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.

Central serous chorioretinopathy (CSC) is a common macular disease, which can lead to the loss of central vision in young patients. Although the disease is self-limited to some extent, there is no shortage of patients with prolonged course and recurrent attacks, eventually leading to irreversible visual impairment. Therefore, taking reasonable treatment in a certain period is particularly important for the visual prognosis of patients. Although thermal laser photocoagulation of leakage points and photodynamic therapy (PDT) have achieved good effects, there are risks of retinal damage and retinal pigment epithelium atrophy. Subthreshold micropulse laser (SMLP) is a kind of subthreshold short pulse laser, which does not cause visible damage to the retina and is safer. In the era of lack of PDT drugs, SMLP has gradually become an important means of clinical treatment for CSC, especially for patients with no obvious leakage point or subfoveal leakage point. An in-depth understanding of the mechanism of action of SMLP and its efficacy and safety in the treatment of CSC is helpful for the promotion and application of SMLP in the clinical treatment of CSC.

We researched the mechanism of African swine fever virus (ASFV) protein E248R in regulating the cGAS-STING pathway. First, we verified via the dual-luciferase reporter assay system that E248R protein inhibited the secretion of IFN-β induced by cGAS-STING or HT-DNA in a dose-dependent manner. The relative quantitative PCR analysis indicated that the overexpression of E248R inhibited HT-DNA-induced transcription of IFN-b1, RANTES, IL-6, and TNF-α in PK-15 cells. Next, we found that E248R interacted with STING by co-immunoprecipitation assay and laser confocal microscopy. Finally, we demonstrated that E248R inhibited the expression of STING protein by using Western blotting. We demonstrated for the first time that the E248R protein of ASFV suppressed the host innate immune response via inhibiting STING expression. The results are pivotal in extending the understanding of the ASFV immune escape and can guide the design of vaccines against ASFV.
African Swine Fever Virus/genetics* ; Animals ; DNA ; Immunity, Innate ; Nucleotidyltransferases/metabolism* ; Signal Transduction ; Swine

Objective:To evaluate the effect of obesity on the dose-effect relationship of remimazolam when combined with alfentanil in painless gastroscopy.Methods:American Society of Anesthesiologists physical status Ⅰor Ⅱ patients of both sexes, scheduled for elective painless gastroscopy, aged 18-64 yr, were divided into 2 groups according to the body mass index (BMI): normal (BMI 19-24 kg/m 2) group and obese (BMI≥28 kg/m 2) group.Alfentanil 5 μg/kg combined with remimazolam was given intravenously in all the patients, and the dose of remimazolam was determined by the modified Dixon′s up-and-down method.The initial dose of remimazolam was 0.25 mg/kg, and each time the dose was increased or decreased by 0.05 mg/kg based on the sedative effect.The response was defined as positive when the responses that affected the operation of examination developed during insertion of the gastroscope and within the first 2 min of examination such as swallowing, bucking or body movement.This process was repeated until the seventh intersection occurred.The 50% effective dose (ED 50), 95% effective dose (ED 95), and 95% confidence interval ( CI) of remimazolam were calculated by probit method. Results:There were 26 patients in normal group and 18 patients in obese group.The ED 50 (95% CI) of remimazolam was 0.196 (0.087-0.274) mg/kg, and the ED 95 (95% CI) was 0.322 (0.256-1.397) mg/kg in normal group.The ED 50 (95% CI) of remimazolam was 0.125 (0.102-0.148) mg/kg, and the ED 95 (95% CI) was 0.161 (0.141-0.242) mg/kg in obese group.The ED 50 and ED 95 were significantly lower in obese group than in normal group ( P<0.001). Conclusions:Obesity increases the potency of remimazolam when combined with alfentanil 5 μg/kg in the patients undergoing painless gastroscopy.

Background and Objectives: Human umbilical cord mesenchymal stem cells (HUC-MSCs) are promising candidates for cell-based therapy in regenerative medicine or other diseases due to their superior characteristics, including higher proliferation, faster self-renewal ability, lower immunogenicity, a noninvasive harvest procedure, easy expansion in vitro, and ethical access, compared with stem cells from other sources. Methods: and Results: In the present study, we knocked down the expression of SOX9 in HUC-MSCs by lentivirus interference and found that knockdown of SOX9 inhibited the proliferation and migration of HUC-MSCs and influenced the expression of cytokines (IL-6 and IL-8), growth factors (GM-CSF and VEGF) and stemness-related genes (OCT4 and SALL4). In addition, the repair effect of skin with burn injury in rats treated with HUC-MSCs transfected with sh-control was better than that rats treated with HUC-MSCs transfected with shSOX9 or PBS, and the accessory structures of the skin, including hair follicles and glands, were greater than those in the other groups. We found that knockdown of the expression of SOX9 obviously inhibited the expression of Ki67, CK14 and CK18. Conclusions In conclusion, this study will provide a guide for modifying HUC-MSCs by bioengineering technology in the future.

Objective: To evaluate the effectiveness on informational support of the parenting sense of competence and parenting stress in primiparas. Methods: Ninety-five primiparas in the First Affiliated Hospital of Zhengzhou University were recruited from November 2017 to April 2018, mothers of premature infants discharged from hospital from November 2017 to January 2018 were divided into the control group,and which discharged from February 2018 to April 2018 were divided into the experimental group conveniently.Seven cases in the control group and 5 cases in the experimental group dropped out. The control group received routine nursing care, 4 times of informational support were implemented to the mothers of premature infants at the first 4 months after discharged in the experimental group,included team teaching, live demonstration, set up a wechat group, et al. All primiparas were investigated using the Chinese version of Parenting Sense of Competence Scale(C-PSOC) and the Parenting Stress Index-Short Form(PSI-SF) at the 1^th,3^th,6^th month postpartum. Results: At the 6^th month postpartum, total scores of the Chinese version of Parenting Sense of Competence Scale and subscale scores of self-efficacy, satisfaction of the mothers of premature infants were 82.60±4.45, 39.19±3.25, 43.40±3.47, respectively in the experimental group,and the scores were 76.83±7.88, 36.90±4.82, 39.93±5.16, respectively in the control group, the difference between the two groups was statistically significant(t=4.117, 2.541, 3.613, P<0.05). At the 6^th month postpartum,total scores of the Parenting Stress Index-Short Form and subscale scores of parenting distress,parent-child dysfunctional interaction,difficult child of the mothers of premature infants were 80.31±9.50, 28.62±4.54, 23.98±4.91, 26.14±5.15, respectively in the experimental group,and the scores were 87.36±8.58, 32.55±4.88, 25.95±4.15, 28.84±4.88, respectively in the control group,the difference between the two groups was statistically significant(t=-3.568-3.823, P<0.05). Conclusions Informational support can effectively improve the parenting sense of competence and relieve the parenting stress in primiparas.

OBJECTIVE:To provide reference for strengthening the safety of the combination use of CYP3A4 inhibitors with statins in clinical treatment. METHODS:30 cases per month(totally 300 cases)(the hospitalization time was more than 10 days) discharged from the cardiology department of a third-level class A hospital during Jan. to Oct. 2013 were selected randomly,and statistical analysis was made into general information of patients,whether to use statins and CYP3A4 inhibitor,and whether to monitor safety indicators of liver and kidney function and creatine kinase. RESULTS:Totally 291 patients were treated with statins with a total use rate of 97%,including 265 cases of atorvastatin and 11 cases of simvastatin. The CYP3A4 inhibitors were com-bined with amlodipine,diltiazem,verapammy,amiodarone,Ginkgo biloba leaf,fenofibrate and clarithromycin,etc.,and 162 (59%) patients were given the combination use of simvastatin or atorvastatin with CYP3A4 inhibitors. But the liver and kidney function,creatine kinase and other safety indicators were not monitored by laboratory examination during medication. CONCLU-SIONS:Atorvastatin and simvastatin are used commonly in patients with cardiovascular disease,and the combination use rate with CYP3A4 inhibitor is relatively higher and needs long-term medication,drug dosage should be limited according to the direction of instructions and the adverse reactions induced by drug interactions should be noticed to strengthen medication monitor and education for patients.

Recently, neuroimging techniques are widely applied in the nervous systemic disease. With the development of neuroimaging, the neuroimaging studies of Alzheimer's disease (AD) are more and more in-depth. The main purpose is to identify AD patients in the early stage (clinically normal), to treat and prevent the disease in the early stage. This article reviewed the progress of various of imaging studies in AD disease.

Objective To explore the possibility of heterogenous gene to express in juvenile Schistosoma japonicum and the application of electroporation in transformation of schistosomulae. Methods The plasmids of pEGFP-C1 were introduced into mechanically transformed schsitosomula with electroporation. The presence, transcription and translation of the transgene in electroporated schistosomula were confirmed by PCR, RT-PCR and Western blotting analysis respectively using the genomic DNA, total RNA and protein extracted and isolated from schistosomula cultured in vitro for 48 hours. Meanwhile, localization of EGFP within electroporated schistosomula was performed with confocal laser scanning microscope. Results 760 bp and 276 bp amplified products by PCR and RT-PCR were found coincident with the expected size and expression of EGFP gene in elctroporated schistosomula was confirmed by Western blotting. Fluorescence of EGFP was localized in tegument and subtegument of the electroporated schistosomula with confocal microscopy, especially in the anterior part of the worm. Conclusion The heterogenous gene of EGFP has been successfully introduced into juvenile S. japonicum by electroporation and the expression of transgene was confirmed with molecular and microscopical methods.