Objective To construct and identify a patient-derived organoid model,and to investigate the sensitivity of chemotherapy drugs using this model.Methods Pancreatic cancer cells were obtained from the surgical specimens of two female patients with a confirmed diagnosis of pancreatic cancer after tumor tissue digestion,and then the cells were inoculated into a culture dish using matrigel for three-dimensional culture.Paraffin sections were prepared for HE staining and immunohistochemical staining and were compared with the parent tumor tissue to determine whether the histopathological features of the tumor in vivo were preserved.The pancreatic cancer organoids were treated with seven chemotherapy drugs at different concentrations;Cell Titer-Glo?3D reagent was used to measure cell viability,and the results of drug sensitivity were analyzed.Results Two patient-derived pancreatic cancer organoids were successfully constructed,and HE staining and immunohistochemical staining showed that the pancreatic cancer organoids had consistent histopathological features with the tumors of the corresponding patient.Both pancreatic cancer organoids were more sensitive to gemcitabine monotherapy and the combination of oxaliplatin+SN38+fluorouracil,and patient 1 was more sensitive than patient 2.There were individual differences in the response to drugs between the organoids from different patients.Conclusion The pancreatic cancer organoid model successfully constructed in this study can reflect the histological classification of parent pancreatic tumors and can be used for in vitro chemotherapy drug sensitivity test,which is expected to provide a reference for clinical medication.

Objective:To investigate the serum lactate level in patients with rheumatoid arthritis(RA)and its relationship with disease activity,and to analyze the effect of sodium lactate on the activation of CD4+T cells,the ability of secreting cytokines and CD4+T cell subsets in peripheral blood of the RA patients.Methods:The peripheral blood of healthy controls(HC)and RA patients was collected,and the content of lactate in the supernatant was detected by lactate detection kit,the correlation between the content of lactate and the disease score of the RA patients was analyzed;the activation level of CD4+T cells,the proportion of CD4+T cell subsets and the cytokines secreted by CD4+T cells in peripheral blood of all the RA patients were detected by flow cytometry after being stimulated with sodium lactate.Results:The serum lactate level in the RA patients(n=66)was significantly higher than that in the HC(n=60,P＜0.001),and there was a certain correlation with disease activity score in 28 joints(DAS28)-C-reactive protein(CRP)(r=0.273,P=0.029),The levels of rheumatoid factor[RF,197.50(26.03,783.00)IU/mL vs.29.30(0.00,102.60)IU/mL,P＜0.01],CRP[37.40(11.30,72.60)mg/L vs.5.83(2.36,12.45)mg/L,P＜0.001],were increased in patients with the lactate concentration greater than 5 mmol/L were significantly higher than those in patients with the lactate concentration less than or equal 5 mmol/L,however,there was no significant difference in the expres-sion of erythrocyte sedimentation rate[ESR,42.00(19.00,77.00)mm/h vs.25.00(12.50,45.50)mm/h,P＞0.05]and anti-cyclic citrullinated peptied(CCP)antibody[82.35(17.70,137.00)RU/mL vs.68.60(25.95,119.70)RU/mL,P＞0.05].Compared with the control group,the expression of PD-1(46.15％±8.54％vs.41.67％±9.98％,P＜0.001),inducible costimulatory molecule(ICOS,5.77％±8.60％vs.18.65％±7.94％,P＜0.01)and CD25(25.89％±5.80％vs.22.25％±4.59％,P＜0.01)on the surface of CD4+T cells in the RA patients treated with sodium lactate was significantly increased.Compared with the control group,the proportion of Th17(4.62％±1.74％vs.2.93％±1.92％,P＜0.05)and Tph(28.02％±6.28％vs.20.32％±5.82％,P＜0.01)cells in CD4+T cells of the RA patients in the sodium lactate treatment group increased.Compared with the con-trol group,the expression of IL-21(5.73％±1.59％vs.4.75％±1.71％,P＜0.05)inCD4+Tcells was up-regulated in the RA patients treated with sodium lactate.Conclusion:The level of serum lactate in RA patients is increased,which promotes the activation of CD4+T cells and the secretion of IL-21,and up-regulates the proportion of Th 17 and Tph cells in the RA patients.

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment

Objective: To analyze the risk factors of cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy. Methods: 530 patients with esophageal cancer underwent thoracoscopic-lapacoscopic esophagectomy at the Cancer Hospital, Chinese Academy of Medical Sciences from Jan 2011 to Dec 2015. The demographic, surgical and clinical data of patients were retrospectively analyzed. Multivariate logistic regression was used to evaluate risk factors of cervical anastomotic leakage in these patients. Results: A total of 530 patients undergoing thoracoscopic-lapacoscopic esophagectomy were enrolled in this study. There were 421 males and 109 females. The mean age was (59.40±8.08) years old, and 91 patients with cervical anastomotic leakage. Sigle factor analysis revealed that the risk grading by American Society of Aneshesiologists, previous history of chest surgery, respiratory comorbidity, diffusion capacity for carbon monoxide of the lung, operation time, anastomosis, average days of postoperative hospitalization, death within 30 days after surgery, respiratory complications, pleural effusion or empyema, and poor healing of the incision were statistically associated with cervical anastomotic leakage (all P<0.05). Multivariate analysis showed that previous history of chest surgery, hepatic insufficiency, manual anastomosis, prolonged postoperative hospitalization, and poor healing of the incision were independent risk factors for cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy (all P<0.05). Conclusions Previous history of chest surgery, hepatic insufficiency, poor healing of the incision, manual anastomosis and prolonged postoperative hospitalization were significantly associated with cervical anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy. It′s important to strengthen perioperative nursing and surgical techniques to prevent anastomotic leakage after thoracoscopic-lapacoscopic esophagectomy.

Objective To analyze whether free fatty acids(FFA)are associated with anxiety and depression in elderly patients with chronic heart failure(CHF).Methods A cross-sectional study was conducted in patients by using questionnaires.According to the Zung Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale(SDS),126 patients were divided into the depression group (n=94),non-depression group (n =32),and anxiety group (n =48),and non-anxiety group (n =78).The difference in FFA levels between the two groups was analyzed.Moreover,the association of FFA with anxiety and depression was analyzed Results The incidence of anxiety in elderly patients with CHF was 38.1％(48 cases),and the incidence of depression was 74.6％ (94 cases).FFA levels were higher in both the anxiety and depression groups than in the non-anxiety and non-depression groups [(559.9 ± 256.2)μmol/L vs.(393.8 ± 147.8) μmol/L,(573.8 ± 264.7)μmol/L vs.(483.2 ± 225.2)μmol/L,P＜0.05 and 0.01)].The FFA level was positively correlated with SAS and SDS in elderly patients with CHF(r=0.214 and 0.275,P＜0.05 and 0.01).Multivariate regression analysis showed that the FFA level was a risk factor for elderly CHF patients with anxiety(β=0.074,95％CI:0.024～0.125,P=0.004)and depression(β=0.084,95％CI:0.022～0.145,P=0.008).Conclusions FFA levels are correlated with anxiety and depression in elderly patients with CHF.The FFA level is a risk factor for anxiety and depression in elderly patients with CHF.Psychological intervention should be carried out early in CHF patients with high levels of FFA to reduce the incidence of anxiety and depression.

Objective To compare the safety and effectiveness of intravenous thrombolysis treatment in large artery atherosclerosis (LAA) and cardioembolic (CE) strokes in patients with acute anterior circulation ischemic stroke.Methods Two hundred and thirty-eight patients with acute anterior circulation ischemic stroke, admitted to and treated with intravenous thrombolysis in our hospital from January 2017 to June 2018 were chosen in our study. These patients were divided into either a LAA group (n=158) or a CE group (n=80) according to etiological subtypes. The differences in baseline data and outcomes 90 d after the onset between the two groups were compared. Baseline data of patients in the good outcome group and the poor outcome group were compared and independent risk factors for poor outcome were determined by multivariate Logistic regression analysis.Results As compared with the patients from the LAA group, patients from the CE group had older age and higher proportion of patients combined with atrial fibrillation, with significant differences (P<0.05); there were no statistically significant differences in the good outcome rate, mortality rate and incidence of symptomatic intracranial hemorrhage between the two groups (P>0.05). Among the 238 patients, 112 were into the good outcome group and 126 were into the poor outcome group; as compared with patients from the poor outcome group, patients from the good outcome group had younger age, and lower National Institute of Health Stroke Scale (NIHSS) scores and lower levels of fasting blood glucose before and after thrombolysis, with statistically significant differences (P<0.05); multivariate Logistic regression analysis showed that older age (odds ratio [OR]=1.040, 95％ confidence interval [CI]: 1.010-1.071,P=0.008) and higher NIHSS scores 24 h after thrombolysis (OR=1.259, 95％CI: 1.175-1.350,P=0.000) were independently associated with poor outcome.Conclusion The outcomes of intravenous thrombolysis in patients with acute anterior ischemic stroke are only associated with age and severity of stroke, and not associated with TOAST etiological subtypes; intravenous thrombolysis for cardiogenic stroke is safe and effective.

Objective To analyze the risk factors of cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy. Methods 530 patients with esophageal cancer underwent thoracoscopic?lapacoscopic esophagectomy at the Cancer Hospital, Chinese Academy of Medical Sciences from Jan 2011 to Dec 2015. The demographic, surgical and clinical data of patients were retrospectively analyzed. Multivariate logistic regression was used to evaluate risk factors of cervical anastomotic leakage in these patients. Results A total of 530 patients undergoing thoracoscopic?lapacoscopic esophagectomy were enrolled in this study. There were 421 males and 109 females. The mean age was (59.40±8.08) years old, and 91 patients with cervical anastomotic leakage. Sigle factor analysis revealed that the risk grading by American Society of Aneshesiologists, previous history of chest surgery, respiratory comorbidity, diffusion capacity for carbon monoxide of the lung, operation time, anastomosis, average days of postoperative hospitalization, death within 30 days after surgery, respiratory complications, pleural effusion or empyema, and poor healing of the incision were statistically associated with cervical anastomotic leakage (all P＜0.05). Multivariate analysis showed that previous history of chest surgery, hepatic insufficiency, manual anastomosis, prolonged postoperative hospitalization, and poor healing of the incision were independent risk factors for cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy ( all P＜0.05 ). Conclusions Previous history of chest surgery, hepatic insufficiency, poor healing of the incision, manual anastomosis and prolonged postoperative hospitalization were significantly associated with cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy. It′s important to strengthen perioperative nursing and surgical techniques to prevent anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy.

Objective To analyze the risk factors of cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy. Methods 530 patients with esophageal cancer underwent thoracoscopic?lapacoscopic esophagectomy at the Cancer Hospital, Chinese Academy of Medical Sciences from Jan 2011 to Dec 2015. The demographic, surgical and clinical data of patients were retrospectively analyzed. Multivariate logistic regression was used to evaluate risk factors of cervical anastomotic leakage in these patients. Results A total of 530 patients undergoing thoracoscopic?lapacoscopic esophagectomy were enrolled in this study. There were 421 males and 109 females. The mean age was (59.40±8.08) years old, and 91 patients with cervical anastomotic leakage. Sigle factor analysis revealed that the risk grading by American Society of Aneshesiologists, previous history of chest surgery, respiratory comorbidity, diffusion capacity for carbon monoxide of the lung, operation time, anastomosis, average days of postoperative hospitalization, death within 30 days after surgery, respiratory complications, pleural effusion or empyema, and poor healing of the incision were statistically associated with cervical anastomotic leakage (all P＜0.05). Multivariate analysis showed that previous history of chest surgery, hepatic insufficiency, manual anastomosis, prolonged postoperative hospitalization, and poor healing of the incision were independent risk factors for cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy ( all P＜0.05 ). Conclusions Previous history of chest surgery, hepatic insufficiency, poor healing of the incision, manual anastomosis and prolonged postoperative hospitalization were significantly associated with cervical anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy. It′s important to strengthen perioperative nursing and surgical techniques to prevent anastomotic leakage after thoracoscopic?lapacoscopic esophagectomy.

BACKGROUND: Simultaneity multiple primary lung cancer always is a rare disease, but in recent years due to the progress of the diagnosis and treatment means detection rate increased. This study summarized the clinical data of 31 cases of synchronous multiple primary lung cancer (sMPLC) analysis, further to explore the diagnosis, treatment and prognosis of MPLC. METHODS: Sum up the clinical data of 31 cases of simultaneous multiple primary lung cancer, the diagnostic method, surgical methods, pathology, were retrospectively analyzed. RESULTS: All the patients are thoracoscope surgery, no deaths. Thin high resolution computed tomography (CT) in preoperative found multiple lung nodules. Lesions located in the same side of the same period surgical treatment, the operation method is given priority to with under the thoracoscope lung + the lobectomy; Lesions located in bilateral, all staged operation, the time interval for 3 months-4 months. CONCLUSIONS Thin layer distinguish CT preoperative diagnosis is the best way to simultaneous multiple primary lung cancer. Multiple primary lung cancer incidence of ipsilateral lung at the same time higher than that of bilateral lung (23:8), type, around 94%, the most common histology to adenocarcinoma, 80.6% (25/31). Primary lesions under thoracoscope lobectomy plus the lobectomy of secondary lesions is the most commonly used.
Adult ; Aged ; Female ; Humans ; Lung Neoplasms ; diagnosis ; diagnostic imaging ; surgery ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; diagnosis ; diagnostic imaging ; surgery ; Retrospective Studies ; Tomography, X-Ray Computed

AIM:To investigate the neuroprotective effect of hydrogen sulfide ( H2 S) after cardiopulmonary re-suscitation in rats with cardiac arrest ( CA) , and to explore the effects of H2 S on neuron autophagy.METHODS:The CA model was established through asphyxia.Male Wistar rats were randomly divided into sham group, model group and NaHS group.The levels of beclin-1 and LC3 II/I were measured by Western blot at 2 h, 4 h, 12 h and 24 h after the restoration of spontaneous circulation (ROSC).At 12 h after ROSC, the formation of autophagic vacuole with LC3 dots was deter-mined by immunohistochemical ( IHC) method.The phenomenon of neuron autophagy was observed under transmission electron microscope.The numbers of apoptotic neurons were counted by TUNEL staining at 72 h after ROSC.The neurolo-gic deficit score ( NDS) was used to evaluate the neurologic function after ROSC.RESULTS: The level of beclin-1 was gradually increased in model group, but it was increased and then gradually recovered in NaHS group ( P<0.05 ) .The conversion of LC3 II in the cerebral cortex was the same as beclin-1.The results of IHC showed that LC3-positive nuclei in model group were more than those in NaHS group ( P<0.05) .The number of autophagic vacuole in model group was more than that in NaHS group (P<0.05).The number of the TUNEL-positive cells in model group was more than that in NaHS group (P<0.05).The NDS of the animals in NaHS group after ROSC was lower than that in model group(P<0.05). CONCLUSION:H2 S inhibits neuronal autophagy, decreases apoptosis and improves neurologic function in CA rats after ROSC.