Objective To investigate the predictive value of the prognostic nutritional index(PNI)in all-cause mortality in pa-tients with acute and critical illness.Methods Acute and critically ill patients admitted to the Department of Emergency,Beijing Chao-yang Hospital,Capital Medical University,from March to July 2021 were selected as study subjects,and the relevant clinical data within 24h of their admission to the emergency department were collected and analyzed descriptively.The receiver operating characteristic(ROC)curve of PNI was drawn with all-cause mortality of patients within 28days as the endpoint,and the patients were divided into high PNI and low PNI groups according to the optimal cut-off value,and the clinical characteristics of the two groups were compared.Patients were divided into survival and death groups according to whether they died within 28days,and the clinical characteristics of the two groups were compared,and univariate and multivariate Logistic regression analysis was used to explore the risk factors for all-cause mortality within 28days in patients with acute and critical illness.Results A total of 603 patients were included,and the optimal cut-off value of PNI was 43.825,according to which all patients were divided into the high PNI group(n=334)and low PNI group(n=269),and it was found that the proportion of patients who all-cause mortality within 28days was significantly higher in the low PNI group than in the PNI group(P＜0.05).All patients died within 28days of admission to the emergency department in 127 cases,and the pro-portion of malnourished patients was significantly higher in the death group than that in the survival group(P＜0.05).Logistic regression analysis showed that malnutrition at admission to the emergency department screened by PNI was an independent risk factor for all-cause mortality within 28days in patients with acute and critical illness(OR=1.805,95％CI:1.157-2.817,P=0.009),and advanced age,low body mass index,and low hemoglobin levels were also independent risk factors for all-cause mortality within 28days.Conclu-sion Patients with acute and critical illness are at high risk of malnutrition,and malnutrition at admission to the emergency department,advanced age,low body mass index,and low hemoglobin levels screened by PNI are independent risk factors for all-cause mortality with-in 28 days.

Objective:To analyze germline pathogenic mutations in patients with upper tract urothelial carcinoma(age≤60 years old), and to explore the clinicopathological characteristics of germline pathogenic mutation carriers.Methods:The data of 124 patients (age≤60 years old) with upper tract urothelial carcinoma who underwent germline genetic testing at Fudan University Shanghai Cancer Center from September 2008 to February 2023 were retrospectively analyzed. There were 86 males and 38 females, and the median age was 55.0(49.8, 58.0)years old. The primary tumors were located in the renal pelvis in 81 cases (65.3%), the ureter in 34 cases (27.4%), and both in 9 cases (7.3%). There were 13 patients (10.5%) with low-grade UTUC and only 8 patients (6.5%) with carcinoma in situ. Twelve patients (9.7%) had a history of bladder cancer and 12 (9.7%) had a history of malignancy other than bladder cancer. Whole gene exome sequencing or target region sequencing was performed to explore germline mutations associated with patients with UTUC. The germline genetic testing data were interpreted in accordance with the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP)2015 edition guideline to clarify the germline pathogenic mutation rate and elucidate the clinicopathological characteristics of germline pathogenic mutation carriers. Germline pathogenic mutation rates were further compared with those of healthy East Asian populations to analyze germline mutations associated with the risk of carcinogenesis in UTUC.Results:In this study, 31 germline pathogenic mutations were detected in 28 (22.6%) of 124 patients with UTUC. There were no statistically significant differences in age [54.0 (47.0, 58.0) years old vs. 56.0 (50.8, 58.0) years old], gender (male/female: 21/7 vs. 65/31), history of bladder cancer (0 vs. 12/96), T-stage (T 3-4: 12/28 vs. 41/96), and proportion of histologic high-level (26/28 vs. 85/96) between patients with and without germline pathogenic mutations ( P>0.05). The 31 germline pathogenic mutations were located in 22 genes, including BRCA2 (4, 12.9%), MSH2 (3, 9.7%), RAD54L (2, 6.5%), BRCA1 (2, 6.5%), BRIP1 (2, 6.5%), NOTCH3 (2, 6.5%), XRCC2 (1, 3.2%), VEGFA (1, 3.2%), TBX3 (1, 3.2%), RET (1, 3.2%), PRKN (1, 3.2%), PALB2 (1, 3.2%), NTRK1 (1, 3.2%), NCOA3 (1, 3.2%), MSH6 (1, 3.2%), LRP1B (1, 3.2%), KMT2D (1, 3.2%), KMT2A (1, 3.2%), FANCA (1, 3.2%), BARD1 (1, 3.2%), ARID1A (1, 3.2%), and AR (1, 3.2%). The germline pathogenic mutation rates of 124 patients were compared with those of the healthy East Asian population. The results showed that germline pathogenic mutations in BRCA2 ( OR = 11.9, 95% CI 3.8 - 37.7, P<0.001), MSH2 ( OR = 11.9, 95% CI 3.2-44.5, P<0.001), RAD54L ( OR=14.2, 95% CI 2.7-73.8, P=0.002) and BRCA1 ( OR=11.8, 95% CI 2.4-59.1, P=0.003) genes significantly increase the risk of developing UTUC. Conclusions:The rate of germline pathogenic mutations in ≤60 years old UTUC patients in this study was 22.6%, and germline pathogenic mutations carrying germline BRCA2, MSH2, RAD54L or BRCA1 genes significantly increased the risk of developing UTUC.

Objective:To investigate the effect of adenosine deaminase acting on RNA 1 (ADAR1) on 5-serotonin-2c receptor in alleviating aggression in socially isolated mice.Methods:Sixty healthy male BALB / c mice aged 21 days were randomly divided into six groups: social isolation group, social control group, ADAR1 inducer social isolation group, ADAR1 inhibitor social isolation group, ADAR1 inducer social control group and ADAR1 inhibitor control group.The mice fed in single cage for 4 weeks were used as social isolation model while the mice fed in group were used as control group.ADAR1 inducer (5.0×10 4 U/kg) and inhibitor (10 mg/kg) were given intraperitoneally to mice in the ADAR1 inducer social isolation group and the ADAR1 inhibitor social isolation group respectively.The aggressive behavior of mice was evaluated by resident-intruder test.The expression of ADAR1 and 5-serotonin-2c receptors in the brain of mice was detected by immunohistochemistry and Western blot. Results:The attack latency of social isolation group was significantly lower than that of social control group ((43.15±6.99) s, (542.40±30.50) s; t=15.906, P<0.01), and the latency of attack ((256.70±29.49) s) in the ADAR1 inducer social isolation group was significantly higher than that in the social isolation group ( t=7.046, P<0.01). The latency of attack ((15.25±2.18)s) in the ADAR1 inhibitor social isolation group was significantly lower than that in the social isolation group ( t=3.809, P<0.01). The optical density of ADAR1 immunoreactive cells in the amygdala of the social isolation group mice was significantly lower than that in the corresponding brain area of the social control group (BLA: (0.038±0.002), (0.074±0.004); LaDL: (0.033±0.002), (0.060±0.002); LaVM: (0.045±0.003), (0.073±0.004); Lavl area: (0.044±0.003), (0.070±0.003); t=8.428, 9.037, 6.462, 5.698, all P<0.01). The optical density of ADAR1 immunoreactive positive cells in the amygdala (BLA: (0.060±0.003), LaDL: (0.042±0.002), LaVM: (0.056±0.004), Lavl: (0.054±0.003) in the ADAR1 inducer social isolation group was significantly higher than those in the corresponding brain area of the social isolation group mice ( t=6.055, 2.876, 2.312, 2.492; all P<0.05). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in amygdala of social isolation group were significantly lower than those of social isolation group ( t=11.37, 12.65; P<0.01). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in the amygdala of the ADAR1 inducer social isolation group were significantly higher than those of the social isolation group ( t=3.02, 4.401; P<0.05). Conclusion:ADAR1 inducer alleviates the aggressive behavior of social isolated BALB / c mice by enhancing the protein expression of 5-serotonin-2c receptor in the amygdala of social isolated BALB/c mice.

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.

Objective To explore the effects of ADAR1 inducer and inhibitor on cognition and ADAR1 expression of isolated BALB/c mice.Methods Sixty healthy BALB/c mice were divided into 6 groups according to randomized design with 10 animals each group,the gregarious control group (GH),social isolation model group (SI),ADAR1 inducer treated gregarious group (GH+IFN-γ),ADAR1 inhibitor treated gregarious group (GH+EHNA),ADAR1 inducer treated isolation group (SI+IFN-γ) and ADAR1 inhibitor treated isolation group (SI+EHNA).Mice in drug treatment groups were treated with ADAR1 inducer (5.0? 104 U/kg,20 ml/kg,ip) and inhibitor (10 mg/kg,20 ml/kg,ip).Objection recognition test was used to measure cognition.Immunohistochenmistry was used to measure ADARI immunoreactivity and Western blotwas used to measure ADAR1 protein expression.Results In the objection recognition test,the non-spatial discrimination index of mice in SI group (-0.16±0.09) was significantly lower than that of GH group (0.41 ±0.17,P＜0.01),the non-spatial discrimination index of mice in SI+IFN-γ group (0.20±0.09) and in SI+ EHNA group (-0.29±0.12) was higher (P＜0.01) and lower (P＜0.05) than that of the SI group respectively.The immunohistochemistry results showed that the ADAR1 immunoreactivity in hippocampus of mice in SI group (Hilus:(0.013±0.003),CAI:(0.021±0.005)) decreased significantly compared to those of GH group(Hilus:(0.021 ±0.002),(0.047±0.004);both P＜0.05).And GH+IFN-γgroup mice showed increased ADAR1 immunoreactivity obviously in Hilus ((0.013±0.003) vs (0.023±0.004),P＜0.01) and in CA1 ((0.021±0.005) vs (0.040±0.005),P＜0.01) compared with that of SI group,ADAR1 inducer recovered the above abnornal ADAR1 immunoreactivity.Western blot results showed that the ADAR1 protein expression of mice in SI group (0.48 ±0.07) in hippocampus was significantly decreased (P＜0.01) compared to that of GH group (1.00 ±0.00).The level of ADAR1 protein in SI+IFN-γgroup(0.82 ±0.04) increased compared with that of SI group.Conclusions Four weeks of social isolation can reduce the non-spatial cognitive ability of BALB/c mice and decrease the expression of ADAR1 in the hippocampus.The ADAR1 inducers and inhibitors can reverse and aggravate the cognitive impairment caused by social isolation respectively.The related mechanisms may be related to the expression of ADAR1.

Objective To investigate the current situation in Chinese rheumatologic physicians' clinical diagnosis and evaluation of Takayasu's arteritis (TA).Methods Nineteen rheumatology experts and three vascular surgery specialists in China were invited to make the nationwide investigation for the first time about the diagnosis and disease activity evaluation of TA in China,through the questionnaire survey on the internet.Weighted average was used to calculate the average scores of corresponding problems.Results Chinese experts mainly adopted 1990 American College of Rheumatology (ACR) classification criteria for clinical diagnosis of TA.In details,symptoms of age,limb claudication and amaurosis,signs including pulselessness or pulse weakening,vascular bruits,increasing bilateral pulse pressure and hypertension and acute phase reactants (APR) were critical to the clinical diagnosis of TA.Besides,noninvasive imaging examinations,such as computed tomography angiography (CTA),magnetic resonance angiography (MRA),vascular ultrasonography,and positron emission tomography (PET) were also of great importance.In the aspect of disease activity assessment,Chinese experts mainly used Kerr scoring tool.APR and noninvasive radiological examinations were considered with vital value.Some TA patients with carotid artery involvement were recommended using vascular ultrasonography,while others with pulmonary artery and thoracic/abdominal aorta trunk involvement were preferred CTA other than MRA.Conclusions APR and noninvasive imaging examinations were thought with great help to make clinical diagnosis and evaluation of TA for Chinese physicians.

OBJECTIVETo investigate the frequency of USP6 gene rearrangement in nodular fasciitis (NF) and to evaluate its clinical application.

METHODSTwenty nine cases of previously diagnosed NF were screened for the presence of the USP6 gene rearrangement by interphase fluorescence-in-situ hybridization (FISH) on formalin-fixed paraffin-embedded tissue. Fifteen of these cases, which had available tissue, were also analysed for MYH9-USP6 fusion transcripts by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSTwenty four of the 29 cases (83%) were positive for the USP6 gene rearrangement by interphase FISH. The 15 cases with RT-PCR showed the following results: 11 positive, one deletion and three negative for USP6 gene rearrangement. Of these 15 cases, eight (8/15) showed MYH9-USP6 fusion transcript by RT-PCR. Of these eight cases, seven were positive for USP6 gene rearrangement and one showed USP6 deletion by FISH.

CONCLUSIONSUSP6 gene rearrangement is a recurrent genetic event in NF. It is a valuable ancillary tool for the pathological diagnosis of these lesions.

Fasciitis ; genetics ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Interphase ; Proto-Oncogene Proteins ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic ; Ubiquitin Thiolesterase ; genetics

Objective To evaluate the capability of 18 F-FLT uptake and investigate the early radiation response of human colorectal cancer cells HCT116 exposed to 6 MV X-rays.Methods 3.7 kBq 18F-FLT was added to HCT116 cells with different cell numbers (1.0 × 105-1.5 × 106) and cultured with different times (36,60,84 h).The 18F-FLT uptake rate was measured with a γ-counter after exposed to different does of 6 MV X-rays (0,2,4,6,8 Gy) after 24,48,and 72 h of irradiation.Then the cell uptake inhibition rate,cell proliferation,and cell cycle phase were measured.Results The uptake rate of 18F-FLT in HCT116 was (18.97 ± 1.16)％.The 18F-FLT uptake inhibition rates at 24 h after different does of irradiation (2,4,6,8 Gy) were (32.10±0.02)％,(54.46 ±0.04)％,(62.74 ±0.04)％,and (65.81 ±4.81)％,respectively,which was positively correlated with radiation dose.Conclusions The 18F-FLT uptake rate of human colorectal cancer HCT116 cells could be used to evaluate the early radiation response.