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.

Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial.

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

Rapid and facile detection of largemouth bass ranavirus with CRISPR/Cas13a.

Largemouth bass ranavirus (LMBV) is an epidemic disease that seriously jeopardizes the culture of largemouth bass（Micropterus salmoides）, and it has a very high incidence in largemouth bass. Once an outbreak occurs, it may directly lead to the failure of the culture, resulting in substantial economic losses, but there is no effective vaccine or special effective drug yet. Consequently, it is important to establish an accurate, sensitive, convenient and specific detection approach for preventing LMBV infection. The recombinant enzyme-assisted amplification (RAA) technology was used in combination with clustered regularly interspaced short palindromic repeats (CRISPR), and associated protein 13a (CRISPR/Cas13a) to detect LMBV. We designed RAA primers and CRISPR RNA (crRNA) that targeted the conserved region in the LMBV main capsid protein (MCP) gene, amplified sample nucleic acids using the RAA technology, performed CRISPR/Cas13a fluorescence detection and evaluated the sensitivity and specificity of the established method with qPCR as a control method. This technique was able to determine the results by collecting fluorescence signals, visualizing fluorescence by UV excitation and combining with lateral flow strips (LFS). The sensitivity and specificity of the established method were consistent with the qPCR method. Besides, it was performed at a constant temperature of 37 °C and the sensitivity of the reaction system was 3.1 × 101 copies/µL, with no cross-reactivity with other common aquatic pathogens. Further, the positive detection rate of the proposed method in 32 clinical samples was consistent with that of qPCR. In conclusion, our established RAA-CRISPR/Cas13 method for detecting LMBV is sensitive, simple and specific, which is applicable in the rapid on-site detection and epidemiological monitoring of LMBV.

Clinical evaluation of autonomous robotic-assisted full-arch implant surgery: A 1-year prospective clinical study.

OBJECTIVES: This prospective clinical study aimed to evaluate the accuracy and 1-year clinical follow-up performance of dental implant placement with an autonomous dental implant robot (ADIR) system in full-arch implant surgery. MATERIALS AND METHODS: Twelve patients with edentulous arches or final dentition received 102 implants using the ADIR system. Global platform deviation, global apex deviation, and global angular deviation between the planned and actual implants were calculated after surgery. Data were statistically analyzed for factors including jaws, implant positions, patient sequences, implant systems, and implant length. Surgery duration was recorded. Patients were followed for 3 months and 1 year after surgery. Periodontal parameters, buccal bone thickness (BBT), and facial vertical bone wall peak (IP-FC) were recorded. RESULTS: Among the 102 implants, the mean (SD) global platform deviation, global apex deviation, and global angular deviation were 0.53 (0.19) mm, 0.58 (0.17) mm, and 1.83 (0.82)°, respectively. The deviation differences between the mandible and maxilla did not show statistical significance (p > .05). No statistically significant differences were found for the jaws, implant positions, patient sequences, implant systems, and implant length to the deviations (p > .05). The periodontal parameters, the BBT, and IP-FC remained stable during 1-year follow-up. CONCLUSION: The ADIR system showed excellent positional accuracy. The 1-year follow-up after full-arch implant surgery indicated that the ADIR system could achieve promising clinical performance. Additional clinical evidence is requisite to furnish guidelines for the implementation of the ADIR system in full-arch implant surgery.

The lncRNA20718-miR6022-RLPs module regulates tomato resistance to Phytophthora infestans.

KEY MESSAGE: Sl-lncRNA20718 acts as an eTM of Sl-miR6022 regulating its expression thereby affecting SlRLP6/10 expression. SlRLP6/10 regulate PRs expression, ROS accumulation, and JA/ET content thereby affecting tomato resistance to P. infestans. Tomato (Solanum lycopersicum) is an important horticultural and cash crop whose yield and quality can be severely affected by Phytophthora infestans (P. infestans). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are widely involved in plant defense responses against pathogens. The involvement of Sl-lncRNA20718 and Sl-miR6022 in tomato resistance to P. infestans as well as the targeting of Sl-miR6022 to receptor-like protein genes (RLPs) were predicted in our previous study. However, uncertainty exists regarding their potential interaction as well as the molecular processes regulating tomato resistance. Here, we found that Sl-lncRNA20718 and Sl-miR6022 are positive and negative regulators of tomato resistance to P. infestans by gain- and loss-of-function experiments, respectively. Overexpression of Sl-lncRNA20718 decreased the expression of Sl-miR6022, induced the expression of PRs, reduced the diameter of lesions (DOLs), thereby enhanced disease resistance. A six-point mutation in the binding region of Sl-lncRNA20718 to Sl-miR6022 disabled the interaction, indicating that Sl-lncRNA20718 acts as an endogenous target mimic (eTM) of Sl-miR6022. We demonstrated that Sl-miR6022 cleaves SlRLP6/10. Overexpression of Sl-miR6022 decreases the expression levels of SlRLP6/10, induces the accumulation of reactive oxygen species (ROS) and reduces the content of JA and ET, thus inhibiting tomato resistance to P. infestans. In conclusion, our study provides detailed information on the lncRNA20718-miR6022-RLPs module regulating tomato resistance to P. infestans by affecting the expression of disease resistance-related genes, the accumulation of ROS and the phytohormone levels, providing a new reference for tomato disease resistance breeding.

Accuracy of implant placement using CAD-CAM tooth-supported surgical guides for an auricular prosthesis in vitro.

PURPOSE: To evaluate the accuracy of tooth-supported surgical guides used to place implants in auricular prostheses. The accuracy (trueness and precision) of the implant positions was evaluated, and the difference between the surgical guide with and without retention of the external auditory canal (EAC) was compared. MATERIALS AND METHODS: This study simulated implant placement in vitro for the treatment of right auricle malformation. Surgical guides and other casts were fabricated using additive manufacturing technology. The casts were divided into 2 groups according to the surgical guide, with 10 bone blocks in each group (with or without the EAC plug (Guides 1 and 2)). Three implant positions (Implants 1-3) were prepared for each bone block using surgical guides. Implant positions were registered using light-body silicone impressions combined with optical surface scans to measure the coronal, apical, depth, and angular deviations. Four deviations of trueness and precision were reported as the mean ± standard deviation, which was analyzed by Student's t-test. RESULTS: Each group of 10 bone blocks with 30 implant positions was successfully prepared and digitally reproduced as implants. The accuracies of implant position with surgical guides were acceptable when compared with the preoperatively planned implant positions. Compared with the Guide 2 group, there was a significant difference in the apical, depth, and angular deviations of Guide 1 group in terms of precision (p = 0.001). There was a significant difference in the depth deviation of Implant 1 (p = 0.028) and apical deviation of Implant 2 (p < 0.001) compared two groups in terms of trueness. In terms of precision, there was a significant difference in the coronal (p = 0.002), apical (p = 0.001), and depth (p < 0.001) deviation of Implant 1; apical (p = 0.036) and angular (p < 0.001) deviation of Implant 2 also existed significant difference; the coronal deviation of Implant 3 (p = 0.018) also existed significant difference. Moreover, the group with the EAC plug showed lower deviation in precision and a smaller volume in the 95% confidence ellipsoid. CONCLUSION: Both types of tooth-supported surgical guides can provide acceptable accuracy. A surgical guide with an EAC plug was considered to be more precise.

Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

Influences of standardized clinical probing on peri-implant soft tissue seal in a situation of peri-implant mucositis: A histomorphometric study in dogs.

BACKGROUND: Clinical probing is commonly recommended to evaluate peri-implant conditions. In a situation of peri-implant mucositis or peri-implantitis, the peri-implant seal healing from the disruption of soft tissue caused by probing has not yet been studied. This study aimed to investigate soft tissue healing after standardized clinical probing around osseointegrated implants with peri-implant mucositis in a dog model. METHODS: Three transmucosal implants in each hemi-mandible of six dogs randomly assigned to the peri-implant healthy group or peri-implant mucositis group were probed randomly in the mesial or distal site as probing groups (PH or PM), the cross-sectional opposite sites as unprobed control groups. Histomorphometric measurements of implant shoulder (IS)-most coronal level of alveolar bone contact to the implant surface (BCI), apical termination of the junctional epithelium (aJE)-BCI, mucosal margin (MM)-BCI, and MM-aJE were performed at 1 day, 1 week, and 2 weeks after probing. Apoptosis, proliferation, proinflammatory cytokines, and matrix metalloproteinases (MMPs) of peri-implant soft tissue were estimated by immunofluorescent analysis. RESULTS: In the PM group, apical migration of junctional epithelium was revealed by significantly decreased aJE-BCI from 1 day to 2 weeks in comparison to unprobed sites (p < 0.05), while no significant differences were found in the PH group. Immunofluorescent analysis showed higher levels of interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), MMP-1, and MMP-8, together with exaggerated apoptosis and proliferation of peri-implant soft tissue in the PM group. CONCLUSION: Within the limitations, standardized clinical probing might lead to apical migration of the junctional epithelium in a situation of peri-implant mucositis.

Adipose Derived Mesenchymal Stem Cells-Derived Mitochondria Transplantation Ameliorated Erectile Dysfunction Induced by Cavernous Nerve Injury.

PURPOSE: Erectile dysfunction (ED) is a common postoperative complication of pelvic surgery for which there is currently no effective treatment. This study investigated the therapeutic effects and potential mechanisms of adipose derived mesenchymal stem cells-derived mitochondria (ADSCs-mito) transplantation in a rat model of bilateral cavernous nerve injury (CNI) ED. MATERIALS AND METHODS: We isolated mitochondria from ADSCs and tested their quality. In vivo, twenty male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI groups that received intracavernous injection of either phosphate buffer solution, ADSCs-mito or ADSCs. Two weeks after therapy, the erectile function of the rats was evaluated and the penile tissues were harvested for histologic analysis and western blotting. In vitro, the apoptosis rate, reactive oxygen species (ROS), mitochondria derived active oxygen (mtROS) and adenosine triphosphate (ATP) levels were detected in corpus cavernosum smooth muscle cells (CCSMCs) after the incubation with ADSCs-mito. In addition, intercellular mitochondrial transfer was visualized by co-culture of ADSCs and CCSMCs. RESULTS: The ADSCs, ADSCs-mito and CCSMCs were isolated and identified successfully. ADSCs-mito transplantation notably restored the erectile function and smooth muscle content of CNI ED rats. Moreover, the levels of ROS, mtROS and cleaved-caspase 3 were reduced and the levels of superoxide dismutase and ATP were increased after ADSCs-mito transplantation. In CNI ED rats, the mitochondrial structure of cells in penile tissues was destroyed. ADSCs could transfer its own mitochondria to CCSMCs. Pre-treatment with ADSCs-mito could significantly decrease apoptosis rate, ROS levels and mtROS levels as well as restore the ATP level in CCSMCs. CONCLUSIONS: ADSCs-mito transplantation significantly ameliorated ED induced by CNI, with similar potency to ADSCs treatment. The ADSCs-mito might exert their effects via anti-oxidative stress, anti-apoptosis and modulating energy metabolism of CCSMCs. Mitochondrial transplantation should be a promising therapeutic method for treating CNI ED in the future.

Loop-Mediated Isothermal Amplification (LAMP): Potential Point-of-Care Testing for Vulvovaginal Candidiasis.

PURPOSE: The aim of this study is to establish a loop-mediated isothermal amplification (LAMP) method for the rapid detection of vulvovaginal candidiasis (VVC). METHODS: We developed and validated a loop-mediated isothermal amplification (LAMP) method for detecting the most common Candida species associated with VVC, including C. albicans, N. glabratus, C. tropicalis, and C. parapsilosis. We evaluated the specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and Kappa value of the LAMP method to detect different Candida species, using the conventional culture method and internal transcribed spacer (ITS) sequencing as gold standards and smear Gram staining and real-time Rolymerase Chain Reaction (PCR) as controls. RESULTS: A total of 202 cases were enrolled, of which 88 were VVC-positive and 114 were negative. Among the 88 positive patients, the fungal culture and ITS sequencing results showed that 67 cases (76.14%) were associated with C. albicans, 13 (14.77%) with N. glabratus, 5 (5.68%) with C. tropicalis, and 3 (3.41%) with other species. Regarding the overall detection rate, the LAMP method presented sensitivity, specificity, PPV, NPV, and Kappa values of 90.91%, 100%, 100%, 93.4%, and 0.919, respectively. Moreover, the LAMP had a specificity of 100% for C. albicans, N. glabratus, and C. tropicalis, with a sensitivity of 94.03%, 100%, and 80%, respectively. Moreover, the microscopy evaluation had the highest sensitivity, while the real-time PCR was less specific for C. albicans than LAMP. In addition, CHROMagar Candida was inferior to LAMP in detecting non-albicans Candida (NAC) species. CONCLUSIONS: Based on the cost-effective, rapid, and inexpensive characteristics of LAMP, coupled with the high sensitivity and specificity of our VVC-associated Candida detection method, we provided a possibility for the point-of-care testing (POCT) of VVC, especially in developing countries and some laboratories with limited resources.

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.

Ultrasound-targeted microbubble destruction mediates PDE5i/NO integration for cavernosum remodeling and penile rehabilitation.

Erectile dysfunction (ED) caused by cavernous nerve injury (CNI) is refractory to heal mainly ascribed to the adverse remodeling of the penis induced by ineffectual microvascular perfusion, fibrosis, and neurotrophins scarcity in cavernosum. Phosphodiesterase type V inhibitors (PDE5i) have been regarded as an alternative candidate drug for avoiding penile neuropathy. However, the therapeutic efficacy is severely limited due to poor accumulation under systemic medication and endogenous nitric oxide (NO) deficiency in cavernosum. Herein, an innovative liposomal microbubble (MB) loaded with both Sildenafil (one of PDE5i) and NO was designed. Ultrasound-targeted MB destruction (UTMD)-mediated efficient release and integration erectogenic agents into corpus cavernosum with high biosafety. On a bilateral CNI rat model, the multifunctional MB-cooperated UTMD improved microvascular perfusion in penis, simultaneously, alleviated hypoxia and oxidative stress, indicating successful activation of NO-cyclic guanosine monophosphate pathway. Also, evaluation of the endothelial/muscular composition, intracavernosal pressure, and neural integrity in the penis proved that coordinated intervention reversed the abnormal structural remodeling and promoted the recovery of functional erection. Our work demonstrates that MB loading Sildenafil and NO combined with UTMD hold great promise to "awaken" the efficacy of PDE5i in neurogenic ED, which provided a superior option for ensuring penile rehabilitation.

Catalytic Asymmetric Reverse Prenylation of Indol-2-one Enabled a Synthesis of (-)-Debromoflustramine A.

A catalytic asymmetric nucleophilic reverse prenylation of indol-2-ones in situ generated from 3-bromooxindoles with prenyltributylstannane promoted by Ni(II)/chiral N,N'-dioxide was developed. This reaction provides facile access to C3 reverse-prenylated oxindoles in good to excellent enantioselectivities, which enabled the asymmetric synthesis of debromoflustramine A in five steps.

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

Implantation of skin-derived precursor Schwann cells improves erectile function in a bilateral cavernous nerve injury rat model.

BACKGROUND: This study was conducted to investigate the therapeutic potential of the skin-derived precursor Schwann cells for the treatment of erectile dysfunction in a rat model of bilateral cavernous nerve injury. RESULTS: The skin-derived precursor Schwann cells-treatment significantly restored erectile functions, accelerated the recovery of endothelial and smooth muscle tissues in the penis, and promoted nerve repair. The expression of p-Smad2/3 decreased after the treatment, which indicated significantly reduced fibrosis in the corpus cavernosum. CONCLUSIONS: Implantation of skin-derived precursor Schwann cells is an effective therapeutic strategy for treating erectile dysfunction induced by bilateral cavernous nerve injury.

RéSUMé: CONTEXTE: Cette étude a été menée pour étudier le potentiel thérapeutique des cellules de Schwann dérivées de la peau pour le traiter la dysfonction érectile survenue dans un modèle de lésion bilatérale du nerf caverneux chez le rat. RéSULTATS: Le traitement par des cellules de Schwann dérivées de la peau a significativement restauré les fonctions érectiles, accéléré la récupération des tissus endothéliaux et des tissues musculaires lisses du pénis, et a favorisé la réparation nerveuse. L'expression de p-Smad2/3 a diminué après le traitement, ce qui indique une fibrose significativement réduite dans le corps caverneux. CONCLUSION: L'implantation de cellules de Schwann dérivées de la peau est une stratégie thérapeutique efficace pour traiter la dysfonction érectile induite par une lésion bilatérale du nerf caverneux.

Construction of a Localized and Long-Acting CCN2 Delivery System on Percutaneous Ti Implant Surfaces for Enhanced Soft-Tissue Integration.

Soft-tissue integration (STI) plays an essential role in the long-term success of percutaneous Ti implants since it acts as a biological barrier that protects the soft and hard tissue around implants. Surface modification of Ti implants with drug-release properties to achieve soft-tissue regeneration has been proven to be effective in STI. However, the short-acting effect caused by the uncontrolled drug release of the topical delivery system limits long-term STI enhancement. Herein, a long-acting protein delivery system for Ti implants that involved micro-arc oxidation of Ti surfaces (MAO-Ti) and localized immobilization of cellular communication network factor 2 (CCN2) bearing mesoporous silica nanoparticles (MSNs) on MAO-Ti was prepared, namely, CCN2@MSNs-Ti. The CCN2 release study of CCN2@MSNs-Ti demonstrated a sustained-release profile for 21 days, which was able to maintain long-term stable STI. In addition, in vitro cell behavior evaluation results indicated that CCN2@MSNs-Ti could promote the STI-related biological response of human dermal fibroblasts via the FAK-MAPK pathway. More importantly, the system could effectively enhance STI after 4 weeks and proinflammatory factors in the soft tissue decreased significantly in a rat model of implantation. These results denote that CCN2@MSNs-Ti showed an appealing application prospect for enhanced STI around transcutaneous Ti implants, which would ultimately result in an increased success rate of percutaneous Ti implants.

A formal synthesis of (-)-erinacine B enabled by asymmetric organocatalysis.

A unified strategy for accessing the core structure of cyathane diterpenoids has been developed, enabling the formal synthesis of (-)-erinacine B. The key feature includes an organocatalyzed asymmetric intramolecular vinylogous aldol reaction for convergently building up the 5-6-6 tricyclic ring system. This strategy also highlights a hydroxyl-directed cyclopropanation/ring opening sequence to stereoselectively set up 1,4-anti and -cis angular-methyl quaternary carbon centers.

Biorefining of rapeseed meal: A new and sustainable strategy for improving Cr(VI) biosorption on residual wastes from agricultural byproducts after phenolic extraction.

Phenolic recovery from agricultural byproducts has been highlighted due to their health-promoting bioactivities. However, uncontrolled discard of residues after extraction process would induce environmental pollution and bioresource waste. In this study, biorefining of phenolic-rich rapeseed meal (RSM) and its defatted sample (dRSM) was attempted by holistic utilization of phenolic extract and residue separately. Phenolic removal could significantly improve residues' Cr(VI) adsorption capacities by about 21%, which presented extended physical surface and more released functional groups. Moreover, simulating raw material by remixing 3% separated phenolic extracts or main component sinapic acid therein with corresponding residues further improved about 12% adsorption efficiencies. These indicated that the different present forms of phenolics had opposite effects on Cr(VI) removal. While natural conjugational form inhibited hosts' biosorption, free form had enhanced functions for either extract or residue. Four optimal adsorption parameters (pH, adsorbent dosage, contact time and initial Cr(VI) concentration), three kinetic (pseudo-first order, pseudo-second order and intra-particle diffusion) models and two isotherms (Langmuir and Freundlich) were used to reveal the adsorption process. The maximum Cr(VI) adsorption capacity on residues could reach about 100 mg/g, which was superior to that of most biosorbents derived from agricultural byproducts, even some biochar. Together with the residues' advantages with everlasting capacity after 3 adsorption-desorption cycles and excellent abilities for adsorbing multiple co-existed metal ions (Cr(VI), Cd(II), Cu(II), Pb(II), Ni(II) and Zn(II)), phenolic recovery was first proved to be a new and sustainable strategy for modifying biosorbents from agricultural byproducts with zero waste.

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.

Roxarsone Delivery Nanocomposite Based on Nitrite-Functionalized Mesoporous Polydopamine for Multidrug-Resistant Bacterial Infections via Enhanced Chemo-Photothermal Therapy.

Current treatments for infections caused by multidrug-resistant bacteria still remain challenging and therapeutic materials with high efficacy are of demand. Herein, a bactericidal nanocomposite was constructed by loading Roxarsone (ROX) onto nitrosylated mesoporous polydopamine (named mPDA@NO-ROX). The designed nanocomposite exhibited considerable photothermal effect and controlled NO and ROX co-delivery under the irradiation of near-infrared laser (NIR) to achieve enhanced chemo-photothermal antibacterial therapy. The in vitro antibacterial evaluation of the mPDA@NO-ROX demonstrated the effective elimination of the Gram-negative tetracycline-resistant Escherichia coil and Gram-positive methicillin-resistant Staphylococcus aureus under mild NIR irradiation compared to merely ROX loaded unmodified mPDA, indicating the NO enhanced chemo-photothermal therapy. In addition, the cytotoxicity experiments indicated that mPDA@NO-ROX exhibited only 5 % of hemolysis rate and high cell viability at 1 mg mL-1 against mammalian fibroblasts, suggesting the excellent biocompatibility. In conclusion, the mPDA@NO-ROX could be a promising candidate for anti-infection therapy of multidrug-resistant bacteria.