AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.

CD73,also known as Ecto-5'-nucleotidase(eNT),is a multifunctional transmembrane glycoprotein with a molecular weight of 70 kD,which is anchored to the cell membrane by glycosyl phosphatidylinositol(GPI),exists in various cells of human body and plays different biological functions in various diseases.Studies have found that CD73 can cooperate with CD39 to complete the adenosine signaling pathway,ATP and ADP can catalyze AMP to generate adenosine in CD39,and then CD73 can catalyze AMP to generate adenosine.In recent years,more and more studies have focused on the role of CD73 in digestive diseases.This review aims to elucidate the biological role of CD73,analyze the research progress of immune regulation mechanism of CD73 in gastrointestinal dis-eases from the aspects of inflammation and tumor,and point out the importance of CD73 in the treatment and prognosis of intestinal diseases.

CD73,also known as Ecto-5'-nucleotidase(eNT),is a multifunctional transmembrane glycoprotein with a molecular weight of 70 kD,which is anchored to the cell membrane by glycosyl phosphatidylinositol(GPI),exists in various cells of human body and plays different biological functions in various diseases.Studies have found that CD73 can cooperate with CD39 to complete the adenosine signaling pathway,ATP and ADP can catalyze AMP to generate adenosine in CD39,and then CD73 can catalyze AMP to generate adenosine.In recent years,more and more studies have focused on the role of CD73 in digestive diseases.This review aims to elucidate the biological role of CD73,analyze the research progress of immune regulation mechanism of CD73 in gastrointestinal dis-eases from the aspects of inflammation and tumor,and point out the importance of CD73 in the treatment and prognosis of intestinal diseases.

AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.

Objective:To compare the diagnostic efficacy of 68Ga-PSMA-11 PET/ CT and multi-parameter magnetic resonance imaging (mpMRI) for pelvic lymph node metastases in prostate cancer patients who received neoadjuvant endocrinology or not after initial diagnosis. Methods:Data of 52 patients with moderate and high-risk prostate cancer admitted to Xijing Hospital from February to October 2023, aged (65.8±6.6) years, preoperative prostate-specific antigen (PSA) 26.67 (13.09, 84.89) ng/ml, were retrospectively analyzed. Before operation, there were 28 cases of cT 2stage, 16 cases of cT 3 stage and 8 cases of cT 4 stage. There were 22 cases of cN 0 and 30 cases of cN 1. All patients underwent 68Ga-PSMA-11 PET/CT and mpMRI at the same time, and were diagnosed positive lymph nodes in 28 and 21 cases, respectively. Risk stratification were high risk in 45 cases, and medium risk in 7 cases. According to the preoperative endocrine treatment, they were divided into the newly diagnosed group without treatment (24 cases) and the endocrine treated group (28 cases), whose ages were (65.0±7.1) years and (66.8±6.1) years, respectively. Preoperative PSA was 26.17 (16.73, 61.18) ng/ml and 27.32 (11.94, 130.18) ng/ml, respectively. Gleason scores ≤7 were in 10 cases (41.7%) and 6 cases (21.4%), and Gleason scores >7 were in 14 cases (58.3%) and 22 cases (78.6%), respectively. There were 15 (62.5%) and 13 (46.4%) cases of cT 1-2 stage, and 9 (37.5%) and 15 (53.6%) cases of cT 3-4 stage, respectively. There were 16 (66.7%) and 6 (21.4%) cases of stage N 0, 8 (33.3%) and 22 (78.6%) cases of stage N 1, respectively. There were 22 (91.7%) and 20 (71.4%) cases of stage M 0, 2 (8.3%) and 8 (28.6%) cases of stage M 1, respectively. PET/CT diagnosis of lymph node positive was in 9 cases (37.5%) and 19 cases (67.9%), and mpMRI diagnosis of lymph node positive was in 5 cases (20.8%) and 16 cases (57.1%). The number of positive lymph nodes diagnosed by PET/CT was 13 (72.2%) and 47 (90.1%), and the number of positive lymph nodes diagnosed by mpMRI was 8 (44.4%) and 32 (61.5%). There was no significant difference ( P>0.05). All patients underwent radical prostatectomy as well as enlarged pelvic lymph node resection. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two imaging examinations in the diagnosis of lymph node metastasis were compared according to the results of postoperative pathological examination of lymph nodes. Receiver operating characteristic (ROC) curve was used to compare the accuracy of the two imaging tests in the diagnosis of pelvic lymph node metastasis in the newly diagnosed untreated group and the endocrine treated group. Results:In this study, of 52 cases, 26 (50.0%) had positive lymph nodes by pathological examination. In this study, a total of 681 lymph nodes were dissected, with 70 lymph nodes (10.28%) being pathologically positive, and the positive rate of 26 patients was 17.99% (70/389). The PET/CT and mpMRI detection rates of 26 node-positive patients were 92.3% (24/26) and 57.7% (15/26), respectively. There were 9 (37.5%) and 17 (60.7%) lymph node positive patients in the untreated group and the endocrine therapy group, respectively. There were 320 and 361 lymph nodes were clear, with 18 (5.6%) and 52 (14.4%) positive lymph nodes, respectively. The detection rates of PET/CT and mpMRI were 88.89% (8/9) and 94.12% (16/17)in the untreated group, and 44.44% (4/9) and 64.71% (11/17)in the endocrine treated group, respectively. In the newly treated group, the area under the curve (AUC) of PET/CT and mpMRI for diagnosing positive lymph nodes were 0.911 and 0.689 ( P=0.027), the sensitivity were 88.9% and 44.4%, and the specificity were 93.3% and 93.3%, respectively. PPV were 88.9% and 80.0%, and NPV were 93.3% and 73.7%, respectively. In the endocrine therapy group, the AUC of PET/CT and mpMRI for lymph node positive diagnosis were 0.834 and 0.596 ( P=0.011), the sensitivity were 94.1% and 64.7%, the specificity were 72.7% and 54.5%, and the PPV were 84.2% and 68.8%, respectively. NPV were 88.9% and 50.0%, respectively. Conclusions:For prostate cancer patients, regardless of whether they receive neoadjuvant endocrine therapy, 68Ga-PSMA-11 PET/CT can accurately detect pelvic lymph node metastasis, and the diagnostic efficacy is significantly better than that of mpMRI.

Abstract: Objective This study aimed to investigate the expression of CD73 in colonic tissues in Crohn's disease (CD) and its significance and possible mechanism of action. Methods Thirty male BALB/c mice were randomly divided into normal control group, model group and intervention group. The control group was fed normally, and the model group was treated with TNBS+40% alcohol enema to establish a mouse model of Crohn's disease induced by chronic inflammation. The intervention group was treated with AB-680 intraperitoneally on the second day of each enema based on the model group. Mice body weight, fecal traits and fecal occult blood were recorded for disease activity index (DAI) score of inflammatory bowel disease. The animals were sacrificed at 7th week, their colonic tissues were removed, weighed and measured. The tissue inflammation was observed by standard hematoxylin-eosin (HE) staining. Masson staining was used to measure the area of collagen in colon tissue of mice. CD73 was detected by fluorescence quantitative PCR and immunohistochemistry. The expression levels of TGF-β, TNF-α and IL-6 in colon tissue of mice were determined by ELISA. Results The DAI score was (0.10±0.16) in the control group, (2.80±0.79) in the model group, and (3.07±0.34) in the intervention group. Compared with the control group, the DAI scores of the model and intervention groups were increased significantly (P<0.05). Compared with the model group, the DAI score of the intervention group was significantly increased (P<0.05). HE staining showed that there was no inflammation in the colon of the control group, while the colon of the model group and the intervention group showed typical inflammatory manifestations such as edema and congestion, inflammatory cell infiltration, and mucosal ulcer. The area ratio of collagen in the control group was (4.95±0.82)%, in the model group was (24.62±1.46)%, and in the intervention group was (54.47±2.75)%. Compared with the control group, the area ratio of collagen in the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the area ratio of collagen in the intervention group was significantly increased (P<0.05). Compared with the control group, the expression of CD73 in colon tissue of the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the expression of CD73 in colon tissue of the intervention group was decreased (P<0.05). Compared with the control group, the expressions of TGF-β, TNF-α and IL-6 in the model group and the intervention group were significantly increased (P<0.05). Compared with the model group, the expression of TGF-β, TNF-α and IL-6 in the intervention group decreased (P<0.05). Conclusions CD73 is upregulated in colon tissue of CD mice, it can inhibit inflammatory reaction and improve fibrosis by up-regulating TGF-β expression. On the other hand, CD73 can aggravate the inflammatory response in CD intestinal inflammation and fibrosis by up-regulating the expression of IL-6 and TNF-α. Therefore, CD73 may play a bidirectional regulatory role in intestinal inflammation and fibrosis of CD.

BACKGROUND/OBJECTIVES: Inonotus obliquus has been used as antidiabetic herb around the world, especially in the Russian and Scandinavian countries. Diabetes is widely believed to be a key factor in Alzheimer’s disease (AD), which is widely considered to be type III diabetes. To investigate whether I. obliquus can also ameliorate AD, it would be interesting to identify new clues for AD treatment. We tested the anti-AD effects of raw Inonotus obliquus polysaccharide (IOP) in a mouse model of AD (3×Tg-AD transgenic mice).MATERIALS/METHODS: SPF-grade 3×Tg-AD mice were randomly divided into three groups (Control, Metformin, and raw IOP groups, n = 5 per group). β-Amyloid deposition in the brain was analyzed using immunohistochemistry for AD characterization. Gene and protein expression of pertinent factors of the ubiquitin-proteasome system (UPS) was determined using real-time quantitative polymerase chain reaction and Western blotting. RESULTS: Raw IOP significantly reduced the accumulation of amyloid aggregates and facilitated UPS activity, resulting in a significant reduction in AD-related symptoms in an AD mouse model. The presence of raw IOP significantly enhanced the expression of ubiquitin, E1, and Parkin (E3) at both the mRNA and protein levels in the mouse hippocampus. The mRNA level of ubiquitin carboxyl-terminal hydrolase isozyme L1, a key factor involved in UPS activation, also increased by approximately 50%. CONCLUSIONS Raw IOP could contribute to AD amelioration via the UPS pathway, which could be considered as a new potential strategy for AD treatment, although we could not exclude other mechanisms involved in counteracting AD processing.

Breast cancer is globally the most common invasive cancer in women and remains one of the leading causes of cancer-related deaths. Surgery, radiotherapy, chemotherapy, immunotherapy, and endocrine therapy are currently the main treatments for this cancer type. However, some breast cancer patients are prone to drug resistance related to chemotherapy or immunotherapy, resulting in limited treatment efficacy. Consequently, traditional Chinese medicinal materials (TCMMs) as natural products have become an attractive source of novel drugs. In this review, we summarized the current knowledge on the active components of animal-derived TCMMs, including Ophiocordycepssinensis-derived cordycepin, the aqueous and ethanolic extracts of O.sinensis, norcantharidin (NCTD), Chansu, bee venom, deer antlers, Ostreagigas, and scorpion venom, with reference to marked anti-breast cancer effects due to regulating cell cycle arrest, proliferation, apoptosis, metastasis, and drug resistance. In future studies, the underlying mechanisms for the antitumor effects of these components need to be further investigated by utilizing multi-omics technologies. Furthermore, large-scale clinical trials are necessary to validate the efficacy of bioactive constituents alone or in combination with chemotherapeutic drugs for breast cancer treatment.
Animals ; Breast Neoplasms/drug therapy* ; Cell Cycle Checkpoints ; China ; Deer ; Female ; Humans ; Immunotherapy

Objective:To compare the assisted-reproduction outcomes of two long-acting gonadotropin-releasing hormone agonists (GnRH-a) in patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) during the long-term early follicular phase. Methods:A retrospective cohort study was conducted in the Reproductive Center of the Second Affiliated Hospital of Wenzhou Medical University from March 1, 2019 to July 31, 2019. A total of 802 patients were divided into leuprorelin acetate group (group A) and triptorelin group (group B) according to the difference of long-acting GnRH-a in the long-term early follicular phase, and the clinical and laboratory outcomes between the two groups were compared.Results:There were no significant differences in age, infertility duration, body mass index (BMI), basic hormone levels, infertility type, sex hormone level on the day of initiation of injection of gonadotropin (Gn), total duration and dosage of Gn used, duration of down-regulation, estradiol level and endometrial thickness on hCG injection day, the number of embryos transferred, clinical outcomes, total treatment cost, and owing to the uneven inner membrane, elevated progesterone, embryo quality problems, individual factors resulting in cancelling the transplant, between the two groups ( P>0.05). However, antral follicle count (AFC) (19.59±7.93), the number of retrieved oocytes (15.39±7.59), fertilized oocytes (11.20±6.53), cleaved oocytes (10.85±6.42), good-quality embryos on Day 3 (3.01±2.66), and blastocysts (5.27±4.02) in group B was larger than that in group A (17.68±7.23, 13.70±6.94, 9.50±5.43, 9.26±5.34, 2.57±2.33, 4.49±3.40) ( P=0.001, P=0.002, P<0.001, P=0.001, P=0.017, P=0.007). The levels of luteinizing hormone (LH) [(0.78±0.64) IU/L] and progesterone [(0.72±0.39) μg/L] on hCG injection day in group A were higher than those in group B [(0.55±0.30) IU/L, (0.64±0.36) μg/L] ( P<0.001, P=0.005). The rate of preventing the occurrence of ovarian hyperstimulation syndrome (OHSS) in group A [28.52% (75/263)] was higher than that in group B [14.95% (16/107), P=0.006]. Conclusion:Two long-acting GnRH-a drugs can achieve satisfactory down-regulation effect, laboratory and clinical outcomes in the long-term early follicular phase. Compared with the triptorelin, leuprolide acetate is relatively mild to pituitary inhibition, with an increasing trend of the clinical pregnancy rate.