Traditional Chinese medicine （TCM） therapy has unique clinical advantages in the treatment of atrial fibrillation， mainly reflected in five aspects， improving quality of life， enabling early diagnosis and treatment， promoting cardiac rehabilitation， making up for the limitations of Western medicine， and improving the success rate of catheter ablation. However， there is insufficient evidence in current clinical research. Based on the current status of TCM research in the treatment of atrial fibrillation， it is suggested that future studies should focus on standardized research on syndrome differentiation and classification. This can be achieved through clinical epidemiological surveys， expert consensus， and other methods to establish a unified syndrome differentiation and classification standard for atrial fibrillation. Clinical efficacy evaluation indicators should be standardized， and core outcome measures for clinical research on TCM treatment of atrial fibrillation should be developed through systematic reviews， patient interviews， and other methods. Additionally， clinical research design， implementation， and data management should be improved. By leveraging modern information technologies such as artificial intelligence， the scientific and standardized nature of TCM intervention research on atrial fibrillation can be enhanced， ultimately improving the quality of research.

The occurrence of diabetes mellitus （DM） is closely related to insulin resistance and islet β cell dysfunction. Modern studies have found that macrophages are widely present in the liver，fat，skeletal muscle，islets， and other tissues and organs. Macrophage M1/M2 polarization plays an important role in the occurrence and development of diabetes mellitus and its related complications by intervening in inflammatory response，improving insulin resistance，and promoting tissue repair. Most of the traditional Chinese medicines that regulate the activation and polarization of macrophages are Qi-replenishing and Yin-nourishing，heat-clearing， and detoxicating medicinal，which are consistent with the etiology and pathogenesis of diabetes and its related complications. Therefore，by summarizing the mechanisms between macrophage activation，polarization， and insulin resistance in various tissues，this paper reviewed traditional Chinese medicine and its effective components and compounds in improving diabetes mellitus and its related complications through multi-channel regulation of macrophage polarization and regulation of M1/M2 ratio，providing references for the future treatment of DM and its related complications with traditional Chinese medicine.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:To retrospectively analyze the bone marrow characteristics of methimazole-induced agranulocytosis and other hematologic damage, and to explore its correlation with clinical features and prognosis.Methods:The bone marrow and clinical parameters of 20 patients of Graves′ disease diagnosed with methimazole-induced agranulocytosis at the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to December 2022 were collected. The intergroup differences in bone marrow characteristics and granulocyte recovery time were analyzed. Differences in peripheral blood and bone marrow characteristics between patients with single agranulocytosis and pancytopenia were compared. Besides, literature review of the bone marrow characteristics of methimazole-induced hematologic diseases was conducted.Results:Compared to patients with bone marrow characteristics of granulocyte and precursor maturation disorders(Type Ⅱ), patients with aplastic marrow(Type Ⅰ) had significant decreases in the proportions of granulocytes in all phases( P<0.05). Patients with bone marrow characteristics of Type Ⅰ had a significant increase in the proportion of the lymphocyte system [51.00%(41.50%, 75.50%) vs 22.00%(14.00%, 35.00%), P=0.002], and got a longer to recovery time [(6.58±1.68)d vs(3.71±1.60)d, P=0.003]; Correlation analysis suggested the granulocyte to erythrocyte ratio was negatively correlated with the granulocyte recovery time( r=-0.520, P=0.023), and the proportion of the bone marrow lymphocyte was positively correlated with granulocyte recovery time( r=0.622, P=0.004). Compared to patients with single agranulocytosis, patients with pancytopenia had a markedly longer hospital stay duration [(27.14±5.27)d vs(14.15±7.36)d, P=0.001]. Literature review suggestsed that methimazole may cause various degrees of damage to blood system and bone marrow. Conclusion:Methimazole can induce a variety of hematologic damages. Analysis of bone marrow characteristics can aid in further prognosis assessment. Clinicians should be vigilant about potential hematologic adverse reactions when using methimazole and promptly diagnose and treat them to prevent serious consequences.

Objective To investigate the effects of Yitangkang on browning of white adipose and PINK1/Parkin pathway of mitophagy in adipose tissue of db/db mice.Methods Totally 30 six-week db/db mice were randomly divided into model group,Yitangkang Group(30 g/kg)and liraglutide group(200 μg/kg),and another 10 C57BL/6 mice of the same age were set as normal group.All groups were treated with corresponding drugs or normal saline for 5 weeks.During the period of administration,the body mass and fasting blood glucose(FBG)of mice in each group were detected regularly,the samples of liver,white and brown adipose of mice were weighed,the contents of serum triglyceride cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical analyzer,HE staining was used to observe the pathological changes of inguinal white adipose tissue(iWAT),immunohistochemical staining was used to detect the expression of browning marker protein uncoupling protein-1(UCP1)in iWAT,Western blot was used to detect the expressions of browning-related proteins UCP1,PRDM16,PGC-1α and mitophagy-related proteins PINK1,Parkin,Beclin-1,p62 in iWAT.Results Compared with the normal group,the body mass,liver,white adipose and brown adipose mass of the model group significantly increased(P<0.01),the FBG and serum TG,TC and LDL-C contents significantly increased(P<0.01),and the content of HDL-C significantly decreased(P<0.01);large vacuoles in iWAT adipocytes,the diameter of adipocytes increased obviously,some adipocytes were extruded and deformed,and the edge of adipocytes was not clear,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins decreased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins increased(P<0.01).Compared with the model group,the body mass,liver and white adipose mass significantly decreased in Yitangkang group and the liraglutide group(P<0.01),FBG and serum contents of TC,TG and LDL-C were significantly decreased(P<0.05,P<0.01),while HDL-C content significantly increased(P<0.01);the diameter of iWAT adipocytes decreased,the number increased,and the morphology was regular,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins increased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins decreased(P<0.05,P<0.01).Conclusion Yitangkang can improve glucose and lipid metabolism and promote browning of white adipose in db/db mice,which may be related to mitophagy mediated by PINK1/Parkin pathway.

Objective To monitor and evaluate the synergistic antitumor effects of programmed death-1(PD-1)checkpoint inhibitor combined with radiation therapy through whole-body dynamic 18 F-Fluorodeoxy glucose positron emission computed tomography(18F-FDG PET/CT)and Patlak multi-parametric analysis.Methods B16F10 mel-anoma dual-tumor mouse model was established and randomly divided into control,PD-1 monoclonal antibody,ra-diation-only,and combination groups(n=6).Whole-body 18F-FDG PET/CT imaging was performed before and 24 hours post-treatment.The changes of maximum standardized uptake value(SUVmax)and metabolic rate of FDG(MRFDG)changes were analyzed and compared.Mice were then euthanized,tumors excised and underwent histo-pathology with HE,CD8,Ki-67 staining to assess immune infiltration and proliferation.Distal tumor volumes were monitored during treatment.Results At 24 hours post-treatment,in the primary tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group(P＜0.000 1),while they decreased in the combination treatment group(P＜0.000 1),with statistically significant differences.In the distal tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group,PD-1 monoclonal antibody group,and radiothera-py-alone group.The SUVmax differences were statistically significant in the control group before and after treatment(P＜0.000 1).MRFDG values in the distal tumors showed statistically significant differences in all three groups(P＜0.01 or P＜0.000 1).In the combination treatment group,SUVmax and MRFDG values in the distal tumors de-creased significantly compared to pre-treatment(P＜0.000 1).Post-treatment comparison of SUVmax and MRFDG values in the distal tumors showed that statistically significant differences in SUVmax and MRFDG values were observed among all groups except between the radiotherapy-alone and PD-1 monoclonal antibody groups(all P＜0.05).Im-munohistochemistry results showed that the mean absorbance value of CD8 T lymphocytes in the distal tumor was significantly higher than that in the other three groups(P＜0.001);the mean absorbance value of Ki-67 immuno-histochemistry in the distal tumor proliferation index was significantly lower than that in the other three groups(P＜0.001).Conclusion The synergistic effects of combined treatment reduced distal tumor growth.Whole-body 18F-FDG PET/CT Patlak multi-parametric imaging can monitor the synergistic effects of PD-1 antibody and radiotherapy in B16F10 melanoma,providing reliable imaging parameters for optimizing combinatorial therapies.

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 investigate the immunological features of 135 patients with corona virus disease 2019 (COVID-19), and to provide reference for the pathogenesis of the disease.Methods:The clinical and laboratory data of 135 confirmed COVID-19 patients in Guangzhou Eighth People′s Hospital from January 23 to February 29, 2020 were collected. The features of lymphocytes (CD4 + and CD8 + T lymphocytes, B lymphocytes, natural killer cells and natural killer T cells), and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) of patients at a median of 19 (14, 27) days of admission were analyzed. Kruskal-Wallis test, Mann-Whitney U test, chi-square test and Spearman rank correlation were used for statistical analysis. Results:Patients were divided into three groups according to the relevant diagnostic criteria, including mild group (14 cases), ordinary group (92 cases) and severe group (29 cases). Decreased CD4 + T lymphocytes were found in 44.4% (60/135) patients, while decreased CD8 + T lymphocytes were found in 42.2%(57/135) patients. Compared to mild group and ordinary group, level of CD4 + T lymphocytes in severe group was significant lower ( Z=4.379 and 3.799, respectively, both P<0.01), and level of CD8 + T lymphocytes was also significant lower ( Z=2.684 and 3.306, respectively, P=0.022 and 0.003, respectively). Decreased B lymphocytes were found in 25.3% (24/95) patients and significant different among the three groups, with the lowest levels ((88(56, 189)/μL; Z=6.199, P=0.045) and most frequency of decreased levels ((52.2%(12/23); χ2=11.723, P=0.003) in the severe group. Compared to the mild group and the ordinary group, IL-6 level in severe group was significant higher ( Z=-4.022 and -4.108, respectively, both P<0.01) and IL-10 level was also significant higher ( Z=-3.261 and -4.006, respectively, both P<0.01). Similar levels of IL-2, IL-4, TNF-α and IFN-γ were found among three groups (all P>0.05). The IL-6 level was positively correlated with the persistence of viral shedding ( r=0.301, P=0.007). Conclusion:The immune-mediated inflammation may be the important cause of disease deterioration of COVID-19, which might be the key target of the treatment of severe cases.

Objective To study the therapeutic effect and safety of orthokeratology in the teenagers with high myopia.Methods A retrospective cohort study was carried out.The clinical data of 120 eyes from 60 high myopia patients wearing orthokeratology contact lens for 1 year in Henan Eye Hospital from June 2013 to June 2014 was analyzed,and the data of contemporaneous 118 eyes from 59 matched high myopia patients wearing conventional glasses were used as controls.The initial spherical equivalent (SE) of all the patients was-6.00 to-9.00 D.The maximum correction amplitude of the orthokeratology contact lens was set as 6.00 D based on the Regulation of China Food & Drug Administration.The contact lenses were worn for 1 month firstly and then the conventional glasses were used at daytime and contact lenses were consecutively worn at night for 1 year in the contact lenses group,and only glasses were worn in the conventional glasses group.The uncorrective visual acuity (UCVA),SE,corneal fluorescein staining were examined 1 week,1 month,3 months,6 months and 12 months after wearing lenses.The changes of corneal endothelial cells were examined 6 and 12 months after wearing lenses.Results The UCVA was improved and SE was reduced 1 month and 3,6 and 12 months after wearing lenses in comparison with 1 week after wearing lenses in the contact lenses group (all at P＜0.01);while no significant change was seen in UCVA in the conventional glasses group (all at P＞0.05).Compared with wearing contact lenses,the SE was increased in various time points after wearing glasses in the conventional glasses group (all at P＜0.01).The axial length and SE extended by (0.08±0.12)mm and (0.19±0.21)D in the contact lenses group and those in the conventional glasses group were (0.29±0.14)mm and (0.69±0.27)D,showing significant differences between the two groups (t =10.024,5.691,both at P＜0.01).No significant differences were found in corneal endothelial cell density,percentage of hexagonal cells and coefficient of variation of corneal endothelial cells in various time points after wearing contact lenses (corneal endothelial cell density:Fgroup =0.090,P =0.769;Ftime =0.133,P =0.563.percentage of hexagonal cells:Fgroup =0.071,P=0.836;Ftime =1.091,P =0.203.coefficient of variation:Fgroup =0.107,P =0.734;Ftime =1.948,P =0.156).The incidence of corneal fluorescein staining was 31.67％ in the contact lens group,which was much higher than 3.51％ in the conventional glasses group (x2 =97.910,P =0.001).Conclusions Compared with wearing only conventional glasses,orthokeratology can improve UCVA and control axial length extension in juvenile with high myopia,but orthokeratology is more likely to damage the corneal superficial layer.

Objective · To investigate the relationship between the results of thin prep cytologic test (TCT), high-risk human papillomavirus (Hr-HPV) detection and vaginalintraepithelial neoplasia (VAIN) after hysterectomy. Methods · A retrospective study was conducted of 56 patients with VAIN after hysterectomy. The analysis included TCT and Hr-HPV examination, clinical data and the relationship between Hr-HPV examinenation and histopathological examination of colposcopy. Results · Postoperative follow-up of TCT and Hr-HPV parallel pathological examination showed that 56 patients had vaginal stump lesions, including cervical factor hysterectomy accounted for 5.81% (45/775) and non cervical factor hysterectomy accounted for 0.19% (11/5933). The difference was statistically significant (P=0.000). In 56 cases of patients with vaginal stump lesions, Hr-HPV infection were 40 cases (accounting for 71.43%), uninfected patients were 16 cases (accounting for 28.57%). The Hr-HPV infection rates of cervical hysterectomy and non cervical factor hysterectomy patients were 80.00% (36/45) and 36.36% (4/11) respectively, and the difference was statistically significant (χ2= 6.248, P=0.012). TCT results showed that the incidence of squamous intraepithelial lesions were 42.22% (19/45) and 9.09% (1/11) respectively. Conclusion · The Hr-HPV infection rate and the morbidity of VAIN of the patients undergone hysterectomy due to the cervical lesionfactors is higher than those who had none cervical lesion factors. In order to identify VAIN early, patients who have the history of hysterectomy should undergo careful evaluation of cervical and vaginal circumstance before surgery and the routine examinations of TCT and Hr-HPV in the follow-up.