthropathy.In recent years,many experts and scholars have done in-depth studies in Kashin-Beck disease.There is a series of research achievements having been made.In this paper we reviewed the latest progress in the condition,etiology and pathogenesis of Kashin-Beck disease.

Objective To study the change of rats serum malondialdehyde (MDA) and the expression levels of 4-hydroxy acid nonene (4-HNE) and 8-hydroxy uridine (8-OHdG) of articular cartilage under low selenium (Se) and T-2 toxin poisoning,to explore oxidative damage of articular cartilage in rats.Methods Thirtytwo healthy male SD rats were divided into two groups by weight which were normal diet group and Se-deficiency group,16 rats in each group.Rats in normal diet group was fed with selenium 101.5 μg/kg diet,and rats in Sedeficiency group was fed with selenium 1.1 μg/kg diet for 30 d.Normal diet group was divided into control group and T-2 toxin group,and low selenium diet group was randomly divided into Se-deficiency group and Se-deficiency plus T-2 toxin group,8 rats in each group.After that,rats in T-2 toxin and Se-deficiency plus T-2 toxin groups were administrated intragastrically with T-2 toxin (100 mg/kg) everyday for 30 d.Rats were put to death,the left knee was taken and stained with hematoxylin-eosin and Safranin-Fast green,pathological changes of rat's knee joint cartilage were observed under light microscopy,expression levels of 8-OHdG and 4-HNE in rat's articular cartilage cells were determined by immunohistochemical method and rat's MDA content was determined by glucosinolates barbituric acid method.Results Chondronecrosis in deep zone of articular cartilage of knee joint stained with hematoxylin-eosin was seen in Se-deficient plus T-2 toxin diet group under light microscope.Significantly less Safranin-Fast green staining was observed in the cartilage of knee joints in the Se-deficient plus T-2 toxin diet group compared to the control group.Compared with control group [(3.41 ± 2.48)％,(2.28 ± 1.74)％],8-OHdG and 4-HNE in Se-deficient plus T-2 toxin group [(62.61 + 10.97)％,(75.03 ± 7.92) ％] positive expression rate increased significantly (F =16.24,18.61,all P ＜ 0.05).Comparison of serum MDA content in each group,the difference was statistically significant (F =4.32,P ＜ 0.05).The Se-deficiency group [(2.803 ± 0.163) μmol/L] was compared with control group [(1.873 ± 0.475) μmol/L] that the contents of serum MDA were increased.The T-2 toxin group [(2.890 ± 0.453) μmol/L] was compared with control group [(1.873 ± 0.475) μmol/L] that the content of serum MDA was increased (P ＜ 0.05).The Se-deficiency plus T-2 toxin group [(3.521 ± 0.292) μmol/L] was compared with Sedeficiency group and control group that the contents of serum MDA were increased (all P ＜ 0.05).Conclusions The marker of peroxidation products are increased in articular cartilage of SD rats under the condition of Sedeficiency and T-2 toxin poisoning.The cartilage damage and chondronecrosis due to Se-deficiency and T-2 toxin poisoning are related to oxidative damage.

Through analyzing the characteristics of inpatients in the hospitals of universities, this paper dis-cussed the importance of doctor-patient communication and humanistic care in the construction of harmonious doc-tor-patient relationship, and then put forward the ethical consideration of improving the doctor-patient relation-ship. It should strengthen humanistic care, improve the consciousness and ability of doctor-patient communica-tion, play the role of echelon, and actively carry out health education and health care service.

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.

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 To investigate the expressions of matrix metalloproteinases(MMPs) in Kashin-Beck disease(KBD) cartilage as well as in a KBD rat model of T-2 toxin poisoning under selenium deficient conditions, and to investigate the effect of T-2 toxin on MMP-13 expression in human chondrocytes in vitro in order to determine a possible mechanism underlying KBD. Methods Samples of articular cartilage were divided into 2 groups:controls(samples from 5 normal children, traffic accident or operation), and KBD(samples from 5 children with KBD, auctopsy). Thirty-two Sprague-Dawley rats were divided into two groups by body weight using random number table: normal diet group(n = 16) and selenium-deficient diet group(n=16). The selenium level in normal diet was 101.500μg/kg, and in selenium-deficient diet was 1.118μg/kg. Rats were fed for 4 weeks with selenium-deficient or normal diet, respectively. After successful build up of the low selenium rat model, normal diet group was then subdivided into 2 sub-groups: normal group(n = 8) and normal diet plus low T-2 toxin group(n = 8);and selenium-deficient diet group was also subdivided into 2 sub-groups: selenium-deficient group ( n = 8 ) and selenium-deficient diet plus T-2 toxin group ( n = 8 ) . T-2 toxin of 100 μg·kg-1·d-1 was administered by intragastric administration for 30 days. Then the rats were sacrificed, and their knee joints were processed for histopathological evaluation. MMP-1 and MMP-13 locations in cartilages were performed by inmmunohistochemistry. Human chondrocytes C28/I2 were cultured in vitro. The experiment was divided into 4 groups: empty vector plasmid group, MMP-13 promoter plasmid group, MMP-13 promoter plasmid plus 20 μg/L T-2 toxin group and MMP-13 promoter plasmid plus 40 μg/L T-2 toxin group. MMP-13-luciferase reporter plasmid and vector plasmid were transiently transfected into C28/I2 cells for 24 hours, and then treated with 20 - 40 μg/L T-2 toxin for 24 hours. Transactivation of human MMP-13 promoter was analyzed using luciferase reporter constructs containing sequences spanning-1602 to+20 bp in C28/I2 chondrocytes. Results The percentages of chondrocytes staining for MMP-1 in the superficial and middle zones of KBD samples [(29.73 ± 10.12)%, (28.27 ± 0.91)%] were significantly higher than those of controls[(2.47 ± 0.11)%, (0.00 ± 0.00)%, all P < 0.05]. The percentages of chondrocytes staining for MMP-13 in the superficial and middle zones of KBD samples [(13.21 ± 4.32)%, (41.85 ± 6.32)%] were significantly higher than those of controls[(5.72 ± 0.31)%, (0.00 ± 0.00)%, all P<0.05]. The percentages of chondrocytes staining for MMP-13 in the superficial and middle zones of rats fed with selenium-deficient diet plus T-2 toxin group[(13.21 ± 4.32)%, (61.85 ± 8.68)%] were significantly higher than those of the normal and selenium-deficient groups[(2.43 ± 0.22)%, (5.89 ± 0.69)%, (3.03 ± 0.29)%, (25.99 ± 0.57)%, all P < 0.05]. Moreover, T-2 toxin activated the MMP-13 promoter detected with luciferase reporter assays in C28/I2 cells. The luciferase activities in MMP-13 promoter plasmid plus 20 μg/L T-2 toxin group and MMP-13 promoter plasmid plus 40μg/L T-2 toxin group(0.082 78 ± 0.008 40, 0.103 35 ± 0.013 19) were significantly higher than those in empty vector plasmid group and MMP-13 promoter plasmid group(0.024 19 ± 0.000 96, 0.040 32 ± 0.003 56, all P < 0.05). Conclusions These data suggest that T-2 toxin induces cartilage matrix degradation through up-regulation of MMP-13 promoter expression. Increased MMPs staining intensity in KBD cartilage and the rat KBD model of T-2 toxin poisoning under selenium deficient conditions suggest that matrix degradation appear to be driven by MMPs activity.

Objective To investigate the relationship between erythrocyte immune function and selenium (Se)level. Methods Forty-nine Kashin-Beck patients in endemic area aged 13- 16 years were divided into two groups and were orally given either selenized yeast or sodium selenite to provide 200 μg selenium per day for 12 weeks. Erythrocyte selenium level, glutathione peroxidase activity, the rosette formation rates of red blood cells complement receptor type Ⅰ(CR1), the immune function of red blood cells, and circulating immune complexes(CIC) were determined. Results After supplementing with selenium for 12 weeks, erythrocyte selenium level, glutathione peroxidase activity, the rosette formation rates of red blood cells CR1 were significantly increased. But the difference in rosette formation rates of IC and CIC content was not significant between before and after Se supplementation. Conclusion The increase of the immune function of the erythrocyte by selenium-supplement may be one of the effective mechanisms for the prevention of Kashin-Beck disease.