Objective To investigate the relationship between changes of cholinergic system and memory ability impairment in rats long-term exposed to hypoxia-hypercapnia.Methods Forty-eight SD rats were randomly divided into control group,2 weeks hypoxia-hypercapnia group and 4 weeks hypoxiahypercapnia group.The chronic hypoxia-hypercapnia rat model was set up.The memory ability was assessed by eight-arm radial maze.Morphological changes were observed by the HE staining and Nissl staining.Acetylcholine(ACh) content,choline acetyl-transferase (ChAT) activity and acetyl-cholinesterase (AChE) activity in the hippocampus were detected by spectrophotometry,while expression of α7 neuronal nicotinic acetylcholine receptor (α7 nAChR) protein by Western blot.Results Memory ability,especially the working memory was impaired in rats exposed to chronic hypoxia-hypercapnia.And the memory ability decreased more markedly in four weeks group.Compared with those of normoxic rats,the levels of ACh and the activities of AChE and ChAT in the hippocampus of the two weeks group were significantly decreased (ACh:(58.9 ±2.7) vs (47.4 ±3.2) μg/mg (protein) ; AChE:(0.326 ±0.019) vs (0.247 ±0.020) U/mg (protein) ; ChAT:(127.1 ±8.6) vs (90.4 ±6.9) U/g (tissue wet weight),t =7.674,8.139,9.408,all P ＜ 0.05).Compared with the two weeks group,those changes were more obvious in the four weeks group rats (ACh:(47.4 ±3.2) vs (32.5 ±3.2) μg/mg (protein); AChE:(0.247 ±0.020),(0.170±0.019) U/mg (protein); ChAT:(90.4 ±6.9),(55.6 ±6.0) U/g (tissue wet weight),t =9.279,8.036,10.781,all P ＜ 0.05).Compared with the normoxic rats,the expressions of α7 nAChR protein were significantly decreased in two weeks group rats (t =4.481,P ＜ 0.05).Moreover,the expressions of α7 nAChR protein were significantly decreased in four weeks group rats comparing with the two weeks group (t =4.965,P ＜ 0.05).Conclusions An impairment of rat' s memory ability may be induced by hypoxia-hypercapnia,and the injury degree is correlated with the exposure time.Cholinergic system dysfunctions may contribute to the memory function defects in chronic hypoxia-hypercapnia rats.

Objective To systematically evaluate the efficacy and safety of duloxetine and sertraline for Chinese depression patients.Methods The randomized controlled trials(RCTs)comparing the efficacy and safety of duloxetine and sertraline in the treatment of depression were retrieved from databases and the quality of literature was evaluated.Meta-analysis was performed with the software Revman 5.2.Results Eighteen RCTs involving 1 557 Chinese depression patients were included.The results of Meta-analysis showed that there were no significant differences in efficacy and cure rate between duloxetine and sertraline groups(OR=1.28, 95%CI:0.94 -1.73, P =0.11; OR =1.25,95%CI:0.97 -1.62,P =0.09, respectively).The Hamilton Depression Scale(HAMD)scores were significantly lower in duloxetine group than those in sertraline group at 1,2 weeks after treatment;however,there were no significant differences at 8-weeks after treatment between duloxetine and sertraline groups.The score of Medical Outcomes Study Pain Measures(MOSPM)in duloxetine group was significantly lower than that in sertraline group(P<0.01). The rate of insomnia in duloxetine group was significantly lower than that in sertraline group(RR=0.57, 95%CI:0.32 -1.00, P=0.04).There were no significant differences in other common side reactions between the two groups(P>0.05).Conclusions Duloxetine has similar long term treatment effect as sertraline,but it has a rapid-action profile.Duloxetine is more effective than sertraline in depression with painful physical symptoms;besides,duloxetine is less likely to induce insomnia.

Objective To investigate the safety and efficacy of embolization of inferior phrenic artery as nonbronchial systemic artery(NBSA) for hemoptysis.Methods Imaging and clinical data of 1 1 patients with inferior phrenic artery as NBSA were analyzed retrospectively, and complications and hemoptysis recurrence rate were recorded.Results Seven patients underwent enhanced CT examination and 4 patients underwent plain CT examination before embolization.Six of those patients who underwent enhanced CT examination were found abnormal arteries,and were confirmed as NBSA by angiography.The other 5 patients were found unmatch of lesion distribution and bronchial arteries during procedure,and inferior phrenic artery as NBSA were found by expanding angiography.All procedure were successfully performed,3 cases occurred hiccup and need not treatment.No serious complications occurred,such as incontinence and paraplegia.During (1 8.7 ± 1 3.8)months follow-up,only 1 patient recurrence of hemoptysis,and successful after conservative treatment,and the other 10 patients had no recurrence of hemoptysis.Conclusion The inferior phrenic artery as NBSA can induce hemoptysis.It is safe to embolization of the inferior phrenic artery,which can reduce the recurrent rate of hemoptysis.

Purpose To investigate the clinicopathological and molecular genetic features of oncocytic carcinoma of the thy-roid(OCA).Methods The clinicopathological and immuno-histochemical data of 25 patients with oncocytic carcinoma of the thyroid were retrospectively reviewed.Genetic features were determined by fluorescence quantitative PCR.Results The male to female ratio of the 25 patients was 1 ∶ 1.8,and the aver-age age was 49 years.The tumor was confined to the thyroid gland.Of the 22 cases with a single nodule,5 cases were ill-de-marcated and 3 cases were multiple nodular lesions.The average size was 2.7 centimeter in diameter.Cytologically,the tumor cells were arranged in detached clusters with abundant eosino-philic and granular cytoplasm and hyperchromatic nuclei with prominent nucleoli.Histologically,the oncocytic tumor cells mainly arranged in trabecular and solid architecture.Capsular,blood and lymphoid vascular invasion could be observed in a cer-tain extent.Among 25 cases of OCA,8 cases were minimally in-vasive,14 cases were encapsulated angio-invasive and 3 cases were widely invasive.Positive immunoreaction with TTF-1,thy-roglobulin and CD56 supported the thyroid epithelial origination of the tumour.One recurrent case was found to have cervical lymph node metastasis,and another case was presented with bone metastasis,which was determined to harbor TERT promoter mu-tation(C228T)in each case.Different point mutation of RAS gene was determined in 2 cases(8%),respectively.Conclu-sion Oncocytic carcinoma of the thyroid shows typical eosino-philic and granular cytoplasm,immunohistochemical staining is helpful in differential diagnosis with other oncocytic lesions.It lacks BRAF-like mutation.Low frequency of RAS mutations could be found.Rare TERT promoter mutation has significant mutation with clinical behavior of OCA.

Objective:To summarize the thoracic and abdominal CT presentations after endoscopic full-thickness resection (EFR) and to analyze its significance in the evaluation and management of postoperative complications.Methods:Data of 82 patients who underwent gastrointestinal EFR at the Endoscopy Center of Zhongshan Hospital, Fudan University and received a chest and/or abdominal CT within 1 week from September 2016 to September 2021 were collected retrospectively. The patients were divided into the intervention group ( n=38) and the control group ( n=44) according to the presence or absence of special postoperative interventions or prolonged hospital stays. The differences in the incidence of abnormal CT presentations between the two groups were analyzed. Risk factors for abnormal CT presentation were explored by multifactorial analysis. Results:Among the 82 patients, the main CT presentations were pneumoperitoneum in 51 patients (62.2%), abdominal and pelvic effusion in 30 patients (36.6%), pneumothorax in 5 (6.1%), pleural effusion in 43 (52.4%), and pulmonary inflammation in 16 (19.5%). The incidence of pelvic and abdominal effusions ( W=637.48, P=0.031) and pleural effusions ( W=622.06, P=0.031) in CT was higher in the intervention group than that in the control group. Age was an independent risk factor for air-related complications after EFR (>60 years old VS ≤60 years old: OR=0.17, 95% CI: 0.05-0.56, P=0.002). Conclusion:CT presentations of pelvic and abdominal effusion and pleural effusion after EFR is of great significance in suggesting complications, while patients with other CT presentations often do not require special intervention or prolonged hospital stay. Postoperative CT in elderly patients is less likely to detect air-related complications.

Objective:To evaluate the feasibility and clinical efficiency of robot-assisted laparoscopic radical prostatectomy (RARP) via extraperitoneal PORT-free single incision approach.Methods:The data of 33 patients with prostate cancer underwent the extraperitoneal PORT-free single incision RARP from November 2020 to January 2021 in Sichuan Provincial People's Hospital was retrospectively reviewed. The average age was 66.7 (58-78) years, the median PSA was 20.77 (2.89, 56.44) ng/m, and the mean Gleason score was 7.0 (6.0-9.0). The mean prostate volume was 48.4 (25.0-220.0) ml. Clinical stage: 32 cases was in cT 2a-2cN 0M 0, 1 case in cT 3aN 0M 0. 16 cases had a history of operation. All 33 operations were performed by the same operator. All operations were performed by extraperitoneal PORT-free single-incision approach. The surgical condition, postoperative complication, pathology, and follow-up results were observed. Results:In this study, 33 operations were successfully completed without conversion to open or additional single hole channel instruments. The average operation time was 61.3 (38.0-120.0) min, with the mean intraoperative bleeding volume of 72.2 (45.0-220.0) ml and the mean bladder neck urethral anastomosis time of 11.7 (8.5-15.7) min. The mean postoperative hospital stay was 7.9 (6.0-15.0) d, the mean postoperative indwelling time of urinary catheter was 6.8 (6.0-14.0) d, and the mean postoperative evacuation time was 1.0 (0.5-3.0) d. The average incision length was 5.2 (4.6-5.8) cm. There was no obvious complications. The postoperative pathological stage: 21 cases were in < pT 3a, 12 cases were in ≥ pT 3a, and 6 cases (18.8%) had positive resection margin. 29 cases (88.9%) acquired satisfactory urinary continence after operation, and the frequency of urinary pad use was ≤ 1 tablet/day. Conclusions:The extraperitoneal single-incision RARP surgical channel without PORT is safe and feasible with a satisfying cosmetic effect, which saves costs and requires less specific channel device. Simultaneously, the new approach has strong replicability, short-term tumor control and urinary control effect with rapid postoperative recovery. However, the sample size of this study is relatively small, which needs further research and demonstration

Abstract: To investigate the effect of capsaicin on retinal vascular permeability in diabetic rats(DM). Methods: 24 eight-week-old male sprague-dawley(SD) rats were randomly categorized into four groups(n=6): control group(NC), diabetic group(DM), diabetic group with 3 mg/kg capsaicin treatment(CAP3) and diabetic group with 6 mg/kg capsaicin treatment(CAP6). Type 2 diabetic rat(T2 DM) model was established by high-fat diet combined with small-dose streptozotocin(STZ)induction. The body weight and fasting blood glucose in 4 groups were monitored. Total cholesterol(TC), triglycerides(TG), low density lipoprotein(LDL), high density lipoprotein(HDL) concentrations in serum were detected according to manufacturer′s instructions. Evans blue angiography was used to observe the changes of retinal vascular permeability.Immunofluorescence was used to measure the distribution and expression of transient receptor potential vanillic 1(TRPV1) in retina. Western blot was used to detect the expression of TRPV1, vascular endothelial growth factor(VEGF) and occludin in rat retina. Results: Compared with the DM group, serum total cholesterol(TC), triglyceride(TG) and low density lipoprotein(LDL) levels in the CAP3 and CAP6 groups significantly decreased(P<0.01). The results of angiography showed that the retinal vascular permeability increased in the DM group and that there were many strong fluorescent leakage areas, while the leakage was reduced in CAP3 and CAP6 groups. In CAP3 and CAP6 groups, immunofluorescence showed the activation of TRPV1 in the retinal ganglion cell layer, inner nuclear layer and outer nuclear layer. Western blot indicated that the expression of TRPV1 and occludin increased while the expression of VEGF decreased(P<0.01). Conclusion Capsaicin may exert the effect of improving diabetic retinopathy, underlying which the mechanism may be that capscicin activates retinal TRPV1, resulting in the downregulation of VEGF and upregulation of occuldin.

Objective : To evaluate the effect of maternal hypothyroidism on lipid metabolism in the early life of emale offspring by constructing a murine model during pregnancy． Methods : Female mice C57BL /6J were ran- domly divided into normal control group ( NC0 ) ，hypothyroidism complicated with pregnancy group ( PH0 ) and pregnancy complicated with hypothyroidism group ( GH0) ．Firstly，PH0 group was given 0．15% propylthiouracil di- et for 28 days，while NC0 and GH0 groups were given normal diet．After the successful modeling of PH0 was con- firmed，female mice in GH0 and PH0 groups were given 0．15% propylthiouracil diet during pregnancy，and NC0 group was still given normal diet．After delivery，the levels of free triiodothyronine ( FT3) ，free thyroxine ( FT4) ， thyroid stimulating hormone (TSH) and total cholesterol (TC) ，triglyceride (TG) in each group were detected at 3 weeks of age for female offspring．The pathological changes of thyroid and liver were observed by HE staining．West- ern blot detected the levels of proteins associated with lipid metabolism. Results : Compared with the NC0 group， the levels of serum FT3 and FT4 decreased，the levels of serum TSH，serum TC，hepatic TC and TG increased in the female offspring of the PH0 and GH0 groups，and lipid deposition was observed in their livers．The expression levels of HMGCR , FAS and CD36 related to lipid metabolism in livers increased，while the expressions of CPT1A and LDL-R were down-regulated. Conclusion Hypothyroidism during pregnancy may lead to the disturbance of lipid metabolism in the early life of female offspring mice.

Objective : To investigate the effect and mechanism of celecoxib on retinal vascular endothelial growth factor(VEGF) in rats with diabetic retinopathy. Methods : Forty - five SD rats were divided into normal control group (NC) , diabetic retinopathy group (DR) , celecoxib intervention diabetic retinopathy group ( DR + C) . The diabetic model was established by intraperitoneal injection of 1% STZ. After one month , celecoxib (50 mg/kg) was given intragastric administration (1/day) in the DR + C group. Two months later, serum total cholesterol (TC) and insulin were detected. The histopathological changes of the retina were observed. The expression of junctional adhesion molecule⁃like protein (JAML) , VEGF and their signal pathway proteins and the distributions of interleukin⁃10 (IL⁃10) , vascular cell adhesion molecules⁃1(VCAM⁃1) were detected by Western blot. HUVEC cells were divided into normal glucose group (NG) , high glucose group (HG) and high glucose plus celecoxib group (HG + C) to detect the expression of the above proteins. Results : Compared with DR , retina in DR + C group was thinner. The retina in the DR + C group was thicker than that in the NC group. The levels of retinal JAML ,phosphatidylinositol kinase3(PI3K), phosphorylphosphatidylinositol kinase3(P⁃PI3K) , hypoxia⁃inducible factor1 ⁃α (HIF1 ⁃α ) , and VEGF in DR + C group were lower than those in DR group ,while higher than those in NC group. The expression of retinal IL⁃10 and VCAM⁃1 decreased . The content of TC in DR + C and DR group was higher than those in NC group (P < 0. 01) , while the content of insulin in DR + C and DR group was lower than thlse in NC group (P < 0. 001) . Compared with HG group , the expressions of JAML , PI3K , P ⁃PI3K , HIF1 ⁃α , VEGF in HG + C group decreased , but was higher than those in NG group. There was no significant difference in PI3K among the three groups. Conclusion Celecoxib can decrease the expression of VEGF , IL⁃10 , VCAM⁃1 in retina of DR rats , which may be related to the PI3K/HIF1 ⁃α signaling pathway mediated by JAML.

Objective:To investigate the clinicopathological characteristics of giant cell tumor of bone (GCTB) in children.Methods:A total of 35 cases of GCTB diagnosed at Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiaotong University School from 2016 to 2023 were collected, and a retrospective analysis of clinicopathological features and imaging findings was conducted.Results:Pediatric GCTB accounted for approximately 4.6% of total GCTB cases during the study period. There were 11 males and 24 females. The onset age ranged from 9 to 18 years (mean age 15 years, median age 16 years), with 8 cases (8/35, 22.9%) experiencing postoperative recurrence. Twenty-eight cases (28/35, 80%) primarily affected long bones, while 7 cases involved small or irregular bones. Imaging revealed osteolytic changes as the predominant feature, with 3 cases exhibited open physis, one of which had the tumor primarily at the diaphysis without crossing the physis. Histologically, pediatric GCTB resembled adult cases, characterized by mononuclear cells and osteoclast-like giant cells. Seven cases with denosumab treatment demonstrated degrees of giant cell disappearance, increased fibrous tissue and reactive bone proliferation in the stroma. One case was diagnosed as pediatric multicentric GCTB, and three cases as pediatric primary malignant GCTB, with malignant transformation into osteosarcoma. In all 35 cases, mutations in the H3F3A gene were identified, comprising 32 cases with H3.3 p.G34W mutations, one case with H3.3 p.G34V mutation, and 2 cases with H3.3 p.G34L mutations. Notably, the former two categories were successfully validated at the protein level through immunohistochemical staining, utilizing highly specific antibodies tailored for these mutation types: H3.3 p.G34W antibody and H3.3 p.G34V antibody. However, immunohistochemical staining was not available for the last category.Conclusions:Pediatric GCTB predominantly affects females and occurs primarily in long bones, mainly around the knee joint, the majority of tumors predominantly arise in the epiphysis and extend into the metaphysis; however, in cases where the epiphyseal plates are still unclosed, the tumors may be restricted to the metaphysis. Detection of H3F3A gene mutation is crucial for the diagnosis and differential diagnosis of pediatric GCTB.