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.

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 systematically evaluate the efficacy and safety of different administration methods of recombinant human endostatin(Endostatin)in the treatment of malignant pleural effusion in non-small cell lung cancer(NSCLC),and to provide more evidence-based bases for the clinical standardization of the use of Endostatin beyond the drug specification.Methods PubMed,The Cochrane Library,Web of Science,Embase,ChiCTR,VIP,CNKI,WanFang,and SinoMed databases were searched by computer for randomized controlled trials(RCT)of Endostatin alone or combined with chemotherapy for malignant pleural effusion in NSCLC.Network Meta-analysis was performed using Stata 14.0 software.Results A total of 50 RCTs involving 3 429 patients were included,covering 5 intervention measures.Network Meta-analysis showed that in terms of clinical effectiveness,there was no statistically significant difference between Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and Endostatin(intravenous drip)+chemotherapeutic drug(thoracic perfusion or intravenous drip),and Endostatin(thoracic perfusion)and chemotherapeutic drug(thoracic perfusion)(P＞0.05);there were statistically differences between Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and Endostatin(thoracic perfusion)[OR=3.44,95％CI(2.29,4.50),P＜0.05],and Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and chemotherapeutic drug(thoracic perfusion)[OR=3.78,95％CI(3.16,4.51),P＜0.05](P＜0.05).The surface under the cumulative ranking curve(SUCRA)showed that Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)＞Endostatin(intravenous drip)+chemotherapeutic drug(thoracic perfusion or intravenous drip)＞Endostatin(thoracic perfusion)＞chemotherapeutic drug(thoracic perfusion)＞chemotherapeutic drug(intravenous drip).In terms of adverse effects,such as gastrointestinal reaction,and reduction of white blood cells and platelets,there was no statistically significant difference among the different interventions(P＞0.05).Conclusion Endostatin either by pleural instillation or combined with first-line chemotherapy drugs significantly improves clinical efficacy in malignant pleural effusion in NSCLC,and it is better and safer with thoracic perfusion efficacy.

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.

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.