A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

OBJECTIVE: To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: In a retrospective, single center, single arm study, we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) at our center from March 2021 to December 2024. The clinical characteristics of the patients, the conditioning regimen details, treatment-related toxicities and adverse reactions, post-transplant disease remission status, and survival outcomes were analyzed. RESULTS: A total of 28 patients were included. Among them, 19 patients received ASCT as first-line consolidation therapy in complete response (CR) or partial response (PR) status, and 9 patients with relapsed/refractory disease underwent salvage ASCT. The median time to neutrophil engraftment was 9 days (range: 5-11 days), and the median time to platelet engraftment was 10 days (range: 6-13 days). All patients achieved CR at the initial efficacy evaluation post-ASCT. The main complications during the transplantation period were febrile neutropenia (26 cases) and grade 3 diarrhea (9 cases). No transplantation-related mortality occurred. Post-ASCT, 19 patients received maintenance therapy, which was demonstrated to be safe and effective. Three patients relapse, and one patient died. The median progression-free survival (PFS) and overall survival (OS) of patients were not reached. The estimated 1-year and 2-year cumulative PFS rates were 88.4% and 66.3%, respectively, while the 1-year and 2-year OS rates were both 94.1%. CONCLUSION The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.
Humans ; Thiotepa/therapeutic use* ; Retrospective Studies ; Transplantation, Autologous ; Transplantation Conditioning/methods* ; Central Nervous System Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Adult ; Lymphoma/therapy* ; Treatment Outcome ; Aged

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

Aim To investigate the regulatory effects of 3-bromopyruvate (3-BrPA) on apoptosis and autophagy of fibroblast-like synoviocytes (FLS) in rats based on AMPK/mTOR signaling pathway and the underlying mechanism. Methods FLS of rats in vitro were cultured and induced by tumor necrosis factor-α (TNF-α) to construct a model of rheumatoid arthritis (R A). MTT assay was used to explore the optimal concentration of TNF-α and 3 -BrPA for induction and treatment of FLS. The effects of 3-BrPA on the migration and invasion of FLS were detected by Wound healing assay and Transwell assay. The apoptosis of FLS was tested by flow cytometry and mitochondrial membrane potential assay kit (JC-1). Moreover, FLS autophagic flux was detected by mCherry-EGFP-LC3B-overexpressed plasmids, and the expression of apoptosis/autophagy-related proteins as well as AMPK/mTOR pathway-related proteins were detected by Western blot. Results 3-BrPA (15 μmol • L) significantly inhibited the proliferation, migration, and invasion of FLS stimulated by TNF-a (25 μg • L

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective: A multicenter Chinese mainland survey was conducted to investigate the sensitization distribution characteristics of cat, dog and horse dander in patients with allergic diseases, so as to provide clinicians with epidemiological data of common animal allergens and useful information for the prevention and treatment of allergies in cats, dogs and horses. Methods: The epidemiological investigation and design was adopted. This study is based on the national epidemiological survey of allergic diseases led by the first affiliated Hospital of Guangzhou Medical University. From January to December in 2021, a total of 2 122 patients diagnosed with allergic diseases were included in the outpatient department of respiratory department/pediatrics/allergy department of 14 units such as the First Affiliated Hospital of Guangzhou Medical University, and 222 healthy subjects were included as controls from the physical examination center of the above units in the same period. All the subjects filled out the allergic disease questionnaire under the guidance of doctors, and the allergen-specific immunoglobulin E (sIgE) of cats, dogs and horses of all subjects were detected by magnetic particle chemiluminescence system. The epidemiological characteristics of three animal allergens in different diseases, ages and regions were analyzed. Chi square test was used to analyze the frequency difference between groups, t test or Mann Whitney U test was used to test the distribution difference between two groups, and one-way ANOVA or Kruskal Wallis H test was used to compare the distribution difference between multiple groups. Bar chart, Venn-plot and radar chart were drawn to show the sensitization distribution characteristics. A small number of missing values caused by subjects' omission have been excluded during the analysis. Results: The 2 122 patients with allergic diseases were 57.35% male (1 217/2 122) and 40.95% female (869/2 122), and 1.70% (36/2 122) patients had loss of gender information. The age of patients with allergic diseases was 9.0 (6.0, 28.0) years, while that of healthy controls was 29.0 (13.0, 39.0) years old, and there were 1.7% (36/2 122) and 0.9% (2/222) subjects with missing age information, respectively. The proportion of caesarean section in allergic patients was significantly higher than that in healthy controls (31.4% vs. 17.6%,χ²=16.582,P<0.001) [2.5% (54/2 122) of the patient group and 5.4% (12/222) of the control group had missing birth mode information], and the proportion of patients with allergic diseases who reported that both parents had allergic diseases was significantly higher than that of the control group (35.7% vs. 9.5%, χ²=65.171,P<0.001). Patients with allergic diseases are mainly school-age (6-12 years old) and adolescents (12-18 years old). 16.4% of patients with allergic diseases were sensitized to cat dander, 10% and 6% to dog and horse dander. The sensitization rate of cat dander in patients with rhinitis, asthma, conjunctivitis, food allergy and atopic dermatitis was the highest (16.4%-21.6%), followed by dog dander (10.2%-15.2%). The prevalence of allergic rhinitis was the highest among different animal sensitized populations. The proportion of cat, dog and horse allergens sensitized at the same time is between 10%-15%, and the proportion of any two or more animal dander sensitized at the same time is about 45%. Animal allergens are associated with respiratory allergic diseases, especially allergic rhinitis with allergic conjunctivitis. There were significant differences in the distribution of positive rates of three animal allergens in different regions, and the highest positive rate of cat dander was found in all provinces of the country. Conclusion: The sensitization rate of animal dander allergens increased significantly, and the highest was in children and adolescents. Cat dander is the most common animal allergen, followed by dog. Different animals show obvious cross or common sensitization due to their high homology.
Allergens ; Animals ; Cats ; Cesarean Section ; Dander ; Dogs ; Female ; Horses ; Immunoglobulin E ; Male ; Pregnancy ; Rhinitis, Allergic

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

OBJECTIVE: To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+). METHODS: MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot. RESULTS: Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05). CONCLUSION Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.
Apoptosis ; Benzothiazoles ; Cell Line, Tumor ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Paclitaxel/therapeutic use* ; Phenylurea Compounds ; RNA, Messenger ; STAT5 Transcription Factor/pharmacology* ; Signal Transduction ; fms-Like Tyrosine Kinase 3

Objective:To analyze the source of infection， clinical symptoms and epidemiological characteristics of pertussis surveillance cases in Minhang District of Shanghai from 2017 to 2019，so as to provide the basis for pertussis surveillance and immunization strategy. Methods:Descriptive epidemiological method was used to analyze the pertussis surveillance cases. Results:A total of 334 cases were included in the pertussis active surveillance system， 237 cases were confirmed cases. There were 13 towns or streets in Minhang District， except for Pujin Street， all the other 12 towns or streets had cases. The high risk group （131/237， 55.27% of the cases） were the infants under five months old who did not reach the age of immunization or did not complete the basic immunization of diphtheria， tetanus， and acellular pertussis combined vaccine （DTaP）. The cases mainly occurred in March to July， accounting for 71.31% （169/237）. The highest culture-positive rate of Bordetella pertussis was in August （82.76%， 24/29）； the highest positive rate of polymerase chain reaction （PCR） detection was in March （58.82%， 20/34）. All the monitored cases had cough symptoms with an average cough days of 22.05±9.81 in confirmed cases. A total of 64 clustered outbreaks were detected， with an attack rate of 37.45% （94/251）. 32.91% （78/237） of the cases had contact history with coughing patients 21 days before the onset， and 94.87% （74/78） of them were family members. The aggregation of pertussis was mainly transmitted from adults to infants and infants to adults. Conclusion:Children under five months old are the high incidence population of pertussis， and family members are the main source of infection. It is suggested that pertussis monitoring and prevention should be carried out in adolescents and adults.