Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Rhamnogalacturonan Ⅱ(RG-Ⅱ)is one of the structural domains of pectin whose structure is highly conserved among species.The main chain of RG-Ⅱ consists of approximately nine galacturonic acids linked by α-1,4 glycosidic bonds,with six well-defined side chains replacing them(A-F).The structures of the disaccharide side chains C and D and the monosaccharide side chains E and F in RG-Ⅱ from different sources remain essentially the same.In contrast,the oligosaccharide side chains A and B showed slight variability.Structural characterization of RG-Ⅱ can be achieved by molecular weight,monosaccharide composition,and mass spectrometry.The polysaccharides containing RG-Ⅱ structural domains in traditional Chinese medicines(TCMs)have high medicinal value.Isolation of RG-Ⅱ can be achieved using endo-polygalacturonase(Endo-PG)and Penicillium oxalicum.A substantial number of RG-Ⅱ standards can be rapidly prepared from red wine for the development of new quantitative methods to realize the quality control of active polysaccharides from traditional Chinese medicines and to promote the research process of polysaccharides from traditional Chinese medicines.

Consumptive thirst such as dry mouth and polydipsia,frequent urination polyuria,fear of heat and hyperhidrosis and loss of other body fluids,yin deficiency and internal heat expression,and irritability and other abnormal emotional symptoms are common.The Synopsis of Golden Chamber need to be further explored for the treatment of miscellaneous diseases.The dialectical thought has a high clinical application value.Lily disease treatment recommendations in the Synopsis of Golden Chamber are explored.The symptoms of lily disease are varied and uncertain,which are caused by the scattering and wandering aimlessly of heat pathogen.The pathogenesis of lily disease can be examined through external symptoms such as bitter taste in mouth,red urine,and faint and rapid pulse.Diabetes is also closely related to yin deficiency and internal heat,and the pathogenesis of the two is similar.Mental symptoms are common characteristics of lily disease and diabetes.The method taken from the Synopsis of Golden Chamber and Baihe-like prescriptions for the treatment of diabetes are effective.By identifying different patterns,symptoms,and indicators,we can select lily bulb,common anemarrhena,rhizome,figwort root,unprocessed rehmannia root,and other drugs to treat diabetes,in order to improve our understanding of lily disease and provide new ideas for diabetes treatment.

Objective:To investigate the expression of programmed cell death ligand 1 (PD-L1), clinicopathologic features, immunohistochemical expression and molecular characteristics in fumarate hydratase (FH)-deficient renal cell carcinoma and to explore the potential application of immunotherapy in the patients.Methods:There were six patients with FH-deficient renal cell carcinoma treated at the First Affiliated Hospital of Fujian Medical University between January 2020 and October 2022. The clinical data, histological morphology, immunophenotype, PD-L1 expression and next-generation sequencing results were tabulated and analyzed.Results:There were 6 patients, all male, age ranged from 37 to 72 years (mean 45.7 years). Four cases were high-grade (WHO/ISUP grade3-4) with 2 or more histologic patterns, including papillary (most common), glandular, tubular, vesicular, ethmoid, nest-like, cystic and solid structures. Two cases were low-grade which showed nest-like, glandular, or tubular arrangement with eosinophilic flocculent cytoplasm and small intracellular vacuoles. Immunohistochemical analysis revealed strong expression of 2SC in all 6 cases, negative expression of FH in 5 cases, and positive expression of GATA3 in 5 cases. In high-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes in advanced tumor invasion were 180.3/mm 2 and 130.5/mm 2, respectively. PD-L1 combined positive scores (CPS) were 20, 50, 5 and 30, respectively. The Ki-67 proliferative index were 20%, 20%, 10% and 30%, respectively. In low-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes were 123.0/mm 2 and 100.5/mm 2, respectively. The PD-L1 CPS score was 1, and the Ki-67 proliferation index was 3%. High-throughput sequencing showed FH gene somatic mutation in 3 cases, FH gene germline mutation in 2 cases, and FH gene mutation was not detected in one case. Conclusion:FH-deficient renal cell carcinoma is more commonly high-grade than low grade. FH and 2SC are immunohistochemical markers used in the diagnosis of FH-deficient renal cell carcinoma, and GATA3 positivity is supportive of the diagnosis. The tumor infiltration of high-grade FH-deficient renal cell carcinoma shows an increase in CD4 and CD8 positive T-lymphocytes, and high expression of PD-L1; thus, anti-PD-L1 immunotherapy can be used as a treatment option.

Objective To simultaneously collect and analyze the kinematic and dynamic parameters for two techniques of traditional Chinese cervical manipulation ( TCCM), and quantitatively describe its biomechanical characteristics. Methods A senior practitioner completed the TCCM (positioning and directional rotation pulling, lateral flexion, respectively) on 10 healthy subjects, and the fluorescent marker balls were pasted on the operator to capture manipulation movements. The dynamic parameters and the surface electromyography ( sEMG) signals were collected by pressure-sensitive gloves and wireless sEMG acquisition system. Results The upper arm muscle was the main force muscle during TCCM, and biceps brachii had the highest contribution rate. The range of motion (ROM), speed, pulling force, and time during cervical spine positioning and directional rotation pulling were all greater than those during cervical spine lateral flexion. The integrate electromyography ( iEMG) and root mean square (RMS) for each muscle of the operator during cervical spine positioning and directional rotation pulling were higher than those during cervical spine lateral flexion. Conclusions The overall ROM, three-dimensional (3D) motion angle, load intensity and time during CCTM have the characteristics of high speed, low amplitude and strong force, reflecting the biomechanical characteristics of ‘ cunjin ’ ( one-inch punch ) in traditional Chinese medicine. This study provides references for further standardizing manual teaching and training and improving clinical safety.

Background:Duodenal neuroendocrine tumors(DNETs)are rare tumors,their disease characteristics are currently not well understood.At present,there are no research data on non-ampullary region DNETs in China.Aims:To analyze the clinical characteristics of patients with non-ampullary region DNETs in order to guide clinical practice.Methods:The clinical data ofnon-ampullary region DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected.Using the method of retrospective study,analyze the clinical characteristics of patients.Results:Twenty-two non-ampullary region DNETs patients were screened.Among them,8(36.4%)patients'tumor diameter<2 cm,14(63.6%)patients'tumor diameter≥2 cm.When non-ampullary region DNETs were diagnosed,the main clinical symptoms were abdominal distension(59.1%),followed by abdominal pain(41.0%).When diagnosed,half(50%)of patients with non-ampullary DNETs with tumor diameter<2 cm have no clinical symptoms.The clinical symptoms of non-ampullary DNETs patients with tumor diameter≥2 cm were mainly abdominal distension(85.7%),followed by abdominal pain(57.1%),and a few(14.3%)patients had no clinical symptoms.After diagnosed,the survival time of patients with tumor diameter<2 cm was longer than that of patients with tumor diameter≥2 cm(P=0.048).By the end of follow-up,the median survival time of patients with non-ampullary region DNETs was 451.0 months.Six patients had died,all of their tumor diameter were≥2 cm at diagnosis.Three of patients who died had stage Ⅳ at diagnosis,and all had liver metastases.Patients with tumor diameter<2 cm underwent surgical treatment and all survived after surgery.Conclusions:Abdominal distension is the main clinical manifestation of non-ampullary region DNETs patients,and the organ that is more likely to metastasize is the liver.The survival time of patients with non-ampullary region DNETs with tumor diameter<2 cm was longer than that of patients with tumor diameter≥2 cm.

Objective:To dynamically trace the migration and therapeutic effects of human bone marrow mesenchymal stem cells (MSCs) in mice with liver injury after cell transplantation through in vivo bioluminescent imaging (BLI).Methods:The MSCs were transfected with the lentivirus CMV-Luciferase2-mKate2 and mKate2 positive cells were purified and screened by fluorescence-activated cell sorting (FACS) after 96 h. The purified MSCs-R (MSCs-CMV-Luciferase2-mKate2) were used by in vitro and in vivo BLI. The mice (male BALB/c nude mice) were divided into 4 groups with 9 mice per group by random number table method, including (1) Liver injury experimental group: The liver injury model was established by intraperitoneal injection of CCl 4, and MSCS-R transplantation through spleen injection was performed 24 h later; (2) Control experimental group: The same volume of phosphate buffer (PBS) was injected intraperitoneally, and MSCS-R transplantation through spleen injection was performed 24 h later; (3) Liver injury group: Liver injury model was established and PBS was injected into the spleen;(4) Blank group: The mice were intraperitoneally injected of PBS.BLI was performed daily after cell transplantation until light signals disappeared in the liver region, and the pathological examination of liver tissue was obtained 14 d after MSCs-R transplantation. Linear regression analyses were performed to determine the correlation between the optical signal intensity and the number of cells, and statistical differences of the optical signal intensity between liver injury experimental group and control experimental group were evaluated using the Student′s t test. Results:The MSCs were readily transfected with lentivirus CMV-Luciferase2-mKate2 for 96 h. The transfected MSCs were purified by FACS and more than 95% of MSCs were mKate2 positive. The optical signal intensity of MSCs-R detected by BLI in vitro significantly correlated with cell numbers in vitro (R 2=0.980). In both of liver injury experimental group and control experimental group, cell migration to the liver was observed on the first day after intrasplenic transplantation of MSCs-R, and the optical signal intensity in the area of liver of liver injury experimental group was higher than that of control experimental group ( t=15.476, P<0.001). The optical signal intensity in the hepatic area was observed in 11 d after transplantation in liver injury experimental group, compared to control experimental group in 5 d. Optical signal was not detected in mice in the other two groups. Histopathology showed that the degree of liver injury after MSCs-R transplantation was significantly lower in liver injury experimental group than control experimental group. Conclusions:The dynamical migration of MSCs transplanted to the spleen and settled in the damaged liver could be tracked by BLI, and liver injury can prompt MSCs directionally migrate to the damaged tissues and play their role in repairing liver injury.

Background and Objectives: Tracking of the tumor progression by MSCs-based therapy is being increasingly important in evaluating relative therapy effectively. Herein, Bioluminescence imaging (BLI) technology was used to dynamically and quantitatively track the hepatocellular carcinoma suppressive effects by human umbilical cord mesenchymal stem cells (UC-MSCs). Methods: and Results: The stem cells present typical phenotypic characteristics and differentiation ability by morphology and flow cytometry analysis of marker expression. Then, the growth inhibition effect of conditioned medium and UC-MSC on H7402 cells was studied. It is found both the conditioned medium and UC-MSC can effectively decrease the proliferation of H7402 cells compared with the control group. Meanwhile, the relative migration of UC-MSC to H7402 is also increased through the transwell migration assay. In addition, a mice hepatoma tumor model was built by H7402 cells which can express a pLenti-6.3/DEST-CMV-luciferase 2-mKate2 gene. The effect of stem cells on growth inhibition of tumor in a mice transplantation model was dynamically monitored by bioluminescence imaging within 5 weeks. It has shown the bioluminescence signal intensity of the tumor model was significantly higher than that of the UC-MSC co-acting tumor model, indicating that the inhibition of UC-MSC on liver cancer resulted in low expression of bioluminescent signals. Conclusions The microenvironment of UC-MSCs can effectively inhibit the growth of liver cancer cells, and this therapeutic effect can be dynamically and quantitatively monitored in vivo by BLI. This is of great significance for the imaging research and application of stem cells in anticancer therapy.

Objective     To investigate the early safety and efficacy of transapical transcatheter aortic valve implantation (TAVI) for high-risk elderly patients with pure aortic valve insufficiency. Methods     A prospective multicenter clinical study of domestic J-valveTM TAVI for high-risk native non-calcified aortic valve insufficiency was conducted from April 2014 to May 2018, and the early postoperative results were analyzed. A total of 82 patients were enrolled, including 62 patients from West China Hospital, Sichuan University, 16 patients from Zhongshan Hospital, Fudan University, and 4 patients from Beijing Fuwai Hospital, National Center for Cardiovascular Diseases. There were 55 males and 27 females. The age was 61-90 (73.8±6.3) years. The logistic EuroSCORE was 10.0%-44.4% (17.5%±8.1%). All patients underwent TAVI using J-ValveTM system. Clinical evaluation and echocardiography were performed preoperatively and 1 month postoperatively. Multislice spiral CT was reviewed before discharge. Results     Three patients were transferred to thoracotomy for cardiopulmonary bypass operation, and 1 patient had decreased cardiac function due to leakage of the valve 1 week after surgery. The overall technical and procedural success rate was 95.1% and 93.9%, respectively. During hospitalization, 1 patient died of moderate pericyclosis complicated with multiple organ failure, and 1 patient died of pulmonary infection. Six (7.6%) patients received pacemaker implantation due to new onset Ⅲ° atrioventricular block. Echocardiographic follow-up showed paravalvular leak was observed in the few of patients, mild paravalvular leak was in 13 patients on the 30th day. Two patients showed moderate paravalvular leak. Left ventricular end-diastolic volume decreased from 197.7±66.8 mL (pre-TAVI) to 147.2±53.3 mL (30-day post-TAVI) (P<0.05). Mean pressure gradient was 9.5±4.1 mm Hg (30-day post-TAVI). Conclusion     This multicenter study demonstrates that TAVI with the J-Valve system for the treatment of pure aortic regurgitation is associated with sustained clinical and functional cardiovascular benefits in high-risk patients with symptomatic aortic regurgitation early-term follow-up. Our results further support that TAVI with the specific designed J-Valve system is an acceptable alternative therapy for high-risk patients with pure AR. Our result demonstrates good early-term durability and preserved hemodynamic function. The procedure appears to offer an adequate and lasting resolution for selected patients with pure aortic regurgitation.