Mitochondria, functioning not only as the central hub of cellular energy metabolism but also as semi-autonomous organelles, orchestrate cellular fate decisions through their endogenous mitochondrial DNA (mtDNA), which encodes core components of the electron transport chain. Emerging research has identified microRNAs localized within mitochondria, termed mitochondria-located microRNAs (mitomiRs). Recent studies have revealed that mitomiRs are transcribed from nuclear DNA (nDNA), processed and matured in the cytoplasm, and subsequently transported into mitochondria. mitomiRs regulate mtDNA through diverse mechanisms, including modulation of mtDNA expression at the translational level and direct binding to mtDNA to influence transcription. Aberrant expression of mitomiRs leads to mitochondrial dysfunction and contributes to the pathogenesis of metabolic diseases. Restoring mitomiR expression to physiological levels using mitomiRs mimics or inhibitors has been shown to improve mitochondrial function and alleviate related diseases. Consequently, the regulatory mechanisms of mitomiRs have become a major focus in mitochondrial research. Given that mitomiRs are located in mitochondria, targeted delivery strategies designed for mtDNA can be adapted for the delivery of mitomiRs mimics or inhibitors. However, numerous intracellular and extracellular barriers remain, highlighting the need for more precise and efficient delivery systems in the future. The regulation of mtDNA expression mediated by mitomiRs not only expands our understanding of miRNA functions in post-transcriptional gene regulation but also provides promising molecular targets for the treatment of mitochondrial-related diseases. This review systematically summarizes recent research progress on mitomiRs in regulating mtDNA expression and discusses the underlying mechanisms of mitomiRs-mtDNA interactions. Additionally, it provides new perspectives on precision therapeutic strategies, with a particular emphasis on mitomiRs-based regulation of mitochondrial function in mitochondrial-related diseases.

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

Through a compound induction method, combined with neurobehavioral, macroscopic characterization and objective pathological evaluation indicators, a murine depression model of liver depression transforming into fire syndrome was constructed and confirmed. The model was constructed using a combination of sleep deprivation, light exposure, and alternate-day food deprivation. Evaluation was conducted at three levels: face validity, constructs validity, and predictive validity. The establishment of the liver depression transforming into fire syndrome depression model was further validated through the counterproof of traditional Chinese medicine formulas. In terms of face validity, compared to the control group, mice in the model group exhibited typical depressive symptoms in neurobehavioral assessments; the general observation of the model group mice reveals disheveled and lackluster fur, along with delayed and easily agitated responses. Additionally, there is a substantial increase in water consumption. In the sleep phase detection of mouse, the model group showed a significant increase in the proportion of time spent in the wake phase during sleep, accompanied by a significant decrease in the proportions of time spent in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep phases. There are significant differences in physiological indicators such as average blood flow velocity, blood flow rate, tongue, urine, and claw color (r values) in the internal carotid artery. Structural validity demonstrated that levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and γ-aminobutyric acid (GABA) in the hippocampus of model mice decreased significantly, while acetylcholine (ACh), tryptophan (Try), and glutamic acid (Glu) levels increased significantly. Treatment with Danzhi Xiaoyao San led to varying degrees of restoration in the aforementioned neurotransmitters. In terms of predictive validity, the antidepressant paroxetine effectively ameliorated depressive behaviors in the model mice, and the classic formula Danzhi Xiaoyao San demonstrated varying degrees of improvement in depression-related indicators. In conclusion, this study has established a novel animal model of liver-stagnation with the fire depression, thereby expanding the repertoire of traditional Chinese medicine depression models. This development contributes to the diversification of melancholic syndrome models in Chinese medicine, offering a broader spectrum of options for scientific exploration, efficacy evaluation, and drug screening in the future prevention and treatment of depression with traditional Chinese medicine. Animal experiments were conducted with the approval and supervision of the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (ethics number: 20230313040).

The advent of gene editing represents one of the most transformative breakthroughs in life science, making genome manipulation more accessible than ever before. While traditional CRISPR/Cas-based gene editing, which involves double-strand DNA breaks (DSBs), excels at gene disruption, it is less effective for accurate gene modification. The limitation arises because DSBs are primarily repaired via non-homologous end joining (NHEJ), which tends to introduce indels at the break site. While homology-directed repair (HDR) can achieve precise editing when a donor DNA template is provided, the reliance on DSBs often results in unintended genome damage. HDR is restricted to specific cell cycle phases, limiting its application. Currently, gene editing has evolved to unprecedented levels of precision without relying on DSB and HDR. The development of innovative systems, such as base editing, prime editing, and CRISPR-associated transposases (CASTs), now allow for precise editing ranging from single nucleotides to large DNA fragments. Base editors (BEs) enable the direct conversion of one nucleotide to another, and prime editors (PEs) further expand gene editing capabilities by allowing for the insertion, deletion, or alteration of small DNA fragments. The CAST system, a recent innovation, allows for the precise insertion of large DNA fragments at specific genomic locations. In recent years, the optimization of these precise gene editing tools has led to significant improvements in editing efficiency, specificity, and versatility, with advancements such as the creation of base editors for nucleotide transversions, enhanced prime editing systems for more efficient and precise modifications, and refined CAST systems for targeted large DNA insertions, expanding the range of applications for these tools. Concurrently, these advances are complemented by significant improvements in in vivo delivery methods, which have paved the way for therapeutic application of precise gene editing tools. Effective delivery systems are critical for the success of gene therapies, and recent developments in both viral and non-viral vectors have improved the efficiency and safety of gene editing. For instance, adeno-associated viruses (AAVs) are widely used due to their high transfection efficiency and low immunogenicity, though challenges such as limited cargo capacity and potential for immune responses remain. Non-viral delivery systems, including lipid nanoparticles (LNPs), offer an alternative with lower immunogenicity and higher payload capacity, although their transfection efficiency can be lower. The therapeutic potential of these precise gene editing technologies is vast, particularly in treating genetic disorders. Preclinical studies have demonstrated the effectiveness of base editing in correcting genetic mutations responsible for diseases such as cardiomyopathy, liver disease, and hereditary hearing loss. These technologies promise to treat symptoms and potentially cure the underlying genetic causes of these conditions. Meanwhile, challenges remain, such as optimizing the safety and specificity of gene editing tools, improving delivery systems, and overcoming off-target effects, all of which are critical for their successful application in clinical settings. In summary, the continuous evolution of precise gene editing technologies, combined with advancements in delivery systems, is driving the field toward new therapeutic applications that can potentially transform the treatment of genetic disorders by targeting their root causes.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

In infants with severe bronchopulmonary dysplasia(sBPD),severe pulmonary lobar emphysema may occur as a complication,contributing to significant impairment in ventilation.Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation.However,prior to the lobectomy,it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively.In addition,preoperative planning and perioperative management are also quite challenging in these patients.This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema.Since infants with sBPD already have poor lung development and significant lung injury,lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution.Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema.However,given the technical difficulty,successful application of this technique requires close collaboration of an experienced interdisciplinary team.

Objective To verify the safety and efficacy of a new portable extracorporeal membrane oxygenation(ECMO)system(Xijing Advanced Life Support System JC-Ⅲ)in large animals.Methods A total of 10 healthy small fat-tail sheep underwent veno-arterial extracorporeal membrane oxygenation(VA-ECMO)support by carotid arterial-jugular catheterization to evaluate the performance of the JC-Ⅲ ECMO system.Systemic anticoagulation was achieved by continuous infusion of heparin.Active coagulation time(ACT)was recorded every 2 hours during the experiment,and the ACT was maintained between 200-250 s.Centrifugal pump speed is set at 3 000-3 500 r/min.The changes of hemoglobin,blood cell counts,hematocrit,liver and kidney function were monitored before and 24 h after ECMO initiation,respectively.After the experiment,the pump and oxygenator were dissected to probe the thrombosis.Results The success rate of VA-ECMO operation was 100％,and there was no hemolysis,pump thrombosis and oxygenator thrombosis after 24 h of ECMO.Before and after the operation,there were no significant changes in indicators such as hemoglobin content,white blood cell counts,platelet counts,alanine aminotransferase concentration,aspartate aminotransferase concentration,urea,creatinine,high-sensitivity troponin Ⅰ,and N-terminal pro-brain natriuretic peptide(all P＞0.05).Conclusions This in vivo study confirms that Xijing Advanced Life support System JC-Ⅲ is safe and effective.

AIM:To predict the active compo-nents and targets of Piperlongum L.and the associ-ated signaling pathways involved in pulmonary fi-brosis using network pharmacology and molecular docking technique and evaluate the mechanism of Piperlongum L against pulmonary fibrosis by in vi-tro experiments.METHODS:The active ingredients and targets were retrieved from TCMSP,Swiss Tar-get Prediction and PubChem databases.The dis-ease-related targets were retrieved from Gene-Cards and OMIM databases.The intersection tar-gets of the drugs and disease-related targets were identified using jvenn online tool.String database was used to construct the"drug-component-tar-get"and PPI network and the networks were visual-ized using Cytoscape 3.9.1 software.GO and KEGG enrichment analysis were performed on the inter-section targets using the DAVID tool.The top 20 KEGG pathways,core targets and drug components were used to construct a"component-target-path-way"network and the network visualization was performed using Cytoscape 3.9.1 software.The in-teractions between drug compounds and the tar-gets were evaluated by molecular docking,and the docking results were visualized using Discovery stu-dio.HFL-1 cells were cultured and the effect of the drug compounds on cell viability was determined by MTT assay.The inhibition rate was then calculat-ed to determine the optimal drug concentration.HFL-1 cells were cultured in vitro and were as-signed into 4 groups:control group,TGF-β1 group,TGF-β1+LD group(LD group),TGF-β1+HD group(HD group).CCK-8 kit was used to evaluate the anti-proliferative activity of the drug compounds against HFL-1 cells at 24,48 and 72 h.Plate clone formation assay was performed to evaluate the ef-fect of drugs on the colony formation ability of HFL-1 cells.RT-qPCR and western blot were conducted to determine the effect of the compounds on the mRNA and protein expression levels of α-smooth muscle actin(α-SMA),collagen type Ⅰ(COI-Ⅰ),and collagen type Ⅲ(COI-Ⅲ)in each group.RESULTS:A total of 197 intersection targets of Piperlongum L and anti-pulmonary fibrosis were identified.The core PPI network comprised 29 nodes(targets)and 199 edges(interactions).GO functional analysis showed that the significantly enriched biological processes associated with the compounds in Piper-longum L included negative regulation of apopto-sis,signal transduction,and protein phosphoryla-tion.Significantly enriched cellular components in-cluded cytoplasm,nuclear cytoplasm,plasma mem-brane.Enriched molecular functions associated with the compounds included the same protein binding,serine/threonine/tyrosine kinase activity,and protein binding.A total of 155 significantly en-riched KEGG signaling pathways were identified,with PI3K-Akt signaling pathway was highly associ-ated with PF and was the fourth most enriched pathway.PIK3CA,MAPK3,MAPK1,MTOR,SRC,CCND1,EGFR,PRKCA,BCL2,and GSK3B had the highest connectivity in the components-target-pathway network.Piperlongine,N-(2,5-dimethoxy-phenyl)-4-methoxybenzamide,tetrahydrotanshi-none,pisigenin and piperine were the key com-pounds in Piperlongum L.The molecular docking results showed that all the compounds except N-(2,5-dimethoxyphenyl)-4-methoxybenzamide had good binding activities with interactions observed with 10 proteins.The proliferation ability of the cells in the LD group was significantly lower than that of the TGF-β1 group at 48 h and 72 h(P＜0.05).The proliferation ability of cells HD group was sig-nificantly lower than the LD group at 24,48 and 72 h.The number of clones in each drug group was significantly reduced after treatment with the drugs(P＜0.05).The mRNA and protein expression levels of α-SMA,COI-Ⅰ,COI-Ⅲ in LD and HD groups were significantly lower than the expression levels in the TGF-β1 group.The protein expression levels of p-PI3K/PI3K and p-Akt/AKT were significantly lower in the two dose groups compared with the TGF-β1 group(P＜0.01).CONCLUSION:The results showed that the effect of Piperlongum L against PF is probably through modulation of the PI3K-Akt sig-naling pathway.