Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis， and its pathogenesis is complex and remains unclear. In recent years， more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota， including bile salt metabolism， dynamic changes of microbiota， inflammatory response， and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma， especially gut microbiota dysbiosis， abnormal bile salt metabolism， chronic inflammatory response， and immune system interaction， this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.

Pancreatic cancer is characterized by nerve invasion and a high mortality rate， and its pathological process depends on the complex interaction network between tumor and the nervous system. Based on the concept of “pancreatic cancer neuroecology”， this article analyzes the mechanism of action of peripheral motor nerve， sensory nerve， and central nerve in tumorigenesis， pain regulation， and cachexia formation and emphasizes the synergistic regulatory role of immune cells， Schwann cells， and extracellular matrix in the microenvironment of perineural invasion. At the same time， this article further elaborates on the metabolic interaction and chemotaxis between neuraxis and tumor， the effect on promoting chemotherapy resistance， and the dynamic relationship between neuroplasticity and tumor adaptability. In clinical practice， this article summarizes the key value of perineural invasion in prognostic evaluation， preoperative evaluation， and the selection of surgical strategy. In addition， this article reviews the basic research advances in the biomarkers and potential targets associated with perineural invasion in pancreatic cancer and points out the limitations of current model and transformation research. In the future， systematically analyzing the nerve-tumor-immune network and targeting its key nodes may provide multi-dimensional strategies and new breakthroughs for the precise intervention of pancreatic cancer， the reversal of drug resistance， and the relief of symptoms.

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

Objective To evaluate the clinical efficacy of 125I seeds implantation combined with transcatheter arterial infusion(TAI)in treating advanced pancreatic carcinoma(PC).Methods By using envelope sealing method,76 patients who met enrollment criteria were divided into observation group and control group.Finally,a total of 67 patients were enrolled in this study.The observation group had 31 patients and the patients received 125I seeds implantation combined with TAI therapy,and the control group had 36 patients and the patients received TAI therapy.After 3 courses of treatment,the clinical efficacy,pain score,incidence of obstructive jaundice(OJ),and survival time were compared between the two groups.Results In the observation group and the control group,the objective response rate(ORR)was 48.4％and 25.0％respectively,and the difference was statistically significant(P＜0.05);the disease control rate(DCR)was 83.9％and 66.7％respectively,and the difference was not statistically significant(P＞0.05).In both groups,the postoperative one-month and 3-month pain scores were decreased obviously when compared with the preoperative values(P＜0.05),but the reduction of pain score in the observation group was more obvious than that in the control group(P＜0.05).In the observation group and the control group,the pain relief rates were 23.06％and 13.4％respectively,and the difference was statistically significant(P=0.0252);the incidences of OJ were 19.4％and 50.0％respectively,and the difference was statistically significant(P＜0.05);the median survival time was 7.9 months and 5.1 months respectively,and the difference was statistically significant(P＜0.05).In both groups,the postoperative one-month and 3-month CA199 levels were decreased,and the difference was statistically significant(P＜0.05).No statistically significant difference in the incidences of adverse reactions such as nausea,vomiting,diarrhea and leukopenia existed between the two groups(P＞0.05).Conclusion 125I seeds implantation combined with TAI therapy can effectively relieve cancer pain,prolong survival time in patients with advanced PC,and it is clinically safe.Therefore,this therapy is worthy of clinical promotion.

OBJECTIVE To investigate the related factors of central lymph node metastasis(CLNM)in papillary thyroid carcinoma(PTC)with capsular invasion,and to construct a clinical nomogram prediction model.Its purpose is to provide theoretical basis for clinical diagnosis and treatment.METHODS The clinical data of PTC patients with capsule invasion admitted to the Department of General Surgery,Baoding First Central Hospital from October,2020 to October,2023 were retrospectively analyzed.The data included gender,age,body mass index(BMI),aspect ratio,tumor location,multifocality,microcalcification,Hashimoto thyroiditis(HT)and tumor diameter.According to the presence or absence of CLNM,the patients were divided into the normal group(107 cases)and the metastasis group(108 cases).Univariate and multivariate analysis of the data were performed to construct a visual nomogram prediction model,and the receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of the model.The nomogram model was internally verified using a Bootstrap test with 1000 repeated samples.Consistency index(C-index)and calibration curve were used to describe the prediction performance and prediction accuracy of the model.Finally,the clinical decision curve(DCA)was drawn to determine the clinical application ability of the model.RESULTS A total of 215 PTC patients with capsular invasion were included,of whom 108(50.23%)had CLNM.Univariate analysis showed that the occurrence of CLNM was associated with tumor diameter,aspect ratio>1,tumor located in the lower pole,multifocality,and HT(P<0.05).Multivariate regression analysis showed that tumor diameter,aspect ratio>1,tumor located in the lower pole and multifocus were independent risk factors for CLNM(OR=1.401,1.875,2.291,2.303,P<0.05),and HT was a protective factor for CLNM(OR=0.501,P<0.05).Based on the above risk factors,a nomogram prediction model for CLNM in patients with PTC with capsule invasion was constructed.The ROC curves showed that the area under the curve(AUC)was 0.859(95%CI:0.792-0.925,Yoden Index was 0.734,the sensitivity was 0.878,a specificity was 0.856),and the model had higher predictive value.Internal validation consistency index(C-index)was 0.83(95%CI,0.748 to 0.959).The calibration curve showed that the predictive value was close to the ideal curve,and it had good consistency.The DCA curve showed that the model had good clinical efficacy.CONCLUSION Larger tumor size,aspect ratio>1,tumor located in the lower pole and multifocality suggest higher risk of CLNM in PTC with capsular invasion,while HT is a protective factor for CLNM.The nomogram model based on the above risk factors has high discrimination and calibration,which is helpful for clinicians in preoperative evaluation and intraoperative exploration,so that high-risk patients can be prevented and treated as soon as possible.

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.
Acute Disease ; Animals ; Brain ; diagnostic imaging ; metabolism ; Brain Mapping ; Disease Models, Animal ; Fluorodeoxyglucose F18 ; Glucose ; metabolism ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; metabolism ; Male ; Neural Pathways ; diagnostic imaging ; metabolism ; Positron-Emission Tomography ; Radiopharmaceuticals ; Random Allocation ; Rats, Sprague-Dawley

Positron emission tomography (PET) imaging of functional metabolism has been widely used to investigate functional recovery and to evaluate therapeutic efficacy after stroke. The voxel intensity of a PET image is the most important indicator of cellular activity, but is affected by other factors such as the basal metabolic ratio of each subject. In order to locate dysfunctional regions accurately, intensity normalization by a scale factor is a prerequisite in the data analysis, for which the global mean value is most widely used. However, this is unsuitable for stroke studies. Alternatively, a specified scale factor calculated from a reference region is also used, comprising neither hyper- nor hypo-metabolic voxels. But there is no such recognized reference region for stroke studies. Therefore, we proposed a totally data-driven automatic method for unbiased scale factor generation. This factor was generated iteratively until the residual deviation of two adjacent scale factors was reduced by < 5%. Moreover, both simulated and real stroke data were used for evaluation, and these suggested that our proposed unbiased scale factor has better sensitivity and accuracy for stroke studies.
Animals ; Computer Simulation ; Disease Models, Animal ; Female ; Fluorodeoxyglucose F18 ; Image Processing, Computer-Assisted ; methods ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; Male ; Positron-Emission Tomography ; methods ; Rats ; Rats, Sprague-Dawley ; Stroke ; diagnostic imaging

One algorithm is designed to implement longitudinal auto-tracking of the the detector on X-ray in the digital radiography system (DR) with manual collimator. In this study, when the longitudinal length of field of view (LFOV) on the detector is coincided with the longitudinal effective imaging size of the detector, the collimator half open angle ( ), the maximum centric distance ( ) between the center of X-ray field of view and the projection center of the focal spot, and the detector moving distance for auto-traking can be calculated automatically. When LFOV is smaller than the longitudinal effective imaging size of the detector by reducing , the can still be used to calculate the detector moving distance. Using this auto-tracking algorithm in DR with manual collimator, the tested results show that the X-ray projection is totally covered by the effective imaging area of the detector, although the center of the field of view is not aligned with the center of the effective imaging area of the detector. As a simple and low-cost design, the algorithm can be used for longitudinal auto-tracking of the detector on X-ray in the manual collimator DR.

BACKGROUND:Considering the risk of lack of bone in revision and the bone coverage of component,it is advisable to use bone grafting to increase bone stock in patients with adult Crowe type Ⅲ developmental dysplasia of the hip (DDH) in the first total hip arthroplasty (THA).OBJECTIVE:To investigate the effectiveness of impaction bone grafting with morselized bone and bone paste for acetabular defects of adult Crowe type Ⅲ DDH in THA.METHODS:Forty cases (45 hips) of Crowe type Ⅲ DDH were enrolled,including 8 males and 32 females,aged 31-68 years.All the components were reconstructed at the anatomic acetabulum combined with deepening acetabulum and putting the centre of rotation medially and distally during THA procedures.The patients were all followed up and evaluated with Harris score,limp length,displacement of the centre of rotation,cup coverage,and postoperative complications.RESULTS AND CONCLUSION:The average follow-up was 32.7 months.Acetabular rotation centers of all the cases were recovered (near) to normal.The incisions healed by first intention and there was no complication such as infection,dislocation,prosthesis loosening.The acetabular cup prosthesis did not displace and was covered well by bone at the last follow-up,the grafted bone particles got radiological osseointegration and the bone sclerosis zone disappeared.No radiolucent lines and screw fracture were detected.The Harris scores of affected hips at the last follow-up were significantly higher than those before surgery(P=0).The average leg length was increased (2.31 ±0.18) cm.The mean cup coverage was 78.1％.The postoperative horizontal and vertical distance of the hip center were shorter than those before surgery (P=0).Reconstructing the acetabulum with autogenous morselized bone graft impaction can effectively restore the acetabular coverage,maintain the stability of acetabular cup and provide better relative bone stock in THA for Crowe type Ⅲ DDH in adult,and moreover,the short-term effect is satisfactory.

BACKGROUND:Legacy posterior stabilized prosthesis has advantages in theoretic design,in vitro kinematics and abrasion, but it remains unclear whether its clinical outcomes for vaglus knee deformity are better than Legacy constrained condylar knee prosthesis. OBJECTIVE:To explore the midterm folow-up effect of Legacy posterior stabilized prosthesis in total knee arthroplasty in patients with valgus knee deformity. METHODS: From February 2006 to November 2013 in Department of Bone and Joint Surgery, Affiliated Hospital of Luzhou Medical Colege, total knee arthroplasty was used to treat valgus knee deformity in 33 cases (35 knees). Parapatelar medial approach was used. Precise osteotomy was utilized to correct limb alignment. Lateral soft tissue received selective release. Finaly, an equal type of Legacy posterior stabilized prosthesis (Zimmer, USA) was implanted and fixed with antibiotic bone cement. The differences in hospital for special surgery knee score, range of motion of knee, femoral tibial angle, and maximum flexion and extension angle, as wel as X-ray film results were compared and analyzed before and after replacement. The complications including deep vein thrombosis, peri-prosthetic infection, patelar clicking, unstable knee, and common peroneal nerve injury were recorded after surgery. RESULTS AND CONCLUSION: Al patients were folowed up for 24-50 months. The incision was healed in one-stage. No complications such as peri-prosthetic infection appeared. Three patients suffered from common peroneal nerve palsy, which was cured at half a year after surgery by expectant treatment such as trophic nerve. Two cases suffered from knee instability after replacement, which was improved at 1 month after external fixation with a brace. One case experienced deep vein thrombosis in the lower extremity, which was improved after treatment with low molecular weight heparin anticoagulation. During final folow-up, hospital for special surgery knee score increased from (51.85±4.15) preoperatively to (85.77±2.50) postoperatively (P < 0.01). There were excelent in 20 knees, good in 11 knees, with an excelent and good rate of 89%. X-ray films showed that hindlimb alignment was apparently corrected, prosthetic position was good, no loosening occurred. These data indicate that total knee arthroplasty, using parapatelar medial approach, obtained good correction outcomes through the accurate amputation to correct hindlimb alignment and selective release of the soft tissue with Legacy posterior stabilized prosthesis in the treatment of valgus knee deformity.