OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

Prostate cancer is recognized as a malignant tumor intricately linked to metabolic dysregulation, and its association with diabetes is notably complex. In recent years, there has been a surge in the development and clinical application of numerous oral antidiabetic medications, which have yielded promising results. Concurrently, an increasing body of research has uncovered the beneficial roles of these oral antidiabetic medications in the management of prostate cancer. This article provides a comprehensive review of the current research exploring the association between the use of oral antidiabetic medication and the treatment of prostate cancer.

【Objective】 To summarize the key points of robot assisted radical nephrectomy combined with resection of metastatic lymph nodes around inferior vena cava. 【Methods】 The patients undergoing the operation during Jan.2019 and Dec.2021 were analyzed and followed up. The surgical procedures and key points for right renal cancer with huge lymph node metastasis around inferior vena cava were illustrated. 【Results】 A total of 5 patients completed operation successfully, including 4 cases of clear cell carcinoma and 1 case of papillary carcinoma. The average operation time and estimated blood loss were 135 min and 300 mL, respectively, with no major complications. 【Conclusion】 It is feasible to perform robot assisted radical nephrectomy with resection of metastatic lymph nodes for selected patients of renal cancer especially with large lymph node metastasis around vena cava. The value of minimally invasive surgery in the comprehensive treatment of renal cancer deserves further attention and research.

Objective:To evaluate the efficacy of preoperative three-dimensional (3D) image reconstruction combined with intraoperative dynamic ultrasonography (IOUS) in laparoscopic precision hepatectomy for intrahepatic bile duct stones.Methods:The clinical data of 66 patients with intrahepatic bile duct stones undergoing laparoscopic hepatectomy in the First People's Hospital of Fuyang District, Hangzhou from January 2018 to January 2023 were retrospectively analyzed, including 32 males and 34 females, aged (49.6±15.2) years old. Patients were divided into the study group ( n=32), who underwent laparoscopic precision hepatectomy using 3D reconstruction combined with IOUS, and the control group ( n=34), who underwent conventional laparoscopic hepatectomy. Perioperative data including the operation time, intraopera-tive blood loss, total volume of drainage on postoperative day (POD) 3, and the rates of complications were compared between the groups. Serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), liver function indices including total bilirubin (TBil) and alanine aminotransferase (ALT) were monitored preoperatively and on POD 1, 3, 5, and 7. Results:The operation time was shorter in the study group [(178±17) min vs. (189±18) min, t=2.55, P=0.010]. The intraoperative blood loss was reduced in the study group [(218±19) ml vs. (395±21) ml, P<0.001]. The incidence of total volume of drainage >300 ml on POD 3 were comparable between the groups [9.4%(3/32) vs. 14.7%(5/34), P=0.507]. There were no significant differences in preoperative serum level of TBil, ALT, CRP and IL-6 between the groups (all P>0.05). Compared to the control group, serum levels of TBil, ALT and CRP in the study group were decreased on POD 1, 3, 5 and 7, and IL-6 was decreased on POD 1 and 3 (all P<0.05). The occurrences of postoperative bile leakage [9.4% (3/32) vs. 29.4% (10/34)] and liver cutting surface fluid accumulation [12.5% (4/32) vs. 35.3% (12/34)] and the rate of stone retention [3.0% (1/32) vs. 20.6% (7/34)] were lower in the study group (all P<0.05). Conclusion:Preoperative 3D image reconstruction combined with IOUS in laparoscopic precision hepatectomy for intrahepatic bile duct stones could reduce intra-operative blood loss, hepatic inflammatory response, and postoperative complications.

Prostate cancer is the most common malignancy of male genitourinary system, with a high risk of invasion, recurrence and metastasis in its high risk subtype. Neoadjuvant therapy would provide improvement in therapy after radical prostatectomy for high risk prostate cancers. This review would discuss several hot issues of neoadjuvant therapy and radical prostatectomy for high risk prostate cancer.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Many studies have shown that abnormal expression and modification of lamin are closely related to aging.Hutchinson-Gilford progeria syndrome(HGPS)is a rare and severe premature aging disease caused by mutations in the gene encoding nuclear envelope proteins of A-type lamins (LMNA).The pathogenesis of HGPS is similar to the aging process of normal individuals,thus research on HGPS will be helpful for understanding the mechanisms of senescence and developing antiaging drugs.This paper reviews recent advances in lamin and the pathogenesis and treatment of HGPS,in order to provide a reference for further basic and clinical research on HGPS.

Objective: To study laparoscopic ultrasound assisted hepatectomy in treatment of intrahepatic and extrahepatic bile duct stones. Methods: The data of 52 patients with hepatolithiasis who underwent laparoscopic hepatectomy from May 2014 to January 2019 at the Fuyang District First People's Hospital in Hangzhou were analyzed retrospectively. There were 28 men and 24 women. The median age was 56 years. Operative laparoscopic ultrasonography was used to detect the location, size, distribution of stones and their relations to blood vessels. A total of 43 patients underwent anatomic hepatectomy, while 38 patients underwent choledochoscopic stone extraction. A " T" tube was used according to intraoperative conditions. Results: Laparoscopic surgery was successfully carried out in 50 patients, while conversion to open surgery was required in 2 patients because of adhesions and bleeding. Laparoscopic ultrasonography revealed intrahepatic calcifications in 5 patients and choledochoscopy in 2 patients. Postoperative complications included 5 patients who devleoped abdominal abscesses. The operation time was (289.0±132.0) minutes. The intraoperative blood loss was (451.0±256.0) ml. The hospitalization after operation was (12.0±3.0) days. In 52 patients, 4 patients had residual stones and the residual rate was 7.7%. All of them were completely removed by T-tube sinus 8 weeks after operation. Conclusions Laparoscopic ultrasound helped to detect relevant bile ducts containing stones, reduced chance of bleeding in surgery, helped to clarify location and distribution of stones, improved accuracy of diagnosis, and reduced unnecessary hepatectomy by clearly defining intrahepatic bile duct stones intraoperatively. The residual intrahepatic and intrahepatic bile duct stones rates were reduced, and the safety and accuracy of the operations were improved.

Objective To study the safety,efficacy and advantages of enhanced recovery after surgery (ERAS) combined with clinical pathway management in laparoscopic common bile duct exploration and lithotomy (Laparoscopic common bile duct exploration,LCBDE).Methods 78 patients who underwent LCBDE in the Department of Hepatobiliary and Pancreatic Surgery in the First Hospital of Fuyang District in Hangzhou were selected as the non-ERAS group (the control group).76 patients who underwent LCBDE treated with fast track surgery and ERAS clinical pathway management were selected as the ERAS group.The data between the two groups which included the postoperative insulin resistance index,changes in C-reactive protein,duration of postoperative analgesic use and analgesia,timing of first passage of postoperative flatus,postoperative abdominal tube removal,postoperative bile leakage,recurrence of biliary stones,intestinal ileus and other complications.Results All the two groups were discharged home successfully.On preoperative 7 day,the differences on the postoperative insulin resistance index and the levels of C reactive protein were significantly different (P＜0.05).The time to first get out of bed after operation,the postoperative analgesic use,the time to first passage of flatus,the time to postoperative abdominal drainage tube removal,and the time to clamping of the T tube after operation were significantly different (all P＜0.05).The postoperative complications of pulmonary infection,abdominal infection and the incidence of prolonged intestinal ileus were significantly different (all P＜0.05).Conclusions ERAS combined with clinical pathway management reduced postoperative stress reaction and complication rate.The treatment accelerated recovery and shortened hospital stay for patients who underwent LCBDE,which led to good social and economic benefits.

Objective    To clearly define and describe the difference of analgesic actions and side effects between dezocine and parecoxib sodium in video-assisted thoracic surgery (VATS) lobectomy. Methods    Ninety patients underwent thoracotomy (lobectomy) and were hospitalized in the Department of Thoracic Surgery, West China Hospital, Sichuan University between August 2015 and January 2016. Patients were randomly divided into two groups including a parecoxib sodium group (a PG group, 43 patients) and a dezocine group (a DG group, 47 patients). We analyzed the occurrence of side effects in the two groups, as well as other outcomes including visual analogous scores and location of the pain et al. Results    The occurrences of nausea, vomit and abdominal distention in the PG group (9.30%, 2.33%, 13.95%) were significantly lower than those of the DG group (25.53%, 17.02%, 40.43% , P=0.046, P=0.032, P=0.009) in the early period after operation. Pain scores at the postoperative 12 h, 24 h, 48 h and 72 h in the PG group (2.56±0.96, 2.47±0.96, 1.93±0.99, 0.98±1.24) were better than those of the DG group (4.00±1.60, 3.62±1.48, 3.36±1.55, 2.47±1.78, P=0.000, P=0.000, P=0.000, P=0.002). And the same results were found in the postoperative coughing VAS assessment. The mostly reported pain location was the chest drainage, incision site and chest wall in turn. Postoperative pain properties, in turn, were swelling, stabbing pain and numbness. Conclusion    Postoperative pain after VATS lobectomy may be adequately controlled using parecoxib sodium. The low pain scores and decreased adverse effects are achieved.