Perfusion outcomes with near-infrared indocyanine green imaging system in laparoscopic total mesorectal excision for mid-rectal or low-rectal cancer (POSTER): a study protocol.

INTRODUCTION: Anastomotic leakage (AL) is defined as the failure of complete healing or disruption of the anastomosis subsequent to rectal cancer surgery, resulting in the extravasation of intestinal contents into the intra-abdominal or pelvic cavity. It is a serious complication of rectal cancer surgery, accounting for a considerable increase in morbidity and mortality. The use of fluorescence imaging technology in surgery allows surgeons to better evaluate blood perfusion. However, the conclusions of some existing studies are not consistent, so a consensus on whether the near-infrared indocyanine green (NIR-ICG) imaging system can reduce the incidence of AL is needed. METHODS: This POSTER trial is designed as a multicentre, prospective, randomised controlled clinical study adhering to the "population, interventions, comparisons, outcomes (PICO)" principles. It is scheduled to take place from August 2019 to December 2024 across eight esteemed hospitals in China. The target population consists of patients diagnosed with rectal cancer through pathological confirmation, with tumours located≤10 cm from the anal verge, eligible for laparoscopic surgery. Enrolled patients will be randomly assigned to either the intervention group or the control group. The intervention group will receive intravenous injections of ICG twice, with intraoperative assessment of anastomotic blood flow using the near-infrared NIR-ICG system during total mesorectal excision (TME) surgery. Conversely, the control group will undergo conventional TME surgery without the use of the NIR-ICG system. A 30-day follow-up period postoperation will be conducted to monitor and evaluate occurrences of AL. The primary endpoint of this study is the incidence of AL within 30 days postsurgery in both groups. The primary outcome investigators will be blinded to the application of ICG angiography. Based on prior literature, we hypothesise an AL rate of 10.3% in the control group and 3% in the experimental group for this study. With a planned ratio of 2:1 between the number of cases in the experimental and control groups, and an expected 20% lost-to-follow-up rate, the initial estimated sample size for this study is 712, comprising 474 in the experimental group and 238 in the control group. ETHICS AND DISSEMINATION: This study has been approved by Ethics committee of Beijing Friendship Hospital, Capital Medical University (approval number: 2019-P2-055-02). The results will be disseminated in major international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04012645.

The Role and Prospects of Mesenchymal Stem Cells in Skin Repair and Regeneration.

Mesenchymal stem cells (MSCs) have been recognized as a cell therapy with the potential to promote skin healing. MSCs, with their multipotent differentiation ability, can generate various cells related to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. In addition, MSCs promote neovascularization, cellular regeneration, and tissue healing through mechanisms including paracrine and autocrine signaling. Due to these characteristics, MSCs have been extensively studied in the context of burn healing and chronic wound repair. Furthermore, during the investigation of MSCs, their unique roles in skin aging and scarless healing have also been discovered. In this review, we summarize the mechanisms by which MSCs promote wound healing and discuss the recent findings from preclinical and clinical studies. We also explore strategies to enhance the therapeutic effects of MSCs. Moreover, we discuss the emerging trend of combining MSCs with tissue engineering techniques, leveraging the advantages of MSCs and tissue engineering materials, such as biodegradable scaffolds and hydrogels, to enhance the skin repair capacity of MSCs. Additionally, we highlight the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies as a future direction in stem cell-based treatments, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.

Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer (NECTAR): a multi-center phase 2 study.

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) / mismatch repair-proficient (pMMR) tumors is an attractive, but debatable strategy. This phase 2, multicenter, prospective, single-arm study enrolled patients from 6 centers from June 2021 to November 2022. Locally advanced rectal cancer (LARC, cT3-4aN0M0 and cT1-4aN1-2M0) patients aged ≥18 years with the distance from distal border of tumor to anal verge ≤10 cm (identified by Magnetic Resonance Imaging) were qualified for inclusion. The patients received long-course radiotherapy (50 Gy/25 fractions, 2 Gy/fraction, 5 days/week) and three 21-day cycles capecitabine (850-1000 mg/m2, bid, po, day1-14) and three 21-day cycles tislelizumab (200 mg, iv.gtt, day8) as neoadjuvant. Total mesorectal excision (TME) was 6-12 weeks after the end of radiotherapy to achieve radical resection. A total of 50 patients were enrolled in this study. The pathological complete response rate was 40.0% [20/50, 95% confidence interval (CI): 27.61-53.82%], while 15 (30.0%, 95% CI: 19.1-43.75%), 9 (18.0%, 95% CI: 9.77-30.8%), 2 (4.0%, 95% CI: 1.10-13.46%) patients respectively achieved grade 1, 2, and 3 tumor regression. Treatment-related adverse events (TRAEs) occurred in 28 (56.0%) LARC patients, including 26(52.0%) with grade I-II and 2 (4.0%) with grade III (1 with grade 3 immune-related colitis and 1 with grade 3 rash). PD-1 blockade plus long-course chemoradiotherapy (CRT) showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients. A larger randomized controlled study is desired to further validate the above findings.

Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis.

Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10-3). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.

Study on the mechanism of salt relief and growth promotion of Enterobacter cloacae on cotton.

AIMS: In-depth studies on plant ion uptake and plant growth-promoting rhizobacteria (PGPR) at the molecular level will help to further reveal the effects of PGPR on plants and their interaction mechanisms under salt stress. METHODS: Cotton was inoculated with a PGPR-Enterobacter cloacae Rs-35, and the ion uptake capacity, membrane transporter protein activity, and expression of key genes were determined under salt stress. Changes in the endogenous hormone content of cotton were also determined. Further, the genome-wide metabolic pathway annotation of E. cloacae Rs-35 and its differential enrichment pathway analysis of multi-omics under salinity environments were performed. RESULTS: In a pot experiment of saline-alkali soil, E. cloacae Rs-35-treated cotton significantly increased its uptake of K+ and Ca2+ and decreased uptake of Na+, elevated the activity of the H+-ATPase, and increased the sensitivity of the Na+/H+ reverse transporter protein on the vesicle membrane. Meanwhile, inoculation with E. cloacae Rs-35 could promote cotton to maintain the indole-3-acetic acid (IAA) content under salt stress. Genome-wide annotation showed that E. cloacae Rs-35 was respectively annotated to 31, 38, and 130 related genes in osmotic stress, phytohormone and organic acid metabolism, and ion uptake metabolic pathway. Multi-omics differences analysis showed that E. cloacae Rs-35 were enriched to tryptophan metabolism, multiple amino acid biosynthesis, carbon and glucose synthesis, and oxidative phosphorylation metabolic pathways at the transcriptome, proteome, and metabolome. CONCLUSION: E. cloacae Rs-35 can promote cotton balance cell ion concentration, stabilize intracellular IAA changes, stimulate induction of systemic tolerance, and promote the growth of cotton plants under salt stress.

Enhanced CO2 Reactive Capture and Conversion Using Aminothiolate Ligand-Metal Interface.

Metallic catalyst modification by organic ligands is an emerging catalyst design in enhancing the activity and selectivity of electrocatalytic carbon dioxide (CO2) reactive capture and reduction to value-added fuels. However, a lack of fundamental science on how these ligand-metal interfaces interact with CO2 and key intermediates under working conditions has resulted in a trial-and-error approach for experimental designs. With the aid of density functional theory calculations, we provided a comprehensive mechanism study of CO2 reduction to multicarbon products over aminothiolate-coated copper (Cu) catalysts. Our results indicate that the CO2 reduction performance was closely related to the alkyl chain length, ligand coverage, ligand configuration, and Cu facet. The aminothiolate ligand-Cu interface significantly promoted initial CO2 activation and lowered the activation barrier of carbon-carbon coupling through the organic (nitrogen (N)) and inorganic (Cu) interfacial active sites. Experimentally, the selectivity and partial current density of the multicarbon products over aminothiolate-coated Cu increased by 1.5-fold and 2-fold, respectively, as compared to the pristine Cu at -1.16 VRHE, consistent with our theoretical findings. This work highlights the promising strategy of designing the ligand-metal interface for CO2 reactive capture and conversion to multicarbon products.

The first chromosome-level Fallopia multiflora genome assembly provides insights into stilbene biosynthesis.

Fallopia multiflora (Thunb.) Harald, a vine belonging to the Polygonaceae family, is used in traditional medicine. The stilbenes contained in it have significant pharmacological activities in anti-oxidation and anti-aging. This study describes the assembly of the F. multiflora genome and presents its chromosome-level genome sequence containing 1.46 gigabases of data (with a contig N50 of 1.97 megabases), 1.44 gigabases of which was assigned to 11 pseudochromosomes. Comparative genomics confirmed that F. multiflora shared a whole-genome duplication event with Tartary buckwheat and then underwent different transposon evolution after separation. Combining genomics, transcriptomics, and metabolomics data to map a network of associated genes and metabolites, we identified two FmRS genes responsible for the catalysis of one molecule of p-coumaroyl-CoA and three molecules of malonyl-CoA to resveratrol in F. multiflora. These findings not only serve as the basis for revealing the stilbene biosynthetic pathway but will also contribute to the development of tools for increasing the production of bioactive stilbenes through molecular breeding in plants or metabolic engineering in microbes. Moreover, the reference genome of F. multiflora is a useful addition to the genomes of the Polygonaceae family.

Interim result of phase II, prospective, single-arm trial of long-course chemoradiotherapy combined with concurrent tislelizumab in locally advanced rectal cancer.

Background: Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer, with modest benefits on tumor regression and survival. Since chemoradiotherapy combined with immune checkpoint inhibitors has been reported to have synergic effects. This study aims to explore the safety and efficacy of long-course chemoradiotherapy combined with concurrent tislelizumab as a neoadjuvant treatment regimen for patients with locally advanced rectal cancer. Methods: This manuscript reported the interim result of a prospective, multicenter, single-arm, phase II trial. Patients with mid-to-low locally advanced rectal cancer with clinical stages of cT3-4a N0M0 or cT1-4a N1-2M0 were included. The patients received long-course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles of capecitabine (1000 mg/m2, bid, day1-14) plus concurrent three 21-day cycles of tislelizumab (200 mg, day8), followed by a radical surgery 6-8 weeks after radiotherapy. The primary endpoint was the pathological complete response rate. (Clinical trial number: NCT04911517). Results: A total of 26 patients completed the treatment protocol between April 2021 and June 2022. All patients completed chemoradiotherapy, 24 patients received three cycles of tislelizumab, and 2 patients received two cycles. The pathological complete remission (ypT0N0) was achieved in 50% (13/26) of the patients with all proficient mismatch repair tumors. The immune-related adverse event occurred in 19.2% (5/26) of patients. Patients with no CEA elevation or age less than 50 were more likely to benefit from this treatment regimen. Conclusion: Long-course chemoradiotherapy combined with concurrent tislelizumab in patients with locally advanced low rectal cancer had favorable safety and efficacy, and does not increase the complication rate of surgery. Further study is needed to confirm these results.

Incidence and Risk Factors of Surgical Complications and Anastomotic Leakage After Transanal Total Mesorectal Excision for Middle and Low Rectal Cancer.

PURPOSE: Transanal total mesorectal excision (taTME) is a promising surgical procedure for middle and low rectal cancer; however, it is linked to significant morbidity. This study aimed to determine the incidence of postoperative surgical complications and anastomotic leakage following taTME and to identify their associated risk factors. METHODS: The prospective clinical data of 114 patients, who underwent taTME and primary anastomosis for mid-low rectal cancer between November 2016 and June 2022, were retrospectively analyzed. Univariate and multivariate analyses were performed to identify clinical characteristics and risk factors for predicting surgical complications and anastomotic leakage. RESULTS: Surgical complications occurred in 40 (35.1%) patients within the first 30 days following surgery. Based on the Clavien-Dindo classification, minor complications (Clavien-Dindo grades I + II) accounted for 30.7%, while major complications (Clavien-Dindo grades III + IV) accounted for only 4.4%. None of the patients died within 30 days. The incidence of anastomotic leakage was 15.8%: 4.4% as grade A (5 cases), 9.6% as grade B (11 cases), and 1.8% as grade C (2 cases). Preoperative T3-4 was identified as an independent risk factor for surgical complications (p = 0.031) by multivariate analysis. American Society of Anesthesiology score ≥ 3 (P = 0.021) and incomplete total mesorectal excision specimens (P = 0.030) were significantly associated with the risk of anastomotic leakage. CONCLUSIONS: In this study, the incidence of surgical complications and anastomotic leakage in taTME aligned with previously reported rates. Preoperative T3-4 was significantly associated with surgical complications. American Society of Anesthesiology score ≥ 3 and incomplete TME specimens independently increased the risk of anastomotic leakage.

Prognostic nutrition index predicts short-term surgical complications in patients with rectal cancer after laparoscopic surgery.

Purpose: Surgical complications following laparoscopic rectal cancer surgery remain a major clinical problem. The prognostic nutritional index (PNI) is reportedly associated with postoperative outcomes. We aimed to evaluate the correlation between PNI and short-term surgical complications in patients with rectal cancer after laparoscopic surgery. Methods: The prospective clinical data of 225 patients with rectal cancer receiving laparoscopic surgery between January 2021 and April 2022 were retrospectively analyzed. The cut-off values and diagnostic accuracy of PNI preoperatively and on postoperative day (POD) 1 were determined using receiver operating characteristic (ROC) curves. Univariate and multivariate analyses were performed to identify clinical characteristics and risk factors for surgical complications. Results: In total, 81 (36.0%) patients developed surgical complications. The optimal cut-off value for preoperative PNI was 40.15, and that for PNI on POD 1 was 35.28. The DeLong test found no statistically between-group difference in the area under the ROC curve (P = 0.598). Multivariate analysis identified that a preoperative PNI ≤40.15 [odds ratio (OR): 2.856, 95% confidence interval (CI): 1.287-6.341, P = 0.010] and PNI on POD 1 ≤35.28 (OR: 2.773, 95% CI: 1.533-5.016, P = 0.001) were independent risk factors for surgical complications. Patients with a preoperative PNI ≤40.15 or PNI on POD 1 ≤35.28 were more likely to have surgical complications after laparoscopic surgery for rectal cancer (61.1% vs. 31.2%, P = 0.001; 53.0% vs. 28.9%, P = 0.001). Conclusion: Preoperative and POD 1 PNI were independent predictors of short-term surgical complications after laparoscopic surgery for rectal cancer.

The taTME learning curve for mid-low rectal cancer: a single-center experience in China.

PURPOSE: As transanal total mesorectal excision (taTME) is performed worldwide, the optimization of existing training and guidance programs to enhance new taTME learners' competence in performing this procedure is warranted. This study aimed to evaluate the taTME learning curve in patients with mid-low rectal cancer. METHODS: Patients who underwent taTME for mid-low rectal cancer between October 2015 and August 2021 at a single center were included. A cumulative sum (CUSUM) learning curve analysis was performed with the total operation time as the study outcome. The learning curve was analyzed using risk-adjusted CUSUM analysis, with postoperative complications and anastomotic leakage (AL) as outcomes. RESULTS: In total, 104 consecutive patients were included in this study. The CUSUM learning curve for total operative time started declining after 42 cases (309.1 ± 84.4 vs. 220.2 ± 46.4, P < 0.001). The risk-adjusted CUSUM (RA-CUSUM) learning curve for postoperative complications fluctuated in cases 44-75 and declined significantly after case 75. The RA-CUSUM learning curve for AL declined after 68 cases. CONCLUSIONS: taTME had learning curves of 42, 75, and 68 cases for total operative time, postoperative complications, and AL, respectively. A surgeon may require 42 and 75 cases to achieve "proficiency" and "mastery" in taTME procedures, respectively.

Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer.

Immunotherapies, especially the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, have revolutionized the therapeutic strategies of various cancers. As for colorectal cancer (CRC), the current clinical application of PD-1/PD-L1 inhibitors are mainly used according to the mutation pattern, which is categorized into deficient mismatch repair (dMMR)/high levels of microsatellite instability (MSI-H) and proficient mismatch repair (pMMR), or non-high levels of microsatellite instability (non-MSI-H). PD-1/PD-L1 inhibitors have been proven to have favorable outcomes against dMMR/MSI-H CRC because of more T-cell infiltration into tumor tissues. Nevertheless, the effectiveness of PD-1/PD-L1 inhibitors in pMMR/non-MSI-H CRC is still uncertain. Because of the quite-lower proportion of dMMR/MSI-H in CRC, PD-1/PD-L1 inhibitors have been reported to combine with other antitumor treatments including chemotherapy, radiotherapy, and targeted therapy for better therapeutic effect in recent clinical trials. Neoadjuvant therapy, mainly including chemotherapy and radiotherapy, not only can reduce clinical stage but also benefit from local control, which can improve clinical symptoms and the quality of life. Adding immunotherapy into neoadjuvant therapy may change the treatment strategy of primary resectable or some metastatic CRC. In this review, we focus on the development of neoadjuvant anti-PD-1/PD-L1 therapy and discuss the future perspectives in CRC.

Abdomen anatomic characteristics on CT scans as predictive markers for short-term complications following radical resection of colorectal cancer.

Background: Prediction and management of short-term postoperative complications in patients with colorectal cancer are essential in postoperative rehabilitation. Through CT scan images, we can easily measure some parameters of abdomen anatomic characteristics. This study aimed to assess whether there is a relationship between the abdomen anatomic characteristics and short-term postoperative complications. Materials and methods: We conducted a retrospective study. Eighty patients in each complication group and non-complication group were recruited with propensity score match. Demographics, perioperative laboratory results and surgical information were collected and compared between groups with univariate analysis. Significant elements were brought into subsequent logistic regression analysis and ROC analysis for further identification. Results: Univariate analysis showed that preoperative white blood cells, preoperative neutrophil counts, rectus abdominis thickness (RAT), subcutaneous fat thickness (SFT), and abdomen depth (AD) were significantly different between the complication group and non-complication group. Logistic regression analysis demonstrated that higher RAT (p = 0.002), SFT (p < 0.001) and AD (p < 0.001) independently predicted the incidence of short-term postoperative complications. Conclusions: In this study on patients undergoing radical resection of colorectal cancer, abdomen anatomic characteristics including higher RAT, SFT and AD are associated with an increased risk of short-term postoperative complications.

Rationale and design of a prospective, multicenter, cohort study on the evaluation of postoperative Venous ThromboEmbolism incidence in patients with ColoRectal Cancer (CRC-VTE trial).

Background: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication after abdominal surgery. The incidence of VTE after colorectal malignancy is higher than that after general surgery. Although more attention has been paid to the prevention of VTE, there is still a large gap between clinical practice and guideline recommendation. Methods: The Venous ThromboEmbolism incidence in patients with ColoRectal Cancer (CRC-VTE trial) will be a prospective, multicenter, cohort study to determine the current status of the incidence, diagnosis, treatment, and prevention of VTE after colorectal cancer surgery in China, as well as to further improve the level of prevention and treatment of VTE events in these fragile patients. In this study, 1,217 patients will be enrolled at 40 centers in China and evaluated on VTE events and adverse events related to VTE prevention at 5-9 and 21-28 days after surgery. The primary outcome is the incidence of VTE events during the follow-up, and secondary outcome is the incidence of adverse events associated with VTE prevention. Discussion: This study will comprehensively evaluate the incidence and prevention of VTE after colorectal cancer surgery in China, balance the relationship between VTE prevention and bleeding adverse events, and the formulate a guideline for the prevention of VTE after colorectal surgery that might suitable for national conditions. Trial Registration: Clinical trial registration number NCT04588805 (The CRC-VTE trial).

An Evaluation of Traits, Nutritional, and Medicinal Component Quality of Polygonatum cyrtonema Hua and P. sibiricum Red.

Polygonati rhizoma (Huangjing in Chinese) is a traditional and classic dual-purpose material used in food and medicine. Herbalists in China and Japan have noticed several different rhizome types in Huangjing with different qualities. Rhizome of Polygonatum cyrtonema Hua and P. sibiricum Red. is divided into five types: "Jitou-type" Polygonati rhizoma (JTPR), atypical "Jitou-type" Polygonati rhizoma (AJTPR), "Jiang-type" Polygonati rhizoma (JPR), "Cylinder-type" Polygonati rhizoma (CPR), and "Baiji-type" Polygonati rhizoma (BJPR). This study observed the microstructure and histochemical localization of polysaccharides, saponins, and proteins in Huangjing. Nutritional and medicinal component data and antioxidant capacity (DPPH and ABTS) were analyzed to evaluate the quality of different types of Huangjing. The results showed that the comprehensive quality of the rhizomes, BJPR and JTPR, was better, regardless of their nutritional or medicinal values. Altogether, these results could recommend future breeding efforts to produce Huangjing with improved nutritional and medicinal qualities.

Rationale and design of a prospective, multicenter, phase II clinical trial of safety and efficacy evaluation of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorectal excision for locally advanced rectal cancer (NCRT-PD1-LARC trial).

BACKGROUND: Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. However, the safety and efficacy of long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab followed by TME for LARC is still uncertain. METHODS: This NCRT-PD1-LARC trial will be a prospective, multicenter and phase II clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. This trial will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 7 cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6-8 weeks after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes. DISCUSSION: To our knowledge, this trial is the first multicenter clinical trial in China to assess the safety and efficacy of NCRT plus anti-PD1 therapy followed by TME to treat patients with LARC. NCRT followed by TME was recognized as the most recommended treatment against LARC while could not be completely satisfied in clinic. This study expects to provide a solid basis and encouraging outcomes for this promising combination of radiotherapy, chemotherapy and immunotherapy in LARC. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04911517. Date of registration: 23 May 2021. URL of trial registry record: https://www. CLINICALTRIALS: gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1 .

Clinical benefits of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Immunotherapy for colorectal cancer has developed rapidly in the past decade. Many high-quality clinical trials examining the application of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer (mCRC) have been conducted in recent years. However, the clinical benefits, including the efficacy and safety of these treatments against mCRC, remain controversial. Hence, we conducted this meta-analysis on the clinical benefits of PD-1/PD-L1 inhibitors in patients with mCRC. METHODS: We searched online databases including MEDLINE, Embase, Cochrane Library, and Web of Science, from inception to January 4, 2021. The outcomes related to efficacy and safety were extracted and analyzed. Subgroup analyses were conducted according to the categories of dMMR-MSI-H (tumors with mismatch repair deficiency and high levels of microsatellite instability) ≥ 5% vs. dMMR-MSI-H < 5%, monotherapy vs. combination therapy, PD-1 inhibitors vs. PD-L1 inhibitors, and nivolumab vs. pembrolizumab. RESULTS: Fourteen studies including 1129 subjects were included in our systematic review. The overall complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD) rates were 0.01 (95% CI 0.00-0.04), 0.04 (95% CI 0.05-0.26), 0.27 (95% CI 0.22-0.32), and 0.44 (95% CI 0.30-0.58), respectively. The overall objective response rate (ORR) and disease control rate (DCR) were 0.16 (95%CI 0.06-0.31) and 0.50 (95%CI 0.35-0.65), respectively. The overall rate of adverse events (AEs) and severe adverse responses (SAEs) were 0.84 (95% CI 0.72-0.92) and 0.30 (95% CI 0.20-0.41), respectively. The ORRs of the dMMR-MSI-H ≥ 5% and dMMR-MSI-H < 5% subgroups were 0.40 (95% CI 0.30-0.51) and 0.04 (95% CI 0.00-0.09), respectively. CONCLUSIONS: PD-1/PD-L1 inhibitors produced encouraging clinical benefits including the response rate in the treatment of dMMR-MSI-H mCRC. They actually have been influenced by the present state of mCRC therapy including pMMR-MSI-L mCRC. Nevertheless, additional multi-center prospective studies are still expected. TRIAL REGISTRATION: We have registered this study in the International Prospective Register of Systematic Reviews (PROSPERO), and the registration number is CRD42021249601 .

Nano-oxygenated hydrogels for locally and permeably hypoxia relieving to heal chronic wounds.

Exposed chronic wounds are usually covered by hypoxic tissues accompanied with necrosis, persistent inflammation and anaerobic infections. Since atmospheric oxygen air can only penetrate about 0.3 mm tissues, meanwhile oxygen from the circulation is difficult to reach chronic wounds through the destroyed blood vessels, a solution to deliver oxygen locally and permeably is urgently needed. Herein we report a technique to reform traditional gel-based wound dressings by adding lyophilized oxygen encapsulated nanoparticles, which can deliver dissolved oxygen locally into wound surface. This delivery technique can potentially evaluate the therapeutic effects on hypoxic epithelial, endothelial and fibroblasts in vitro. Further experiments confirm the effects on both open wounds bearing and flap transplanted diabetic mice models. Considering its biocompatibility, effectiveness and practicality, we believe our hydrogel has significant transformation value to care and accelerate the healing of various clinical wounds, especially chronic wound.

Current Progress and Outlook of Nano-Based Hydrogel Dressings for Wound Healing.

Wound dressing is an important tool for wound management. Designing wound dressings by combining various novel materials and drugs to optimize the peri-wound environment and promote wound healing is a novel concept. Hydrogels feature good ductility, high water content, and favorable oxygen transport, which makes them become some of the most promising materials for wound dressings. In addition, nanomaterials exhibit superior biodegradability, biocompatibility, and colloidal stability in wound healing and can play a role in promoting healing through their nanoscale properties or as carriers of other drugs. By combining the advantages of both technologies, several outstanding and efficient wound dressings have been developed. In this paper, we classify nano-based hydrogel dressings into four categories: hydrogel dressings loaded with a nanoantibacterial drug; hydrogel dressings loaded with oxygen-delivering nanomedicines; hydrogel dressings loaded with nanonucleic acid drugs; and hydrogel dressings loaded with other nanodelivered drugs. The design ideas, advantages, and challenges of these nano-based hydrogel wound dressings are reviewed and analyzed. Finally, we envisaged possible future directions for wound dressings in the context of relevant scientific and technological advances, which we hope will inform further research in wound management.