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.Application value of a joint prediction model based on lymph node imaging features in evalua-ting lymph node metastasis of locally advanced rectal cancer patients after neoadjuvant che-moradiotherapy
Haitao ZHU ; Huici ZHU ; Xiaoting LI ; Yingshi SUN ; Xiaoyan ZHANG
Chinese Journal of Digestive Surgery 2025;24(6):769-776
Objective:To investigate the application value of a joint prediction model based on lymph node imaging features in evaluating lymph node metastasis of locally advanced rectal cancer (LARC) patients after neoadjuvant chemoradiotherapy (nCRT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 215 LARC patients who were admitted to Peking University Cancer Hospital & Institute from July 2010 to June 2015 were collected. There were 131 males and 84 females, aged (56.7±10.1)years. All 215 patients were randomly divided into a training set of 143 cases and a testing set of 72 cases using a 2∶1 ratio of random seed numbers. The training set was used to construct the prediction model, and the testing set was used to validate the performance of prediction model. Observation indicators: (1) lymph node metastasis in LARC patients after nCRT; (2) imaging feature selection and model construction and evaluation. Com-parison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were conducted using the Logistic regression model. Performance evaluation of prediction model was conducted using the receiver operating characteristic (ROC) curve. The area under the curve (AUC), accuracy, sensitivity, and specificity were calculated. Calibration curves and decision curves were used to evaluate the consistency and clinical application value of the prediction model. Results:(1) Lymph node metastasis in LARC patients after nCRT. Of the 215 LARC patients after nCRT, results of postoperative pathological examination showed that there were 162 cases with negative lymph node metastasis and 53 cases with positive lymph node metastasis, showing significant differences in age and maximum short-axis diameter of lymph node between them ( t=2.178, Z=-5.305, P<0.05). (2) Imaging feature selection and model construction and evaluation. Forty-one imaging features were extracted from the 215 LARC patients after nCRT, including 9 gray-level first-order features, 24 gray-level co-occurrence matrix features and 8 shape features. The score of lymph node (LNscore) in 162 cases with negative lymph node metastasis and 53 cases with positive lymph node metastasis were 0.18(0.10,0.33) and 0.39(0.23,0.54), respectively, showing a significant difference between them ( Z=-5.487, P<0.05). Results of multivariate analysis showed that maximum short-axis diameter of lymph node and LNscore were independent factors influencing lymph node metastasis of LARC patients after nCRT ( odds ratio=1.277, 25.514, 95% confidence interval as 1.010-1.614, 2.003-324.964, P<0.05). A Logistic regression joint prediction model was constructed by incorporating the maximum short-axis diameter of lymph node and LNscore. The ROC curves results showed that the AUC, accuracy, sensitivity, and specificity of the joint prediction model in the training set were 0.779 (95% confidence interval as 0.702-0.844), 72.7%, 71.4%, and 73.2%, respectively. The above indicators in the testing set were 0.805 (95% confidence interval as 0.694-0.889), 80.6%, 66.7%, and 85.2%, respectively. Calibration curves in both training set and test set showed good agreement with the ideal curve, indicating high calibration. Decision curves demonstrated the model′s clinical utility with a high net benefit. Conclusion:The maximum short-axis diameter of lymph node and LNscore are independent factors influencing lymph node metastasis of LARC patients after nCRT. The joint prediction model constructed based on the above indicators can be used to predict lymph node metastasis in LARC patients after nCRT.
3.Development of an artificial intelligence-based automatic MRI scoring model for extramural vascular invasion in rectal cancer and its prognostic value
Haitao HUANG ; Yunrui YE ; Lifen YAN ; Yanfen CUI ; Lili FENG ; Huifen YE ; Yulin LIU ; Ying ZHU ; Zhongwei CHEN ; Zhenhui LI ; Ke ZHAO ; Zaiyi LIU ; Changhong LIANG
Chinese Journal of Radiology 2025;59(11):1267-1274
Objective:To develop an artificial intelligence (AI)-based automatic scoring model for magnetic resonance imaging-detected extramural vascular invasion (AI-mrEMVI) and evaluate its performance and prognostic value in patients with rectal cancer.Methods:In this multicenter retrospective cohort study, a total of 2 501 rectal cancer patients from seven centers between November 2012 and December 2020 were included and divided into completely independent training ( n=1 830) and validation ( n=671) cohorts. A nnUNet-based AI-mrEMVI scoring model was constructed. Manual mrEMVI scores assigned by two radiologists served as the reference standard for accessing the accuracy of the AI-mrEMVI scoring. Kaplan-Meier survival analysis and Cox regression were used to evaluate the prognostic stratification ability of the AI-mrEMVI scores. The concordance index (C-index) was calculated to evaluate prognostic performance. Results:In the validation cohort, the manual mrEMVI scores were 0-2 in 425 patients (63.3%), 3 in 89 (13.4%), and 4 in 157 (23.4%). The AI-mrEMVI model identified 0-2 in 375 patients (55.9%), 3 in 95 (14.2%), and 4 in 201 (30.0%), with an overall accuracy of 81.1% (544/671, 95% CI 77.9%-84.0%). The 3-year disease-free survival (DFS) rates for patients with AI-mrEMVI scores of 0-2, 3, and 4 were 85.2%, 70.0%, and 58.2%, respectively, and the 5-year overall survival (OS) rates were 87.2%, 81.6%, and 62.6%, respectively (DFS: χ2=48.74, P<0.001; OS: χ2=30.04, P<0.001). Multivariable Cox regression showed that for DFS, AI-mrEMVI scores of 3 and 4 were associated with hazard ratios ( HR) of 1.75 (95% CI 1.11-2.77, P=0.016) and 2.65 (95% CI 1.86-3.78, P<0.001), respectively. For OS, an AI-mrEMVI score of 4 was associated with an HR of 2.56 (95% CI 1.62-4.03, P<0.001). The C-index values of the AI-mrEMVI scoring model for predicting DFS and OS were 0.647 (95% CI 0.608-0.686) and 0.650 (95% CI 0.598-0.702), respectively. Conclusion:The proposed AI-mrEMVI automatic scoring model demonstrated high diagnostic accuracy and performed favorably in predicting DFS and OS prognostic risk in patients with rectal cancer.
4.Optimization of"Honghuangbai"Gel Extraction Process and Establishment of Content Determination Method
Yanguo GAO ; Haitao ZHU ; Liangyong HUANG ; Fang YE ; Qibin WANG ; Tao ZHENG ; Li CHEN
Herald of Medicine 2025;44(8):1322-1329
Objective To optimized the extraction process of the"Honghuangbai"gel and to establish the content determination method of the gel.Methods The contents of salidroside,berberine hydrochloride and 1,4-bis[4-(glucose-oxy)benzyl]-2-isobutyl malate in"honghuangbai"extract were determined by HPLC with gradient elution;the content of total polysaccharide was determined by anthrone-sulfuric acid method.AHP-CRITIC composite weighting method was used to calculate the weight coefficient of 4 indicators,and the comprehensive score was taken as the evaluation index.Combined with L9(34)orthogonal experiment design,the effects of solid-liquid ratio,extraction time and times on the extraction process of"honghuangbai"gel were investigated,and the optimal extraction process was selected and verified.The method for the determination of 4 index components in the gel was established and the methodology was investigated.Results The optimal solid-liquid ratio was 1∶45,the optimal extraction time was 2 h and the optimal extraction times was twice.The linear relationships of the four indexes were good in their respective linear ranges,with R2>0.999 0.The average recoveries were 98.67%~102.09%,and RSD was 0.77%~3.17%.Good precision,repeatability and stability,RSD≤2.28%.Conclusion The optimal extraction process of"honghuangbai"gel optimized by AHP-CRITIC combined with orthogonal test is stable and economical.The method of the gel content determination is feasible and the result is reliable,which provides experimental basis for the establishment of the quality standard of the gel.
5.To investigate effect of adipose-derived mesenchymal stem cells on fistula wound repair in fistular-type Crohn's disease model rats based on miR-146a-IRAK axis
Jian NI ; Xiaowen ZHU ; Haitao YU
Chinese Journal of Immunology 2025;41(2):320-327
Objective:To investigate investigate repairing effect of adipose tissue-derived mesenchymal stem cell(ADSC)on fistula wounds in a rat model of fistula Crohn's disease(CD)and its regulation mechanism on miR-146a/interleukin-1 receptor-associ-ated kinase(IRAK)signaling axis.Methods:RT-PCR was used to detect the expression of miR-146a and mRNA expression of IRAK in the serum of 80 fistula-type CD patients treated with fistula after operation.Dual-luciferase gene reporter was used to analysis the re-lationship between miR-146a and IRAK.The rat CD successfully prepared fistula lesions and divided into control group(Con),ADSC intervention group(ADSC),ADSC+miR-146a-antagomir intervention group(ADSC+antagomir),ADSC+miR-146a-antagomir+siR-NA-IRAK intervention group(ADSC+antagomir+si),with 10 rats in each group.One hour after successful modeling,rats in ADSC group were injected with 2×106 cells/ml ADSC suspension into the area around the fistula,and subcutaneously injected 2 μg/kg of miR-146a-antagomir-NC.Rats in the ADSC+antagomir group were injected with 2×106 cells/ml ADSC suspension into the area around the fistula,and subcutaneously injected with 2 μg/kg of miR-146a-antagomir.Rats in the ADSC+antagomir+si group were injected with 2×106 cells/ml ADSC suspension into the area around the fistula,and subcutaneously injected with 2 μg/kg of miR-146a-an-tagomir+siRNA-IRAK.Rats in the Con group,were injected a dose of normal saline into the area around the fistula,and subcutaneous-ly injected 2 μg/kg of miR-146a-antagomir-NC.Each group was treated twice a day for 14 consecutive days.Flow cytometry was used to detect the apoptosis of fistula wound tissue in rats;kits were used to detect the contents of TNF-α and IL-6 in rats serum.Immuno-histochemistry was used to detect angiogenesis in the fistula wound tissue of the rats in each group.Western blot was used to detect the expressions of IRAK,apoptosis protein B-lymphoma-2(Bcl-2),Bcl-2-related x protein(Bax),vascular endothelial growth factor(VEGF)in fistula wound tissue.Results:The expression of miR-146a in the postoperative serum of patients with CD fistulae was sig-nificantly decreased,the mRNA expression of IRAK was significantly increased,and the differences were statistically significant(both P<0.05).miR-146a regulated the expression of IRAK.Compared with the Con group,the apoptosis rate,the contents of TNF-α and IL-6,the expressions of IRAK and Bax in the rat fistula wound of ADSC group,ADSC+antagomir group,ADSC+antagomir+si group were significantly decreased,the number of new blood vessels and the expression of Bcl-2 and VEGF in the fistula tissue were significantly increased.Compared with ADSC group,the apoptosis rate,the contents of TNF-α and IL-6,the expressions of IRAK and Bax in the rat fistula wound of ADSC+antagomir group,ADSC+antagomir+si group were significantly increased,the number of new blood vessels and the expressions of Bcl-2 and VEGF in the fistula tissue were significantly decreased.Compared with ADSC+an-tagomir group,the contents of TNF-α and IL-6,the expressions of IRAK and Bax in the rat fistula wound of ADSC+antagomir+si group were significantly decreased,the number of new blood vessels and the expressions of Bcl-2 and VEGF in the fistula tissue were significantly increased,and the differences were statistically significant(all P<0.05).Conclusion:ADSCs can significantly heal fistu-las after fistula lesions in CD model rats,which may be related to regulating the expression of miR-146a/IRAK,inhibiting cell apopto-sis,and promoting wound angiogenesis.
6.Preparation and Quality Standard Formulation of Compound Bupleurum Suppository
Zhizhen YU ; Zegan LIU ; Libo WANG ; Liangyong HUANG ; Fang YE ; Haitao ZHU ; Ziyan XU ; Shiming DU
Herald of Medicine 2025;44(9):1482-1489
Objective To explore the prescription and preparation technology of compound Bupleurum suppository and draft its quality standard.Methods The volatile oil of Bupleurum was extracted by steam distillation,and the compound Bupleurum-based suppository was prepared by mixing the volatile oil with taurine using the melting method.The quality standard of the preparation was formulated according to the quality inspection items of the general rule 0107 of the Pharmacopoeia of the People's Republic of China(2020 Edition,Volume IV);The contents of n-hexanoic acid and n-heptanoic acid in the preparation were determined by gas chromatography-mass spectrometry(GC-MS).The content of taurine in the preparation was determined by high-performance liquid chromatography(HPLC).Results The optimized distillation time of the volatile oil was 1.5 h,The linear ranges of n-hexanoic acid,n-heptanoic acid and taurine are 23.175 0-115.875 0 μg·mL-1(R2=0.999 4),4.590 0-68.850 0 μg·mL-1(R2=0.998 9)and 15-125 μg·mL-1(R2=0.999 6),respectively.The average recoveries are 99.83%,101.96%,98.89%with RSDs of 2.84%,1.36%,2.88%,respectively.The RSDs of precision,stability,and repeatability tests are less than 5%.The properties,mass difference,melting time,microbial limit,and stability assessment of the preparationwere all in accordance with the Pharmacopoeia of the People's Republic of China.Conclusion Compound Bupleurum suppository preparation technology is reasonable and feasible,which meets the quality standard.
7.Efficacy of a fascia-locking circular continuous suture ostomy technique in parastomal hernia prevention
Haitao MA ; Xiaofeng ZHU ; Ying WANG ; Enlai JIANG ; Weidong XIAO ; Yuan QIU
Chinese Journal of Gastrointestinal Surgery 2025;28(4):408-411
Objective:To evaluate the feasibility and preventive efficacy of a fascia- locking circular continuous suture ostomy technique in reducing parastomal hernia incidence.Methods:This technique was applied to patients undergoing permanent colostomy following radical rectal cancer resection. Surgical steps included: (1) A circular incision was made 1-2 cm medial to the intersection of the lateral margin of the rectus abdominis muscle and the line connecting the umbilicus to the left anterior superior iliac spine. Subcutaneous tissues were dissected vertically to expose the anterior rectus sheath, followed by blunt separation of the rectus abdominis after longitudinal incision of the sheath. The posterior rectus sheath and peritoneum were similarly incised. (2) Eight equidistant interrupted sutures (anchoring knots) were placed through the anterior rectus sheath, partial rectus abdominis, posterior rectus sheath, and peritoneum. (3) The terminal colon was exteriorized, and continuous sutures were applied to secure the anchoring knots and seromuscular layers of the bowel between knots, forming a circular locking mechanism by tying the terminal suture to the initial knot's tail. (3) The skin and seromuscular layers of the bowel margin were intermittently sutured (8-12 stitches) to achieve mucosal eversion.Results:From February to October 2023, 13 patients (11 males, 2 females; age: 67 ± 10 years; BMI: 23.8 ± 4.0 kg/m2) underwent this technique at the Second Affiliated Hospital of Army Medical University. Mean stoma creation time was 15.7 ± 3.0 minutes. During a follow-up of 14.6 ± 3.1 months, physical examinations and abdominal CT scans identified parastomal hernias in 2 male patients at 10 and 7 months postoperatively. Only one patient experienced a Clavien-Dindo grade ≥Ⅲ complication, which resolved with treatment. No stoma-related complications (e.g., infection, stenosis, or prolapse) occurred in any patient.Conclusion:The fascia-locking circular continuous suture ostomy technique is safe and feasible, demonstrating potential efficacy in preventing parastomal hernia following colostomy.
8.Ultrasound vascular classification at C6 transverse process region for ultrasound-guided cervical sympathetic block
Haitao QU ; Hongyu CHEN ; Hui YAO ; Jingjing LI ; Feng ZHU
Chinese Journal of Interventional Imaging and Therapy 2025;22(9):561-565
Objective To observe the application value of ultrasound classification of blood vessels at C6 transverse process region during ultrasound-guided cervical sympathetic block(CSB).Methods A total of 42 pain patients were retrospectively enrolled.According to vascular distribution morphology and variation,as well as the minimum vertical distance from carotid artery to C6 transverse process shown by ultrasound,blood vessels at C6 transverse process region was classified into type Ⅰ(standard type),Ⅱ(short arterial spacing type),Ⅲ(puncture path obstruction type)and Ⅳ(vascular variation type in blockade zone).CSB needle insertion strategy was adjusted according to the results of ultrasound classification.The needle tip directly reached the puncture target for type Ⅰ,"fluid push method"was used for type Ⅱ and type Ⅲ,while the needle tip needed to be guided to reach the area between carotid sheath and variant blood vessels in the puncture target area for type Ⅳ.The effectiveness and safety of this method were observed.Results Among 42 cases,type Ⅰ was observed in 18 cases(18/42,42.86%),type Ⅱ was noticed in 3 cases(3/42,7.14%),and type Ⅲ and Ⅳ was detected in 9(9/42,21.43%)and 12(12/42,28.57%)cases,respectively.CSB was successfully performed in all 42 cases,Horner syndrome was successfully induced and relieved spontaneously within 1-2 h.No adverse reactions such as local hematoma,pneumothorax,nor local pain was observed.Conclusion Ultrasound classification of blood vessels at C6 transverse process region during CSB was effective and safe,having certain promotion value.
9.Clinical distribution and drug resistance of Klebsiella pneumoniae strains isolated from hospitalized patients between 2018 to 2022
Xinyue LUO ; Zhongdan ZHANG ; Haitao WANG ; Peigeng GU ; Yi LIU ; Shaofu DU ; Binghua ZHU
Chinese Journal of Nosocomiology 2025;35(9):1396-1400
OBJECTIVE To understand the epidemiological characteristics and change of drug resistance of Klebsiel-la pneumoniae strains from a hospital so as to adjust the use of antibiotics and control the transmission of hospital-associated infection caused by the K.pneumoniae.METHODS The K.pneumoniae strains were isolated from the patients who were hospitalized in The 305 Hospital of PLA from 2018 to 2022.The data of drug susceptibility tes-ting were exported by using WHONET 5.6,the clinical data and changing trend of drug resistance were retro-spectively analyzed with the use of SPSS 25.0 software.RESULTS Totally 9157 strains of bacteria were isolated from the patients who were hospitalized from 2018 to 2022,1502(16.40%)of which were K.pneumoniae,and the isolation rate showed a downward trend(x2=15.054,P<0.001).Sputum(77.16%)was the major type of specimen;the strains were mainly isolated from intensive care unit(55.26%).The patients aged more than 79 years old were dominant,accounting for 65.58%.The result of drug susceptibility testing showed that there were significant differences in the drug resistance rates to the commonly used antibiotics from 2018 to 2022(P<0.05).The drug resistance rates to aztreonam,ertapenem and tigecycline showed upward trends with the years(P<0.05),while the drug resistance rates to the rest of drugs such as cefoperazone-sulbactam,ceftazidime and amika-cin showed downward trends(P<0.05).CONCLUSIONS There is significant difference in the clinical distribution of the K.pneumoniae strains in recent 5 years.The key populations and departments should be attached great im-portance to.The drug resistance rates of the K.pneumoniae strains to many types of antibiotics show downward trends,but the situation of drug resistance is still serious.It is necessary to continue to implement the prevention and control policies for drug resistance and reasonably use antibiotics based on the result of drug susceptibility testing.
10.Preliminary research on the anti-caries effect of Lactobacillus plantarum mouthwash
Han ZHU ; Yuankai FANG ; Haitao CAO ; Rong WU ; Dihong QIU
STOMATOLOGY 2025;45(11):849-853
Objective To evaluate the inhibitory effect of Lactobacillus plantarum mouthwash on the progression of caries in isolated teeth.Methods Human isolated teeth were infected with Streptococcus mutans solution,and treated with saline,commercial mouth-wash,and Lactobacillus plantarum mouthwash,respectively,for 28 days.Tooth changes were recorded to assess their inhibitory effect on caries progression by light microscopy and scanning electron microscopy.Results Lactobacillus plantarum had an inhibitory effect on caries progression,with significant effects on deep dentinal caries in pit and fissure,and similar efficacy to commercial mouthwash on smooth surface caries.Calcium loss in dentin tubules was observed under an electron microscope,with Lactobacillus plantarum group less than commercial group and saline group.Conclusion Lactobacillus plantarum mouthwash can inhibit the growth of Streptococcus mutans and effectively prevent caries,particularly in controlling the progression of deep pit and fissure caries.

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