The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

Diabetic nephropathy（DN） is a common and severe microvascular complication of diabetes. In recent years， the classical herbal formula Shenqi dihuang decoction has demonstrated unique advantages in the clinical treatment of DN. This article conducts a systematic review of the mechanisms of action and clinical applications of Shenqi dihuang decoction in the treatment of DN. It reveals that the mechanism by which this formula improves DN involves multi-target synergistic regulation. For instance, Shenqi dihuang decoction exerts multiple pharmacological effects by regulating signaling pathways including phosphatidy linostiol 3-kinase/protein kinase B， AMP-activated protein kinase/silent information regulator 1/forkhead box O1， and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathways.These effects include regulating glucose and lipid metabolism， inhibiting oxidative stress， reducing inflammation， improving insulin resistance， modulating cell death （apoptosis/autophagy/ferroptosis/pyroptosis）， and preventing renal fibrosis. Existing clinical studies indicate that Shenqi dihuang decoction and its modified formulas， alone or in combination with other therapeutic methods， can significantly improve glucose and lipid metabolism， reduce proteinuria， and delay renal function decline in patients with DN. These effects are superior to those of Western medicines such as irbesartan， valsartan， and empagliflozin， and the treatment demonstrates good safety. Future research should leverage systems biology and artificial intelligence technologies to further elucidate the integrated mechanisms in the treatment of DN by Shenqi dihuang decoction， thereby advancing the precision and standardization of its clinical application.

ObjectiveTo evaluate the efficacy and possible mechanism of Wei's Huoxue Tongluo Formula （韦氏活血通络方，WHTF） in treating atrophic-stage non-arteritic anterior ischemic optic neuropathy （NAION） with qi deficiency and blood stasis. MethodsA total of 82 atrophic-stage NAION patients with qi deficiency and blood stasis were randomly divided into a treatment group and a control group， with 41 cases in each group. The treatment group was given oral administration of WHTF twice a day plus acupoint injection of distilled water 2 ml at Taiyang （EX-HN5） once daily， while the control group received injection of compound anisodine injection 2 ml at Taiyang （EX-HN5） once daily and oral administration of WHTF placebo twice a day. Both groups received treatment for a course of 14 days. The best-corrected visual acuity （BCVA）， optic disc perfusion density （PD）， flux index （FI）， macular superficial PD， vascular density （VD）， and traditional Chinese medicine （TCM） syndrome scores were compared between groups before treatment and on day 7 and day 14 of treatment. Additionally， mean defect （MD） and mean sensitivity （MS） of visual fields were measured before treatment and on day 14， along with safety evaluation. ResultsAfter treatment， both groups showed significant improvement in BCVA， visual field MD and MS， and TCM syndrome scores （P＜0.05 or P＜0.01）. On day 14 of treatment， the TCM syndrome score in the treatment group was significantly lower than that in the control group （P＜0.05）. There was no significant improvement in optic disc PD and FI， and macular superficial PD and VD after treatment in either group （P＞0.05） except that on day 7 the macular superficial foveal PD in the control group was significantly better than that in the treatment group （P＜0.05）. During the treatment period， no serious adverse events occurred in either group. ConclusionWHTF can improve the visual function indicators including visual acuity and visual field， as well as TCM syndrome scores in atrophic-stage NAION patients with qi deficiency and blood stasis. It shows clinical safety， although it does not appear to have a significant effect on optic disc or macular blood flow.

Objective:To construct a multimodal induction educational system suitable for standardized pediatric residency training bases, and to evaluate its effectiveness, thereby obtaining suggestions for further improvement.Methods:Twelve residents newly enrolled in the 2023 standardized residency training program who commenced their first-year training were included as study subjects. The induction educational system comprised multiple modules: department introduction, training plan and assessment requirements, departmental workflow, routine diagnosis and treatment of major diseases, specialized skills/procedures, and lifestyle guidance. Training materials and methods were tailored to the characteristics of each training module. Checklists were used for supervision and review, and a competency checklist was designed to evaluate residents' mastery of the training at two weeks of induction, which would guarantee the effectiveness of the training. A questionnaire survey, powered by wjx.cn, was used to obtain the experience and suggestions from the residents and ward instructors on induction education, and content ranking analysis was performed on the survey results.Results:The survey revealed that, before starting a new rotation, residents' top three educational needs were departmental workflow, routine diagnosis and treatment of common diseases, and specialized skills/procedures. Residents preferred face-to-face lectures and demonstrations by attending physicians or senior residents; instructors suggested improving relevant materials (such as resident physician manuals and video materials) and face-to-face lectures. The residents considered the current induction educational system to be greatly beneficial in basic theories, treatment principles, basic skills, and auxiliary examination processes.Conclusions:Through the above research, a multimodal induction educational system suitable for the standardized pediatric residency training base in the Peking University First Hospital has been preliminarily established, and suggestions for further improvement have been obtained, which is conducive to further improving the system and residents' post competency.

Objective:To explore the clinical application effect of double eyelid plasty using the levator palpebrae superioris aponeurosis fiber flap.Methods:In March 2021, 3-mm-wide tissue strips were vertically harvested from the mid-upper eyelids from 5 adult Han cadavers with single eyelids, provided by the Anatomy Lab of Nanchang Vocational Health College, and then Masson staining was performed to track the levator aponeurosis fiber. A descriptive case series study was performed. From February 2021 to February 2022, eligible patients who were prospectively collected from the Outpatient Department of the First Affiliated Hospital of Nanchang University underwent double eyelid plasty. The levator palpebrae superioris aponeurosis fiber flap was dissected and repositioned between the orbicularis oculi muscles at the upper and lower edge of incision. The surgical site was closed by a three-layer multi-faceted suture fixation: the muscle of orbicularis oculi at lower edge of incision was sutured to the flap root and tarsal upper edge; the upper and the muscle of orbicularis oculi at the upper and lower edge were sutured to the flap end; the skin was sutured to the muscle of orbicularis oculi and flap end. Postoperatively, incision healing and complications were monitored. Twelve months after surgery, two independent attending plastic surgeons evaluated double eyelid height, curvature, symmetry, and incision scar. The patients were asked to evaluate the effect as satisfied, relatively satisfied, or dissatisfied.Results:Masson staining of 5 lateral upper eyelid specimens revealed that in single-eyelid cases, the levator palpebrae superioris aponeurosis diverged into fibers at the white line, penetrated the orbicularis oculi loosely, and extended to the eyelid margin. Fourty female patients with single or hidden double eyelids were included, aged 18-38 years. After 12 months’ follow-up, all patients had good incision healing without major complications. Twelve months after the operation, the result of doctor evaluation was as followed: 40 cases had proper line height and natural curvature; 38 cases had good line retention, 2 cases had shallower lines; 39 cases had good symmetry, 1 case had asymmetry; 40 cases had no sunken scar. The result of patient satisfaction was as satisfied (35 cases), relatively satisfied (2 cases), dissatisfied (3 cases), with a 92.5% (37/40) satisfaction rate.Conclusion:The levator palpebrae superioris aponeurosis fiber flap method can reconstruct upper eyelid tissue, with natural dynamic double eyelids with few complications and high patient satisfaction.

Objective:To explore the clinical utility of peripheral immune-inflammatory markers in predicting late-life depression with cognitive impairment(LLD+ CI + ). Methods:A cross-sectional study was conducted between January 2020 and December 2021, collecting demographic data, peripheral blood inflammatory markers, and cognitive function scores from 40 patients with LLD+ CI + , 38 patients with late-life depression without cognitive impairment(LLD+ CI -), and 26 healthy controls(HCs). Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were employed to assess the value of peripheral blood inflammatory markers in differentiating LLD+ CI + . Results:Patients with LLD+ CI + exhibited significantly different levels of lymphocytes, C-reactive protein(CRP), systemic immune-inflammation index(SII), systemic inflammation response index(SIRI), neutrophil-to-high-density lipoprotein cholesterol ratio(NHR), and neutrophil-to-lymphocyte ratio (NLR)compared with the LLD+ CI - group and the HGs group( F=4.000, 11.642, 13.541, 10.441, 6.623, 4.193; P=0.022, 0.003, 0.001, 0.005, 0.036, 0.018). The multivariate logistic regression analysis of factors influencing LLD+ CI + revealed that elevated levels of CRP( OR=4.933, 95% CI: 1.385-17.563, P=0.014), SII( OR=5.534, 95% CI: 1.336-22.927, P=0.018), and NLR( OR=3.386, 95% CI: 1.470-7.797, P=0.004)constitute risk factors for geriatric depression with cognitive impairment, while an increased lymphocyte count( OR=0.206, 95% CI: 0.058-0.725, P=0.014)serves as a protective factor.Further analysis identified CRP, lymphocytes, SII, and NLR as significant predictors for LLD+ CI + , with areas under the curve (AUC) values of 0.849(95% CI: 0.760-0.934), 0.847(95% CI: 0.761-0.933), 0.860(95% CI: 0.777-0.943), and 0.857(95% CI: 0.777-0.938), respectively, in distinguishing LLD with or without cognitive impairment. Conclusions:Peripheral immune-inflammatory markers represent an economical and effective approach for investigating the pathophysiological changes and predictive factors associated with LLD+ CI + .These findings provide valuable insights into the underlying mechanisms and potential therapeutic avenues.

Objective To explore the diagnostic value of serum C-reactive protein(CRP),serum amyloid A(SAA)and procalcitonin(PCT)combined with lactate dehydrogenase(LDH)and adenosine deaminase(ADA)in cerebrospinal fluid for elderly patients with central nervous system infection and their differential significance for different infection types.Methods A total of 97 elderly patients with central nervous system infection were enrolled as the infection group,including 31 cases with tuberculous meningitis(tuberculous meningitis group),36 cases with suppurative meningitis(suppurative meningitis group)and 30 cases with viral meningitis(viral meningitis group).A total of 97 patients with normal laboratory examination indexes who were treated due to primary headache during the same period were enrolled as the control group.The samples of fasting elbow venous blood were collected in the early morning of the next day after admission,and the serum was isolated to detect CRP and SAA levels.When consultation,lumbar puncture was performed to collect cerebrospinal fluid for the detection of LDH and ADA levels.The differences in above indexes were compared between groups,and diagnostic efficiency of each index and combined detection for central nervous system infection in elderly was analyzed by receiver operating characteristic(ROC)curves.Results The serum levels of CRP,SAA and PCT,and LDH and ADA in cerebrospinal fluid were higher in the infection group than those in the control group(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)values of serum CRP,SAA and PCT,and cerebrospinal fluid LDH and ADA,and combined detection in the diagnosis of central nervous system infection were all>0.70(P＜0.05),showing good predictive efficiency and diagnostic efficiency,and the diagnostic efficacy of combined detection was the best.The cut-off values of serum CRP,SAA and PCT,cerebrospinal fluid LDH and ADA were 6.32 mg/L,33.86 mg/L,2.81 μg/L,33.53 U/L and 1.99 U/L,respectively.The serum levels of CRP,SAA and PCT were the highest in the suppurative meningitis group,while which were the lowest in the viral meningitis group.The cerebrospinal fluid levels of LDH and ADA were the highest in the tuberculous meningitis group,while which were the lowest in the viral meningitis group(P＜0.05).Conclusion The combined detection of serum CRP,SAA and cerebrospinal fluid PCT and LDH has certain diagnostic value for elderly central nervous system infection,which is beneficial to identify infection types.

Research indicates that microbe activity within the human body significantly influences health by being closely linked to various diseases.Accurately predicting microbe-disease interactions(MDIs)offers critical insights for disease intervention and pharmaceutical research.Current advanced AI-based technologies automatically generate robust representations of microbes and diseases,enabling effec-tive MDI predictions.However,these models continue to face significant challenges.A major issue is their reliance on complex feature extractors and classifiers,which substantially diminishes the models' generalizability.To address this,we introduce a novel graph autoencoder framework that utilizes decoupled representation learning and multi-scale information fusion strategies to efficiently infer po-tential MDIs.Initially,we randomly mask portions of the input microbe-disease graph based on Bernoulli distribution to boost self-supervised training and minimize noise-related performance degradation.Secondly,we employ decoupled representation learning technology,compelling the graph neural network(GNN)to independently learn the weights for each feature subspace,thus enhancing its expressive power.Finally,we implement multi-scale information fusion technology to amalgamate the multi-layer outputs of GNN,reducing information loss due to occlusion.Extensive experiments on public datasets demonstrate that our model significantly surpasses existing top MDI prediction models.This indicates that our model can accurately predict unknown MDIs and is likely to aid in disease discovery and precision pharmaceutical research.Code and data are accessible at:https://github.com/shmildsj/MDI-IFDRL.

Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. METHODS: Four patients diagnosed with PMS at Guangzhou Women and Children's Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Hospital (Ethics No. 2025-007). RESULTS: All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 Kb to 112.64 Kb, primarily involving the SHANK3 gene. CONCLUSION PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.
Child ; Humans ; Chromosome Deletion ; Chromosome Disorders/genetics* ; Chromosomes, Human, Pair 22/genetics* ; Exome Sequencing ; Nerve Tissue Proteins/genetics* ; Phenotype