ObjectiveTo investigate the expression levels of vascular endothelial growth factor (VEGF)in knee synovial membranes and synovial fluids whether it could be a marker for progressive osteoarthritis.MethodsKnee synovial membranes and synovial fluids of patients with osteoarthritis who were underwent total knee arthroplaaty or arthroscopy were collected. They were classified into four groups according to the radiographic grading[Kellegren-Lawrence(K-L) grade]. Appoint K-L-0-grade patients who suffered from menisci injuries only served as controls. The levels of VEGF in the synovial fluid were measured by enzymelinked immunosorbent assay(ELISA) and VEGF-secreting cells were identified by immunohistochemistry.ANOVA was used for statistical analysis. ResultsVarious degrees of inflammation could be found in all the samplesevaluated histologically on HE-stained sections. Synovial tissue inflammation presented as synovial lining thickening, and inflammatory cells infiltration. VEGF expressed in the synovium linings and surrounding blood vessels. The VEGF levels in the synovial fluids were increased accordingly with K-L grades, which reached the peak level in the late stage of osteoarthritis. The levels of VEGF in the synovial fluids were significantly higher in patients with osteoarthritis[from (1181±116), (1632±140) to (2252±216) pg/ml]than in those with menisci injury (P＜0.01); The percent ages positive cell in each groups were (5±4)％ , (9±4)％,(16±6)％ and (21±6)％ respectively, there were significantly differences too (P＜0.01). ConclusionVEGF originated from synovial tissue may play a role in the pathogenesis of osteoarthritis. High levels of VEGF in the synovial fluids can be regarded as the marker of active osteoarthritis.

ObjectiveTo evaluate the clinical value of contrasted X-ray in diagnosis of breast lesions.Methods29 patients who were confirmed as breast lesions verified by surgery and histopathology were enrolled in this study.All the lesions were evaluated by plain and contrasted X-ray.The lesion detectability of X-ray,and contrasted series.Results29 patients had 26 malignant and 5 benign lesions.There were significant differences between benign and malignant tumors on enhancement homogenity,morphology and margin characteristics.According to the morphology character and enhancement pattem.The distribution proved significantly different ( x2 =26.43,P ＜ 0.05 ).The diagnostic indices for the lesions morphology had the sensitivity of 83.8％ (26/31) and specificity of 76.9％ (20/26).ConclusionEnhanced X-ray was better than plain exam on lesion detection.Benign and malignant breast tumors could be differentiated according to the morphology characteristic and enhancement pattern.

Objective To examine the anticancer effect of a novel histone deacetylase inhibitor (HDACi), JZ004, on colon cancer cells HCT-8 and HT-29, and to investigate the molecular mechanisms of proliferation inhibition and apoptosis induction of cancer cells treated by JZ 004.Methods Colon cancer cells were treated with a series of concentrations of JZ004 .MTT assay was used to detect the proliferation of cancer cells .The cell cycle distribution and apoptosis were deter-mined by flow cytometry .Rhodamine 123 and DCFH-DA were applied to detect the mitochondrial membrane potential (ΔΨm) and reactive oxygen species ( ROS) production.The protein expressions of acetyl-histone H3, p21, cyclin-dependent kinase(CDK)4, Bcl-2, Mcl-1 and Bax were assayed by Western blotting .Results JZ004 was found to inhibit proliferation and induce apoptosis of colon cancer cells in a time-and dose-dependent manner , accompanied by a dose-dependent hyperacetylation of histone H3.JZ004 induced the cancer cell arrest in G 0/G1 phase by increasing the expres-sion level of p21 while CDK4 was downregulated .JZ004 also increased cellular ROS production and reduced ΔΨm by regu-lating the expressions of Bcl-2 family proteins .Conclusion As a novel HDACi , JZ004 effectively inhibits proliferation and increases ROS production to induce apoptosis of colon cancer cells .The results indicate that JZ004 is a potential compound to be developed as an anti-colon cancer agent for clinic application .

Objective:To investigate the distribution of iron deposition in the substantia nigral (SN) subregions on quantitative susceptibility mapping (QSM) and the change of swallow tail sign (STS) in patients with relapsing-remitting multiple sclerosis (RRMS) of different disease stages.Methods:The clinical and imaging data of 53 patients with RRMS (case group) diagnosed at the First Hospital of Chongqing Medical University from November 2019 to December 2021 were retrospectively analyzed. The case group was divided into 0-5 years subgroup, 6-10 years subgroup, and >10 years subgroup according to the disease duration; another 37 age-and gender-matched healthy volunteers were recruited as the control group during the same period. All subjects underwent MRI and QSM reconstruction. First, the SN was divided into four subregions: rostral anterior-SN (aSNr), rostral posterior-SN (pSNr), caudal anterior-SN (aSNc), and caudal posterior-SN (pSNc) on the QSM, and the quantitative susceptibility value (QSV) of each subregion was measured, and then the STS of the SN was observed and scored on the susceptibility weighted imaging (SWI) generated by post-processing. ANOVA was used to compare the differences in the QSV of each subregion of SN among the groups, and the probability of abnormal STS was compared using the χ 2 test. Spearman′s test was used to analyze the correlation between the QSV of each subregion of SN and the STS score. Results:The differences in QSV of aSNr, pSNr, aSNc, and pSNc were statistically significant among the 0-5 years subgroup, 6-10 years subgroup,>10 years subgroup of RRMS patients and the control group ( P<0.05). The QSV of aSNr, pSNr, and aSNc in 0-5 years subgroup was higher than those in the control group ( P was 0.039, 0.008, 0.039, respectively). The QSV of aSNr, aSNc, and pSNc in the 6-10 years subgroup were higher than those in the 0-5 years subgroup ( P was <0.001, 0.020, 0.015, respectively). The QSV of the aSNc, pSNc in >10 years subgroup were lower than those in the 6-10 years subgroup ( P=0.037, 0.006). The QSV of aSNr, pSNr in >10 years subgroup were higher than those in the control group ( P was <0.001, 0.001). There were 7 cases of abnormal STS in the 0-5 years subgroup, 11 cases in the 6-10 years subgroup, 12 cases in >10 years subgroup, and 9 cases in the control subgroup, and there was a statistically significant difference in the probability of abnormal STS among the subgroups of the RRMS patients and the control subgroup (χ 2=16.20, P=0.011). Both the scores of STS in the 6-10 years subgroup and >10 years group were positively correlated with the QSV in pSNc ( r s=0.65, P=0.006; r s=0.48, P=0.045). Conclusions:In RRMS patients, SN iron deposition is concentrated on aSNr, pSNr, and aSNc in the 0-5 years subgroup and on aSNr, aSNc and pSNc in the 6-10 years subgroup. The QSVs of all SN subregions have a downward trend in >10 years subgroup compared with that in the 6-10 years subgroup. Both the QSVs of the pSNc in the 6-10 years group and >10 years group are positively related to STS scores. These help explore the potential progression pattern of SN iron deposition in RRMS patients and the cause of abnormal STS in RRMS patients.

Objective:To investigate the clinicopathological and molecular features, diagnosis and differential diagnosis of TFE3-rearranged epithelioid hemangioendothelioma (EHE). Methods Two cases of TFE3-rearranged EHE arising from soft tissues, diagnosed by the Pathology Department of the First Affiliated Hospital of Nanjing Medical University from 2013 to 2020 were observed. EnVision method was used for immunophenotyping, fluorescence in situ hybridization (FISH) was used to test TFE3 gene rearrangements and WWTR1-CAMTA1 fusion gene,and next-generation sequencing (NGS) was used to delineate the fusion transcripts.Results:Details of these two cases were as follows: case 1, male, 51 years old, with tumor in the right temporal region; case 2, female, 42 years old, with tumor in the right neck. The tumors showed progressive painless enlargement. Grossly, the tumor of case 1 was multinodular with unclear boundary and grayish red cut surface, while the tumor of case 2, originating from a vein, appeared as a firm, tan mass within vessel wall. Microscopically, both tumors showed moderate cellularity and were consisted of plump, epithelioid, or histiocytoid cells with eosinophilic cytoplasm and mild-to-moderate nuclear pleomorphism. Most of the tumor cells were arranged in solid or alveolar growth patterns, while some tumor cells showed intraluminal papillary growth pattern in case 1 and anastomosing vascular channels and extramedullary hematopoiesis in case 2. Immunohistochemically, the tumor cells showed diffuse positivity for CD31, CD34, ERG, and TFE3. FISH revealed TFE3 break-apart signals in two cases, but WWTR1-CAMTA1 gene fusion was not detected. NGS identified YAP1 (exon1)-TFE3 (exon6) fusion gene in case 2. Clinical follow-up information was available in both cases for a follow-up period of 15 and 59 months respectively. Patient 1 had a relapse 22 months after surgery, and was currently alive with the tumor. Patient 2 remained disease-free.Conclusions:TFE3-rearranged EHE is a rare molecular subtype of EHE, with accompanying characteristic morphologic features. However the morphologic spectrum remains under-recognized, and more experience is needed. Immunohistochemical and molecular examinations are helpful for the diagnosis and differential diagnosis of the disease.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system whose clinical manifestations and diagnostic criteria are non-specific and absence of golden criteria when diagnosing. Magnetic resonance imaging (MRI) can not only observe the focal lesions of demyelination, but also evaluate microstructural damages and iron deposition in the white/gray matter in MS patients by applying various developing sequences. MRIs play an irreplaceable role in revealing pathological evolution, prognosis and monitoring after treatment of MS patients. This paper reviewed the clinical value and application of MRIs for the MS patients in recent years.

Objective:To investigate the changes in structural brain network topology and microstructural damage in patients with multiple sclerosis (MS), and to analyze its correlation with cognitive function.Methods:Clinical and imaging data of 114 patients with MS (MS group) diagnosed in the First Affiliated Hospital of Chongqing Medical University from May 2021 to September 2022 were analyzed retrospectively. In addition, 71 volunteers were recruited as a healthy control group (HC group) during the same period. All subjects were performed on cognitive assessment and 3D-T 1 magnetization-prepared rapid gradient echo, 3D-fluid-attenuated inversion recovery, and diffusion kurtosis imaging (DKI) scans. GRETNA software was used to obtain network topology attributes, and global attributes included global efficiency, local efficiency, and small-world attributes [clustering coefficient(Cp), shortest path length(Lp), normalized Cp(γ), normalized Lp, and small-world index (σ)]. Local attributes included betweenness centrality (BC), degree centrality (DC), nodal clustering coefficient (NCp), nodal efficiency, nodal local efficiency (NLe) and nodal shortest path length. The DKI parameter map generated by the post-processing software was used to extract the DKI parameter values of the brain region with abnormal local topology of the brain structure network. The differences of global attributes, local attributes and DKI parameter values [kurtosis fractional anisotropy (KFA), mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) values] were analyzed by independent sample t-test or Mann-Whitney U test, and corrected by false discovery rate (FDR). Spearman or Pearson correlation analysis was used to evaluate the correlation between abnormal brain structure network topology attributes and cognitive scale scores in the MS group. Results:Both the MS group and the HC group structure network showed small-world attributes, and the γ and σ values of the MS group were significantly lower than those in the HC group (FDR correction, P<0.05). Compared with the HC group, BC, DC, NCp and NLe broadly reduced in the MS group, mainly involving in bilateral frontal, temporal, precuneus, amygdala, and thalamus (FDR correction, P<0.05). After FDR correction, compared with the HC group, the KFA, MK, RK and AK values of 23 brain regions with abnormal local attributes of the network in the MS group were significantly changed in several brain regions (FDR correction, P<0.05). The correlation analysis showed, after FDR correction, the DC value of the right putamen in MS patients was positively correlated with the digit span test (DST) scores ( r=0.318 ,P=0.001). Conclusion:There are extensive changes in the structural brain network of MS patients, accompanied by varying degrees of microstructural damage, and the reduction of degree centrality in the basal ganglia putamen region is associated with cognitive impairment.

Objective: To investigate the effect of irradiation to anastomosis from preoperative radiotherapy for patients with rectal cancer by studying the pathological changes. Methods: In this retrospective study, patients enrolled in the FOWARC study from January 2011 to July 2014 in the Sixth Affiliated Hospital of Sun Yat-Sen University were included. In the FOWARC study, enrolled patients with local advanced rectal cancer were randomly assigned to receive either neoadjuvant chemo-radiotherapy or chemotherapy. Among these patients, 23 patients were selected as radiation proctitis (RP)group, who fulfilled these conditions: (1) received neoadjuvant chemo-radiotherapy followed by sphincter-preserving surgery; (2) developed radiation proctitis as confirmed by preoperative imaging diagnosis; (3) had intact clinical samples of surgical margins. Twenty-three patients who had received neoadjuvant chemo-radiotherapy but without development of radiation proctitis were selected as non-radiation proctitis (nRP) group. Meanwhile, 23 patients received neoadjuvant chemotherapy only were selected as neoadjuvant chemotherapy (CT) group. Both nRP and CT cases were selected by ensuring the basic characteristics such as sex, age, tumor site, lengths of proximal margin and distal margin all maximally matched to the RP group. Both proximal and distal margins were collected for further analysis for all selected cases. Microscopy slices were prepared for hematoxylin & eosin staining and Masson staining to show general pathological changes, and also for immunohistochemistry with anti-CD-34 as primary antibody to reveal the microvessel. Microvessel counting in submucosal layer and proportion of macrovessel with stenosis were used to evaluate the blood supply of the proximal and distal end of anastomosis. A modified semi-quantitative grading approach was used to evaluate the severity of radiation-induced injury. Either ANOVA analysis, Kruskal-Wallis rank-sum test or χ² test was used for comparison among three groups, and Mann-Whitney U test was used for comparison between two groups. Results: Compared to group of neoadjuvant chemotherapy only, patients receiving neoadjuvant chemo-radiotherapy had lower microvessel count in both proximal and distal margins (M(Q_R): proximal, 25.5 (19.6) vs. 50.0 (25.0), Z=3.915, P=0.000; distal, 20.5 (17.5) vs. 49.0 (28.0), Z=3.558, P=0.000), higher proportions of macrovessel with stenosis (proximal, 9.5% (23.8%) vs. 0, Z=3.993, P=0.000; distal, 11.5%(37.3%) vs. 0 (2.0%), Z=2.893, P=0.004), higher histopathologic score (proximal, 4.0 (2.0) vs. 1.0 (2.0), Z=6.123, P=0.000; distal, 5.0 (3.0) vs. 2.0 (1.0), Z=4.849, P=0.000). In patients receiving neoadjuvant chemo-radiotherapy, compared to nRP group, RP group had lower microvessel count in both proximal and distal margins (proximal, 19.0 (23.0) vs. 30.4 (38.0), Z=2.845, P=0.004; distal, 19.0 (13.0) vs. 30.0(29.1), Z=2.022, P=0.043), higher proportions of macrovessel with stenosis (proximal, 23.0% (40.0%) vs. 0(11.0%), Z=3.248, P=0.001; distal, 27.0% (45.0%) vs. 3.0% (19.0%), Z=2.164, P=0.030). Rate of anastomotic leakage for CT, nRP and RP group were 8.7% (2/23), 30.4% (7/23), and 52.2% (12/23), and the differences among three groups were statistically significant (χ²=10.268, P=0.007). Conclusion Radiation-induced injury existed on both margins of the resected rectal site after preoperative radiotherapy, and those diagnosed as radiation proctitis had more severe microvascular injury.

Objective: To investigate the safety and efficacy of surgical treatment for chronic radiation intestinal injury. Methods: A descriptive cohort study was performed. Clinical data of 73 patients with definite radiation history and diagnosed clinically as chronic radiation intestinal injury, undergoing operation at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 1, 2012 to February 28, 2019, were reviewed and analyzed retrospectively. Patients did not undergo operation or only received adhesiolysis were excluded. All the patients had preoperative examination and overall evaluation of the disease. According to severity of intestinal obstruction and patients′ diet, corresponding nutritional support and conservative treatment were given. Surgical methods: The one-stage bowel resection and anastomosis was the first choice for surgical treatment of chronic radiation intestinal injury. Patients with poor nutritional condition were given enterostomy and postoperative enteral nutrition and second-stage stoma closure and intestinal anastomosis if nutritional condition improved. For those who were unable to perform stoma closure, a permanent stoma should be performed. Patients with severe abdominal adhesion which was difficult to separate, enterostomy or bypass surgery after adhesiolysis would be the surgical choice. For patients with tumor metastasis or recurrence, enterostomy or bypass surgery should be selected. Observation parameters: the overall and major (Clavien-Dindo grades III to V) postoperative complication within 30 days after surgery or during hospitalization; mortality within postoperative 30 days; postoperative hospital stay; time to postoperative recovery of enteral nutrition; time to removal of drainage tube. Results: Of the 73 patients who had been enrolled in this study, 10 were male and 63 were female with median age of 54 (range, 34-80) years. Preoperative evaluation showed that 61 patients had intestinal stenosis, 63 had intestinal obstruction, 11 had intestinal perforation, 20 had intestinal fistula, 3 had intestinal bleeding, and 6 had abdominal abscess, of whom 64(87.7%) patients had multiple complications. Tumor recurrence or metastasis was found in 15 patients. A total of 65(89.0%) patients received preoperative nutritional support, of whom 35 received total parenteral nutrition and 30 received partial parenteral nutrition. The median preoperative nutritional support duration was 8.5 (range, 6.0-16.2) days. The rate of one-stage intestine resection was 69.9% (51/73), and one-stage enterostomy was 23.3% (17/73). In the 51 patients undergoing bowel resection, the average length of resected bowel was (50.3±49.1) cm. Among the 45 patients with intestinal anastomosis, 4 underwent manual anastomosis and 41 underwent stapled anastomosis; 36 underwent side-to-side anastomosis, 5 underwent end-to-side anastomosis, and 4 underwent end-to-end anastomosis. Eighty postoperative complications occurred in 39 patients and the overall postoperative complication rate was 53.4% (39/73), including 39 moderate to severe complications (Clavien-Dindo grade III-V) in 20 patients (27.4%, 20/73) and postoperative anastomotic leakage in 2 patients (2.7%, 2/73). The mortality within postoperative 30 days was 2.7% (2/73); both patients died of abdominal infection, septic shock, and multiple organ failure caused by anastomotic leakage. The median postoperative hospital stay was 13 (11, 23) days, the postoperative enteral nutrition time was (7.2±6.9) days and the postoperative drainage tube removal time was (6.3±4.2) days. Conclusions Surgical treatment, especially one-stage anastomosis, is safe and feasible for chronic radiation intestine injury. Defining the extent of bowel resection, rational selection of the anatomic position of the anastomosis and perioperative nutritional support treatment are the key to reduce postoperative complications.

Objective:To investigate the clinical efficacy of redo rectal resection and coloanal anastomosis.Methods:The retrospective and descriptive study was conducted. The clinicopatholo-gical data of 49 patients who underwent redo rectal resection and coloanal anastomosis for the treatment of local recurrence of tumors and failure of colorectal or coloanal anastomosis after rectal resection in the Sixth Affiliated Hospital of Sun Yat-sen University from November 2012 to December 2021 were collected. There were 32 males and 17 females, aged 57(range,31-87)years. Redo rectal resection and coloanal anastomosis was performed according to the patient′s situations. Observa-tion indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distri-bution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers or percentages. Results:(1) Surgical situations. All 49 patients underwent redo rectal resection and coloanal anastomosis successfully, with the interval between the initial surgery and the reopera-tion as 14.2(7.1,24.3)months. The operation time and volume of intraoperative bold loss of 49 patients in the redo rectal resection and coloanal anastomosis was 313(251,398)minutes and 125(50,400)mL, respectively. Of the 49 patients, there were 38 cases receiving laparoscopic surgery including 12 cases with transanoscopic laparoscopic assisted surgery, 11 cases receiving open surgery including 2 cases as conversion to open surgery, there were 20 cases undergoing Bacon surgery, 14 cases undergoing Dixon surgery, 12 cases undergoing Parks surgery, 2 cases undergoing intersphincter resection and 1 case undergoing Kraske surgery, there were 20 cases undergoing rectum dragging out excision and secondary colonic anastomosis, 13 cases undergoing dragging out excision single anastomosis, 12 cases undergoing rectum dragging out excision double anastomosis, 4 cases undergoing first-stage manual anastomosis, there were 21 cases with enterostomy before surgery, 16 cases with prophylactic enterostomy after surgery, 12 cases without prophylactic enterostomy after surgery. The duration of postoperative hospital stay of 49 patients was (14±7)days. (2) Postoperative situations. Fifteen of 49 patients underwent postoperative complications, including 8 cases with grade Ⅱ Clevien-Dindo complications and 7 cases with ≥grade Ⅲ Clevien-Dindo complications. None of 49 patient underwent postoperative transferring to intensive care unit and no patient died during hospitalization. Results of postoperative histopathological examination in 23 patients with tumor local recurrence showed negative incision margin of the surgical specimen. (3) Follow-up. All 49 patients underwent post-operative follow-up of 90 days. There were 42 cases undergoing redo rectal resection and coloanal anastomosis successfully and 7 cases failed. Of the 37 patients with enterostomy, 20 cases failed in closing fistula, and 17 cases succeed. There were 46 patients receiving follow-up with the median time as 16.1(7.5,34.6)months. The questionnaire response rate for low anterior resection syndrome (LARS) score was 48.3%(14/29). Of the patients who underwent redo coloanal anastomosis and closure of stoma successfully, there were 9 cases with mild-to-moderate LARS.Conclusion:Redo rectal resection and coloanal anastomosis is safe and feasible for patients undergoing local recurr-ence of tumors and failure of colorectal or coloanal anastomosis after rectal resection, which can successfully restore intestinal continuity in patients and avoid permanent enterostomy.