Purpose To explore the clinical and pathological characteristics of gastric amphicrine carcinoma(AC).Methods Clinical data of 12 patients with gastric AC were collected,and their clinical pathological character-istics and histological morphology were observed.Immunohistochemical staining,special staining,and electron micros-copy techniques were used to analyze their immune phenotype and ultrastructure.Molecular pathology was used to de-tect microsatellite status.Relevant literature was reviewed.Results Ten cases of gastric AC were located at the junc-tion of the esophagus and stomach/cardia,1 case at the gastric angle,and 1 case in the gastric antrum.The average maximum diameter of tumors was 4.25 cm.There were different proportions of tumor cells with signet-ring like charac-teristics in all cases.Four cases had neuroendocrine carcinoma components,and another 4 had adenocarcinoma.Elev-en cases had nerve invasion and vascular cancer thrombus.Eleven cases invaded the serosal layer/submucosal layer,and 1 case invaded the submucosal layer.Ten cases had lymph node metastasis.All 12 cases showed diffuse expression of CKpan and Syn,with 3 cases showed diffuse expression of CgA and 7 cases showed diffuse expression of CD56.The average proliferation index of Ki67 was 78.9％.Special staining showed clear intracellular mucus.Electron microscopy examination revealed electron dense particles and mucus particles within the tumor cells.A total of 10 patients were fol-lowed up,of which 7 survived,and 3 patients died from multiple systemic metastases at 0,24,and 30 months postop-eratively.Conclusion Gastric AC was more common in the junction of the esophagus and stomach/cardia,and histol-ogy shows a higher invasiveness.Their clear diagnosis depends on histological morphology,immunohistochemistry,and special staining.

Purpose To summarize the clinical pathological and immunohistochemical characteristics of esophage-al carcinoma with ductal differentiation of esophageal gland,and analyze the somatic mutation characteristics,key driv-ing mutation genes,and significantly mutated genes based on whole exome sequencing.Methods The clinicopatho-logical features of 9 cases of esophageal carcinoma with esophageal duct differentiation were retrospectively analyzed,and the immunohistochemistry EnVision two-step method was used to stain them,and 3 of the samples were subjected to whole exome sequencing and data analysis.Results Among the 9 patients,6 were males and 3 were females.The average age was 68.3 years old(61-80 years old).All 9 cases were located in the middle-lower segment of the e-sophagus.The diameter of the lesion was from 1.5 cm to 3.5 cm.Most areas of the tumor had a double-layer epithelial structure,including the inner layer of luminal epithelium and the outer layer of basal epithelium.Focal areas could be seen with keratinization and mucinous cells.Immunohistochemistry showed that CK7 was positive in the inner epitheli-um,while p63 was positive in the outer basal epithelium.S-100,SOX10 and c-myb were all negative,and p53 was mutated(diffuse strongly positive).The results of whole exome sequencing analysis showed somatic mutation character-istics(796 SNV,37 InDel,482 CNV),key driving mutation genes(12),and significantly mutated genes(TP53).No intraepithelial neoplasia was observed on the surface squamous epithelium of all cases,and no Barrett's esophagus or ectopic gastric mucosa was observed.The average follow-up time was 21.9 months(8 days-51 months),with 8 ca-ses surviving and 1 case dying of severe pulmonary infection 8 days after surgery.Conclusion Esophageal carcinoma with ductal differentiation of esophageal gland is a rare epithelial derived malignant tumor of the esophagus,character-ized by unique morphological,immunohistochemical,and molecular changes.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

The persistence of obesity is rooted in energy storage mechanisms formed through millions of years of evolution, combined with the systematic influence of the modern "obesogenic environment", constituting a complex regulatory network involving coordinated neural, endocrine, and metabolic systems. Current mainstream treatment methods exhibit significant limitations: glucagon-like peptide-1 receptor agonists demonstrate remarkable short-term weight loss effects but present issues with tolerance development and post-discontinuation weight regain; bariatric metabolic surgery similarly faces long-term weight recurrence challenges, with approximately one-third of patients experiencing weight regain within five years after surgery. Therefore, comprehen-sive obesity treatment must establish a new paradigmatic framework: utilizing cognitive behavioral intervention as the therapeutic foundation, employing multi-dimensional strategies including mindful eating training, nutritional management, and exercise intervention to help patients establish sustain-able lifestyle changes; repositioning pharmaceutical and surgical medical interventions as supportive measures for behavioral change; constructing multi-level social support environments encompassing policy, community, and family domains to achieve transformation from treatment goals focused solely on weight reduction to metabolic health improvement, from success definition based on short-term weight loss to long-term maintenance, and from medical-dominated treatment systems to patient-centered multidisciplinary collaborative approaches. Ultimately, through the deep integration of biomedical precision, patient cognitive initiative, and social support inclusiveness, a sustainable collaborative pathway for obesity treatment can be established. Based on twenty years of clinical experience in bariatric and metabolic surgery, the authors provide an in-depth analysis of the treat-ment challenges faced by obesity as a complex disease and proposes the necessity of transitioning from traditional single medical interventions to a biopsychosocial comprehensive treatment model.

With advancements in interventional radiology, the interventional diagnosis and treatment are widely applicable for pediatric cardiac diseases. The ionizing radiation during interventional procedures can result in an elevated cancer risk, directly proportional to the radiation dose received. Moreover, it may induce tissue reactions beyond a specific threshold. Given that children are about 2-3 times susceptible to radiation as much as adults, it will be crucial to improve dose control during pediatric interventions, establish the corresponding diagnostic reference level and optimize the diagnosis and treatment procedures. Some countries have carried out dose monitoring and evaluation of pediatric cardiac interventional procedures and established corresponding diagnostic reference levels, but it has yet been in the process of research. This paper reviews the current research status on assessing radiation doses and setting diagnostic reference levels for children receiving congenital heart disease interventions so as to provide a baseline for future measurements and investigations.

Objective:To explore the distribution of pathogenic bacteria causing postoperative infections in chil-dren undergoing surgery for Hirschsprung's disease(HD),and the clinical significance of serum triggering receptor ex-pressed on myeloid cells-1(sTREM-1)and high mobility group box 1(HMGB1).Methods:98 children with HD admit-ted from January 2021 to January 2025 were divided into infection group(n=42)and non-infection group(n=56)accord-ing to whether the children were complicated with infection after operation.Automatic bacterial identification system was used to detect the distribution of pathogenic bacteria in secretion samples from infected sites of HD children after operation.ELISA was used to measure serum sTREM-1 and HMGB1.ROC was used to explore the diagnostic value of serum sTREM-1 and HMGB1 for severe infection in children with HD.Results:A total of 49 strains of pathogenic bac-teria were isolated from 42 children with HD in infection group,of which 63.27%(31/49)were gram-negative bacteria,accounting for the highest proportion,followed by Gram positive bacteria at 30.61%(15/49)and fungi at 6.12%(3/49).Among them,Pseudomonas aeruginosa had the highest proportion of 24.49%(12/49)among Gram negative bacteria.there were 15 cases of mild infection(15 strains of pathogens),16 cases of moderate infection(17 strains of pathogens)and 11 cases of severe infection(17 strains of pathogens).With the aggravation of the infection degree of HD children,the distribution pattern of pathogenic bacteria changed,and gradually changed to mainly gram-negative bacteria infec-tion.Compared with non infected group,the levels of serum sTREM-1 and HMGB1 in infected group were higher(P<0.05).The levels of serum sTREM-1 and HMGB1 in children with severe HD infection are higher than those in children with mild and moderate HD infection(P<0.05).The AUC of the combined diagnosis of serum sTREM-1 and HMGB1 for severe infection in HD children was the highest,at 0.985,which was superior to the separate diagnosis of serum sTREM-1 and HMGB1(Zcombination-sTREM-1=1.988,P=0.047;Zcombination-HMGB1=2.126,P=0.034).Conclusion:Serum sTREM-1 and HMGB1 are elevated in HD children with postoperative infection,and the pathogenic bacteria are mainly gram-negative bacteria.In addition,the combined detection of the two provides a reference for the clinical diagnosis of severe infection in HD children.

The persistence of obesity is rooted in energy storage mechanisms formed through millions of years of evolution, combined with the systematic influence of the modern "obesogenic environment", constituting a complex regulatory network involving coordinated neural, endocrine, and metabolic systems. Current mainstream treatment methods exhibit significant limitations: glucagon-like peptide-1 receptor agonists demonstrate remarkable short-term weight loss effects but present issues with tolerance development and post-discontinuation weight regain; bariatric metabolic surgery similarly faces long-term weight recurrence challenges, with approximately one-third of patients experiencing weight regain within five years after surgery. Therefore, comprehen-sive obesity treatment must establish a new paradigmatic framework: utilizing cognitive behavioral intervention as the therapeutic foundation, employing multi-dimensional strategies including mindful eating training, nutritional management, and exercise intervention to help patients establish sustain-able lifestyle changes; repositioning pharmaceutical and surgical medical interventions as supportive measures for behavioral change; constructing multi-level social support environments encompassing policy, community, and family domains to achieve transformation from treatment goals focused solely on weight reduction to metabolic health improvement, from success definition based on short-term weight loss to long-term maintenance, and from medical-dominated treatment systems to patient-centered multidisciplinary collaborative approaches. Ultimately, through the deep integration of biomedical precision, patient cognitive initiative, and social support inclusiveness, a sustainable collaborative pathway for obesity treatment can be established. Based on twenty years of clinical experience in bariatric and metabolic surgery, the authors provide an in-depth analysis of the treat-ment challenges faced by obesity as a complex disease and proposes the necessity of transitioning from traditional single medical interventions to a biopsychosocial comprehensive treatment model.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Coronavirus,a major pathogen infecting humans,mammals,and birds,causes primarily respiratory diseases af-ter infecting humans.Seven coronaviruses have been found to infect humans and subsequently cause varying degrees of respira-tory symptoms.From 2019 to 2023,millions of people died from severe acute respiratory syndrome coronavirus 2 infections,and the virus continues to mutate.Therefore,drug screening research must urgently be expanded to develop more effective,broad-spectrum anti-coronavirus drugs.In-depth research has indicated that the coronavirus 3C-like protease and RNA polymer-ase are necessary for viral reproduction and are highly conserved among strains,and consequently are anti-virus targets of great interest.This article summarizes the enzymes encoded by coronaviruses and drug screening methods,to provide a reference for coronavirus prevention and control.