Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver injury of unknown etiology. The onset of this disease involves the activation and recruitment of diverse immune and non-immune cells, which in turn trigger hepatic damage. Immune checkpoint molecules (ICM) are expressed on the surface of multiple cell types. By regulating cellular functional states, they help limit the intensity and duration of immune responses, thereby preventing excessive inflammation and tissue damage, and maintaining immune homeostasis. In AIH, however, this natural "braking" mechanism is impaired, leading to aberrant activation of both immune and non-immune cells and the breakdown of immune homeostasis. Consequently, ICM are likely to play a critical role in the pathogenesis of AIH. A deeper understanding of the function of ICM in AIH not onlyadvances our insight into the disease mechanism, but also suggests that targeting these molecules may represent a promising therapeutic strategy for the treatment of AIH.

Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and congenital chronic pseudo intestinal obstruction (CIIPX). METHODS: A pedigree presented at the First Hospital of Lanzhou University for CVDPX combined with CIIX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15). RESULTS: Both the proband and his affected younger brother were found to harbor a hemizygous c.443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded in the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+PS4+PP2+PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. CONCLUSION This study confirmed the diagnosis of CVDPX/CIIX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.
Adult ; Female ; Humans ; Male ; Exome Sequencing ; Filamins/genetics* ; Genetic Diseases, X-Linked/genetics* ; Heart Defects, Congenital/genetics* ; Heart Valve Diseases/genetics* ; Pedigree ; East Asian People/genetics*

Objective:To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and chronic idiopathic intestinal pseudo-obstruction (CIIPX).Methods:A pedigree presented at the First Hospital of Lanzhou University in June 2024 for CVDPX combined with CIIPX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15).Results:Both the proband and his affected younger brother were found to harbor a hemizygous c. 443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded by the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+ PS4+ PP2+ PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. Conclusion:This study confirmed the diagnosis of CVDPX/CIIPX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.

Objective:To explore the method of CT quantitative evaluation of silicosis fibrosis in artificial stone and analyze its correlation with the stage of chest X-ray and lung function impairment.Methods:The clinical data of 142 patients with artificial stone silicosis who were treated at Shanghai Pulmonary Hospital from January 2018 to December 2022 were collected. These patients were diagnosed based on GBZ 70-2015 Diagnosis of Occupational Pneumoconiosis and underwent chest X-rays, chest CT scans, and lung function tests within a two-month period. The chest CT scoring method is based on the CT characteristics of silicosis, including ground-glass shadows, small nodule shadows, point-line shadows/cord-line shadows, emphysema/pulmonary bullae and patch shadows/mass shadows, with a scoring range of 0 to 25 points. Lung function indicators included FVC, FEV 1 and DLco. For inter-group comparisons of normally distributed quantitative data, one-way ANOVA was employed with LSD post-hoc test for multiple comparisons. Chi-square test was used for multi-group ratio comparisons. Kruskal-Wallis H test was applied to non-normally distributed quantitative data, followed by LSD post-hoc test. Spearman's rank correlation was used to analyze the relationship between pulmonary function indicators and CT fibrosis scores, Trend test was conducted using the Pearson test. Results:As the silicosis stage progressed, both the CT fibrosis score ( R=0.87, Ptrend<0.001) and the degree of lung function impairment (FVC: R=-0.41, Ptrend<0.001; FEV 1: R=-0.52, Ptrend<0.001) ; DLco: R=-0.38, Ptrend<0.001) showed an increasing trend. The CT fibrosis Score demonstrated a strong positive correlation with silicosis stage ( rs=0.85, Ptrend<0.001) and a moderate negative correlation with FVC, FEV 1, and DLco ( rs=-0.48, -0.56, and -0.45, respectively, with all P<0.05) . Over an average follow-up period of 14 months, it was observed that changes in the CT score had a strong to moderate negative correlation with variations in FVC and FEV 1 ( rs=-0.63 and -0.52, P<0.05) . Additionally, there was a moderate negative correlation between ground glass opacity and DLco ( rs=-0.52, P<0.001) . Conclusion:The CT fibrosis score not only reflects pathological changes associated with artificial stone-related silicosis but also provides a more precise representation of lung function injury.

Objective:To predict mechanical complications (MC) following spinal deformity surgery for adult spine deformity (ASD) using machine learning models, identify key risk factors, and develop a visualizable tool for individualized risk assessment.Methods:Clinical and radiological data from 525 patients with ASD who underwent surgery in our hospital between January 2017 and December 2021 were collected. Patients were randomly assigned to a training set (70%) and a test set (30%) for model development. The cohort included 88 males and 437 females, with a mean age of 42.2±18.1 years. Variables included demographic data, comorbidities, local and systemic radiological parameters, paraspinal muscle fat infiltration (FI), and vertebral bone quality (VBQ) scores. Multiple machine learning algorithms: Random Forest (RF), Gaussian Naive Bayes (GNB), Light GBM, Support Vector Machine (SVM), XGBoost (XGB), and Logistic Regression (LR) were trained and evaluated. Model performance was compared using the receiver operating characteristic curve (ROC) and precision-recall curve (PRC). SHAP (Shapley Additive Explanations) was used to rank risk factors, while LIME (Local Interpretable Model-Agnostic Explanations) was applied to visualize MC risk in individual cases.Results:Of the 525 patients, 135 (25.7%) developed postoperative MC. Among these, 80 (59.3%) experienced proximal junction kyphosis or failure (PJK/PJF), 7 (5.2%) had distal junction kyphosis or failure (DJK/DJF), 28 (20.7%) sustained rod fractures, and 29 (21.5%) showed significant loss of correction. In the validation cohort, the RF model achieved the highest area under the curve (AUC=0.80), followed by GNB (0.77), XGB (0.76), LR (0.74), LightGBM (0.73), and SVM (0.66). The RF model also demonstrated the best PRC value (0.58), highest sensitivity (0.65), and lowest Brier score (0.20). GNB, Light GBM, and LR models achieved the highest accuracy (0.78 each), while LightGBM exhibited the highest specificity (0.93). SHAP analysis identified higher preoperative VBQ scores, larger T 1 pelvic angle (TPA), and higher paraspinal muscle FI as the main risk factors for MC. Based on the RF model, a LIME-based tool was successfully constructed for individualized MC risk estimation. Conclusion:The RF model demonstrated the best overall predictive performance for MC. A machine learning-based prediction model has the potential to provide valuable guidance for surgical decision-making in ASD patients.

OBJECTIVE: This review summarized the first 10-year progresses and controversies in the concept of anteromedial cortical support reduction, to provide references for further study and clinical applications. METHODS: Relevant domestic and foreign literature on cortical support reduction was extensively reviewed to summarize the definition of positive, neutral, and negative support, anteromedial cortices at the inferior corner, intraoperative technical tips for fracture reduction, radiographic assessment at different periods, comparison between positive versus neutral and medial versus anterior support, and the clinical efficacy of Chang reduction quality criteria (CRQC) and postoperative stability score. RESULTS: Anteromedial cortical support reduction was only focused on the cortex of anteromedial inferior corner, with no concern the status of lateral wall or lesser trochanter. Anteromedial cortex was seldom involved by fracture comminution, it was thicker, denser, and stronger, and was the key for mechanical buttress of the head-neck fragment to share compression load. Positive, neutral, and negative support were also called "extramedullary, anatomic, and intramedullary reduction", respectively. There was hardly seen parallel cortical apposition, but characterized by some kinds of head-neck rotation, for example 10°-15° flexed rotation for positive cortical contact and support. Due to intraoperative compression and postoperative impaction, the status of cortical support may be changed at different time of radiographic examination. The positive medial cortex support was more reliable with less reduction loss than its neutral counterpart, and the anterior cortex contact was more predictive than the medial cortex for final results. As incorporation the bearing of cortex apposition and using a 4-point score, CRQC demonstrated more efficacy and was gradually accepted and applied in the evaluation of trochanteric fracture reduction quality. Postoperative stability score (8 points) provided a assessment tool for early weight-bearing in safety to prevent mechanical failure. CONCLUSION Anteromedial cortical support reduction is a key point for stability reconstruction in the treatment of trochanteric femur fractures. Evidence has definitely shown that non-negative (positive and neutral) is superior to negative (loss of cortical support). There is a tendency that positive cortex support is superior to neutral, but high quality study with large sample size is needed for a clear conclusion.
Humans ; Femur/diagnostic imaging* ; Fracture Fixation, Internal/methods* ; Hip Fractures/diagnostic imaging* ; Treatment Outcome ; Fracture Fixation, Intramedullary/methods*

OBJECTIVE: To analyze the gene mutation characteristics and survival time of patients with newly diagnosed acute myeloid leukemia (AML) based on next-generation sequencing(NGS) gene detection. METHODS: A retrospective analysis was conducted on the clinical data of 92 patients with AML (non APL) admitted to our hospital from January 2018 to May 2022. AML related genes tested were using NGS, the mutation characteristics and survival time of AML patients were analyzed. RESULTS: Among the 92 patients, 41 were males and 51 were females. A total of 38 types of gene mutations were detected. Six-two patients carried at least one gere mutation, while no gene mutations were detected in 30 patients. In the group with favourable prognosis (n =14), the frequencies of higher gene mutations were NRAS, KIT (21.43%, n =3), KRAS (14.29%, n =2). In the group with intermediate prognosis (n =64), the gene mutation frequencies from high to low were DNMT3A (18.75%, n =12), NPM1 (17.19%, n =11), IDH2, FLT3-ITD, CEBPA (12.50%, n =8), TET2 (10.94%, n =7). In the poor prognosis group (n =14), ASXL1, TP53, EZH2, NRAS had higher gene mutation frequency than others(14.29 %, n =2 ). Statistical analysis revealed that KIT had a relative hotspot of mutations in the intermediate-risk group, and DNMT3A had a relative hotspot of mutations in the high-risk group (P < 0.05). The correlation analysis of genes with high mutation rates in different prognostic groups, such as NRAS, KIT, IDH2, DNMT3A, NPM1, and FLT3-ITD, with prognosis found that KIT was a factor affecting OS (P < 0.05), while no significant differences were observed for the others(P >0.05). CONCLUSION The frequency of gene mutations is high in AML patients, 67.4% of the patients carried at least one gene mutation. The mutation frequency varies among different genes in patients with different karyotypes, and there are obvious dominant mutations. KIT and DNMT3A can be used as factors for evaluating the prognosis of AML.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Mutation ; Prognosis ; Retrospective Studies ; Male ; Female ; High-Throughput Nucleotide Sequencing ; Middle Aged ; DNA Methyltransferase 3A ; Adult ; Aged ; Survival Analysis ; Proto-Oncogene Proteins c-kit/genetics*

OBJECTIVE: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. METHODS: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. RESULTS: Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. CONCLUSION TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.
Mitophagy/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Macrophages/virology* ; Inflammasomes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Influenza A virus/physiology* ; Interleukin-1beta/metabolism* ; Cell Line ; Injections