BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

AIM: To investigate the impacts of periocular injection of triamcinolone acetonide on healing effect and inflammatory factor in patients with acute iridocyclitis.METHODS:Totally 90 patients(90 eyes)with acute iridocyclitis, admitted to our hospital between September 2018 and September 2023, were grouped via random number table, including a triamcinolone acetonide group and a control group, each comprising 45 patients(45 eyes). The control group underwent conventional treatment, whereas the triamcinolone acetonide group adopted triamcinolone acetonide through periocular injection. The healing effect, levels of inflammatory cytokines, anterior chamber inflammatory cell scores, keratic precipitates(KP)scores, best-corrected visual acuity(BCVA), untoward reactions, and relapse rates of the two groups of patients were compared.RESULTS:The triamcinolone acetonide group had significantly higher overall efficacy rate than the control group(P<0.05). The levels of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interferon-γ(IFN-γ)decreased in both groups at 30 d after treatment, and the levels in the triamcinolone acetonide group were lower(all P<0.05). After treatment for 30 d, the scores of anterior chamber inflammatory cells and KP in both groups decreased, and the scores in the triamcinolone acetonide group were lower than those in the control group(all P<0.05); the BCVA of both groups improved, and the triamcinolone acetonide group had a better BCVA(all P<0.05). There was no statistically significant difference in untoward reactions between the two groups(P=1.000). The relapse rate of the triamcinolone acetonide group was lower than that of the control group(P=0.030).CONCLUSION: Periocular injection of triamcinolone acetonide has obvious healing effects on patients with acute iridocyclitis, and it can alleviate the inflammatory state of patients and reduce the relapse rate of inflammation.

Critical care medicine(CCM)is a multifaceted discipline challenged by the inherent heterogeneity and complexity of critical illnesses.Establishing precise,standardized diagnostic and therapeutic systems has emerged as a crucial challenge requiring urgent resolution in this field.Surgical critical care,a pivotal branch of CCM,plays an indispensable role in managing patients with severe trauma,postoperative intra-abdominal infections,solid organ transplantation,and other life-threatening conditions.Evidence-based,etiology-guided therapy serves as the cornerstone of surgical critical care,where accurate identification and timely interventions constitute vital determinants for enhancing patient survival rates and improving prognoses.This article proposes an innovative diagnostic and therapeutic paradigm termed the urgency/physics-biology-chemistry(U/P-B-C)model.Built upon the established principle of urgent(urgency,U)life support in surgical critical care,this model emphasizes a novel conceptual framework centered on etiology-based(physics-biology-chemistry,P-B-C)diagnosis and treatment.Implementing the U/P-B-C innovative diagnostic and therapeutic model in surgical critical care facilitates precise identification of the fundamental pathological mechanisms underlying critical clinical conditions with complex and dynamic clinical environments,enables systematic clarification of clinical reasoning,and ultimately supports evidence-informed decision-making.Its core objectives encompass enhancing surgical intensivists' diagnostic-therapeutic capabilities and ensuring rigorous adherence to the principle of etiology-guided therapy,thereby providing both theoretical foundation and practical guidance for improving the success rate of patient resuscitation and optimizing prognosis in surgical critical care settings.

Objective To observe the effects of Yinqin Qingfei Granules on oxidative injury in lung tissue of mice with mycoplasma pneumoniae infection;To explore the mechanism of the Keap1/Nrf2/HO-1 signaling pathway in it.Methods Totally 100 BALB/c mice were randomly divided into blank group,model group,Yinqin Qingfei group,Azithromycin group and combination group,with 20 mice in each group.Except for the blank group,the other groups of mice were used to establish mycoplasma pneumoniae pneumonia model through bacterial solution nasal drip,and the blank group was given the same amount of normal saline nasal drip for 3 days.After modeling,the drug groups were given corresponding drugs by gavage,the blank group and the model group were given the same amount of distilled water by gavage,and the materials were taken at 3 and 7 days after administration,respectively.HE staining was used to observe the morphology of lung tissue,ELISA was used to detect the contents of interleukin(IL)-1β and tumor necrosis factor(TNF)-α in serum,biochemical method was used to detect the contents of nitric oxide(NO),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in lung tissue,Western blot was used to detect the expressions of Kelch like ECH associated protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)protein in lung tissue.Results Compared with the blank group,the lungs of mice in the model group showed severe inflammatory changes on day 3 and 7,with alveolar fusion or disappearance,and lung consolidation,which were more severe on day 7;the contents of IL-1β and TNF-α in serum significantly increased(P<0.05),the contents of SOD and GSH in lung tissues significantly decreased(P<0.05),and the contents of MDA and NO significantly increased(P<0.05),the protein expression of Keap1 in lung tissues increased(P<0.05),and Nrf2 and HO-1 protein expressions decreased(P<0.05).Compared with the model group,the histopathological changes in lung tissue showed different degrees of improvement on day 3 and 7 of drug treatment in Yinqin Qingfei group,Azithromycin group and combination group groups,the serum contents of IL-1β and TNF-α were significantly decreased(P<0.05),the contents of SOD and GSH in lung tissue were significantly increased on day 7 of drug treatment(P<0.05),the contents of MDA and NO significantly decreased(P<0.05),the protein expression of Keap1 in lung tissue decreased on day 3 and 7 of drug treatment(P<0.05),and the protein expressions of Nrf2 and HO-1 increased(P<0.05).Conclusion Yinqin Qingfei Granules can regulate the level of inflammatory factors,reduce lung inflammation and oxidative damage of mice with mycoplasma pneumoniae infection.The mechanism may be related to down-regulating the expression of Keap1,up-regulating the expressions of Nrf2 and HO-1,reducing the contents of NO and MDA,improving the activities of SOD and GSH,and playing an antioxidant role.

As the longest and most widely distributed pair of nerves in the brain,the vagus nerve is involved in the regulation of many systems and organs.Recent studies have found that the vagus nerve may be involved in the occurrence of a variety of neuropsychiatric diseases by regulating the release of neurotransmitters(such as norepinephrine,5-hydroxytryptamine,gamma-aminobutyric acid and acetylcholine)and regulating the immune system and gut-brain axis.This article focuses on the regulatory mechanisms of the vagus nerve on neurotransmitters,immune system function,and the gut-brain axis,as well the therapeutic advances in vagus nerve stimulation for neurological and psychi-atric diseases such as epilepsy,depression and anxiety disorders.

Objective:To study the effect of traditional Chinese medicine (TCM) formula in the treatment of brucellosis.Methods:Patients with brucellosis who were treated at the Beidahuang Industry Group General Hospital from March to November 2024 were selected and their clinical data were collected. A case-control study was conducted, thirty patients treated with conventional therapy plus TCM formula were selected as the TCM group, and 35 patients treated with conventional therapy were selected as the control group. Blood routine, C-reactive protein (CRP), lymphocyte subsets (CD45 +, CD3 +, CD4 +, CD8 +, CD19 +), and related cytokines [interleukin (IL)-6, IL-10] were determined before and after treatment to observe the clinical effect of TCM formula in the treatment of brucellosis. Survival curve was draw, and Log-Rank test was used to compare the differences in clinical symptom relief time between the two groups of patients. Results:Compared with pre-treatment, there were statistically significant differences in the numbers of CD45 +, CD3 +, CD4 +, CD8 +, CD19 + lymphocytes, neutrophil (NEUT), and the levels of CRP, IL-6, and IL-10 in the TCM group after treatment ( P < 0.05). After treatment, the comparison of each index between the two groups showed that there were statistically significant differences in the numbers of CD45 +, CD3 +, CD4 +, and CD8 + lymphocytes [control group vs TCM group: 2 470.00 (1 895.50, 3 207.00) vs 1 991.00 (1 720.75, 2 367.25), 1 920.00 (1 364.50, 2 428.00) vs 1 591.00 (1 343.00, 1 884.00), 1 021.00 (785.00, 1 205.50) vs 839.50 (704.25, 1 010.25), (686.42 ± 294.47) vs (596.97 ± 205.32) pieces/μl, P < 0.05]. There was no statistically significant difference in the number of CD19 + lymphocytes, NEUT, and the levels of CRP, IL-6 and IL-10 ( P > 0.05). The Log-Rank test results showed that there were statistically significant differences in the relief time of hyperhidrosis and night sweats ( P = 0.016), fatigue ( P = 0.016), and muscle soreness ( P = 0.004) between the two groups of patients. Conclusion:TCM formula has certain effects in the adjuvant therapy of brucellosis, which can improve the immune function of lymphocytes and relieve clinical symptoms, and has clinical application value.

Objective:To explore the clinical characteristics of patients with brucellosis complicated with epididymo-orchitis (Brucellar epididymo-orchitis, BEO), so as to provide reference for clinical diagnosis and treatment of BEO.Methods:General and clinical data of 293 male patients with acute brucellosis admitted to the Beidahuang Industry Group General Hospital from January 2023 to December 2024 were retrospectively collected. They were divided into a BEO group (30 cases) and a non-BEO group (263 cases) based on the presence or absence of epididymo-orchitis. Epidemic characteristics, clinical manifestations and laboratory examination results were compared and analyzed.Results:Among 293 male patients with acute brucellosis, the incidence of BEO was 10.24% (30/293). Their age was mainly concentrated in 45 - < 60 years old (53.33%, 16/30), and occupation was mostly farmers (63.33%, 19/30). There were no statistically significant differences in the distribution of age, occupation, exposure history and onset season between the BEO group and the non-BEO group ( P > 0.05). The distribution of abdominal pain and urinary frequency/urgency/pain symptoms was compared, and the differences were statistically significant ( P < 0.05). White blood cell count (WBC), neutrophil count (NEUT), and C-reactive protein (CRP) levels in the BEO group were higher than those in the non-BEO group ( P < 0.05), while the levels of cytokines interleukin (IL)-6 and interferon-γ (IFN-γ) were lower than those in the non-BEO group ( P < 0.05). After 6 - 8 weeks of hospitalization, the levels of WBC, NEUT, CRP, albumin, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, α-hydroxybutyrate dehydrogenase, lactate dehydrogenase, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-α, and IFN-γ in patients of the BEO group were significantly different from before treatment ( P < 0.05). Twenty-eight patients were cured, 1 patient underwent orchiectomy, and 1 patient experienced recurrence. Conclusions:Middle-aged male patients with brucellosis are more prone to BEO. Clinical manifestations and laboratory tests have certain diagnostic value for BEO. Suspected BEO patients should be diagnosed and treated as early as possible to reduce the occurrence of adverse prognosis.

Objective:To learn about the clinical characteristics of patients with neurobrucellosis (NB) and provide references for clinical diagnosis and treatment of NB.Methods:The clinical data of 22 NB patients diagnosed and treated at Beidahuang Industry Group General Hospital from January 2018 to November 2024 and 178 healthy individuals undergoing physical examinations during the same period were retrospectively collected. The epidemiological characteristics, clinical manifestations, laboratory tests, treatment and prognosis of NB patients were analyzed.Results:Among the 22 NB patients, 12 were males (54.55%) and 10 were females (45.45%). The age was (51.77 ± 12.75) years old, ranging from 27 to 80 years old. Most of the patients were farmers (95.45%, 21/22), and 16 cases (72.73%) had contacted with cattle/sheep. The onset seasons were mainly in summer (40.91%, 9/22) and spring (31.82%, 7/22). Among all NB patients, there were 10 cases of encephalitis/meningoencephalitis, 9 cases of myelitis, and 3 cases of meningitis. The general symptoms were mainly fever (68.18%, 15/22), the neurological symptoms were mainly nausea and vomiting (36.36%, 8/22), and the physical signs were mainly muscle weakness (50.00%, 11/22) and pathological signs (45.45%, 10/22). The laboratory test results showed that the levels of hemoglobin, hematocrit, C-reactive protein, total protein, albumin, γ-glutamyl transpeptidase, α-hydroxybutyric acid dehydrogenase, lactate dehydrogenase, and glutathione reductase in NB patients were significantly different from those in healthy individuals ( P < 0.001). Brain magnetic resonance imaging revealed ischemic changes in 5 cases (22.73%), abnormal brain signals in 2 cases (9.09%), and demyelinating lesions in white matter in 1 case (4.55%). After treatment, 18 NB patients were followed up and showed good prognosis, with only 2 cases exhibiting varying degrees of sequelae (walking disorders or memory impairment). Conclusions:The clinical manifestations of NB patients are diverse. A comprehensive judgment should be made by combining epidemiological characteristics, clinical manifestations, laboratory tests and imaging examinations.