Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective To investigate the correlation between arterial stiffness(AS)and incident chronic kidney disease(CKD)among the elderly individuals taking health checkup.Methods A retrospective study was conducted on 857 elderly individuals without CKD at baseline who taking physical exams in our medical center from December 2009 to May 2021.Their clinical and labora-tory data were collected.Brachial-ankle pulse wave velocity(baPWV)was used to assess the se-verity of AS,and then the subjects were divided into normal elasticity group(201 cases),and moderate(490 cases)and severe AS group(166 cases).Kaplan-Meier curves were plotted to dis-play cumulative incidence rates of incident CKD across different AS groups.Restricted cubic splines(RCS)and Cox regression models were applied to analyze the correlation of baPWV and incident CKD risk.Results The severe AS group had significantly advanced age,greater ratio of hypertension,larger waist circumference,higher HR,SBP and DBP,increased urinary albumin/creatinine ratio(UACR),elevated levels of TG and fasting blood glucose,and baPWV than the normal elasticity group(P＜0.05).During the follow-up period,37 participants developed CKD.The incidence of CKD was obviously higher in the severe AS group than the normal arterial elas-ticity group(9.04％vs 3.48％).RCS analysis revealed a U-shaped relationship between baPWV and incident CKD risk.When baPWV ≥1 400 cm/s,each standard deviation increase in baPWV indicates the risk of incident CKD increasing by 71％(HR=1.71,95％CI:1.30-2.25,P＜0.01).Regardless of adjustment for covariates or not,baPWV remained positive correlation with inci-dent CKD risk(P＜0.05).Conclusion Among the elderly individuals undergoing health check-up,increased AS severity is significantly associated with higher risk of incident CKD when baP-WV ≥1400 cm/s.

Objective To investigate the effects and molecular mechanisms of regenerating islet-derived 3-Alpha(REG3A)on the proliferation,apoptosis and cisplatin(DDP)resistance of ovarian cancer(OC)cells.Methods Cancer tissue and adjacent tissue samples of 97 ovarian cancer patients admitted to Qinghai Fifth People's Hospital from January 2021 to December 2022 were collected.Quantitative reverse transcriptase-mediated PCR(qRT-PCR)and immunohis to chemistry(IHC)were used to detect the expression of REG3A in cancer tissues and adjacent tissues,and the relationship between its expression and the clinical pathological characteristics and prognosis of patients was analyzed.QRT-PCR was used to detect the expression of REG3A in human normal ovarian epithelial cell line OSE and human OC cell lines(ES2,HEY,A2780,and SKOV3).SKOV3 and DDP resistant OC cell lines(SKOV3/DDP)were selected and randomly divided into siNC group and siREG3A group.Cell counting kit-8(CCK-8)was used to detect cell proliferation activity.Determination of cell drug resistance by methylthiazolyl tetrazolium(MTT).Flow cytometry was used to detect proliferation cycle and apoptosis.Immunoblotting was used to detect the expression of resistance,proliferation,apoptosis and phsphatidylinostol 3-kinase(PI3K)/protein kinase B(Akt)pathway related proteins in OC cells.Results The expression of REG3A mRNA in ovarian cancer tissues was higher than that in adjacent tissues(1.46±0.43 vs 0.52±0.11),and the difference was statistically significant(t=20.858,P<0.001).The 5-year survival rate of patients with high expression of REG3A was 24.49%(12/49),which was lower than the 91.67%(44/48)of patients with low expression of REG3A,and the difference was statistically significant(χ2=44.841,P<0.001).The proportion of patients with FIGO stages III-IV,moderate to high differentiation and tumor size>3cm in the high expression group of REG3A was higher than that in the low expression group of REG3A,and the differences were statistically significant(χ2=4.537～9.972,all P<0.05).Compared with OSE,the mRNA and protein expression of REG3A in ES2,HKY,A2780 and SKOV3 increased significantly(t=6.725～30.234,all P<0.01).Compared with the siNC group,the expression of REG3A was downregulated in SKOV3 cells in the siREG3A group(0.23±0.02 vs 0.99±0.06),cell activity decreased at 24,48 and 72 hours of transfection,the proportion of G1 phase cells increased,while the proportion of S and G2 phase cells and apoptosis rate,MDR-1,Cyclin D1 and Cleaved caspase 3 protein expression,p-PI3K/PI3K and p-Akt/Akt ratios were decreased,and the differences were statistically significant(t=6.584～22.730,all P<0.01).After treatment with DDP at concentrations of 1.25,2.5,5,7.5 and 15 μg/ml,compared with the siNC group,the survival rates of SKOV3 and SKOV3/DDP cells in the siREG3A group gradually decreased,and the differences were statistically significant(t=2.888～11.135,all P<0.05).Conclusion REG3A is highly expressed in OC tissues and is associated with malignant progression and poor prognosis of OC.Its up-regulation promotes cancer cell proliferation and DDP resistance by activating the PI3K/Akt pathway,and inhibits apoptosis.

Objective To investigate the effects and molecular mechanisms of regenerating islet-derived 3-Alpha(REG3A)on the proliferation,apoptosis and cisplatin(DDP)resistance of ovarian cancer(OC)cells.Methods Cancer tissue and adjacent tissue samples of 97 ovarian cancer patients admitted to Qinghai Fifth People's Hospital from January 2021 to December 2022 were collected.Quantitative reverse transcriptase-mediated PCR(qRT-PCR)and immunohis to chemistry(IHC)were used to detect the expression of REG3A in cancer tissues and adjacent tissues,and the relationship between its expression and the clinical pathological characteristics and prognosis of patients was analyzed.QRT-PCR was used to detect the expression of REG3A in human normal ovarian epithelial cell line OSE and human OC cell lines(ES2,HEY,A2780,and SKOV3).SKOV3 and DDP resistant OC cell lines(SKOV3/DDP)were selected and randomly divided into siNC group and siREG3A group.Cell counting kit-8(CCK-8)was used to detect cell proliferation activity.Determination of cell drug resistance by methylthiazolyl tetrazolium(MTT).Flow cytometry was used to detect proliferation cycle and apoptosis.Immunoblotting was used to detect the expression of resistance,proliferation,apoptosis and phsphatidylinostol 3-kinase(PI3K)/protein kinase B(Akt)pathway related proteins in OC cells.Results The expression of REG3A mRNA in ovarian cancer tissues was higher than that in adjacent tissues(1.46±0.43 vs 0.52±0.11),and the difference was statistically significant(t=20.858,P<0.001).The 5-year survival rate of patients with high expression of REG3A was 24.49%(12/49),which was lower than the 91.67%(44/48)of patients with low expression of REG3A,and the difference was statistically significant(χ2=44.841,P<0.001).The proportion of patients with FIGO stages III-IV,moderate to high differentiation and tumor size>3cm in the high expression group of REG3A was higher than that in the low expression group of REG3A,and the differences were statistically significant(χ2=4.537～9.972,all P<0.05).Compared with OSE,the mRNA and protein expression of REG3A in ES2,HKY,A2780 and SKOV3 increased significantly(t=6.725～30.234,all P<0.01).Compared with the siNC group,the expression of REG3A was downregulated in SKOV3 cells in the siREG3A group(0.23±0.02 vs 0.99±0.06),cell activity decreased at 24,48 and 72 hours of transfection,the proportion of G1 phase cells increased,while the proportion of S and G2 phase cells and apoptosis rate,MDR-1,Cyclin D1 and Cleaved caspase 3 protein expression,p-PI3K/PI3K and p-Akt/Akt ratios were decreased,and the differences were statistically significant(t=6.584～22.730,all P<0.01).After treatment with DDP at concentrations of 1.25,2.5,5,7.5 and 15 μg/ml,compared with the siNC group,the survival rates of SKOV3 and SKOV3/DDP cells in the siREG3A group gradually decreased,and the differences were statistically significant(t=2.888～11.135,all P<0.05).Conclusion REG3A is highly expressed in OC tissues and is associated with malignant progression and poor prognosis of OC.Its up-regulation promotes cancer cell proliferation and DDP resistance by activating the PI3K/Akt pathway,and inhibits apoptosis.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective To investigate the correlation between arterial stiffness(AS)and incident chronic kidney disease(CKD)among the elderly individuals taking health checkup.Methods A retrospective study was conducted on 857 elderly individuals without CKD at baseline who taking physical exams in our medical center from December 2009 to May 2021.Their clinical and labora-tory data were collected.Brachial-ankle pulse wave velocity(baPWV)was used to assess the se-verity of AS,and then the subjects were divided into normal elasticity group(201 cases),and moderate(490 cases)and severe AS group(166 cases).Kaplan-Meier curves were plotted to dis-play cumulative incidence rates of incident CKD across different AS groups.Restricted cubic splines(RCS)and Cox regression models were applied to analyze the correlation of baPWV and incident CKD risk.Results The severe AS group had significantly advanced age,greater ratio of hypertension,larger waist circumference,higher HR,SBP and DBP,increased urinary albumin/creatinine ratio(UACR),elevated levels of TG and fasting blood glucose,and baPWV than the normal elasticity group(P＜0.05).During the follow-up period,37 participants developed CKD.The incidence of CKD was obviously higher in the severe AS group than the normal arterial elas-ticity group(9.04％vs 3.48％).RCS analysis revealed a U-shaped relationship between baPWV and incident CKD risk.When baPWV ≥1 400 cm/s,each standard deviation increase in baPWV indicates the risk of incident CKD increasing by 71％(HR=1.71,95％CI:1.30-2.25,P＜0.01).Regardless of adjustment for covariates or not,baPWV remained positive correlation with inci-dent CKD risk(P＜0.05).Conclusion Among the elderly individuals undergoing health check-up,increased AS severity is significantly associated with higher risk of incident CKD when baP-WV ≥1400 cm/s.

OBJECTIVE: Because of the limited number of studies and small sample sizes, whether metabolic syndrome (MS) leads to the occurrence and progression of osteoporosis and the possible underlying mechanisms require further investigation. This study aimed to investigate the association between MS and osteoporosis, along with its influencing factors. METHODS: This observational cross-sectional study included 139,470 individuals aged ≥ 18 years who underwent health examinations from September 2014 to March 2022. Based on bone mineral density (BMD) screening results, the participants were categorized into a suspected osteoporosis or non-osteoporosis group (control). Participants were further divided into those who met 0 MS criteria, 1 MS criterion, 2 MS criteria, and ≥ 3 MS criteria (MS group). Participants who had undergone health examinations at least twice formed the follow-up cohort; a self-matched analysis was performed on those with follow-up periods ≥ 5 years and unchanged MS grouping. RESULTS: Several examination indicators in the suspected osteoporosis group showed statistically significant differences compared with the control group. The proportion of suspected osteoporosis in the MS group was significantly increased compared with that in the 0 MS criteria group (odds ratio [ OR]: 1.215, Z = 29.11, P < 0.001, 95% confidence interval: 1.199-1.231). After adjusting for age, sex, smoking, and alcohol consumption, the 2 MS criteria group and MS group still had OR values > 1 ( P < 0.001). In the follow-up cohort, the proportion of suspected osteoporosis increased gradually with an increase in the number of MS criteria met at baseline and during each follow-up visit ( P < 0.05), with the highest proportion observed in the MS group. However, the proportion of suspected osteoporosis did not increase significantly over time in the different MS groups ( P > 0.05). In the follow-up cohort, the proportion of individuals transitioning from normal BMD to suspected osteoporosis was higher in the MS group after ≥ 5 years of follow-up compared with the group meeting 0 MS criteria (0.08% versus 1.15%, χ ² = 10.76, P = 0.001). There was no significant difference in BMD values for the 0 MS criteria group after 5 years ( P > 0.05), whereas the other three groups experienced a significant decrease in BMD values after 5 years ( P < 0.05). CONCLUSION MS is an independent risk factor for osteoporosis, and the effect of risk factors related to MS on osteoporosis may exceed that of aging alone. The specific mechanisms warrant further investigation.
Humans ; Osteoporosis/etiology* ; Female ; Male ; Metabolic Syndrome/complications* ; Middle Aged ; Cross-Sectional Studies ; China/epidemiology* ; Aged ; Adult ; Bone Density ; Risk Factors

Taking Wuzhou as an example,this paper investigates the construction of the standardized Party affairs system in public hospitals and the path for enhancing Party building quality.It clarifies the connotations and relationships of Party build-ing,Party affairs,and Party affairs standardization,and elaborates on the necessity and path of Party affairs standardization.Sub-sequently,an analysis of the current situation and existing problems,such as insufficient understanding,weak implementation,limited capabilities,and poor integration,is presented.Then,improvement measures,including Party committee guidance,pre-cise training,system construction,and practical promotion of relevant work,are proposed.Finally,the paper discusses the con-struction and improvement of the standardized Party affairs system,team building,and the deep integration of Party building and hospital operations,providing a reference for improving Party building quality in public hospitals.

Objective To explore the automated identification and diameter measurement methods for inferior vena cava (IVC) based on clinical ultrasound images of IVC. Methods An automated identification and localization method based on topology and automatic tracking algorithm was proposed. Tracking algorithm was used for identifying and continuously locating to improve the efficiency and accuracy of measurement. Tests were conducted on 18 sets of ultrasound data collected from 18 patients in intensive care unit (ICU),with clinicians' measurements as the gold standard. Results The recognition accuracy of the automated method was 94.44％ (17/18),and the measurement error of IVC diameter was within the range of±1.96s (s was the standard deviation). The automated method could replace the manual method. Conclusion The proposed IVC automated identification and localization algorithm based on topology and automatic tracking algorithm has high recognition success rate and IVC diameter measurement accuracy. It can assist clinicians in identifying and locating IVC,so as to improve the accuracy of IVC measurement.

Objective:To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province.Methods:A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti -HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results:There were 104 children in the case group and 159 in the control group. The median ( Q1, Q3) level of anti -HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group ( P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 ( OR=1.18, 95% CI: 1.03-1.35) and 93 ( OR=1.21, 95% CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion:The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.