OBJECTIVE To explore the efficacy and safety of ruxolitinib in the treatment of myelofibrosis （MF）. METHODS A retrospective collection of data was conducted on 42 MF patients who were treated with ruxolitinib in a standardized manner for more than 6 months in the Third People’s Hospital of Bengbu from September 2018 to April 2024. The clinical symptom scores， spleen size reduction， and MF grading of the patients before and after treatment were analyzed. Additionally， the occurrence of adverse reactions with a causality assessment result of “definite”“probable” or “possible” was recorded. The patients’ survival status was followed up. RESULTS After 6 months of treatment， both clinical symptom scores and the total score were significantly decreased than before treatment （P＜0.05）. The length and thickness of the spleen were significantly shorter than before treatment （P＜0.05）. MF classification in 5 patients decreased by 1 level compared with baseline， 1 case was level 2 and dropped to level 0， 14 patients remained stable. The main adverse reactions were anemia （26 cases）， thrombocytopenia （14 cases）， infection （11 cases）， and gastrointestinal discomfort （9 cases）. Thirty-nine patients survived， with a survival rate of 92.86%. CONCLUSIONS Ruxolitinib can effectively improve the clinical symptoms of patients with MF， shrink the spleen， stabilize and even improve MF grading， and holds promise for bringing long-term survival benefits to MF patients. Adverse reactions are mainly anemia， thrombocytopenia， infection and gastrointestinal discomfort.

Objective:We applied a hypoxia-induced model of human fetal retinal microvascular endothelial cell (RMEC) to study the effect of carbonic anhydrase 9 (CA9) on cell proliferation.Methods:The eyeballs of spontaneously aborted fetuses in Guangdong Women and Children's Hospital were obtained, and the retinas were isolated. RMEC was obtained by trypsin and collagenase two-step enzyme digestion, and endothelial cells were identified by CD34. The fetal RMEC and the purchased adult RMEC were cultured in normoxic and hypoxic incubators (1%O 2+5%CO 2+94%N 2), and the expression of CA9 was detected by qPCR and Western blot. After knocking down the CA9 by small interference RNA technique, the cell proliferation was detected by CCK-8 method, and the cell viability was detected by CCK-8 after adding CA9 inhibitor U-104. Results:The primary RMEC was extracted successfully. Immunofluorescence staining showed the percentage of CD34 positive cells in the third-generation cells was nearly 100%. The expression of CA9 mRNA in immature fetus and adult RMEC under hypoxia culture was higher than that under normoxic culture (fetal 1% O 2 group vs. fetal 21% O 2 group: 67.80±10.31 vs. 1.00±0.04, P<0.001; adult 1% O 2 group vs. adult 21% O 2 group: 1.72±0.22 vs. 1.00±0.02, P=0.014). Western blot analysis showed significantly increased expression of CA9 in the fetal RMEC exposed to hypoxia, which aligned with the expression of CA9 mRNA. When fetal RMEC was transfected with siCA9 20 nM, the knockdown rate of CA9 was 95% ( P<0.001). CCK-8 assay showed significantly lower proliferation of fetal RMEC cells in siCA9 group compared to siNC group (0.57±0.05 vs. 0.90±0.03, P<0.001), which was reflected by the OD value. With the addition of 100 μM CA9 inhibitor U-104, the viability of fetal RMEC in the treated groupwas significantly lower than that in the untreated group (99.16%±3.82% vs. 119.10% ±1.72%, P=0.002). Conclusions:The expression of CA9 differed between adult and preterm fetus in our hypoxia-induced RMEC model. Inhibiting CA9 can inhibit the proliferation of retinal microvascular endothelial cells of preterm fetus.

ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg^-1） and Captopril group （0.002 57 g·kg^-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

Objective To investigate the efficacy of sakubatril valsartan combined with tolvaptan in the treatment of heart failure patients with reduced ejection fraction(HFrEF)and the effects on echocardiography and cardiovascular events.Methods According to the random number table method,400 patients with HFrEF admitted to the First People's Hospital from September 2017 to January 2022 were divided into the control group and the combination group with 200 cases each.Both groups were given conventional treatment,based on which the control group was given sacubitril valsartan and the combination group was given sacubitril valsartan combined with tolvaptan.The efficacy,echocardiographic indexes[left ventricular ejection fraction(LVEF),left ventricular end-diastolic internal diameter(LVEDD),left ventricular end-systolic internal diameter(LVESD)],myocardial injury indexes[serum brain natriuretic peptide(BNP),high-sensitivity troponin T(hs-CTnT),growth transforming factor-15(GDF-15)],urine output,neuroendocrine factors[antidiuretic hormone(ADH),angiotensin(PRA),angiotensin Ⅱ(Ang Ⅱ)],cardiovascular events and adverse effects were compared between the two groups.Results The total effective rate was 94.50%(189/200)higher in the combined group than 86.00%(172/200)in the control group(P＜0.05);LVEF was high-er in the combined group than in the control group after treatment,and LVEDD and LVESD were lower than in the control group(P＜0.05);BNP,hs-CTnT,GDF-15,ADH PRA,and Ang II were lower in the combined group than in the control group,and urine volume was higher than in the control group(P＜0.05);at 6-month follow-up after treatment,there were no statistically significant differences in the rehospitalization rate of heart failure,the incidence of non-fatal infarction,post-discharge cardiovascular mortali-ty and all-cause mortality in the combined group compared with those of the control group(P＞0.05);there were no statistically significant differences in the incidence of adverse events in the combined group compared with that of the control group(P＞0.05).Conclusion Sacubitril valsartan combined with tolvaptan is effective in treating HFrEF,by reducing myocardial inju-ry,promoting urination,and improving patients'cardiac function without increasing the risk of cardiovascular events and adverse reactions.

OBJECTIVE To study the pharmacokinetics of paeoniflorin， hesperidin， naringenin， formononetin and enoxolone from Chitong xiaoyanling granules in rats. METHODS Six male SD rats fasted but not deprived of water for 12 h were given Chitong xiaoyanling granules （5.0 g/kg） intragastrically at one time. Blood was collected from inner canthus of rats at different time points after administration. Plasma samples were pretreated with acetonitrile precipitated protein （sulfamethoxazole as internal standard）， and the concentrations of 5 ingredients in plasma were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. The pharmacokinetic parameters of each ingredient were calculated using DAS 3.0 software. RESULTS After intragastric administration of Chitong xiaoyanling granules， tmax and t1/2 of formononetin were the shortest among 5 ingredients （0.25 h and 0.39 h， respectively）. For naringenin and enoxolone， the tmax was shorter， but t1/2 was longer， and there was an obvious double-peak phenomenon in the drug-time curve of naringenin. Compared with the other three components， cmax and AUC of paeoniflorin and hesperidin were not directly proportional to the content of in vitro components. CONCLUSIONS Formononetin， naringin and enoxolone in Chitong xiaoyanling granules were absorbed rapidly in rats， while paeoniflorin and hesperidin were absorbed slowly.

Objective: To investigate the epidemiological characteristics of influenza outbreaks in Zhejiang Province from 2013 to 2022, so as to provide insights into influenza prevention and control. Methods: Data pertaining to influenza outbreaks reported in Zhejiang Province from 2013 to 2022 were collected from National Influenza Surveillance System in China, including time, region, cases and pathogen types of influenza outbreaks. The temporal, spatial and pathogen distribution of influenza outbreaks were analyzed using a descriptive epidemiological method. Results: A total of 577 influenza outbreaks involving 448 698 individuals were reported in Zhejiang Province from 2013 to 2022, and the overall attack rate was 5.34% (23 974 cases), with no death reported. The lowest attack rate of influenza was 0.26%, and the highest was 80.00%, with a median attack rate of 10.89% (interquartile range, 24.26%). The outbreak had the shortest duration of 1.00 day, and the longest duration of 59.00 days, with a median duration of 9.00 (interquartile range, 11.00) days. There were 387 influenza outbreaks that occurred between November and January of the following year (67.07%), and the three highest numbers of outbreaks were reported in Hangzhou City (310 outbreaks), Wenzhou City (51 outbreaks) and Jinhua City (46 outbreaks). There were 395 outbreaks reported in urban regions (68.46%), 93 in counties and townships (16.12%) and 89 in rural regions (15.42%), and influenza outbreaks predominantly occurred in primary schools (487 outbreaks, 84.40%). In addition, the types of pathogens were alternately prevalent, with influenza B virus (241 outbreaks, 41.77%) and A/H3N2 virus (232 outbreaks, 40.21%) as predominant subtypes. Conclusions Influenza outbreaks mainly occurred in winter in Zhejiang Province from 2013 to 2022, and primary schools were main places of influenza outbreaks, while influenza B virus and A/H3N2 virus were predominant subtypes. It is necessary to reinforce the surveillance and report of influenza-like illness in schools and improve the coverage of influenza vaccination to prevent influenza outbreaks.

Due to limited options and modalities for the etiological treatment of autoimmune liver diseases, it is urgent to seek new therapeutic methods for liver autoimmune diseases. As the most common source of cells for stem cell therapy, mesenchymal stem cells (MSCs) play an important role in regulating innate and adaptive immune responses and have been widely used in clinical trials for the treatment of autoimmune diseases and inflammatory diseases. Recent experimental and clinical studies have shown that MSCs and MSC-EVs can inhibit the activation and proliferation of a variety of liver proinflammatory cells (such as Th1, Th17, and M1 macrophages), regulate the differentiation of different subsets of T and B cells, reduce the secretion of proinflammatory cytokines, and promote the proliferation of anti-inflammatory cells, thereby playing an immunoregulatory role. This article reviews the clinical trials of MSCs and MSC-EVs in the treatment of autoimmune liver diseases and their mechanism in regulating immune function and promoting hepatocyte regeneration and briefly describes the potential application and limitations of MSCs and MSC-EVs in clinical practice.

Objective:To understand the current situation of postpartum maternal perceived spouse support for breastfeeding, and explore its mediating role in the spouse support for breastfeeding and maternal breastfeeding self-efficacy.Methods:From October 2021 to October 2022, convenience sampling was used to select 602 postpartum women (42 days postpartum) and their spouses who underwent follow-up visits at Obstetric Clinics in four ClassⅢ hospitals in Shanghai as the research subject. A questionnaire survey was conducted using the General Information Questionnaire, Partner Breastfeeding Influence Scale (PBIS) , and Breastfeeding Self-efficacy Scale Short Form (BSES-SF) .Results:The PBIS score of 602 postpartum women was (121.07±25.41) , and the PBIS score of 602 maternal spouses was (134.37±18.94) . Pearson correlation analysis results showed that maternal perceived spouse support has a positive correlation with spouse support ( P<0.01) , and a positive correlation with maternal self-efficacy in breastfeeding ( P<0.01) ; spouse support was positively correlated with maternal self-efficacy in breastfeeding ( P<0.01) . The mediating effect analysis that maternal perceived spouse support played a complete mediating role between spouse support and maternal self-efficacy in breastfeeding. Conclusions:There are both connections and differences between maternal perceived spouse support and spouse support, and the positive promoting effect of spouse support on maternal self-efficacy in breastfeeding can be completely mediated by maternal perception. Medical and nursing staff should pay attention to the assessment of maternal perceived spouse support and guide spouse breastfeeding support behavior based on maternal needs and experiences of spouse support, so as to improve breastfeeding outcomes.

The pure breastfeeding rate in China is relatively low, and excellent father's support can improve the outcome of breastfeeding. The current situation and influencing factors of father's support for breastfeeding at home and abroad are not clear, and the evaluation methods are not yet unified. Starting from the concept of father's support for breastfeeding, this paper introduces the evaluation tools for father's support for breastfeeding according to specific and non-specific classifications, focusing on analyzing and comparing the structure and application status of various tools, so as to provide a basis for finding or constructing evaluation tools suitable for China. At the same time, this paper summarizes the influencing factors of father's support for breastfeeding from four aspects, including father's sociodemographic characteristics, breastfeeding knowledge, attitude towards breastfeeding, and psychological state, providing reference for formulating interventions to improve father's support for breastfeeding and further promote breastfeeding.

Poly ADP-ribose polymerase-1 (PARP-1) plays a vital role in organisms, including regulating repair of DNA, maintaining genome stability, regulating cell proliferation, differentiation, and death.At present, PARP inhibitors have been made some breakthrough in the treatment of breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.However, PARP inhibitors have certain limitations in other malignant tumors and patients who are resistant to PARP-1 inhibitors.This article summarizes the research on PARP inhibitors in lung cancer, hepatocellular carcinoma, glioblastoma, leukemia and cervical cancer, and introduces the strategies of combining other anti-tumor drugs such as DNA repair inhibitors, immune checkpoint inhibitors, anti-angiogenic drugs and other chemotherapeutic drugs to solve their drug resistance, which provides some reference for the wide clinical application of PARP inhibitors in the future.