Objective To investigate the association between intraoperative hypotension and post-operative acute kidney injury(AKI)in patients undergoing brain tumor resections.Methods A total of 428 patients undergoing elective craniotomy for tumor resection were selected,276 males and 152 females,aged≥18 years,BMI 15-36 kg/m2,ASA physical statusⅡ orⅢ.Based on postoperative occurrence of AKI,the patients were divided into two groups:the AKI group and the control group.This study defined three thresholds for hypotension,including MAP during surgery below 65 mmHg,60 mmHg,and 55 mmHg.Multivariate logistic regression was used to analyze the correlation between intraoperative hypotension and postoperative AKI under three thresholds.Results A total of 107 patients had postoperative AKI.The re-sults of multivariable regression analysis indicated that intraoperative MAP＜65 mmHg(OR = 1.11,95%CI 1.03-1.20,P = 0.010)and intraoperative MAP＜60 mmHg(OR = 1.12,95%CI 1.02-1.23,P = 0.017)were associated with postoperative AKI.Conclusion Intraoperative MAP＜65 mmHg or 60 mmHg is associated with postoperative AKI in patients undergoing brain tumor resection.

Objective To compare and analyze the application value of domestic Octoparms and imported Celect inferior vena cava filter(IVCF)in the interventional treatment of venous thromboembolism(VTE).Methods Forty patients with VTE were randomly divided into Octoparms group(experimental group)and Celect group(control group)according to the double-blinded method of the central random system.All the patients underwent filter placement,catheter-directed thrombolysis and filter retrieval.The primary end point was the success of filter placement and retrieval,and the secondary end point included indwelling complications such as the occurrence of pulmonary embolism(PE)and filter tilt and migration.Results Forty patients were enrolled in this study,22 patients and 18 patients were divided into the experimental group and the control group,respectively.Among them,11 cases were identified with right lower extremity deep vein thrombosis,29 cases with left lower extremity deep vein thrombosis,17 cases with PE,and 6 cases with inferior vena cava thrombosis.The success rate of IVCF placement was 100%in all participants.Immediately after filter place-ment,the angle of filter tilt was(3.8±2.3)° in the experimental group and(4.9±2.8)° in the control group(t=1.44,P=0.16).Filter retrieval was successful in 21 cases(21/22,95.5%)of the experimental group and 17 cases(17/18,95.5%)of the control group.There was no significant difference between the two groups(t=0.14,P=0.89).The mean indwelling time of filter was(8.0±2.1)days in the experimental group and(9.7±3.1)days in the control group(t=0.73,P=0.47).The angle of filter tilt was(5.3±3.4)° in the experimental group and(5.7±7.7)° in the control group(t=0.19,P=0.85).There was no significant difference for filter placement and retrieval between the two groups(t=0.48 and 2.00,P=0.06 and 0.64,respectively).There were no complications of filter migration,strut penetration or new PE in both groups.Conclusion The application value of domestic Octoparms and impor-ted Celect IVCF is similar in interventional treatment of VTE.

Objective:To compare the diagnostic efficacy of 68Ga-PSMA-11 PET/ CT and multi-parameter magnetic resonance imaging (mpMRI) for pelvic lymph node metastases in prostate cancer patients who received neoadjuvant endocrinology or not after initial diagnosis. Methods:Data of 52 patients with moderate and high-risk prostate cancer admitted to Xijing Hospital from February to October 2023, aged (65.8±6.6) years, preoperative prostate-specific antigen (PSA) 26.67 (13.09, 84.89) ng/ml, were retrospectively analyzed. Before operation, there were 28 cases of cT 2stage, 16 cases of cT 3 stage and 8 cases of cT 4 stage. There were 22 cases of cN 0 and 30 cases of cN 1. All patients underwent 68Ga-PSMA-11 PET/CT and mpMRI at the same time, and were diagnosed positive lymph nodes in 28 and 21 cases, respectively. Risk stratification were high risk in 45 cases, and medium risk in 7 cases. According to the preoperative endocrine treatment, they were divided into the newly diagnosed group without treatment (24 cases) and the endocrine treated group (28 cases), whose ages were (65.0±7.1) years and (66.8±6.1) years, respectively. Preoperative PSA was 26.17 (16.73, 61.18) ng/ml and 27.32 (11.94, 130.18) ng/ml, respectively. Gleason scores ≤7 were in 10 cases (41.7%) and 6 cases (21.4%), and Gleason scores >7 were in 14 cases (58.3%) and 22 cases (78.6%), respectively. There were 15 (62.5%) and 13 (46.4%) cases of cT 1-2 stage, and 9 (37.5%) and 15 (53.6%) cases of cT 3-4 stage, respectively. There were 16 (66.7%) and 6 (21.4%) cases of stage N 0, 8 (33.3%) and 22 (78.6%) cases of stage N 1, respectively. There were 22 (91.7%) and 20 (71.4%) cases of stage M 0, 2 (8.3%) and 8 (28.6%) cases of stage M 1, respectively. PET/CT diagnosis of lymph node positive was in 9 cases (37.5%) and 19 cases (67.9%), and mpMRI diagnosis of lymph node positive was in 5 cases (20.8%) and 16 cases (57.1%). The number of positive lymph nodes diagnosed by PET/CT was 13 (72.2%) and 47 (90.1%), and the number of positive lymph nodes diagnosed by mpMRI was 8 (44.4%) and 32 (61.5%). There was no significant difference ( P>0.05). All patients underwent radical prostatectomy as well as enlarged pelvic lymph node resection. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two imaging examinations in the diagnosis of lymph node metastasis were compared according to the results of postoperative pathological examination of lymph nodes. Receiver operating characteristic (ROC) curve was used to compare the accuracy of the two imaging tests in the diagnosis of pelvic lymph node metastasis in the newly diagnosed untreated group and the endocrine treated group. Results:In this study, of 52 cases, 26 (50.0%) had positive lymph nodes by pathological examination. In this study, a total of 681 lymph nodes were dissected, with 70 lymph nodes (10.28%) being pathologically positive, and the positive rate of 26 patients was 17.99% (70/389). The PET/CT and mpMRI detection rates of 26 node-positive patients were 92.3% (24/26) and 57.7% (15/26), respectively. There were 9 (37.5%) and 17 (60.7%) lymph node positive patients in the untreated group and the endocrine therapy group, respectively. There were 320 and 361 lymph nodes were clear, with 18 (5.6%) and 52 (14.4%) positive lymph nodes, respectively. The detection rates of PET/CT and mpMRI were 88.89% (8/9) and 94.12% (16/17)in the untreated group, and 44.44% (4/9) and 64.71% (11/17)in the endocrine treated group, respectively. In the newly treated group, the area under the curve (AUC) of PET/CT and mpMRI for diagnosing positive lymph nodes were 0.911 and 0.689 ( P=0.027), the sensitivity were 88.9% and 44.4%, and the specificity were 93.3% and 93.3%, respectively. PPV were 88.9% and 80.0%, and NPV were 93.3% and 73.7%, respectively. In the endocrine therapy group, the AUC of PET/CT and mpMRI for lymph node positive diagnosis were 0.834 and 0.596 ( P=0.011), the sensitivity were 94.1% and 64.7%, the specificity were 72.7% and 54.5%, and the PPV were 84.2% and 68.8%, respectively. NPV were 88.9% and 50.0%, respectively. Conclusions:For prostate cancer patients, regardless of whether they receive neoadjuvant endocrine therapy, 68Ga-PSMA-11 PET/CT can accurately detect pelvic lymph node metastasis, and the diagnostic efficacy is significantly better than that of mpMRI.

BACKGROUND: Although previous studies have shown that meteorological factors such as temperature are related to the incidence of bacillary dysentery (BD), researches about the non-linear and interaction effect among meteorological variables remain limited. The objective of this study was to analyze the effects of temperature and other meteorological variables on BD in Beijing-Tianjin-Hebei region, which is a high-risk area for BD distribution. METHODS: Our study was based on the daily-scale data of BD cases and meteorological variables from 2014 to 2019, using generalized additive model (GAM) to explore the relationship between meteorological variables and BD cases and distributed lag non-linear model (DLNM) to analyze the lag and cumulative effects. The interaction effects and stratified analysis were developed by the GAM. RESULTS: A total of 147,001 cases were reported from 2014 to 2019. The relationship between temperature and BD was approximately liner above 0 °C, but the turning point of total temperature effect was 10 °C. Results of DLNM indicated that the effect of high temperature was significant on lag 5d and lag 6d, and the lag effect showed that each 5 °C rise caused a 3% [Relative risk (RR) = 1.03, 95% Confidence interval (CI): 1.02-1.05] increase in BD cases. The cumulative BD cases delayed by 7 days increased by 31% for each 5 °C rise in temperature above 10 °C (RR = 1.31, 95% CI: 1.30-1.33). The interaction effects and stratified analysis manifested that the incidence of BD was highest in hot and humid climates. CONCLUSIONS This study suggests that temperature can significantly affect the incidence of BD, and its effect can be enhanced by humidity and precipitation, which means that the hot and humid environment positively increases the incidence of BD.
Beijing/epidemiology* ; China/epidemiology* ; Dysentery, Bacillary/epidemiology* ; Humans ; Humidity ; Temperature

BACKGROUND: Bladder cancer stem cells could promote the recurrence and drug resistance of bladder cancer. Numerous studies have shown that keratin 6B (KRT6B) is involved in the production and progression of tumors, and is closely related to the prognosis of tumors. OBJECTIVE: To observe the expression of keratin 6B in CD44+ bladder cancer stem cells and to show the influence of keratin 6B on proliferation, migration, and self-renewal of bladder cancer stem cells, and to further explore the effect of keratin 6B expression on the prognosis of bladder cancer patients. METHODS: (1) CD44+ 5637 bladder cancer stem cells were isolated by magnetic active cell sorting. Cancer stem cell-related gene expression of SOX2, OCT4, and NANOG was detected via real-time polymerase chain reaction. The spheroid formation assay was used to detect the ability of self-renewal of cancer stem cells in CD44+ cells. Keratin 6B expression was detected in CD44+ bladder cancer stem cells by real-time polymerase chain reaction. (2) The CD44+5637 bladder cancer stem cells were divided into two groups. In the keratin 6B siRNA group, keratin 6B small interfering RNA was transfected into CD44+ bladder cancer stem cells. Untransfected CD44+ bladder cancer stem cells were used as the black control group. Cells were collected at 2 days post-transfection. The proliferation, migration, and self-renewal capacity of keratin 6B siRNA CD44+ bladder cancer stem cells were detected by the colony and wound healing assay and spheroid formation respectively. (3) Totally 24 bladder cancer tissues were used by immunohistochemistry to analyze the expression of CD44v6 and keratin 6B. (4) ONCOMINE database was used to analyze the effect of keratin 6B expression on the overall survival of bladder cancer. RESULTS AND CONCLUSION: (1) Cancer stem cell-related genes (SOX2, OCT4, NANOG) and keratin 6B expression was higher in CD44+ cells isolated by magnetic active cell sorting compared with CD44- cells (P < 0.05). Cell proliferation, migration, and in vitro spheroid formation were significantly increased (P < 0.05). Keratin 6B small interfering RNA down-regulated the expression of keratin 6B in CD44+ bladder cancer stem cells (P < 0.05). (2) Compared with the blank control group, the proliferation and migration of CD44+ bladder cancer stem cells after transfection of keratin 6B small interfering RNA (P < 0.05), and the number of tumorsphere significantly diminished (P < 0.05); the expression of Notch1 and Hes1 mRNA increased (P < 0.05). (3) Keratin 6B and CD44v6 were significantly different in bladder cancer tissue (P=0.006). The overall survival rate of bladder cancer patients with high expression of keratin 6B was lower than that of patients with low expression of keratin 6B. (4) The results showed that keratin 6B was highly expressed in CD44+ bladder cancer stem cells, and could promote the proliferation, migration, and self-renewal capacity of bladder cancer stem cells. The high expression of keratin 6B contributes to improving the survival of bladder cancer patients.

Objective:To investigate the characteristics and cytotoxicity in vitro of the residual leukemia cells in the culture system that caused the accidental transfer of CD19 chimeric antigen receptor (CAR) into leukemia cells during the preparation of autologous CD19 CAR-T cells of relapsed/refractory B-cell acute lymphoblastic leukemia.Methods:①Peripheral blood mononuclear cells (PBMC) of 30 patients with relapsed/refractory B-cell acute lymphoblastic anemia (R/R B-ALL) who accepted CD19 CAR-T cell therapy and six healthy volunteers were collected. ②The residual leukemia cells were analyzed by flow cytometry in the system after the PBMCs of R/R B-ALL patients were sorted by CD3 magnetic beads. ③ CD3 + T cells from patients and healthy volunteers were transfected with CD19 CAR and CD22 CAR lentivirus to prepare CD19 CAR-T and CD22 CAR-T cells. ④The Nalm-6 cell line was resuscitated and the Nalm-6 cells with CD19 CAR lentivirus were transfected to prepare CD19 CAR-Nalm-6 cells. The patient's primary ALL cells were transfected with CD19 CAR lentivirus at the same time. ⑤The transfection rates were analyzed by flow cytometer, the cell proliferation was analyzed by the CCK-8 method, and the cell-killing activities were detected by the lactate dehydrogenase method. Results:① Among the 30 R/R B-ALL patients who received CD19 CAR-T cell therapy, two patients had 2.04% and 3.32% residual leukemia cells in CD3 + T cells. After 4 days in culture, the residual leukemia cells disappeared and could not be detected by a flow cytometer with prolonged cultivation in vitro. ② The proliferation of CD19 CAR-Nalm-6 cells was higher than that of the Nalm-6 cells. ③ The killing activity of the CD19 CAR-T cells on Nalm-6 cells was higher than that of the CD19 CAR-Nalm6 cells at a target ratio of 1∶1 on 24, 48, 72 h, respectively. The cytotoxicity of CD22 CAR-T cells on CD19 CAR-Nalm-6 cells was significantly higher than that of CD19 CAR-T cells. ④ The cytotoxicity of CD22 CAR-T alone on CD19 CAR-Nalm-6 cells was higher than that of CD19 CAR-T combined with CD22 CAR-T at the same target ratio. Conclusion:The residual leukemia cells in the culture system in the preparation of CD19 CAR-T cells may lead to the introduction of CD19 CAR into leukemia cells and results in the failure of the CD19 CAR-T cell therapy. Detecting the residual leukemia cells in the culture system via flow cytometry before transfection with CD19 CAR lentivirus is needed. Thus, CD22 CAR-T cell therapy could be used as one of the salvage treatments.

Objective : To learn the effects of cassia seed extract,ginkgo biloba leaf extract,salvia miltiorrhiza extract and red yeast rice compounds on blood lipid level of rats with hyperlipidemia. Methods : The model of hyperlipidemia in SD rats was established. The rats in the low,moderate and high dose groups were given 0.267 g/kg body weight,0.533 g/kg body weight and 1.600 g/kg body weight of cassia seed,red yeast rice,ginkgo biloba leaf and salvia miltiorrhiza compounds by gavage for 30 days. A blank control group and a model control group were also set. The levels of serum total cholesterol（TC）,triglyceride（TG）,high-density lipoprotein cholesterol（HDL-C）and low-density lipoprotein cholesterol（LDL-C）in the five groups were measured before and after the intragastric administration. Results : One week after the model was founded,the levels of serum TC,TG and LDL-C in the model control group were higher than those in the blank control group（P<0.05）. Before the intragastric administration,there were no significant differences in the levels of serum TC,TG,HDL-C and LDL-C between the model control group and each dosage group（P>0.05）. After the intragastric administration,there were no significant differences in the levels of serum HDL-C and LDL-C between the model control group and each dosage group（P>0.05）. The levels of serum TC and TG in the high dose group were significantly lower than those in the model control group（P<0.05）;There was no significant differences in the levels of serum TC and TG between the moderate dose,low dose group and the model control group（P>0.05）. Conclusion The compounds of cassia seed extract,red yeast rice,ginkgo biloba extract and salvia miltiorrhiza extract with a dosage of 1.600 g/kg body weight can reduce serum TC and TG levels in rats with hyperlipidemia.

Objective: To Evaluation the effect of PD-1 inhibitor Nivolumab on the proliferation and cytotoxicity of anti-CD19 chimeric antigen receptor T cells (CD19-CAR-T) in vitro. Methods: Five patients with high PD-1 expression in peripheral blood and five healthy volunteers were selected. These peripheral blood mononuclear cells were used as the source of T cells to prepare CD19-CAR-T cells. Different doses (72, 36, 18 μg/ml) of Nivolumab was added on day 8 to the culture medium. Patient T cells incubated with 72 μg/ml Nivolumab and CD19-CAR-T cells of healthy volunteers were used as controls. CCK-8, lactate dehydrogenase (LDH) cytotoxicity assay and ELASA were used to detect the proliferation capacity, the specific cytotoxicity and the inflammatory factor secretion. Results: ①T cells from patients with high expression of PD-1 as the source of CD19-CAR-T cells did not affect transfection rate compared with that of healthy volunteers [(32.80±7.22)% vs (35.10±5.84)%, t=-0.554, P=0.593]. ②Incubation of CD19-CAR-T cells with 72 μg/ml Nivolumab did not affect CD19-CAR-T cell proliferation, but its cytotoxicity was significantly higher than that of CD19-CAR-T cells alone or patients’ T cells +72 μg/ml Nivolumab (all P<0.001), there was no significant difference in the killing activity between the 72 μg/ml and 36 μg/ml Nivolumab treated CD19-CAR-T cells on Pfeiffer cells (P=0.281, 0.267, respectively), and they were all higher than those of 18 μg/ml Nivolumab treated CD19-CAR-T cells (all P<0.001). ③Different doses of PD-1 inhibitor Nivolumab combined with CD19-CAR-T cells does not affect the secretion of IFN-γ and IFN-α (all P>0.05). Conclusion Combination of 36 μg/ml PD-1 inhibitor and CD19-CAR-T cells could reduce the drug toxicity and enhance the cytotoxicity.

OBJECTIVETo summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

METHODSClinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.

RESULTSAmong 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.

CONCLUSIONSThe choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.

Objective To evaluate the clinical effect of reduced glutathione in protecting the liver function for patients with hepatocellular carcinoma (HCC) after receiving international therapy.Methods The clinical data of 110 HCC patients,who were admitted to authors' hospital during the period from January 2010 to June 2013,were retrospectively analyzed.According to the random number table method the patients were divided into the control group (n=50) and the treatment group (n=60),and transcatheter arterial chemoembolzation (TACE) and transcatheter arterial infusion (TAI) were carried out in all patients.After the treatment,intravenous infusion of 2.0 g vitamin C,0.2 g vitamin B6,2.0 g inosine,and 250 ml branched chain amino acid was employed per day for one week for the patients of both groups,and additional intravenous dripping of 1.8 g reduced glutathione (added in 250 ml of 5％ glucose solution) was adopted for the patients of the treatment group.Various liver function indexes were tested before and one week after the treatment,the results were compared between the two groups.Results Before the treatment,no obvious differences in the hepatic functions and in the clinical condition existed between the two groups.One week after the treatment,in both groups the aminotransferase (ALT and AST) and total bilirubin (TBIL) were significantly increased when compared with the preoperative data (P＜0.05),while the serum pre-albumin (PA) was remarkably decreased when compared with the preoperative data (P＜0.05);these changes of various indexes in the treatment group were apparently better than those in the control group (P＜0.05).Conclusion The use of reduced glutathione can effectively relieve the liver function damage caused by interventional therapy in HCC patients,therefore,reduced glutathione has a very good clinical application value.