BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

OBJECTIVES: To investigate the role of active glucose monitoring in preventing hypoglycemia during the perioperative period of gastrointestinal endoscopy in children with glycogen storage disease type Ⅰb (GSD-Ⅰb). METHODS: A retrospective analysis was performed for the clinical data of children with GSD-Ⅰb who were diagnosed and treated in Guangdong Provincial People's Hospital from June 2021 to August 2024. The effect of active glucose monitoring on hypoglycemic episodes during the perioperative period of gastrointestinal endoscopy was analyzed. RESULTS: A total of 14 children with GSD-Ⅰb were included, among whom there were 7 boys and 7 girls, with a mean age of 10.0 years. Among 34 hospitalizations, there were 15 cases of hypoglycemic episodes (44%), among which 6 symptomatic cases (1 case with blood glucose level of 1.6 mmol/L and 5 cases with blood glucose level of <1.1 mmol/L) occurred without active monitoring, while 9 asymptomatic cases (with blood glucose level of 1.2-3.9 mmol/L) were detected by active monitoring. The predisposing factors for hypoglycemic episodes included preoperative fasting (5 cases, 33%), delayed feeding (7 cases, 47%), vomiting (2 cases, 13%), and parental omission (1 case, 7%). Two children experienced two hypoglycemic episodes during the same period of hospitalization, and no child experienced subjective symptoms prior to hypoglycemic episodes. Treatment methods included nasogastric glucose administration (1 case, 7%), intravenous injection of glucose (14 cases, 93%), and continuous glucose infusion (4 cases, 27%). Blood glucose returned to 3.5-6.9 mmol/L within 10 minutes after intervention and remained normal after dietary resumption. CONCLUSIONS Active glucose monitoring during the perioperative period of gastrointestinal endoscopy can help to achieve early detection of hypoglycemic states in children with GSD-Ⅰb, prevent hypoglycemic episodes, and enhance precise diagnosis and treatment.
Humans ; Female ; Male ; Child ; Retrospective Studies ; Blood Glucose/analysis* ; Hypoglycemia/etiology* ; Glycogen Storage Disease Type I/blood* ; Endoscopy, Gastrointestinal ; Perioperative Period ; Child, Preschool ; Adolescent

OBJECTIVES: To investigate the efficacy and safety of empagliflozin in patients with glycogen storage disease (GSD)-associated inflammatory bowel disease (IBD). METHODS: A cross-sectional study was conducted, enrolling 25 patients with GSD-associated IBD who received empagliflozin treatment. General data, details of empagliflozin use, and adverse events were collected. Clinical symptoms and biochemical parameters before and after empagliflozin therapy were compared. RESULTS: Twenty-five patients with GSD-associated IBD were included, with a median age at diagnosis of 0.7 years, and a mean age at initiation of empagliflozin therapy of (11 ± 6) years. The initial dose of empagliflozin was (0.30 ± 0.13) mg/(kg·d), with a maintenance dose of (0.40 ± 0.21) mg/(kg·d), and a treatment duration of (34 ± 6) months. Seventy-eight percent (18/23) of patients' parents reported that empagliflozin therapy reduced the frequency of infections and oral ulcers, and increased neutrophil counts. Clinically, the number of patients with anorexia decreased from 12 to 5 after treatment, and 30% showed improved appetite (P<0.05). The numbers of patients with diarrhea, mucus/bloody stools, perianal disease, and oral ulcers decreased from 19, 9, 11, and 21 before treatment to 7, 1, 0, and 10 after treatment, respectively (P<0.05). Laboratory findings showed that absolute neutrophil counts increased, while platelet counts, lactate, and uric acid levels decreased significantly after empagliflozin treatment (P<0.05). Adverse reactions occurred in 7 patients (28%) during empagliflozin treatment. Two cases occurred in the treatment initiation phase, presenting as hypotension or profuse sweating with dehydration, along with urinary tract infections (UTIs); empagliflozin was discontinued in both cases. During the maintenance phase, 3 cases of UTIs and 2 cases of hypoglycemia (one with profuse sweating) were reported. CONCLUSIONS Empagliflozin therapy can increase neutrophil counts, reduce the incidence of infections and oral ulcers, alleviate diarrhea and abdominal pain, improve appetite, and ameliorate platelet count, lactate, and uric acid levels in patients with GSD-associated IBD, demonstrating significant clinical benefit. UTIs, hypoglycemia, hypotension, profuse sweating, and dehydration may be potential adverse reactions associated with empagliflozin therapy.
Humans ; Benzhydryl Compounds/adverse effects* ; Male ; Female ; Glucosides/adverse effects* ; Inflammatory Bowel Diseases/etiology* ; Child ; Child, Preschool ; Cross-Sectional Studies ; Adolescent ; Glycogen Storage Disease/drug therapy* ; Infant

OBJECTIVE: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. METHODS: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. RESULTS: Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. CONCLUSION TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.
Mitophagy/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Macrophages/virology* ; Inflammasomes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Influenza A virus/physiology* ; Interleukin-1beta/metabolism* ; Cell Line ; Injections

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective To analyze the relationship between MyD88L265P and CD79B mutations in tumor tissue and the prognosis of primary central nervous system lymphoma(PCNSL).Methods 18 PCNSL patients with normal immune function(no history of HIV infection and immunosuppressants administration)who were diagnosed by craniotomy or stereotaxic biopsy in the Second Hospital of Lanzhou University from August 2018 to November 2020 were retrospectively analyzed.Real-time quantitative PCR and first-generation sequencing techniques were respectively used to detect MyD88L265P and CD79B mutations in tumor tissues of 18 PCNSL patients.Univariate analysis and Cox regression multivariate analysis were performed for indicators that may be associated with first progression-free survival(PFS)and overall survival in PCNSL.Results The mutation rate of MyD88L265P was 38.9%,the mutation rate of CD79B was 33.3%,and the co-mutation rate of MyD88L265P/CD79B was 27.8%in PCNSL tissue of 18 patients.Univariate analysis showed that the PCNSL patients with multiple lesions,deep involvement of lesions,and tissue CD79B mutation had a statistically significant shorter time of PFS(P<0.05).Multivariate analysis showed that deep lesion involvement(HR=0.135,95%CI 0.023-0.799,P<0.05)and CD79B mutation(HR=0.149,95%CI 0.028-0.800,P<0.05)in PCNSL tissue were independent prognostic factors for PCNSL patients.Conclusion The frequency of MyD88L265P and CD79B mutations was high in tumor tissues of 18 PCNSL patients,and these two gene mutations may be associated with poor prognosis of PCNSL,especially CD79B mutation.

BACKGROUND:Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism.The present study aimed to establish a new scoring system to predict mechanical ventilation(MV)for botulism patients. METHODS:A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022.Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system.The area under the receiver operating characteristic(ROC)curve was calculated. RESULTS:A total of 153 patients with botulism(66 males and 87 females,with an average age of 43 years)were included.Of these,49 patients(32.0%)required MV,including 21(13.7%)with invasive ventilation and 28(18.3%)with non-invasive ventilation.Multivariate analysis revealed that botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement were independent risk factors for MV.These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system.Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization([botulinum toxin type A:1],[pneumonia:2],[incubation period≤1 day:2],[hypoxia<90%:2],[severity of muscle involvement:grade II,3;grade III,7;grade IV,11]).The scoring system achieved an area under the ROC curve of 0.82(95%CI 0.75-0.89,P<0.001).At the optimal threshold of 9,the scoring system achieved a sensitivity of 83.7%and a specificity of 70.2%. CONCLUSION:Our study identified botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement as independent risk factors for MV in botulism patients.A score≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients.This scoring system needs to be validated externally before it can be applied in clinical settings.