OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Objective To analyze personal external exposure dose monitoring results of pet hospital radiation workers in Beijing from 2022 to 2024, and to provide scientific evidence for developing effective monitoring protocols, standardizing radiological practices in pet hospitals, and protecting the health of both workers and the public. Methods Personal dose equivalents, H_p(10), were measured using GR-200A thermoluminescent dosimeters. Monitoring included radiation workers at 286 pet hospitals across all 16 districts of Beijing from 2022 to 2024. Each monitoring cycle lasted no more than 90 days. Annual effective doses were calculated by summing the results of four consecutive quarterly cycles. Data were processed and analyzed using Access and TLPS 6.41 software. All evaluations complied with national laws, regulations, and technical standards. Results A total of 1,579 person-time measurements were recorded. Only 51.87% of workers completed the full four-cycle annual monitoring schedule. Over the study period, the mean annual effective dose was 0.29 mSv, and the median dose was 0.14 mSv. The collective effective dose was 238.34 man-mSv. Notably, 94.26% of workers had annual effective doses below 1.0 mSv, and only 0.12% had doses at or above 5 mSv. Dose levels showed a statistically significant downward trend (P<0.05). Both independent and chain-branded clinics had a median annual effective dose of 0.14 mSv. In independent clinics, the proportion of workers with doses below 1.0 mSv increased from 80.77% in 2022 to 98.82% in 2024. In chain-branded clinics, this proportion rose from 96.88% to 98.11% over the same period. Conclusion Radiation exposure among pet hospital workers in Beijing remains at low levels, well below regulatory limits, and shows an overall declining trend. The disparity in personal doses between independent and chain-branded pet hospitals has diminished over time. Nevertheless, the industry still faces challenges such as high staff turnover and low monitoring completion rates. Expanding monitoring coverage and harmonizing protection standards would provide a scientific basis for precise, nationwide regulation.

Steroid-associated osteonecrosis of the femoral head (SANFH) is a progressive osteoarticular disorder associated with prolonged or high-dose glucocorticoid exposure. Its development involves local ischemia, oxidative stress, dysregulated bone metabolism, and disruption of the osteoimmune microenvironment. Macrophages exhibit marked phenotypic plasticity, and their polarization is essential for maintaining the dynamic balance among inflammation, angiogenesis, and bone remodeling. Persistent glucocorticoid stimulation, hypoxia, excessive reactive oxygen species, and damage-associated signals released from necrotic tissues can shift macrophages toward a pro-inflammatory phenotype. Classically activated macrophages (M1 macrophages) predominantly mediate inflammatory responses. By releasing tumor necrosis factor-α, interleukin-1β, interleukin-6, and other mediators, promoting osteoclast activation, suppressing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and impairing vascular endothelial function, M1 macrophages accelerate trabecular destruction and expansion of the necrotic lesion. In contrast, alternatively activated macrophages (M2 macrophages) contribute to inflammation resolution, neovascularization, osteogenic repair, and tissue remodeling, thereby supporting regeneration within the necrotic region. Macrophage-derived exosomes further influence disease progression through intercellular communication. Exosomes from different macrophage phenotypes can differentially regulate adipogenic differentiation, neutrophil extracellular trap formation, and endothelial phenotypic transition, thereby affecting the repair capacity of the necrotic area. These findings indicate that macrophage polarization shapes the local microenvironment not only through soluble mediators but also through vesicle-mediated communication with BMSCs, neutrophils, endothelial cells, and other cell populations. At the molecular level, the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3) inflammasome, nuclear factor kappa B (NF‑κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathways jointly regulate macrophage polarization and its downstream osteoimmune effects. Dysregulation of these pathways may sustain inflammatory activation, aggravate oxidative and vascular injury, inhibit osteogenesis, and impair tissue repair. NLRP3 inflammasome activation links danger signals and oxidative stress to inflammatory cytokine maturation and pyroptotic injury; NF-κB signaling promotes pro-inflammatory gene transcription and M1 polarization; JAK/STAT signaling participates in the balance between inflammatory and reparative macrophage programs; and PI3K/Akt/mTOR signaling regulates cellular metabolism, survival, autophagy, and regeneration. Notably, the biological effects of PI3K/Akt/mTOR signaling are cell-type dependent, and Akt-mediated repair signaling should be distinguished from mTOR-related autophagy regulation. The pathological significance of macrophage polarization in SANFH is not determined simply by an increase or decrease in a single phenotype. Rather, disease progression appears to result from an imbalance between persistent pro-inflammatory activity and insufficient reparative responses at different stages of the disease. Such an imbalance disrupts the coordinated coupling of inflammation resolution, vascular regeneration, and bone remodeling, ultimately contributing to structural deterioration of the femoral head. This review summarizes the pathological roles, signaling regulation, and exosome-mediated intercellular communication associated with macrophage polarization imbalance in SANFH. A more precise understanding of these mechanisms may clarify the osteoimmune basis of SANFH and support the development of macrophage-targeted interventions. However, most available evidence is derived from cellular and animal studies, and the temporal evolution of macrophage phenotypes in patients remains insufficiently characterized. Therapeutic strategies should therefore move beyond the simple suppression of M1 macrophages or enhancement of M2 macrophages and instead aim to restore a stage-appropriate balance between inflammatory control and tissue repair while promoting angiogenesis and bone reconstruction.

A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

Ulcerative colitis（UC） is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa， and its complex pathogenesis involves immune abnormality， oxidative stress and other factors. The nuclear transcription factor E₂-related factor 2（Nrf2）， encoded by the Nfe212 gene， plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1（HO-1） and quinone oxidoreductase 1（NQO1）， but also enhances the activity of glutathione-S-transferase（GST） and superoxide dismutase 1（SOD1）， effectively eliminating reactive oxygen species（ROS） accumulated in the body， and mitigating oxidative stress-induced damage to intestinal mucosa. In addition， Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response， cell apoptosis and autophagy pathways， thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this， this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2， the molecular mechanism of activation， the protective effect in the pathological process of UC， and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory， promoting autophagy， inhibiting apoptosis， protecting the intestinal mucosal barrier， and promoting intestinal mucosal repair， providing new ideas and methods for the multi-faceted treatment of UC.

Objective To analyze the effect of Hsa-circ-0101216 on gemcitabine(GEM)chemotherapy resistance in pancreatic cancer and its mechanism.Methods Differentially expressed circRNAs between GEM-resistant pancreatic cancer cells and parent cells were screened using the GEO database.Pancreatic cancer GEM resistant cell lines(BxPC-3-GEM and Capan-1-GEM)were constructed by intermittent concentration gradient method.qRT-PCR was used to detect the expression of Hsa-circ-0101216 in cells.GEM resistant pancreatic cancer cell lines were taken and divided into sh-circ-0101216 group(knockdown of circ-0101216),sh-NC group(transfected with sh-NC),and blank control group(untreated).CCK-8 assay and EdU proliferation assay were used to detect the half inhibitory concentration(IC50)of GEM and proliferation ability of cells in each group.Western blotting was performed to detect the expression of multidrug resistance-related protein 1(MRP1),breast cancer resistance protein(BCRP),and human equilibrative nucleoside transporter-1(hENT-1).A subcutaneous xenograft tumor model of human pancreatic cancer in nude mice was constructed,and sh-NC+GEM group and sh-circ-0101216+GEM group(n=6)were set up.The volume and weight of xenograft tumor in nude mice were compared between the two groups.Western blotting and immunohistochemistry were used to detect the expression of MRP1,BCRP,and hENT-1 proteins in xenograft tumor tissues,and EDU proliferation assay was used to detect the proliferation ability of tumor cells.Results The GEO database screening showed that Hsa-circ-0101216 was up-regulated in GEM-resistant pancreatic cancer cell lines.Pancreatic cancer GEM-resistant cell lines were successfully constructed,and the expression levels of Hsa-circ-0101216 and the IC50 value in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly higher than those in parental cells(P<0.05).In sh-circ-0101216 group,the IC50 values of GEM,cell viability,EdU positivity rate,and the expression levels of MRP1 and BCRP proteins in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly lower than those in blank control group and sh-NC group,while the expression level of hENT-1 protein was significantly higher(P<0.05 or P<0.001).In sh-circ-0101216+GEM group,the weight and volume of subcutaneous xenograft tumors in nude mice,the expression levels and positive expression rates of MRP1 and BCRP proteins in tumor tissues,and the EdU positive rate were significantly lower than those in sh-NC+GEM group,while the expression level and positive expression rate of hENT-1 protein were significantly higher(P<0.05).Conclusions Hsa-circ-0101216 is highly expressed in GEM-resistant pancreatic cancer cell lines.Its knockdown can inhibit the proliferation of pancreatic cancer cells and enhance the chemosensitivity of pancreatic cancer cells to GEM.The mechanism may be related to the regulation of transmembrane transporter protein expression.

Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

Objective To analyze the clinical characteristics,treatment,and prognosis of immune checkpoint inhibitor-related diabetes mellitus(ICI-DM).Methods The clinical characteristics,laboratory examinations,treatment regimens,and follow-up outcomes of 10 ICI-DM patients who were diagnosed and treated in the First Medical Center of Chinese PLA General Hospital between July 2019 and December 2024 were retrospectively analyzed.Relevant literatures were retrieved from domestic and foreign databases such as PubMed,CNKI,and VIP.The clinical characteristics of ICI-DM were summarized based on the literature results.Results All 10 patients were PD-1 inhibitor users,including 5 males and 5 females,with a median age of 54.5(51.3,64.0)years and a body mass index(BMI)of(22.0±2.15)kg/m2.Among them,9 cases(90.0%)were fulminant type 1 diabetes mellitus(FT1DM);9 cases(90.0%)had a severity of adverse events reaching grade 3-4 according to the Common Terminology Criteria for adverse events(CTCAE).The median time from PD-1 inhibitor treatment to the occurrence of the classic diabetes symptoms referred to as"three more and one less"(polyuria,polydipsia,polyphagia,and weight loss)in all patients was 145.5(110.5,204.8)days,and the medication duration was 6.0(4.3,7.8)cycles.The average blood glucose level of the 10 patients at the time of consultation was 25.3(10.0-41.4)mmol/L,and the glycated hemoglobin(HbA1c)level was 8.0%(6.6%-10.9%).Eight patients had fasting and 2-hour C-peptide levels<0.1 ng/ml(fasting C-peptide from<0.010 to 0.067 ng/ml,2-hour C-peptide from<0.010 to 0.077 ng/ml).Nine of the 10 patients were negative for diabetes autoantibodies,while 1 was not tested.All 10 patients were successfully treated with insulin and other therapies.During the follow-up after discharge,all patients still relied on insulin treatment,and no significant recovery of pancreatic islet β cell function was observed compared with that at discharge.Literature review revealed that ICI-DM was more common in PD-1 inhibitor users,with clinical mainly manifested as diabetic ketoacidosis(DKA)(65.4%)and diabetic ketosis(13.1%).Patients had severely impaired pancreatic islet function and required long-term insulin treatment,and some cases were complicated by thyroid or pituitary dysfunction.Conclusions ICI-DM typically presents as FT1DM,often manifesting with DKA or diabetic ketosis at onset.It is characterized by severe and irreversible loss of pancreatic islet function,necessitating lifelong insulin therapy.To enable early detection and prompt treatment,close monitoring of blood glucose is essential during ICI treatment.

Exercise-induced metabolic remodeling is a fundamental adaptive process whereby the body reorganizes systemic and cellular metabolism to meet the dynamic energy demands posed by physical activity. Emerging evidence reveals that such remodeling not only enhances energy homeostasis but also profoundly influences immune function through complex molecular interactions involving glucose, lipid, and protein metabolism. This review presents an in-depth synthesis of recent advances, elucidating how exercise modulates immune regulation via metabolic reprogramming, highlighting key molecular mechanisms, immune-metabolic signaling axes, and the authors’ academic perspective on the integrated “exercise-metabolism-immunity” network. In the domain of glucose metabolism, regular exercise improves insulin sensitivity and reduces hyperglycemia, thereby attenuating glucose toxicity-induced immune dysfunction. It suppresses the formation of advanced glycation end-products (AGEs) and interrupts the AGEs-RAGE-inflammation positive feedback loop in innate and adaptive immune cells. Importantly, exercise-induced lactate, traditionally viewed as a metabolic byproduct, is now recognized as an active immunomodulatory molecule. At high concentrations, lactate can suppress immune function through pH-mediated effects and GPR81 receptor activation. At physiological levels, it supports regulatory T cell survival, promotes macrophage M2 polarization, and modulates gene expression via histone lactylation. Additionally, key metabolic regulators such as AMPK and mTOR coordinate immune cell energy balance and phenotype; exercise activates the AMPK-mTOR axis to favor anti-inflammatory immune cell profiles. Simultaneously, hypoxia-inducible factor-1α (HIF-1α) is transiently activated during exercise, driving glycolytic reprogramming in T cells and macrophages, and shaping the immune landscape. In lipid metabolism, exercise alleviates adipose tissue inflammation by reducing fat mass and reshaping the immune microenvironment. It promotes the polarization of adipose tissue macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Moreover, exercise alters the secretion profile of adipokines—raising adiponectin levels while reducing leptin and resistin—thereby influencing systemic immune balance. At the circulatory level, exercise improves lipid profiles by lowering pro-inflammatory free fatty acids (particularly saturated fatty acids) and triglycerides, while enhancing high-density lipoprotein (HDL) function, which has immunoregulatory properties such as endotoxin neutralization and macrophage cholesterol efflux. Regarding protein metabolism, exercise triggers the expression of heat shock proteins (HSPs) that act as intracellular chaperones and extracellular immune signals. Exercise also promotes the secretion of myokines (e.g., IL-6, IL-15, irisin, FGF21) from skeletal muscle, which modulate immune responses, facilitate T cell and macrophage function, and support immunological memory. Furthermore, exercise reshapes amino acid metabolism, particularly of glutamine, arginine, and branched-chain amino acids (BCAAs), thereby influencing immune cell proliferation, biosynthesis, and signaling. Leucine-mTORC1 signaling plays a key role in T cell fate, while arginine metabolism governs macrophage polarization and T cell activation. In summary, this review underscores the complex, bidirectional relationship between exercise and immune function, orchestrated through metabolic remodeling. Future research should focus on causative links among specific metabolites, signaling pathways, and immune phenotypes, as well as explore the epigenetic consequences of exercise-induced metabolic shifts. This integrated perspective advances understanding of exercise as a non-pharmacological intervention for immune regulation and offers theoretical foundations for individualized exercise prescriptions in health and disease contexts.