ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease （CHD） based on real-world clinical data， to establish a risk prediction model of integrated traditional Chinese and western medicine， in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD， who were divided into a training set and a validation set at a 7∶3 ratio. General information， traditional Chinese medicine （TCM）-related data， and laboratory test results were uniformly collected. After a one-year follow-up， patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination， calibration， and clinical decision curve analysis. ResultsA total of 682 patients were included， with 477 in the training set and 205 in the validation set， among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history ［OR = 6.93， 95% CI （1.58， 30.45）］， wiry pulse ［OR = 2.58， 95% CI （1.42， 4.72）］， weak pulse ［OR = 3.97， 95% CI （2.06， 7.67）］， teeth-marked tongue ［OR = 4.38， 95% CI （2.32， 8.27）］， blood stasis constitution ［OR = 2.17， 95% CI （1.06， 4.44）］， phlegm-stasis mutual syndrome ［OR = 3.64， 95% CI （1.87， 7.09）］， and elevated non-high-density lipoprotein cholesterol ［OR = 1.30， 95% CI （1.01， 1.69）］ as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability， with an area under the receiver operating characteristic curve （AUC） of 0.818 ［95% CI （0.781， 0.852）］ in the training set and 0.816 ［95% CI （0.779， 0.850）］ in the validation set. The Hosmer-Lemeshow test showed good calibration （χ² = 4.55， P = 0.80）， and the model's predictive ability was stable. When the threshold probability exceeded 5%， the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure， teeth-marked tongue， weak pulse， wiry pulse， phlegm-stasis mutual syndrome， blood stasis constitution， and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors， which showed good discrimination， calibration， and clinical utility， providing a scientific basis for predicting readmission events in patients with stable angina.

ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

Objective:To investigate the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of pediatric pancreaticobiliary maljunction (PBM).Methods:Data of 40 pediatric patients under 14 with PBM diagnosed and treated by ERCP at Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from November 2012 to September 2022 were collected. PBM types, ERCP-related diagnosis and treatment, adverse events and prognosis were retrospectively analyzed.Results:Nineteen cases were P-B type (joining of common bile duct with pancreatic duct), 17 were B-P type (joining of pancreatic duct with common bile duct), and 4 were complex type. Forty children with PBM underwent 50 ERCP-related operations, among which 48 procedures succeeded. One case failed during cannulation of ERCP, replaced by rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP) afterwards. There were no serious postoperative adverse events such as bleeding, perforation or death. Thirty-four patients (85%) were followed up successfully, among which 14 underwent further surgery and 20 continued conservative treatment.Conclusion:ERCP is the golden standard to diagnose pediatric PBM, and it is also safe and effective treatment for PBM.

Objective:To explore the effectiveness and safety of endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD).Methods:A retrospective analysis was conducted on data of 16 patients who underwent EUS-PD because of endoscopic retrograde pancreatography (ERP) failure, poor effectiveness or anatomical changes and couldn't undergo the routine ERP in Nanjing Drum Tower Hospital from June 2018 to July 2022. The technical success of EUS-PD, clinical efficacy and post-procedure adverse events were analyzed.Results:In the 16 patients, there were 14 males and 2 females, with age of 50.69±12.95 years. A total of 19 times of EUS-PD operations were included, 3 of them were rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP), 15 transgastric or transenteric EUS-guided stent placement and 1 was EUS-guided nasopancreatic duct placement. Technical success was achieved in 84.21% (16/19) patients, and among whom 93.75% (15/16) achieved clinical success. The overall incidence of postoperative adverse events was 52.63% (10/19) including 47.37% (9/19) abdominal pain, 15.79% (3/19) fever and 15.79% (3/19) postoperative pancreatitis. All adverse effects were relieved after general conservative treatment and no primary disease or surgery-related death occurred. The mean follow-up was 17.6 (8.2,22.3) months and 93.75% (15/16) of the patients were followed up. By the time of follow-up, 76.92% (10/13) of the patients who had successfully received EUS-PD had no recurrence of abdominal pain or distension.Conclusion:EUS-PD is a safe and effective alternative therapy for those with pancreatic diseases with ERP failure, poor efficacy or anatomical changes.

Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.

OBJECTIVE: To observe the therapeutic effect of tetramethylpyrazine on immune-mediated bone marrow failure (BMF) induced by different doses of X-ray exposure in C57 mice. METHODS: C57BL6 mice were randomized into 4 groups, including a blank control group and 3 X-ray exposure groups with X-ray exposure at low (5.0 Gy), moderate (5.75 Gy), and high (6.5 Gy) doses. After total body irradiation with 0.98 Gy/min X-ray. The mice as recipient received injections of 4×10 lymphocytes from DBA/2 mice via the tail vein within 4 h. The survival rate of the recipient mice, peripheral blood cell counts, bone marrow nucleated cell count, and bone marrow pathology were examined at 14 days after the exposure. In the subsequent experiment, C57 mice were exposed to 5.0 Gy X-ray and treated with intraperitoneal injection of tetramethylpyrazine at the low (5 mg/mL), moderate (10 mg/mL), or high (20 mg/mL) doses (12 mice in each group) for 14 consecutive days, and the changes in BMF were observed. RESULTS: X-ray exposure, especially at the high dose, resulted in significantly lowered survival rate in the mouse models of BMF at 14 days. As the X-ray dose increased, the mice showed significantly reduced peripheral blood counts of red blood cells, white blood cells, platelets and lowered bone marrow nucleated cell counts with obvious bone marrow congestion and reduction of nucleated cells ( < 0.05 or 0.001). In the mice exposed to 5.0 Gy X-ray, tetramethylpyrazine at the high dose most obviously increased bone marrow nucleated cells ( < 0.01) and red blood cells ( < 0.001), and even at the low dose, tetramethylpyrazine significantly increased the counts of white blood cells ( < 0.05) and platelets ( < 0.01) following the exposure. Tetramethylpyrazine dose-dependently alleviated bone marrow hyperemia, increased bone marrow nucleated cell counts, and lowered Fas protein expression in the bone marrow. CONCLUSIONS X-ray irradiation at 5.0 Gy is suitable for establish mouse models of immune-mediated BMF. Tetramethylpyrazine promotes bone marrow repair by regulating Fas cell apoptosis signals, which further expands the traditional Chinese medicine theory of "removing blood stasis to create new."
Animals ; Bone Marrow ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Pyrazines ; Whole-Body Irradiation

Objective To investigate the clinicopathological characteristics and the expression of related molecular markers of heterotopic pancreas for better understanding and avoiding overtreatment of this disease.Methods From 24th March 2009 to 10th November 2016,92 patients with heterotopic pancreas in upper digestive tract diagnosed after endoscopic submucosal dissection(ESD),were collected. Tissues were sectioned and pathologically classified by Heinrich classification.The expressions of seven different molecular markers including cytokeratin(CK)19,insulin,trypsin,Ki-67,p53,CD133 and CD56 were detected by immunohistochemistry staining. Clinical features, pathological features and immunohistochemical results were retrospectively analyzed.Analysis of variance and Kruskal-Wallis test were used.Results According to Heinrich classification,the percentages of type Ⅰ,Ⅱ,and Ⅲ of heterotopic pancreas were 27.2%(25/92),63.0%(58/92)and 9.8%(9/92),respectively.There was no type Ⅳ patients.The heterotopic pancreas mainly located in stomach with proportion being about 91.3%(84/92)of the total heterotopic pancreas.CK19(the marker of pancreas ducts),insulin(as marker of endocrine function)and trypsin(as the marker of exocrine function)were all expressed in heterotopic pancreas.The positive rate of CD56,a pancreatic neuroendocrine marker,was 66.3%(61/92).The umbilicus like depression was the typical endoscopic appearance of heterotopic pancreas,which only found in 29 patients(31.5%).The average rate of Ki-67,cell proliferation index,was(2.08 ± 1.41)%.The expression of mutant p53 was negative in all 92 cases of heterotopic pancreas.The average staining area of CD133,a marker of pancreatic cancer stem cell,was(2.53 ± 2.43)%.The average follow-up period of 92 patients was(43.6 ± 27.5)months.No relapse and malignant change were found and all patients survived after ESD.Conclusions Heterotopic pancreas has normal pancreatic construction and function.The cell proliferation index is low in heterotopic pancreas and no mutant p53 expression is found.The expression of CD133 is also low.Heterotopic pancreas is a congenital benign disease which requires a long-term follow-up rather than overtreatment.

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

Objective To evaluate the potential malignancy, prognosis and risk factors for intraductal papillary mucinous neoplasm(IPMN), which were classified into different risk levels based on Fukuoka guideline. Methods A retrospective analysis of patients with IPMN diagnosed at Nanjing Drum Tower Hospital from 2009 to 2016 was conducted. Clinical characteristics,treatment and prognosis of IPMNs were analyzed. Results A total of 94 IPMN patients were included and divided into 3 groups according to Fukuoka guideline,46 patients in high-risk(HR)group,30 in group of worrisome features(WF), and 18 in low-risk(LR)group. For patients undergoing surgery treatment, there were 5 cases(19.2%,5/26)in HR group and 2 cases(12.5%,2/16)in WF group whose postoperative pathological findings were malignant (P=0.690). The 5-year survival rates after operations were 73.9% and 77.0% in HR and WF group, respectively(P=0.830). For patients without surgery treatment, in a 5-year follow-up, there were 6 cases (33.3%,6/18),2 cases(16.7%,2/12)and 0(0.0%,0/18)progressing into pancreatic cancers in HR, WF and LR groups,respectively(P<0.05). In addition,among the three groups,the 5-year survival rates were 49.5%,85.7% and 100.0%(P=0.025). Jaundice was significantly related to prognosis(P<0.01) and the hazard ratio was 8.883(95%CI:2.953-26.721). Conclusion Jaundice is a predictive risk factor for survival of IPMN. As for the treatment to IPMN, patients in HR group should receive surgery treatment while those in LR group can be followed up. For patients in WF group,the treatment should be customized, with evaluation of predictive risk factors,and operations can be performed when needed.

Objective To study the influence of bFGF gene transfected bone marrow-derived mesenchymal stem cells (BMSCs) on the inflammatory cytokines of COPD rat. Methods The BMSCs were separated from SD rat and cultured and then bFGF gene was imported to BMSCs by liposome transfection method. The samples were prepared into six groups: normal control group, COPD group (A), BMSCs group (B), pcDNA3.1-BMSCs group (C), bFGF-pcDNA3.1-BMSCs group (D), and bFGF group (E). The expressions of TNF-α and IL-1β by QRT-PCR were detected. Results Compared with COPD group, TNF-α and IL-1β genes from groups B to D dropped significantly (P < 0.05). The changes of TNF-α and IL-1β genes among groups B to D showed no significant difference (P > 0.05). Conclusion BFGF transfected BMSCs, sample BMSCs and pcDNA3.1 transfected BMSCs can inhibit the expression of inflammatory cytokines of TNF-α and IL-1β, but there is no obvious advantage in comparison to bFGF transfected BMSCs and sample BMSCs in respect of inhibiting the expression of inflammatory cytokines of TNF-α and IL-1β.