Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

BackgroundArrhythmia and obsessive-compulsive disorder （OCD） frequently co-occur in clinical and epidemiological settings， yet their shared genetic basis and potential heart-brain axis mechanisms remain unclear. ObjectiveTo systematically evaluate the genetic correlation between arrhythmia and OCD， and to elucidate their underlying molecular genetic mechanisms， so as to provide molecular evidence for the "heart-brain axis" to support risk assessment and integrated clinical strategies for these comorbidities. MethodsThe aggregated data from the genome-wide association study （GWAS） of arrhythmia in the UK Biobank （7 207 cases and 477 391 controls） and the GWAS data of OCD released by the Psychiatric Genomics Consortium （2 688 cases and 7 037 controls） were integrated， all of which were limited to individuals of European ancestry. The genome-wide genetic correlations were estimated using the linkage disequilibrium score regression （LDSC） and the high-definition likelihood （HDL）. Local genetic correlation analysis was conducted using the local analysis of variance annotation （LAVA）. Multi-trait analysis of GWAS （MTAG） was employed to identify pleiotropic loci. Shared risk genes were identified by combining summary-data based Mendelian randomization （SMR） and transcriptome-wide association study （TWAS）. Functional enrichment analysis was performed based on the functional mapping and annotation （FUMA） platform. ResultsBoth LDSC （r_g=0.248， 95% CI： 0.159–0.336， P=4.82×10^-3） and HDL （r_g=0.294， 95% CI： 0.237–0.351， P=5.87×10^-4） revealed significant positive genetic correlation between arrhythmia and OCD. LAVA identified 23 significantly local correlated regions in the genome （P<2.0×10^-5）. MTAG discovered 11 genome-wide significant pleiotropic SNPs， among which rs12754189 （intron of KCNN3） had potential functional harmfulness （CADD>12.37）. SMR and TWAS jointly identified 20 shared genes， enriched in neural-cardiovascular tissues such as the cerebral cortex， amygdala， and left ventricle， and involved in DNA damage response， RNA metabolism， transcriptional regulation， and FAS signaling pathway （FDR<0.05）. ConclusionArrhythmia and OCD share a common genetic basis. The co-morbidity mechanism may involve the common vulnerability of neurons and cardiac muscle cells in terms of gene expression regulation and stress response， supporting the role of the brain-heart axis in the pathophysiology of both conditions.

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.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

Objective:To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL).Methods:A child who was admitted to Ningbo Women and Children′s Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063).Results:Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, pathogenic copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia. Conclusion:For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.

Objective:To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ).Method:A child with OFDSⅠ who received treatment at the Women and Children′s Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children′s Hospital (Ethic No.: EC 2024-063).Results:The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c. 710dup(p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child′s parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+ PS4_Moderate+ PM2-Supporting+ PM6_Supporting+ PP4). Conclusion:Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c. 710dup(p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.

Objective:To investigate the clinical characteristics and prognostic significance of germline mutations in patients with myelodysplastic neoplasms (MDS) .Methods:Clinical data from 407 patients with MDS [male, 252; female, 155; median age, 64 (range, 19-85) years] diagnosed at the First Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The clinical features and prognostic effects of germline mutations were evaluated.Results:The prevalence of germline mutations in patients with MDS was 5.9% (24/407), peaking at 20.0% in the group aged 21-30 years. The spectrum of germline mutations comprised DDX41 (9 cases, 2.2%), TP53 (3 cases, 0.7%), and single cases of RUNX1, TET2, MPL, CBL, ATRX, CEBPA, ETV6, IDH1, KDM5C, SBDS, GNAS, and CTC1. Patients with germline mutations exhibited significantly lower peripheral WBC counts than those without (1.87×10 9/L vs 2.50×10 9/L, P=0.018), but showed comparable median overall survival (21.3 months vs 21.1 months, P=0.97). Patients with DDX41 germline mutations, compared with those with other germline mutations, had a significantly older median age (65 vs 54 years, P=0.010), lower WBC counts (1.51×10 9/L vs 2.31×10 9/L, P=0.040), increased mean corpuscular volume (111.80 fl vs 97.25 fl, P=0.003), and a higher prevalence of normal karyotypes (100.0% vs 53.3%, P=0.022). The most frequently co-occurring somatic mutations in DDX41 germline mutation carriers were ASXL1, TET2, and RUNX1. Conclusion:In this study, the detection rate of germline mutations in MDS patients was 5.9% (24/407), peaking at 20% in the group aged 21-30 years. DDX41 and TP53 were the most prevalent germline mutations. DDX41 mutation carriers displayed distinct clinical characteristics; however, germline mutations overall showed no significant prognostic effect.