Objective To development and validate a predictive model for distinguishing between malignant pleural effusion(MPE)and benign pleural effusion(BPE).Methods A total of 428 patients diagnosed with pleural effusion(PE)and hospitalized at the First Hospital of Huai'an Affiliated to Nanjing Medical University from July 2020 to May 2022 were selected.The patients were divided into BPE group(211 cases)and MPE group(217 cases)according to diagnostic criteria.The basic information and clinical data of these patients were collected.Boruta method was used for univariate screening,followed by multivariate Logistic regression to construct a basic nomogram model.Bootstrap method was used for internal validation to evaluate the performance of the nomogram,including dis-crimination,accuracy,and clinical applicability.Results The model included 8 key variables:dyspnea,chest pain,general symp-toms,X-ray/CT with malignant tumor features,serum carcinoembryonic antigen,serum neuron-specific enolase,pleural lactate dehy-drogenase,and pleural carcinoembryonic antigen.Internal validation showed that the area under the receiver operating characteristic curve(AUCROC)of the model was 0.933(95%confidence interval:0.912-0.954),with good accuracy(P＞0.05).Decision curve a-nalysis(DCA)indicated that this predictive model for predicting MPE risk had a significant net benefit when the probability threshold exceeded 1%.Conclusion The constructed prediction model could effectively distinguish between MPE and BPE.

Objective To development and validate a predictive model for distinguishing between malignant pleural effusion(MPE)and benign pleural effusion(BPE).Methods A total of 428 patients diagnosed with pleural effusion(PE)and hospitalized at the First Hospital of Huai'an Affiliated to Nanjing Medical University from July 2020 to May 2022 were selected.The patients were divided into BPE group(211 cases)and MPE group(217 cases)according to diagnostic criteria.The basic information and clinical data of these patients were collected.Boruta method was used for univariate screening,followed by multivariate Logistic regression to construct a basic nomogram model.Bootstrap method was used for internal validation to evaluate the performance of the nomogram,including dis-crimination,accuracy,and clinical applicability.Results The model included 8 key variables:dyspnea,chest pain,general symp-toms,X-ray/CT with malignant tumor features,serum carcinoembryonic antigen,serum neuron-specific enolase,pleural lactate dehy-drogenase,and pleural carcinoembryonic antigen.Internal validation showed that the area under the receiver operating characteristic curve(AUCROC)of the model was 0.933(95%confidence interval:0.912-0.954),with good accuracy(P＞0.05).Decision curve a-nalysis(DCA)indicated that this predictive model for predicting MPE risk had a significant net benefit when the probability threshold exceeded 1%.Conclusion The constructed prediction model could effectively distinguish between MPE and BPE.

Objective:To explore the value of multi-gene copy number variation (CNV) analysis in the clinical prognostic prediction of patients with multiple myeloma (MM).Methods:A retrospective case series study was conducted. The clinical data of 79 MM patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to March 2023 were collected. The whole-genome CNV status was obtained by using whole-genome low depth sequencing (sWGS) of bone marrow blood cells. The outcomes of remission, minimal residual disease (MRD) turning negative, progression-free survival (PFS) and overall survival (OS) in patients with and without CNV were compared. The Cox proportional hazards model was used to analyze the influencing factors of PFS and OS.Results:Among the 79 patients with MM, 43 were males and 36 were females. The median age [ M ( Q1, Q3)] was 65 years old (55 years old, 71 years old). In the revised international staging system, there were 20, 51 and 8 cases in stage Ⅰ, Ⅱ and Ⅲ, respectively. The results of fluorescence in situ hybridization (FISH) were abnormal in 17 cases. CNV was detected in 55 patients (69.6%), and the abnormality of chromosome 1q (27 cases, 49.1%) was the most frequently detected, followed by the abnormality of chromosome 13 (26 cases, 47.3%), chromosome 6 (22 cases, 40.0%), chromosome 11 (19 cases, 34.5%), chromosome 8 (18 cases, 32.7%), chromosome 14 (14 cases, 25.5%), and chromosome 17 (11 cases, 20.0%). The ≥ very good partial remission rate in the detected CNV group was lower than that in the undetected CNV group [29.1% (16/55) vs. 45.8% (11/24)], but the difference was not statistically significant ( χ2 = 2.08, P = 0.149). The MRD negative conversion rate of detected CNV group was lower than that of undetected CNV group [21.8% (12/55) vs. 58.3% (14/24)], and the difference was statistically significant ( χ2 = 10.09, P = 0.001). Survival analysis showed that PFS in the detected CNV group was worse than in the undetected CNV group [median PFS time: 36.7 months (95% CI: 6.1-67.4 months) vs. not reached], and the difference between the two groups was statistically significant ( χ2 = 6.61, P = 0.010), while the difference in OS between the two groups was not statistically significant ( χ2 = 1.84, P = 0.175). There was no significant difference in PFS and OS between patients with 1 and ≥2 abnormal copy sequences (both P > 0.05). PFS of patients with CNV on chromosomes 1q, 17, 8, 11 and 13 was worse than that of patients without CNV at these sites (all P < 0.05), while there was no statistical difference in OS (all P > 0.05). Results of univariate analysis showed that lactate dehydrogenase (LDH) level was correlated with PFS and OS of patients (both P < 0.05), and CNV was correlated with PFS of patients (P = 0.010). Results of multivariate analysis showed that LDH > 250 U/L was an independent factor for poor PFS and OS of patients ( HR = 0.135, 95% CI: 0.019-0.983, P = 0.048; HR = 0.132, 95% CI: 0.018-0.951, P = 0.045). Conclusions:Multi-gene CNV analysis can assist in predicting the prognosis of MM patients, and it is more sensitive than traditional CNV detection methods such as FISH. Patients with CNV on chromosomes 1q, 17, 8, 11, and 13 have poor prognosis.

Objective:To explore the value of multi-gene copy number variation (CNV) analysis in the clinical prognostic prediction of patients with multiple myeloma (MM).Methods:A retrospective case series study was conducted. The clinical data of 79 MM patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to March 2023 were collected. The whole-genome CNV status was obtained by using whole-genome low depth sequencing (sWGS) of bone marrow blood cells. The outcomes of remission, minimal residual disease (MRD) turning negative, progression-free survival (PFS) and overall survival (OS) in patients with and without CNV were compared. The Cox proportional hazards model was used to analyze the influencing factors of PFS and OS.Results:Among the 79 patients with MM, 43 were males and 36 were females. The median age [ M ( Q1, Q3)] was 65 years old (55 years old, 71 years old). In the revised international staging system, there were 20, 51 and 8 cases in stage Ⅰ, Ⅱ and Ⅲ, respectively. The results of fluorescence in situ hybridization (FISH) were abnormal in 17 cases. CNV was detected in 55 patients (69.6%), and the abnormality of chromosome 1q (27 cases, 49.1%) was the most frequently detected, followed by the abnormality of chromosome 13 (26 cases, 47.3%), chromosome 6 (22 cases, 40.0%), chromosome 11 (19 cases, 34.5%), chromosome 8 (18 cases, 32.7%), chromosome 14 (14 cases, 25.5%), and chromosome 17 (11 cases, 20.0%). The ≥ very good partial remission rate in the detected CNV group was lower than that in the undetected CNV group [29.1% (16/55) vs. 45.8% (11/24)], but the difference was not statistically significant ( χ2 = 2.08, P = 0.149). The MRD negative conversion rate of detected CNV group was lower than that of undetected CNV group [21.8% (12/55) vs. 58.3% (14/24)], and the difference was statistically significant ( χ2 = 10.09, P = 0.001). Survival analysis showed that PFS in the detected CNV group was worse than in the undetected CNV group [median PFS time: 36.7 months (95% CI: 6.1-67.4 months) vs. not reached], and the difference between the two groups was statistically significant ( χ2 = 6.61, P = 0.010), while the difference in OS between the two groups was not statistically significant ( χ2 = 1.84, P = 0.175). There was no significant difference in PFS and OS between patients with 1 and ≥2 abnormal copy sequences (both P > 0.05). PFS of patients with CNV on chromosomes 1q, 17, 8, 11 and 13 was worse than that of patients without CNV at these sites (all P < 0.05), while there was no statistical difference in OS (all P > 0.05). Results of univariate analysis showed that lactate dehydrogenase (LDH) level was correlated with PFS and OS of patients (both P < 0.05), and CNV was correlated with PFS of patients (P = 0.010). Results of multivariate analysis showed that LDH > 250 U/L was an independent factor for poor PFS and OS of patients ( HR = 0.135, 95% CI: 0.019-0.983, P = 0.048; HR = 0.132, 95% CI: 0.018-0.951, P = 0.045). Conclusions:Multi-gene CNV analysis can assist in predicting the prognosis of MM patients, and it is more sensitive than traditional CNV detection methods such as FISH. Patients with CNV on chromosomes 1q, 17, 8, 11, and 13 have poor prognosis.

Chronic hepatitis B (CHB) causes approximately 30% cirrhosis and 53% liver cancer in the world, and is still a serious threat to human health. Treatment CHB through therapeutic vaccination has long been a urgent goal of the medical community. In the past two decades, various therapeutic vaccines have been developed and studied in clinical trials, however, few has achieved satisfactory results. Recently, a nanoparticle therapeutic vaccine for CHB, εPA-44, has entered pahse III clinical trial. Results of phase II trial for εPA-44 showed that the vaccine had good safety profile and achieved profound clinical benefits in patients with CHB. Here, we first introduce the rational of therapeutic vaccine for CHB and summarize the progress of clinical trials. Finally, we t review the phase II clinical trial data of εPA-44 and discuss the posssible impact to the development of next generation therapeutic vaccine for CHB.

AIM:To investigate the effect of Notch-1 knockdown on the growth of dihydroartemisinin-inhibited human osteosarcoma cell line U-2OS.METHODS:U-2OS cells treated with different concentrations of dihydroartemisinin (5, 10, 15 and 20μmol/L) were collected.The expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels was measured by real-time PCR and Western blotting, respectively.U-2OS cells were transfected with Notch-1 siRNA for 24 h and incubated with dihydroartemisinin for another 24 h.The cell apoptotic rate , protein expression of MMP-2, MMP-9 and Hes-1, and the migration ability were measured by MTT assay , Western blotting and Transwell experiment , respectively.RESULTS:Dihydroartemisinin (5, 10, 15 and 20 μmol/L) decreased the expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels in a dose-dependent manner .Down-regulation of Notch-1 significantly en-hanced the effect of dihydroartemisinin on the cell apoptosis , the protein expression of MMP-2, MMP-9 and Hes-1, and mi-gration ability ( P<0.05 ) .CONCLUSION: Notch-1 pathway is involved in the process of dihydroartemisinin-inhibited U-2OS cell growth.Knockdown of Notch-1 augments the inhibitory effect of dihydroartemisinin on U-2OS cell viability.

Objective:To predict and analyze the secondary structure and B cell epitopes of Izumo protein.Methods: The secondary structure and flexible regions of Izumo protein were predicted by the methods of Chou-Fasman,Gamier-Robson and Karplus-Schulz.Moreover,hydrophilicity plot,surface probability plot and antigenic index of Izumo protein were predicted by the methods of Kyte-Doolitde,Emini and Jameson-Wolf,respectively.Results: Izumo protein contained moreαhelix regions.There were several centers ofαhelix in the regions of 6-17,30-40,88-99,103-120,153-160,173-188,249-260,283-297,334-338 and 339-346 of Izumo protein,and several centers of βsheet in the regions of 21-25,198-200,245-248 and 320-323.Moreover,many distinct B cell epitopes in Izumo protein possibly localized in the regions of 3642,62-66,94-99,118-122,129-132,151-154,161-164,173-177,205-208,212-216,256-265,271-276,283-288,314-318 and 336-350.Conclusion:These results are helpful for identification of the dominant B cell epitopes and the functional domains of Izumo protein.

Objective: To investigate the impact of stroke unit (SU) on the compliance of secondary prevention in patients with stroke at 12 months after stroke. Methods: Research subjects were stroke patients who were treated in SU (n = 500) and in general ward (GW) (n =445) using a design of retrospective study. The patients in the SU group were followed up by hospital, telephone and home interviews for 12 months, and the patients in the GW group were followed up by telephone interview for 12 months. The main outcome measures were the rate of using antithrombotics, the rate of smoking cessation, and the rates of awareness of early stroke symptom and stroke risk factors of patients. Results: he rate of using antithrombotics was 92.76% in the SU group, and it was significantly higher than 51.49% in the GW group (P ＜0.01); the rate of smoking cessation, and the rates of awareness of early stroke symptom and stroke risk factors of patients were 82.33%, 91.04%, and 94.03% respectively in the SU group, and they were significantly higher than 54.75%, 6.53%, and 70.37% in the GW group(P all ＜ 0.01 ). Conclusions: SU attaches importance to the secondary stroke prevention and emphasizes standardized treatment, and the compliance of the secondary stroke prevention in patient with stroke is improved significantly.

Objective To investigate the effect of thymosin ?1 (T?1) on cellular immune function in gastric cancer patients through observing its treatment on the differentiation of T-lymphocyte subsets from screened peripheral blood mononuclear cells (PBMCs). Methods PBMCs were obtained by centrifugation of blood samples from 18 healthy subjects and 32 patients with gastric cancer,and then cultured in the presence of culture medium with addition of T?1 at 50,10 and 1 ?g/ml for 2 d. T lymphocyte subsets (such as CD4+,CD8+ and CD4+ CD25+ Foxp3+ T cells) and Th1/Th2 multiplex cytokines were detected by flow cytometry (FCM). Results After PBMCs isolated from healthy people and patients were incubated with or without T?1,there was no significant change in percentage of CD4+,CD8+ peripheral lymphocyte subsets and ratio of CD4+/CD8+. There was no obvious change in the percentage of CD4+ CD25+ Foxp3+ T lymphocyte subsets in the normal control,but a significant increase was observed in the cells from patients with gastric cancer after treatment (P