ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription （ZJSP） on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy （DCM）， with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin （STZ） while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group， the low-dose（14.43 g·kg^-1）and high-dose（28.86 g·kg^-1） ZJSP groups， and the metformin group （0.25 g·kg^-1）， with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks， fasting blood glucose （FBG） and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin （FINS） and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin （HE） staining， and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of AMPK， FoxO1， and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK， p-AMPK， FoxO1， p-FoxO1， and CD36. ResultsCompared with the control group， the model group showed significantly increased levels of FBG and FINS （P<0.01）， elevated levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.01）， and significantly decreased left ventricular ejection fraction （EF） and fractional shortening （FS） values （P<0.01）. HE staining revealed marked cardiomyocyte hypertrophy， disarray， and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased， while FoxO1 and CD36 mRNA expressions were significantly increased （P<0.01）. The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced， while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased （P<0.01）. Compared with the model group， all treatment groups exhibited significantly reduced FBG （P<0.01）， decreased FINS and blood lipid levels （TG， TC， LDL-C） （P<0.05， P<0.01）， improved cardiac function （P<0.05）， noticeable amelioration of myocardial histopathological morphology and lipid deposition， increased AMPK mRNA expression （P<0.01）， with significantly downregulated FoxO1 and CD36 mRNA expressions （P<0.01）， elevated p-AMPK/AMPK protein expression levels in myocardial tissue （P<0.05）， significantly decreased p-FoxO1/FoxO1 ratios （P<0.01）， and downregulated CD36 protein expression levels （P<0.05， P<0.01）. ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice， and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.

ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription （ZJSP） on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy （DCM）， with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin （STZ） while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group， the low-dose（14.43 g·kg^-1）and high-dose（28.86 g·kg^-1） ZJSP groups， and the metformin group （0.25 g·kg^-1）， with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks， fasting blood glucose （FBG） and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin （FINS） and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin （HE） staining， and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of AMPK， FoxO1， and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK， p-AMPK， FoxO1， p-FoxO1， and CD36. ResultsCompared with the control group， the model group showed significantly increased levels of FBG and FINS （P<0.01）， elevated levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.01）， and significantly decreased left ventricular ejection fraction （EF） and fractional shortening （FS） values （P<0.01）. HE staining revealed marked cardiomyocyte hypertrophy， disarray， and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased， while FoxO1 and CD36 mRNA expressions were significantly increased （P<0.01）. The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced， while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased （P<0.01）. Compared with the model group， all treatment groups exhibited significantly reduced FBG （P<0.01）， decreased FINS and blood lipid levels （TG， TC， LDL-C） （P<0.05， P<0.01）， improved cardiac function （P<0.05）， noticeable amelioration of myocardial histopathological morphology and lipid deposition， increased AMPK mRNA expression （P<0.01）， with significantly downregulated FoxO1 and CD36 mRNA expressions （P<0.01）， elevated p-AMPK/AMPK protein expression levels in myocardial tissue （P<0.05）， significantly decreased p-FoxO1/FoxO1 ratios （P<0.01）， and downregulated CD36 protein expression levels （P<0.05， P<0.01）. ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice， and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.

Periampullary carcinoma is a malignant tumor of the biliopancreatic system originating from the ampulla of Vater， with the main pathological subtypes of intestinal-type and pancreatobiliary-type adenocarcinoma. Primary periampullary squamous cell carcinoma is relatively rare in clinical practice， with great difficulties in preoperative diagnosis and a lack of clinical experience and standardized diagnosis and treatment regimens. This article reports a case of primary periampullary squamous cell carcinoma in a male patient aged 55 years. The patient was admitted due to cutaneous and scleral jaundice for 2 weeks. Laboratory examination revealed obstructive jaundice， impaired liver function， and an increase in carbohydrate antigen 19-9， and radiological examination showed obstruction of the distal common bile duct and a space-occupying lesion in the ampullary region， leading to a preliminary clinical diagnosis of periampullary carcinoma of Vater. After admission， endoscopic retrograde cholangiopancreatography was first performed to relieve obstructive jaundice， and then biopsy of the ampullary lesion was conducted， with pathological findings highly suspicious for malignancy. Radical pancreaticoduodenectomy was performed after improvement in liver function， and postoperative pathology confirmed the diagnosis of moderately differentiated squamous cell carcinoma of the ampulla. PET-CT reexamination on day 52 after surgery showed well-healed surgical anastomosis and multiple hypermetabolic nodules in the right hepatic lobe， which could not rule out tumor metastasis. This case report can provide a reference for improving awareness of this rare disease and optimizing related diagnosis and treatment decisions in clinical practice.

Although epilepsy is first known as a disease of seizures and convulsions, most patients with epilepsy also suffer from seizure-associated behavioral abnormalities in motor functions, psychiatric status, and cognition. These neurobehavioral comorbidities may have greater impacts on the quality of life of people with epilepsy than the seizures themselves and can profoundly interfere with the treatment compliance. While repeated seizures often lead to behavioral comorbidities, certain types of comorbid conditions may potentially increase the risk for epileptic seizures, indicative of some common mechanisms that might underlie these two conditions. As such, emerging evidence supports that inflammation within the brain might represent a key component of such a shared mechanism, given that neuroinflammation can be induced by seizures and various behavioral stressors, and in turn may exacerbate both conditions. Among inflammatory pathways that arise after prolonged seizures, PGE₂ signaling via the EP2 receptor promotes cytokine induction, blood-brain barrier disruption, reactive gliosis, neuronal death, and eventually, contributes to behavioral dysfunctions. Pharmacological inhibition of EP2 by small-molecule drug-like antagonists affords broad therapeutic benefits including anti-inflammatory and neuroprotective effects in several rodent seizure models, leading to long-lasting alleviation of neurobehavioral comorbidities, particularly cognitive impairments. Targeting this key inflammatory prostaglandin receptor might provide an adjunctive strategy, along with the current anti-seizure medications, to mitigate cognitive dysfunctions associated with seizure disorders.

Objective: To investigate the chemical compositions of Maxing Shigan Decoction (麻杏石甘汤, MXSGD) and elucidate its anti-influenza A virus (IAV) mechanism from prediction to validation. Methods: Ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the chemical compositions of MXSGD. Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV. A protein-protein interaction (PPI) network was then constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations. A total of 24 BALB/c mice were infected with IAV to build IAV mouse models. After successful modelling, the mouse models were randomly divided into model, MXSGD high-dose (2.8 g/kg), MXSGD low-dose (1.4 g/kg), and oseltamivir (20.14 mg/kg) groups, with an additional normal mice as control group (n = 6 per group). The treatments were administered by gavage daily between 8:00 a.m. and 10:00 a.m. for five consecutive days. Upon completion of the administration, the body weight ratio, lung index, protein content in the bronchoalveolar lavage fluid (BALF), and the levels of inflammatory factors including interleukin (IL)-6 and tumor necrosis factor (TNF)-α in mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection. Furthermore, the expression levels of mechanistic target of rapamycin (mTOR), hypoxia inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF) proteins in the HIF-1 signaling pathway, which was enriched by network pharmacology, were detected by Western blot. Results: A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method. These chemical components can be classified into 9 primary categories and 31 secondary categories. After intersecting the chemical component targets with IAV-related targets, a total of 567 potential MXSGD components targeting IAV were identified. The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways, including apoptosis, TNF, HIF-1, and IL-17 signaling pathways. The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α, mTOR, and VEGF were all lower than – 5.0 kcal/mol. Furthermore, molecular dynamics simulations confirmed the structural stability of the resulting complexes. Animal experiments showed that compared with the normal controls, IAV-infected mice showed significantly reduced body weight ratio, markedly increased lung index, protein content in BALF, and the levels of inflammatory factors such as IL-6 and TNF-α (P < 0.01), thereby causing damage to the lung tissue; consequently, the expression levels of mTOR, HIF-1α, and VEGF proteins in the lung tissues of these mice were significantly elevated (P < 0.01). However, after MXSGD treatment, the mouse models presented a significant increase in body weight ratio, as well as marked decreases in lung index, protein content in BALF, and the levels of inflammatory factors including IL-6 and TNF-α (P < 0.01). Furthermore, the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR, HIF-1α, and VEGF proteins in lung tissues (P < 0.01 or P < 0.05). Conclusion MXSGD exerts anti-IAV effects through multi-component, multi-target, and multi-pathway synergism. Among them, 1-methoxyphaseollin is identified as a potential key component, which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway, providing experimental evidence for the clinical application of MXSGD.

Objective:This study aimed to compare the clinical efficacy of da Vinci robot-assisted subtotal colectomy with laparoscopic surgery in the treatment of slow transit constipation.Methods:A retrospective cohort study was performed. The clinical and follow-up data of 95 patients with slow transit constipation who underwent robotic or laparoscopic subtotal colectomy at the First Affiliated Hospital of Harbin Medical University from July, 2022 to August, 2024 and had a follow-up period of 6 months were retrospectively analyzed. Patients were divided into a robotic surgery group (43 cases) and a laparoscopic surgery group (52 cases) according to surgical approaches. All patients underwent preoperative colonic transit study, barium enema radiography, defecography, and colonoscopy to confirm the diagnosis of slow transit constipation. There were no statistically significant differences in baseline data between the two groups (all P>0.05). Primary observation indicators included Wexner constipation score, gastrointestinal quality of life score, and the time of first ambulation after surgery. Secondary observation indicators included operation time, intraoperative blood loss, first defecation time, length of hospital stay, postoperative defecation frequency, postoperative complications, surgical satisfaction, and postoperative pain. The Wexner constipation score was evaluated at 6 months after surgery as well, and a total score of 15 or above was defined as constipation; the higher the score, the more severe the constipation. The gastrointestinal quality of life index was also evaluated at 6 months after surgery; the lower the score, the poorer the quality of life. Pain assessment was conducted on the 2nd day after surgery using the visual analogue scale (VAS) for self-assessment, and here a higher score indicated greater pain intensity. Observe the patients' intraoperative and pastoperative conditions. Results:Both groups completed the surgery unevenifullg without conversion to laparotomy, and no severe intraoperative complications occurred. Compared to the laparoscopic surgery group, the robotic surgery group had significantly shorter first ambulation time ([18.5±1.3] hours vs. [24.5±0.6] hours, t=-30.437, P<0.001), first defecation time ([21.2±2.2] hours vs. [24.9±0.9] hours, t=-10.818, P<0.001), and hospital stay ([7.8±1.5] days vs. [9.4±3.3] days, t=-3.069, P=0.003), all P<0.05. There were no statistically significant differences between the two groups in terms of operation time, intraoperative blood loss, postoperative pain score, defecation frequency, or incidence of postoperative complications (all P>0.05). Follow-up at 6 months post-operation also showed no statistically significant differences between the two groups in terms of Wexner score, gastrointestinal quality of life score, daily defecation frequency, or surgical satisfaction (all P>0.05). When comparing the follow-up scores between postoperative and preoperative periods in each group, both Wexner scores (laparoscopic group: [2.2±1.2] vs. [17.7±0.9], t=83.580, P<0.001; robotic group: [2.6±1.2] vs. [17.5±0.8], t=69.274, P<0.001) and gastrointestinal quality of life scores (laparoscopic group: [108.6±4.4] vs. [76.0±4.6], t=-41.442, P<0.001; robotic group: [109.3±6.1] vs. [77.8±6.4], t=-29.939, P<0.001) were significantly improved. No additional complications or recurrence were observed in both groups at 6 months post-operation. Conclusion:Compared to laparoscopic subtotal colectomy, da Vinci robot-assisted subtotal colectomy for slow transit constipation is associated with faster postoperative recovery and shorter hospital stays, and the operative times and therapeutic efficacy are similar between the two approaches.

Objective:This study aimed to compare the clinical efficacy of da Vinci robot-assisted subtotal colectomy with laparoscopic surgery in the treatment of slow transit constipation.Methods:A retrospective cohort study was performed. The clinical and follow-up data of 95 patients with slow transit constipation who underwent robotic or laparoscopic subtotal colectomy at the First Affiliated Hospital of Harbin Medical University from July, 2022 to August, 2024 and had a follow-up period of 6 months were retrospectively analyzed. Patients were divided into a robotic surgery group (43 cases) and a laparoscopic surgery group (52 cases) according to surgical approaches. All patients underwent preoperative colonic transit study, barium enema radiography, defecography, and colonoscopy to confirm the diagnosis of slow transit constipation. There were no statistically significant differences in baseline data between the two groups (all P>0.05). Primary observation indicators included Wexner constipation score, gastrointestinal quality of life score, and the time of first ambulation after surgery. Secondary observation indicators included operation time, intraoperative blood loss, first defecation time, length of hospital stay, postoperative defecation frequency, postoperative complications, surgical satisfaction, and postoperative pain. The Wexner constipation score was evaluated at 6 months after surgery as well, and a total score of 15 or above was defined as constipation; the higher the score, the more severe the constipation. The gastrointestinal quality of life index was also evaluated at 6 months after surgery; the lower the score, the poorer the quality of life. Pain assessment was conducted on the 2nd day after surgery using the visual analogue scale (VAS) for self-assessment, and here a higher score indicated greater pain intensity. Observe the patients' intraoperative and pastoperative conditions. Results:Both groups completed the surgery unevenifullg without conversion to laparotomy, and no severe intraoperative complications occurred. Compared to the laparoscopic surgery group, the robotic surgery group had significantly shorter first ambulation time ([18.5±1.3] hours vs. [24.5±0.6] hours, t=-30.437, P<0.001), first defecation time ([21.2±2.2] hours vs. [24.9±0.9] hours, t=-10.818, P<0.001), and hospital stay ([7.8±1.5] days vs. [9.4±3.3] days, t=-3.069, P=0.003), all P<0.05. There were no statistically significant differences between the two groups in terms of operation time, intraoperative blood loss, postoperative pain score, defecation frequency, or incidence of postoperative complications (all P>0.05). Follow-up at 6 months post-operation also showed no statistically significant differences between the two groups in terms of Wexner score, gastrointestinal quality of life score, daily defecation frequency, or surgical satisfaction (all P>0.05). When comparing the follow-up scores between postoperative and preoperative periods in each group, both Wexner scores (laparoscopic group: [2.2±1.2] vs. [17.7±0.9], t=83.580, P<0.001; robotic group: [2.6±1.2] vs. [17.5±0.8], t=69.274, P<0.001) and gastrointestinal quality of life scores (laparoscopic group: [108.6±4.4] vs. [76.0±4.6], t=-41.442, P<0.001; robotic group: [109.3±6.1] vs. [77.8±6.4], t=-29.939, P<0.001) were significantly improved. No additional complications or recurrence were observed in both groups at 6 months post-operation. Conclusion:Compared to laparoscopic subtotal colectomy, da Vinci robot-assisted subtotal colectomy for slow transit constipation is associated with faster postoperative recovery and shorter hospital stays, and the operative times and therapeutic efficacy are similar between the two approaches.

Objective:To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial.Methods:We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models.Results:The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD 3) after induction therapy was independently associated with relapse risk ( HR=2.535, 95% CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk ( HR=1.869, 95% CI 1.034-3.379, P=0.039). Based on MRD 3 and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD 3-negative and IKZF1 gene deletion-negative) and high-risk (MRD 3-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % ( P<0.001) and (61.6±8.3) % vs (25.5±6.5) % ( P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS ( HR=3.937, 95% CI 1.975-7.850, P<0.001) and CIR ( HR=4.037, 95% CI 2.095-7.778, P<0.001) . Conclusion:The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

Objective:To invastigate the targets and signaling pathways of Gubiao Fanggan Modified Formula in regulating the defense against influenza A virus in immunosuppressed mice by network pharmacology,and the key targets were verified by immuno-suppressive mice model.Methods:TCMSP database was used to search the active ingredients of Gubiao Fanggan Modified Formula,and GeneCard,OMIM,PharmGkb databases were used to obtain the potential targets of the active ingredients to prevent influenza,and take their intersection targets were taken;STRING11.5 database was used to make protein-protein interaction network analyzed and finded the core targets;Cytoscape3.8.1 was used to build a traditional Chinese medicine-ingredient-disease target network,and GO enrichment analysis and KEGG enrichment analysis were performed.Intraperitoneal injection of cyclophosphamide was used to construct a mouse model of immune function suppression,normal group,model control group,Gubiao Fanggan Modified Formula group and oseltamivir group were set up,followed by prophylactic administration,and influenza virus intervention was performed on the fourth day.After 7 days of intragastric administration,the key targets were verified by mouse spleen index,HE staining,RT-qPCR and immunohistochemistry.Results:There were 82 active ingredients in five traditional Chinese medicines in Gubiao Fanggan Modi-fied Formula,and 72 common targets of drugs and diseases such as IL-6,TNF-α,IL-2,etc,mainly involving IL-17,TNF and AGE-RAGE signaling pathway.Gubiao Fanggan Modified Formula could increase spleen index and significantly reduce mRNA and protein expressions of IL-6 and TNF-α in spleen tissue of mice(P<0.05 or P<0.01).Conclusion:Gubiao Fanggan Modified Formula may regulate body's immune function through targets such as IL-6 and TNF-α,thereby preventing influenza virus infection.

As the main weapon of cellular immunity,CD4+ T cells play a vital role in controlling and eliminating infections,and are an important barrier for the body to resist infections.Respiratory tract infectious diseases caused by influenza virus infection have extremely high infectivity,morbidity and mortality.The infection mechanism is relatively complicated and has not been fully ex-plained.The exuberant immune response induced by the body after influenza virus infection is described as a"cytokine storm"which is related to pro-inflammatory cytokines and tissue damage,which may eventually lead to acute lung injury.Therefore,this article sum-marizes the current research progress,focusing on the mechanism of CD4+T cells in the cytokine storm induced by influenza virus in-fection and the impact of acute lung injury,providing relevant ideas and theoretical guidance for follow-up research,with a view to the disease caused by influenza virus bring new and effective methods of diagnosis and treatment.