ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.Static exercise can effectively improve skeletal muscle insulin resistance,but the mechanism remains unclear. OBJECTIVE:To explore the mechanism of static exercise on insulin resistance in the skeletal muscle of type 2 diabetic mice based on the phosphatidyl inositol 3-kinase(PI3K)/protein kinase B(AKT)/glucose transporter(GLUT4)signaling pathway. METHODS:After 1 week of adaptive feeding,7 out of 40 C57BL/6 mice were randomly selected as blank group and fed common diet,while the other mice were fed high-fat diet and taken to prepare type 2 diabetes models through the low-dose streptozotocin intraperitoneal injection.Twenty-four mice were successfully modeled and they were randomly divided into model group(n=8),metformin group(n=8)and static exercise group(n=8),which continued to be fed high-fat diet.The metformin group was given 200 mg/kg metformin dissolved in normal saline(2 ml/kg)by gavage,once a day,for 6 weeks.The static exercise group was given normal saline daily by gavage and carried out static exercise,30 minutes a day,6 days per week.The model group was given the same dose of normal saline daily by gavage without exercise intervention.After the intervention,the fasting blood glucose of each group was detected,the intraperitoneal glucose tolerance test was performed,and the area under the glycemic curve was calculated.Glycosylated hemoglobin,serum insulin,insulin resistance index were detected by ELISA.Total cholesterol,triglyceride,high-density lipoprotein,low-density lipoprotein were detected using biochemical methods.The mRNA expression levels of PI3K,AKT and GLUT4 in the gastrocnemius of mice were detected by real-time quantitative PCR.Morphological changes of the gastrocnemius were observed by hematoxylin-eosin staining,and the cross-sectional area of muscle fibers was calculated. RESULTS AND CONCLUSION:Compared with the blank group,fasting blood glucose,glycosylated hemoglobin,area under the glycemic curve,insulin resistance index,total cholesterol,triglyceride and low-density lipoprotein levels were significantly increased in the model group(P<0.01,P<0.05).Whereas,these indicators were significantly lower in the static exercise and metformin group than the model group(P<0.01,P<0.05).Compared with the blank group,serum insulin and high-density lipoprotein levels were significantly declined in the model group(P<0.01)and the mRNA expression of PI3K,AKT and GLUT4 in the gastrocnemius of mice were also significantly reduced(P<0.01).These indicators were significantly elevated in the metformin group and static exercise group compared with the blank group(P<0.01).Compared with the blank group,the muscle fibers in the model group were disordered,and the muscle cells atrophied and the muscle fiber gap widened.The cross-sectional area of muscle fibers was significantly decreased in the model group compared with the blank group(P<0.01).Compared with the model group,atrophy of the gastrocnemius fibers and muscle fiber space were improved in the static exercise group and the metformin group,and the cross-sectional area of muscle fiber was significantly increased in both groups(P<0.01).These findings indicate that static resistance training may promote glucose uptake and utilization by up-regulating the expression of PI3K,AKT and GLUT4 mRNA in skeletal muscle tissue,thereby improving the morphology and function of skeletal muscle tissue,alleviating insulin resistance and regulating glucose homeostasis.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.
Humans ; Mice ; Animals ; Hyperalgesia/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Hypothermia/metabolism* ; Neuralgia ; Brachial Plexus/injuries* ; Edema/metabolism*

Objective To investigate the association between baseline IgM level and treatment response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). Methods A retrospective analysis was performed for the clinical data of 637 PBC patients who were diagnosed and treated with UDCA for the first time in The Fifth Medical Center of Chinese PLA General Hospital from January 2010 to January 2020. The PBC patients were divided into UDCA complete response group with 436 patients and UDCA poor response group with 201 patients, and baseline clinical data were compared between the two groups. According to the optimal cut-off value of IgM determined by the area under the ROC curve (AUC) of baseline indices in predicting the risk of poor treatment response, the patients were divided into IgM ≥1.5×ULN group and IgM < 1.5×ULN group, and baseline parameters, treatment response, and prognostic model score were compared between groups. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Cochran-Mantel-Haenszel test was used for subgroup analysis, and forest plots were plotted for related risk values. Results Compared with the UDCA complete response group, the UDCA poor response group had significantly higher proportion of patients with liver cirrhosis, levels of total bilirubin, aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid, total cholesterol (TC), IgA, and IgM, and positive rate of anti-Gp210 antibody at baseline ( χ 2 =4.596, Z =-9.932, -8.931, -8.361, -7.836, -4.694, -3.242, and -2.115, χ 2 =15.931, all P < 0.05). The UDCA poor response group had significantly higher Mayo Risk Score, Globe score, and UK-PBC risk score than the UDCA complete response group ( t =4.092, Z =-10.910 and -11.646, all P < 0.001). Compared with the normal IgM group, the elevated IgM group had significantly higher levels of AST, ALP, TC, IgA, and IgG and a significantly higher positive rate of anti-Gp210 antibody ( Z =-3.774, -5.063, -4.344, -2.051, and -6.144, χ 2 =25.180, all P < 0.05). IgM had an AUC of 0.552 in predicting poor treatment response. Compared with the IgM < 1.5×ULN group, the IgM ≥1.5×ULN group had significantly higher levels of AST, ALP, TC, and IgG, a significantly higher positive rate of anti-Gp210 antibody, and a significantly higher poor UDCA response rate ( Z =-4.193, -5.044, -3.250, and -5.465, χ 2 =25.204 and 8.948, all P < 0.05). IgM ≥1.5×ULN had an odds ratio of 1.416 (95% confidence interval [ CI ]: 1.129-1.776, P =0.003) in predicting poor response. The subgroup analysis showed that for patients without liver cirrhosis, IgM ≥1.5×ULN had an odds ratio of 1.821 (95% CI : 1.224-2.711, P =0.003) in predicting poor response. Conclusion Baseline IgM level has an important value in predicting UDCA response. IgM level should be closely monitored during treatment in PBC patients with a high baseline IgM level, and second-line drugs should be given in time if the abnormality persists.

Objective: To explore the mechanism of herbal cake-partitioned moxibustion in Crohn disease (CD) treatment by observing the effect of herbal cake-partitioned moxibustion on protein expressions of colonic M2 macrophage marker CD206, AMP-activated protein kinase (AMPK) and tuberous sclerosis complex (TSC) 2. Methods: Twenty-six specific pathogen free male rats were randomly divided into a normal group, a model group and a herbal cake-partitioned moxibustion group. The CD model was prepared by enema with the mixture of 5％ (W/V) 2,4,6- trinitrobenzene sulfonic acid (TNBS) and 50％ ethanol at 2:1 (volume ratio). After the model was successfully prepared, rats in the herbal cake-partitioned moxibustion group received herbal cake-partitioned moxibustion at Qihai (CV 6) and bilateral Tianshu (ST 25). Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of rat colon; immunohistochemical technique was used to detect the expression of colonic CD206 protein; Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) technologies were used to detect the protein and mRNA expressions of colonic AMPK and TSC2. Results: Compared with the normal group, rats in the model group showed damaged colonic mucosa, missing of the epithelial layer, thickened submucosa, vascular proliferation, massive infiltration of monocytes and lymphocytes, and cracked ulcers that reached the muscle layer. Rats in the herbal cake-partitioned moxibustion group showed reduced intestinal inflammation and healing intestinal epithelium ulcers. Compared with the normal group, rat colonic CD206 protein expression, and the protein and mRNA expressions of colonic AMPK and TSC2 were decreased in the model group (all P<0.01); compared with the model group, rat colonic CD206 protein expression was increased (P<0.01), as well as the protein and mRNA expressions of AMPK and TSC2 in the herbal cake-partitioned moxibustion (all P<0.05). Conclusion: Herbal cake-partitioned moxibustion can reduce intestinal inflammation in CD rats, increase colonic CD206 protein expression, and up-regulate the protein and mRNA expressions of colonic AMPK and TSC2.