Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To investigate the risk factors of pleural effusion after spinal separation surgery for patients with spinal metastatic tumors.Methods:A total of 427 patients with spinal metastatic tumors from January 2014 to January 2022 in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. There were 252 males and 175 females, with an average age of 59±12 years (range, 15-87 years). All patients underwent separation surgery. Based on the chest CT within 1 month after surgery, the volume of pleural effusion was measured individually by reconstruction software. Pleural effusion was defined as small volume (0-500 ml), moderate volume (500-1 000 ml), and large volume (above 1 000 ml). Baseline data and perioperative clinical outcomes were compared between the groups, and indicators with statistically significant differences were included in a binary logistic regression analysis to determine the independent risk factors for the development of pleural effusion after isolation of spinal metastatic cancer. Receiver operating characteristic (ROC) curves were conducted to calculate the area under the curve (AUC) for each independent risk factor.Results:All patients successfully completed the operation. Among the 427 patients, there were 35 cases of large pleural effusion, 42 cases of moderate pleural effusion, and 350 cases of small pleural effusion. There were significant differences in tumor size (χ 2=9.485, P=0.013), intraoperative blood loss ( Z=-2.503, P=0.011), blood transfusion ( Z=-2.983, P=0.003), preoperative total protein ( Z=2.681, P=0.007), preoperative albumin ( Z=1.720, P= 0.085), postoperative hemoglobin ( t=2.950, P=0.008), postoperative total protein ( Z=4.192, P<0.001), and postoperative albumin ( t=2.268, P=0.032) in the large pleural effusion group versus the small and moderate pleural effusion group. Logistic regression analysis showed that decreased preoperative albumin ( OR=0.89, P=0.045) and metastases located in the thoracic spine ( OR=4.01, P=0.039) were independent risk factors for the occurrence of large pleural effusion after separation surgery. The ROC curve showed that the AUC and 95% CI for preoperative albumin, lesion location, and the combined model were 0.637 (0.54, 0.74), 0.421 (0.36, 0.48), and 0.883 (0.81, 0.92). The combined predictive model showed good predictive value. Conclusion:The volume of pleural effusion can be measured individually and quantitatively based on chest CT. Decreased preoperative albumin and metastases located in the thoracic spine are independent risk factors for the occurrence of large pleural effusion after separation surgery. The combined prediction of the two factors has better predictive efficacy.

Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.

Objective:To summarize the best evidence for exercise intervention in elderly patients with sarcopenia in intensive care unit (ICU) through literature search, and provide a reference for clinical implementation of early exercise intervention in this population through evidence-based practice.Methods:① Summary of best evidence: relevant literature on exercise intervention for elderly patients with sarcopenia in ICU, including guideline, evidence summary, expert consensus, systematic review, and original study [quasi-experiment and randomized controlled trial (RCT)] from UpToDate Clinical Advisor, Ovid database, National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence (NICE), Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed/Medline, SinoMed, CNKI, Wanfang Database, VIP, and Yimai Tong Guideline Network were systematically searched. The search period covered from the establishment of these databases up to August 24, 2023. The quality of the literature was evaluated by two researchers with methodological expertise in evidence-based medicine, and the evidences were extracted and summarized. ② Evidence-based practice: the elderly patients with high risk of sarcopenia who had been hospitalized in the ICU for more than 7 days from January to April 2024 were enrolled as the research subjects, and they were divided into a control group and an intervention group using convenience sampling method. The control group received routine intensive care nursing. The intervention group implemented exercise intervention based on the actual situation of the patients, the baseline review was conducted before evidence application, and the effectiveness of evidence application at 7 days and 14 days was evaluated.Results:① A total of 19 pieces of literature were included, including 4 guidelines, 1 summary of evidence, 4 expert consensuses, 4 systematic reviews, and 6 original studies (1 quasi-experiment, 5 RCT). After literature quality evaluation, all 19 articles were enrolled. Finally, 31 pieces of best evidence were extracted from eight aspects, including assessment and diagnosis, multidisciplinary cooperation, indication, preparation before intervention, intervention program, safety monitoring, post-intervention evaluation, and special task. ② Finally, a total of 30 patients were enrolled in the intervention group, of which 17 completed 14 days of rehabilitation exercise, and 13 completed 7 days of rehabilitation exercise. Twenty-seven patients were enrolled in the control group, of which 17 completed 14 days of monitoring, and 10 completed 7 days of monitoring. Clinical evidence application results showed that the patients in the intervention group did not experience adverse events such as increased heart rate, extubation, or physical discomfort. The skeletal muscle mass index (SMI) in both groups was gradually decreased with the prolongation of intervention duration, but the 7-day SMI in the intervention group was significantly higher than that in the control group (kg/m 2: 8.61±2.66 vs. 6.65±1.50, P < 0.01). Conclusion:By summarizing the best evidence and evidence-based practice of exercise intervention for elderly patients with sarcopenia in ICU, this study confirmed the feasibility due to safe and effective of implementing early exercise intervention for elderly sarcopenia patients in ICU.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To discuss the relationship between 18F-FDG PET/CT metabolic parameters and clinical pathological indicators and prognosis in cutaneous malignant melanoma (CMM). Methods:A total of 100 CMM patients (62 males, 38 females, age (56.5±2.5) years) who underwent 18F-FDG PET/CT scans at the Second Xiangya Hospital of Central South University from August 2013 to November 2022 were retrospectively enrolled. Clinical pathological indicators (such as primary site, TNM staging, sentinel lymph node (SLN) status) and metabolic parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG), whole-body MTV (wb-MTV), and whole-body TLG (wb-TLG)) were collected. ROC curve analyses were used to determine the PET parameters thresholds for progression-free survival (PFS) and melanoma-specific survival (MSS). Kaplan-Meier survival analysis, univariate and multivariate Cox proportional hazards regression models were used to analyze the prognosis of patients′ PFS and MSS, and a nomogram survival prediction model was constructed. Results:Results of ROC curve analyses showed that the thresholds of SUV max of primary tumor (p-SUV max), MTV of primary tumor (p-MTV), TLG of primary tumor (p-TLG), wb-MTV and wb-TLG for predicting PFS and MSS were 7.13, 2.24 cm 3, 6.98 g, 2.57 cm 3, 8.04 g and 9.09, 2.34 cm 3, 7.44 g, 2.24 cm 3, 9.17 g, respectively. Results of univariate analysis indicated that several clinical pathological indicators and metabolic parameters were prognostic risk factors for PFS and MSS. Results of multivariate analysis indicated that metastases of SLN (hazard ratio( HR)=2.54, 95% CI: 1.09-5.90; P=0.030) and wb-TLG>8.04 g( HR=2.58, 95% CI: 1.17-5.72; P=0.019) were independent prognostic risk factors for PFS, while metastases of SLN ( HR=4.53, 95% CI: 1.54-13.35; P=0.006) and wb-TLG>9.17 g ( HR=2.48, 95% CI: 1.26-4.89; P=0.009) were independent risk prognostic factors for MSS. A nomogram survival prediction model based on PET metabolic parameter (wb-TLG) and clinical pathological indicator (SLN status) can effectively predict the prognosis of CMM patients. Conclusions:Clinical pathological parameters and PET parameters are associated with the prognosis of CMM patients. SLN status is critical for prognosis.

Objective:To investigate the efficacy of 99Tc m-pyrophosphate (PYP) SPECT imaging for the differential diagnosis of transthyretin-related cardiac amyloidosis (ATTR-CA) and hypertrophic cardiomyopathy (HCM). Methods:Data of patients who were definitively diagnosed with ATTR-CA (35 patients (28 males, 7 females); age 62.5(58.6, 64.3) years) or HCM (14 patients (13 males, 1 female); age 60.5(57.3, 68.7) years) by extracardiac biopsy and echocardiography in the Second Xiangya Hospital of Central South University between June 2020 and March 2023 were retrospectively analyzed. All patients underwent planar and SPECT imaging 1 h after injection of 370-720 MBq 99Tc m-PYP. Visual scoring was performed (0-1 was negative, 2-3 was positive), and heart-to-contralateral lung uptake ratio (H/CL) was calculated based on planar images. The χ2 test was used to compare the difference in visual scores between ATTR-CA and HCM groups, and the diagnostic efficacy of the visual score was calculated. The H/CL differences between ATTR and HCM groups were compared with Mann-Whitney U test, and the ROC curve was used to analyze the efficacy of H/CL for the differential diagnosis of ATTR-CA and HCM. Results:There were 34 patients with visual scores≥2 and 1 patient with visual score<2 in the ATTR-CA group, 6 patients with visual scores =2 and 8 patients with visual scores <2 in HCM group, and there were significant differences between the 2 groups ( χ2=16.20, P<0.001). The diagnostic sensitivity of the visual score was 97.1%(34/35), and the specificity was 8/14. The H/CL in the ATTR-CA group was significantly higher than that in the HCM group (2.08(1.97, 2.20) vs 1.26 (1.17, 1.35), z=-5.09, P<0.001). The ROC curve analysis suggested that the optimal cut-off value was 1.45 (AUC: 0.980, 95% CI: 0.946-1.000; P<0.001); the sensitivity of H/CL differential diagnosis between HCM and ATTR-CA was 97.1%(34/35), and the specificity was 14/14. Conclusion:99Tc m-PYP SPECT imaging is useful in differentiation of ATTR-CA and HCM, and the optimal cut-off value of H/CL for differential diagnosis of these 2 diseases is 1.45.

Objective:To explore and analyze the predictive value of EuroSCORE Ⅱ and SYNTAX Ⅱ scores for clinical outcomes in patients undergoing coronary artery bypass grafting (CABG) surgery.Methods:A total of 500 coronary artery disease (CAD) patients who underwent CABG in Shanxi Cardiovascular Hospital from April 2014 to July 2023 were selected as the study subjects, all patients were given EuroSCORE Ⅱand SYNTAX Ⅱ scores to evaluate the predictive value of EuroSCOREⅡfor perioperative mortality and SYNTAX Ⅱ for 4-year mortality. Univariate and multivariate Logistic analysis were employed to analyze the independent risk factors for perioperative and 4-year mortality.Results:There were 3 deaths during the perioperative period, with a mortality rate of 0.60%, the predicted mortality rate of EuroSCOREⅡwas 1.71%; there were 21 deaths at 4 years after surgery, with a mortality rate of 4.23% and the predicted mortality rate of SYNTAX Ⅱwas 9.02%. Logistic regression analysis showed that left ventricular ejection fraction (LVEF) was the only independent protective factor for perioperative mortality, and advanced age was the only independent risk factor for 4-year postoperative mortality in patients ( P<0.05). The analysis of the working characteristic curve of the subjects found that the area under the receiver operating characteristic curve ( ROC) of EuroSCORE Ⅱ for perioperative mortality was 0.782, and the area under ROC curve of SYNTAX Ⅱfor postoperative 4-year mortality was 0.743. Conclusion:Both EuroSCORE Ⅱand SYNTAX Ⅱhave certain predictive value for perioperative mortality and postoperative 4-year mortality in patients undergoing CABG, respectively, but the predicted mortality rate is relatively higher.