Intracorporeal versus extracorporeal anastomosis in laparoscopic right hemicolectomy for overweight colon cancer patients: a case-control study.

INTRODUCTION: Either extracorporeal anastomosis (EA) or intracorporeal anastomosis (IA) could be selected for digestive reconstruction in laparoscopic right hemicolectomy (LRH). However, whether LRH with IA is feasible and beneficial for overweight right-side colon cancer (RCC) is unclear. This study aims to investigate the feasibility and advantage of IA in LRH for overweight RCC. METHODS: Forty-eight consecutive overweight RCC patients undergoing LRH with IA were matched with 48 consecutive cases undergoing LRH with EA. Both clinical and surgical data were collected and analyzed. RESULTS: The incidence of postoperative complications was 20.8% (10/48) in the EA group and 14.6% (7/48) in the IA group respectively, with no statistical difference. Compared to the EA group, patients in the IA group revealed faster gas (40.2 + 7.8 h vs. 45.6 + 7.9 h, P = 0.001) and stool discharge (4.0 + 1.2 d vs. 4.5 + 1.1 d, P = 0.040), shorter assisted incision (5.3 + 1.3 cm vs. 7.5 + 1.2 cm, P = 0.000), and less analgesic used (3.3 + 1.3 d vs. 4.0 + 1.3 d, P = 0.012). There were no significant differences in operation time, blood loss, or postoperative hospital stays. In the IA group, the first one third of cases presented longer operation time (228.4 + 29.3 min) compared to the middle (191.0 + 35.0 min, P = 0.003) and the last one third of patients (182.2 + 20.7 min, P = 0.000). CONCLUSION: LRH with IA is feasible and safe for overweight RCC, with faster bowel function recovery and less pain. Accumulation of certain cases of LRH with IA will facilitate surgical procedures and reduce operation time.

Nanodrug modified with engineered cell membrane targets CDKs to activate aPD-L1 immunotherapy against liver metastasis of immune-desert colon cancer.

Immunotherapy based on the PD-1/PD-L1 axis blockade has no benefit for patients diagnosed with colon cancer liver metastasis (CCLM) for the microsatellite stable/proficient mismatch repair (MSS/pMMR)) subtype, which is known as an immune-desert cancer featuring poor immunogenicity and insufficient CD8+ T cell infiltration in the tumor microenvironment. Here, a multifunctional nanodrug carrying a cyclin-dependent kinase (CDK)1/2/5/9 inhibitor and PD-L1 antibody is prepared to boost the immune checkpoint blockade (ICB)-based immunotherapy against MSS/pMMR CCLM via reversing the immunosuppressive tumor microenvironment. To enhance the MSS/pMMR CCLM-targeting efficacy, we modify the nanodrug with PD-L1 knockout cell membrane of this colon cancer subtype. First, CDKs inhibitor delivered by nanodrug down-regulates phosphorylated retinoblastoma and phosphorylated RNA polymerase II and meanwhile arrests the G2/M cell cycle in CCLM to promote immunogenic signal release, stimulate dendritic cell maturation, and enhance CD8+ T cell infiltration. Moreover, CDKi suppresses the secretion of immunosuppressive cytokines in tumor-associated myeloid cells sensitizing ICB therapy in CCLM. Notably, the great efficacy to activate immune responses is demonstrated in the patient-derived xenograft model and the patient-derived organoid model as well, revealing a clinical application potential. Overall, our study represents a promising therapeutic approach for targeting liver metastasis, remolding the tumor immune microenvironment (TIME), and enhancing the response of MSS/pMMR CCLM to boost ICB immunotherapy.

Nrf2 enhances the therapeutic efficiency of adipose-derived stem cells in the treatment of neurogenic erectile dysfunction in a rat model.

BACKGROUND: Erectile dysfunction (ED) caused by intraoperative nerve injury is a major complication of pelvic surgery. Adipose-derived stem cells (ADSCs) have presented therapeutic potential in a rat model of bilateral cavernous nerve injury (BCNI), while inadequate in vivo viability has largely limited their application. Nuclear factor-E2-related Factor (Nrf2) is a key transcription factor that regulates cellular anti-oxidative stress. In this work, we investigated the effect of Nrf2 expression regulation on the viability of ADSCs, and explore its repair potential in a BCNI rat model. RESULTS: The survival time of tert-Butylhydroquinone (tBHQ)-ADSCs in BCNI model increased obviously. In addition, the tBHQ-ADSCs group presented better restoration of major pelvic ganglion (MPG) nerve contents and fibers, better improvement of erectile function, and less penile fibrosis than the other groups. Moreover, the expression of Nrf2 and superoxide dismutase 1 (SOD1) were higher than those of other groups. CONCLUSION: Nrf2 could enhance the anti-oxidative stress ability of ADSCs, so as to improve the therapeutic effect of ADSCs on BCNI rat model.

RéSUMé: CONTEXTE: La dysfonction érectile (DE) causée par une lésion nerveuse peropératoire est une complication majeure de la chirurgie pelvienne. Les cellules souches dérivées du tissu adipeux (ADSC) ont constitué un potentiel thérapeutique dans un modèle de lésion bilatérale des nerfs caverneux (BCNI) chez le rat, mais une viabilité insuffisante in vivo a largement limité leur application. Nrf2 est un facteur de transcription clé qui régule le stress antioxydant cellulaire. Dans ce travail, nous avons étudié l'effet de la régulation de l'expression de Nrf2 sur la viabilité des ADSC, et exploré son potentiel de réparation dans un modèle de BCNI chez le rat. RéSULTATS: Le temps de survie des cellules tert-butylhydroquinone (tBHQ)-ADSC dans le modèle BCNI a significativement augmenté. De plus, le groupe tBHQ-ADSC a présenté une meilleure restauration du contenu et des fibres nerveuses des ganglions pelviens majeurs, une meilleure amélioration de la fonction érectile et une moindre fibrose pénienne que les autres groupes. Par ailleurs, l'expression de Nrf2 et de la superoxyde dismutase 1 était plus élevée dans ce groupe que dans les autres groupes. CONCLUSIONS: Nrf2 pourrait améliorer la capacité de stress anti-oxydatif des cellules ADSC, améliorant ainsi l'effet thérapeutique des ADSC sur le modèle de BCNI chez le rat.

Preservation versus resection of Denonvilliers' fascia in total mesorectal excision for male rectal cancer: follow-up analysis of the randomized PUF-01 trial.

Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers' fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.

The status of low anterior resection syndrome: data from a single-center in China.

AIM: The incidence and risk factors of low anterior resection syndrome (LARS) largely variate in different studies. In addition, there is lack of study on how patients evaluate the therapeutic effect of LARS. This single-center retrospective study aims to investigate the status of LARS in Chinese patients undergoing laparoscopic low anterior resection (LAR). METHODS: Consequent patients undergoing laparoscopic LAR and free from disease recurrence from January 2015 to May 2021 were issued with both LARS questionnaire and satisfaction survey. Related data were collected and analyzed. RESULTS: Both LARS questionnaires and self-made satisfaction survey were received from 261 eligible patients. The overall incidence of LARS was 47.1% (minor in 19.5%, major in 27.6%), decreased with the passage of postoperative time (64.7% within 12 months, and 41.7% within 12-36 months), and became stable 36 months later (39.7%). The most common symptoms were defecation clustering (n = 107/261, 41.0%) and defecation urgency (n = 101/261, 38.7%). According to the multivariable regression analysis, risk factors of major LARS were: 1 year increase in age (OR 1.035, 95% CI 1.004-1.068), protective stoma (OR 2.656, 95% CI 1.233-5.724) and T3 - 4 stage (OR 2.449, 95% CI 1.137-5.273). Most patients complained defecation disorder (87.3%) to doctors and 84.5% got suggestions or treatments for it. However, only 36.8% patients thought the treatments worked for them. CONCLUSIONS: LARS frequently occurs after laparoscopic LAR, while the therapeutic effect is not satisfying. Elder, advanced T-stage and protective stoma were risk factors for postoperative major LARS.

Systematic identification of anticancer drug targets reveals a nucleus-to-mitochondria ROS-sensing pathway.

Multiple anticancer drugs have been proposed to cause cell death, in part, by increasing the steady-state levels of cellular reactive oxygen species (ROS). However, for most of these drugs, exactly how the resultant ROS function and are sensed is poorly understood. It remains unclear which proteins the ROS modify and their roles in drug sensitivity/resistance. To answer these questions, we examined 11 anticancer drugs with an integrated proteogenomic approach identifying not only many unique targets but also shared ones-including ribosomal components, suggesting common mechanisms by which drugs regulate translation. We focus on CHK1 that we find is a nuclear H2O2 sensor that launches a cellular program to dampen ROS. CHK1 phosphorylates the mitochondrial DNA-binding protein SSBP1 to prevent its mitochondrial localization, which in turn decreases nuclear H2O2. Our results reveal a druggable nucleus-to-mitochondria ROS-sensing pathway-required to resolve nuclear H2O2 accumulation and mediate resistance to platinum-based agents in ovarian cancers.

Identification of LSM family members as potential chemoresistance predictive and therapeutic biomarkers for gastric cancer.

Introduction: The Like-Smith (LSM) family plays a critical role in the progression of several cancers. However, the function of LSMs in chemoresistance of gastric cancer (GC) is still elusive. Methods: The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database and Tumor Immune Estimation Resource Analysis (TIMER) were utilized to analyze the expression, prognostic value and immune infiltration of LSMs in GC patients. Moreover, qPCR and immunohistochemistry (IHC) experiment were conducted with clinical samples. Results: The expression of LSMs was upregulated in GC tissues and most of LSMs were negatively correlated with overall survival of GC patients with 5-fluorouracil (5-FU) treatment. We further revealed that LSM5, 7 and 8 were hub genes of GEO (GSE14210). Besides, the qPCR results demonstrated that a higher level of LSM5 and LSM8 was associated with 5-FU chemoresistance in GC. Moreover, both TIMER and IHC revealed that a lower expression of LSM5 and LSM8 was correlated with high infiltration of T cells, regulatory T cells, B cells, macrophages, and neutrophils. Discussion: Our study systematically investigated the expression pattern and biological features of LSM family members in GC, and identified LSM5 and LSM8 as potential biomarkers in GC with 5-FU chemotherapy.

New staging systems for left-sided colon cancer based on the number of retrieved and metastatic lymph nodes provide a more accurate prognosis.

Objectives: We aimed to explore reasonable lymph node classification strategies for left-sided colon cancer (LCC) patients. Methods: 48,425 LCC patients from 2010 to 2015 were identified in the US Surveillance, Epidemiology, and End Results database. We proposed an innovative revised nodal (rN) staging of the 8th American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification based on the cut-off value of retrieved lymph nodes and survival analyses in patients with LCC. Log odds of positive lymph nodes (LODDS) stage is a numerical classification strategy obtained by a formula that incorporates the numbers of retrieved and positive lymph nodes. To develop the TrN or TLODDS classification, patients with similar survival rates were grouped by combining T and rN or LODDS stage. The TrN or TLODDS classification was further evaluated in a validation set of 12,436 LCC patients from 2016 to 2017 in the same database and a Chinese application set of 958 LCC patients. Results: We developed novel TrN and TLODDS classifications for LCC patients that incorporated 7 stages with reference to the AJCC staging system. In comparison to the 8th AJCC TNM and TrN classifications, TLODDS classification demonstrated significantly better discrimination (area under the receiver operating characteristic curve, 0.650 vs. 0.656 vs. 0.661, p < 0.001), better model-fitting (Akaike information criteria, 309,287 vs. 308,767 vs. 308,467), and superior net benefits. The predictive performance of the TrN and TLODDS classifications was further verified in the validation and application sets. Conclusion: Both the TrN and TLODDS classifications have better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represent an alternative to the current TNM classification for LCC patients.

Identification of chemotherapy targets reveals a nucleus-to-mitochondria ROS sensing pathway.

Multiple chemotherapies are proposed to cause cell death in part by increasing the steady-state levels of cellular reactive oxygen species (ROS). However, for most of these drugs exactly how the resultant ROS function and are sensed is poorly understood. In particular, it's unclear which proteins the ROS modify and their roles in chemotherapy sensitivity/resistance. To answer these questions, we examined 11 chemotherapies with an integrated proteogenomic approach identifying many unique targets for these drugs but also shared ones including ribosomal components, suggesting one mechanism by which chemotherapies regulate translation. We focus on CHK1 which we find is a nuclear H 2 O 2 sensor that promotes an anti-ROS cellular program. CHK1 acts by phosphorylating the mitochondrial-DNA binding protein SSBP1, preventing its mitochondrial localization, which in turn decreases nuclear H 2 O 2 . Our results reveal a druggable nucleus-to-mitochondria ROS sensing pathway required to resolve nuclear H 2 O 2 accumulation, which mediates resistance to platinum-based chemotherapies in ovarian cancers.

Synchronous Colorectal Liver Metastases considering Infectious Complications: Simultaneous or Delayed Surgery?

Background: Simultaneous or delayed surgery for synchronous colorectal liver metastases is performed in the clinic; which method is better is still up for debate. In particular, infectious complications are rarely compared. This study aims to investigate the differences between simultaneous and delayed surgery for synchronous colorectal liver metastases by comparing infectious complications and prognosis. Methods: Firstly, the patients' information from a single institution's database was retrospectively analyzed. Then the patients were divided into a simultaneous group and a delayed group according to synchronous colorectal liver metastases. Analyzing the postoperative complications within 30 days, the progression-free survival, and the overall survival in the two groups. Results: The simultaneous group had a higher neo-adjuvant chemotherapy rate (42.0% VS. 16.0% in the delayed group, P < 0.05) and laparoscopic surgery rate (89.8% VS. 72.0% in the delayed group, P < 0.05) than the delayed group. Moreover, the simultaneous group had a higher liver-related infection rate (17.0 VS. 0.0% in the delayed group, P < 0.05). Conclusion: Although there was no difference in survival rate between delayed and simultaneous surgeries, the delayed surgery have fewer liver-related infections compared with the simultaneous surgery in synchronous colorectal liver metastases patients. Delayed surgery could be a better treatment method for synchronous colorectal liver metastases patients.

Π electron-stabilized polymeric micelles potentiate docetaxel therapy in advanced-stage gastrointestinal cancer.

Gastrointestinal (GI) cancers are among the most lethal malignancies. The treatment of advanced-stage GI cancer involves standard chemotherapeutic drugs, such as docetaxel, as well as targeted therapeutics and immunomodulatory agents, all of which are only moderately effective. We here show that Π electron-stabilized polymeric micelles based on PEG-b-p(HPMAm-Bz) can be loaded highly efficiently with docetaxel (loading capacity up to 23 wt%) and potentiate chemotherapy responses in multiple advanced-stage GI cancer mouse models. Complete cures and full tumor regression were achieved upon intravenously administering micellar docetaxel in subcutaneous gastric cancer cell line-derived xenografts (CDX), as well as in CDX models with intraperitoneal and lung metastases. Nanoformulated docetaxel also outperformed conventional docetaxel in a patient-derived xenograft (PDX) model, doubling the extent of tumor growth inhibition. Furthermore, micellar docetaxel modulated the tumor immune microenvironment in CDX and PDX tumors, increasing the ratio between M1-and M2-like macrophages, and toxicologically, it was found to be very well-tolerated. These findings demonstrate that Π electron-stabilized polymeric micelles loaded with docetaxel hold significant potential for the treatment of advanced-stage GI cancers.

Effect of Denonvilliers' Fascia Preservation Versus Resection During Laparoscopic Total Mesorectal Excision on Postoperative Urogenital Function of Male Rectal Cancer Patients: Initial Results of Chinese PUF-01 Randomized Clinical Trial.

OBJECTIVE: To compare the outcomes of laparoscopic total mesorectal excision (L-TME) with Denonvilliers' fascia (DVF) preservation versus resection on urogenital function of male patients with rectal cancer. BACKGROUND: The protective effect of DVF during L-TME on pelvic autonomic nerves and postoperative urogenital function remains controversial. METHODS: Between August 26, 2015 and July 18, 2019, 253 male patients with cT1-4 (T1-2 for anterior wall) N0-2M0 rectal cancer from 11 institutions were enrolled, and randomly assigned to L-TME with DVF preservation (Exp-group, n = 123) or resection procedures (Con-group, n = 130). Urinary function was assessed by residual urine volume, maximal flow rate, and International Prostate Symptom Score; sexual function was assessed by 5-item version of the International Index of Erectile Function (IIEF-5) and ejaculation grading. RESULTS: The Exp-group patients showed a lower urinary dysfunction rate (6.8% vs 25.4%, P = 0.003), higher maximal flow rate (16.25 ±â€Š8.02 vs 12.40 ±â€Š7.05 mL/s, P = 0.007), and lower International Prostate Symptom Score (6.55 ±â€Š5.86 vs 8.57 ±â€Š5.85, P = 0.026) than the Con-group patients at 2 weeks after surgery. The incidence of erectile dysfunction (IIEF-5 ≤ 11) at 12 months after surgery was lower in the Exp-group than in the Con-group (12.5% vs 34.2%, P = 0.023); Exp-group manifested superior IIEF-5 (16.63 ±â€Š6.28 vs 12.26 ±â€Š6.83, P = 0.018). The incidence of ejaculation dysfunction was lower in the Exp-group than in the Con-group at 12 months after surgery (10.0% vs 29.4%, P = 0.034). CONCLUSIONS: DVF preservation during L-TME revealed protective effects on postoperative urogenital function, and could be a better choice for male rectal cancer patients with specific staging and location. TRIAL REGISTRATION NUMBER: NCT02435758.

Identification of the surgical indication line for the Denonvilliers' fascia and its anatomy in patients with rectal cancer.

BACKGROUND: The high rate of urogenital dysfunction after traditional total mesorectal excision (TME) has caused doubts among scholars on the standard fashion of dissection. We have proposed the necessity to preserve the Denonvilliers' fascia in patients with rectal cancer. However, how to accurately locate the Denonvilliers' fascia is unclear. This study aimed to explore anatomical features of the Denonvilliers' fascia by comparing autopsy findings and observations of surgical videos so as to propose a dissection method for the preservation of pelvic autonomic nerves during rectal cancer surgery. METHODS: Five adult male cadaver specimens were dissected, and surgical videos of 135 patients who underwent TME for mid-low rectal cancer between January 2009 and February 2019 were reviewed to identify and compare the structure of the Denonvilliers' fascia. RESULTS: The monolayer structure of the Denonvilliers' fascia was observed in 5 male cadaver specimens, and it was located between the rectum, the bottom of the bladder, the seminal vesicles, the vas deferens, and the prostate. The Denonvilliers' fascia was originated from the rectovesical pouch (or rectum-uterus pouch), down to fuse caudally with the rectourethral muscle at the apex of the prostate, and fused to the lateral ligaments on both sides. The fascia was thinner on the midline with a thickness of 1.06 ± 0.10 mm. The crown shape of the Denonvilliers' fascia was slightly triangular, with a height of approximately 5.42 ± 0.16 cm at midline. Nerves were more densely distributed in front of the Denonvilliers' fascia than behind, especially on both sides of it. Under laparoscopic view, the Denonvilliers' fascia was originated at the lowest point of the rectovesical pouch (or rectum-uterus pouch), with a thickened white line which was a good mark for identifying the Denonvilliers' fascia. CONCLUSION: Identification of the surgical indication line for the Denonvilliers' fascia could help us identify the Denonvilliers' fascia, and it would improve our ability to protect the pelvic autonomic function of patients undergoing TME for rectal cancer.

Co-overexpression of VEGF and GDNF in adipose-derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model.

OBJECTIVES: To evaluate the rapid repair potential of adipose-derived stem cells (ADSCs) co-overexpressing VEGF and GDNF on bilateral cavernous nerve injury (BCNI) in rat models. Progressive fibrosis of the penis that occurs shortly after BCNI is a key cause of clinical treatment difficulty of erectile dysfunction (ED). Traditional medications are ineffective for ED caused by BCNI. ADSCs have shown therapeutic effects in animal models, but disappointing in clinical treatment suggests that we should explore optimal treatment of it. MATERIALS AND METHODS: We extracted ADSCs from rat epididymis. Lentiviral transfection was verified by western blot and immunofluorescence. Thirty-six SD rats (10 weeks old) were randomly divided into six groups (n = 6 per group): sham surgery, and remaining five BCNI groups transplanted PBS or ADSCs which were genetically modified by vehicle, VEGF (ADSC-V), GDNF (ADSC-G), or VEGF&GDNF (ADSC-G&V) around major pelvic ganglion (MPG). We investigated the therapeutic effects of BCNI rat model which is characterized by ED, penile tissue fibrosis and hypoxia, and lack of nitrogen nerves or vascular atrophy. RESULTS: Erectile function was almost recovered after 2 weeks of transplantation of ADSC-G&V, promoted cavernous nerve repair, prevented penile fibrosis and preserving the vascular endothelium, which was significant differences amongst ADSC-V or ADSC-G. Moreover, GM-ADSCs were detected in MPG and penis, indicating that their participation in repair of target organs and transverse nerves. CONCLUSIONS: These promising data indicate that ADSCs co-overexpressed VEGF and GDNF-induced synergistic effects, make it a potential tool for recovering of erectile function speedily after BCNI.

Endothelial progenitor cells promote viability and nerve regenerative ability of mesenchymal stem cells through PDGF-BB/PDGFR-ß signaling.

Denervation-induced erectile dysfunction (ED) is a prevailing health problem. Our previous study revealed that endothelial progenitor cells (EPCs) promoted the effect of mesenchymal stem cells (MSCs) on restoration of denervation-induced ED in rats. However, underling mechanisms are still largely elusive. In this study, EPCs and MSCs were co-cultured and resorted to co-EPCs and co-MSCs. EPCs-derived paracrine factors containing PDGF-BB (platelet-derived growth factor) were detected, and MSCs were pre-treated with PDGF-BB, while co-MSCs were pre-treated with PDGFR inhibitor AG1296. Either viability or nerve regenerative ability of MSCs was evaluated. In addition, inhibition of either PI3K/Akt or MEK/Erk pathway was performed to evaluate the role of PI3K/Akt and MEK/Erk pathway in PDGF-BB-induced viability of MSCs. The results revealed that PDGF-BB significantly increased the proportion of PDGFR-ß+ MSCs, and promoted both in-vitro and in-vivo viability, as well as nerve regenerative capacity and erectile function restoration of MSCs in rats. Inhibition of PI3K/Akt, MEK/Erk pathway or mTOR led to decrease of PDGF-BB/PDGFR-ß induced viability of MSCs. To our knowledge, our study first demonstrates that EPCs promote viability and potential nerve regenerative ability of MSCs through PDGF-BB/PDGFR-ß signaling and its downstream PI3K/Akt and MEK/Erk pathways. mTOR acts as a co-mediator in PI3K/Akt and MEK/Erk pathways.

Transplantation of induced pluripotent stem cell-derived mesenchymal stem cells improved erectile dysfunction induced by cavernous nerve injury.

Erectile dysfunction (ED) is an important kind of postoperative complication of pelvic surgery that affects patients' quality of life. Transplantation of mesenchymal stem cells (MSC) has been found to alleviate ED caused by cavernous nerve injury (CNI) in rats. However, little is known about whether induced pluripotent stem cell-derived mesenchymal stem cells (iMSC) have a therapeutic effect on CNI ED. We established an ED model on rats and evaluated the effect of iMSC on it. Methods: Eight-week-old male Sprague-Dawley rats were assigned to four groups and received following operation: sham operation (sham group); bilateral CNI and phosphate-buffered saline (PBS) injections (PBS group); bilateral CNI and adipose-derived mesenchymal stem cells transplantation (adMSC group); or bilateral CNI and iMSC injection (iMSC group). After therapy, the cavernous nerve was stimulated by electricity and the intracavernous pressure (IAP)/mean arterial blood pressure (MAP) was measured. The endothelial and smooth muscle tissue in the penis was assessed histologically with Masson's trichrome stain. Immunofluorescence/immunohistochemical stains were applied for the detection of nNOS, vWF, eNOS, SMA, Desmin, S100ß, and caspase-3. Nude rats CNI ED model was established for the evaluation of iMSC longevity and differentiation capacity. The paracrine factors were assessed by real-time PCR. Results: Transplantation of iMSC significantly restored the IAP/MAP in this CNI ED model and showed long-term effects. It could rescue the expression of vWF, eNOS, SMA, and Desmin, which indicated the alleviation of endothelial and smooth muscle tissues of the penis. iMSC therapy also could increase the expression of nNOS in the cavernosum and S100ß in the major pelvic ganglia (MPG) which contributed to the erectile function. Moreover, the level of BAX and caspase-3 were reduced and Bcl-2 was increased, which indicated the anti-apoptosis effects of iMSC. The iMSC showed little transdifferentiation and exerted their function by activating the secretome of the host. Conclusion: Transplantation of iMSC significantly improved ED induced by CNI. The iMSC may exert their effects via paracrine factors and may be a promising therapeutic candidate for treating CNI ED in the future.

Morphology Evolution and Rheological Behaviors of PP/SR Thermoplastic Vulcanizate.

The thermoplastic vulcanizates (TPVs) of polypropylene (PP)/silicone rubber (SR) were prepared by dynamic vulcanization (DV) technology. The mixing torque, morphology, viscoelasticity, and creep response of PP/SR TPVs were investigated by torque rheometer, scanning electron microscope (SEM), transmission electron microscope (TEM), rotational rheometer, and dynamic mechanical analysis (DMA). A mixing-torque study showed that torque change and dynamic-vulcanization time increased with SR content increasing in the DV process, but DV rate was independent of SR content. TEM images indicated that the phase inversion of PP/SR-60 TPV from bicontinuous to a sea⁻island structure took place in the DV process, and a hot press would break the rubber aggregates and shrink a large SR phase. Dynamic-strain measurement demonstrated that PP/SR TPVs exhibit a distinct "Payne effect", which can be attributed to the destruction and reconstruction of SR physical networks. Complex viscosity indicated that SR content did not affect the processability of PP/SR TPVs at high shear rates. Furthermore, the creep deformation and recovery of PP/SR TPVs at solid and melt states were studied, respectively.

Reconsideration of the Anterior Surgical Plane of Total Mesorectal Excision for Rectal Cancer.

INTRODUCTION: Previous studies on total mesorectal excision suggested dissection anterior to Denonvilliers' fascia, which might lead to intraoperative pelvic autonomic nerves injury and a high incidence of urogenital dysfunction. TECHNIQUE: We dissected 4 cases of cadavers, mainly focusing on anatomy of Denonvilliers' fascia, to study the relationship between Denonvilliers' fascia and rectum. In practice, instead of dissection 1 cm above peritoneal reflection, dissection of the peritoneum was performed at the lowest level of peritoneal reflection during laparoscopic resection for mid-low rectal cancer. RESULTS: The cadaveric study revealed that there were loose tissues between Denonvilliers' fascia and rectal specimen, thus a surgical plane posterior to Denonvilliers' fascia did exist. During laparoscopic resection for mid-low rectal cancer, some loose reticulate structures between Denonvilliers' fascia and proper fascia of rectum would present after dissection of peritoneum at the lowest level of peritoneal reflection. Then dissection within the surgical plane posterior to Denonvilliers' fascia became easy and feasible. In this plane, both the pelvic nerves and postoperative urogenital function could be well protected by Denonvilliers' fascia. CONCLUSIONS: The anterior surgical plane for total mesorectal excision should be reconsidered, and dissection posterior to Denonvilliers' fascia is feasible and practicable for patients without risk of positive anterior circumferential resection margin.

RSPO2 enhances cell invasion and migration via the WNT/ß-catenin pathway in human gastric cancer.

R-spondins comprise a group of secreted WNT agonists. R-spondin2 (RSPO2) plays a crucial role in the activation of the WNT/ß-catenin pathway and oncogenesis, though its specific role in human gastric cancer (GC) remains unclear. In the current study, RSPO2 expression levels were upregulated in cancer specimens and cell lines (AGS and BGC-823). Inhibition of RSPO2 expression levels had distinct effects on cell invasion, migration, and epithelial-mesenchymal transition (EMT) in AGS and BGC-823 cells in vitro. Furthermore, RSPO2 positively correlated with leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), the receptor of RSPO2. Silencing RSPO2 reduced the expression of LGR5 and WNT/ß-catenin effector molecule ß-catenin together with downstream targets TCF-4 and Cyclin-D1. These observations demonstrate that upregulation of RSPO2 in GC specimens and cell lines is closely related to tumor invasion and migration and that RSPO2 promotes EMT in gastric cancer cells by activating WNT/ß-catenin signaling.