OBJECTIVE To investigate the effects of galangin on rheumatoid arthritis （RA） in rats by regulating the Janus kinase 3 （JAK3）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Fifty male SD rats were taken， and an emulsion composed of bovine type Ⅱ collagen and Freund’s complete adjuvant was injected subcutaneously to establish an induced arthritis model. The rats that were successfully modeled were randomly divided into model group， low， medium and high dose groups of galangin （1， 5， 15 mg/kg）， and methotrexate group （positive control， 2 mg/kg）， with 10 rats in each group. Another 10 normal rats were taken as the normal group. Starting from the 15th day of modeling， each group of rats was gavaged with the corresponding drug solution or normal saline containing 0.5% Tween 80 once a day for 28 consecutive days. The arthritis index （AI） scores and paw volume of rats were compared before and after gavage administration. Twenty-four hours after the last administration， the serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-4 and IL-10 were determined， the pathological changes in ankle joint synovial tissue were observed， and the protein expressions of UNC-51 like kinase 1 （ULK1）， Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， B cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， caspase-3， JAK3， phosphorylated JAK3 （p-JAK3）， STAT3 and phosphorylated STAT3 （p-STAT3） in the synovial tissue of the ankle joint were detected， as well as the fluorescence intensity of LC3-positive areas. RESULTS Compared with the model group， the pathological changes such as cellular proliferation of ankle joint synovial tissue and infiltration of inflammatory cells in rats of each administration group showed improvement. Moreover， their AI scores and paw pad volumes （on day 28 after gavage）， the levels of IL-6 and TNF-α， the protein expression of Bcl-2， and the phosphorylation levels of JAK3 and STAT3 were all significantly reduced （ P ＜0.05）. The levels of IL-4 and IL-10， the protein expressions of ULK1， Beclin-1， Bax， caspase-3 and LC3， as well as the fluorescence intensity of LC3-positive areas， were all significantly increased （ P ＜0.05）. Moreover， the effect of galangin was in a dose-dependent manner （ P ＜0.05）. CONCLUSIONS Galangin can induce sustained autophagy in synovial tissue cells of RA rats， promote cell apoptosis， inhibit synovial cell proliferation， and alleviate persistent inflammatory responses. The above anti-RA effects may be related to the inhibition of the JAK3/STAT3 pathway.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.

Adrenocortical carcinoma（ACC）is a rare and highly aggressive malignant tumor. Currently，mitotane is the first-line treatment. However，reports on neoadjuvant therapy for ACC using mitotane combined with immune checkpoint inhibitors remain scarce. This article reports a case of ACC. The patient was asymptomatic，and a right adrenal mass was detected during examination. Diagnostic imaging and endocrine evaluation confirmed the diagnosis of ACC. Due to the large tumor size，radical resection was initially considered unfeasible. After 7 months of mitotane therapy and two courses of tislelizumab，significant tumor shrinkage was achieved，allowing for successful open resection of the large right adrenal tumor combined with right nephrectomy. Postoperative histopathological examination confirmed the diagnosis of ACC. During the 3-month postoperative follow-up，no evidence of recurrence or metastasis was observed.

Objective:To explore the differences in clinicopathological features and prognosis between conventional adrenocortical carcinoma（ACC）and oncocytic ACC.Methods:The clinical and pathological data of patients with conventional ACC and oncocytic ACC who were admitted to Peking Union Medical College Hospital from March 2012 to Fabruary 2025 were retrospectively analyzed. Differences in clinical and pathological characteristics between the two groups were compared. Survival curves were plotted using the Kaplan-Meier method，and differences in survival rates were compared using the log-rank test.Results:The conventional ACC group comprised 137 cases，with a mean age of（47.5 ± 12.6）years and 37.2%（51/137）being male. The oncocytic ACC group included 22 cases，with a mean age of（49.1 ± 15.3）years and 59.1%（13/22）being male. No statistically significant differences were observed in age or gender distribution between the two groups（ P > 0.05）. The conventional ACC group exhibited a significantly higher prevalence of classic Cushing’s syndrome symptoms compared to the oncocytic ACC group［35.2%（45/128）vs. 5.3%（1/19）； χ2 = 6.876， P < 0.01］. Additionally，the proportion of hypertension was higher in the conventional ACC group［49.2%（65/132）vs. 22.2%（4/18）； χ2 = 5.319， P < 0.05］，whereas the prevalence of adrenal sex characteristics was lower［22.0%（28/127）vs. 63.2%（12/19）； χ2 = 14.043， P < 0.01］. The Ki-67 proliferation index was significantly higher in conventional ACC patients［20%（10%，40%）vs. 12%（9%，20%）； Z = -2.113， P < 0.05］. Furthermore，the conventional ACC group demonstrated a lower 5-year overall survival rate than the oncocytic ACC group（44.5% vs. 67.3%， P < 0.05）. Conclusions:Conventional ACC patients have a higher proportion of Cushing’s symptoms and hypertension，and oncocytic ACC patients have a higher proportion of adrenal sexual characteristics abnormalities. The prognosis of oncocytic ACC is better than that of conventional ACC.

[Objective]To clarify the botanical origin of the exotic herb Poluode in Bencao Shiyi.[Methods]By consulting ancient,modern,domestic and foreign literature,the botanical origin of Poluode was demonstrated from the aspects of drug name,transmission route and origin distribution,plant morphological characteristics and medical efficacy.[Results]The names of Poluode and Uyghur medicine Baladu both originate from the Sanskrit word"bhallātaka",which is the Sanskrit name for Semecarpus anacardium L.f.(S.anacardium).S.anacardium and mainly distributed in India,which coincides with the origin of Poluode,and their morphological characteristics are consistent,with similar medical efficacy.[Conclusion]The botanical origin of Poluode is S.anacardium,and it is also one of the plant sources of Baladu,a Uyghur medicine.Clarifying the Chinese herbs in Bencao Shiyi and bringing back the lost Chinese herbs from history is not only inheritance and promotion of the"Zhejiang school of materia medica"masterpiece Bencao Shiyi,but also promotes the"sinicization"of foreign excellent medicinal resources and advances the high-quality development of traditional Chinese medicine.

In recent years, advancements in big data availability and computer computing power have driven significant progress in deep learning, particularly in image recognition, speech recognition, and natural language processing. These new developments have also provided new directions for the development of medicine, such as intelligent medical consultation, personalized diagnosis and treatment plan planning, medical image-assisted interpretation, etc. However, deep learning faces challenges such as weak reusability and insufficient interpretability in specific applications. This article reviews the development history of deep learning and some of its latest developments in the field of medicine, and examines some of its problems in medical applications.

Objective To observe the effects of electroacupuncture on IL-4/STAT6/SPDEF pathway-related protein expressions in model mice of ulcerative colitis(UC);To explore the mechanism of electroacupuncture improving the intestinal mucus barrier.Methods Totally 48 BALB/c mice were randomly divided into blank group(12 mice)and modeling group(36 mice).The UC models were established in the modeling group using 3%dextran sulfate sodium free drinking.After successful modeling,mice were further randomly divided into model group,electroacupuncture group and sulfasalazine(SASP)group,with 12 mice in each group.The electroacupuncture group received electroacupuncture at"Guanyuan","Tianshu","Zusanli"and"Shangjuxu"acupoints for 20 minutes per day,the SASP group was administered sulfasalazine enteric-coated tablet suspension(500 mg/kg)by gavage,the blank group received no intervention,the model group was only confined for continuous 7 days.The general conditions were observed and disease activity index(DAI)score were recorded,HE staining was used to observe the morphology of colonic tissue and evaluate the colonic mucosal damage index(CMDI)score,AB-PAS staining was used to observe the number of goblet cells in colonic tissue,and immunofluorescence staining was used to detect the expression of mucin 2(MUC2)protein in colonic tissue,ELISA was used to detect the contents of serum tumor necrosis factor-α(TNF-α)and γ interferon(IFN-γ),and Western blot was used to detect the protein expressions of interleukin(IL)-4,signal transducer and activator of transcription(STAT)6 and epithelial specific transcription factor(SPDEF)in colonic tissue.Results Compared with the blank group,the model group showed mucous stool,bloody stool,reduced intake of food and water,reduced body mass,increased DAI and CMDI scores(P<0.01),with intestinal villi shedding and necrosis,destruction of colonic crypt villi structure,accompanied by severe neutrophil infiltration,thinning of mucus layer,atrophy and reduction of goblet cells(P<0.01),the expression of MUC2 in colonic tissue significant decreased(P<0.01),the contents of TNF-α and INF-γ in serum significantly increased(P<0.01),while the protein expressions of IL-4,STAT6 and SPDEF in colonic tissue significantly decreased(P<0.01).Compared with the model group,both the electroacupuncture group and SASP group showed improved mucous stool,bloody stool,increased body mass,decreased DAI and CMDI scores(P<0.05),the morphology of the intestinal epithelium was basically normal,the glandular structure has improved,there was a small amount of inflammatory cell infiltration and slight edema,the thickness of the mucus layer was restored,the atrophy reduced and number of goblet cells increased(P<0.05),the expression of MUC2 in colonic tissue significantly increased(P<0.05),while the contents of TNF-α and IFN-γ in serum significantly decreased(P<0.05),the expressions of IL-4,STAT6 and SPDEF protein in colonic tissue significantly increased(P<0.05).Conclusion Electroacupuncture can facilitate the repair of the intestinal mucus barrier and inhibit inflammation,potentially through the activation of IL-4/STAT6/SPDEF pathway-related protein expressions.

One of the most common adverse reactions associated with cancer and its treatment is sarcopenia,a syndrome primarily caused by the disruption of muscle homeostasis,leading to excessive muscle atrophy and decreased muscle strength.For cancer patients,sarcopenia reflects not only a state of muscle mass loss but also serves as an important factor affecting treatment efficacy and survival rates.However,cancer-related sarcopenia often has a more insidious onset,is not visible to the naked eye,and is easily overlooked.Therefore,it is necessary to recognize the dangers of sarcopenia throughout the cancer treatment process and to identify low muscle mass early.In recent years,as healthcare professionals have increasingly focused on sarcopenia,research on cancer-related sarcopenia has gradually deepened,with new advancements in its assessment,diagnosis,intervention,and impact on anti-cancer treatment.This article provides a review of these key areas to offer a theoretical basis for the clinical practice of cancer-related sarcopenia.

BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.