Objective:To evaluate the therapeutic efficacy,safety,and factors influencing overall survival(OS)in patients with newly dia-gnosed acute myeloid leukemia(unfit AML)treated with venetoclax(VEN)plus low-dose cytarabine(LDAC)treatment regimen.Methods:In this study,we retrospectively analyzed clinical data from 33 patients with unfit AML treated with VEN plus LDAC at the Affiliated Hospital of Jiangsu University between December 2019 and January 2024.The efficacy and survival outcomes of this regimen were assessed.Results:Thirty-three patients(median age:72 years)were enrolled,including 29 with de novo AML and four with secondary AML.The median follow-up duration was 781 days,with a median OS and progression-free survival(PFS)of 467 days(range:104-812 days)and 395 days(range:104-637 days),respectively.After induction chemotherapy,the overall response rate(ORR)was 69.7%,with a composite rate of complete response(CR)and CR with incomplete blood count recovery(CRi)reaching 36.4%.Morphologic leukemia-free state(MLFS)and partial re-mission(PR)were observed in 3%and 30.3%of patients,respectively.The median number of treatment cycles was three(range:1-6.5).Treatment-related adverse events were primarily hematological,with high rates of grade 3-4 hematologic toxicities.Kaplan-Meier analysis revealed significant associations between survival and ECOG performance status,TP53 mutation status,treatment cycles,and response(P<0.05).Univariate and multivariate Cox regression analyses identified treatment cycles as an independent risk factor for OS(P<0.05).Con-clusions:The VEN plus LDAC regimen demonstrated feasibility and efficacy in patients with newly diagnosed AML;initial response and con-tinuous treatment were associated with favorable survival.

Objective:To evaluate the therapeutic efficacy,safety,and factors influencing overall survival(OS)in patients with newly dia-gnosed acute myeloid leukemia(unfit AML)treated with venetoclax(VEN)plus low-dose cytarabine(LDAC)treatment regimen.Methods:In this study,we retrospectively analyzed clinical data from 33 patients with unfit AML treated with VEN plus LDAC at the Affiliated Hospital of Jiangsu University between December 2019 and January 2024.The efficacy and survival outcomes of this regimen were assessed.Results:Thirty-three patients(median age:72 years)were enrolled,including 29 with de novo AML and four with secondary AML.The median follow-up duration was 781 days,with a median OS and progression-free survival(PFS)of 467 days(range:104-812 days)and 395 days(range:104-637 days),respectively.After induction chemotherapy,the overall response rate(ORR)was 69.7%,with a composite rate of complete response(CR)and CR with incomplete blood count recovery(CRi)reaching 36.4%.Morphologic leukemia-free state(MLFS)and partial re-mission(PR)were observed in 3%and 30.3%of patients,respectively.The median number of treatment cycles was three(range:1-6.5).Treatment-related adverse events were primarily hematological,with high rates of grade 3-4 hematologic toxicities.Kaplan-Meier analysis revealed significant associations between survival and ECOG performance status,TP53 mutation status,treatment cycles,and response(P<0.05).Univariate and multivariate Cox regression analyses identified treatment cycles as an independent risk factor for OS(P<0.05).Con-clusions:The VEN plus LDAC regimen demonstrated feasibility and efficacy in patients with newly diagnosed AML;initial response and con-tinuous treatment were associated with favorable survival.

Objective:To predict the incidence, prevalence, and mortality of dementia in China from 2020 to 2040.Methods:The age-standardized incidence rate (ASIR), incidence number, age-standardized prevalence rate (ASPR), prevalence number, age-standardized mortality rate (ASMR), and death number of dementia in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease Study (GBD) database. We used the overall change rate and estimated annual percentage change (EAPC) to describe the epidemic situation of dementia and compared the trend of dementia between genders. A T-test was used to determine whether EAPC was statistically significant. Every five years, we divided the age into 17 groups to analyze the incidence, prevalence, and mortality of dementia. The prophet model predicted ASIR, ASPR, ASMR, incidence, prevalence, and death from dementia in China from 2020 to 2040.Results:The ASIR, ASPR, and ASMR of dementia showed an increasing trend from 1990 to 2019, with an average annual increase of 0.33%, 0.66%, and 0.15% ( t=10.13, 14.49 and 3.62, all P<0.05). The ASIR, ASPR, and ASMR in males increased faster annually than in females. In 2019, the number of incidence, prevalence, and death from dementia in groups aged≥80 years was the highest among all age groups (685 057 cases, 5 772 861 cases, and 217 827 cases). Prediction results of the prophet model showed that the ASIR, ASPR, and ASMR of dementia were further increased in China from 2020 to 2040, with an average annual increase of 0.55%, 0.78%, and 0.06% ( t=177.63, 161.21, and 7.91, all P<0.05). In 2040, the ASIR, ASPR, and ASMR will reach 117.72/10 5, 940.98/10 5, and 23.64/10 5, respectively. In addition, the number of incidence, prevalence, and death from dementia will show an upward trend from 2020 to 2040. In 2040, the incidence, prevalence, and death will reach 3 334 770 cases, 25 303 146 cases, and 590 138 cases, respectively. Conclusion:From 2020 to 2040, the ASIR, ASPR, ASMR, number of incident cases, number of prevalent cases, and number of deaths due to dementia in China will continue to grow.

Objective To observe area of coagulation necrosis after microwave ablation(MWA)of rabbit liver showed on contrast-enhanced ultrasound(CEUS)in comparison with pathological findings.Methods Twenty-five healthy male experimental rabbits were equally randomly divided into L0,M0,H0,M7 and M14 groups.MWA was achieved with different power and time,and then CEUS and pathological examinations were performed,respectively.Four target areas of rabbit liver were ablated under 20 W for 1 min in L0 group,under 30 W for 1 min in M0 group and under 30 W for 3 min in H0 group,and the ablated areas were observed on the same day after MWA,while 2 target areas of rabbit liver were ablated under 30 W for 1 min in M7 and M14 groups,and the ablated areas were observed 7 days and 14 days after MWA,respectively.The ablated foci and ablated foci+edema band(inflammatory reaction band,IRB)showed on CEUS and pathology were compared,and their differences and changes with time going were analyzed.Results On the day of ablation,the extent of ablation foci,ablation foci+IRB as well as IRB in L0,M0 and H0 groups showed on CEUS were all larger than pathological findings under light microscopy(all P＜0.05),and the difference value of the length of the ablation foci between 2 methods increased sequentially among group L0,M0 and H0(all adjusted P＜0.05).Seven days after ablation,the area of ablation foci measured with CEUS in M 7 group was slightly larger than that measured with pathology(adjusted P=0.045),but no significant difference of the length nor the short diameter was found(both adjusted P＞0.05).Fourteen days after ablation,no significant difference of the length,the short diameter nor the area of ablation foci was detected between 2 methods in M14 group(all adjusted P＞0.05).The length,short diameter and area of ablation foci in M0 group measured with CEUS or pathology were all smaller than those in M 7 and M14 groups(all adjusted P＜0.05),while no significant difference was found between the latter 2 groups(all adjusted P＞0.05).Conclusion On the day of MWA of rabbit liver with different power and time settings,the areas of ablation foci,ablation foci+IRB and IRB showed on CEUS were larger than pathological findings.The range of ablation foci showed on CEUS 7 days after ablation was basically in line with pathology,indicating that CUES should be reexamined 7 days after ablation to evaluate the actual extent of coagulation and necrosis of ablation foci.

Objective:To explored the feasibility and efficacy of a rapid ramp-up,2-week maximum regimen of venetoclax(VEN)plus low-dose cytarabine(LDAC)for treating relapsed/refractory acute myeloid leukemia(R/R AML).Methods:We retrospectively analyzed patients with venetoclax-na?ve R/R AML treated with VEN+LDAC between October 2018 and November 2023.On the first day,patients received 200 mg of VEN,and the dose was quickly increased to 400 mg for the rest of the treatment;cytarabine was administered subcutaneously at a low dose of 20 mg/m2/day.The treatment duration was 10 or 14 days,depending on the condition of bone marrow hyperplasia determined on the 8th day of treatment.No patients received venetoclax monotherapy.All patients responding to salvage therapy received VEN+LDAC until disease progression or transplantation.Results:Among the patients,the median follow-up duration was 27.5 months.No clinical mani-festations of tumor lysis syndrome(TLS)occurred during the treatment.The overall response rate(ORR)was 68.75%,including four com-plete responses(CR),one complete remission with incomplete hematologic recovery(CRi),and six partial responses(PR).The median num-ber of best treatment result cycles was one cycle.The median overall survival(OS)in the whole cohort was 5.8(0.5-47.2)months;the medi-an progression-free survival(PFS)was 22.2(7.3-42.9)months.The major adverse events were grade 3-4 hematologic adverse events and in-fections.Conclusions:The 8th-day myelosuppression-adjusted VEN+LDAC regimen is a feasible salvage option with a reasonable safety pro-file in patients with venetoclax-na?ve R/R AML.Most patients tolerated the 14-day treatment;the response was generally rapid in the re-sponding patients.

Objective:To predict the incidence, prevalence, and mortality of dementia in China from 2020 to 2040.Methods:The age-standardized incidence rate (ASIR), incidence number, age-standardized prevalence rate (ASPR), prevalence number, age-standardized mortality rate (ASMR), and death number of dementia in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease Study (GBD) database. We used the overall change rate and estimated annual percentage change (EAPC) to describe the epidemic situation of dementia and compared the trend of dementia between genders. A T-test was used to determine whether EAPC was statistically significant. Every five years, we divided the age into 17 groups to analyze the incidence, prevalence, and mortality of dementia. The prophet model predicted ASIR, ASPR, ASMR, incidence, prevalence, and death from dementia in China from 2020 to 2040.Results:The ASIR, ASPR, and ASMR of dementia showed an increasing trend from 1990 to 2019, with an average annual increase of 0.33%, 0.66%, and 0.15% ( t=10.13, 14.49 and 3.62, all P<0.05). The ASIR, ASPR, and ASMR in males increased faster annually than in females. In 2019, the number of incidence, prevalence, and death from dementia in groups aged≥80 years was the highest among all age groups (685 057 cases, 5 772 861 cases, and 217 827 cases). Prediction results of the prophet model showed that the ASIR, ASPR, and ASMR of dementia were further increased in China from 2020 to 2040, with an average annual increase of 0.55%, 0.78%, and 0.06% ( t=177.63, 161.21, and 7.91, all P<0.05). In 2040, the ASIR, ASPR, and ASMR will reach 117.72/10 5, 940.98/10 5, and 23.64/10 5, respectively. In addition, the number of incidence, prevalence, and death from dementia will show an upward trend from 2020 to 2040. In 2040, the incidence, prevalence, and death will reach 3 334 770 cases, 25 303 146 cases, and 590 138 cases, respectively. Conclusion:From 2020 to 2040, the ASIR, ASPR, ASMR, number of incident cases, number of prevalent cases, and number of deaths due to dementia in China will continue to grow.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Objective:To explore the value of video-electroencephalography (VEEG) combined with amplitude-integrated electroencephalography (aEEG) in evaluating the condition and prognosis of neonatal hyperbilirubinemia brain injuries.Methods:A total of 120 children with hyperbilirubinemia treatedin the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from July 2019 to July 2020 were enrolled. According to MRI with or without T 1 weighted imging (T 1WI) hyperintensity changes in the globus pallidus, they were divided into the brain injury group (52 cases) and the normal group(68 cases). According to the severity of brain injury, the brain injury group was divided into bilirubin encephalopathy group (23 cases) and subclinical bilirubin brain injury group (29 cases). According to the scores of Gesell Development Scale, the brain injury group was divided into good prognosis group (37 cases)and poor prognosis group (15 cases). The diagnostic value in brain injury with hyperbilirubinemia, the evaluation of the severity of brain injury and the predictive value of VEEG and aEEG were analyzed. Results:The abnormal rates of VEEG and aEEG in the brain injury group were higher than those in the normal group: 76.92% (40/52) vs. 8.82% (6/68), 80.77% (42/52) vs. 11.76% (8/68), the differences were statistically significant ( χ2 = 57.81 and 57.73, P<0.01). The abnormal rates of VEEG and aEEG in bilirubin encephalopathy group were higher than those in subclinical bilirubin brain injury group: 91.30% (21/23) vs. 65.52% (19/29), 95.65% (22/23) vs. 68.97% (20/29), the differences were statistically significant ( χ2 = 4.80 and 5.88, P<0.05). There was no significant difference in abnormal rates of VEEG and aEEG between the good prognosis group and poor prognosis group ( P>0.05). The results of operating characteristic curve analysis showed that the areas under the curve of VEEG combined with aEEG in the diagnosis of brain injury with hyperbilirubinemia, evaluation of the severity of brain injury, predicting the prognosis of children were higher than those of each examination method used alone ( P<0.05). Conclusions:VEEG combined with aEEG has diagnostic value for neonatal brain injury with hyperbilirubinemia, and has evaluation value for severity and prognosis of the disease.

Objective:To explore the effect of mini-clinical evaluation exercise (MiniCEX) and direct observation of procedural skills (DOPS) formative evaluation in standardized residency training of respiratory and critical care medicine.Methods:The residents who participated in standardized residency training of Zhongshan Hospital, Fudan Unviersity in 2019 were collected in study group, and the residents received the training in previous were collected in control group. The graduation examination scores, the effect of progressive rotations and the satisfaction of residents and examiners were compared between the two groups.Results:The scores of medical history writing, operation and clinical abilities were higher in the study group who were received MiniCEX-DOPS formative evaluation than those in the control group ( P<0.05). The scores of MiniCEX-DOPS evaluation in the third rotation were better than those in the first rotation ( P<0.05). The residents and examiners were generally satisfied with MiniCEX-DOPS evaluation. Conclusion:MiniCEX-DOPS evaluation is effective in residents training of respiratory and critical care medicine, and it is worth popularizing.

OBJECTIVE: To explore the effect of heparanase (HPSE) on apoptosis of microvascular endothelial cells (MVECs) and trans-endothelial migration of hepatocellular carcinoma (HCC) cells. METHODS: A HCC cell line with high HPSE expression was selected by real-time quantitative PCR (qRT-PCR) and Western blotting and transefected with a lentiviral vector containing an interfering RNA sequence of HPSE. Transwell migration assay was performed to detect the trans-endothelial migration (TEM) rate of the transfected HCC cells across human umbilical vein endothelial cells (HUVECs). In a Transwell indirect co-culture system, the effect of HPSE silencing in the HCC cells was determined on apoptosis of HUVECs . A nude mouse model of HCC was used to verify the effect of HPSE on apoptosis of MVECs and liver metastasis of the tumor. RESULTS: HCCLM3 cell line highly expressing HPSE was selected for the experiment. Transfection of the HCC cells with the lentiviral vector for HPSE interference the HCC cells resulted in significantly lowered TEM rate as compared with the cells transfected with the control vector ( < 0.01). In the indirect co-culture system, the survival rate of HUVECs co-cultured with HCCLM3 cells with HPSE interference was significantly higher and their apoptotic index was significantly lower than those in the control group ( < 0.05). Ultrastructural observation showed no obvious apoptosis of HUVECs co-cultured with HCCLM3 cells with HPSE interference but revealed obvious apoptotic changes in the control group. In the animal experiment, the tumor formation rate in the liver was 100% (6/6) in the control group, significantly higher than that in RNAi group (33.3%, 2/6) ( < 0.05). Under optical microscope, necrosis and apoptosis of the MVECs was detected in the liver of the control mice, while the endothelial cells remained almost intact in RNAi group. CONCLUSIONS HPSE promotes the metastasis of HCC cells by inducing apoptosis of MVECs.
Animals ; Apoptosis ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Endothelial Cells ; Gene Expression Regulation, Neoplastic ; Glucuronidase ; Humans ; Liver Neoplasms ; Mice