Objective : To investigate the effect of adeno⁃associated virus ( AAV) delivery of short hairpin RNA ( shRNA) against the Ptger3 gene in the lateral parabrachial nucleus (LPB) on the fever induced by microinjection of prostaglandin E2 (PGE2 ) into the LPB and the intraperitoneal injection of lipopolysaccharide (LPS) . Methods: AAV2⁃shRNA⁃Ptger3(EP3) ⅣEGFP ( shRNA⁃EP3) and AAV2⁃ CMV⁃ EGFP ( shRNA⁃control) viruses were constructed and transfected the rat LPB by stereotaxic injection. Four weeks later, the transfection efficiency of AAV viruses was observed by fluorescence microscopy , and the knockdown efficiency was determined by real⁃time PCR of EP3 receptor mRNA on the LPB. The effects of microinjection of saline or PGE2 in the LPB or intraperitoneal injection of LPS on body temperature (Tcore ) and energy expenditure (EE) of shRNA⁃control group and shRNA⁃EP3 group were monitored using an animal monitoring system with temperature telemetry. Results : AAV virus transfecnificant difference in basal body temperature between shRNA⁃control group and shRNA⁃EP3 group. Tcore and EE were briefly and slightly increased after microinjection of saline in the LPB , but there was no significant difference between the two groups. Compared with the shRNA⁃control group , the febrile response induced by LPB PGE2 was attenuated in the shRNA⁃EP3 group (P < 0. 05) . Furthermore , the knockdown of EP3 receptor of LPB also attenuated the LPS⁃induced fever, and the Tcore 5. 5 h post⁃LPS in the shRNA⁃EP3 rats increased compared with the baseline (P < 0. 05) , which was lower than that in the shRNA⁃control rats ( P < 0. 01) . Conclusion EP3 receptor knockdown in LPB attenuates the febrile response induced by microinjection of PGE2 in the LPB and intraperitoneal injection of LPS , suggesting that EP3 receptors of LPB mediate the pyrogenic action of LPB PGE2 and partly participate in LPS⁃induced fever.

Objective : To investigate the effect of Arginine Vasopressin (AVP) on the median preoptic glutamatergic (MnPOVglut2 ) neurons and its mechanism． Methods : Brain slices were prepared from male Vglut2-tdTomato mice．MnPOVglut2 neurons expressing red fluorescent protein were located by using fluorescence microscope．Wholecell patch clamp technique was used to observe the effect of AVP on the firing frequency of MnPOVglut2 neurons，the effect of synaptic transmission blockers ( STBs) on the AVP-induced change in the firing frequency of MnPOVglut2 neurons，and the effect of AVP V1a receptor antagonist on the AVP-induced change in the firing frequency of MnPOVglut2 neurons. Results: The mean firing frequency of MnPOVglut2 neurons increased during perfusion with artificial cerebrospinal fluid (ACSF) and AVP compared with that during perfusion with ACSF (P＜0. 01) ，indicating that AVP excited the MnPOVglut2 neurons．The mean firing frequency of MnPOVglut2 neurons still increased during perfusion with ACSF，STBs，and AVP compared with that during perfusion with ACSF and STBs (P＜0. 001) ; moreover，the magnitude of AVP-induced increase in firing frequency didn't change significantly during perfusion with ACSF，STBs，and AVP compared with that during perfusion with ACSF and AVP (P ＞0. 05 ) ，suggesting that AVP excited the MnPOVglut2 neurons directly in a postsynaptic manner．The magnitude of AVP-induced increase in the firing frequency of MnPOVglut2 neurons declined during perfusion with ACSF，STBs，AVP，and V1areceptor antagonist compared with that during perfusion with ACSF，STBs，and AVP (P＜0. 01) ，suggesting that AVP excited MnPOVglut2 neurons directly via V1a receptor． Conclusion AVP can excite MnPOVglut2 neurons via V1areceptor directly in a postsynaptic manner．This study reveals the molecular marker of MnPO neurons which AVP act on.

Objective:To provide genetic counseling and prenatal diagnosis for a fetus with mosaic trisomy 20.Methods:Chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a pregnant woman with advanced maternal age. Results:The karyotype of amniotic fluid sample was 47, XN, + 20, whilst the result of CMA was normal. To verify this discrepancy, CMA was performed again with the cultured amniotic fluid, which yielded a result of 47, XN, + 20. FISH assay of the amniotic fluid sample was nuc ish(D20Z1)×3[11]/(D20Z1)×2[89], which indicated that about 11% of fetal cells were trisomy 20. After the fetus was born, the karyotype of peripheral blood sample was normal.Conclusion:The amniotic fluid sample might be mosaic trisomy 20, and a dominant growth of 47, XN, + 20 cells had occurred during the culture process, resulting in alteration of amniotic fluid cell composition. Mosaic trisomy 20 indicated by FISH may be attributed to confined placental mosaicism or somatic mosaicism of trisomy 20.

Objective:To investigate the risk factors that were associated with the death of elderly patients who were admitted to the intensive care unit (ICU) after elective abdominal surgery, and to find reliable and sensitive predictive indicators for early interventions and reducing the mortality.Methods:A retrospective case-control study was conducted. The clinical data of elderly (age≥65 years old) patients after elective abdominal surgery admitted to the ICU of the Affiliated Hospital of Guizhou Medical University from January 1st 2016 to December 31st 2020 were collected, including the patient's gender, age, body mass index (BMI), medical history, American Society of Anesthesiologists (ASA) grades, surgical classification, intraoperative blood loss, duration of operation, interval time between end of operation and admission to the ICU, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score and the worst laboratory examination results within 24 hours of ICU admission, the first blood gas analysis in ICU, the duration of invasive mechanical ventilation, and the length of ICU stay. Postoperative abdominal infection was evaluated by the pathogenic culture of peritoneal drainage fluid and clinical symptoms and signs. The patients were divided into death group and survival group based on clinical outcomes, and clinical data were compared between the two groups. Binary multivariate Logistic regression analysis was used to screen the risk factors of death, and the receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive values of these risk factors.Results:A total of 226 elderly patients with elective abdominal surgery were admitted to the ICU of our hospital during the past 5 years, of whom, two patients who did not undergo laboratory examinations within 24 hours of admission to the ICU were excluded. Finally, 224 patients met the criteria, with 158 survivors and 66 deaths. Univariate analysis showed that: compared with survival group, APACHEⅡscore, blood lactate acid (Lac) and the proportion of postoperative abdominal infection were higher in death group [APACHEⅡ score: 27.5 (25.0, 31.3) vs. 23.0 (18.0, 27.0), Lac (mmol/L): 2.9 (1.8, 6.6) vs. 1.8 (1.1, 2.8), the proportion of postoperative abdominal infection: 65.2% (43/66) vs. 35.4% (56/158), all P < 0.01], prothrombin time (PT), activated partial thromboplastin time (APTT) and interval time between end of surgery and admission to ICU were longer [PT (s): 17.20 (14.50, 18.63) vs. 14.65 (13.90, 16.23), APTT (s): 45.15 (38.68, 55.15) vs. 39.45 (36.40, 45.70), interval time between end of surgery and admission to ICU (hours): 39.2 (0.7, 128.9) vs. 0.7 (0.3, 2.0), all P <0.01], postoperative hemoglobin (Hb), platelet count (PLT), prealbumin (PA), mean arterial pressure (MAP) and oxygenation index (PaO 2/FiO 2) were lower in death group [Hb (g/L): 95.79±23.64 vs. 105.58±19.82, PLT (×10 9/L): 138.5 (101.0, 177.5) vs. 160.5 (118.5, 232.3), PA (g/L): 80.88±43.63 vs. 116.54±50.80, MAP (mmHg, 1 mmHg = 0.133 kPa): 76.8±19.1 vs. 91.6±19.8, PaO 2/FiO 2 (mmHg): 180.0 (123.5, 242.5) vs. 223.5 (174.8, 310.0), all P < 0.05]. Binary multivariate Logistic regression analysis showed that APACHEⅡscore [odds ratio ( OR) = 1.187, 95% confidence interval (95% CI) =1.008-1.294, P < 0.001], interval time between end of operation and admission to ICU ( OR = 1.005, 95% CI = 1.001-1.009, P = 0.016) and postoperative abdominal infection ( OR = 2.630, 95% CI = 1.148-6.024, P = 0.022) were independent risk factors for prognosis in these patients. MAP ( OR = 0.978, 95% CI = 0.957-0.999, P = 0.041) and PaO 2/FiO 2 ( OR = 0.994, 95% CI = 0.990-0.998, P = 0.003) were protective factors for the patients' prognosis. Lac, Hb, PLT, PA, PT and APTT had no predictive value for the prognosis of elderly patients admitted to ICU after elective abdominal surgery [ OR value and 95% CI were 1.075 (0.945-1.223), 1.011 (0.99-1.032), 1.000 (0.995-1.005), 0.998 (0.989-1.007), 1.051 (0.927-1.192) and 1.003 (0.991-1.016), respectively, all P > 0.05. ROC curve analysis showed that APACHEⅡscore, interval time between end of operation and admission to the ICU and the postoperative abdominal infection had certain predictive values for the prognosis of elderly patients, the area under ROC curve (AUC) were 0.755, 0.732 and 0.649 respectively, all P < 0.001; When the cut-off of APACHEⅡscore and interval time between end of operation and admission to the ICU were 24.5 scores and 2.15 hours, the sensitivity were 78.8% and 66.7%, respectively, and the specificity were 62.0% and 76.6%, respectively. The combined predictive value of the three variables was the highest, which AUC was 0.846, the joint prediction probability was 0.27, the sensitivity was 83.3%, and the specificity was 75.3%. Conclusion:APACHEⅡscore, interval time between end of surgery and admission to ICU, and postoperative abdominal infection may be independent risk factors for the death of elderly patients who were admitted to the ICU after elective abdominal surgery, there would be far greater predictive values when the three variables were combined.

Objective:To explore the value of tumor diameter to preoperative carcinoembryonic antigen (CEA) ratio (TCR) in predicting prognosis of patients with non-metastatic colorectal cancer.Methods:The clinical data of 144 patients with colorectal cancer in Hainan Hospital of PLA General Hospital between July 2012 and December 2017 were retrospectively analyzed. Patients were divided into the low TCR group and the high TCR group according to the optimal value of TCR in predicting the disease-free survival (DFS) determined by the receiver operating characteristic curve (ROC). The clinicopathological features of both groups were analyzed, and the influencing factors of DFS were also analyzed by using Cox proportional hazard model.Results:ROC analysis showed that TCR had a certain value in predicting DFS, and area under the curve (AUC) was 0.614 (95% CI 0.507-0.722); when the value of TCR was set at 0.690, the sensitivity and specificity of predicting the 3-year DFS rate was 46.3% and 70.9%, respectively. According to 0.690 of TCR, there were 50 cases in the low TCR (< 0.690) group and 94 cases in the high TCR (≥0.690) group. There were no statistically significant differences in the high and low TCR between the two groups for patients stratified by gender, age, tumor location, differentiation degree, invasive depth, lymph node metastasis, TNM stage (all P > 0.05). Univariate analysis showed that TCR, preoperative CEA level and TNM stage played a role in predicting DFS of patients (all P < 0.05), while Cox multivariate analysis indicated that TCR < 0.690 ( HR = 2.369, 95% CI 1.279-4.388, P = 0.006) and Ⅲ stage in TNM stage ( HR = 2.214, 95% CI 1.346-3.640, P = 0.002) were the independent risk factors of influencing DFS (all P < 0.01). The 3-year DFS rate of patients in the low TCR group was lower than that of those in the high TCR group (62.0% vs. 83.0%, P = 0.007). Conclusion:TCR could have a certain value in judging the prognosis of non-metastatic colorectal cancer patients, and low TCR patients have a poorer prognosis.

Objective:To compare death causes and the survival time in elderly patients undergoing hemodialysis versus peritoneal dialysis in the nephrology department of Beijing Hospital in the last 10 years.Methods:This was a retrospective study.Patients aged more than 60 years who had undergone dialysis and died in the dialysis center of Beijing Hospital between January 2010 and January 2019 were enrolled.A detailed medical history including gender, age, primary diseases, diabetes mellitus, time of dialysis initiation, time of death and direct cause of death were recorded.Results:A total of 153 elderly dialysis patients were enrolled, with a mean age of 76.6±7.7 years, a median dialysis vintage of 54.1(26.9, 86.4)months, including 83(54.2%)cases with diabetes.Patients were divided into the hemodialysis group(HD, n=114)and the peritoneal dialysis group(PD, n=39)according to the dialysis method.The mean ages of patients in the HD and PD groups were 77.1±7.9 and 75.0±7.0 years, and the median dialysis vintages were 56.5(27.4, 104.2)and 48.3(26.3, 66.6)months, respectively.The primary diseases of patients undergoing HD and PD were diabetic nephropathy(DN, 32.5% vs.48.7%), chronic glomerulonephritis(29.8% vs.17.9%)and hypertensive renal damage(21.1% vs.10.3%). The top three causes of mortality in patients undergoing HD and PD were cardiovascular diseases(32.4% vs.43.6%), infections(29.8% vs.28.2%)and cerebrovascular diseases(11.4% vs.15.4%). The compositions of primary diseases and death causes were similar between the two groups, with no significant difference.Kaplan-Meier curves indicated that the survival time of dialysis patients with diabetes mellitus was shorter than that of patients without diabetes mellitus(chi-square value was 12.829, P<0.001), and the survival time of HD patients was longer than that of PD patients(chi-square value was 8.161, P=0.004). In patients without diabetes mellitus, the survival time of HD patients was longer than that of PD patients( Z=-2.716, P=0.007). In patients with diabetes mellitus, HD and PD had similar survival outcomes( Z=-0.581, P=0.561). Conclusions:The proportion of patients with diabetic nephropathy is high in elderly dialysis patients.Cardiovascular and cerebrovascular diseases and infections are the main causes of death in elderly dialysis patients.The survival time is longer in HD patients than in PD patients.

Objective To evaluate the prognostic value of combined examination of pre-operative carcinoembryonic antigen (CEA) and CD44v6 for colorectal cancer patients. Methods A total of 140 patients with complete clinical data pathologically diagnosed as colorectal cancer from December 2012 to December 2017 in Hainan Hospital of PLA General Hospital were enrolled. Finally, 69 validated cases excluding CEA (-) or CD44v6(-) patients were registered according to pre-operative CEA detection and immunohistochemistry results of CD44v6. Kaplan-Meier method was used to analyze the progression-free survival (PFS) time for single factors. Multiple-factor analysis was done by using Cox proportional hazard model. Results Sixty-nine patients included 29 cases of double positive and 40 cases of double negative in CEA and CD44v6. There were statistical significances of the expressions of double positive and double negative in patients with different gender, M stage, TNM stage. Double positive was more apparent in female (χ2 = 4.42, P= 0.04), presenting of metastasis (χ2=5.06, P=0.02) and advanced cases (χ2=4.38, P= 0.04); univariable analysis showed the N stage (P=0.00), M stage (P=0.00), TNM stage (P=0.00) and double positive/double negative in CEA and CD44v6 (P= 0.04) were likely to affect the PFS, however, multivariable analysis showed that N stage (HR= 0.15, 95 ％ CI: 0.03-0.86, P= 0.03), TNM stage (HR= 23.83, 95 ％ CI: 3.65-155.51, P=0.00) were the independent prognostic factors for PFS. PFS in double positive patients was shorter than that in double negative ones [24.0 months (3-84) vs. 31.0 months (8-94), P=0.04]. Conclusion Pre-operative combined examination of CEA and CD44v6 could be helpful in judging the prognosis for colorectal cancer patients.

Objective To analyze the causes of death of maintenance hemodialysis (MHD) patients,and to compare the long term survival rate between elderly patients and non-elderly patients and between diabetic nephropathy (DN) patients and non-DN patients at our hemodialysis center during last 20 years.Methods A total of 317 MHD patients were collected,and divided into elderly (≥60 years) and non-elderly (＜60 years) groups based on the age at starting hemodialysis.Besides,data of gender,primary diseases,and the direct cause of death in maintenance hemodialysis patients from 1996 to 2016 were collected.Results Cardiogenic diseases,infections,and cerebrovascular accidents were the three leading causes of death.The mean dialysis age was shorter in elderly MHD patients than in non-elderly MHD patients[(51.8 ± 45.7) months vs.(81.6 ± 66.5) months,t =4.271,P=0.000]with a lower survival rate (x2 =32.422,P =0.000).The mean dialysis age was significantly lower in DN patients than in non-DN patients[(44.1±33.8) months vs.(69.4±60.6) months,t=3.632,P =0.000)] with a lower survival rate (x2 =13.361,P =0.000).The overall survival rate was 59.8％ after the fifth year of MHD,was 33.3％ after the 10th year,was 8.4％ after the 20th year,in our dialysis center.Conclusions The long-term survival rate of patients receiving maintenance hemodialysis in our center is as high as that in the developed countries and in other hospitals in Beijing.The top three death causes are cardiac diseases,infections,and cerebrovascular accidents.For old or DN patients,the overall prognosis is poor.

Objective To obtain myoclonic epilepsy with ragged-red fibers (MERRF)-specific cardiomyocytes by the differentiation in vitro of inducing pluripotent stem cells (iPSC) derived from a MERRF patient and evaluate the application of the prepared cardiomyocytes in construction of MERRF syndrome model.Methods The patient-derived iPSCs and H9 embryonic stem (ES) cells,the control cell line,were unidirectionally differentiated into cardiomyocytes n in vitro.The obtained cardiomyocytes were identified and validated by detecting the presence of cardiomyocyte-specific markers using immunofluorescence staining and RT-PCR.The beating frequencies were recorded to compare the functional evaluation for the two groups of cardiomyocyte.Results Both the patient-derived iPSC and H9 ES cells were differentiated into cardiomyocytes successfully.The average beating frequencies of MERRF-induced cardiomyocytes (iCMs) were 13,24,15 and 18 times/min on the day 10,13,15 and 16 during the cell differentiation process.The average beating frequencies of H9-iCMs were 80,96,120 and 120 times/min,respectively.The beating ability of iPSC-differentiated cardiomyocytes was significantly lower than that of corresponding control (all P ＜ 0.05).Conclusion The patient-derived iPSCs may differentiated into cardiomyocytes.Based on the functional evaluation for these cardiomyocytes,the model for MERRF syndrome with mitochondrial mutations was generated and characterized in vitro.

Radiomics and radiogenomics are used to provide comprehensive tumor biological characte-ristics and further clinical information by extracting,screening and analyzing the most valuable quantitative ra-diomics features. In recent years,numerous studies have shown that radiomics plays a role in the diagnosis, treatment and predicting efficacy and prognosis of lung cancer. Radiogenomics shows a great value in the pre-diction of lung cancer gene phenotype and individualized precision treatment by combining radiomics features with genomics,proteomics and so on. Radiomics and radiogenomics are non-invasive,quantitative,and repro-ducible,and they can provide multidirectional tumor biological characteristics,which are expected to be widely used in the precise medical treatment of lung cancer in the future.