Objective:To investigate the clinicopathological characteristics of patients with early gastric carcinoma with lymphoid stroma(EGCLS).Methods:A retrospective analysis was conducted on 27 consecutive patients with EGCLS who underwent radical surgery at The Second People's Hospital of Changzhou between January 2007 and December 2023.Sixty-nine cases of conventional early gastric carcinoma with matched T stages were randomly selected as controls.Immunohistochemical staining was performed to detect the expression of P53,mismatch repair(MMR)proteins,programmed death-ligand 1(PD-L1),E-cadherin,and human epidermal growth factor receptor 2(HER2)in the study cohort.FISH analysis was conducted on HER2 2+cases,and in situ hybridization was used to detect Epstein-Barr virus(EBV).Res-ults:No significant differences were observed between the two groups in terms of patient sex,age,tumor location,size,ulceration,lymph-ovascular or perineural invasion,tumor budding grade,P53 expression,or MMR protein deficiency.The EGCLS group showed significantly higher proportions of SM2 invasion(88.9%),poor tumor differentiation(70.4%),pushing tumor border(48.1%),PD-L1 positivity(59.3%),Epstein-Barr virus-encoded small RNA(EBER)positivity(55.6%),and abnormal E-cadherin expression(48.1%)compared to the control group(59.4%,46.4%,18.8%,24.6%,1.4%,and 23.2%,respectively;P<0.05).The frequency of lymph node metastasis(7.4%)and the pro-portion of elevated macroscopic type(14.8%)in the EGCLS group were significantly lower than in the control group(30.4%and 40.6%,re-spectively;P<0.05).Lymphovascular invasion,tumor budding grade,and non-EGCLS status were identified as risk factors for lymph node metastasis,with lymphovascular invasion being the only independent risk factor.Conclusions:EGCLS is a rare subtype of early gastric car-cinoma characterized by a low frequency of lymph node metastasis and a high proportion of EBER positivity or MMR protein deficiency.En-doscopic resection or immunotherapy may be preferred treatment options for patients who are not suitable candidates for surgery.

Objective To observe the effect of sevoflurane(SEV)on the expression of myocardial biological clock gene aromatic hydrocarbon receptor nuclear transport-like protein 1(BMAL1)in diabetic rats and to explore its changes.Methods Sixty healthy male SD rats with a body mass of 200-250 g were divided into oxygen inhalation group(NC)and sevoflurane inhalation group(SEV).The diabetic model was routinely replicated,and the model was divided into oxygen group(DM)and sevoflurane group(DM+SEV)with an inhalation time of 5 h(n=15).Four groups of experimental animals were executed at 0,12 and 24 h after the anesthesia was stopped and then myocardial tissue was isolated.Western blot was used to determine the expression level of biological clock gene BMAL1 protein and its activation enzyme USP9X;HE staining microspy to observe the pathological changes of my-ocardial tissue and immuno-fluorescence co-localization to observe the relationship between USP9X and BMAL1.Results At 0 and 12 h after stopping anesthesia,the expression of BMAL1 and USP9X in the DM+SEV group was significantly down-regulated as compared with the DM group,and the expression of BMAL1 and USP9X in the DM+SEV group was significantly down-regulated(P<0.05)at 24 h after stopping anesthesia(P>0.05).HE staining microscopy found changes of myocardial tissue structure in the DM+SEV group at 0 and 12 hrs after stopping anes-thesia.This change was most significant at 0 h after stopping anesthesia,but the myocardial tissue structure was neatly arranged at 24 h.The results of immuno-fluorescence colocalization showed that USP9X and BMAL1 proteins were mainly distributed in the cytoplasm of cardio-myocardium with and overlapping parts between them.Under the influence of sevoflurane,there was less overlap between the two at 0 and 12 hrs after stopping anesthesia and more overlap between the two at 24 h,which was close to that of the DM group.Conclusions Sevoflurane reversibly changes the expression of myocardial circadian clock gene BMAL1 in diabetic rats and this change still existe for 12 h after stopping anesthesia,then significantly fade away 24 hrs after stopping anesthesia.

Objective:To investigate the clinicopathological characteristics of patients with early gastric carcinoma with lymphoid stroma(EGCLS).Methods:A retrospective analysis was conducted on 27 consecutive patients with EGCLS who underwent radical surgery at The Second People's Hospital of Changzhou between January 2007 and December 2023.Sixty-nine cases of conventional early gastric carcinoma with matched T stages were randomly selected as controls.Immunohistochemical staining was performed to detect the expression of P53,mismatch repair(MMR)proteins,programmed death-ligand 1(PD-L1),E-cadherin,and human epidermal growth factor receptor 2(HER2)in the study cohort.FISH analysis was conducted on HER2 2+cases,and in situ hybridization was used to detect Epstein-Barr virus(EBV).Res-ults:No significant differences were observed between the two groups in terms of patient sex,age,tumor location,size,ulceration,lymph-ovascular or perineural invasion,tumor budding grade,P53 expression,or MMR protein deficiency.The EGCLS group showed significantly higher proportions of SM2 invasion(88.9%),poor tumor differentiation(70.4%),pushing tumor border(48.1%),PD-L1 positivity(59.3%),Epstein-Barr virus-encoded small RNA(EBER)positivity(55.6%),and abnormal E-cadherin expression(48.1%)compared to the control group(59.4%,46.4%,18.8%,24.6%,1.4%,and 23.2%,respectively;P<0.05).The frequency of lymph node metastasis(7.4%)and the pro-portion of elevated macroscopic type(14.8%)in the EGCLS group were significantly lower than in the control group(30.4%and 40.6%,re-spectively;P<0.05).Lymphovascular invasion,tumor budding grade,and non-EGCLS status were identified as risk factors for lymph node metastasis,with lymphovascular invasion being the only independent risk factor.Conclusions:EGCLS is a rare subtype of early gastric car-cinoma characterized by a low frequency of lymph node metastasis and a high proportion of EBER positivity or MMR protein deficiency.En-doscopic resection or immunotherapy may be preferred treatment options for patients who are not suitable candidates for surgery.

Objective To investigate whether discontinuous sleep supplementation can reduce myocardial ischemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder.Methods The rats were injected intra-peritoneal with 1％streptozotocin(STZ)30 mg/kg combined with high-fat and high-glucose diet to replicate diabetic model.Forty diabetic rats were randomly divided into four groups with 10 in each:sham surgery group(Sham group),ischemia-reperfusion group(I/R group),in which the left anterior descending coronary artery(LDA)was ligated for thirty minutes and reperfusion for 2 h,circadian rhythm disorder group(Crd group,24 h daily light and food),discontinuous sleep supplementation group(Dss group,every 3 hours of illumination and 1.5 hours break at night).We analyzed the myocardial infarct size(by 2,3,5-triphenyltetrazolium chloride stai-ning),determined serum creatine kinase-myoglobin(CK-MB)activity and cardiac troponinⅠ(cTnⅠ)concentrations;the expression level of BMAL1 and REV-ERBα was determined by Western blot.Results Compared to the sham group,the I/R group showed a significantly increased in myocardial infarct size,serum CK-MB activity and cTnⅠ concentration.The expression of the myocardial biological clock gene BMAL1 was down-regulated,while the ex-pression of REV-ERBα was up-regulated(P<0.05).Compared to the I/R group,the Crd group showed a signifi-cantly increase in myocardial infarct size,serum CK-MB activity and cTnⅠ concentration.The expression of the myocardial biological clock gene BMAL1 was down-regulated,while the expression of REV-ERBα was up-regulated(P<0.05).Compared to the Crd group,Dss group showed a significantly decrease in the myocardial infarct size,serum cTn concentration and CK-MB activity.Furthermore,there was an increased protein expression of BMAL1 and a decrease of REV-ERBα(P<0.05).Conclusions Discontinuous sleep supplementation can reduce myocardial is-chemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder.

Objective:To evaluate the effect of electroacupuncture on P2X4R-p38 mitogen-activated protein kinase (p38 MAPK)-brain-derived neurotrophic factor (BDNF) signaling pathway in trigeminal ganglion of rats with trigeminal neuralgia.Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), and electroacupuncture group (E group). The model was developed by chronic constriction of the infraorbital nerve in anesthetized animals. The infraorbital nerve was only exposed without ligation in group S. Rats received electroacupuncture stimulation at the Baihui and Xiaguan acupoints on the affected side for 20 min after developing the model, with a frequency of 80 Hz, twice a day, for 14 consecutive days in E group. Facial mechanical pain threshold (FMT) was measured at 1 day before developing the model and 3, 7, 14, 21 and 28 days after developing the model. The rats were sacrificed after the last behavioral testing, and the trigeminal ganglia were taken for examination of histopathological changes of trigeminal ganglion (by HE staining) and for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the FMT was significantly decreased at each time point after developing the model, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased ( P<0.05), the pathological changes of the trigeminal ganglion were obvious in group TN. Compared with group TN, the FMT was significantly increased at each time point after developing the model, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased ( P<0.05), and the pathological changes of the trigeminal ganglion were significantly attenuated in group E. Conclusions:The mechanism by which electroacupuncture alleviates trigeminal neuralgia may be related to inhibiting the activity of P2X4R-p38MAPK-BDNF signaling pathway and reducing neuroinflammation in rats.

We report a rare case of prostate cancer presenting with gallbladder metastasis as the first manifestation. The patient was a 79-year-old male who presented to the hospital with recurrent right upper abdominal pain and yellow urine for one month. The preoperative diagnosis, based on clinical symptoms and imaging findings, was choledocholithiasis with cholecystitis and cholelithiasis. Preoperative ultrasonography revealed an enlarged prostate, and the serum PSA level was >100 ng/ml. The patient refused further examinations. A cholecystectomy was performed, and postoperative pathology revealed metastatic prostatic follicular adenocarcinoma (Gleason score 5+ 4) and chronic cholecystitis. Immunohistochemical staining of the tumor cells was positive for PSAP and NKX3.1. Postoperatively, the patient was treated with a combination of abiraterone and goserelin.The patient survived with the tumor for 34 months after the pathological diagnosis, with a serum PSA level of 1.16 ng/ml at the time of follow-up. Prostate cancer presenting with gallbladder metastasis as the first manifestation is extremely rare. The combination of clinical examination, imaging findings, and immunohistochemistry can aid in the diagnosis and differentiation of metastatic prostate cancer.

We report a rare case of prostate cancer presenting with gallbladder metastasis as the first manifestation. The patient was a 79-year-old male who presented to the hospital with recurrent right upper abdominal pain and yellow urine for one month. The preoperative diagnosis, based on clinical symptoms and imaging findings, was choledocholithiasis with cholecystitis and cholelithiasis. Preoperative ultrasonography revealed an enlarged prostate, and the serum PSA level was >100 ng/ml. The patient refused further examinations. A cholecystectomy was performed, and postoperative pathology revealed metastatic prostatic follicular adenocarcinoma (Gleason score 5+ 4) and chronic cholecystitis. Immunohistochemical staining of the tumor cells was positive for PSAP and NKX3.1. Postoperatively, the patient was treated with a combination of abiraterone and goserelin.The patient survived with the tumor for 34 months after the pathological diagnosis, with a serum PSA level of 1.16 ng/ml at the time of follow-up. Prostate cancer presenting with gallbladder metastasis as the first manifestation is extremely rare. The combination of clinical examination, imaging findings, and immunohistochemistry can aid in the diagnosis and differentiation of metastatic prostate cancer.

Objective:To evaluate the role of P2X4 receptor (P2X4R) in the maintenance of trigeminal neuralgia and the relationship with p38 mitogen-activated protein kinase (p38 MAPK)/brain-derived neurotrophic factor (BDNF) signaling pathway in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), trigeminal neuralgia+ dimethylsulfoxide (DMSO) group (TN+ DMSO group), and trigeminal neuralgia+ P2X4R specific antagonist 5-BDBD group (TN+ 5-BDBD group). The model was developed by chronic constriction of the infraorbital nerve. The infraorbital nerve was only exposed without ligation in group S. At 3, 7, 10 and 14 days after developing the model, 5 μg/μl 5-BDBD 10 μl was intrathecally injected in TN+ 5-BDBD group, and 2% DMSO 10 μl was intrathecally injected in TN+ DMSO group. The facial mechanical pain withdrawal threshold (MWT) was measured at 1 day before developing the model and 1, 3, 7, 10, 14 and 28 days after developing the model (T 0-6). The rats were sacrificed and the trigeminal ganglia were taken for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased at T 1-6, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in TN group ( P<0.05). Compared with TN group, the MWT was significantly increased at T 3-6, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in TN+ 5-BDBD group ( P<0.05), and no significant change was found in the indexes mentioned above in TN+ DMSO group ( P>0.05). Conclusions:P2X4R is involved in the maintenance of trigeminal neuralgia in rats, which may be related to the activation of p38 MAPK/BDNF signaling pathway and the increase in inflammatory mediator release.

Objective:To identify the potential pathogenic genes for perioperative neurocognitive disorder (PND) in the patients with digestive system tumors.Methods:The gene expression data of esophageal cancer, gastric cancer, colon cancer, rectal cancer and liver cancer in The Cancer Genome Atlas database were analyzed by bioinformatics analysis method, and the differentially expressed genes in tumor tissues in above-mentioned disease samples were identified compared with para-carcinoma tissues.Secretory proteome differential genes with the same expression trend in digestive system tumors were obtained by comparing with human secretory proteome genes.The correlation between secretomics and PND was determined by comparing with the GeneCards database.Hub genes were identified through PPI network construction and calculation, and the functions and signaling pathways of the above-mentioned differential genes were identified through GO and KEGG enrichment analysis.Results:Compared with para-carcinoma tissues, the expression of 2 640 genes was significantly up-regulated and the expression of 1 423 genes was down-regulated in esophageal cancer tissues; the expression of 3 748 genes was up-regulated and the expression of 908 genes was down-regulated in gastric cancer samples; the expression of 2 684 genes was up-regulated and the expression of 2 678 genes was down-regulated in colon cancer samples; the expression of 2 876 genes was up-regulated and the expression of 2 945 genes was down-regulated in rectal cancer samples; the expression of 1 484 genes was up-regulated and the expression of 723 genes was down-regulated in hepatocellular carcinoma samples.Among them, the expression of the encoding genes of 53 secreted proteins was uniformly up-regulated and the expression of the encoding genes of 20 secreted proteins was uniformly down-regulated in the above tumors.Twenty up-regulated genes and 3 down-regulated genes were associated with PND.PPI network analysis showed that MMP9 was the hub gene.The results of GO and KEGG analysis suggested that differentially expressed genes were mainly related to receptor-ligand activity, cytokine activity and chemokine activity, and were mainly enriched in signaling pathways related to cell cycle and cellular senescence.Conclusions:About 23 differentially expressed genes in digestive system tumors are potentially related to PND, of which MMP9 and other genes may be the hub genes, mainly acting on receptor-ligand binding, regulation of cytokine and chemokine activity, cell cycle, cellular senescence and other related signaling pathways.

Objective:To evaluate the role of acetaldehyde dehydrogenase 2 (ALDH2) in hippocampus in memory decline after myocardial ischemia-reperfusion (I/R) in rats.Methods:Twenty-four healthy male Sprague-Dawley rats, aged 2-3 months, weighing 220-280 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (group S), myocardial I/R group (group I/R) and ALDH2 agonist ALDA-1 group (group ALDA-1). Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion in anesthetized animals.ALDA-1 10 mg/kg was intraperitoneally injected at 5 min before ischemia in group ALDA-1.The positioning navigation training in Morris water maze test was started from 6 days before developing the model.The spatial exploration in Morris water maze test was performed at 24 h after developing the model.The rats were sacrificed after the end of behavioral experiment, and the hippocampus was extracted for microscopic examination of the pathological changes (by hematoxylin and eosin staining) and for determination of the apoptosis index (AI) (by TUNEL staining), activity of ALDH2 (by colorimetry), contents of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) (by enzyme-linked immunosorbent assay), and expression of ALDH2 and 4-HNE (by Western blot). Results:Compared with group S, the number of crossing the original platform was significantly decreased, the time spent in the target quadrant was shortened, the activity of ALDH2 in the hippocampus was decreased, the expression of 4-HNE was up-regulated, and the contents of 4-HNE and MDA and AI were increased in group I/R ( P<0.05). Compared with group I/R, the number of crossing the original platform was significantly increased, the time spent in the target quadrant was prolonged, the ALDH2 activity was increased, the expression of 4-HNE was down-regulated, and the contents of 4-HNE and MDA and AI were decreased in group ALDA-1 ( P<0.05). There was no significant difference in ALDH2 expression in hippocampus among the three groups ( P>0.05). Conclusions:The mechanism of memory decline developed after myocardial I/R may be related to the decrease in ALDH2 activity and promotion of accumulation of aldehydes in the hippocampus of rats.