Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Objective:To investigate the expression and clinical significance of SKA3 protein in cholangiocarcinoma, and the effect of interfering SKA3 expression in vitro on the proliferation, invasion, and migration of cholangiocarcinoma SSP-25 cells, as well as its possible mechanism.Methods:The clinicopathological data, cancer tissues, and paracancerous tissues from 172 patients with distal cholangiocarcinoma in Beijing Friendship Hospital, Capital Medical University between January 2015 and December 2020 were retrospectively collected. Immunohistochemical method was used to detect the expression level of SKA3 protein in cancer tissues and paracancerous tissues. Transfection of SKA3 small interfering RNA (siRNA) into cholangiocarcinoma SSP-25 cells was used as si-SKA3 group, and the untreated SSP-25 cells were used as the control group. Cell immunofluorescence staining and Western blot were used to detect the transfection effect; CCK-8 method and cell colony formation experiment were used to observe changes in cell proliferation; cell scratch assay was used to monitor cell invasion; Western blot was used to detect the expression of PI3K-AKT signaling pathway related proteins.Results:Among 172 patients with cholangiocarcinoma, there were 116 males and 56 females; the age of 54 cases was under 60 years, and age of 118 cases was equal to or more than 60 years. The positive rate of SKA3 protein in cholangiocarcinoma tissues was higher than that in paracancerous tissues [78.49% (135/172) vs. 13.95% (24/172)], and the difference was statistically significant ( χ2 = 42.78, P < 0.01). The positive rate of SKA3 protein in cancer tissues of cholangiocarcinoma patients with nerve invasion [84.35% (124/147) vs. 44.00% (11/25)] and lymph node metastasis [88.78% (87/98) vs. 64.86% (48/74)] was higher than that of patients without nerve invasion and without lymph node metastasis, and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in the positive rate of SKA3 protein in cancer tissues of patients stratified by age, gender, tumor diameter, TNM stage, and tumor differentiation (all P > 0.05). The CCK-8 method showed that after 72 h of cultivation, the proliferation ability of SSP-25 cells in the si-SKA3 group (expressed as absorbance value at 450 nm) was lower than that in the control group (0.56±0.05 vs. 0.83±0.06), and the difference was statistically significant ( t = 3.06, P = 0.06). After 2 weeks of cultivation, the colony formation experiment showed that the number of colony formation of SSP-25 cells in the si-SKA3 group was lower than that in the control group. After 24 h of cultivation, the scratch healing rates of SSP-25 cells in the si-SKA3 group and the control group were (31±6) % and (72±5)%, respectively, and the difference was statistically significant ( t = 5.63, P = 0.013).Western blot analysis showed that the relative expression levels of p-PI3K and p-AKT proteins in the PI3K-AKT signaling pathway were lower than those in the control group, and the difference was statistically significant (all P < 0.05). Conclusions:SKA3 protein is highly expressed in cholangiocarcinoma tissues, and may related to nerve invasion and lymph node metastasis. Interfering SKA3 expression can inhibit the proliferation and invasion of cholangiocarcinoma SSP-25 cells, and its mechanism may be related to the inhibition of the PI3K-AKT signaling pathway.

Objective To investigate the temporal properties of dynamic functional connectivity of brain networks and the variability of network topology in patients with end-stage renal disease(ESRD).Methods Data of 30 ESRD patients(ESRD group)and 33 healthy subjects(control group)were retrospectively analyzed.Based on cranial resting-state functional MRI(rs-fMRI),dynamic functional connectivity(dFC)and graph theory analysis were employed,and the abnormalities in network topology and dFC in ESRD patients were assessed through comparison of groups.Pearson correlation analysis was used to observe the correlation between abnormal dFC indicators and clinical variables.Results Compared with control group,temporal scores and the mean residence time in ESRD group were significantly higher under state Ⅱ but significantly lower under state Ⅲ(both P＜0.05).The abnormal functional connectivity in ESRD patients under states Ⅱ and Ⅲ distributed mainly within and between default mode network,sensorimotor network,subcortical nuclei,execution and attention network,visual network and cerebellum networks.Network density and bilateral superior temporal gyrus nodal degrees in ESRD group were all significantly lower than those in control group(all P＜0.05).No significant correlation was found between the abnormal parameters of functional connectivity and graph theory attributes in ESRD group and clinical indicators under states Ⅱ nor Ⅲ(all P＞0.05).Conclusion ESRD patients had abnormal temporal attributes and network topology of brain dynamic networks related to cognitive impairments.

Objective To observe the value of multiparametric MRI-based radiomics model and deep learning(DL)model for distinguishing benign and malignant myxoid soft tissue tumors(MSTT).Methods A total of 141 MSTT patients confirmed with pathology were retrospectively collected.The patients were randomly divided into training set(n=98,including 51 cases of malignant MSTT and 47 cases of benign MSTT)and test set(n=43,including 22 cases of malignant MSTT and 21 cases of benign MSTT)at the ratio of 7∶3.Based on T1WI and fat suppression(FS)-T2WI in training set,radiomics features and DL features were extracted and selected,then a radiomics model and a DL model were constructed,respectively.Receiver operating characteristic(ROC)curves,calibration curves and decision curves were drawn,and the discrimination,calibration and net benefit of these 2 models were compared.Results In training set,the radiomics model for differentiating benign and malignant MSTT was constructed according to 9 optimal radiomics features,including 2 first order features,1 shape feature,3 gray level co-occurrence matrix features,1 gray level dependence matrix feature and 2 gray level size zone matrix features,while DL model was built based on 7 optimal DL features.In test set,the area under the ROC curve of radiomics model and DL model was 0.758 and 0.911,respectively,the latter was higher than the former(P=0.017).Both models had good calibration,and DL model had higher overall net benefit.Conclusion Compared with radiomics model,DL model based on MRI had better ability to differentiating benign and malignant MSTT,also higher overall net benefit.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective To isolate the secondary metabolites of endophytic fungus Aspergillus sp. J218 from Anectochilus roxburhii. Methods Different chromatographic methods, including Sephadex LH-20 and silica gel chromatography as well as HPLC, were used to isolate compounds from the EtOAc fraction of the solid fermentation of J218, and their structures were identified by spectral methods. Results Ten compounds were isolated from the fermentation of J218 and their structures were individually identified as kotanin（1）, flavasperone（2）, aurasperone B（3）, fonsecinone B（4）, fonsecinone D（5）, ensidol A（6）, fonsecinone A（7）, fonsecinone C（8）, aurasperone A（9）, and fonsecinone F（10）. Conclusion Most compounds isolated from endophytic fungus Aspergillus sp. J218 in Anectochilus roxburhii were identified as dimeric naphthopyrones. These results suggest that this strain contains rich dimerization synthase, which could provide clues for the further exploration of the rational biosynthesis pathway of dimeric naphthopyrones in this strain.

Objective:To investigate the effect of the duration of preoperative biliary drainage on postoperative complications after pancreaticoduodenectomy.Methods:The clinical data of 102 patients with benign and malignant hepatopancreatic ductal periampullary tumors who underwent pancreaticoduodenectomy and preoperative biliary drainage in Beijing Friendship Hospital, Capital Medical University from January 2016 to July 2020 were retrospectively analyzed. According to the median duration of preoperative biliary drainage, the patients were divided into short-term drainage group (≤ the median duration of biliary drainage) and long-term drainage group (> the median duration of biliary drainage). The general data, the effect of biliary drainage, inflammation-related indicators and postoperative complications were compared between the two groups. Multivariate logistic regression was used to screen the risk factors related to the postoperative severe complications.Results:Of the 102 patients, 68 (66.7%) were males and 34 (33.3%) were females, with a median age of 63 years (43-80 years). The median duration of preoperative biliary drainage was 14 d. There were 68 patients in short-term drainage group and 34 patients in long-term drainage group. There were no statistically significant differences in age, gender, body mass index (BMI), hypertension, diabetes mellitus, surgery history of upper abdominal, American Society of Anesthesiologists (ASA) grade, carcinoembryonic antigen, carbohydrate antigen 125, alpha-fetoprotein, prothrombin time, pancreaticojejunostomy method, operation time, and pathological type between the two groups (all P > 0.05). However, patients in long-term drainage group had higher conversion rate, more blood loss and longer hospital stay compared with those in short-term drainage group (all P < 0.05). Before biliary drainage, alanine aminotransferase (ALT) level in short-term drainage group was higher than that in long-term drainage group ( Z = -2.59, P = 0.009), and there were no statistically significant differences in aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TB) and direct bilirubin (DB) levels between the two groups before biliary drainage (all P > 0.05). After biliary drainage, DB in short-term drainage group was higher than that in long-term drainage group ( Z = -3.34, P = 0.001), and there was no statistically significant difference in ALT, AST, ALB, TB levels between the two groups (all P > 0.05). There were no statistically significant differences in the levels of white blood cells, neutrophils, lymphocytes and the ratio of neutrophils to lymphocytes between the two groups on the 1st and 3rd day after the operation (all P > 0.05). The total incidence of postoperative related complications in short-term drainage group and long-term drainage group was 63.2% (43/68), 70.6% (24/34), respectively, and the difference was statistically significant ( χ2 = 0.54, P = 0.461); the incidences of bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying, all grades of pancreatic leakage, grade B and C pancreatic leakage were not statistically different between the two groups (all P > 0.05); the incidence of severe postoperative related complications in short-term drainage group was higher than that in long-term drainage group [27.9% (19/68) vs. 8.8% (3/34), χ2 = 4.90, P = 0.027]. Multivariate logistic regression analysis showed that the long-term preoperative biliary drainage was an independent protective factor for postoperative severe complications (long-term drainage vs. short-term drainage: OR = 0.253, 95% CI 0.066-0.975, P = 0.046), while BMI ( OR = 1.174, 95% CI 0.986-1.398, P = 0.071) and pathological type (benign or borderline vs. malignant tumor: OR = 0.247, 95% CI 0.043-1.419, P = 0.117) were not independent influencing factors for postoperative severe complications. Conclusions:Short-term biliary drainage (≤14 d) is a risk factor for postoperative severe complications in patients with hepatopancreatic ductal periampullary tumor undergoing preoperative biliary drainage. Preoperative biliary drainage time is not associated with postoperative total complications, pancreatic leakage, bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying.

Objective:To investigate the influencing of preoperative biliary drainage on surgery-related complications after pancreaticoduodenectomy.Methods:The retrospective case-control study was conducted. The clinical data of 267 patients with periampullary space-occupying lesion who were admitted to Beijing Friendship Hospital of Capital Medical University from January 2016 to July 2020 were collected. There were 166 males and 101 females, aged 61 (range, 54?84)years. Observation indicators: (1) comparison of preoperative situations in patients with and without preoperative biliary drainage; (2) comparison of intraoperative and postoperative situations in patients with and without preoperative biliary drainage; (3) methods and efficacy of preoperative biliary drainage; (4) factors influencing surgery-related complications after pancreaticoduodenec-tomy. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(rang) or M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Comparison of preoperative situations in patients with and without preoperative biliary drainage. Of the 267 patients, there were 104 cases with preoperative biliary drainage and 163 cases without preoperative biliary drainage. Cases with malignant tumor, cases with borderline tumor, cases with chronic pancreatitis were 89, 13, 2 in patients with preoperative biliary drainage, versus 111, 41, 11 in patients without preoperative biliary drainage, showing significant differences in pathology type between them ( χ2=10.652, P<0.05). (2) Comparison of intraoperative and postoperative situations in patients with and without preoperative biliary drainage. There was no significant difference in operation time, volume of intra-operative blood loss, postoperative complications, grade B pancreatic fistula, grade C pancreatic fistula, biliary leakage, abdominal or gastrointestinal bleeding, incidence of abdominal infection, white blood cell count at postoperative day 1, white blood cell count at postoperative day 3, neutrophil-to-lymphocyte ratio at postoperative day 1, neutrophil-to-lymphocyte ratio at postoperative day 3, C-reactive protein-albumin ratio at postoperative day 1, C-reactive protein-albumin ratio at post-operative day 3, duration of hospital stay between the 104 patients with preoperative biliary drainage and the 163 patients without preoperative biliary drainage ( P>0.05). (3) Methods and efficacy of preoperative biliary drainage. Of the 104 patients with preoperative biliary drainage, there were 40 cases receiving endoscopic nasobiliary drainage with drainage time as (12±2)days, there were 38 cases receiving percutaneous transhepatic cholangial drainage with drainage time as (7±1)days, and there were 26 cases receiving endoscopic retrograde biliary drainage with drainage time as (19±2)days. The total bilirubin, direct bilirubin, aspartate transaminase, alanine aminotrans-ferase in 104 patients were (223±18)μmol/L, (134±11)μmol/L, (112±10)U/L, (160±16)U/L before biliary drainage and (144±13)μmol/L, (84±8)μmol/L, (79±8)U/L, (109±12)U/L after biliary drainage, showing significant differences in the above indicators ( t=3.544, 3.608, 2.523, 2.509, P<0.05). (4) Factors influencing surgery-related complications after pancreatocoduodenectomy. Results of multi-variate analysis showed that operation time was an independent factor influencing surgery-related complications after pancreaticoduodenectomy ( odds ratio=1.005, 95% confidence interval as 1.002?1.008, P<0.05). Conclusions:Preoperative biliary drainage does not increase the incidence of complications related to pancreaticoduodenectomy in patients with periampullary space-occupying lesion. Operation time is an independent factor influencing postoperative surgery-related complications.

Objective:To investigate the immune effects of Clostridium difficile toxoid B (CdtB) vaccine formulated with different mucosal adjuvants through microneedle immunization, and to provide ideas for the prevention and treatment of Clostridium difficile infection. Methods:CdtB vaccine was prepared with purified Clostridium difficile toxin B(TcdB) after formaldehyde detoxification. Female BALB/c mice were immunized with different doses of vaccine alone or in combination with mucosal adjuvants. The titers of specific serum IgG and fecal IgA were detected at 0 d, 7 d, 14 d, 28 d and 42 d after immunization. The protective effects of CdtB vaccine were evaluated by cell neutralization assay and Clostridium difficile challenge infection. Results:(1) With the increase of immune dose, the mice immunized with CdtB vaccine alone by microneedle not only produced better serum specific IgG, but also had higher level of IgA in feces. (2) When the mice were immunized with CdtB vaccine containing LT or CTB adjuvant by microneedle, the trend of serum specific IgG titer in each group increased with the increase of immune dose, especially in the group containing LT adjuvant. There were significant differences in the trend of specific IgA titer in feces between the adjuvant groups and the group without adjuvant, but the adjuvant effect was not obvious. (3) No significant difference in serum IgG titer was observed between the mice immunized with 10 μg CdtB by microneedle or intraperitoneal injection, but microneedle immunization significantly increased fecal IgA level. (4) The neutralization titers of specific antibodies in mouse serum after immunization and the test results of challenge protection in mice confirmed that the use of CdtB vaccine had certain protective effects.Conclusions:CdtB vaccine had better immune effects in mice through microneedle immunization, but the adjuvant effects of LT and CTB were not significant.

Objective:To explore the effect of self-made dynamic cardiovascular three-dimensional model combined with CBL (case-based learning) teaching method in the clerkship of valvular heart disease for medical students.Methods:Sixty five-year clinical medical undergraduates from Nanjing Medical University (Batch 2016) were randomly divided into experimental group and control group. The experimental group received dynamic cardiovascular 3D model combined with CBL teaching method, while the control group received traditional model combined with CBL teaching method. After the course, the teaching effect was evaluated by examination and questionnaire. SPSS 19.0 was used for independent sample t test and chi-square test. Results:Compared with the control group, the students in experimental group had higher scores of basic theoretical knowledge [(43.10±3.51) vs. (40.87±3.19)] and clinical thinking ability [(42.20±3.15) vs. (40.20±3.81)], with significant differences ( P<0.05). Furthermore, they showed higher evaluation and satisfaction to learning initiative and enthusiasm, mastery of theoretical knowledge, clinical thinking ability, classroom learning interest, classroom activity and clarity of knowledge teaching, with significant differences ( P<0.05). Conclusion:In the teaching of valvular heart disease clerkship, the application of self-made dynamic cardiovascular three-dimensional model combined with CBL teaching method, can cultivate students' clinical diagnostic thinking ability and improve teaching quality.