ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

objective:To investigate the factors influencing failure of preoperative optimisation with exclusive enteral nutrition(EEN)in patients with Crohn's disease(CD)and to construct a predictive model.Methods:Clinical data of 161 patients with Crohn's disease who underwent surgical treatment after preoperative EEN optimization at the Inflammatory Bowel Disease Center of General Surgery of the Eastern Theater General Hospital from June 2021 to November 2023 were retrospectively analyzed.Patients were divided into two groups according to the preoperative EEN optimisation effect:optimisation success and optimisation failure.Logistic regression analysis was used to determine the factors influencing optimisation failure,and a column line graphical model was constructed using R4.4.0 software.Results:After at least 4 weeks of EEN treatment,a total of 44 patients(27.33%)failed preoperative optimization.Multifactorial analysis showed that FC>500 μg/g and use of corticosteroids were independent risk factors for failure of preoperative optimization,and an increase in prealbumin after 1 week of treatment was a protective factor for successful preoperative optimization.Based on the results of the multivariate analysis,a column graph was constructed,and the C-index was 0.873(95%CI=0.783～0.964).The calibration curve shows that the probability of failure predicted by the nomogram model prior to optimization is in good agreement with the actual probability.The clinical decision curve confirms that the risk threshold is between 0.03～0.96,and the nomogram model can be used to predict the failure of preoperative EEN optimization over other treatment options.Conclusion:FC>500μg/g and history of corticosteroid use were independent risk factors for failure of preoperative optimization,and an increase in prealbumin after 1 week of treatment was a protective factor for successful preoperative optimization.The nomogram constructed on the basis of these results has a good predictive value and is clinically applicable.

Gastric polyps, as a common digestive system disease, have shown an increasing detection rate and are regarded as one of the precancerous states of gastric cancer. In TCM, gastric polyps can be classified as diseases such as "stomachache" and "fullness and distension in the stomach". TCM holds that the disease is often related to the accumulation of pathogenic factors such as phlegm and blood stasis in the body to form "kenang", which has the characteristics of insidiousness, stubbornness, and recurrence. Deficiency of healthy qi and disorder of qi movement can lead to the adhesion of phlegm and blood stasis, which highly aligns with the etiology and pathogenesis of gastric polyps. The treatment principles are promoting blood circulation to remove blood stasis, regulating qi movement, and strengthening the body resistance to consolidate the essence. Understanding the etiology, pathogenesis, and treatment principles of gastric polyps from the theory of "kenang" has important guiding significance for clinical diagnosis and treatment, providing new ideas and methods for the treatment of gastric polyps.

Objective To investigate the effects of penehyclidine hydrochloride(PHC)admin-istered at different time points on neurological function and the blood-brain barrier(BBB)in rat model of severe intracerebral hemorrhage(ICH),and to preliminarily explore its potential mechanism of action based on the growth arrest-specific protein 6(GAS6)/receptor tyrosine kinase(Axl)signaling pathway.Methods ICH model rats were established via intracerebral injection of a collagenase type Ⅳ solu-tion.The model rats were randomly divided into sham operation group(intracerebral injection of an equal volume of saline),model group(intracerebral injection of 0.4 μL of collagenase type Ⅳ solu-tion),24 h drug administration group(intracerebral injection of 0.4 μL of collagenase type Ⅳ solu-tion combined with intraperitoneal injection of 2 mg/kg PHC 24 h after successful model establish-ment),6 h drug administration group(intracerebral injection of 0.4 μL of collagenase type Ⅳ solu-tion combined with intraperitoneal injection of 2 mg/kg PHC 6 h after successful model establish-ment),pre-drug administration group(intraperitoneal injection of 2 mg/kg PHC before modeling combined with intracerebral injection of 0.4 μL of collagenase type Ⅳ solution),and pathway in-hibitor group(intraperitoneal injection of 2 mg/kg PHC before modeling combined with intracerebral injection of 0.4 μL of collagenase type Ⅳ solution and intraperitoneal injection of 75 mg/kg R428,a GAS6/Axl signaling pathway inhibitor,after successful model establishment).The degree of neu-rological impairment in rats was assessed after successful model establishment and at the end of treat-ment;brain tissue water content in rats was calculated;brain tissue damage and Evans blue(EB)content in rats were evaluated using hematoxylin-eosin(HE)and EB staining methods;western blot was used to detect the expression levels of Claudin-5,zonula occludens-1(ZO-1),Occludin,ma-trix metalloproteinase-9(MMP-9),and proteins related to the GAS6/Axl signaling pathway in brain tissue.Results HE staining revealed that compared with the sham operation group,the model group exhibited irregular arrangement of brain tissue cells,a large number of necrotic cells,and sig-nificant infiltration of inflammatory cells;compared with the model group,the 24 h drug administra-tion,6 h drug administration,pre-drug administration,and pathway inhibitor groups showed more orderly brain tissue cells,reduced cell gaps,and decreased infiltration of inflammatory cells;com-pared with the 24 h drug administration group,the 6 h drug administration,pre-drug administration,and pathway inhibitor groups exhibited more intact brain tissue cell structures,reduced cell gaps,and decreased infiltration of inflammatory cells;compared with the pre-drug administration group,the 6 h drug administration and pathway inhibitor groups showed slight swelling of brain tissue cells and a small amount of inflammatory cell infiltration.Compared with the sham operation group,the model group had increased neurological function scores,brain tissue water content,EB content in brain tissue,and MMP-9 protein levels,along with decreased levels of ZO-1,Occludin,Claudin-5 proteins,and GAS6 and p-Axl protein expression;compared with the model group,the 24 h drug administration,6 h drug administration,pre-drugadministration,and pathway inhibitor groups had decreased neurological function scores,brain tissue water content,EB content in brain tissue,and MMP-9 protein levels,along with increased levels of ZO-1,Occludin,Claudin-5 proteins,and GAS6 and p-Axl protein levels in brain tissue;compared with the 24 h drug administration group,the 6 h drug administration,pre-drug administration,and pathway inhibitor groups had decreased neurological function scores,brain tissue water content,EB content in brain tissue,and MMP-9 protein levels,along with increased levels of ZO-1,Occludin,Claudin-5 proteins,and GAS6 and p-Axl protein expression;compared with the pre-drug administration group,the 6 h drug administra-tion and pathway inhibitor groups had increased neurological function scores,brain tissue water con-tent,EB content in brain tissue,and MMP-9 protein levels,along with decreased levels of ZO-1,Occludin,Claudin-5 proteins,and GAS6 and p-Axl protein expression in brain tissue;the between-group differences mentioned above were statistically significant(P＜0.05).Conclusion Early ad-ministration of PHC can improve neurological function and the BBB in ICH rats by reducing brain tissue damage and brain edema,and its mechanism may be related to the activation of the GAS6/Axl signaling pathway.

Objective To investigate the effects of Erhuang Quzhi Granules combined with Silibinin Capsules on fatty liver index,inflammatory factors and autophagy-related gene levels in patients with nonalcoholic fatty liver disease(NAFLD).Methods A total of 126 patients with NAFLD of phlegm blended with blood stasis type were randomly divided into control group and observation group,with 63 cases in each group.The control group was treated with oral use of Silibinin Capsules,and the observation group was treated with oral use of Erhuang Quzhi Granules on the basis of treatment for the control group.The course of treatment lasted for 3 months.Before and after treatment,the two groups were observed in the changes of fatty liver index,and the levels of inflammatory factors of interleukin 6(IL-6)and tumor necrosis factor alpha(TNF-α),liver function and blood lipid indicators of alanine aminotransferase(ALT),aspartate aminotransferase(AST),γ-glutamyl transpeptidase(GGT),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C),and autophagy-related genes of autophagy-related gene 7(ATG7)and myosin-like BCL2 binding protein(Beclin 1).After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 3 months of treatment,the total effective rate of the observation group was 90.48％(57/63),and that of the control group was 71.43％(45/63).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the fatty liver index of the two groups was significantly decreased compared with that before treatment(P＜0.05),and the decrease of fatty liver index in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the serum levels of inflammatory factors of IL-6 and TNF-α in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum IL-6 and TNF-α levels in the observation group was significantly superior to that in the control group(P＜0.05).(4)AAfter treatment,the serum levels of liver function indicators of ALT,AST and GGT in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum ALT,AST and GGT levels in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the serum levels of blood lipids of TG,TC and LDL-C in the two groups were significantly lower than those before treatment(P＜0.05),and the serum HDL-C level was significantly higher than that before treatment(P＜0.05).The decrease of serum TG,TC and LDL-C levels and the increase of serum HDL-C level in the observation group were significantly superior to those in the control group(P＜0.05).(6)After treatment,the serum levels of autophagy-related genes of ATG7 and Beclin 1 in the two groups were significantly higher than those before treatment(P＜0.05),and the increase of serum ATG7 and Beclin 1 levels in the observation group was significantly superior to that in the control group(P＜0.05).(7)During the medication,no liver or kidney function damage or serious adverse reactions were found in the two groups.Conclusion Erhuang Quzhi Granules combined with Silibinin Capsules are effective for the treatment of NAFLD patients with phlegm blended with blood stasis type,which is helpful to relieve the symptoms of fatty liver,reduce the levels of inflammatory factors,improve liver function and blood lipid levels,and regulate the expression of autophagy-related genes.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Objective To investigate the relationship between serum periostin (POSTN) level and bone mineral density in patients undergoing maintenance hemodialysis (MHD). Methods Ninety-five patients who had received MHD treatment for more than 3 months in the Hemodialysis Center of Qingdao Municipal Hospital from October 2022 to October 2023 were enrolled as experimental group. Meanwhile, 50 healthy individuals undergoing health examinations in the Physical Examination Center of the same hospital during the same period were selected as the control group. Clinical data such as gender and age were collected for both groups. Fasting venous blood samples were collected before dialysis to measure parathyroid hormone (PTH), alkaline phosphatase (ALP), urea nitrogen, serum creatinine, serum calcium, serum phosphorus, and other indicators. Serum POSTN levels in MHD patients and healthy individuals were determined using enzyme-linked immunosorbent assay (ELISA). The correlation between serum POSTN levels and bone mineral density in MHD patients was explored. Univariate and multivariate binary Logistic regression analyses were performed to identify risk factors for low bone mineral density in MHD patients and assess the clinical value of serum POSTN level in predicting low bone mineral density in these patients. Results The serum POSTN level in the experimental group were significantly higher than those in the control group (P < 0.05). These patients were divided into two groups based on T-values: normal bone mass group(47 cases, T value >-1.0) and low bone mineral density (48 cases, T value≤-1.0). The low bone mineral density group had significantly higher serum POSTN levels, dialysis vintage, PTH, ALP, serum phosphorus, β₂-microglobulin levels, and a higher proportion of females compared to the normal bone mass group (P < 0.05). Pearson correlation analysis revealed negative correlations of bone mineral density T values with serum POSTN, dialysis vintage, C-reactive protein, PTH, ALP, serum phosphorus, and β₂-microglobulin in MHD patients (r=-0.695, -0.688, -0.246, -0.528, -0.216, -0.309, -0.293; P < 0.05). Multivariate binary Logistic regression analysis showed that after adjusting for confounding factors such as dialysis vintage, PTH, and ALP, high serum POSTN level was an independent risk factor for low bone mineral density in MHD patients. The receiver operating characteristic (ROC) curve indicated that the area under the curve (AUC) for serum POSTN level in predicting low bone mineral density in MHD patients was 0.901, with a cut-off value of 29.66 ng/L. Conclusion MHD patients have higher serum POSTN levels than healthy individuals, and this marker is associated with low bone mineral density in MHD patients.

Posner-Schlossman syndrome(PSS)is a sporadic and recurrent self-limiting anterior uveitis, and its pathogenesis remains unclear. It was considered to be a prostaglandin-mediated inflammatory response. In recent years, it has been found to be related to viral infection, immune genetics, vascular endothelial dysfunction, and other factors. Clinically, the disease is predominantly unilateral. The patients with PSS suffer from increased intraocular pressure, mild pain in the affected eye, as well as blurred vision, and irisopsia. Seldom damage to the optic nerve and visual field was reported. The commonly treatment of PSS is local medication, such as anti-inflammatory drugs and intraocular pressure lowering drugs; otherwise systemic medication can be employed in severe cases. Surgical treatment can be performed for PSS if uncontrolled intraocular pressure elevation, frequent attacks, and optic nerve damage and visual field defect due to prolonged disease course. Early diagnosis and treatment of PSS can effectively reduce glaucoma-related damages. This review discussed the research progress of PSS from various aspects, aiming to provide references for the etiology, pathogenesis, and clinical diagnosis and treatment of this disease.

Objective:To report our experience in using the Ilizarov technique to treat bone defects secondary to Gustilo Ⅲb open tibial fractures with negative clinical signs and serological inflammatory markers.Methods:A retrospective study was performed to analyze the 19 patients with bone defects secondary to Gustilo Ⅲb open tibial fracture who had been treated at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital between January of 2010 and June of 2021. They were 15 males and 4 females with an age of (41±11) years. Their inclusion criteria: undergoing treatment with Ilizarov technique (consecutive compression-distraction or bone transport), soft tissue coverage procedures resulting in wound closure and negative clinical infection signs for at least 3 months and normal serological inflammatory markers, and follow-up for more than 3 months after frame removal. Three-phase bone scan was performed for the patients before the present surgery. Debridement, sampling of deep tissues for bacterial culture, and external stabilization with a fixator were performed in the present surgery. Osteotomy for compression-distraction or bone transport technique was carried out at 1 stage or 2 stages. Systemic antibiotic therapy for 6 weeks was continued for those with positive microbiological analysis guided by antibiogram. Recorded were results of intra-operative pus detection around defects, microbiological findings, length of bone defect reconstructed, rate and time of infection recurrence during treatment, fracture union rate, bone healing index, bony and functional results.Results:The interval between primary injury to the present surgery was (10±8) months. The preoperative three-phase bone scan showed infection free in 8 cases, chronic osteomyelitis in 7 cases, and suspicious infection in 4 cases. No pus was found during intra-operative debridement in all. The intra-operative microbiological detection was positive in 1 sample in 1 patient (infection free indicated by bone scan), and in ≥2 samples in 3 patients (bone scan indicating non-infection, infection not excluded and osteomyelitis in 1 case each). The length of bone defect reconstructed was (8±3) cm. The follow-up after the present surgery was (37±15) months. Fracture union was achieved in all cases, with a bone healing index of (1.7±0.5) months/cm. Clinical infection signs were observed 1 (1, 1) month after the present surgery in 6 patients whose microbiological results were all negative. All the 6 patients ended up with no clinical recurrence after empirical use of systemic antibiotics in 5 and radical debridement in one. The bony results showed 16 excellent and 3 good cases while the functional results showed 10 excellent and 9 good cases.Conclusions:In treatment of bone defects secondary to Gustilo Ⅲb open tibial fractures with negative clinical signs and serological inflammatory markers, constant vigilance is needed against low-grade infection. Intra-operative multiple sampling of deep tissues with a standardized protocol and microbiological testing are extremely valuable for diagnosis of fracture-related infections.

Objective:To study the outcome of realignment for genu varum with tibial bone defect managed with antegrade bone transport.Methods:To retrospectively study 11 patients with tibial bone defect and genu varum treated with antegrade bone transport from January 2012 to December 2020. All the patients were males, aged 42±16 years, left in 8 cases and right in 3. The segmental bone defect was secondary to fractures with amount of 7.9±2.1 cm. 10 cases were congenital genu varus, and 1 case was genu varus caused by malunion of proximal tibial fracture. The anatomical lateral tibio-femoral angle (aLTFA) was 179°(178°, 180°), the anatomical lateral distal femoral angle (aLDFA) was 82°(81°, 83°), joint line convergence angle (JLCA) was 0°(0°, 1°) and the anatomical medial proximal tibial angle (aMPTA) was 83.1°±3.9° before treatment. 7 cases were treated with unilateral external fixators, 3 cases with circular external fixators, and 1 case with hybrid external fixator. Antegrade bone transport surgeries were performed to treat bone defects and varus deformities. Among them, 3 cases using unilateral external fixators were additionally corrected for varus using swinging clamps, while 1 case using a circular external fixator was corrected for varus by installing hinges on the lateral side of the proximal tibia and distracting the medial-positioned threaded rod. The data including the angles between proximal pins in monorail fixators or proximal ring orientation in ring fixators and knee joint line, post-operative mechanic axis deviation (MAD) of lower extremity, the position of the mechanical axis relative to the width of the tibial plateau, mechanic medial proximal tibial angle (mMPTA), the amount of deformity correction in radiographic AP view, bone healing time, bone healing index (BHI), functional score and complications according to Paley's criteria were studied.Results:All 11 patients were followed up, and the follow-up time after removing the external fixators was 11(3, 25) months. The angles between pins in proximal clamp in monorail frame of 7 cases and hybrid frame of 1 case and joint line were 0° (-1°, 1°), while those between proximal ring orientation in circular fixators of 3 cases and joint line were 0°, 0° and 2° respectively. The MAD were -6±6 mm, mMPTA was 90°(89°, 92°), the amount of correction was 7.2°±3.9° in the last follow-up. The final mechanic axis passed through the lateral plateau at 58%±9% of its width (counting from medial knee edge). Well consolidation was achieved for all patients with 12±4 months (range, 7-20 months) of bone healing time. BHI was 1.6±0.6 months/cm (range, 1.2-2.9 months/cm). Functional score according to Paley's criteria was excellent in 7 cases and good in 4. Complications were 5 problems (3 of pin site infections and 2 of soft tissue infections) and 1 obstacle (soft tissue invagination). All the cases with problems were resolved with oral antibiotics. In the one with the obstacle of soft tissue invagination, the skin and docking site bone healing were noticed after invaginated tissue resection and refreshment procedure.Conclusion:It is advisable for genu varum with tibial bone defect to be realigned while managed with antegrade bone transport.