Hepatolenticular degeneration， also known as Wilson disease （WD）， is a hereditary disease caused by mutations in the ATP7B gene， leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein， and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs， ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin， this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease， and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis， this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.

ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with neuromuscular electrical stimulation （NMES） in the treatment of dysphagia in Wilson disease （WD） with combined phlegm and stasis. MethodsA total of 80 WD patients with dysphagia due to combined phlegm and stasis treated in the Department of Encephalopathy， the First Affiliated Hospital of Anhui University of Chinese Medicine were randomized into a control group and an observation group， with 40 patients in each group. In addition， 40 healthy volunteers were recruited as the normal group. The control group was treated with basic copper drainage combined with NMES. The observation group was treated with Gandouling Decoction on the basis of the therapy in the control group. Each course of treatment lasted for 8 days， and the patients were treated for a total of 4 courses. All subjects underwent video fluoroscopic swallowing study （VFSS） before and after treatment. During the examination， contrast agents with 4 different characters were used for the swallowing action， and the passing time was recorded. The TCM syndrome score， water swallow test score， standard swallowing assessment （SSA） score， and 24-h urinary copper level before and after treatment were analyzed. ResultsWhen performing VFSS， the passing time of contrast agents of different characters in the oral stage was longer in the WD group than in the normal group （P<0.01）， while it had no significant difference in the pharyngeal stage. After treatment， the passing time in the oral stage shortened in the control and observation groups （P<0.01）， and the observation group outperformed the control group （P<0.01）. After treatment， both the control and observation groups showed declines in TCM syndrome score and SSA score （P<0.01） and an increase in water swallow test score （P<0.01）， and the changes were more obvious in the observation group than in the control group （P<0.01）. In addition， the treatment in the control and observation groups elevated the 24-h urinary copper level （P<0.01）， and the elevation in the observation group was more obvious than that in the control group （P<0.01）. Neither group showed obvious adverse reaction. ConclusionGandouling decoction combined with NMES can significantly ameliorate dysphagia in WD patients with the syndrome of combined phlegm and stasis regarding the TCM syndrome score， water swallow test score， and SSA score， demonstrating definite clinical efficacy and high safety.

Introduction: Early identification of patients at risk for severe multisystem inflammatory syndrome in children (MIS-C) is essential for favourable clinical outcomes. This study aims to identify the clinical characteristics, factors and outcomes associated with severe MIS-C. Materials and methods: In this retrospective cohort study involving 14 major hospitals in Malaysia, children <15 years who met the United States Centres for Disease Control and Prevention case definition for MIS-C were included. Severe MIS-C was defined as children who required inotropic support, ventilatory support (invasive or non-invasive ventilation), or left ventricular ejection fraction of <55%. The factors investigated for severe MIS-C were demographic characteristics, the presence of comorbidities, clinical characteristics, and laboratory measures. Multivariable logistic regression was used to compute the adjusted odds ratio (aORs) of factors associated with severe MIS-C. Results: Among the 155 patients, 91 (58.7%) presented with severe MIS-C. Severe MIS-C was more likely in patients aged ≥5 years old (aOR 2.13, 95% confidence interval [CI] 1.08-4.21), with dehydration (aOR 3.80, 95% CI 1.53-9.45), lethargy (aOR 2.02, 95% CI 0.97-4.18), tachycardia (aOR 8.33, 95% CI 3.27-21.22), albumin <30g/L (aOR 3.36, 95% CI 1.58-7.13), creatine kinase >200U/L (aOR 3.68, 95% CI 1.57-8.64), D-dimer >3.0µg/mL (aOR 2.11, 95% CI 1.08-4.13), ferritin >500ng/mL (aOR 3.77, 95% CI 1.88-7.55), prothrombin time >12.7 seconds (aOR 3.22, 95% CI 1.61-6.43), and urea >6mmol/L (aOR 5.09, 95% CI 2.04-12.71). Conclusion: Identification of these associated factors of severity in MIS-C could aid in early recognition and prompt escalation of care, leading to better outcomes.

Wilson disease is a copper metabolism disorder caused by mutations in the ATP7B gene， which encodes a copper-transporting ATPase β， and can result in multisystem damage. The kidneys are the third most commonly affected organs after the liver and brain. In recent years， numerous diagnostic and treatment guidelines for Wilson disease have emerged. However， most of these focus primarily on hepatic and neurological manifestations and their management， with limited coverage of renal involvement. The high incidence， low awareness， and lack of clinical specificity of Wilson disease-related renal damage （WDRD） have made early detection and intervention particularly challenging in clinical practice. To further optimize the treatment of patients with WDRD， improve clinical diagnosis and management， and enhance patients' quality of life， the Neurology Committee of the Chinese Association of Integrative Medicine， in April 2024， initiated a revision of the first expert consensus on the integrated diagnosis， treatment， and management of WDRD. This effort brought together experts in hepatology， encephalopathy （neurology）， and nephrology from many tertiary-level grade A hospitals and research institutions across China. Through comprehensive literature review and integration of frontline clinical experience， the expert group jointly developed Chinese Expert Consensus on Integrated Chinese and Western Medicine Management of Wilson Disease-related Renal Damage （hereinafter referred to as the "Consensus"）. This article provides a detailed interpretation of the Consensus in terms of diagnostic criteria， traditional Chinese medicine （TCM） syndrome differentiation and treatment classification， and comprehensive disease management， aiming to better guide clinical application. Regarding diagnostic criteria， the Consensus integrates the latest standards in China and abroad， highlights the importance of biochemical diagnosis， and compensates for the limitations of genetic testing. In the area of TCM syndrome differentiation and treatment， the Consensus refines four major syndrome types， introduces a newly defined syndrome， i.e.， phlegm， blood stasis， and heat accumulation， and elaborates on treatment principles， prescriptions， and clinical modification rules for each syndrome. For comprehensive disease management， the Consensus emphasizes multi-dimensional intervention strategies， including diet， exercise， emotional regulation， medication， and medical care， with the goal of maximally controlling the progression of renal dysfunction and helping patients achieve a better quality of life.

Based on the literature review and the analysis of specific cases of postpartum frequent micturition,pediatric enuresis,elderly uremia complicated with bradyarrhythmia in clinic,the clinical application of the action of Ephedrae Herba in stimulating yang qi is discussed.Ephedrae Herba has the meridian tropism of the lung and bladder meridians,and is pungent,warm and dispersing,which is the most important medicine for the treatment of external contraction.Ephedrae Herba has the actions of inducing diaphoresis,calming asthma and inducing diuresis,and is widely used for the treatment of external contraction,coughing and asthma,and edema.For the patients with deficiency of both kidney yin and kidney yang without obvious bias of yin-yang consumption which result from the postpartum impairment of qi and blood,deficient innate endowment,and gradually exhaustion of essence in the kidney in the elderly or during chronic illness,a small dosage of Ephedrae Herba can stimulate yang qi during the treatment of warming kidney yang,which is helpful for promoting the drug arriving at the back shu-points of the internal organs distributed along the bladder meridian and enhancing the recovery of zang-fu organ function.Ephedrae Herba is strong in inducing diaphoresis with an intense action.When Ephedrae Herba is used to stimulate yang,the dosage of 3～9 g is appropriate,and medicines for warming yang are needs to be used together.The course of treatment with Ephedrae Herba should be avoided to be too long,in order to prevent the vital energy from the damage by its large cumulative dose.

Objective To observe the therapeutic effect of Shenshuai Formula(composed of Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine,Citri Reticulatae Pericarpium,Poria,Atractylodis Macrocephalae Rhizoma,Bambusae Caulis in Taenia,Morindae Officinalis Radix,Centellae Herba,Rhei Radix et Rhizoma,etc.)on patients with chronic kidney disease(CKD)at stage 3-4 of spleen-kidney qi deficiency with internal accumulation of turbid-phlegm and stasis type.Methods Seventy patients with CKD at stage 3-4 of spleen-kidney qi deficiency with internal accumulation of turbid-phlegm and stasis type were randomly divided into a treatment group and a control group,with 35 patients in each group.The control group was given the conventional western medicine integrated treatment for CKD,and the treatment group was given the Chinese herbal decoction of Shenshuai Formula on the basis of treatment for the control group.The course of treatment for the two groups covered 8 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function indicators of serum creatinine(Scr),blood urea nitrogen(BUN),serum cystatin C(CysC),blood uric acid(UA)and estimated glomerular filtration rate(eGFR),and the level of hypersensitive C-reactive protein(hs-CRP)in the two groups before and after the treatment were observed.Moreover,the TCM syndrome efficacy and clinical safety in the two groups were evaluated.Results(1)During the trial,5 cases in the treatment group and 3 cases in the control group fell off,and eventually a total of 62 patients were included in the trial,including 30 cases in the treatment group and 32 cases in the control group.(2)After 8 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 86.67%(26/30),and that of the control group was 59.38%(19/32).The intergroup comparison showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the scores of TCM syndromes in the two groups were significantly decreased when compared with those before treatment(P＜0.01),and the decrease in the treatment group was more obvious than that in the control group(P＜0.01).(4)After treatment,the renal function indicator levels of Scr,BUN,CysC and UA in the two groups were decreased when compared with those before treatment(P＜0.05),and the level of eGFR was increased when compared with that before treatment(P＜0.05).The intergroup comparison showed that the decrease in the levels of Scr,BUN,CysC and UA and the increase in the level of eGFR in the treatment group were superior to those in the control group(P＜0.05).(5)After treatment,the inflammatory factor level of serum hs-CRP in the two groups was improved when compared with that before treatment(P＜0.05),and the improvement in the treatment group was superior to that in the control group(P＜0.05).(6)During the treatment period,no significant changes in the safety indicators such as blood routine test,stool routine test and occult blood test,liver function,electrolyte,and electrocardiogram were presented in the two groups.Conclusion Shenshuai Formula exerts certain effect in the treatment of patients with CKD at stage 3-4 of spleen-kidney qi deficiency with internal accumulation of turbid-phlegm and stasis type.It can relieve the clinical symptoms of the patients to certain extent,effectively decrease the levels of Scr,BUN,CysC and UA,increase the eGFR,improve renal function,lower the level of serum hs-CRP,reduce the micro-inflammatory state of patients,and delay the progress of the disease.

Objective:To evaluate the relationship of early tumor shrinkage and depth of tumor response with the clinical efficacy and pro-gnosis of programmed death-1(PD-1)inhibitor combined with trastuzumab and first-line chemotherapy in the treatment of HER-2-positive advanced gastric cancer.Methods:We retrospectively analyzed data from 40 patients treated with this combination at Nanjing Drum Tower Hospital,The Affliated Hospital of Nanjing University Medical School from June 2018 to March 2023.Key metrics included early tumor shrinkage(ETS),depth of response(DpR),objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and adverse reactions.Survival analysis using Log-rank test and Kaplan-Meier method,and plot PFS and OS survival curves.COX regression analysis for correlation testing.Results:The patient's ORR was 77.5%,DCR was 100%,complete response rate was 15.0%,medi-an PFS(mPFS)was 11.10 months,and median OS(mOS)was 30.77 months.COX univariate analysis showed that tumor differentiation,liver metastasis,distant lymph node metastasis,DpR were related to PFS and OS(all P<0.05),ETS was only related to PFS(P=0.010),and PD-L1 ex-pression was not related to PFS and OS.There was a significant difference in mPFS between patients with ETS≥35%and ETS<35%(P=0.008),while there was no significant difference in mOS(P=0.076);There were significant differences in mPFS and mOS between patients with DpR≥40%and DpR<40%(P=0.001).COX multivariate analysis showed that DpR is an independent factor affecting PFS and OS,and distant lymph node metastasis is an independent factor affecting OS.The overall tolerance to treatment of the patients was good,with no grade 4 or above treatment-related adverse reactions or death.Conclusions:ETS and DpR may be predictive indicators of the efficacy and prognosis of PD-1 inhibitors combined with trastuzumab and first-line chemotherapy for HER-2 positive advanced gastric cancer.

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
Humans ; U937 Cells ; RUNX1 Translocation Partner 1 Protein ; Leukemia/genetics* ; Core Binding Factor Alpha 2 Subunit/genetics* ; Oncogene Proteins, Fusion/genetics* ; Leukemia, Myeloid, Acute/genetics*

OBJECTIVE: To explore the extrinsic regulation mechanism of bone marrow microenvironment in leukemia cells, and investigate the promoting effect of osteoblast niche on the proliferation and self-renewal of leukemia stem cell by up-regulating the expression of interleukin-1 (IL-1) in leukemia cell. METHODS: The gene expression profiles on leukemia cells derived from AE9a mouse bone marrow endosteum and central bone marrow were determined by RNA sequencing and gene set enrichment analysis (GSEA). Quantitative real-time PCR (qRT-PCR) was used to detect the expression of IL-1 in AE9a mouse leukemia cells co-cultured with or without osteoblasts in vitro. In addition, qRT-PCR was also used to determine the expression of IL-1 in bone marrow mononuclear cell (BMMNC) from 43 patients with acute myeloid leukemia (AML). For leukemia cells co-cultured with osteoblasts or treated with IL-1β, colony forming ability of AE9a leukemia cells was determined by colony formation assay. RESULTS: In AE9a leukemia mouse, RNA-seq data and GSEA showed that the enrichment of the upregulated genes in leukemia cells located in endosteum fell into inflammatory response gene set, among them, IL-1α and IL-1β were significantly higher expressed in AE9a leukemia cells that located osteoblast niche (IL-1α: P<0.001, IL-1β:P<0.001). After AE9a leukemia cells were co-cultured with osteoblasts in vitro, the expression of IL-1α and IL-1β in leukemia cells were increased by 2.5 and 3.5 times respectively. In colony formation assay, the number of colonies was increased significantly after leukemia cells were co-cultured with osteoblasts (P<0.001). In addition, when AE9a leukemia cells were treated with IL-1β, the number of colonies was also increased significantly (P<0.01). In AML patients, BMMNC with high percentage of CD34 positive cells exhibited higher level of IL-1 expression. CONCLUSION Osteoblast niche can promote leukemia cell proliferation and self-renewal through up-regulating the expression of IL-1 in leukemia cells. In AML patients, the expression level of IL-1 was correlated to the percentage of CD34 positive cells in BMMNC.
Animals ; Antigens, CD34/metabolism* ; Bone Marrow/metabolism* ; Cell Proliferation ; Leukemia, Myeloid, Acute/metabolism* ; Mice ; Osteoblasts/metabolism* ; Stem Cells ; Tumor Microenvironment

Lung cancer is one of the leading causes of cancer deaths worldwide. Many options including surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy have been applied in the treatment for lung cancer patients. However, how to develop individualized treatment plans for patients and accurately determine the prognosis of patients is still a very difficult clinical problem. In recent years, radiomics, as an emerging method for medical image analysis, has gradually received the attention from researchers. It is based on the assumption that medical images contain a vast amount of biological information about patients that is difficult to identify with naked eyes but can be accessed by computer. One of the most common uses of radiomics is the diagnosis and treatment of non-small cell lung cancer (NSCLC). In this review, we reviewed the current researches on chest CT-based radiomics in the diagnosis and treatment of NSCLC and provided a brief summary of the current state of research in this field, covering various aspects of qualitative diagnosis, efficacy prediction, and prognostic analysis of lung cancer. We also briefly described the main current technical limitations of this technology with the aim of gaining a broader understanding of its potential role in the diagnosis and treatment of NSCLC and advancing its development as a tool for individualized management of NSCLC patients.