1.Gut microbiota-derived tryptophan metabolites regulated by Wuji Wan to attenuate colitis through AhR signaling activation.
Wanghui JING ; Sijing DONG ; Yinyue XU ; Jingjing LIU ; Jiawei REN ; Xue LIU ; Min ZHU ; Menggai ZHANG ; Hehe SHI ; Na LI ; Peng XIA ; Haitao LU ; Sicen WANG
Acta Pharmaceutica Sinica B 2025;15(1):205-223
Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.
2.Establishment and validation of nomogram prediction model of cefoperazone/sulbactam-induced thrombocytopenia
Hehe BAI ; Lirong PENG ; Yuanji WANG ; Xiaojing NIE ; Jinping WANG ; Li MA ; Guan WANG
China Pharmacy 2024;35(8):980-985
OBJECTIVE To explore the predictive factors of cefoperazone/sulbactam-induced thrombocytopenia in adult inpatients, and to establish and validate the nomogram prediction model. METHODS Data of adult inpatients treated with cefoperazone/sulbactam in Xi’an Central Hospital from Jun. 30th, 2021 to Jun. 30th, 2023 were retrospectively collected. The training set and internal validation set were randomly constructed in a 7∶3 ratio. Singler factor and multifactor Logistic regression analysis were used to screen the independent predictors of cefoperazone/sulbactam-induced thrombocytopenia. The nomogram was drawn by using “RMS” of R 4.0.3 software, and the predictive performance of the model was evaluated by the receiver operating characteristic curve and C-index curve. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the calibration degree of the model. Using the same standard, the clinical data of hospitalized patients receiving cefoperazone/sulbactam in Xi’an First Hospital in the same period were collected for external validation of the nomogram prediction model. RESULTS A total of 1 045 patients in Xi’an Central Hospital were included in this study, among which 67 patients suffered from cefoperazone/sulbactam-induced thrombocytopenia, with an incidence of 6.41%. After the false positive patients were excluded, 473 patients were included finally, including 331 in the training set and 142 in theinternal validation set. Multifactor Logistic regression analysis showed that age [OR=1.043, 95%CI (1.017, 1.070)], estimated glomerular filtration rate (eGFR) [OR=0.988,95%CI(0.977, 0.998)], baseline platelet (PLT) [OR=0.989, 95%CI(0.982, 0.996)], nutritional risk [OR=3.863, 95%CI(1.884, 7.921)] and cumulative defined daily doses (DDDs) [OR=1.082, 95%CI(1.020, 1.147)] were independent predictors for cefoperazone/sulbactam-induced thrombocytopenia (P<0.05). The C-index values of the training set and the internal validation set were 0.824 [95%CI (0.759, 0.890)] and 0.828 [95%CI (0.749, 0.933)], respectively. The results of the Hosmer-Lemeshow test showed that χ 2 values were 0.441 (P=0.802) and 1.804 (P=0.406). In the external validation set, the C-index value was 0.808 [95%CI (0.672, 0.945)], the χ 2 value of the Hosmer-Lemeshow test was 0.899 (P=0.638). CONCLUSIONS The independent predictors of cefoperazone/sulbactam-induced thrombocytopenia include age, baseline PLT, eGFR, nutritional risk and cumulative DDDs. The model has good predictive efficacy and extrapolation ability, which can help clinic identify the potential risk of cefoperazone/sulbactam-induced thrombocytopenia quickly and accurately.
3.Analysis of DRG grouping effect and influential factors of hospitalization cost of diabetic patients
Xiaojing NIE ; Haofei FU ; Hehe BAI ; Yaping LI ; Jinping WANG
China Pharmacy 2023;34(24):3020-3024
OBJECTIVE To explore the grouping efficacy of diagnosis related group (DRG) and the influential factors of hospitalization cost in diabetes cases, and to provide theoretical support for improving DRG payment system, reducing medical cost and enhancing the efficiency of medical insurance funds. METHODS The information of 4 368 diabetic patients who were hospitalized in a 3A hospital in Xi’an from January 1, 2021 to June 30, 2023 was retrospectively analyzed, and DRG grouping of them was summarized; the hospitalization costs of patients in different DRG groups were analyzed by using one way ANOVA and Bonferroni multiple comparison. Coefficient of variation (CV) was used for evaluation within the group, and the influential factors of hospitalization costs were analyzed by one-way linear regression analysis and multi-factor linear regression analysis. RESULTS & CONCLUSIONS The CV values of the four DRG groups were all lower than 0.8, indicating good grouping results and good consistency within the group; the difference of hospitalization cost among the four groups was statistically significant (P<0.05), and the hospitalization cost of China Healthcare Security-DRG version 1.1 FW11 group was significantly higher than those of other three groups (P<0.05). Length of stay, drug cost, the number of other diagnoses, test cost and payment method have significant positive effects on the hospitalization cost of diabetic patients. Whether there is pharmacist intervention has a significant negative influence on the hospitalization cost of patients. Under the DRG payment method, medical institutions can consider multidisciplinary linkage and incorporate a variety of management and service tools, including pharmacist’s intervention, to develop refined management measures, to reduce the economic burden of patients’ families and society.
4.Sepsis-related mortality and family socioeconomic features of septic patients in pediatric intensive care unit in the Yangtze River Delta
Zhengzheng ZHANG ; Hehe CHEN ; Guoquan PAN ; Hongjun MIAO ; Yucai ZHANG ; Xiaodong ZHU ; Ying LI ; Chenmei ZHANG ; Guoping LU ; Ying WANG
Chinese Pediatric Emergency Medicine 2021;28(9):751-755
Objective:To investigate pediatric sepsis-related mortality of pediatric intensive care unit(PICU) and family socioeconomic status in Yangtze River Delta.Methods:A prospective, multicenter observational study was conducted to collect sepsis cases from eight PICUs in Jiangsu, Zhejiang and Shanghai from August 2016 to July 2017.Sepsis cases were divided into normal sepsis group and severe sepsis group.The primary outcome was in-hospital death.Patient data were prospectively collected including age, gender, medical insurance status, long-term residence, source of admission, first-day pediatric sequential organ failure score(pSOFA) score, underlying diseases and socioeconomic characteristics including family education level, family annual economic income.Results:A total of 4, 983 patients admitted in PICUs, of which 651 patients were diagnosed sepsis on admission.The prevalence of sepsis was 13.1% (651/4 983), and overall mortality was 11.7% (76/651). The prevalence of severe sepsis was 28.3% (184/651), and the mortality was 20.1% (37/184). The overall median age was 0.9 years old.The infant group accounted for 50.8%, including 331 cases, followed by toddler group 19.8% (129 cases), preschool group 13.0% (86 cases), school group 11.8% (77 cases), and adolescent group 4.3% (28 cases). The median pSOFA score was 4.Logistic regression analysis showed that the OR value was 1.4(95% CI 1.3-1.5) of pSOFA score corresponding to the death of sepsis in hospital.There were 14.6% patients left hospital in medical insurance group, while 27.4% in non-medical insurance group, and there was significant difference between these two groups.The median of daily cost was 5, 446 RMB, among which the median of daily cost of sever sepsis was 6, 678 RMB.The median of total cost for sepsis was 36, 109 RMB, and that for severe sepsis was 41, 433 RMB. Conclusion:The sepsis-related mortality was high in PICU.The pSOFA score has a certain predictive value for the prognosis of sepsis.The burden of sepsis is still heavy.Compared with medical insurance families, non-medical insurance families have a higher proportion of choosing left hospital.
5.Diagnostic value of wide-detector energy spectrum CT combined with high concentration iodine contrast agent in Budd-Chiari syndrome
Peijie LI ; Lei SU ; Hehe GUO ; Jianbo GAO ; Yonggao ZHANG
Chinese Journal of Radiology 2020;54(5):408-412
Objective:To investigate the diagnostic value of energy spectrum CT combined with high concentration iodine contrast agent (400 mg/ml) for hepatic venous system CT angiography in patients with Budd-Chiari syndrome (BCS).Methods:A total of 48 patients with BCS who underwent the hepatic venous system CT angiography were prospectively collected from March to August 2019 at the First Affiliated Hospital of Zhengzhou University. Patients were randomly divided into control group (350 mg /ml) and study group (400 mg /ml). In the control group, the dosage of iodine contrast agent was 1.6 ml/kg, and the flow rate was 4.0 ml/s. In the study group, the dosage of iodine contrast agent was 1.4 ml/kg. Double-flow rate injection protocol was used in the study group, i.e. 3.50 ml/s (80% dosage), 1.75 ml/s (20% dosage), 3.50 ml/s (40 ml normal saline). Revolution CT scanner was used for energy spectrum scanning. Quantitative parameters, qualitative visual parameters and radiation dose were compared between the two groups. Wilcoxon test, t test, χ 2 test and Mann-Whitney U test were used. Results:The dosage of iodine contrast agent in the study group [(94.53±16.02) ml] was lower than that in the control group [(106.40±20.19) ml, t=2.257, P<0.05]. The injection speed of the control group was higher than that of the study group (4.00 ml/s and 3.15 ml/s). CT values of portal vein, hepatic vein, inferior vena cava, and hepatic parenchyma, signal to noise ratio, contrast noise ratio, CT dose index, dose length product, effective dose and subjective scores showed no significant differences between the 2 groups (all P>0.05). Conclusion:For patients with BCS, high quality images could be obtained to meet the requirement of diagnosis in hepatic vein system CT angiography using high concentration iodine contrast agent (400 mg/ml) with low dosage of contrast agent and low flow rate.
6.The clinical values of ultra-early enteral nutrition combined with microecopharmaceutics on patients with severe acute pancreatitis
Zhaolei QIU ; Zhenjie WANG ; Feng CHENG ; Qi SONG ; Zhipeng XU ; Zhilin SHAO ; Chuanming ZHENG ; Lei LI ; Hai JIANG ; Zhaohui DU ; Hehe DOU
Chinese Journal of Emergency Medicine 2018;27(9):967-971
Objective To analyze the clinical values of super early enteral nutrition combined with microecopharmaceutics and delayed enteral nutrition on patients with severe acute pancreatitis. Methods Clinical data of thirty patients diagnosed as severe acute pancreatitis in our emergency department during January 2013 and December 2017 were reviewed retrospectively. Patients were divided into the treatment group (n=15, patients given enteral nutrition combined with microecopharmaceutics within 24 h after admission) and the control group (n=15, patients given delayed enteral nutrition after 48 h of admission). Two weeks after the treatment, the serum variables of C-reactive protein, total protein, albumin, recovery time of urine and blood amylase, length of hospital stay and APACHE Ⅱ score were compared between the two groups by using paired samples t test. Results The C-reactive protein [(46.7±13.1) mg/L vs. (190.72±19.3) mg/L, t=10.4, P<0.01] and APACHE Ⅱ score [(7.2±1.9) vs.(9.3±2.4),t=2.7,P<0.05] of the treatment group were significantly lower than those in the control group. The total protein [(58.1±6.3)g/L vs.(52.6±5.4)g/L, t=2.5, P<0.05] and albumin [(29.9±3.2)g/L vs.(22.0±2.8)g/L, t=7.12, P<0.01] of the treatment group were significantly higher than those in the control group. The recovery time of urine amylase [(13.2±2.1)d vs.(18.7±3.9)d, t=4.9, P<0.01] and blood amylase [(7.5±3.0)d vs.(11.1±3.4)d, t=3.1, P<0.01], and length of hospital stay[(14.9±4.5)d vs.(27.1±5.3)d, t=6.9, P<0.01] were significantly shorter in the treatment group compared with those in the control group. Conclusions Ultra-early enteral nutrition combined with microecopharmaceutics can shorten the length of hospital stay of patients with severe acute pancreatitis, and is safe and effective.
7.Protection of Tongxinluo Against Myocardial Ischemia/Reperfusion Injury Relates to Enhancing Endothelial Barrier in Diabetic Rats
Kang QI ; Leipei JIANG ; Xiangdong LI ; Hehe CUI ; Chen JIN ; Na LI ; Qing LI ; Xiaqiu TIAN ; Yuejin YANG
Chinese Circulation Journal 2014;(12):1020-1023
Objective: To clarify that protection of Tongxinluo against myocardial ischemia/reperfusion injury relates to enhancing endothelial barrier in diabetic rats.
Methods: A total of 32 Zucker diabetic rats were randomized into 4 groups:Sham group, Model group, Insulin group and Tongxinluo group, n=8 in each group. In addition, there was a Control group containing 8 non-diabetic Zucker rats. Myocardial ischemia/reperfusion injury model was established by a 45-min ischemia and 3-h reperfusion protocol. The size of infarction was detected by pathological staining, the microvascular permeability was examined by Miles assay to obtain the lfuorescein isothiocyanate concentration in myocardial tissue, the Triton X-100 soluble and insoluble VE-cadherin was measured by membrane protein extraction and western blot analysis.
Results:The size of infarction in Model group was obviously higher than that in Control group (55.2 ± 1.4)%vs (36.2± 1.3)%,P<0.05 and the lfuorescein isothiocyanate concentration was also higher in Model group than Control group. Both insulin group and Tongxinluo group had the similar size of infarction with Model group (36.8 ± 1.2)%vs (38.7 ± 1.1)%, P>0.05. Both insulin group and Tongxinluo group got lower lfuorescein isothiocyanate concentration (all P<0.01) and VE-cadherin internalization (all P<0.05) than that in Model group.
Conclusion: Protection of Tongxinluo against myocardial ischemia/reperfusion injury in diabetic rats is as effective as
insulin, but the effect is independent of reducing blood glucose and may be related to enhancing endothelial barrier.
8.The detection and significance of AKAP12 methylation levels in peripheral blood in patients with lung cancer
Hehe LIAO ; Yunfeng ZHANG ; Shuqiang WU ; Hanchun LI ; Lei JIN ; Hong REN
Chongqing Medicine 2014;(15):1834-1836
Objective To detect the levels of AKAP12 methylation by methylation‐specific high‐resolution melting curve(MS‐HRM ) in peripheral blood in patients with colorectal cancer and investigate its clinical significance .Methods We used MS‐HRM technology to detect the levels of AKAP12 methylation in peripheral blood in 60 lung cancer patients ,and analyzed the relationship between the levels of AKAP12 methylation and pathological parameters of lung cancer patients .Results 34(56 .7% ) of the 60 lung cancer patients were found to be methylated at the AKAP12 promoter region by MS‐HRM ,the methylation levels of 18 cases ranged between 1% -20% ,14 cases ranged between 20% -60% ,2 cases ranged between 60% -100% .There was no significant differences between the levels of AKAP12 methylation and lung cancer patients′age and gender(P>0 .05) .However ,it was signifi‐cantly higher in the patients with high pathological stage and differentiation degree (P<0 .05) .Conclusion AKAP12 promoter re‐gion methylation was related to tumor progression and malignant degree .
9.Application of Positron Emission Computed Tomography in Treatment of Cerebral Infarction (review)
Chinese Journal of Rehabilitation Theory and Practice 2014;(4):340-343
Cerebral infarction is caused by cerebral blood supply disturbance, and then results in cerebral hypoxic ischemic lesions, with the manifestation of neurofunction deficit. This article summarized the application of positron emission computed tomography in treat-ment of cerebral infarction.
10.Survey on Physiological and Psychological Symptoms of Drug Abusers under Rehabilitation Period Through Labor
Yuehan SONG ; Feng LI ; Ying JIAO ; Yang LIU ; Xiaolan LIU ; Jing GUAN ; Yan LIU ; Hehe WEI ; Leilei ZANG ; Xuesong ZHAO
Chinese Journal of Rehabilitation Theory and Practice 2009;15(4):378-379
Objective To investigate the physiological and psychological symptoms of drug abusers under rehabilitation period through labor.Methods A self-designed clinical symptoms questionnaire and Eysenck Personality Questionaire (EPQ) were used to evaluate 1 004 drug abusers under rehabilitation period through labor, and the related symptoms were analyzed.Results The mainly physiological symptoms were fatigue, forgetfulness, aching pain of joints, arrhythmia and discomfort of limbs, and the mainly psychological symptoms are drug craving, insomnia and anxiety. The mean scores of P and E were higher in those who had the drug craving symptoms ( P<0.01), and the mean scores of N were higher in those who had the insomnia or anxiety symptoms ( P<0.01).Conclusion The mainly physiological symptoms of drug abusers under rehabilitation period through labor are fatigue, forgetfulness, aching pain of joints, arrhythmia and discomfort of limbs, which are probably caused by the unbalance of the nervous and internal secretive systems, and the plastisity of the nervous system. The psychological symptoms may due to the effect of morphine and the personality of the drug abusers.


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