Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To investigate the clinical effect of ultrasound induction combined with acupunc-ture points and polyethylene glycol 4000 powder for treating constipation in elderly patients with hip fracture. Methods A randomized parallel controlled method was adopted.A total of 100 inpatients meeting the inclu-sion criteria were divided into the control group and treatment group.Fifty cases in the control group were given polyethylene glycol 4000 powder,10 g/d,taking at a draught in 1 h after lunch.Fifty cases in the treat-ment group adopted the ultrasound induction combined with Shenque acupoint and Guanyuan acupoint,which was implemented at 1 h after lunch every day,once a day,30 min each time,and the intensity was appropriate for the patients to tolerate.The two groups were continuously treated for 1 week.The clinical symptoms be-fore and after treatment in the two groups were observed.The constipation score,quality of life score,treat-ment efficacy and safety were compared between before and after treatment.Results There were 3 dropout cases in the control group and 47 cases were finally included.Among them,14 cases were excellently effective,20 cases were effective,13 cases were ineffective,and the total effective rate was 72.34％;there were 2 dropout cases in the treatment group and 48 cases were finally included.Among them,15 cases were excellently effec-tive,18 cases were effective,15 cases were ineffective,and the total effective rate was 68.75％;the total effec-tive rate had no statistical difference between the two groups (P>0.05).The effect onset time of the treat-ment group was earlier than that of the control group with statistical difference (P<0.05).The abdominal symptom dimension and total score in the constipation scores after treatment in the treatment group were lower than those in the control group,and the differences were statistically significant (P<0.05).After treat-ment,the physiological,satisfaction dimension scores and total score in life quality score in the treatment group were lower than those in the control group,and the differences were statistically significant (P<0.05). During the test process,2 cases in the control group had adverse drug reactions,which manifested by mild di-arrhea at the end of the treatment course,and no adverse reactions were found in the treatment group.Conclu-sion The ultrasound induction combined with acupuncture points for treating constipation in elderly patients with hip fracture has equivalence with polyethylene glycol 4000 powder,moreover which has the advantages in the aspects of effect onset time and improvement of abdominal symptoms.

Objective To explore the safety and efficacy of sequential tirofiban in patients with small artery occlusion(SAO)cerebral infarction after intravenous thrombolysis.Methods A retrospective collection of 90 cases of small artery occlable cerebral infarction who underwent intravenous thrombolytic treatment within the time window at the Department of Neurology,Heji Hospital,Affiliated to Changzhi Medical College from December 2019 to June 2022.It was divided into observation group(receiving tirofiban,conventional antiplatelet aggregation,lipid regulation and stabilization)and control group(conventional antiplatelet aggregation,lipid regulation and plaque stabilization).Baseline feature differences were balanced by propensity score matchingd.The main evaluation index was the long-term prognosis,the ratio of good prognosis(mRS≤2 points)at 3 months.The secondary outcome was early neurological impairment and clinical outcome.Results At 3 months,the long-term functional outcome of the tirofiban group was better than that of the control group(P>0.05).Compared with the control group,the early neurological function NIHSS score of the tirofiban group was significantly reduced(P<0.05).On the 7th day,the total efficiency of tirofiban treatment was higher than that of the control group(P<0.05).On the 14th day,the data was still significantly higher(P<0.05).Conclusion Sequential tirofiban treatment after thrombolysis is safe and effective for SAO,which may be the remedial treatment of AIS patients after thrombolysis and recanalization.

Objective To investigate the application value of amlodipine atorvastatin calcium tablet(AACT)combined with evidence-based emotional nursing mode(EENM)in elderly patients with hypertension complicated by coronary heart disease(HTN-CHD).Methods HTN-CHD patients admitted to the department of cardiology of The Second Affiliated Hospital of Wenzhou Medical University from June 2021 to June 2023 were selected retrospectively as study subjects.According to the intervention methods,the HTN-CHD patients were divided into the AACT group and the EENM group.Patients in the AACT group were given AACT combined with the usual care intervention,and the EENM group was given EENM on the basis of the AACT group.The changes of psychological status(SDS,SAS,and SPBS),adherence(medication compliance,daily exercise behavior,poor management behavior,and dietary management behavior)and blood pressure[(systolic blood pressure,SBP)and diastolic blood pressure(DBP)]were compared between two groups.The incidence of cardiovascular events in the two groups at 6 months was observed and compared.Results A total of 118 HTN-CHD patients(55 in AACT group and 63 in EENM group)were included in this study.Before the intervention,there was no significant statistical difference in the SDS,SAS,SPBS,medication compliance,daily exercise,poor management,diet management scores,SBP and DBP between AACT and EENM groups(P＞0.05).After the intervention,SDS,SAS,SPBP scores,SBP and DBP of the HTN-CHD patients significantly decreased in both AACT and EENM groups compared with before(P＜0.05).However,the medication compliance behavior score,daily exercise behavior score,bad management behavior score and diet management behavior score increased significantly compared with before(P＜0.05);SDS,SAS,SPBS scores,SBP and DBP of the patients in EENM group decreased more than those in the AACT group(P＜0.05),however,the increase of medication compliance,daily exercise,poor management and diet management behavior scores of the EENM group was higher than that in the AACT group(P＜0.05).Furthermore,the incidence of cardiovascular events was lower in the EENM group than in the AACT group(P＜0.05).Conclusion EENM combined with AACT intervention is beneficial to improve the compliance with HTN-CHD patients,improve the psychological status and blood pressure values,and reduce the incidence of cardiovascular events.

Objective:To investigate the mechanism of tissue damage caused by neutrophil matrix metalloproteinase-8 (MMP-8) in Fusarium keratitis. Methods:A total of 108 male C57BL/6J SPF grade mice, 6-8 weeks old, were selected to establish a model of Fusarium keratitis (FK) in the right eyes.Corneal inflammation in mice was observed and scored under a slit lamp microscope.Based on the corneal inflammation scores, the modeling eyes were divided into 0, 12, 24, 48, and 72-hour groups post-modeling.At the corresponding time points, mice were euthanized, and corneal tissues were collected.The expressions of MMP-8, adenylate-activated protein kinase (AMPKα) and its serine 172-site phosphorylated form (p-AMPKα) proteins in corneal tissues were detected by Western blot.The neutrophil count in mice corneal tissues at each time point was determined using hematoxylin and eosin staining.The co-localization of neutrophils and MMP-8 protein in the cornea was observed by immunofluorescence staining.In the in vitro corneal collagen degradation experiment, corneal tissues were divided into MMP-8 group, buffer group, and normal saline group, which were treated with 100 μl of activated recombinant MMP-8, detection buffer, and normal saline, respectively.Hydroxyproline content in corneal tissues was determined using a hydroxyproline assay kit, and the mass fractions of hydroxyproline were compared among the groups.Peripheral blood neutrophils were isolated from human blood samples, and Fusarium spores were collected for experiments.Human neutrophils were divided into four groups, negative control group (cultured neutrophils), co-culture group (neutrophils co-cultured with spores), AICAR-treated group (neutrophils co-cultured with spores and treated with p-AMPK protein kinase activator AICAR), and compound C-treated group (neutrophils co-cultured with spores and treated with the inhibitor compound C).The MMP-8 protein expression levels in each group of human neutrophils were assessed via immunofluorescence staining.The use and care of animals complied with the ARVO statement and Regulations for the Administration of Affairs Concerning Experimental Animals.The animal experiment protocol was approved by the Animal Ethics Committee of Henan Eye Hospital (No.HNEECA-2017-04-02).One healthy adult volunteer was selected and 10 ml of peripheral venous blood was collected.The clinical study protocol was approved by the Clinical Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[16]). Results:At 24 hours post-modeling, corneal opacification was observed in the modeling eyes, and corneal perforation occurred in 72-hour post-modeling group.The corneal inflammation scores in 24, 48, and 72-hour post-modeling groups were all higher than those in 12-hour post-modeling group, and the differences were statistically significant (all at P<0.001).The relative expression levels of MMP-8 protein in the cornea were higher in 12, 24, and 48-hour post-modeling groups compared to 0-hour group, with statistically significant differences (all at P<0.001).There was a moderate positive correlation between the relative expression level of MMP-8 protein in the cornea and the inflammation scores of the modeling eye ( rs=0.50, P<0.05).In the cornea, the p-AMPKα (Thr 172)/AMPKα ratio was higher in 24, 48, and 72-hour post-modeling groups than in 0-hour group, and the differences were statistically significant (all at P<0.05).The p-AMPKα(Thr 172)/AMPKα ratio in the cornea was moderately positively correlated with the relative expression level of MMP-8 protein ( r=0.54, P<0.01).The number of neutrophils in the cornea was significantly higher in 24, 48, and 72-hour post-modeling groups than in 0-hour group, with statistically significant differences (all at P<0.001).The number of neutrophils in the cornea was strongly positively correlated with the inflammation score ( rs=0.77, P<0.001), and was moderately positively correlated with the relative expression level of MMP-8 protein ( r=0.56, P<0.05).MMP-8 protein expression in the cornea of the modeling eyes showed a high degree of co-localization with neutrophils.The hydroxyproline content in the cornea was (0.52±0.02)μg/mg, (0.51±0.03)μg/mg, and (0.27±0.02)μg/mg in buffer group, normal saline group and MMP-8 group, respectively, with a significant overall difference among them ( F=156.63, P<0.01).The corneal hydroxyproline content was lower in MMP-8 group compared to buffer and normal saline groups, and the differences were statistically significant (all at P<0.05).In the experiment involving the infection of cultured Fusarium spores with human neutrophils, the fluorescence intensity of MMP-8 expression was significantly higher in AICAR-treated group than in negative control group and compound C-treated group, with statistically significant differences (all at P<0.05). Conclusions:The MMP-8 secreted by neutrophils in mice with fungal keratitis can degrade corneal stromal collagen fibers, leading to corneal opacification or perforation.The variations in MMP-8 protein expression levels in human neutrophils may be associated with AMPK activation.

OBJECTIVE: To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. METHODS: Twenty-four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. RESULTS: Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P < 0.05) and increased immobile time in forced swimming test (P < 0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P < 0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P < 0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P < 0.05). CONCLUSION The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.
Animals ; Mice ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; Cerebral Cortex ; Depression/physiopathology* ; Frontal Lobe/pathology*

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

Objective:To evaluate the effects of quality improvement (QI) program on the incidence of bronchopulmonary dysplasia (BPD) in very preterm infants (VPIs) [gestational age (GA)<32 weeks].Methods:From July to December 2017,VPIs admitted to the Department of Neonatology of Yancheng Maternity and Child Health Care Hospital were retrospectively enrolled and were assigned into pre-quality improvement program group (Pre-QI group).From July to December 2018, VPIs were assigned into post-quality improvement program group (Post-QI group). QI program included delayed umbilical cord clamping (DCC), early postnatal nasal continuous positive airway pressure ventilation (nCPAP) and minimally invasive pulmonary surfactant therapy (MIST). The clinical data and prognostic indicators of the two groups of VPIs and their mothers were compared. Independent sample t-test or continuity-adjusted Chi-square test (or Fisher's exact test) and Logistic regression were used for statistical analysis. Results:A total of 204 VPIs were enrolled, including 96 cases in Pre-QI group and 108 cases in Post-QI group. 1 min Apgar score and hematocrit on admission to the neonatal intensive care unit (NICU) in the Post-QI group were significantly higher than the Pre-QI group( P<0.05). The incidence of delivery room resuscitation, endotracheal intubation at birth and endotracheal intubation in NICU in the Post-QI group were significantly lower than the Pre-QI group( P<0.05). The application of pulmonary surfactant and mechanical ventilation, the incidence of neonatal respiratory distress syndrome and BPD in the Post-QI group were lower than the Pre-QI group ( P<0.05). After adjusting for confounding factors, Logistic regression analysis showed that DCC ( aOR=0.261,95% CI 0.091~0.718, P=0.023), nCPAP ( aOR=0.284,95% CI 0.123~0.667, P=0.015), MIST ( aOR=0.276,95% CI 0.114~0.627, P=0.011) were protective factors of BPD, and MV ( aOR=2.023,95% CI 1.048~3.918, P=0.036) was risk factor of BPD. Conclusions:The QI program consisting of DCC, early nCPAP and MIST for VPIs can reduce the incidence of BPD.

Objective:To explore the application effect of new whole-course closed sputum specimen collection technology in intensive care unit patients.Methods:From April 2020 to January 2022, the convenient sampling was used to select 442 ICU mechanical ventilation patients admitted to 6 hospitals in Jiaxing City as the research objects. According to the order of admission time, the patients were divided into the control group ( n=221) and the experimental group ( n=221) . The control group adopted the traditional open sputum specimen collection technology, while the experimental group adopted the new whole-course closed sputum specimen collection technology. The heart rate, the incidence of hypooxygen saturation and the incidence of sputum spatter were compared between the two groups after sputum sample sampling. Results:The incidences of hypooxygen saturation and sputum spatter in the experimental group were lower than those in the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The new whole-course closed sputum specimen collection technology can effectively stabilize the oxygen saturation of ICU patients in the process of sputum specimen collection, reduce the incidence of sputum spatter and promote the safety of both patients and medical staff, which is worthy of clinical promotion and application.

Objective:To investigate the effects of terlipressin (TP) combined with norepinephrine (NE) on liver function and prognosis of patients with septic shock.Methods:From June 2018 to December 2019, 96 patients with septic shock and liver function impairment admitted to the ICU of Tianjin First Central Hospital were selected for prospective study. The patients were divided into control group( n=48) and experiment group( n=48) by randomize number table derived by computer. Based on conventional treatment, NE was used in control group, and the low dose continuous infusion of TP combined with NE was used in experiment group. Serial measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum total bilirubin (TBIL), heart rate and mean arterial pressure (MAP), and blood lactic acid levels were made before the treatment and after the treatment at 24 and 48 hours. The mechanical ventilation time, intensive care unit (ICU) stay, and total length of hospital stay of the two groups were compared, and the 28-day mortality and serious adverse reactions of the two groups was also calculated. Results:The levels of ALT, AST, TBIL, heart rate and blood Lac of the two groups were significantly decreased after the treatment (all P<0.01), and the level of MAP was significantly increased (all P<0.01). Compared with the control group, the levels of 24-hour and 48-hour ALT, AST, TBIL, blood Lac of the experiment group were significantly decreased (all P<0.05), and the 48-hour level of MAP was significantly increased (all P<0.05), but there was no statistically significant difference between the two groups in the levels of 24-hour heart rate and 24-hour MAP (all P>0.05). Besides, there was no statistically significant difference between the two groups in the mechanical ventilation time, ICU stay, total length of hospital stay and the 28-day mortality (all P>0.05). And there were no serious adverse reactions such as avascular necrosis of the fingers and myocardial infraction in the two groups. Conclusions:In the treatment of septic shock, on the basic of adequate fluid resuscitation, continuous intravenous pumping of low-dose TP combined with NE can play a certain protective effect on the live, and the mechanisms of action may be mediated by stabilizing hemodynamics, reducing heart rate, reducing the level of blood Lac and improving liver perfusion, thereby protecting liver function in patients with septic shock.