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 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.

Clustered regularly interspaced short palindromic repeats (CRISPR) and its associated protein gene system can limit the horizontal gene transfer, thereby effectively preventing the invasion of foreign gene elements such as bacteriophages. CRISPR arrays of different bacteria are diverse. Based on the differences in the CRISPR system, this review summarizes the application of CRISPR in food-borne pathogen evolution analysis, detection and typing, virulence and antibiotic resistance in recent years. We also address bacterial detection typing method developed based on the characteristics of CRISPR arrays and the association of CRISPR with virulence and drug resistance of food-borne pathogens. The shortcomings of CRISPR in evolution, detection and typing, virulence and resistance applications are analyzed. In addition, we suggest standardizing CRISPR typing methods, improving and expanding the CRISPR database of pathogenic bacteria, and further exploring the co-evolution relationship between phages and bacteria, to provide references for further exploration of CRISPR functions.
Bacteria/genetics* ; Bacteriophages/genetics* ; CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; Drug Resistance, Microbial/genetics* ; Virulence/genetics*

Objective:To check RNA binding protein QKI-5's expression level in breast cancer cells and inhibiting effect on cancer cell proliferation.Methods:QKI-5's expression level was checked in different breast cancer cells by Western blotting,cancer cells of overexpressed QKI-5 gene could be stabilized by slow virus infection construction,MTT and FCM were used to check cell period to express QKI-5's influence on cell proliferation and period.Results:MCF-7 cells have relatively low QKI-5 expression level in three breast cancer cells,MTT experiment result has obvious reduced influence on QKI-5's expression of MCF-7 cell proliferation P＜0.05,mean-while,cell period inspection shows that overexpressed QKI-5's MCF-7 cells have obvious G1 retardant,cells in S and G2/M periods are reduced.Conclusion:High expression of QKI-5'in breast cancer could cause slow cell proliferation by inhibiting cancer cell period,hence causing limited tumor growth.

OBJECTIVETo explore the role of RhoA in regulating vascular endothelial growth factor (VEGF) secretion level in breast cancer cells and in the proliferation, migration and tube formation of human umbilical vascular endothelial cells (HUVECs) under hypoxia.

METHODSEnzyme-linked immunosorbent assay was used to examine the effect of V14RhoA plasmid transfection-induced RhoA activation and RhoA knockdown on VEGF secretion level in breast cancer MCF-7 cells under hypoxic condition. A MCF-7/HUVEC co-culture model was established to assess the effect of the changes in RhoA expressions in MCF-7 cells on HUVEC proliferation, migration, and tube formation under hypoxia.

RESULTSUnder hypoxic condition, RhoA activation promoted VEGF secretion in MCF-7 cells, and RhoA knockdown inhibited VEGF secretion. In the co-culture model, RhoA activation in the MCF-7 cells enhanced HUVEC proliferation, migration, and tube formation, and RhoA knockdown inhibited these changes.

CONCLUSIONUnder hypoxic condition, RhoA indirectly influences HUVECs to affect tumor angiogenesis by regulating VEGF level in breast cancer cells.

Breast Neoplasms ; metabolism ; pathology ; Cell Hypoxia ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Gene Knockdown Techniques ; Human Umbilical Vein Endothelial Cells ; cytology ; secretion ; Humans ; Transfection ; Vascular Endothelial Growth Factor A ; secretion ; rhoA GTP-Binding Protein ; metabolism

Objective To observe effects of intranasal sufentanil on analgesia.Methods Eighty-two patients,who scheduled for selective thyroidectomy were randomly divided into the observed group and the control group with 41 cases in each group.In the observed group,patients received intranasal sufentanil 20 μg before the incision about 10 minutes,then administered local infiltration with 0.5% lidocaine.In the control group,patients received water for injection which was placebo instead sufentanil.By double blind method observed verbal mting scale(VRS)score.The values of NBP,HR,SpO2 and respiration rate(RR)were recorded before intranasal drugs and 5,10,20,40,60 min after intranasal drugs.The amount of local anesthetic,the size of thyroid gland,the time of operation and the satisfaction were compared between the two groups.Nausea vomiting and pruritus were also observed in order to assess the safety of intranasal sufentanil.Results All patients completed the operation successfully.The RR in the observed group decreased to(13.1±0.5),(13.8±0.6),(13.8±0.8)times/min after intranasal sufentanil 10,20,40 min,and had significant difference with those before intranasal drugs(P＜0.05),anastated after 60 min.VRS score of the observed group was(2.0±0.4)scales,less than the control group,and had significant difference when the surgeon was dissecting thyroid gland(P＜0.05).The amount of local anesthetic in the observed group was(42.5±6.9)ml,less than the control group(63.7±4.3)ml(P＜0.05).The satisfaction had significant difference between the two groups(P＜0.05).Conclusion Intranasal sufentanil for analgesia is a safe and useful technology.

AIM: The role of human interleukin-2(IL-2) signal peptide sequence in the effect of human Endostatin (hEndostatin) expression and secretion was investigated in HeG2 cells. METHODS: RT-PCR and Western-blotting were conduct to observe mRNA level difference of hEndostatin gene, its protein expression and secretion level difference between with hIL-2 signal peptide sequence and without it. RESULTS: mRNA level of hEndostatin gene in HepG2 (pBlast-hIL2-hEndo) cells was higher than that in HepG2(pBlast-hEndo)( P