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.

Objective To investigate programmed death including necroptosis,apoptosis,autophagy,ferroptosis,and pyroptosis in bone marrow megakaryocytes of mice during sepsis and its impact on platelet production capacity and coagulation function in mice.Methods C57BL/6J mice were randomly divided into a sham operation group(sham group)and a sepsis model group(CLP group).Peripheral blood platelets and coagulation function were measured by abdominal aortic blood sampling at 24 h postoperatively in both sham and CLP groups.After the mice were sacrificed,long bones of both lower limbs were taken,and bone marrow megakaryocytes were extracted using megakaryocyte separation solution and immunomagnetic bead separation.Laser confocal microscopy was used to observe the activation of programmed death-related marker molecules in mouse bone marrow megakaryocytes.Flow cytometry was used to detect programmed death rate,platelet production phenotype,and platelet surface markers(CD41,CD42b,CD61)of megakaryocytes.Western blotting was used to detect the expression of programmed death-related proteins in megakaryocytes.Results Compared with the sham group,the CLP group showed significant decreases in the number of platelets during acute sepsis(24 h)(P<0.000 1),significant increases in platelet distri-bution width(PDW)and mean platelet volume(MPV)(P<0.01),significant prolonging of thrombin time(TT),prothrombin time(PT),and activated partial thromboplastin time(APTT)(P<0.000 1,P<0.001,P<0.01),and significant reduction in fibrinogen(Fib)(P<0.000 1).Compared with the Con/sham group,the LPS/CLP group exhibited significant increases in the platelet production phenotype of megakaryocyte,the number of PLP in the supernatant,and the expression levels of platelet surface markers(CD41,CD42b,CD61).The rates of megakaryocyte necroptosis/apoptosis,pyroptosis,and ferroptosis were significantly elevated at 24 h post-CLP surgery.Laser confo-cal microscopy showed significant activation of LC3,P-MLKL,Caspase-1,and Fe2+in megakaryocytes of mice after CLP surgery.Western blotting results revealed that the CLP group exhibited a significant increase in the activa-tion rate of necroptosis-related protein P-MLKL(P<0.001),a significant increase in the cleavage of pyroptosis-related proteins GSDMD and GSDMD-N(P<0.01,P<0.001,respectively),a significant increase in the expres-sion of ferroptosis-related protein ACSL4(P<0.01),and a significant decrease in the expression of GPX4(P<0.01)compared to the sham group.Additionally,the CLP group demonstrated significant increases in the expression of apoptosis-related protein Bax,the cleavage of autophagy-related protein LC3B-Ⅱ,and the expression of P62(P<0.05,P<0.001,P<0.001,respectively).Inhibition of apoptosis with programmed cell death inhibitors decreased platelet production function of megakaryocyte,while inhibition of necroptosis and pyroptosis had limited effects on platelet production function of megakaryocyte.Inhibition of ferroptosis and autophagy enhanced platelet production function of megakaryocyte.Conclusion Significant programmed death of megakaryocytes was observed during the acute phase of sepsis(24 h).Among those megakaryocytes,apoptosis is an important mechanism for the differentia-tion of platelet production phenotype and increased platelet production capacity of megakaryocyte.Overactive autophagy and ferroptosis in megakaryocytes lead to megakaryocyte dysfunction,which is an important mechanism for coagulation abnormalities in sepsis.

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.

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.

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.

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.

This study explores the diagnosis and treatment of needle knife therapy for ankylosing spondylitis (AS) at middle and advanced stage based on the theory of meridian tendons, from a holistic perspective and syndrome differentiation. The treatment strategy includes "harmonizing yin and yang" to address root causes and "tendons-based release" to harmonize qi and blood, with the "tendons nodule points" as the core acupoint selection criterion. Based on this approach, the study systematically elaborates on two needle knife methods for AS: "governor vessel bone-piercing technique" and "below-the-umbilicus release technique", covering indications, acupoint location, and procedures. Clinical case examples are provided to enrich needle knife therapy guided by the theory of meridian tendons, offering insights for clinical and research work on AS.
Humans ; Acupuncture Points ; Acupuncture Therapy/methods* ; Meridians ; Spondylitis, Ankylosing/physiopathology* ; Tendons/physiopathology*

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.

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.

Objective: To evaluate the clinical efficacy and safety of micro-percutaneous nephrolithotomy (microPCNL) using Needle-perc in the oblique supine-lithotomy position for treating 1—2 cm lower-pole stones (LPSs)，by comparing it with flexible ureteroscopic lithotripsy (FURL)，so as to identify an effective surgical method for LPSs. Methods: We retrospectively analyzed the clinical data of 56 patients with isolated LPSs of 1—2 cm treated in our hospital during Jan.and Dec.2023.Patients were divided into two groups based on the treatment method：FURL (n=31) and microPCNL (n=25).General information and perioperative data were compared between the two groups. Results: All operations were successfully completed.The operation time was shorter in the microPCNL group than in the FURL group \[(46.5±10.1) min vs.(73.5±18.9) min，P<0.001\].Stone-free rate (SFR) was 92.0% in the microPCNL group and 71.0% in the FURL group (P=0.026).There were no significant differences in the average fall of hemoglobin level，serumc creatinine change level，hospitalization time and postoperative fever between the two groups. Conclusion: MicroPCNL in oblique supine-lithotomy position is a safe and effective treatment for 1-2 cm LPSs，with a higher SFR compared to FURL.