Effect of Nucleolin on Lymphoma Proliferation by Regulating Thymidine Kinase 1 / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of nucleolin (NCL) involved in lymphoma proliferation by regulating thymidine kinase 1 (TK1).@*METHODS@#Twenty-three patients with diffuse large B-cell lymphoma (DLBCL) were selected and divided into initial treatment group (14 cases) and relapsed/refractory group (9 cases). Serum TK1 and C23 protein in peripheral blood mononuclear cells were detected. Cell models of CA46-NCL-KD (CA46-NCL-knockdown) and CA46-NCL-KNC (CA46-NCL-knockdown negative control) were established by lentivirus vector mediated transfection in Burkitt lymphoma cell line CA46. The half maximal inhibitory concentration (IC50) of CA46-NCL-KD, CA46-NCL-KNC, and CA46 to adriamycin were detected by cell proliferation assay (MTS). The expression of NCL mRNA and protein in CA46-NCL-KD and CA46-NCL-KNC cells were dectected by Q-PCR and Western blot, respectively. The cell cycle of CA46-NCL-KD, CA46-NCL-KNC, and CA46 cells were detected by flow cytometry. The expression of TK1 protein in CA46-NCL-KD and CA46-NCL-KNC cells was detected by an enhanced chemiluminescence (ECL) dot blot assay.@*RESULTS@#The level of serum TK1 in the initial treatment group was 0.43(0-30-1.01) pmol/L, which was lower than 10.56(2.19-14.99) pmol/L in the relapsed/refractory group (P<0-01), and the relative expression level of NCL protein in peripheral blood was also significantly lower. The IC50 of CA46-C23-KD cells to adriamycin was (0.147±0.02) μg/ml, which was significantly lower than (0.301±0.04) μg/ml of CA46-C23-KNC cells and (0.338±0.05) μg/ml of CA46 cells (P<0.05). Compared with CA46-NCL-KNC cells, the expression of NCL mRNA and protein, TK1 protein decreased in CA46-NCL-KD cells, and the proportion of S phase and G2/M phase also decreased, while G0/G1 phase increased in cell cycle.@*CONCLUSION@#The increased expression of NCL in DLBCL and CA46 cells indicates low sensitivity to drug. NCL may participate in regulation of lymphoma proliferation by affecting TK1 expression, thereby affecting the drug sensitivity.

Clinical study on the level of neutrophil extracellular trap in the bile of patients with choledocholithiasis / 中华消化杂志

Objective:To investigate the activation level of neutrophil extracellular trap (NET) in the bile of patients with choledocholithiasis and its clinical significance.Methods:From May 2021 to October 2022, 130 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) at the Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University were enrolled. The patients were divided into choledocholithiasis group (90 cases) and non-choledocholithiasis group (40 cases), and the choledocholithiasis group was further divided into large stone group (maximum diameter >1 cm, 36 cases) and small stone group (maximum diameter≤1 cm, 54 cases). The bile samples were collected from 130 patients during operation and 16 choledocholithiasis patients with nasobiliary drainage at 24 h after operation.The levels of myeloperoxidase(MPO), neutrophilelastase(NE), and citrullinated histone H3(CitH3) in bile were detected by enzyme-linked immunosorbent assay.The levels of MPO, NE, and CitH3 were compared between choledocholithiasis group and non-choledocholithiasis group, between large stone group and small stone group, as well as between choledocholithiasis patients before ERCP and after ERCP. Mann-Whitney U test and Wilcoxon signed rank test were used for statistical analysis. Results:The levels of MPO, NE and CitH3 in the bile of choledocholithiasis group were 32.6 U/L(28.5 U/L), 30.6 ng/L(35.2 ng/L) and 0.37 μg/L(0.73 μg/L), respectively, which were all higher than those of non-choledocholithiasis group (19.9 U/L(36.4 U/L), 18.2 ng/L(27.4 ng/L), and 0.10 μg/L(0.25 μg/L)), and the differences were statistically significant ( Z=2.91, 3.20 and 3.34; P=0.004, 0.001 and 0.001). The levels of MPO, NE and CitH3 of large stone group were 47.0 U/L(49.4 U/L), 48.4 ng/L(39.5 ng/L) and 0.83 μg/L(1.08 μg/L), respectively, which were all higher than those of small stone group (29.3 U/L(17.5 U/L), 24.0 ng/L(25.8 ng/L), and 0.27 μg/L(0.45 μg/L)), and the differences were statistically significant ( Z=2.01, 3.58 and 3.63; P=0.044, <0.001 and <0.001). The levels of MPO, NE and CitH3 in the bile of choledocholithiasis patients after ERCP significantly decreased compare with those before ERCP (19.4 U/L(19.8 U/L) vs. 33.6 U/L(36.7 U/L), 12.7 ng/L(15.1 ng/L) vs. 22.7 ng/L(25.9 ng/L), 0.05 μg/L(0.12 μg/L) vs. 0.14 μg/L(0.27 μg/L)), and the differences were statistically significant ( Z=3.52, 3.30 and 3.18; all P<0.001). Conclusion:The activation level of NET in the bile of patients with choledocholithiasis increase, while the activation level of NET decrease after ERCP, which indicate that NET may be involved in the formation of choledocholithiasis.

Changes and formation mechanism of plasma endothelial microparticles in patients with acute pancreatitis / 临床肝胆病杂志

Objective To investigate the changes and formation mechanism of plasma endothelial microparticles (EMPs) in patients with acute pancreatitis (AP). Methods Blood samples were collected from 60 patients with AP who were treated in The First Affiliated Hospital of Anhui Medical University from August 2020 to June 2021, and these patients were divided into mild acute pancreatitis (MAP) group with 23 patients, moderate-severe acute pancreatitis (MSAP) group with 23 patients, and severe acute pancreatitis (SAP) group with 14 patients; 20 individuals who underwent physical examination were enrolled as control group.Differential centrifugation was used to obtain platelet-poor plasma, flow cytometry was used to measure the level of CD31 + CD41 - EMPs, and ELISA was used to measure the levels of endothelin-1(ET-1), von Willebrand factor (vWF), nitric oxide (NO), and vascular cell adhesion molecule-1(VCAM-1).HUVECs were stimulated by the plasma of AP patients, and then flow cytometry and qRT-PCR were used to measure the changes in EMPs, reactive oxygen species (ROS), and mitochondrial membrane potential and the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1(ICAM-1), VCAM-1, NADPH oxidase, and P-selectin.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups and within each group.The chi-square test was used for comparison of categorical data between groups, and the Pearson correlation test was used for correlation analysis. Results Compared with the control group, the MAP, MSAP, and SAP groups had a significant increase in the level of EMPs (all P < 0.05).Compared with the MAP and MSAP groups, the SAP group had a significant increase in the level of EMPs (both P < 0.05).In the patients with AP, the level of EMPs was negatively correlated with Acute Physiology and Chronic Health Evaluation Ⅱ score, Bedside Index for Severity in Acute Pancreatitis, Ranson score, CT score, and C-reactive protein ( r =0.686 2, 0.777 3, 0.713 8, 0.771 8, and 0.473 9, all P < 0.01).Compared with the control group, the MAP, MSAP, and SAP groups had significant increases in the levels of ET-1, vWF, and VCAM-1 and a significant reduction in the level of NO (all P < 0.05).Compared with the control group, the MSAP and SAP groups had the plasma that promoted the release of a large amount of EMPs (both P < 0.05).Compared with the control group, all the other groups, except the MAP group in terms of VCAM-1 and eNOS, had significant increases in the mRNA expression levels of eNOS, iNOS, ICAM-1, P-selectin, VCAM-1, and NADPH oxidase (all P < 0.05).Compared with the HC group, the MAP, MSAP, and SAP groups and the LPS group had a significant increase in the level of ROS and a significant reduction in mitochondrial membrane potential in HUVECs (all P < 0.05). Conclusion There is a significant increase in the plasma level of EMPs in AP patients, which is correlated with the severity of pancreatitis.Meanwhile, the plasma of AP patients can promote the formation of EMPs in HUVECs in vitro, which may be associated with cell oxidative injury.

Analysis on disease burden of occupational coal workers′ pneumoconiosis in Anhui Province / 中国职业医学

@# Objective To analyze the disease burden caused by occupational coal workers' pneumoconiosis (CWP) in Anhui Methods Province. A total of 1 649 patients with occupational CWP diagnosed in Anhui Province from 1950 to 2019 were selected as the study subjects using a retrospective study method. Age, gender, survival time, location, working age of disease onset, age of death, stage and date of diagnosis of CWP, comorbidities at the time of investigation, hospitalization and outpatient expenses in the past year, cost of absence from work, cost of absence from work of caregivers, and cost of nutrition and transportation were investigated. The years of life lost, years lived with disability (YLDs), disability adjusted life years (DALYs) Results and economic losses were calculated. Among these patients, 1 405 cases survived and 244 cases died. In the age range - - - of 20.0 70.0 years, the YLDs of surviving patients were 2.12 22.20 (8.19±3.59) person years. The YLDs of patients with disease vs - P complications was higher than that of patients without complications [(8.55±3.95) (7.87±3.21) person years, <0.01]. The total - - DALYs of the patients was 14 031.59 person years, and the average per capita DALYs was 8.51 person years. Its YLDs accounted for 82.0 % of the total DALYs. The total economic loss caused by CWP in the 1 405 surviving patients was 354.903 0 Conclusion million yuan, and the average per capita economic loss was 252 600 yuan. The disease burden caused by CWP is relatively high in Anhui Province. In addition to early detection, diagnosis and treatment, it is necessary to focus on prevention and treatment of CWP complications to reduce the disease burden.

The influence of HBsAg expression in liver tissue on the postoperative recurrence of HCC patients / 中华肿瘤杂志

Objective: To investigate the influence of HBsAg expression in peritumoral tissue of hepatocellular carcinoma (HCC) patients on their postoperative recurrence. Methods: The HCC patients treated in Shanghai Eastern Hepatobiliary Surgery Hospital from October 2009 to August 2010 were selected. The clinicopathological data and adjacent tissues of 718 patients were collected, and dextran polymer immunohistochemical staining was used to detect the expression of HBsAg in adjacent tissues. According to the expression of HBsAg in adjacent tissues, the tissues were divided into HBsAg positive group and HBsAg negative group. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: Among the 718 patients in the whole group, 153 were HBsAg negative and 565 were HBsAg positive. There was a statistically significant difference in serum HBV DNA level between HBsAg-positive and HBsAg-negative patients (P<0.001). The number of patients with serum DNA≥2 000 IU/ml and<2 000 IU/ml in HBsAg negative group were 52 and 93, while the patients in HBsAg positive group were 325 and 205. The cumulative recurrence rates of all patients at 1, 3, and 5 years after surgery were 30.2%, 54.3%, and 62.7%, respectively. The expression of HBsAg was related to the recurrence (P=0.038). Multivariate analysis showed that γ-GT, PT, multiple tumors, tumor length, and portal vein invasion were independent risk factors for recurrence of HCC (P<0.05). In HBeAg-negative patients with low viral load (HBV DNA <2 000 IU/ml) and without cirrhosis, the recurrence rates of HBsAg-positive patients were 14.3% and 31.0% at 3 and 5 years, respectively, compared with HBsAg negative patients (all 0), the difference was statistically significant (P=0.021). Conclusion: The positive expression of HBsAg in peritumoral tissue increases the postoperative recurrence risk of HCC patients.

Effects of vestibular spontaneous nystagmus on visual smooth pursuit function / 中华耳鼻咽喉头颈外科杂志

Objective: The aim of the study is to analyze the effects of vestibular spontaneous nystagmus(SN) on the smooth pursuit function of visual ocularmotor system. Methods: A total of 46 patients with acute unilateral peripheral vestibular syndrome with SN (26 cases of vestibular neuritis, 6 cases of Ramsay Hunt Syndrome (RHS) with vertigo, 14 cases of sudden deafness with vertigo) were included in this work. In the study group, the results of SPT and SN test with videonystagmography(VNG) were also reviewed. Taking SPT parameters, the influence of SN intensity on SPT gain, asymmetry and waveform and their correlation were analyzed.SPSS19.0 software was used for statistical analysis. Results: Among the 46 patients, there were 36 cases of SN pointing to the healthy side(SN intensity range of 2.68°/s-32.53°/s), and 10 cases of SN pointing to the affected side (SN intensity range of 2.66°/s-16.54°/s). SN intensity was divided into 3 groups, including light(0.50°/s-5.00°/s), medium(5.01°/s-10.00°/s) and strong(>10.01°/s), accounting for 14 cases(30.4%), 18 cases(39.1%) and 14 cases(30.4%), respectively. The differences of the gain of SPT to the fast phase and slow phase direction in the overall groups and light, medium and strong groups of SN intensity respectively were statistically significant(ttotal=13.338, tlight=6.184, tmedium=8.436, tstrong=8.477, all of P<0.001). The difference of SPT gain in SN fast phase direction between groups with different SN intensity was statistically significant(F=9.639, P<0.001),there was no statistically significant difference in SPT gain between the groups on the SN slow phase direction(F=1.137, P=0.330).The SN intensity significantly negatively correlated with the SPT gain of the fast phase direction of SN (r=-0.433, P=0.003), that was, the SPT gain on the fast phase direction of SN decreased with the increase of SN intensity. There was no significant correlation between SN intensity and the gain of SPT on the slow phase direction of SN (r=-0.061, P=0.687). SPT waveform analysis showed that type I, type II and type III accounted for 8 cases(17.4%), 21 cases(45.6%) and 17 cases(37.0%), respectively. The corresponding mean values of SN intensity were (3.71±0.69)°/s, (7.44±1.88)°/s, (20.04±5.53)°/s, respectively, without type IV wave. The intensity of SN was positively correlated with the asymmetric value of the gain of SPT left and right(r=0.450,P=0.002). That was, with the increase of SN strength, the asymmetric value also increased, and the worse the asymmetry of the gain of SPT left and right pursuit was, the worse the SPT waveform was. Conclusion: SPT gain, asymmetry and SPT waveforms are all affected by SN, and the greater the intensity of SN, the greater the influence on the three. When SN is strong, type III waves may occur, suggesting that acute peripheral vestibular syndrome can also affect the visual ocularmotor systems.

Clinical study on the expression of Piezo1 in small intestinal mucosa of 57 patients with Crohn′s disease / 中华消化杂志

Objective:To investigate the expression of Piezo1 in small intestinal mucosal epithelial cells of patients with Crohn′s disease (CD) and its clinical correlation with CD.Methods:From January 1st 2010 to November 30th 2020, the clinical data including age, gender, disease location and biological behavior, etc of 57 patients with CD (CD group) who underwent surgery at The First Affiliated Hospital of Anhui Medical University were retrospectively. And at same time the normal samll intestinal epithelial tissues of 10 healthy individuals who underwent colonoscopy were collected as the healthy control group. The expression of Piezo1 in small intestinal epithelial cells of CD patients with different disease sites, biological behavior and disease activity were detected by immunofluorescence staining and hematoxylin-eosin staining. The histological score system and intestinal fibrosis score were used to analyze the inflammation and fibrosis of the intestinal tissues of patients with CD. Semi-quantitative analysis of Piezo1 in small intestinal epithelial cells was analyzed by ImageJ software. And the correlation between Piezo1 expression and clinical characteristics and pathological features of small intestine was also analyzed. Independent sample t test and analysis of variance were used for statistical analysis. Results:In CD group, there were 37 males (64.9%) and 20 females (35.1%). The age was (39.1±14.2) years old, ranged from 18 to 71 years old, and the average duration of the disease was (26.5±24.1) months. There were 29 cases (50.9%)of ileal type, 26 cases (45.6%) of ileocolonin type and 2 cases (3.5%) of colonic type. There were 12 cases (21.1%) of non-penetrating non-stenotic type, 31 cases (54.4%) of stenotic type and 14 cases (24.6%) of penetrating type. There were 47 cases (82.5%) with moderate activity and 10 cases (17.5%) with severe activity. There were 17 cases (29.8%) of moderate intestinal inflammation, 40 cases (70.2%) of severe intestinal inflammation. The score of intestinal fibrosis in six cases (10.5%) was 1, 28 cases (49.1%) was 2, 18 cases (31.6%) was 3, five cases was 4. The relative expression level of Piezo1 in intestinal mucosal epithelial cells of CD group was higher than that of healthy control group (12.9±4.6 vs. 8.5±1.1), the relative expression of Piezo1 in intestinal mucosal epithelia cells of stenotic type and penetrating type CD patients were both higher than that of non-penetrating and non-stenotic CD patients (12.6±3.8 and 9.8±2.4 vs. 6.0±1.3), and the differences were all statistically significant ( t=3.00, -3.66 and -3.32, all P<0.01). The relative expression of Piezo1 in small intestinal epithelial cells of CD patients with severe intestinal inflammation was higher than that of CD patients with moderate intestinal inflammation (13.1±4.0 vs. 9.7±3.1), and the difference was statistically significant ( t=-2.65, P<0.05). The relative expression levels of Piezo1 in small intestinal epithelial cells of patients with intestinal fibrosis score of 4, 3, 2 and 1 were 17.6±5.2, 12.6±1.7, 9.1±2.1 and 5.8±1.1, respectively; the relative expression levels of Piezo1 in intestinal epithelial cells of patients scored 4 were higher than that of patients scored 3, 2 and 1, and that of patients scored 3 was higher than patients scored 2 and 1, and that of patients scored 2 was higher than that of patients scored 1, and the differences were all statistically significant ( t=-2.98, -5.10, -3.84, 4.60, 6.55 and 2.56, all P<0.05). The relative expression of Piezo1 in intestinal mucosal epithelial cells was related to the severity of intestinal inflammation and fibrosis. The more severe the intestinal inflammation and fibrosis, the higher the relative expression of Piezo1 in intestinal mucosal epithelial cells. Conclusions:The relative expression of Piezo1 in small intestinal epithelial cells is related to the biological behavior and the severity of intestinal inflammation and fibrosis of CD. It is speculated that the expression of Piezo1 in small intestinal epithelial cells may be clinically related to the process of intestinal wall fibrosis in CD to some extent, however whether it plays an important role in the process of intestinal wall fibrosis in CD and its specific mechanism need to be further studied.

Influence of indometacin on the level of platelet microparticles in patients with post-endoscopic retrograde cholangiopancreatography pancreatitis / 中华消化内镜杂志

To observe the effect of indomethacin suppository 100 mg before endoscopic retrograde cholangiopancreatography (ERCP) on the level of platelet microparticles (PMPs) in patients with post-ERCP pancreatitis (PEP). A total of 191 patients receiving ERCP were collected from June 2019 to October 2020 in the First Affiliated Hospital of Anhui Medical University and were randomly divided into the indometacin group ( n=96) and the control group ( n=95) by random number table method. The indometacin group received 100 mg indometacin suppositories before ERCP and the control group received placebo of equal quality. Levels of PMPs before operation, 3 hours and 24 hours after operation were measured by flow cytometry. The levels of IL-1, IL-6 and TNF-α in the plasma before ERCP, 3 hours and 24 hours after ERCP were also detected. The incidence of PEP in the indometacin group was 5.21% (5/96), which was significantly lower than that in the control group [13.68% (13/95), P=0.044]. The preoperative PMPs level in the indometacin group (1 910.01/μL) was slightly lower than that in the control group (2 351.87/μL) with no significant difference ( P>0.05). The PMPs levels in the indometacin group 3 hours and 24 hours after ERCP (1 671.47 /μL, 862.74/μL) were significantly lower than those of the control group (2 443.75/μL, 2 536.76/μL, both P<0.05). Inflammatory cytokines including IL-1, IL-6 and TNF-α showed the same tendency. Indometacin can reduce the incidence of PEP, for the reason that indometacin may decrease the levels of PMPs.

Incidence and risk factors for venous thrombosis among patients with inflammatory bowel disease in China: a multicenter retrospective study

Background/Aims@#Risk of venous thrombosis is increased in patients with inflammatory bowel disease (IBD); data on Asian IBD patients is limited and status quo of thrombosis screening and prophylaxis are unknown. Therefore, we aimed to investigate the incidence, screening, prophylaxis, and risk factors for venous thrombosis among Asian IBD patients. @*Methods@#Medical files of patients with Crohn’s disease (CD) and ulcerative colitis (UC) from 17 hospitals across China between 2011 and 2016 were reviewed for venous thrombosis, use of screening and prophylaxis. A case-control study was performed among hospitalized patients with venous thrombosis and their age-, sex-matched IBD controls hospitalized around the same period; disease characteristics and known provoking factors of venous thrombosis were recorded. Risk factors were analyzed in both univariate and logistic regression analyses. @*Results@#A total of 8,459 IBD patients were followed for 12,373 person-year. Forty-six patients (0.54%) had venous thrombosis, yielding an incidence of 37.18 per 10,000 person-year. Incidence increased with age, especially among CD. Less than 20% of patients received screening tests and 35 patients (0.41%) received prophylaxis. Severe disease flare was an independent risk factor for venous thrombosis (odds ratio [95% confidence interval]: CD, 9.342 [1.813– 48.137]; UC, 5.198 [1.268–21.305]); past use of steroids and extensive involvement were 2 additional risk factors in CD and UC, respectively. @*Conclusions@#Incidence of venous thrombosis in China was 37.18 per 10,000 person-year (0.54%). Use of screening and prophylaxis were rare. Severe disease flare was an independent risk factor for thrombosis among hospitalized patients.

Incidence and risk factors for venous thrombosis among patients with inflammatory bowel disease in China: a multicenter retrospective study

Background/Aims@#Risk of venous thrombosis is increased in patients with inflammatory bowel disease (IBD); data on Asian IBD patients is limited and status quo of thrombosis screening and prophylaxis are unknown. Therefore, we aimed to investigate the incidence, screening, prophylaxis, and risk factors for venous thrombosis among Asian IBD patients. @*Methods@#Medical files of patients with Crohn’s disease (CD) and ulcerative colitis (UC) from 17 hospitals across China between 2011 and 2016 were reviewed for venous thrombosis, use of screening and prophylaxis. A case-control study was performed among hospitalized patients with venous thrombosis and their age-, sex-matched IBD controls hospitalized around the same period; disease characteristics and known provoking factors of venous thrombosis were recorded. Risk factors were analyzed in both univariate and logistic regression analyses. @*Results@#A total of 8,459 IBD patients were followed for 12,373 person-year. Forty-six patients (0.54%) had venous thrombosis, yielding an incidence of 37.18 per 10,000 person-year. Incidence increased with age, especially among CD. Less than 20% of patients received screening tests and 35 patients (0.41%) received prophylaxis. Severe disease flare was an independent risk factor for venous thrombosis (odds ratio [95% confidence interval]: CD, 9.342 [1.813– 48.137]; UC, 5.198 [1.268–21.305]); past use of steroids and extensive involvement were 2 additional risk factors in CD and UC, respectively. @*Conclusions@#Incidence of venous thrombosis in China was 37.18 per 10,000 person-year (0.54%). Use of screening and prophylaxis were rare. Severe disease flare was an independent risk factor for thrombosis among hospitalized patients.

Effect of different cytopathological grading standards on the diagnosis of pancreatic cancer by endoscopic ultrasound-guided fine needle aspiration / 临床肝胆病杂志

ObjectiveTo investigate the effect of different cytopathological grading standards on the efficiency of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of pancreatic cancer. MethodsRelated clinical data and pancreatic cytopathological results were collected from 256 patients with pancreatic space-occupying lesions who underwent EUS-FNA in The First Affiliated Hospital of Anhui Medical University from May 2011 to March 2019, and the influencing factors for the diagnostic efficiency of EUS-FNA were analyzed based on surgical pathology and follow-up results. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of different cytopathological grading standards in the diagnosis of pancreatic cancer. ResultsA total of 67 patients who were lost to follow-up were excluded, and a total of 189 patients were included in the study. According to the Papanicolaou cytopathological standard, there were 47 cases of heterotypic cells, 25 cases of suspected cancer cells, 20 cases of cancer cells, and 97 cases without tumor cells based on EUS-FNA. A total of 133 patients were confirmed to have pancreatic cancer by postoperative pathology and follow-up results, among whom 52 had no tumor cells, 36 had heterotypic cells, 25 had suspected cancer cells, and 20 had cancer cells based on cytopathological results. EUS-FNA had a true positive rate of 6090% (81 patients) and a false negative rate of 39.10% (52 patients) in the diagnosis of pancreatic cancer; for the 56 patients without pancreatic cancer, EUS-FNA had a false positive rate of 19.64% (11 patients) and a true negative rate of 80.36% (45 patients). EUS-FNA had an area under the ROC curve of 0.643 (95% confidence interval: 0.561-0.724) in the diagnosis of pancreatic cancer. In combination with different cytopathological grading standards and with the diagnostic criteria of “the identification of heterotypic cells or suspected cancer cells or cancer cells was considered positive”, “the identification of suspected cancer cells or cancer cells was considered positive”, and “the identification of cancer cells was considered positive”, the results showed that the diagnostic criteria of “the identification of heterotypic cells or suspected cancer cells or cancer cells was considered positive” improved the efficiency of EUS-FNA in the diagnosis of pancreatic cancer, with a sensitivity of 50.38% and a specificity of 75.00%. Among the 189 patients, 13 (6.88%) experienced complications after EUS-FNA, which included hyperamylasemia and abdominal pain. ConclusionThe combination of different cytopathological grading standards can help improve the efficiency of EUS-FNA in the diagnosis of pancreatic cancer.

Establishment of A Mixed Chimeric Mouse Model of Allogeneic Bone Marrow Transplantation and Its Influencing Factors / 中国实验血液学杂志

OBJECTIVE@#To establish a mouse mixed chimerism (MC) model of nonmyeloablative allogeneic bone marrow transplantation(allo-BMT) and explore its affecting factors.@*METHODS@#The MC model was established by nonmyeloablative allo-BMT followed by high-dose post-transplant cyclophosphamide (PTCY). 123 mice in the experiments was retrospectively analyzed, and the factors related with the chimerism were explored with the univariate and multivariate logistic regression analysis. A multivariate linear regression was performed by R project to obtain a mathematical model for predicting the chimeric level with relevant affecting factors.@*RESULTS@#The model presented mixed chimerism on day 14 after transplantation, and was characterized by a donor lymphocyte infusion (DLI) which significantly promoted donor engraftment on day 15, but transfplantation of PBS in control group was failed. Among 123 mice, 47 (38.21%) mice were MC, while 76 (61.79%) mice were non-MC in 123 mice, respectively; univariate analysis showed that the baseline body weight of mice (P=0.001, 17.84±1.19 g vs 18.50±0.94 g), total body irradiation(TBI，P=0.048) and the using of cyclophosphamide (P=0.16) were affected the chimeric state of mice, while the number of infusing cells and the time of detection showed no significant effects. Multivariate regression analysis showed that under certain conditions, the body weight of mice on day 0 was an independent factor affecting chimeric levels (OR=0.493, 95% CI 0.307-0.791, P=0.003). Through R project multiple linear regression, the math model was achieved, which was chimerism=6.09-12×weight(g)+80.03×TBI(Gy)-4.4×cell-counts (× 10@*CONCLUSION@#The experiment presents a method for establishing a mixed chimeric mice model after non-myeloablative bone marrow transplantation and constructs a mathematical model with relevant factors affected chimerism status.

Chemical constituents from Morinda citrifolia and their inhibitory activities on proliferation of synoviocytes in vitro / 中国中药杂志

The chemical constituents from the stems and leaves of Morinda citrifolia were isolated and purified by column chromatography methods with silica gel, ODS, Sephadex LH-20 and preparative high performance liquid chromatography(HPLC). The structures of the isolated compounds were identified by physicochemical properties and spectroscopic analysis, as well as comparisons with the data reported in literature. 17 compounds were isolated from the 90% ethanol extract of the stems and leaves of M. citrifolia, and were identified as 9,10-dihydroxy-4, 7-megastigmadien-3-one(1), 5,12-epoxy-6,9-hydroxy-7-megastigmen-3-one(2), fukinone(3), β-eudesmol(4), sarmentol F(5), 4, 5-dihydroblumenol A(6), 3-hydroxy-β-ionone(7), aristol-8-en-1-one(8), ergosta-7-en-3β-ol(9), ergosta-7-ene-3β,5α,6β-triol(10),(22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol(11), olivil(12), 4-epi-larreatricin(13), chushizisin Ⅰ(14), rabdosia acid A(15), glycerol monolinoleate(16) and(9Z,12Z,15Z)-2,3-dihydroxypropyl octadeca-trienoate(17). All compounds were isolated from M. citrifolia for the first time. All isolated compounds were evaluated for their anti-rheumatoid arthritis activities via examining their inhibitory activities on the proliferation of synoviocytes in vitro using MTS met-hod. Compounds 1-11 showed significant anti-rheumatoid arthritis activities, displaying the inhibitory effects on the proliferation of MH7 A synovial fibroblast cell with the IC_(50) values ranging from(38.69±0.86) to(203.45±1.03) μmol·L~(-1).

Endoscopic ultrasound features of distal biliary stricture / 临床肝胆病杂志

Objective To investigate the endoscopic ultrasound (EUS) features of distal biliary stricture (DBS), and to provide a clinical basis for the evaluation of DBS by EUS. Methods Related clinical data were collected from 175 patients with DBS who underwent EUS examination in The First Affiliated Hospital of Anhui Medical University from April 2016 to March 2020 to analyze their clinical manifestation, laboratory examination results, imaging findings, and EUS findings, and the patients were followed up to summarize the EUS features of DBS. The chi-square test was used for comparison of categorical data between groups, and the t -test was used for comparison of continuous data between groups. Results Among the 175 patients with DBS, 85(48.57%) had benign DBS and 90(51.43%) had malignant DBS. Compared with the patients with benign DBS, the patients with malignant DBS had a significantly longer length of stricture on EUS (14.1±3.0 mm vs 7.9±3.0 mm, t =13.358, P < 0.001) and significantly higher incidence rates of the characteristic changes on EUS such as hypoechoic space-occupying lesions in lumen (57.8% vs 34.1%, χ 2 =9.843, P =0.002), peripheral lymph node enlargement (26.7% vs 12.9%, χ 2 =5.147, P =0.023), and pancreatic duct dilatation (51.1% vs 28.2%, χ 2 =9.532, P =0.002). EUS combined with magnetic resonance cholangiopancreatography had a sensitivity of 70.6% in the diagnosis of benign DBS and a sensitivity of 92.2% in the diagnosis of malignant DBS. Conclusion The characteristic EUS features of DBS, such as long length of stricture, hypoechoic lesion, peripheral lymph node enlargement, and pancreatic duct dilatation, may help with the differential diagnosis of DBS in clinical practice.

Advances in inorganic nanomaterials regulated autophagy in cancer treatment / 医学研究生学报

Autophagy represents one of the essential cellular mechanism to maintain homeostasis within cells, performing multiple biological functions during tumorigenesis. Base on the unique physicochemical properties of inorganic nanomaterials, supplemented by easy modification and targeting and so on, they could be used to regulate autophagy, controlling the occurrence and development of tumor and finally achieve treatment. This article primarily reviews the application of several representative inorganic nanomaterials, such as Gold nanoparticles, Silver nanoparticles, Iron oxide nanoparticles, Fullerene C60 nanomaterials, Graphene oxide nanomaterials in regulating autophagy of tumor cells and achieving treatment in recent years.

Clinical study on the changes of platelet microparticles in inflammatory bowel disease / 中华消化杂志

Objective:To investigate the relationship between the expression level of platelet microparticle (PMP) and the disease activity of inflammatory bowel disease (IBD) in IBD patients, and to explore the ability of PMP from different sources to induce the formation of neutrophil extracellular trap (NET) in vitro. Methods:From May 2018 to July 2019, 118 patients with IBD admitted to the Department of Gastroenterology at The First Affiliated Hospital of Anhui Medical University were selected, among whom 54 cases were ulcerative colitis (UC) patients (UC group) and mild, moderate and severe cases were 17, 25 and 12, respectively; and 64 cases were Crohn′s disease (CD) (CD group), 6 were in remission stage, and mild, moderate, severe cases were 27, 22 and 9, respectively. During the same period, 35 healthy individuals with normal checkups were selected as the healthy control group. Specimens were collected and the expression levels of PMP were measured by flow cytometry.And the correlation between the expression level of PMP and the disease activity index (DAI) score was analyzed.NET formation experiment groups were set up, including neutrophils of healthy control group (6 cases), neutrophils of IBD group (6 cases), neutrophils of healthy controls + PMP of IBD group (12 cases) and neutrophils of healthy controls+ PMP group (6 cases). After immunofluorescence staining, the proportion of NET formation of each group was observed under laser scanning confocal microscopy (LSCM). Mann-Whitney U test, Spearman correlation analysis and Independent-sample t test were used for statistical analysis. Results:The expression levels of PMP in peripheral blood of the UC group and the CD group were 2 184.5(2 817.0)/μL and 2 209.0(2 409.0)/μL, respectively, which were all higher than that of the healthy control group (776.0(407.0)/μL), and the differences were statistically significant ( U=-6.018 and -6.426, both P<0.01). The expression level of PMP of patients with severe UC was 3 873.0(4 611.3)/μL, which was higher than those of patients with mild or moderate UC (1 248.0(1 888.0)/μL and 1 432.0(1 783.0)/μL, respectively), and the differences were statistically significant ( U=-2.745 and -2.547, both P<0.05). The expression level of PMP of patients with severe CD was 5 658.0(5 067.5)/μL, which was higher than those of patients with mild or moderate CD or in remission (1 327.5(1 934.0)/μL, 1 405.0(2 965.0)/μL and 2 300.0(1 552.0)/μL, respectively), and the differences were statistically significant ( U=-1.650, -1.955 and -1.306, all P<0.05). There was no statistically significant difference in the expression level of PMP between the UC group and the CD group, between the mild and moderate UC patients, and between the CD in remission and the mild, moderate patients (all P>0.05). The results of correlation analysis showed that the expression levels of PMP in peripheral blood of patients with UC or CD were positively correlated with DAI score and CRP ( r=0.406, 0.358, 0.325, and 0.256; all P<0.05). The proportion of NET formation in the neutrophils of healthy control+ PMP of IBD group was (14.67±5.35) %, which was higher than those of the neutrophils of healthy control groap, neutrophils of IBD group and neutrophils of healthy control+ PMP group ((2.00±0.63)%, (1.67±0.82)% and (5.83±2.86)%), and the differences were statistically significant ( t=5.694, 8.230 and 3.748, all P<0.05). There was no statistically significant difference in the proportion of NET formation between the neutrophils of healthy control group and the neutrophils of IBD group ( P>0.05). Conclusions:The expression level of PMP in peripheral blood of IBD patients increases and is correlated with the disease activity degree in IBD patients. PMP has the ability to induce the NET formation in neutrophils. Moreover, PMP of IBD patients is more likely to induce NET formation than those of healthy individuals, which may be involved in the intestinal inflammatory process by activating neutrophils to produce NET.

Multicenter long-term follow-up study on the risk factors of dysplasia in ulcerative colitis / 中华消化杂志

Objective:To investigate the risk factors of dysplasia in patients with ulcerative colitis (UC) in China.Methods:From March 1st, 2012 to December 30th, 2013, a total of 154 UC patients were prospectively enrolled from the following 11 hospitals, Xijing Hospital of Digestive Diseases, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Peking Union Medical College Hospital, Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Nanfang Hospital affiliated to Southern Medical University, China-Japan Friendship Hospital, The Second Hospital of Hebei Medical University, West China Hospital affiliated to Sichuan University, The Seventh Medical Center of PLA General Hospital, Zhongshan Hospital affiliated to Xiamen University, and the First Affiliated Hospital of Anhui Medical University. The patients were followed up till December 1st, 2017. All the UC patients underwent colon endoscopy and histopathological evaluation. T test and Chi-square test were used for statistical analysis. Cox proportional risk model was used for identifying the risk factors of dysplasia in UC patients. Results:Finally, 133 UC patients were enrolled, the age was (50.0±11.9) years, the diagnosis age was (35.5±11.6) years, the course of disease was (14.5±6.7) years, and the number of endoscopic examinations was (3.4±1.6) times. A total of 21 patients were detected with dysplasia. No patients were detected with colorectal cancer. The results of univariate analysis revealed that the diagnosis age (hazard ratio ( HR)=1.05, 95% confidence interval ( CI) 1.01 to 1.10, P=0.009) and extensive colitis ( HR=2.92, 95% CI 0.97 to 8.79, P=0.057) were factors with statistically significant difference. The results of multivariate analysis revealed that the old age at diagnosis ( HR=1.06, 95% CI 1.02 to 1.11, P=0.003) and extensive colitis ( HR=3.68, 95% CI 1.21 to 11.19, P=0.022) were independent risk factors of dysplasia in UC patients. The cumulative incidence of dysplasia of UC patients with extensive colitis was higher than that of patients with left-sided colitis (24.3%, 17/70 vs. 6.3%, 4/63), and the difference was statistically significant ( χ2=8.023, P=0.005). Conclusions:Extensive colitis and older age at diagnosis are two independent risk factors of dysplasia in UC patients of our country. The cancer monitoring should be strengthened in UC patients with long course of disease and extensive colitis.

Clinical characteristics and treatment on acute obstructive suppurative pancreatic ductitis / 中华胰腺病杂志

Objective To analyze the clinical characteristics, treatments and prognosis of acute obstructive suppurative pancreatic ductitis ( AOSPD) , and to discuss its pathogenesis, diagnosis and treatment strategy. Methods 63 AOSPD cases reported in Chinese and foreign literature from June 1993 to January 2019 were collected. The sex, age of onset, etiology and potential risk factors, clinical manifestations, laboratory examinations, imaging findings, treatments and prognosis were recorded. Results The male to female ratio was 53 / 10, and the median age of onset was 59 years. The etiology and risk factors included chronic pancreatitis, pancreatic neoplasms, diabetes mellitus, history of endoscopic intervention and alcoholism before the onset of AOSPD. The main clinical manifestations were epigastric pain and fever, and sepsis and shock might occur in a few cases. The serum amylase was 13-1946 ( IU/L) at the early stage of onset and it decreased to varying degrees after treatments. Imaging examination showed that pancreatic duct dilatation was found in 54 patients and pancreatic duct stones were found in 42 patients. Pancreatic juice culture was bacteria-positive in more than 31 cases, and the common pathogenic bacteria were Enterococcus and Escherichia coli. Therapeutic methods included endoscopic pancreatic stent implantation ( n=36 ) , endoscopic nasopancreatic drainage (n=22), surgical operation (n=4) and antibiotic treatment, and the condictions in most of the patients were improved to some extent after treatments. Conclusions Older age, male, chronic pancreatic disease, history of endoscopic intervention and drinking, and diabetes mellitus were the main etiological factors of AOSPD. The clinical manifestations of AOSPD were nonspecific but could be complicated by severe complications. Imaging examination and pancreatic juice culture can help to confirm the diagnosis. Antibiotic therapy, timely endoscopic interventions and surgical procedures can improve the short-term prognosis.

Dose-response Relationship of Dexmedetomidine Combined with Sufentail for Postoperative Intravenous Analgesia in Video-assisted Thoracoscopic Surgery / 中国医学科学院学报

Objective To investigate the 50% effective dose(ED)and 95% effective dose(ED)of dexmedetomidine(DEX)combined with 0.032 μg/(kg·h)sufentanil as well as its analgesic effect for patient-controlled intravenous analgesia(PCIA)after video-assisted thoracoscopic surgery(VATS).Methods Totally 25 patients undergoing elective VATS were enrolled. DEX and 0.032 μg/(kg·h)sufentanil were used for postoperative PCIA. The loading dose of DEX was 0.048 μg/(kg·h),and the dose difference between two adjacent patients was 0.008 μg/(kg·h). The DEX dose of a current patient was determined by whether the previous patient was satisfied with postoperative analgesic effect. If the previous patient was satisfied with postoperative analgesic effect,the DEX dose of the current patient was decreased by 0.008 μg/(kg·h);and if the previous analgestic effect was not satisfactory,DEX dose of the current patient was increased by 0.008 μg/(kg·h). The study endpoint was dexmedetomidine dose was<0.008 μg/(kg· h) within 7 upper and lower cycles in 7 consecutive cases. Finally,the probability unit regression was used to estimate the ED and ED of DEX and their 95% .Results When DEX combined with 0.032 μg/(kg·h) sufentanil was used for postoperative PCIA in young patients undergoing VATS,the ED and EDof DEX were 0.0346 μg/(kg· h)[95%:0.0283-0.0408 μg/(kg·h)] and 0.0459 μg/(kg·h)[95%:0.0400-0.0880 μg/(kg·h)],respectively. No adverse reaction such as vomiting,respiratory depression,or bradycardia occurred. The average Visual Analogue Scale(VAS)scores at rest(=-5.128,=0.000)and cough(Z=-6.642,=0.000)and the Ramsay sedation score(Z=-2.335,=0.020)within 6 hours after surgery were higher than those after 6 hour.Conclusion DEX combined with 0.032 μg/(kg·h) sufentanil are effective for postoperative PCIA in patients undergoing VATS when the ED and ED are 0.0346 μg/(kg·h)and 0.0459 μg/(kg·h),respectively.

Effects of resolvin D1 on the autophagy in acute pancreatitis in mice / 中华消化杂志

Objective@#To investigate the effects of resolvin D1 on autophagy in the prevention of acute pancreatitis (AP) in mice. @*Methods@#Thirty C57BL/6 mice were divided into control group, AP group and resolvin D1 group. AP model was established by intraperitoneal injection of cerulein at 50 μg·kg-1·h-1. Resolvin D1 was intraperitoneally given at 50 μg/kg one hour before and four hours after modeling. The mice of control group were intraperitoneally injected the same volume of 0.9% sodium chloride solution. The serum levels of amylase and lipase were measured by colorimetric method. The pathological injury of the lung and pancreatitis were observed under optical microscope. Autophagic vacuoles in acinar cells of pancreas of mice were evaluated by transmission electron microscope. And the expressions of autophagy related markers Beclin-1, p62 and LC3-Ⅱ at the mRNA and protein levels in pancreas of mice were detected by real time quantitative polymerase chain reaction (RT-qPCR) and Western blotting method. One-way analysis of variance and SNK-q were performed for statistical analysis. @*Results@#There were statistically significant differences in serum amylase and lipase levels between control group, AP group and resolvin D1 group (F=62.99 and 149.69, both P<0.01). The serum amylase and lipase levels of mice in resolvin D1 group were lower than those of AP group ((525.08±41.12) U/L vs. (752.62±42.03) U/L, (758.24±134.77) U/L vs. (1 201.06±112.53) U/L), and the differences were both statistically significant (both SNK-q test and P<0.01). In addition, there were statistically significant differences in the ratio of the pancreas and lung wet mass to body mass between control group, AP group and resolvin D1 group (F=11.36 and 18.51, both P<0.05). Pathological injury scores of pancreas and lung of resolvin D1 group were both lower than those of AP group (3.3±0.6 vs. 5.6±0.6, 5.4±0.5 vs. 8.8±0.4), and the differences were statistically significant (both SNK-q test and P<0.05). The results of transmission electron microscopy observation revealed that the number of autophagic vacuole of resolvin D1 group was less than that of AP group, and the size was smaller. Moreover, there were statistically significant differences in Beclin-1, p62 and LC3-Ⅱ mRNA between control group, AP group and resolvin D1 group (F=270.95, 151.83 and 124.77, all P<0.05). The relative expression mRNA levels of Beclin-1, p62 and LC3-Ⅱ of resolvin D1 group were 1.59±0.12, 2.75±0.27 and 1.34±0.14, respectively, which were lower than those of AP group (2.68±0.13, 3.32±0.30 and 3.37±0.26, respectively), and the differences were statistically significant (all SNK-q test and P<0.05). There were statistically significant differences in the expressions of Beclin-1, p62 and LC3-Ⅱat the protein level between control group, AP group and resolvin D1 group (F=116.63, 384.40 and 192.45, all P<0.05). The expressions of Beclin-1, p62 and LC3-Ⅱ at protein level of resolvin D1 group were 0.98±0.03, 0.57±0.04 and 0.31±0.03, respectively, which were lower than those of AP group (1.34±0.07, 1.02±0.03 and 0.48±0.04, respectively), and the differences were statistically significant (all SNK-q test and P<0.05). @*Conclusion@#Resolvin D1 ameliorates the severity of AP by attenuating the impaired autophagy and restoring autophagic flux in AP mice.