Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， with a complex pathogenesis. Mitochondria play a pivotal role in this disease process， and studies have confirmed that mitochondrial dysfunction can exacerbate metabolic disorders and induce innate immune imbalance， while mitochondrial DNA （mtDNA） is the core molecule mediating these two pathological effects. After the abnormal release of mtDNA， it can be recognized by intracellular pattern recognition receptors， which in turn triggers innate immune responses and causes tissue damage， forming a pathological pathway of “mtDNA release-immune activation-tissue damage”. Currently， there is a lack of systematic reviews summarizing the mechanism of action of this pathway in different stages of MAFLD and the intervention strategies targeting this pathway. This article systematically reviews the core molecular mechanism of this pathway， its pathological role in the development and progression of MAFLD， and the current intervention strategies targeting this mechanism， in order to provide a theoretical basis for analyzing the pathogenesis of MAFLD and developing novel therapeutic strategies.

Based on the traditional Chinese medicine （TCM） theories of body fluid metabolism and turbid phlegm obstructing the orifices， and drawing on recent advances in cerebrospinal fluid-interstitial fluid （CSF-ISF） exchange， glymphatic clearance， and extracellular matrix （ECM） regulation， this article discusses the possible scientific connotation of "invisible phlegm" from the perspectives of pathogenesis， clinical manifestations， and therapeutic implications. Impaired brain fluid exchange may lead to reduced clearance， the retention of metabolic wastes and pathological proteins. Abnormal ECM remodeling may further disrupt molecular diffusion and local microenvironmental homeostasis， resulting in a pathological process characterized by slowed fluid movement， reduced clearance， and abnormal retention. This process bears a certain functional resemblance to the TCM pathogenesis of impaired distribution of body fluids， endogenous formation of turbid phlegm and obstruction of the brain orifices， and may also be associated with manifestations such as a clouded sensation in the head， cognitive abnormalities， and emotional disturbances. On this basis， the potential effects of certain phlegm-dissolving Chinese medicines in improving brain clearance function and extracellular microenvironmental homeostasis warrant further investigation. We therefore propose that， the "invisible phlegm" of TCM in brain tissue may manifest as a pathological retention state characterized by restricted fluid exchange， impaired clearance function， and extracellular microenvironmental imbalance. This perspective may provide a new avenue for investigating TCM treatment of neurological and psychiatric disorders from the perspective of phlegm.

Based on the traditional Chinese medicine （TCM） theories of body fluid metabolism and turbid phlegm obstructing the orifices， and drawing on recent advances in cerebrospinal fluid-interstitial fluid （CSF-ISF） exchange， glymphatic clearance， and extracellular matrix （ECM） regulation， this article discusses the possible scientific connotation of "invisible phlegm" from the perspectives of pathogenesis， clinical manifestations， and therapeutic implications. Impaired brain fluid exchange may lead to reduced clearance， the retention of metabolic wastes and pathological proteins. Abnormal ECM remodeling may further disrupt molecular diffusion and local microenvironmental homeostasis， resulting in a pathological process characterized by slowed fluid movement， reduced clearance， and abnormal retention. This process bears a certain functional resemblance to the TCM pathogenesis of impaired distribution of body fluids， endogenous formation of turbid phlegm and obstruction of the brain orifices， and may also be associated with manifestations such as a clouded sensation in the head， cognitive abnormalities， and emotional disturbances. On this basis， the potential effects of certain phlegm-dissolving Chinese medicines in improving brain clearance function and extracellular microenvironmental homeostasis warrant further investigation. We therefore propose that， the "invisible phlegm" of TCM in brain tissue may manifest as a pathological retention state characterized by restricted fluid exchange， impaired clearance function， and extracellular microenvironmental imbalance. This perspective may provide a new avenue for investigating TCM treatment of neurological and psychiatric disorders from the perspective of phlegm.

To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up.

To analyze the occurrence of early complications after total hip arthroplasty (THA) in patients with systemic lupus erythematosus (SLE).

Traditional Chinese medicine (TCM) represents a paradigmatic approach to personalized medicine, developed through the systematic accumulation and refinement of clinical empirical data over more than 2000 years, and now encompasses large-scale electronic medical records (EMR) and experimental molecular data. Artificial intelligence (AI) has demonstrated its utility in medicine through the development of various expert systems (e.g., MYCIN) since the 1970s. With the emergence of deep learning and large language models (LLMs), AI's potential in medicine shows considerable promise. Consequently, the integration of AI and TCM from both clinical and scientific perspectives presents a fundamental and promising research direction. This survey provides an insightful overview of TCM AI research, summarizing related research tasks from three perspectives: systems-level biological mechanism elucidation, real-world clinical evidence inference, and personalized clinical decision support. The review highlights representative AI methodologies alongside their applications in both TCM scientific inquiry and clinical practice. To critically assess the current state of the field, this work identifies major challenges and opportunities that constrain the development of robust research capabilities-particularly in the mechanistic understanding of TCM syndromes and herbal formulations, novel drug discovery, and the delivery of high-quality, patient-centered clinical care. The findings underscore that future advancements in AI-driven TCM research will rely on the development of high-quality, large-scale data repositories; the construction of comprehensive and domain-specific knowledge graphs (KGs); deeper insights into the biological mechanisms underpinning clinical efficacy; rigorous causal inference frameworks; and intelligent, personalized decision support systems.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Humans ; Precision Medicine ; Decision Support Systems, Clinical

Objective To explore the application value of a holistic nursing model based on the Delphi method in patients with acute myocardial infarction(AMI).Methods A total of 110 AMI patients treated at Diqing Shangri-La People's Hospital in Yunnan Province from January 2019 to January 2020 were enrolled and divided into a control group and an observation group,with 55 patients in each,based on their admission order.The control group received routine nursing care,while the observation group received holistic nursing model intervention based on Delphi in addition to the routine nursing care.After 6 months of nursing,the left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),general self-efficacy scale(GSES)score,complications,and changes in nursing satisfaction were compared and analyzed between the two groups.Results(1)After nursing,the LVEF significantly increased and the LVEDV and LVESV significantly decreased in both groups;the increase in LVEF was more significant,and the decrease in LVEDV and LVESV was more pronounced in the observation group(P<0.05);(2)The GSES scores of patients in both groups improved compared to before nursing,with a more significant improvement in the observation group(P<0.05);(3)The incidence of adverse events during hospitalization was lower in the observation group than in the control group(P<0.05);(4)The satisfaction rate was higher in the observation group than in the control group after nursing(P<0.05).Conclusion The application of a holistic nursing model based on Delphi in AMI patients can effectively improve cardiac function and self-management efficacy,reduce the incidence of complications,and enhance nursing satisfaction,demonstrating high feasibility.

Objective:To prepare 89Zr-labeled anti-human podoplanin (PDPN) monoclonal antibody SZ168 and evaluate its feasibility for melanoma immunoPET imaging. Methods:89Zr-desferrioxamine (DFO)-SZ168 was prepared by conjugating p-isothiocyanatobenzyl (SCN-Bn)-DFO with SZ168 and chelating with 89Zr. Quality control analyses were conducted, including labeling rate, radiochemical purity, and in vitro stability. Melanoma mouse models were created, with experimental group ( n=3) and control group ( n=3) receiving tail vein injections of 89Zr-DFO-SZ168 and 89Zr-DFO-immunoglobulin (Ig)G solutions (3.7MBq) respectively. The experimental group underwent microPET/CT imaging at 12, 24, 48 and 72h post-injection, while the control group underwent imaging at 48h post-injection. Tumor and organ radioactivity uptake was analyzed using the ROI method. Mice were sacrificed at 7d post-injection to assess the ex vivo biodistribution of 89Zr-DFO-SZ168 and 89Zr-DFO-IgG. Independent-sample t test was used to analyze the data. Results:The pH value of the 89Zr-DFO-SZ168 solution was approximately 7.0, with a labeling rate >60%, radiochemical purity >95% after PD10 column purification, and good stability after 72h in vitro. Series microPET/CT imagings showed significant tumor visualization in tumor-bearing mice. Radioactivity uptake in tumors peaked at 48h post-injection, while the tumor was not clearly detected by 89Zr-DFO-IgG microPET/CT imaging. Ex vivo biodistribution indicated that 89Zr-DFO-SZ168 mainly accumulated in tumors, liver, and bones, with tumor uptake significantly higher than that of 89Zr-DFO-IgG ((29.36±7.29) percentage activity of injection dose per gram of tissue (%ID/g) vs (8.78±1.63) %ID/g; t=4.77, P=0.009). Immunohistochemistry of tumor specimens showed high expression of PDPN in tumor tissues. Conclusions:The probe 89Zr-DFO-SZ168 is successfully prepared, showing potential for specific molecular imaging diagnosis of melanoma. This lays a basis for developing PDPN molecular target-based immuno-PET diagnosis and integrated diagnosis and treatment for melanoma.

Objective:To explore the genetic basis for a girl with primary microcephaly and growth retardation.Methods:A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278).Results:DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c. 2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. Conclusion:Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.

BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic