Objective Kisspeptin,a protein encoded by the KISS1 gene,functions as an essential factor in suppressing tumor growth.The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway,which assumes a central role in maintaining cellular homeostasis.In the specific context of this investigation,the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization.This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway,aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion(RSA).Methods We enrolled a cohort comprising 45 individuals diagnosed with RSA,who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020.On the other hand,an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included.To comprehensively assess the molecular landscape,Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin(and its gene KISS1),IGFBP1(an established marker of decidualization),Notch1,Akt,and Foxo1 within the decidua.Human endometrial stromal cells(hESC)were given targeted interventions,including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10(the bioactive fragment of kisspeptin),and were subsequently designated as the siKP group or the KP10 group,respectively.A control group comprised hESC was transfected with blank siRNA,and cell proliferation was meticulously evaluated with CCK8 assay.Following in vitro induction for decidualization across the three experimental groups,immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups.Furthermore,RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1,Notch1,Akt,and Foxo1 across the three cell groups.Subsequently,decidualization was induced in hESC by adding inhibitors targeting Notch1,Akt,and Foxo1.The expression profiles of the aforementioned proteins and genes in the four groups were then examined,with hESC induced for decidualization without adding inhibitors serving as the normal control group.To establish murine models of normal pregnancy(NP)and RSA,CBA/J×BALB/c and CBA/J×DBA/2 mice were used.The mice were respectively labeled as the NP model and RSA model.The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234(acting as a blocker)and were designated as RSA-KP10 and NP-KP234 groups.On the other hand,the control groups received intraperitoneal injections of normal saline(NS)and were referred to as RSA-NS and NP-NS groups.Each group comprised 6 mice,and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes.Results The analysis revealed that the expression levels of kisspeptin,IGFBP1,Notch1,Akt,and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP(P<0.01 for kisspeptin and P<0.05 for IGFBP1,Notch1,Akt,and Foxo1).After the introduction of kisspeptin10 to hESC,there was an observed enhancement in decidualization capability.Subsequently,the expression levels of Notch1,Akt,and Foxo1 showed an increase,but they decreased after interference with KISS1.Through immunofluorescence analysis,it was observed that proliferative hESC displayed a slender morphology,but they transitioned to a rounder and larger morphology post-decidualization.Concurrently,the expression of Notch1 increased,suggesting enhanced decidualization upon the administration of kisspeptin10,but the expression decreased after interference with KISS1.Further experimentation involved treating hESC with inhibitors specific to Notch1,Akt,and Foxo1 separately,revealing a regulatory sequence of Notch1/Akt/Foxo1(P<0.05).In comparison to the NS group,NP mice administered with kisspeptin234 exhibited increased fetal absorption rates(P<0.001)and decreased expression of IGFBP1,Notch1,Akt,and Foxo1(P<0.05).Conversely,RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates(P<0.001)and increased expression levels of the aforementioned molecules(P<0.05).Conclusion It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade.A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization,which in turn might contribute to the development or progression of RSA.

Objective:To investigate the diagnostic value of 11C-Pittsburgh compound B (PIB) in patients with mild cognitive impairment (MCI) and Alzheimer′s disease (AD) and explore the factors that may affect the binding of 11C-PIB. Methods:From January 2017 to December 2019, the 11C-PIB uptake of 6 patients with normal cognitive (NC; 3 males, 3 females, age: (64.5±12.3) years), 11 patients with MCI (4 males, 7 females, age: (64.5±9.8) years) and 21 patients with AD (7 males, 14 females, age: (68.1±9.1) years) from Daping Hospital, Army Medical University were retrospectively analyzed. Regional 11C-PIB binding was assessed by using standardized uptake value ratio (SUVR) and visual reading of 11C-PIB scan. Clinical data, including age, gender, education level, cognitive impairment, neuropsychological scale score, vascular risk factors (VRF), apolipoprotein E (ApoE) gene, were collected and differences among groups were analyzed by using one-way analysis of variance, least significant difference t test or Fisher exact test. Factors that affected the 11C-PIB binding were analyzed by multiple linear regression. Results:SUVR of cerebral lobe among NC, MCI and AD groups were significantly different (range of mean SUVR: 1.16-1.26, 1.19-1.35 and 1.40-1.61; F values: 5.331-9.279, all P<0.05). For positive PIB patients, SUVR of posterior cingulate and precuneus were increased in MCI group compared with NC group (1.20±0.15 vs 1.50±0.12, 1.18±0.15 vs 1.59±0.13; F values: 6.389 and 10.668, t values: -2.33 and -3.10, both P<0.05), and there were no significant differences in all lobes between MCI and AD group ( t values: from -1.29 to -0.51, all P>0.05). Visual analysis showed that the positive rates of PIB in frontal lobe (85.7%(18/21)), posterior cingulate (85.7%(18/21)), precuneus (81.0%(17/21)), temporal lobe (81.0%(17/21)) and occipital lobe (47.6%(10/21)) in AD were higher than those in MCI (4/11, 4/11, 4/11, 3/11 and 1/11, respectively; all P<0.05). Multiple linear regression showed that the degree of cognitive impairment were independent risk factors for SUVR of all lobes ( b values: 0.377-0.536, all P<0.05). The ApoE ε4 gene was independent risk factor for SUVR of precuneus ( b=0.290, P<0.05). Conclusion:11C-PIB is helpful for clinical diagnosis of MCI and AD patients and the degree of cognitive impairment and ApoE ε4 gene may be independent risk factors for increasing 11C-PIB binding.

Objective To study the clinical use of microwave scalpel in hepatectomy for hepatocellular carcinoma without hepatic vascular inflow occlusion.Methods A retrospective study was conducted on the clinical data of 126 consecutive patients with hepatocellular carcinoma who were treated at the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University from December 2015 to August 2018.The patients included 111 males and 15 females,with ages which ranged from 25 to 75 years.These patients were divided into two groups by the different surgical resection methods:the microwave scalpel hepatectomy (MSH) group which employed microwave scalpels to perform hepatectomy (n =42),and the ultrasound scalpel hepatectomy (USH) group which employed ultrasound scalpels (n =84).The perioperative conditions which included baseline data,amount of intraoperative bleeding,liver function after operation,and morbidity of postoperative complications were compared.Results There were no significant differences in the preoperative indexes which included tumor diameter,number of tumors,levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) between the 2 groups (all P ＞ 0.05).In the MSH group,the amount of intraoperative bleeding was 100.0 (100.0,200.0) ml,which was significantly lower than the 300.0 (100.0,400.0) ml in the USH group (P ＜ 0.05).Compared with the USH group,the levels of AST and ALT on postoperative day 1,3,7 after operation in the MSH group were significantly lower (all P ＜ 0.05),and the corresponding albumin levels were significantly higher than the USH group (P ＜0.05).The incidence of complications was 4.8％ (2/42) in the MSH group which was significantly lower than that of 20.2％ (17/84) in the USH group (P ＜ 0.05).Conclusion Microwave scalpel significantly reduced intraoperative bleeding and postoperative complications,and led to less liver functional injury.

Objective: To investigate the correlations among striatal dopamine transporter (DAT) distribution, glucose metabolism and Parkinson′s disease (PD) clinical symptoms. Methods: Twenty-five clinically confirmed idiopathic PD patients (17 males, 8 females, age: (59.8±9.2) years) who underwent ¹¹C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and ¹⁸F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed. The detailed clinical scores were systematically collected from all patients. Correlations between DAT distribution, glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis. Results: There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores, non-motor symptoms scale (NMSS) scores, activity of daily living scale (ADL) scores (r values: 0.580, 0.522, 0.557, all P<0.05). The CFT uptake of ipsilateral caudate nucleus, anterior putamen, and posterior putamen were negatively correlated with UPDRS motor scores (r values: -0.496, -0.492, -0.457, all P<0.05), while those had no significant correlations with NMSS scores (r values: -0.420, -0.402, -0.355, all P>0.05). The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values: -0.502, -0.522, both P<0.05). There were no significant correlations between CFT uptake in contralateral striatal, anterior putamen, posterior putamen and PDRP values, UPDRS motor scores, NMSS scores and ADL scores(r values: from -0.466 to -0.129, all P>0.05). The presence of the significant correlations between UPDRS motor scores, ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values: from -0.90 to -0.47, all P<0.05). The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms. The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values: 0.47-0.90, both P<0.01), precentral gyrus and insula (r values: -0.90 to -0.47, all P<0.01). Conclusion The correlations between DAT distribution, glucose metabolism and PD clinical symptoms are complicated, which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms.

Objective To investigate the application value of biological mesh in the pelvic floor reconstruction of extralevator abdominoperineal excision (ELAPE) for advanced low rectal cancer (RC).Methods The retrospective cohort study was conducted.The clinicopathological data of 228 patients with advanced low RC who underwent ELAPE in the Beijing Chaoyang Hospital of Capital Medical University between August 2008 and December 2016 were collected.Of 228 patients,174 using biological mesh closure and 54 using primary closure were respectively allocated into the biological mesh group and primary closure group.Observation indicators:(1)intra-and post-operative situations;(2) postoperative complications (including short-term and long-term complications);(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative long-term complications,tumor recurrence or metastasis and overall survival up to December,2017.Measurement data with normal distribution were represented as（ x） ±s,and comparison between groups was analyzed using the independent-sample t test.Measurement data with skewed distribution were described as M (range),and comparison between groups was analyzed using the nonparametric test.Comparisons of count data were evaluated by the chi-square test or Fisher exact probability.Results (1)Intra-and post-operative situations:all the patients underwent successful ELAPE.The perineal operation time,time of indwelling perineal drainage-tube and hospital expenses were respectively (60 ± 50)minutes,(11.6 ± 2.4) days,(57 781± 11 337) yuan in the biological mesh group and (50±21) minutes,(8.9± 1.7) days,(53 714± 13 395)yuan in the primary closure group,with statistically significant differences between groups (t =3.327,7.691,-2.203,P＜0.05).The total operation time and duration of postoperative hospital stay were respectively (242±53) minutes,(13.0±5.0) days in the biological mesh group and (228±51) minutes,(12.0±5.0) days in the primary closure group,with no statistically significant difference between groups (t =1.701,1.309,P＞0.05).(2) Postoperative complications:26 and 19 patients in the biological mesh group and primary closure group had respectively perineal wound complications (1 patient combined with multiple complications),showing a statistically significant difference between groups (x2 =10.660,P＜0.05).The perineal wound infection,perineal hernia and disruption of perineal wound were respectively detected in 20,6,1 patients in the biological mesh group and 12,7,3 patients in the primary closure group,showing statistically significant differences between groups (x2 =3.931,5.282,P＜0.05).(3) Follow-up and survival situations:174 patients in the biological mesh group were followed up for 64 months (range,13-112 months),and 54 patients in the primary closure group were followed up for 51 months (range,23-76 months).The local recurrence rate,distal metastasis rate and overall survival rate were respectively 5.17％ (9/174),20.11％ (35/174),77.59％ (135/174) in the biological mesh group and 7.41％(4/54),24.07％(13/54),79.63％(43/54) in the primary closure group,with no statistically significant difference between groups (x2 =0.080,0.389,0.101,P＞0.05).Conclusions The biological mesh in the pelvic floor reconstruction of ELAPE for advanced low RC is safe and feasible.Compared with primary closure,biological mesh closure will extend perineal operation time and time of indwelling perineal drainage-tube,and increase hospital expenses,but doesn't affect total operation time and duration of postoperative hospital stay,meanwhile,it can also reduce the overall perineal wound complications,especially in perineal wound infection,perineal hernia and disruption of perineal wound.

Objective To investigate the safety and effectiveness of different intravenous anesthesia methods for pediatric ERCP . Methods Data of 45 children undergoing ERCP at the Affiliated Hangzhou Hospital of Nanjing Medical University from August 2013 to July 2016, including intravenous anesthesia,the procedure of ERCP, adverse reactions and the waking time were retrospectively studied. Results A total of 45 patients in two groups under intravenous anesthesia successfully underwent ERCP . Seventeen patients ( 37. 8%) whose body weights were over 20 kg and the duration of surgery was predicted less than 30 minutes received deep sedation without airway intubation. Twenty?eight patients ( 62. 2%) with an initial weight of less than 20 kg and the duration of surgery was predicted more than 30 minutes received general anesthesia with airway intubation. In patients with deep sedation, the mean time of waking was 7. 2±6. 3 minutes, body movement reaction occurred in 1 case ( 5. 9%) and with transient decreasing of pulse blood oxygen ( beyond 95%) occurred in 2 cases ( 11. 8%) . In patients receiving endotracheal anesthesia with intubation, the mean waking time was 10. 5±8. 7 minutes without adverse reactions associated with anesthesia. Conclusion Both deep sedation and general anesthesia with airway intubation are safe for pediatric ERCP. However, general anesthesia with airway intubation is an ideal method ensuring the airway safety and oxygen supply for children less than 20 kg undergoing first?time ERCP or the duration of surgery lasting over 30 minutes.

Objective To do screening acute lymphoblastic leukemia patients scFv antibody single chain variable region to cre-ate conditions for the expression and obtain further specificity of antibody fragments.Methods In this study,patients with newly diagnosed acute lymphoblastic leukemia serum as coating antigen using phage display technology,screening phage an-tibody specificity from the semi-synthetic human phage antibody libraries,the first to target the immune antigen-coated tab-let,phage library was added,so that with the target antigen-specific binding phage antibody was immobilized on plates immu-nization,could not be specifically bound phages were rinsed.The eluted specific binding phage,E.coli infection.Could get the specific antibody gene containing phagemid.Results After three “adsorption-elution-amplification”screening process,got stronger leukemia patient antigen-specific phage antibody variable region fragment and identification.Conclusion Got better strain affinity antibody fragments,to create the conditions for the next fragment expression,identification and clinical appli-cation.

Objective To explore the feasibility of low-dose chemotherapy (LDCT) combined with tyrosine kinase inhibitor (TKI) (LDCT+TKI regimen) as the first-line induction regimen for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL).Methods The efficacies and adverse effects of various induction regimens in 61 newly diagnosed patients with Ph+ ALL were retrospectively analyzed.Results The complete remission (CR) rate of the first induction therapy was 73.8 ％ (45/61) for all 61 cases,and that of the second induction therapy was 86.7 ％ (13/15) for non-remission (NR) patients after the first induction.The total CR rate for two-course induction was 95.1％ (58/61).Treatment related mortality happened in one case (1.6 ％) after the first induction therapy.The response rates between conventional-dose chemotherapy (CDCT)±TKI group and LDCT±TKI group were not statistically different [without TKI,65.5 ％ (19/29) vs 60.0 ％(3/5),P =0.812;with TKI,90.5 ％ (19/21) vs 100.0 ％ (6/6),P =0.432].The response rate of LDCT+TKI group was not statistically different from that of CDCT alone group (P =0.089).The introduction of TKI to LDCT and CDCT could improve the response rate (CDCT+TKI group,P =0.041;LDCT+TKI group,P =0.087).The total response rate of the induction therapy with TKI was significantly higher than that without TKI [92.6 ％ (25/27) vs 64.7 ％ (22/34),P =0.01].The response rate of the TKI-based second induction therapy for non-CR cases after the first induction therapy without TKI was significantly higher than that after the first induction therapy with TKI [100.0 ％ (8/8) vs 33.3 ％ (1/3),P =0.011].There were no significant differences in the efficacies of the first induction therapy between various genetic subgroups (all P ＞ 0.05),and the introduction of TKI to the treatment of various genetic subgroups could improve the efficacies to a certain extent without statistical significance (all P ＞ 0.05).The incidences of treatment related infections and bleeding due to the first induction therapy in all patients were 50.8 ％ (31/61) and 4.9 ％ (3/61),respectively.Compared with LDCT±TKI group,the overall incidences of treatment related infections and bleeding in CDCT±TKI group were higher,but there were no statistical significances [infection,56.0 ％ (28/50) vs 27.3 ％ (3/11),P =0.084;bleeding,6.0 ％ (5/30) vs 0 (0/1 1),P =0.405].The incidence of treatment related infections in LDCT+TKI group was significantly lower than that in CDCT+TKI group [0 (0/6) vs 71.4 ％ (15/21),P =0.002] or that in CDCT alone group [0 (0/6) vs 44.8 ％ (13/29),P =0.039].The incidence of bleeding in LDCT+TKI group was not statistically different from that in CDCT+TKI group or that in CDCT alone group (all P ＞ 0.05).Conclusion LDCT+TKI regimen as the first-line induction regimen in Ph+-ALL is deserved to be investigated further.

OBJECTIVETo evaluate the laparoscopy combined with transperineal extralevator abdominoperineal excision (TP-ELAPE) for locally advanced low rectal caner.

METHODSClinical data of 12 patients with locally advanced low rectal cancer undergoing laparoscopy combined with TP-ELAPE in our department from May 2013 to March 2015 were retrospectively analyzed. There were 8 male and 4 female patients with median aged of 63 (46 to 72) years. The median distance from tumor lower margin to anal verge was 3.5(2.0 to 4.0) cm. A self-made transanal suit for minimally invasive operation was used to make a sealed lacuna outside the sphincter, thus laparoscope can be applied to perform transperineal operation.

RESULTSAll the patients underwent operations successfully without conversion to open abdominal operation. The median operating time was 206 (180 to 280) minutes with perineal operating time 95(80 to 120) minutes. The median intraoperative blood loss was 120(50 to 200) ml. The median postoperative hospital stay was 12(9 to 18 ) days. Postoperative pathology revealed that all circumferential margins (CRM) were negative. The area of sample horizontal section was (2 824±463) mm(2), and of outer muscularis propria was(2 190±476) mm(2). Postoperative complications included chronic sacrococcygeal region pain in 2 cases, urinary retention in 3 cases, perineal wound infection in 1 case. No perineal seroma, perineal hernia, wound dehiscence and sinus tract formation were observed. Among 8 patients with preoperative normal sexual function, sexual dysfunction occurred in 2 patients. There was no local recurrence and metastasis during a median follow-up of 21(12 to 34) months.

CONCLUSIONLaparoscopy combined with TP-ELAPE has the potential to simplify the operation procedure for low rectal cancer, can ensure the radical treatment and safety of operation, and may be carried out in experienced centers.

Abdomen ; Aged ; Anal Canal ; Blood Loss, Surgical ; Digestive System Surgical Procedures ; methods ; Female ; Humans ; Laparoscopy ; Length of Stay ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Operative Time ; Perineum ; Postoperative Complications ; Postoperative Period ; Rectal Neoplasms ; surgery ; Rectum ; Retrospective Studies

Objective To investigate the effectiveness of Uromentor virtual reality simulator in flexible ureteroscopy training for catechumen.Methods Fifty-one catechumen were selected.After 1 hour training of basic operation in Uromentor virtual reality simulator, all trainees performed special-purpose exercise ( kidney inspection with flexible ureteroscopy ) for 3 hours. Using right kidney inspection, a preliminary assessment for each trainee was made before the special-purpose exercise and data such as total time, number of trauma from the scopes and tools, percentage of kidney surface examined and global rating scale ( GRS ) were recorded.The same assessment was performed once again after the special-purpose exercise ( secondary assessment ) , and data were recorded and compared to the preliminary assessment. Results Each trainee made a significant improvement in flexible ureteroscopic skill after the special-purpose training.The parameters such as total time, number of trauma from the scopes and tools, percentage of kidney surface examined and GRS of all trainees in preliminary assessment were 14.63 ±1.01 min, 8.62 ± 2.67, 51.05%±20.79%and 10.31 ±2.53, respectively;while in secondary assessment, parameters were 7.71 ±1.13 min, 1.67 ±1.23, 98.04% ±5.42% and 29.14 ±3.01, respectively.The differences between the preliminary assessment and the secondary assessment of each parameter were significant ( P<0.01).Conclusions The Uromentor virtual reality simulator can improve the trainee′s skills of flexible ureteroscopy.It is a good instrument of the flexible ureteroscopic training for catechumen.