Objective: To analyze the trend in the mortality of liver cancer in Ningbo City from 2002 to 2021, so as to provide the evidence for improving the liver cancer control measures. Methods: The liver cancer mortality data in Ningbo City from 2002 to 2021 were collected from Ningbo Municipal Chronic Disease Surveillance System. The crude mortality and standardized mortality by the 2 000 national population census data of liver cancer were estimated, and the proportion of concomitant diseases was analyzed among all dead patients with liver cancer. In addition, the trends in liver cancer mortality were analyzed with annual percentage change (APC) and average annual percentage change (AAPC). Results: Both the crude and standardized mortality of liver cancer appeared a tendency towards a decline year by year in Ningbo City from 2002 to 2021, with AAPC of -3.47% (95%CI: -4.08% to -2.85%, P<0.001) and -6.56% (95%CI: -7.25% to -5.87%, P<0.001), and a the decline in liver cancer mortality was larger during the period between 2006 and 2021 than during the period between 2002 and 2006. The annual mean crude and standardized mortality of liver cancer was 35.39/105 and 20.98/105, and the crude mortality of liver cancer was 52.69/105 in men and 18.13/105 in women, respectively. After adjustment for age, the risk of liver cancer mortality was 3.03 (95%CI: 2.96-3.09) times greater among men than among women, and the mortality of liver cancer appeared a tendency towards a rise with age (χ2trend=45 684.254, P<0.001). Concomitant diseases were found among 9 985 dead cases with liver cancer (24.44%), and the concomitant diseases mainly included digestive system diseases (predominantly liver diseases) and infectious and parasitic diseases (predominantly virus hepatitis). Conclusions The mortality of liver cancer appeared a tendency towards a decline in Ningbo City from 2002 to 2021, and men and middle-aged and elderly residents were at high risk of liver cancer mortality. Digestive system diseases and infectious and parasitic diseases were predominant concomitant diseases among dead patients with liver cancer.

Objective: To investigate the trends in mortality of malignant tumors in Ningbo City, Zhejiang Province from 2002 to 2022, so as to provide the evidence for formulating malignant tumor control strategies in Ningbo City. Methods The data regarding the mortality of malignant tumors in Ningbo City from 2002 to 2022 were collected through the Ningbo Municipal Death Cause Monitoring System, and the crude mortality and age-specific mortality of malignant tumors were calculated in Ningbo City. The mortality of malignant tumors was standardized by the population of the sixth National Population Census in China in 2010 (Chinese-standardized mortality) and the world standard population in 1960 (world-standardized mortality). The trends in mortality of malignant tumors were evaluated with annual percent change (APC) and average annual percent change (AAPC). Methods: The data regarding the mortality of malignant tumors in Ningbo City from 2002 to 2022 were collected through the Ningbo Municipal Death Cause Monitoring System, and the crude mortality and age-specific mortality of malignant tumors were calculated in Ningbo City. The mortality of malignant tumors was standardized by the population of the sixth National Population Census in China in 2010 (Chinese-standardized mortality) and the world standard population in 1960 (world-standardized mortality). The trends in mortality of malignant tumors were evaluated with annual percent change (APC) and average annual percent change (AAPC). Results: The crude mortality of malignant tumors was 186.43/105 to 221.24/105 in Ningbo City from 2002 to 2022, which showed a tendency towards a rise (AAPC=0.76%), and both the Chinese- (AAPC=-2.64%) and world-standardized mortality (AAPC=-2.74%) appeared a tendency towards a decline (all P<0.05). The world-standardized mortality of malignant tumors presented three changes in Ningbo City from 2002 to 2022, with a more remarkable decline from 2011 to 2018 (APC=-3.53%) than from 2002 to 2011 (APC=-2.10%) and from 2018 to 2022 (APC=-2.00%) (all P<0.05). The annual decline in mortality of malignant tumors was higher in men (Chinese-standardized mortality: AAPC=-2.68%; world-standardized mortality: AAPC=-2.75%) than in women (Chinese-standardized mortality: AAPC=-2.45%; world-standardized mortality: AAPC=-2.57%), and higher in urban areas (Chinese-standardized mortality: AAPC=-2.85%; world-standardized mortality: AAPC=-2.92%) than in rural areas (Chinese-standardized mortality: AAPC=-2.45%; world-standardized mortality: AAPC=-2.57%) (all P<0.05). The mortality of malignant tumors appeared a tendency towards a rise with age in Ningbo City, with the highest mortality in residents at ages of 85 years and older (1 447.13/105). Death from malignant tumors were responsible for 31.86% of all causes of death in Ningbo City, and the five most common causes of cancer death included lung cancer, liver cancer, gastric cancer, colorectal cancer and esophageal cancer. In addition, the world-standardized mortality of pancreatic cancer (AAPC=3.92%), prostate cancer (AAPC=4.71%), and cervical cancer (AAPC=1.60%) appeared a tendency towards a rise in Ningbo City (all P<0.05). Conclusions The crude mortality of malignant tumors appeared a tendency towards a rise in Ningbo City from 2002 to 2022, while the standardized mortality showed a tendency towards a decline. Management of malignant tumors should be given a high priority among men and rural residents, and lung cancer, liver cancer, gastric cancer, colorectal cancer and esophageal cancer should be emphasized.

Objective: To investigate the trends in incidence and mortality of gastric cancer in Ningbo City, Zhejiang Province from 2011 to 2022, so as to provide insights into improving gastric cancer control strategy. Methods: The incidence and mortality of gastric cancer in Ningbo City from 2011 to 2022 were collected through Ningbo Municipal Chronic Disease and Cause of Death Monitoring System. The incidence and mortality of gastric cancer were calculated, and standardized by the data from the Sixth Chinese National Population Census in 2020 (Chinese-standardized rate) and the world standard population first introduced by Segi in 1960 (world-standardized rate). The trends in incidence and mortality of gastric cancer were evaluated using annual percent change (APC) and average annual percent change (AAPC). Results : The crude incidence of gastric cancer was 45.69/105 in Ningbo City from 2011 to 2022, with no significant changing patterns seen during the study period (AAPC=-0.02%, P>0.05), and the Chinese- and world-standardized incidence of gastric cancer was 28.61/105 and 21.87/105, which both appeared a tendency towards a decline (AAPC=-3.19% and -3.05%, both P<0.05). The crude, Chinese-standardized and world-standardized mortality rates of gastric cancer were 28.56/105, 17.07/105 and 12.57/105, respectively, all showing a tendency towards a decline (AAPC=-3.00%, -6.26% and -6.34%, all P<0.05). The Chinese- and world-standardized incidence and mortality of gastric cancer all appeared a tendency towards a decline in urban (AAPC=-2.72%, -2.53%, -5.91% and -5.96%, all P<0.05) and rural areas (AAPC=-3.61%, -3.53%, -6.79% and -6.89%, all P<0.05), and the Chinese- and world-standardized incidence and mortality of gastric cancer were significantly higher among urban residents than among rural residents. The Chinese- and world-standardized incidence and mortality of gastric cancer all appeared a tendency towards a decline among men (AAPC=-3.18%, -3.00%, -5.82% and -5.91%, all P<0.05) and women (AAPC=-2.98%, -2.90%, -7.12% and -7.12%, all P<0.05), and the Chinese- and world-standardized incidence and mortality of gastric cancer was significantly higher among men than among women. In addition, the crude incidence and mortality of gastric cancer both appeared a tendency towards a rise with age among residents in Ningbo City (both P<0.05). Conclusions The incidence and mortality of gastric cancer both appeared a tendency towards a decline in Ningbo City from 2011 to 2022; however, the incidence and mortality remained high. Males and urban residents should be given a high priority for gastric cancer control, and gastric cancer screening should be strengthened among individuals at ages of 40 years and older.

Objective To investigate the mechanism of matrine in inhibition of proliferation the proliferation of human chronic myeloid leukemia (CML) K562 cells via MEK-ERK signaling pathway. Methods Western blot was used to detect the expression of MEK1, ERK1/2, Shc and SHP2 (the signal effect molecules of MEK-ERK pathway) in K562 cells. The transcription and translation of bcr-abl and target protein (bcl-xL, Cyclin D1, c-myc and p27) were detected by RT-PCR and Western blot. Results Matrine was able to significantly inhibit the phosphorylation of MEK1, ERK1/2, Shc and SHP2 in K562 cells and suppress the protein and mRNA expression of bcr-abl. Moreover, the expressions of bcl-xL, Cyclin D1 and c-myc were down-regulated significantly, while the expression level of p27 (a negative regulator of cell cycle progression) was increased markedly after matrine treatment. Conclusions Suppression of the growth of human CML K562 cells is related to the inhibition of bcr-abl-mediated MEK-ERK pathway activity. The down-regulation of phosphorylated proteins or protein kinases activity in signaling pathways might be an important molecular mechanism in control the activity of MEK-ERK pathway.

Objective TosummarizeMRIfeaturesofadultreversiblespleniallesionsyndrome(RESLES)andevaluateitsdiagnosticvalue. Methods ClinicalandMRIdataof15patientswithRESLESwereanalyzedretrospectively.Primarydiseasesandcausesincluded:encephalitis disease,cerebrovasculardiseases,metabolicandelectrolytedisorders.Theclinicalsymptomswereheadache,dizziness,changeofconsciousness, epilepticseizuresandothernonspecificneurologicsymptoms.Thecranialimagingexaminationwasperformedat3.0T/1.5TsuperconductingMR, includingT1WI,T2WI,T2FLAIRandDWI,inwhich7casesunderwentMRIenhancedscanand5casesunderwentMRAexamination.Results Among15patients,MRIfindingsofallpatientswerecharacterizedbythecharacteristic"boomerangsign"ortheovoidabnormalitysignalinthe corporiscallosisplenium,whichwaspresentedascytotoxicedema.Besides,4ofthem werecombinedwithposteriorreversibleencephalopathy syndrome(PRES),whichwascharacterizedbyvasogenicedemainthebilateraloccipital,temporal,parietallobeandcerebellarhemisphere.The clinicalsymptomsofallpatientsimprovedafterreasonabletreatment.Conclusion MRIcharacteristicfindingofadultreversiblesple-niallesionsyndromeisthecytotoxicedemaofthecorpuscallosum,whichcanbeshowedas"boomerangsign"orovalform.Imagingfindingsand clinicalsymptomsarereversible.Thecorrectunderstandingofthisdiseaseisofgreatsignificancetoclinicalrationaldiagnosisandtreatment.

OBJECTIVETo correlate the clinical features of patients with acute myeloid leukemia (AML) with mutations of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 genes as well as chromosomal aberrations.

METHODSSomatic mutations of aforementioned genes in 412 newly diagnosed AML patients were detected with PCR and direct sequencing. All patients were also subjected to R-banding chromosomal analysis. The results were correlated with the clinical features and prognosis of the patients.

RESULTSThe mutation rates of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 were 9.0% (26/289), 19.1% (50/262), 18.9% (34/180), 3.4% (7/208), 6.6% (9/137) and 6.9% (4/58), respectively. Patients with poor prognosis based on genetic mutations had lower blood platelet count than those with intermediate and good prognosis (P=0.001 and P=0.001, respectively). None of the three groups attained median overall survival (OS) (P> 0.05). The complete remission (CR) was similar among the three groups (P> 0.05). For patients with different prognosis based on cytogenetic findings, white blood cell count in those with intermediate prognosis was higher than those with good and poor prognosis (P< 0.001 and P=0.004, respectively), while the blood platelet count of the intermediate group was higher than that of the group with good prognosis (P=0.018). No significant difference was found among the three groups in terms of hemoglobin level (P> 0.05). The group with poor prognosis has attained shorter OS compared with those with good and intermediate prognosis (P< 0.001 and P=0.003, respectively). However, the CR rate of the group with good prognosis was higher than that of the intermediate group (P=0.001). For the group with intermediate prognosis, presence of genetic mutations did not correlate with the clinic characteristics such as white blood cell count, blood platelet count, hemoglobin level, OS and CR rate (P> 0.05 for all comparisons).

CONCLUSIONGenetic mutations combined with cytogenetic analysis can facilitate the prognosis and personalized treatment for patients with AML.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Leukemia, Myeloid, Acute ; genetics ; mortality ; Male ; Middle Aged ; Mutation ; Prognosis ; Young Adult

Objective:To investigate the effect of obesity on the efficacy of allogeneic hematopoietic stem cell transplantation.Methods:The clinical data of 81 patients who underwent allogeneic hematopoietic stem cell transplantation from August 2017 to September 2020 in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. According to the body mass index (BMI), the patients were divided into the obese group (BMI≥28 kg/m 2, 11 cases) and the non-obese group (BMI<28 kg/m 2, 70 cases). The clinicopathological characteristics, hematopoietic stem cell implantation, post-transplantation complications, survival and recurrence were compared between the two groups. Univariate and multivariate survival analyses were performed by using Cox proportional hazards regression model. Results:The median follow-up time of 81 patients was 280 d (8-1 218 d). The 1-year overall survival (OS) rate was 77.9%, and the 1-year progression-free survival (PFS) rate was 73.8%. The 1-year OS rates of the non-obese group and the obese group were 82.6% and 46.2% ( χ2 = 15.54, P<0.01), and the 1-year PFS rates were 82.1% and 36.4% ( χ2 = 15.56, P<0.01). The non-recurrence mortality (NRM) rates of the non-obese group and the obese group were 7.1% and 32.7% ( χ2 = 6.463, P = 0.01), and the cumulative recurrence rate was 11.5% and 42.9% ( χ2 = 8.146, P = 0.004). Between the non-obese group and the obese group, the median engraft time of neutrophils and platelets, acute graft-versus-host disease, chronic graft-versus-host disease, hemorrhagic cystitis, cytomegalovirus infection and Epstein-Barr virus infection had no statistical difference ( P > 0.05). The result of multivariate analysis showed that obesity was an independent adverse influencing factor for OS of patients with allogeneic hematopoietic stem cell transplantation ( HR = 3.814, 95% CI 1.343-10.827, P = 0.012). Conclusion:Obesity is an important unfavorable factor that affects patient's survival after allogeneic hematopoietic stem cell transplantation, and the improvement of the efficacy and survival of these patients is worthy of further study.

OBJECTIVETo probe matrine acting on natural killer cell (NK) activating receptor NKG2D ligands expression in CML cell line K562 and its underlying molecular mechanism.

METHODSThe expression of NKG2D ligands (major histocompatibility complex class I chain-related molecule A or B (MICA/B), UL16-binding proteins (ULBP) 1, 2, and 3 on K562 cells were analyzed before and after treated with matrine by FCM. The cytotoxic sensitivity of K562 to NK cell was detected by FCM after CFSE staining at different effect-to-target (E/T) cell ratios. The expression of signal transduction and transcriptional activator 3 (STAT3) protein as well as phosphorylated STAT3 (p-STAT3) were detected by western blot.

RESULTSAfter treatment with matrine, ULBP1 and ULBP2 expression, especially ULBP2 on K562 cells significantly increased, with mean fluorescence intensity (MFI) increasing to 615 and 1614 by 220 and 615 in the untreated cells, respectively. There was no significant change for MICA or ULBP3 expression. Matrine enhanced the susceptibility of K562 cells to NK-mediated cell lysis. At the ratio of E/T with 5:1, the proportion of the killed K562 cells increased to 32.8%, 38.1% and 40.5%, respectively (after 0.2, 0.5 and 0.8 mg/ml matrine treatment) by 29.2% in the untreated cells. The phosphorylated STAT3 protein, but not STAT3 protein, was significantly inhibited by matrine treatment in K562 cells.

CONCLUSIONMatrine induced the expression of NKG2D ligands in K562cells and enhanced the cytotoxicity of NK cells against K562, which was closely related to the inhibition of STAT3 activity in K562 cell.

Alkaloids ; pharmacology ; GPI-Linked Proteins ; immunology ; Humans ; Intercellular Signaling Peptides and Proteins ; immunology ; K562 Cells ; Quinolizines ; pharmacology ; Signal Transduction ; Up-Regulation ; drug effects

OBJECTIVETo investigate the molecular mechanism of the growth inhibitory effect of matrine on K562 cells in JAK/STAT3 mediated signal pathway.

METHODSWestern blot analyses were performed to investigate the differential expression of JAK2, STAT3, phosphor-STAT3 (Tyr705 & Ser727) and phosphor-JAK2 proteins after matrine treatment in K562 cells with or without human recombinant interleukin 6 (IL-6) pretreatment. The expression of STAT3 response gene products such as Bcl-xL, Cyclin D1 and c-Myc, were investigated by Western blot and quantitative real time RT-PCR (qRT-PCR). Expression of IL-6, a potent upstream activating factor of JAK/STAT3 pathway, was analyzed by both real time qRT-PCR and ELISA.

RESUTLSWestern blot revealed that matrine treatment resulted in a strong down-regulation of phosphor-STAT3 both in Tyr705 and Ser727 sites or phosphor-JAK2 proteins expression without significant effects on the total STAT3 and JAK2 proteins. The expression of phosphor-Tyr705 STAT3 and phosphor-Ser727 STAT3 was decreased to 0.370 ± 0.172 in K562 cells treated with 0.5 mg/ml matrine for 48 h, respectively, from 0.690 ± 0.119 and 1.150 ± 0.263 in control cells, accompanied with a dramatical down-regulation of phosphor-JAK2 from 0.670 ± 0.137 to 0.049 ± 0.057 (P<0.05). In addition, it was found that the expression of Bcl-xL, Cyclin D1, c-Myc was decreased both at the transcription and protein level in K562 cells after matrine treatment. Matrine treatment resulted in a significant decrease in the expression level of IL-6 in K562 cells from (35.1 ± 1.93) to (10.74 ± 1.83) and (8.66 ± 1.24) pg/ml at the dose of 0.5 and 0.8 mg/ml, respectively (p<0.05). Matrine treatment could diminish the up-regulation of STAT3, JAK2, phosphor-STAT3 and phosphor-JAK2 protein following pretreatment with IL-6 in K562 cells.

CONCLUSIONMatrine exerts its anti-leukemia effect by interfering with the JAK2/STAT3 signaling pathway. The inhibition of IL-6 expression may play a pivotal role in the disruption of JAK/STAT pathway by matrine.

Alkaloids ; Down-Regulation ; Humans ; Interleukin-6 ; Janus Kinase 2 ; K562 Cells ; Quinolizines ; STAT3 Transcription Factor ; Signal Transduction ; Up-Regulation

OBJECTIVETo investigate the relationship of the mutational status of the ND4 gene and the clinical features of acute myelogenous leukemia (AML) patients with ND4 mutations.

METHODSUsing PCR combined with directly sequencing, we identified somatic mutations of ND4 in 121 primary AML patients to couple with their clinical features.

RESULTSThere were 58 male patients and 63 female patients (median age 49 years, 10-86 years). Eight of 121 patients (6.6%) with de novo AML were found harboring missense mutation of ND4 gene, including 3 patients with A131V (3/8, 37.5%), 2 patients with A404T (2/8, 25%), 1 patient with F149L (1/8, 12.5%), 1 patient with G242D (1/8, 12.5%) and 1 patient with Y409H (1/8, 12.5%), respectively. Patients with ND4 mutations were associated with good karyotype (P=0.049), regardless of gender, age, white blood cell, hemoglobin, platelet, blast cells of bone marrow or immunophenotype (P>0.05). There were no statistical significance in mutations of FLT3-ITD, NPM1, CEBPA, c-KIT and DNMT3A between patients with ND4 mutation and wild-type (wt) ND4 (P>0.05). The median overall survival of patients with ND4 mutations and wt ND4 were all not reached. The median relapse-free survival were not reached and 29(2-53) months, respectively (P>0.05). There was no significance in the ratio of CR and RR patients between wt ND4 and ND4 mutated groups (P>0.05).

CONCLUSIONIt was concluded that novel ND4 mutations could be found in de novo AML patients, especially in patients with good karyotype. Thus, ND4 mutations might play an important role in AML prognosis. However, whether the mitochondria dysfunction contribute to leukemogenesis needs to be further investigated.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; NADH Dehydrogenase ; genetics ; Prognosis ; Young Adult