Autophagy is mediated by multiple molecules and pathways. In cardiovascular diseases， autophagy can play a role through key signaling pathways such as phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， adenosine monophosphate-activated protein kinase （AMPK）/mTOR， mitogen-activated protein kinases （MAPK）， p53， Wnt/β-catenin， etc. Traditional Chinese medicine （TCM） monomers for promoting blood circulation and removing blood stasis such as hydroxysafflor yellow A， ginsenoside Rb1， salidroside， ligustrin， curcumin， etc.， and TCM prescription and preparations such as Huangqi baoxin decoction， Taohong siwu decoction， Tongxinluo capsule， Shuangshen ningxin capsule， Suxiao jiuxin pills， etc. can regulate autophagy through the above-mentioned key signaling pathways， thereby alleviating the progression of cardiovascular diseases.

Interpreting genes of interest is essential for identifying molecular mechanisms, but acquiring such information typically involves tedious manual retrieval. To streamline this process, the fanyi package offers tools to retrieve gene information from sources like National Center for Biotechnology Information (NCBI), significantly enhancing accessibility. Additionally, understanding the latest research advancements and sharing achievements are crucial for junior researchers. However, language barriers often restrict knowledge absorption and career development. To address these challenges, we developed the fanyi package, which leverages artificial intelligence (AI)-driven online translation services to accurately translate among multiple languages. This dual functionality allows researchers to quickly capture and comprehend information, promotes a multilingual environment, and fosters innovation in academic community. Meanwhile, the translation functions are versatile and applicable beyond biomedicine research to other domains as well. The fanyi package is freely available at https://github.com/YuLab-SMU/fanyi.

Objective:To explore the acupoint selection law in acupuncture and moxibustion in treating postpartum incontinence by using data mining technology.Methods:The clinical research literature on acupuncture and moxibustion treatment for postpartum incontinence was retrieved from CNKI, Wanfang Data, VIP, CBM, China Medical Journal Full-text Database, PubMed, Embase, Web of Science from the establishment of the databases to February 1, 2023. The acupoint prescription database was established using Excel 2016 and conducting frequency statistics of acupoints, meridians and specific acupoints. Clustering analysis was performed using SPSS Statistics 25.0, and association rule analysis was performed using SPSS Modeler 18.0.Results:A total of 70 articles were included, involving 70 acupuncture prescriptions and including 31 acupoints with a total frequency of 384 times. The top five acupoints were Sanyinjiao (SP6, 46 times), Guanyuan (CV4, 45 times), Zusanli (ST36, 43 times), Zhongji (RN3, 41 times), and Qihai (CV6, 38 times). The commonly used meridians were Conception Vessel, bladder meridian and spleen meridian. The involved acupoints were mostly located in the lower limbs and belly, and most of them were Jiaohui, Mu and Wushu acupoints. Five effective clustering groups were obtained by clustering analysis of high frequency acupoints. The core acupoint combination of association rules was Sanyinjiao (SP6)-Zusanli (ST36)-Guanyuan (CV4)-Qihai (CV6)-Zhongji (RN3).Conclusions:The pathogenesis of postpartum urinary incontinence is mainly characterized by qi deficiency. Acupuncture and moxibustion treatment of postpartum urinary incontinence follows the principles of invigorating qi and tonifying spleen, nourishing lung and tonifying kidney, paying attention to the use of acupoints in abdomen and lower limbs, and using the methods of upper and lower acupoints, anterior and posterior acupoints.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

The genomic characteristics and cellular tropism of a Mangshi virus(MSV)isolated in China were investigated,thereby establishing a robust foundation for further research on the evolution and pathogenicity of MSV.The genome sequence of MSV strain V301/YNJH/2019 was obtained by next-generation sequencing,followed by phylogenetic tree construction and rearrangement assessment using software IQtree,RPD4,and Simplot.Viral proliferation was assessed in C6/36(Aedes albop-ictus),Vero(African green monkey kidney),and BHK(baby hamster kidney)cells.An initial epidemiological investigation of MSV in local cattle and goats was conducted using the serum neutralization test.The genome of MSV strain V301/YNJ H/2019 was 20623 bp in length,encompassing 12 segments of double-stranded RNA(Seg-1 to Seg-12).Sequence analysis confirmed genomic rearrangement of the Seg-1 and Seg-11 sequences,ex-hibiting high similarity to MSV isolated from lake sediment in China in 2022,while Seg-2 to Seg-10 and Seg-12 were most closely related to a MSV strain isolated from mosquitoes in China in 2013.The virus efficiently proliferated and induced sig-nificant cytopathic effects(CPE)in both C6/36 and BHK cells,but limited replication and no observable CPE in Vero cells.No detectable neutralizing antibodies against MSV were detected in 20 goat serum samples collected in Mangshi,while 2 of 20 bo-vine serum samples were positive with neutralizing antibody titers of 1:128 and 1:54.Whole genome sequencing revealed re-assortment events of the V301/YNJH/2019 strain,which is capable of infecting C6/36,BHK,and Vero cells.MSV infection was confirmed in cattle in Mangshi.

ObjectiveTo investigate the effects of the volatile oil of Linderae Radix on the apoptosis and autophagy of human gastric cancer cell line AGS， and to explore the regulatory role of adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway in this process. MethodThe volatile oil of Linderae Radix was extracted by steam distillation， and the effect of the volatile oil on the viability of AGS cells was detected by thiazolyl tetrazolium （MTT） colorimetry. The optimal intervention dose and time were determined according to the half maximal inhibitory concentration （IC₅₀） for subsequent research. The blank， low， medium， and high-dose volatile oil （0， 15， 30， 60 mg·L^-1） groups and the positive drug cyclophosphamide （CTX， 350 mg·L^-1） group were designed. AGS cells were treated with different doses of volatile oil for 48 h. The changes in cell proliferation， cycle， and migration were measured by colony formation assay， flow cytometry， and cell scratch test， respectively. Hematoxylin-eosin （HE） staining was employed to observe the changes of cell morphology， Annexin-V/propidium iodide （PI） double staining to measure the apoptosis， and acridine orange （AO） staining to measure the autophagy level of the cells. Western blotting was employed to determine the expression of the autophagy effectors Beclin-1， p62， microtubule-associated protein 1-light chain 3 （LC3）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3， cleaved poly ADP-ribose polymerase （PARP）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， mTOR， and phosphorylated mTOR （p-mTOR）. ResultCompared with the blank group， 24 h and 48 h of intervention with the volatile oil of Linderae Radix inhibited the viability of AGS cells in a concentration- and time-dependent manner （P<0.05， P<0.01）. Compared with the blank group， the volatile oil decreased the cell proliferation and migration （P<0.05， P<0.01） and blocked the AGS cell cycle in G₂/M phase （P<0.05， P<0.01） in a concentration-dependent manner. The cells treated with the volatile oil became spherical and smaller， with the formation of apoptotic bodies and increased apoptosis rate （P<0.05， P<0.01）. As the dose of the volatile oil increased， the number of autophagosomes increased and the red fluorescence gradually enhanced， indicating the elevated level of autophagy. Compared with the blank group， different doses of volatile oil up-regulated the protein levels of Beclin-1， LC3 Ⅱ/LC3 Ⅰ， cleaved Caspase-3， cleaved PARP， Bax/Bcl-2， and AMPK （P<0.05， P<0.01） and down-regulated the protein levels of p62 and p-mTOR （P<0.05， P<0.01）. ConclusionThe volatile oil of Linderae Radix induces the apoptosis and exerts the autophagy-mediated growth inhibition of AGS cells by regulating the AMPK/mTOR signaling pathway.

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Fluorescence ; Arthritis, Rheumatoid/drug therapy* ; Interleukin-1 ; Arthritis, Experimental/drug therapy*

ObjectiveTo explore the anti-inflammatory effect of Duhuo Jishengtang （DHJST） on collagen-induced arthritis （CIA） model rats and its effect on the Toll-like receptor 2 （TLR2）/p38 mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） signaling pathway. MethodForty-eight male SD rats were randomly divided into the following six groups （n=8）： normal group， model group， methotrexate （MTX） group， low-dose DHJST （DHJST-L） group， medium-dose DHJST （DHJST-M） group， and high-dose DHJST （DHJST-H） group. The CIA model was established by injecting bovine type Ⅱ collagen into the rat tail root with the collagen antibody induction method. After model induction， rats were treated with drugs by gavage. The rats in the MTX group received MTX at 2.0 mg·kg^-1， three times a week， and those in the DHJST groups received DHJST at 3.8， 7.6， 15.2 g·kg^-1·d^-1 for 28 days. The rats in the normal group and the model group were given the same dose of normal saline. The weight of the rats was recorded， and the paw swelling degree was observed. The arthritis index and immune organ index were measured， and the changes in the microcirculation indexes of the rats were detected with a microcirculation detector. Hematoxylin-eosin （HE） staining was used to detect the pathological morphologic changes in rat synovial tissues and the apoptosis rate of synovial cells was detected by flow cytometry to determine the therapeutic effect of DHJST on rheumatoid arthritis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the changes in serum levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-17A， and interferon-γ （IFN-γ）. The protein expression of TLR2， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， p38 MAPK， and p-p38 MAPK was detected by Western blot. ResultCompared with the normal group， the model group showed reduced body weight （P<0.01）， increased paw swelling degree， arthritis index， and immune organ index （P<0.01）， increased comprehensive microvascular score and vascular resistance （P<0.01）， significant hyperplasia of synovial tissues and massive infiltration of inflammatory cells as revealed by pathological sections， and up-regulated expression levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum， and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.01）. Compared with the model group， the DHJST groups showed increased body weight of rats （P<0.01）， decreased paw swelling degree， arthritis index， and immune organ index （P<0.05， P<0.01）， reduced comprehensive microvascular score and vascular resistance （P<0.05， P<0.01）， improved synovial histopathological injury， increased apoptosis rate of synovial cells （P<0.01）， and down-regulated levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum （P<0.05， P<0.01） and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.05， P<0.01）. ConclusionDHJST may alleviate the inflammatory reaction in CIA rats by regulating the TLR2/p38 MAPK/NF-κB signaling pathway， thus exerting its anti-rheumatoid arthritis effect.

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.
Humans ; Quality of Life ; Drug Delivery Systems ; Arthritis, Rheumatoid/drug therapy* ; Autoimmune Diseases/drug therapy* ; Nanotechnology