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.

The clinical data of 5 patients with autoimmune encephalitis admitted to the psychiatric department of the 904th Hospital of the Joint Logistics Service Force from January 2016 to June 2020 were retrospectively analyzed. Among 5 patients, 4 had stress psychological events within one month before the onset, and 3 had precursor symptoms such as fever and vomiting. They were all characterized by rapid progress of atypical mental and behavioral abnormalities and cognitive impairment. In terms of neurological symptoms, 1 case had faciobrachial dystonic seizures (FBDS), 3 cases had seizures, 2 cases had involuntary movement, and 4 cases had autonomic dysfunction, including central hypopnea, arrhythmia, blood pressure instability and paroxysmal facial flushing. Most neurological symptoms occur within 1 month of the onset. MRI revealed abnormalities in cerebral cortex, thalamus, temporal lobe and insular lobe in 4 cases; EEG demonstrated bilateral short-range medium amplitude θ wave in 2 cases. Abnormal cerebrospinal fluid (CSF) pressure was detected in 4 cases and 2 cases had abnormal cell number CSF. Three patients had positive anti-N-methyl-D-aspartate receptor (NMDAR) antibody, one patient had positive anti-LGI1 antibody, and one patient had positive anti-γ-aminobutyric acid B receptor (GABA BR) antibody. One case was discharged automatically, the remaining 4 patients were treated with glucocorticoid or combined with gamma globulin and cyclophosphamide, antiepileptic drugs, antipsychotic drugs and other symptomatic treatment, and their symptoms were relieved. Patients were followed up for six months, there was slightly slow residual reaction in 2 cases and personality change in 1 case. Autoimmune encephalitis characterized by mental symptoms is likely to be misdiagnosed as mental disorders. Clinicians should identify symptoms different from mental disorders, taking into account of the possibility of autoimmune encephalitis, to make early diagnosis and treatment.

Objective To evaluate the harmful effects of olanzapine and quetiapine therapeusis on swallowing ability in patients with Alzheimer'disease (AD).Methods AD inpatients with behavioral and psychological symptoms were randomly divided into two groups,treated with olanzapine (n=42) or quetiapine (n=38) for 6 weeks.The patients were assessed with Kubota's water swallowing test and arterial oxygen saturation(SaO2) monitoring pre and pro treatment.Results After treatment,a significant higher score of water swallowing test (t =2.682,2.040;both P＜ 0.05)in either of two groups,and a significant raised degrade of SaO2 only in olanzapine group(t=4.313,P＜0.01)but not in quetiapine group (P＞0.05)were observed.There was a significant higher degrade of SaO2 in olanzapine group than that in quetiapine group (t=2.155,P＜0.05)at 6 weekend of the study.Before pharmacon,about 29％ (23/80) AD subjects were diagnosed as dysphagia.After pharmacon,more emerging dysphagia patients were surveyed in olanzapine group compared with that in quetiapine group(9/31 vs 2/26,x2=4.135,P＜0.05).No significant change (both P＞0.05) in scores of mini-mental state examination(MMSE) and a significant reduced score(t=3.019,2.867;both P＜0.01)of behavioral pathology in Alzheimer'disease rating scale (BEHAVE-AD) were found in both two groups at the end of study.There was no difference among the two groups with regard to score of MMSE or BEHAVE-AD after treatment(both P＞0.05).Conclusion Either olanzapine or quetiapine therapeutics might do some harmful effects on swallowing function in patients with AD,especially the former.

Objective To study the liver fat content (LFC) in schizophrenia patients during olanzapine or aripipra?zol treatment, and to explore the relation between LFC and insulin resistance (IR). Methods Schizophrenia patients were randomly administered with olanzapine (10~25 mg/d, n=57) or aripiprazole (15~30 mg/d, n=47) for eight weeks. All sub?jects underwent sonographic quantification of LFC and homeostasis model assessment of insulin resistance index (HOMA-IR) once 0, 4, 8 weeks of treatment. Results Compared with baseline, the levels of HOMA-IR significantly in?creased after a 4-week and an 8-week of olanzapine treatment, and so did the LFC after an 8-week of olanzapine treat?ment (P<0.05). The levels of LFC (P>0.05) or HOMA-IR (P>0.05) did not significantly changed at week 4 and 8 in ar?ipiprazol group. The increment of LFC, HOMA-IR at week 8 was significantly higher in olanzapine group than that in ar?ipiprazol group (P<0.05). The change of LFC after 8-weeks olanzapine treatment was positively correlated with the change of HOMA-IR (r=0.298, P=0.036). Conclusion Olanzapine treatment increases whereas aripiprazol has little ef?fect on liver fat and insulin resistance in schizophrenia.

Objective To investigate the serum retinol-binding protein 4 (RBP4) level in olanzapinetreated schizophrenia with non-alcoholic fatty liver disease (NAFLD) via a case-control study and to explore its relationship with NAFLD.Methods Schizophrenia receiving olanzapine treatment,with or without NAFLD were enrolled as cases (n=60) or controls (n=60).The serum retinol-binding protein 4,metabolic syndrome component including body mass index (BMI),waist-to-hip ratio (WHR),fasting plasma glucose (FPG),total cholesterol (TG),total glycerin (TC) and blood pressure were assayed.TyG index,CT value ratio of liver and spleen were used for insulin resistance or NAFLD diagnosis and severity assessment respectively.Results The serum level of RBP4 was significantly higher in cases than that in controls ((70± 13)mg/L vs (52±12)mg/L ; t =4.943,P＜0.01) and the same result was showed after influencing factor adjustment thru covariance analysis (F=16.797,P＜0.01).Moreover,cases had significantly higher TyG index,BMI,WHR,FPG,TG and systolic pressure (t=2.383-4.300,P＜0.05-0.01).Cases with severe or moderate NAFLD had significantly elevated serum RBP4 level compared with mild cases((79± 16) mg/L,(72±8) mg/L vs (63t9) mg/L,d =16.2,9.9 ; P＜0.01,0.05).A significantly negative correlation between RBP4 level and the CT value ratio of liver and spleen (r=-0.244,P＜0.05),and a significantly positive correlation between RBP4 level and TyG index,BMI,WHR,TG(r=0.197-0.244,all P＜0.05) were observed.The partial coefficient between RBP4 level and CT value of liver and spleen was significant with influence adjusted(r=-0.453,P＜0.01).Logistic regression showed that serum RBP4 level(β3=0.105,P＜0.01)and TyG index,hyperlipidemia,obesity,central obesity or high blood pressure (β =1.288-9.711,P＜ 0.05-0.01) were closely associated with NAFLD.Conclusion A heighten serum RBP4 level may be one of NAFLD risk factors in schizophrenia treated with olanzapine.

Objective:To investigate the relationship between dopamine D1 receptor ( DRD1 ) gene polymorphisms and clozapine efficacy in male schizophrenic patients. Methods:Totally 46 male schizophrenic patients were treated by clozapine for 6-8 weeks. The clinical response was determined by the Positive and Negative Symptom Scale (PANSS). DRD1 gene rs265981, rs5326, rs4532, rs1799914, rs686 and rs4867798 polymorphisms were detected by the gene sequencing, while plasma clozapine levels were monitored during the treatment. Results:The total clinical efficacy of clozapine response group and the non-response group was compared, the distribution of rs265981 genotype TT, TC and CC and allele T and C had statistically significant differences (P=0. 025;P=0. 005), and the distribution of rs686 genotype CC, CT and TC and allele C and T had statistically significant differences ( P=0. 044;P=0. 010). The negative symptom of the response group was compared with that of the non-response group, the distribution of rs4532 gen-otype GG, GA and AA and allele G and A had statistically significant differences (P=0. 034; P=0. 013). Conclusion: The poly-morphisms of DRD1 gene rs265981 and rs686 may have influence on the clinical efficacy of clozapine, and rs4532 may have influence on the negative symptom.

ObjectiveTo explore the relationship between brain iron deposition and pathogenesis of tardive dyskinesia (TD) in schizophrenia.MethodsThe corrected phase (CP) of basal ganglia was measured in schizophrenia with TD( n=18) and without TD( n =18 ) using susceptibility weighted imaging MRI.Abnormal Involuntary Movement Scale (AIMS) was applied for clinical assessment of TD.ResultsAfter adjusting for age,sexual,and antipsychotic dosage,the mean CP of substantia nigra (SN) and caudate nucleus (CN) were significantly lower in schizophrenia patients with TD ( ( - 0.194 ± 0.040 ) rad,( - 0.089 ± 0.023 ) rad) than those without TD ( ( - 0.163 ± 0.033 ) rad,( - 0.076 ± 0.013 ) rad ; P =0.022,0.023 ).Lower mean CP in CN correlated with higher severity score of AIMS in TD patients ( r =- 0.468,P =0.034).Logistic regression analysis showed that the lower CP vaule in SN (β=-72.12,P=0.029) and CN(β=- 156.43,P=0.037),aging (β=0.379,P=0.042)were associated with the onset of TD.ConclusionThe results imply that the excess iron accumulation in basal ganglia may be associated with pathogenesis of TD in schizophrenia.

Objective To study the correlation of fecal calprotectin and lactoferrin with intestinal mucosa lesions in Crohn′s disease (CD). Methods Eighty-eight cases of diagnosed CD patients were selected as study group and 35 irritable bowel syndrome (IBS) patients were as controls. Fecal samples of CD patients were collected in one week before colonoscopy examination and of IBS patients were collected of CD patients, CD activity index (CDAI) was calculated at same visit, and CD endoscopic index (CDEI) was calculated in the subsequent endoscopic examination. The level of fecal calprotectin and lactoferrin were tested by ELISA method. Results The median levels of facal calprotectin and lactoferrin in CD patients were 277.16 mg/kg (from 96.85 to 693.57 mg/kg) and 59.68 mg/kg (from 10.75 to 100.58 mg/kg) respectively, which were significantly higher than those of IBS patients (7.6mg/kg, from 5.54 to 32.3 mg/kg and 0.65 mg/kg from 0.23 to 4.34 mg/kg), (Z=-8.301 and -7.986, respectively both P =0.000). There were no significant difference of calprotectin and lactoferrin level between CD patients with colon pathological changes and without colon pathological changes (Z=-0.424 and -0.699,P=0.672 and 0.485, respectively). There was no significant difference of calprotectin and lacoferrin level between remission and active periods in CD patients (Z=-1.491 and -1.075, P=0.136 and 0.283, respectively). The median values of calprotectin and lactoferrin of patients in moderate and severe active period judged under endoscopy were 663.11 mg/kg (from 263.45 to 2015.63 mg/kg) and 105.64 mg/kg (from 56.52 to 187.44) mg/kg respectively, in mild active period were 344.54 mg/kg (from 132.03 to 722.67 mg/kg) and 86.68 mg/kg (from 21.07 to 100.55 mg/kg) accordingly, and in remission period were 133.94 mg/kg (from 60.54 to 583.33 mg/kg) and 45.31 mg/kg (from 7.59 to 48.31 mg/kg, respectively). Both calprotectin and lactoferrin levels were significantly higher in active period than in remission period (χ2=10.63 and 8.18, while, P=0.005 and 0.017, respectively). Conclusions The level of fecal calprotectin and lactoferrin can reflect the pathological changes and severity of the intestinal mucosa.

Objective To evaluate the effect and mechanism of 5-aminosalicylic acid (5-ASA) on bone marrow suppression caused by thiopurines, and to explore the proper dosage of thiopurines when combined with 5-ASA for inflammatory bowel diseases (IBD) patients.MethodsThe clinical data of IBD patients who took thiopurines were retrospectively analyzed. Thiopurine methyltransferase (TPMT) activity and 6-thioguanine nucleotide (6-TGN) concentration were tested.In prospective study, patients firstly treated with azathioprine (AZA) of 50 mg/d for 4 weeks, then combined with 5-ASA of 3 g/d for another 4 weeks.The concentration of 6-TGN in red blood cells (RBC) was analyzed at the end of 4th and 8th week.Results In retrospective study, there were 45 cases in AZA/6-mercaptopurine (MP) combined with 5-ASA group, 94 patients were in AZA/6-MP.alone group.The incidence of bone marrow suppression in these two groups were 46.7％ and 16.0％, respectively.Multivariates regression analysis indicated co-administration of 5-ASA was the only risk factor of increasing bone marrow suppression incidence (OR=3.45,95％ CI 1.31 ～ 9.04).There was no significant difference of TPMT activity between AZA/6-MP combined with 5-ASA group and AZA/6-MP alone group(t=-0.351 ,P=0.734).The 6-TGN concentration was significantly higher in AZA/6-MP combined with 5-ASA group than that of AZA/6-MP alone group (the median concentration was 384.9 pmol/8× 108 RBC and 286.4 pmol/8× 108 RBC,F=29.15,P=0.00).Prospective study was completed in 8 patients.After treated with AZA of 50 mg/d for 4 weeks, the 6-TGN concentration of 7 patients was lower than 230 pmol/8 × 108 RBC.After added with 5-ASA of 3 g/d for another 4weeks, the 6-TGN concentration of 7 patients was over 230 pmol/8 × 108 RBC, three patients of those was even higher than 420 pmol/8 × 108 RBC, and bone marrow suppression occurred in 2 patients.ConclusionsThe incidence of bone marrow suppression increased in Chinese IBD patients treated with recommended routine dossage of AZA/6-MP when conbined with 5-ASA.The mechanism may be related with the increased concentration of 6-TGN in RBC.To reduce the AZA dosage may possibly keep the efficacy while decrease the incidence of bone marrow suppression.

Objective To assess the predictive value of thiopurine methyltransferase genotyping and enzyme activity in relation to side effects in patients with inflammatory bowel disease (IBD) who were treated with azathioprine (AZA). Methods One hundred and eleven IBD patients (26 with ulcerative colitis and 86 with Cronh's disease) with indication of AZA administration between April 2004 and Dec. 2009 were enrolled. All patients received 2 mg/kg of AZA daily. Polymerase chain reaction and high performance liquid chromatography were used to genotype the TPMT * 2, * 3A, * 3B, * 3C and to detect TPMT activity, respectively. The association of TPMT genotype and activity with side effects was analyzed in patients treated with AZA for 24 weeks or more, or in those discontinued AZA because of adverse effects. Results Adverse effects were reported in 38(33. 9%) patients, the most frequent being myelosuppression (20. 5%). The frequency of TPMT * 3C heterozygous mutation was 0. 9% (1/112). The TPMT activity was (12. 9±4. 8) U/ml RBC with unimodal distribution. One patient with TPMT * 3C heterozygous mutation developed myelosuppression at the 4th week after AZA treatment. The TPMP genotype myelosuppression patients. Conclusions TPMT genotype mutation and low enzyme activity can be used to predict myelosuppression with high specifically and low sensitivity. In patients treated with AZA, co-administration of 5-ASA results in a high frequency of myelosuppression with no effect on TPMT activity.