Objective To investigate the inhibitive effects of viral protein r (Vpr) of human immunodeficiency virus 1 ( HIV-1 ) on human colorectal cancer cell line HCT-8,and to find the possible mechanisms.Methods The HCT-8 cells were divided into the control group,adv group and adv-Vpr group.HCT-8 cells were not treated in the control group; HCT-8 cells were treated with Adv or Adv-Vpr at different multiplicity of infection (MOI) in the Adv group or Adv-Vpr group,respectively.Cell proliferation was detected by MTT assay.Cell cycle,apoptosis and mitochondrial membrane potential were detected by flow cytometry.The expression of apoptosisrelated proteins was detected by Western blot.All data were analyzed by using the q test,t test and one-way or two-way analysis of variance.Results The proliferation of HCT-8 cells was significantly inhibited by Vpr.The MTT value of HCT- 8 cells in the Adv-Vpr group was 1.03 ± 0.04,which was significantly lower than 2.46 ± 0.15 in the Adv group and 2.51 ± 0.14 in the control group at 72 hours after Adv-Vpr transfection ( MOI =200) ( F =144.6,P ＜ 0.05).The ratio of HCT-8 cells in the G2/M phase was 37.31％ ± 5.90％ in the Adv-Vpr group,which was significantly higher than 18.30％ ± 6.04％ in the Adv group and 16.66％ ± 3.51％ in the control group ( F =10.08,P ＜ 0.05 ).The ratio of HCT-8 cells with decreased mitochondrial membrane potential was 32.07％ ±5.64％ in the Adv-Vpr group,which was significantly higher than 3.32％ ±0.79％ in the Adv group and 2.76％ ±1.43 ％ in the control group at 48 hours after Adv-Vpr transfection ( MOI =200) ( F =64.45,P ＜ 0.05).The apoptosis rate of HCT-8 cells was 37.62％ ±6.48％ in the Adv-Vpr group,which was significantly higher than 3.44％ ± 1.11％ in the Adv group and 2.93％ ± 1.07％ in the control group at 72 hours after Adv-Vpr transfection ( MOI =200) ( F =122.4,P ＜ 0.05 ).The results of Western blot showed that Vpr induced cleavage and activation of Caspase-9 and Caspase-3 and phosphorylation of Chk1-S345,while the expression levels of Fas,Fas-L,ERK1,ERK2 remained the same at 48 hours after Adv-Vpr treatment ( MOI =200).Conclusions Vpr inhibits the proliferation of the HCT-8 cells in vitro through G2/M phase arrest and apoptosis.Vpr plays its role by activating DNA damaging pathway and initiating mitochondria apoptotic pathway.Vpr is a potential therapeutic agent for colorectal cancer.

Objective To evaluate the effectiveness and indications of a new minimally invasive surgical procedure,the tension-free vaginal tape-SECUR (TVT-S),in the treatment of female stress urinary incontinence (SUI). Methods Twenty-seven consecutive women with stress urinary incontinence underwent the procedure under local anesthesia.The mean age of the study group was 51 (range 25-69)years,average disease duration was 7 (1-20) years.In one case,repair of pelvic floor defects had been made previously.According to the pelvic organ prolapse quantitive(POP-Q) (American College of Obstetrics and Gynecology),the Aa＞-1 cm.Swab tests have shown that the angle of urethra Was greater than 60 degrees,while the evaluation of clinical symptoms were grade Ⅱ.The urodynamie test preoperatively of 27 cases display that bladder compliance was normal,mean maximum urethral closure pressure was 40cm H2O(25-60 cm H2O),and VLPP was greater than 60 cm H2O.Minimum follow up was three months (range 3-15 months).The pre-operative maximal urethral cloSHre pressure (MUCP) of all patients was above 30 cm H2O.Ninety-six percent of patients had pure USI,one patient had mixed urodynamic incontinence (MUI).Collection of the data included operative time a well as pre-and post-operative complications.Patients were post-operatively assessed by a validated urinary incontinence-specific measure of Quality of Life (QoL) questionnaire which was completed by all patients at least three months after surgery. Results All patients who underwent the procedure were under local anesthesia.Of these patients,4 cases (MUCP＜30 cm H2O) underwent TVT-S with U position while the other 23 underwent TVT-S with Hammock position.The mean operation time was 8 minutes (range 6-15 min) and blood loss during operation was about 10 ml.There were no urethral and bladder injuries during the procedure.Postoperative indwelling duration was 0-1 day.After follow-up,26 patients were cured without pad usage and 1 with mixed UI had prominent improvement in urgency incontinence symptoms.The quality of life was also improved significantly.93 % patients were satisfied with the postoperative improvement in urinary incontinence symptoms,and the more severe preoperative symptoms the higher satisfaction rate postoperatively. Conclusions TVT-S iS a safe,effective and minimally invasive procedure for SUI with less complication.The patients with normal bladder compliance and MUCP,urethral hypermobility are indicated for this surgery,some elderly patients or patients with low urethral pressure were proposed to undergo U position TVT-S or TVT.

AIM: Cystostomy is the traditionary method for detecting urodynamic indexes in mice, which de-stroys the continuity of the bladder, and there are significant differences between this method and the clinically used trans-urethral method.This study aims to develop an appropriate urethral catheter to investigate the advantages and application val-ue of transurethral method for urodynamic test.METHODS:A pediatric intravenous catheter was used for urethral catheter-ization on 8 female mice, and linked to connect the catheter to baroreceptor and micropump.The epidural catheter was also used as manometry tube.RESULTS:Using this method, the following urodynamic indicators has been successfully cap-tured:basal bladder pressure (BBP), bladder leak point pressure (BLPP), maximum voiding pressure (MVP), maxi-mum bladder capacity ( MBC ) , post-void residual urine volume ( PVR ) , voiding volume ( VV ) , efficiency of voiding ( EV) and bladder compliance ( BC) .CONCLUSION:This is the first successful simulation used in human body to a-chieve mouse urodynamic testing through the urethra catheter, which avoids the impact of cystostomy on urodynamics in mice, and the mice are able to keep long-term survival after tests for the follow-up molecular and genetic experiments.

Objective To study the feasibility and results of laparoscopic surgery for cholelithiasis in elderly patients over 80 years old.Methods A retrospective study was conducted on 53 patients over 80 years old who underwent laparoscopic surgery for cholelithiasis from January 2015 to April 2017.Results The operation was successfully carried out on 53 patients.The intraoperative blood loss was 5 ～ 300 ml.The operation time was (93.5 ±41.2) minutes and the postoperative hospital stay was (11.0 ± 3.7) days.Postperative complications included bile leakage (n =5),intra-abdominal infection (n =1),pulmonary infection (n =5),wound seroma (n =2).There were no perioperative deaths.Conclusion Laparoscopic surgery for cholelithiasis was safe and efficacious in elderly patients over 80 years old.

Objective:To compare and explore the clinical efficacy and safety of endoscopic thyroidectomy by gasless unilateral axillary approach for the treatment of papillary thyroid microcar cinoma (PTMC) .Methods:One hundred and ten patients with unilateral PTMC admitted to the Department of Thyroid and Breast Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, from Jan.3 2019 to Mar. 2022 were used as clinical study subjects, and according to the patients' choice of surgical modality, they were divided into 30 cases in the endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) group and 80 cases in the minimally invasive video-assisted thyroidectomy (MIVAT) group. We retrospectively compared and analyzed the differences in the surgery-related indexes, aesthetic satisfaction rate at 3 months postoperatively and functional status of the anterior cervical region between the 2 groups. SPSS 26.0 statistical software was used to process the data, analyze and draw conclusions. P<0.05 was considered a statistically significant difference. Results:The number of lymph nodes cleared in the study group (6.60±4.41) was less than that in the control group (9.63±6.25) ( P<0.05) ; the total operative time (169.83±28.76) min, postoperative drainage (173.60±94.33) ml, and time to remove drainage tubes after surgery (5.73±1.86 ) d was significantly higher than the total operative time (145.56±33.89) min, postoperative drainage (107.28±53.82) ml, and time to remove drainage tubes after surgery (2.88±1.07) d in the control group ( P<0.01) ;the intraoperative bleeding, number of positive lymph nodes, and postoperative hospital stay were not statistically significant between the two groups ( P>0.05) .The aesthetic satisfaction rate of the study group had a significant advantage over the control group (90% vs 70%) ( P<0.01) .Comparing the functional status of the anterior cervical region between the two groups after surgery,the occurrence of swallowing discomfort or with pulling sensation was better in the study group than in the control group 1 week after surgery ( P<0.05), and there was no statistically significant difference between the two groups in the occurrence of neck pain score, abnormal sensory function (neck pressure, foreign body sensation, numbness and pins and needles) and vocal difficulty ( P>0.05) ; 3 months after surgery, abnormal sensory function of the neck in the study group (at 3 months postoperatively, the occurrence of abnormal neck sensory function (neck pressure, foreign body sensation, numbness and pins and needles sensation) and swallowing discomfort or pulling sensation were better in the study group than those in the control group ( P<0.05). There were no signs of local recurrence or distant metastasis in both groups at follow-up to date. Conclusions:Both minimally endoscopic thyroidectomy procedures were safe, feasible, and effective in the treatment of unilateral PTMC. Among them, the ETGUA is more suitable for patients with strong cosmetic needs within the indications because of its concealed incision and its ability to protect the function of the anterior cervical region, and can be the preferred option.

Objective:To evaluate the efficacy and safety of peroral endoscopic myotomy (POEM) in achalasia of cardia (AC) patients with the long course.Methods:A total of 159 AC patients who received POEM from January 2015 to March 2022 in the First Affiliated Hospital of Soochow University were divided into the long course group (≥10 years) and the non-long course group (<10 years). The baseline information, POEM procedure and postoperative recurrence were compared and the differences between the recurrent patients and non-recurrent patients in the long course group were explored.Results:The age (57.09±14.30 years VS 42.08±15.68 years, t=5.569, P<0.001), the rate of treatment history [28.9% (13/45) VS 9.6% (11/114), χ2=9.319, P=0.020], the proportion of Henderson grade Ⅲ esophagus [17.8% (8/45) VS 6.1% (7/114), χ2=7.020, P=0.030] in the long course group were significantly higher than those in the non-long course group. The recurrence rate in the long course group was significantly higher than that in the non-long course group [33.3% (15/45) VS 14.9% (17/114), χ2=6.811, P=0.009]. In the long course group, the age (62.50 ± 16.94 years VS 53.77 ± 12.95 years, t=-2.121, P=0.040), and the rate of treatment history [53.3% (8/15) VS 16.7% (5/30), χ2=6.544, P=0.016] in the recurrent patients were higher than those in the non-recurrent patients. Conclusion:POEM is safe and effective for long-course AC patients. In patients with the long course, the aged patients with previous treatment are more likely to relapse.

Lysine specific demethylase 1 (LSD1), a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9, has become a potential therapeutic target for cancer therapy. LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation, invasion, migration, and differentiation. Recent research has focused on the exploration of its pharmacological inhibitors. Natural products are a major source of compounds with abundant scaffold diversity and structural complexity, which have made a major contribution to drug discovery, particularly anticancer agents. In this review, we briefly highlight recent advances in natural LSD1 inhibitors over the past decade. We present a comprehensive review on their discovery and identification process, natural plant sources, chemical structures, anticancer effects, and structure-activity relationships, and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.
Antineoplastic Agents/therapeutic use* ; Enzyme Inhibitors/therapeutic use* ; Histone Demethylases/metabolism* ; Humans ; Lysine/therapeutic use* ; Neoplasms/drug therapy*