Safety analysis of definitive surgery for chronic radiation intestinal injury / 中华胃肠外科杂志

Objective: To investigate the safety of definitive surgery for chronic radiation intestinal injury. Methods: A descriptive case series study was performed. Clinical data of 105 patients who were diagnosed as chronic radiation intestinal injury, had complete data and received definitive surgery (the radiation-induced intestinal segment and digestive tract reconstruction) at Department of Gastrointestinal Surgery of Beijing Tsinghua Changgung Hospital from June 2016 to May 2020 were retrospectively analyzed. There were 30 males (28.6%) and 75 females (71.4%) with the median age of 58 years (P25, P75: 52, 64 years). Patients who had tumor recurrence or refused surgical treatment were excluded. According to the preoperative evaluation and clinical manifestations, to select the resection range. Outcome parameters: (1) preoperative evaluation (nutrition risk assessment and status of obstruction or fistula); (2) clinical manifestations and treatment strategies; (3) details of surgical parameters; (4) postoperative complications, and Clavien-Dindo classification III to V was defined as main moderate-severe complication. Results: (1) Preoperative evaluation: Eighty-eight patients (83.8%) developed symptoms of chronic radiation intestinal injury more than 1 year after the end of radiotherapy. Ninety-eight patients (93.3%) had preoperative NRS-2002 score ≥3, 74 patients (70.5%) received preoperative parenteral nutritional support, and the median time of nutritional support was 10.5 (7.0, 16.0) days. Sixteen patients (15.2%) received small intestinal decompression tube implantation due to severe obstruction. (2) Clinical manifestations and treatment strategies: Among 105 patients, 87 (82.9%) presented with obstruction and received definitive resection of the radiation-induced intestinal segment plus one-stage digestive tract reconstruction; 18 (17.1%) presented with intestinal fistula and all of them received definitive resection of the radiation-induced intestinal segment, intestinal fistula plus one-stage digestive tract reconstruction. Among above 18 patients with fistula, 3 patients with ileorectal stump fistula received pedicled pelvic closure of greater omentum at the same time; 4 patients had ileal vesical fistula, of whom 2 patients received cystectomy and bladder repair due to preoperative nephrostomy decompression, and the other 2 patients received transection of the small intestine proximal and distal to the fistula and anastomosis of the intestinal loop without fistula resection, intestinal fistula or bladder fistula repair. (3) The details of surgical parameters: Median operative time and intraoperative blood loss was 230 (180, 300) minutes and 50 (20, 50) ml respectively. Ninety-two patients (92/105, 87.6%) underwent ileocolonic anastomosis, and anastomosis on the hepatic flexure or splenic flexure colon were performed in 88 (83.8%) and 4 (3.8%) patients respectively. Ileoileal anastomosis was performed in 13 patients (12.4%). The anastomotic site of 92 patients (87.6%) was strictly located in the contralateral quadrant of the radiation field, and the anastomotic site of 13 patients (12.4%) was far from the radiation field. Nine patients (8.6%) had more than one anastomosis, 5 patients (4.8%) had less than 180 cm of residual small intestine, 7 patients (6.7%) underwent retrograde intestinal permutation, 4 patients (3.8%) underwent abdominal wall reconstruction surgery due to abdominal wall defects, and 87 patients (82.9%) had severe abdominal pelvic adhesions (grade 3-4 adhesions). Intraoperative complications occurred in 3 patients (2.9%), which were found in time and handled properly. The median postoperative hospital stay was 13.0 (12.0, 24.5) days, and all the patients had resumed oral feeding upon discharge. (4) Postoperative complications: Fourteen patients (13.3%) had 18 major complications (grade III to V). The incidence of postoperative anastomotic leakage was 5.7% (6/105), and the incidence of anastomotic leakage for ileocolon anastomosis and ileoileal anastomosis was 2.2% (2/92) and 4/13, respectively (χ(2)=17.29, P<0.001). The incidence of postoperative anastomotic leakage of intestinal fistula and intestinal obstruction was 3/18 and 3.4% (3/87), respectively (χ(2)=4.84, P=0.028). The mortality at 30 days after operation was 1.0% (1/105), after abdominal infection and septic shock caused by postoperative anastomotic leakage resulting in multiple organ failure. Conclusion: For chronic radiation intestinal injury patients with obstruction or fistula, definitive surgical treatment is feasible and safe with acceptable major complications.

Loss of MicroRNA-137 Impairs the Homeostasis of Potassium in Neurons via KCC2

Neuropsychiatric disorders are the leading cause of mental and intellectual disabilities worldwide. Current therapies against neuropsychiatric disorders are very limited, and very little is known about the onset and development of these diseases, and their most effective treatments. MIR137 has been previously identified as a risk gene for the etiology of schizophrenia, bipolar disorder, and autism spectrum disorder. Here we generated a forebrain-specific MIR137 knockout mouse model, and provided evidence that loss of miR-137 resulted in impaired homeostasis of potassium in mouse hippocampal neurons. KCC2, a potassium-chloride co-transporter, was a direct downstream target of miR-137. The KCC2 specific antagonist VU0240551 could balance the current of potassium in miR-137 knockout neurons, and knockdown of KCC2 could ameliorate anxiety-like behavior in MIR137 cKO mice. These data suggest that KCC2 antagonists or knockdown might be beneficial to neuropsychiatric disorders due to the deficiency of miR-137.

Novel noninvasive quantification of penile corpus cavernosum lesions in hyperlipidemia-induced erectile dysfunction in rabbits by two-dimensional shear-wave elastography / 亚洲男科学杂志(英文版)

Structural alterations in fibroelastic components of the penile corpus cavernousum (CC) may impair its compliance, resulting in venous leakage and erectile dysfunction (ED). Our study evaluated the effectiveness of noninvasive two-dimensional shear-wave elastography (2-D SWE) in quantifying penile CC lesions in rabbits with hyperlipidemia-induced ED. A total of 12 New Zealand white rabbits were randomly divided into two groups. Six were fed a high-cholesterol diet containing 2% cholesterol and 8.5% lard for 10 weeks and the other six were fed normal diet as controls. We measured the shear-wave elastic quantitative (SWQ) value of penile CC by 2-D SWE. Erectile function was investigated by intracavernous injection of papaverine, and immunohistochemical (IHC) staining and the western blot analysis to determine the penile CC lesions. After 10 weeks, the SWQ values obtained from penile CC were remarkably higher in the high-cholesterol-fed compared with the control group, and the ΔICP (ICP plateau minus ICP baseline)/MAP (ICP: intracavernous pressure, MAP: mean arterial pressure) was markedly decreased. The IHC staining and western blot revealed extracellular matrix (ECM) accumulation in penile cavernous tissues, and the smooth muscle cell (SMC) phenotypic transition was affected, as indicated by reduced alpha-smooth muscle actin and calponin-1 expression and increased phospho-myosin light chain20 (p-MLC20)/MLC20 and osteopontin expression. Hyperlipidemia resulted in ECM accumulation accompanied with SMC phenotypic transition in penile CC and impaired the erectile function eventually. These might, in turn, lead to variations in the SWQ values. It suggests that 2-D SWE may be a novel, noninvasive and effective approach that distinguishes penile CC lesions secondary to hyperlipidemia from normal.

Huangjing Zanyu Capsule enhances sperm mitochondrial membrane potential in asthenozoospermia patients / 中华男科学杂志

Objective@#To observe the effect of Huangjing Zanyu Capsule (HZC) on sperm mitochondrial membrane potential (MMP) in asthenozoospermia patients.@*METHODS@#We assigned 70 asthenozoospermia patients to a treatment group (n = 39) and a control group (n = 31), the former treated with oral HZC at the dose of 4 capsules tid for 3 months while the latter left untreated. We obtained semen parameters from the patients and detected their sperm mitochondrial membrane potentials (MMP) by JC-1 staining and flow cytometry before and after medication, followed by comparison between the two groups.@*RESULTS@#The total effectiveness rate was 71.05% in the treatment group and natural pregnancy was achieved in 3 cases during the medication. A total of 35 patients in the treatment group and 30 controls completed all the laboratory examinations after a 3-month observation. Compared with the controls, the patients treated with HZC exhibited significant improvement after medication in MMP (variation value: ［1.19 ± 10.36］% vs ［20.28 ± 14.21］%, P <0.01), total sperm motility (variation value: ［3.46 ± 8.67］% vs ［20.68 ± 14.12］%, P <0.01), the percentage of progressively motile sperm (variation value: ［2.26 ± 8.29］% vs ［17.58 ± 12.73］%, P <0.01), and the percentage of morphologically normal sperm (variation value: ［0.23 ± 3.48］% vs ［3.37 ± 3.99］%, P <0.01). MMP was significantly correlated with total sperm motility (r = 0.69, P <0.01), progressive sperm motility (r = 0.75, P <0.01) and normal sperm morphology (r = 0.26, P <0.01).@*CONCLUSIONS@#Huangjing Zanyu Capsule can enhance sperm mitochondrial membrane potential and sperm mitochondrial function, thus improving total sperm motility, progressive sperm motility and normal sperm morphology. It is safe and effective for the treatment of asthenospermia.

Quantification of acupuncture manipulation based on video motion capture / 医用生物力学

Objective To accurately measure the motion angels of hand-related joints during manipulations of acupuncture needle thrusting-pulling and twirling, so as to provide quantitative references for acupuncture manipulation. Methods Six acupuncturists with over 3-year acupuncture experience and one volunteer were enrolled in this study. The angles of the forearm, wrist, metacarpophalangeal & interphalangeal joints of the thumb and index finger in each acupuncturist when performing thrusting-pulling and twirling manipulation were measured by the video motion capture (VMC) system, and the different ranges of above-mentioned angles among the 6 acupuncturists when performing 10 trails of thrusting-pulling and twirling manipulations on the volunteer’s thigh were compared. Results There was no significant difference in the ranges of relevant hand-related angles in the acupuncturist (P>0.05). The manipulation of thrusting-pulling was mainly managed by the wrist joint, with the range of (7.23±1.87)°, while the manipulation of twirling was mainly managed by the interphalangeal joints of the index finger, and the range of the first and second interphalangeal joints of the index finger was (28.33±2.18)°and (10.43±1.69)°, respectively. Conclusions The VMC can be a reliable method to quantify the parameters of acupuncture manipulation. Different acupuncture manipulation shows particular variation of the joint angles, which can be used as a reference to quantify the acupuncture manipulation.

Method for analyzing the signal of hip joint angles during human walking using Hilbert-Huang transform / 医用生物力学

Objective To propose a method for analyzing the hip joint signals during human walking based on Hilbert-Huang transform (HHT) method and verify its feasibility. Methods First, the hip joint angles of one healthy subject were measured by using the hip joint measuring platform composed of acceleration sensors and gyroscopes. Second, all intrinsic mode functions (IMFs) at different scales, which could be further analyzed and combined, were obtained by applying the ensemble empirical mode decomposition (EEMD) to original signals. Finally, the Hilbert spectrum of original signals were plotted and analyzed. Results The signals representing different motion modes as well as gait characteristics indicated by rotating track of the hip joint were obtained. The Hilbert spectrum could show the intra-wave frequency modulation in the main motion mode and the characteristics of walking frequencies. Conclusions This method can be used in rehabilitation and treatment of patients with gait diseases. By using this method, the characteristic signals of the hip joints at different frequency scales can be effectively decomposed, and the post-processing signals can be filtered and centrally corrected, so as to adaptively analyze gait signals of the patients.

Two-micron laser resection of the prostate-tangerine technique for the treatment of large-volume prostate / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficiency and safety of two-micron laser resection of the prostate-tangerine technique (TmLRP-TT) for the treatment of large-volume ( > 70 ml) prostate in patients with benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>This retrospective analysis included 80 BPH patients with the prostatic volume larger than 70 ml, all treated by TmLRP-TT. We comparatively analyzed the levels of hemoglobin and serum sodium before and after surgery, recorded intra- and post-operative com- plications, and followed up the patients at 6 and 12 months after operation for International Prostate Symptom Score (IPSS), quality of life (QOL), maximum flow rate (Qmax), and postvoid residual urine volume (PVR).</p><p><b>RESULTS</b>All the operations were successfully completed. The mean hemoglobin decreased (0.68 +/- 0.43) g/dl intraoperatively, but no apparent reduction was observed in serum sodium. Lower urinary tract symptoms were relieved significantly in all the cases. At 12 months after surgery, IPSS was decreased by 73.89% as compared with the baseline (20.03 +/- 6.9 vs 5.23 +/- 3.59), QOL by 64.55% (4.09 +/- 1.19 vs 1.45 +/- 1.36), and PVR by 79.30% (97.31 +/- 57.90 vs 20.14 +/- 24.20 ml), while Qmax increased by 140.42% ([8.04 +/- 3.62] vs [19.33 +/- 3.28] ml/s). The incidence of complications was low either intraoperatively or during the 12 months after operation.</p><p><b>CONCLUSION</b>TmLRP-TT is a safe and effective surgical endoscopic approach to the treatment of large-volume prostate in BPH patients.</p>

Proportion of intermediate epithelial cells and human prostate cancer / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the different proportions of intermediate epithelial cells in human prostate cancer tissue and their clinical significance.</p><p><b>METHODS</b>We performed immunohistochemical staining for Cytokeratin 5 (CK5) and Cytokeratin 8 (CK8) on 60 samples of human prostate cancer, determined the proportions of intermediate epithelial cells in the cancer tissue, and classified the samples into 2 types, one with a majority of intermediate epithelial cells (CaP-INT, n = 32), and the other composed mostly of luminal epithelial cells (CaP-LUM, n = 28). Then we compared the 2 types of prostate cancer in the expression of the androgen receptor (AR), age of the patient, serum t-PSA, prostate volume, Gleason score, clinical stage, androgen resistance, and incidence of distant metastasis.</p><p><b>RESULTS</b>CaP-INT showed a significantly lower expression of AR ([24.42 +/- 11.41] %) and a higher incidence of distant metastasis (n = 14) than CaP-LUM ([77.21 +/- 10.22] % and n = 4) (P < 0.05). In the CaP-INT group, 6 of the 26 endocrinologically treated cases developed into androgen-independent prostate cancer (AIPC), while in the CaP-LUM group, only 1 out of 23 (P < 0.05). The former also showed remarkably higher clinical stages than the latter (P < 0.05), but no significant differences were found in age, serum t-PSA, prostate volume and Gleason score between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>A higher proportion of intermediate epithelial cells may lead to increased invasiveness and metastasis of human prostate cancer.</p>

Chimeric molecules facilitate the degradation of androgen receptors and repress the growth of LNCaP cells / 亚洲男科学杂志(英文版)

Post-translational degradation of protein plays an important role in cell life. We employed chimeric molecules (dihydrotestosterone-based proteolysis-targeting chimeric molecule [DHT-PROTAC]) to facilitate androgen receptor (AR) degradation via the ubiquitin-proteasome pathway (UPP) and to investigate the role of AR in cell proliferation and viability in androgen-sensitive prostate cancer cells. Western blot analysis and immunohistochemistry were applied to analyse AR levels in LNCaP cells after DHT-PROTAC treatment. Cell counting and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay were used to evaluate cell proliferation and viability after AR elimination in both LNCaP and PC-3 cells. AR was tagged for elimination via the UPP by DHT-PROTAC, and this could be blocked by proteasome inhibitors. Degradation of AR depended on DHT-PROTAC concentration, and either DHT or an ALAPYIP-(arg)(8) peptide could compete with DHT-PROTAC. Inhibition of cell proliferation and decreased viability were observed in LNCaP cells, but not in PC-3 or 786-O cells after DHT-PROTAC treatment. These data indicate that AR elimination is facilitated via the UPP by DHT-PROTAC, and that the growth of LNCaP cells is repressed after AR degradation.

Targeted degradation of androgen receptors in androgen-independent prostate cancer cells: an experimental study / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate targeted degradation of the androgen receptor (AR) by chimeric molecules (DHT-PROTAC) via the ubiquitin-proteasome pathway in androgen-independent prostate cancer CA-2B cells, and explore the proliferation, secretion and apoptosis of the treated cells.</p><p><b>METHODS</b>C4-2B cells were treated with DHT-PROTAC, and then the expressions of the AR protein and caspase3 in the C4-2B cells were detected by immunohistochemistry and Western blot. The concentration of PSA in the supernatant was examined by ELISA. The cells were counted and their proliferation analyzed by a growth curve. The inhibitory effect on the growth of C4-2B cells was evaluated by MIT assay.</p><p><b>RESULTS</b>Compared with the control group, the DHT-PROTAC-treated group showed an obviously decreased expression of AR proteins with a significant attenuation of the band signals (P < 0.05), a 40% reduction of the AR-positive cells and a 60% decrease of the PSA concentration in the supernatant (P < 0.05). DHT-PROTAC exhibited an inhibitory effect on the C4-2B cells in a time-dependant manner (P < 0.05).</p><p><b>CONCLUSION</b>The chimeric molecule (DHT-PROTAC) can target the degradation of androgen receptors, reduce the secretion of PSA and repress the in vitro growth of C4-2B cells.</p>

Androgen receptor functioned as a suppressor in the prostate cancer cell line PC3 in vitro and in vivo / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prostate cancer is one of the most common urogenital tumors in the world with an increasing incidence in China. Androgen deprivation therapy is the major therapeutic option for advanced prostate cancer. However, the role of androgen receptor (AR) in hormone-refractory prostate cancer still remains unclear. This work aimed to investigate the role of AR in an androgen independent prostate cancer cell line by in vitro and in vivo studies.</p><p><b>METHODS</b>The role of AR in the proliferation and invasion/metastasis ability of PC3-AR9 (a PC3 stable clone expressing human AR driven by natural human AR promoter) were examined with MTT assay, soft agar assay, chamber invasion assay, wound healing assay, and also with orthotopic xenograft mouse model.</p><p><b>RESULTS</b>Restoring androgen receptor in PC3 cells resulted in decreased proliferation and invasion/metastasis ability in MTT, soft agar, chamber invasion and wound healing assay. In the mouse orthotopic xenograft model, PC3-AR9 resulted in smaller primary tumors and metastasis tumors, with a lower proliferation rate and higher apoptosis rate.</p><p><b>CONCLUSION</b>The AR might function as a tumor suppressor in PC3 cells both in vitro and in vivo.</p>

Expression and implication of cyclooxygenase-2 mRNA in prostate cancer / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between cyclooxygenase-2 (COX-2) mRNA expression and the biological behaviors of prostate carcinoma (PCa).</p><p><b>METHODS</b>The expression of COX-2 mRNA was detected by RT-PCR method in 32 samples of PCa and the COX-2/GAPDH value was determined. Seven normal prostate tissues were served as control.</p><p><b>RESULTS</b>The expression of COX-2 mRNA in normal tissue of 7 control cases was all negative. There was statistical correlation between the COX-2/GAPDH and the Gleason scores of PCa. There also showed statistical correlation between the COX-2/GAPDH and the stages of PCa.</p><p><b>CONCLUSION</b>COX-2 mRNA play an important role in occurrence and progression of the PCa. COX-2 is a tumor marker which may be the possible prognostic factor of PCa.</p>

Combined treatment applied to advanced cancer of abdominal cryptorchidism (report of 12 cases) / 中华男科学杂志

<p><b>OBJECTIVE</b>To discuss the treatment of advanced cancer of abdominal cryptorchidism.</p><p><b>METHODS</b>The combined method, including preoperation chemotherapy + surgery + postoperation radiotherapy and chemotherapy, was used to treat 12 cases of the advanced cancer of abdominal cryptorchidism and the effects were evaluated.</p><p><b>RESULTS</b>The patients recovered smoothly without complications of operation. The side effect of chemotherapy and radiotherapy was very slight. Eleven out of 12 cases were followed up. All 11 cases survived and had no recurrence.</p><p><b>CONCLUSION</b>The results of combined method to treat advanced cancer of abdominal cryptorchidism is very perfect.</p>