Gut microbiome model predicts response to neoadjuvant immunotherapy plus chemoradiotherapy in rectal cancer.

BACKGROUND: Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT). METHODS: This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT. FINDINGS: A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceaebacterium and Blautiawexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort. CONCLUSIONS: Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC. FUNDING: This research was funded by the China National Natural Science Foundation (82202884).

Ultra-high b-value DWI in rectal cancer: image quality assessment and regional lymph node prediction based on radiomics.

OBJECTIVES: This study aims to evaluate image quality and regional lymph node metastasis (LNM) in patients with rectal cancer (RC) on multi-b-value diffusion-weighted imaging (DWI). METHODS: This retrospective study included 199 patients with RC who had undergone multi-b-value DWI. Subjective (five-point Likert scale) and objective assessments of quality images were performed on DWIb1000, DWIb2000, and DWIb3000. Patients were randomly divided into a training (n = 140) or validation cohort (n = 59). Radiomics features were extracted within the whole volume tumor on ADC maps (b = 0, 1000 s/mm2), DWIb1000, DWIb2000, and DWIb3000, respectively. Five prediction models based on selected features were developed using logistic regression analysis. The performance of radiomics models was evaluated with a receiver operating characteristic curve, calibration, and decision curve analysis (DCA). RESULTS: The mean signal intensity of the tumor (SItumor), signal-to-noise ratio (SNR), and artifact and anatomic differentiability score gradually were decreased as the b-value increased. However, the contrast-to-noise (CNR) on DWIb2000 was superior to those of DWIb1000 and DWIb3000 (4.58 ± 0.86, 3.82 ± 0.77, 4.18 ± 0.84, p < 0.001, respectively). The overall image quality score of DWIb2000 was higher than that of DWIb3000 (p < 0.001) and showed no significant difference between DWIb1000 and DWIb2000 (p = 0.059). The area under curve (AUC) value of the radiomics model based on DWIb2000 (0.728) was higher than conventional ADC maps (0.690), DWIb1000 (0.699), and DWIb3000 (0.707), but inferior to multi-b-value DWI (0.739) in predicting LNM. CONCLUSION: DWIb2000 provides better lesion conspicuity and LNM prediction than DWIb1000 and DWIb3000 in RC. CLINICAL RELEVANCE STATEMENT: DWIb2000 offers satisfactory visualization of lesions. Radiomics features based on DWIb2000 can be applied for preoperatively predicting regional lymph node metastasis in rectal cancer, thereby benefiting the stratified treatment strategy. KEY POINTS: Lymph node staging is required to determine the best treatment plan for rectal cancer. DWIb2000 provides superior contrast-to-noise ratio and lesion conspicuity and its derived radiomics best predict lymph node metastasis. DWIb2000 may be recommended as the optimal b-value in rectal MRI protocol.

Expression of microbial lipase in filamentous fungus Aspergillus niger: a review.

Lipase has high economic importance and is widely used in biodiesel, food, detergents, cosmetics, and pharmaceutical industries. The rapid development of synthetic biology and system biology has not only paved the way for comprehensively understanding the efficient operation mechanism of Aspergillus niger cell factories but also introduced a new technological system for creating and optimizing high-efficiency A. niger cell factories. In this review, all relevant data on microbial lipase enzyme sources and general properties are gathered and updated. The relationship between A. niger strain morphology and protein production is discussed. The safety of A. niger strain is investigated to ensure product safety. The biotechnologies and factors influencing lipase expression in A. niger are summarized. This review focuses on various strategies to improve lipase expression in A. niger. The summary of these methods and the application of the gene editing technology CRISPR/Cas9 system can further improve the efficiency of constructing the engineered lipase-producing A. niger.

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

Perceived stress and influencing factors for the people at high risk to COVID-19 in centralized quarantine camps in Wenzhou, China.

BACKGROUND: This study was designed to assess stress levels and related factors during the coronavirus disease 2019 (COVID-19) epidemic among individuals in centralized quarantine camps in Wenzhou, China. METHODS: The survey was conducted using a questionnaire. The questionnaire included questions on sociodemographic characteristics, life events related to the COVID-19 and stressful situations, as well as Perceived Stress Scale-14. Participants included close contacts of patients with COVID-19 or at-risk individuals in quarantine camps. Multivariate logistic regression was used to analyze different factors affecting perceived stress. RESULTS: The prevalence of high stress among quarantine camp participants was 37.45%. Of the 881 respondents, 51.99% were concerned about the difficulty of controlling the epidemic, 46.20% were concerned about the health of themselves and their family members and 39.61% were concerned about not being able to leave their homes. Multivariate logistic regression analysis revealed statistically significant differences in the prevalence of stress among different groups for certain variables, including occupation, education level and knowledge of COVID-19 (all P < 0.05). Our study found that at-risk individuals and close contacts experienced high levels of stress in quarantine camps during the COVID-19 pandemic. CONCLUSIONS: These findings suggest that centralized quarantine policies should be adapted and optimized to minimize negative psychological effects on quarantined individuals.

Effect of perioperative blood transfusion on complications and prognosis after radical gastrectomy in elderly patients: a retrospective study of 1,666 cases.

Background: Multiple studies have examined the effect of perioperative blood transfusion (BTF) on postoperative complications and the prognosis of gastric cancer patients, but the conclusions remain controversial, and few studies related to elderly patients are present. This study sought to examine the effect of perioperative BTF on postoperative complications and the prognosis of elderly patients who underwent radical gastrectomy. Methods: The clinical data of 1,666 elderly patients (aged ≥60 years) at Xijing Hospital from October 2013 to October 2021 were retrospectively analyzed. The patients were stratified into the perioperative BTF group and the perioperative non-BTF group. The clinicopathological characteristics, postoperative complications, and long-term prognoses of the patients were compared. Results: There were significant differences in terms of sex, tumor location, tumor size, gastrectomy range, tumor differentiation, T stage, N stage, tumor-node-metastasis (TNM) stage, preoperative anemia, and intraoperative blood loss between the two groups (P<0.05). The incidence of postoperative fever in the BTF group was significantly higher than that in the non-BTF group (31.6% vs. 15.4%, P<0.001), but there were no significant differences in the other complications between the two groups (P>0.05). The survival analysis showed that in stage III patients, the prognosis of the BTF group was inferior to that of the non-BTF group [the 3-year overall survival (OS) rates of the groups were 33.7% vs. 47.9% respectively, P<0.001], while there was no significant difference between the two groups among the stage I and stage II patients (P>0.05). There was no significant difference in the prognosis of patients with different transfusion times (preoperative/intraoperative/postoperative) (P>0.05). The multivariate analysis indicated that perioperative BTF was not an independent risk factor for prognosis in elderly patients with gastric cancer overall or elderly patients with gastric cancer in stage III (P>0.05). Conclusions: Perioperative BTF may elevate the incidence of fever but has no significant effect on other complications in elderly patients after radical gastrectomy. Perioperative BTF is not an independent risk factor affecting the postoperative prognosis of elderly patients with gastric cancer.

Prognostic value of dynamic changes of pre- and post-operative tumor markers in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) prognosis assessment is vital for personalized treatment plans. This study investigates the prognostic value of dynamic changes of tumor markers CEA, CA19-9, CA125, and AFP before and after surgery and constructs prediction models based on these indicators. METHODS: A retrospective clinical study of 2599 CRC patients who underwent radical surgery was conducted. Patients were randomly divided into training (70%) and validation (30%) datasets. Univariate and multivariate Cox regression analyses identified independent prognostic factors, and nomograms were constructed. RESULTS: A total of 2599 CRC patients were included in the study. Patients were divided into training (70%, n = 1819) and validation (30%, n = 780) sets. Univariate and multivariate Cox regression analyses identified age, total number of resected lymph nodes, T stage, N stage, the preoperative and postoperative changes in the levels of CEA, CA19-9, and CA125 as independent prognostic factors. When their postoperative levels are normal, patients with elevated preoperative levels have significantly worse overall survival. However, when the postoperative levels of CEA/CA19-9/CA125 are elevated, whether their preoperative levels are elevated or not has no significance for prognosis. Two nomogram models were developed, and Model I, which included CEA, CA19-9, and CA125 groups, demonstrated the best performance in both training and validation sets. CONCLUSION: This study highlights the significant predictive value of dynamic changes in tumor markers CEA, CA19-9, and CA125 before and after CRC surgery. Incorporating these markers into a nomogram prediction model improves prognostic accuracy, enabling clinicians to better assess patients' conditions and develop personalized treatment plans.

Activation of RhoA/ROCK2 signaling by hypoxia-inducible factor 1α in promoting tumor growth and metastasis in human colon cancer.

Background: Recent evidence strongly suggests the profound role of the tumor microenvironment in cancer development and progression. A hypoxic microenvironment is widely acknowledged to be a typical feature of solid tumors, and altered hypoxia-inducible factor 1α (HIF-1α) expression has been associated with the formation and the progression of many solid tumors; however, the underlying mechanism of this relationship remains obscure. Methods: Clinical colorectal cancer tissue samples were collected to detect the differential expression of HIF-1α, Ras homolog family member A (RhoA), and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2). With hypoxic stress, small interfering RNA (siRNA) targeting HIF-1α, lentivirus transfection of RhoA was used to study the mechanism of HIF-1α and RhoA/ROCK2 signaling pathways in the growth and metastasis of colon cancer. Results: According to Cell Counting Kit 8, wound-healing, and Transwell assays, HIF-1α expression activated the RhoA/ROCK2 pathway within colon cancer cell lines, accelerating their growth and expansion. In cells transfected with LV-RhoA, inactivating the RhoA/ROCK2 pathway with the specific inhibitor Y-27632 decreased tumor growth and metastasis under hypoxic conditions, while activating the RhoA/ROCK2 pathway restored these biological properties. The Western blot results showed that the expression levels of pMYPT1, cyclin D1, and MMP2 in the siRNA + LV-RhoA group were also significantly increased compared with those in the siRNA group. Conclusions: For the first time, this study demonstrated that HIF-1α can promote the growth and metastasis of colon cancer via directly affecting RhoA/ROCK2 signaling and thus represents a novel therapeutic target for colon cancer.

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.

Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study.

Background: Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. Materials and methods: This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. Results: The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). Conclusion: The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.

Resolution of N-acetyl-DL-methionine methyl ester by the lipase from Brucella thiophenivorans.

In this study, lipase-catalyzed resolution of N-acetyl-DL-methionine methyl ester (N-Ac-DL-MetOMe) was evaluated. A lipase from Brucella thiophenivorans was prone to exhibit high activity and excellent enantioselectivity toward N-Ac-DL-MetOMe to produce the key chiral intermediate N-acetyl-L-methionine methyl ester (N-Ac-L-MetOMe). The results showed that the enzymatic reaction was carried out in 100 g/L racemic substrate for 2 h, the conversion reached 51.3%, the enantiomeric excess value N-Ac-L-MetOMe exceeded 99%, and the enantiomeric ratio value >200. Therefore, the lipase from B. thiophenivorans has potential prospects for the resolution of N-Ac-DL-MetOMe to produce the important intermediate N-Ac-L-MetOMe.

A higher non-HDL-C/HDL-C ratio was associated with an increased risk of progression of nonculprit coronary lesion in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The ratio of nonhigh-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) has been shown associated with various metabolic diseases and atherosclerosis in primary prevention. However, there is limited evidence on the relationship between the non-HDL-C/HDL-C ratio and progression of nonculprit coronary lesion (NCCL) after percutaneous coronary intervention (PCI). HYPOTHESIS: Our study aimed to investigate the potential association between the non-HDL-C/HDL-C ratio and NCCL progression in patients with acute coronary syndrome (ACS) undergoing PCI. METHODS: We conducted a retrospective analysis of ACS patients who underwent coronary angiography twice at a single center from 2016 to 2022. Lipid measurements, demographic, clinical, and other laboratory data were collected from electronic medical records. NCCLs were evaluated using quantitative coronary angiography. The primary outcome was the progression of NCCL. Patients were categorized based on NCCL progression and tertiles of the non-HDL-C/HDL-C ratio. Associations were analyzed using univariate and multivariate logistic regression analysis. RESULTS: The study included 329 ACS patients who underwent PCI, with a median follow-up angiography of 1.09 years. We found NCCL progression in 95 (28.9%) patients with acceptable low-density lipoprotein cholesterol control (median: 1.81 mmol/L). Patients in the top tertile of the non-HDL-C/HDL-C ratio had a higher risk of NCCL progression. After adjusting for potential confounding factors, the non-HDL-C/HDL-C ratio remained a significant predictor for NCCL progression (adjusted odds ratio: 1.45; 95% confidence interval: 1.14-1.86; p < 0.05). CONCLUSIONS: The non-HDL-C/HDL-C ratio predicts NCCL progression in ACS patients following PCI, providing a valuable tool for risk assessment and enhancing secondary prevention of atherosclerotic cardiovascular disease.

Small extracellular vesicles-mediated cellular interactions between tumor cells and tumor-associated macrophages: Implication for immunotherapy.

The tumor microenvironment consists of cancer cells and various stromal cells, including macrophages, which exhibit diverse phenotypes with either pro-inflammatory (M1) or anti-inflammatory (M2) effects. The interaction between cancer cells and macrophages plays a crucial role in tumor progression. Small extracellular vesicles (sEVs), which facilitate intercellular communication, are known to play a vital role in this process. This review provides a comprehensive summary of how sEVs derived from cancer cells, containing miRNAs, lncRNAs, proteins, and lipids, can influence macrophage polarization. Additionally, we discuss the impact of macrophage-secreted sEVs on tumor malignant transformation, including effects on proliferation, metastasis, angiogenesis, chemoresistance, and immune escape. Furthermore, we address the therapeutic advancements and current challenges associated with macrophage-associated sEVs, along with potential solutions.

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.

Prognostic value of normal levels of preoperative tumor markers in colorectal cancer.

Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and alpha-fetoprotein (AFP) are widely used tumor markers for colorectal cancer (CRC), but their clinical significance is unknown when the levels of these tumor markers were within the normal range. This retrospective study included 2145 CRC patients. The entire cohort was randomly divided into training and validation datasets. The optimal cut-off values of tumor markers were calculated using X-tile software, and univariate and multivariate analyses were performed to assess its association with overall survival (OS). The nomogram model was constructed and validated. The entire cohort was randomly divided into a training dataset (1502 cases, 70%) and a validation dataset (643 cases,30%). Calculated from the training dataset, the optimal cut-off value was 2.9 ng/mL for CEA, 10.1 ng/mL for CA19-9, 13.4 U/mL for CA125, and 1.8 ng/mL for AFP, respectively. Multivariate analysis revealed that age, tumor location, T stage, N stage, preoperative CA19-9, and CA125 levels were independent prognostic predictors. Even within the normal range, CRC patients with relatively high levels of CA19-9 or CA125 worse OS compared to those with relatively low levels. Then, based on the independent prognostic predictors from multivariate analysis, two models with/without (model I/II) CA19-9 and CA125 were built, model I showed better prediction and reliability than model II. Within the normal range, relatively high levels of preoperative CA19-9 and CA125 were significantly associated with poor OS in CRC patients. The nomogram based on CA19-9 and CA125 levels showed improved predictive accuracy ability for CRC.

Remote guidance of percutaneous coronary intervention: A pilot study.

The safety and effectiveness of remote guidance of percutaneous coronary interventions (PCI) have not been fully appraised in controlled studies. We hereby presented the results of a study on remote guidance (vs on-site guidance) of PCI to explore its feasibility, safety, and effectiveness. Patients were recruited from those who received PCI procedures from January 2018 to June 2019 in a secondary hospital (Jincheng, Shanxi, China), in collaboration with a tertiary medical center (Beijing, China) approximately 680 km away. According to the type of guidance during the procedure, the patients were assigned to two groups: the remote guidance group and the on-site guidance group. Remote guidance was assisted with an advanced commercial telemedicine system. Interventional strategies, procedural success rate, peri-procedural complications, procedural duration, radiation doses, and the amount of contrast medium were compared between the two groups. A total of 352 patients were included in this study, with a total of 411 PCI procedures and 446 target lesions. The baseline clinical characteristics, as well as the distribution and characteristics of coronary artery lesions, did not differ significantly between the two groups. No significant differences were noticed in procedural success rate, peri-procedural complications, procedural duration, radiation dose, and in-hospital major adverse cardiovascular events. However, the amount of contrast medium was slightly higher in the remote guidance group. The results of the present pilot study showed the feasibility of remotely guided PCI, with safety and effectiveness measures at acceptable levels comparable to the traditional on-site guidance. Randomized studies with long-term follow-up are warranted to further confirm our findings.

Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment.

The role of mast cells (MCs) in colorectal cancer (CRC) remains unclear, and a comprehensive single-cell study on CRC MCs has not been conducted. This study used a multi-omics approach, integrating single-cell sequencing, spatial transcriptomics, and bulk tissue sequencing data to investigate the heterogeneity and impact of MCs in CRC. Five MC signature genes (TPSAB1, TPSB2, CPA3, HPGDS, and MS4A2) were identified, and their average expression was used as a marker of MCs. The MC density was found to be lower in CRC compared to normal tissue, but MCs in CRC demonstrated distinct activation features. Activated MCs were defined by high expression of receptors and MC mediators, while resting MCs had low expression. Most genes, including the five MC signature genes, were expressed at higher levels in activated MCs. The MC signature was linked to a better prognosis in both CRC and pan-cancer patient cohorts. Elevated KITLG expression was observed in fibroblasts and endothelial cells in CRC samples compared to normal tissue, and co-localization of MCs with these cell types was revealed by spatial transcriptome analysis. In conclusion, this study finds decreased MC density in CRC compared to normal tissue, but highlights a shift in MC phenotype from CMA1high resting cells to activated TPSAB1high, CPA3high, and KIThigh cells. The elevated KITLG expression in the tumor microenvironment's fibroblasts and endothelial cells may activate MCs through the KITLG-KIT axis, potentially suppressing tumor progression.

A nomogram was developed using clinicopathological features to predict postoperative liver metastasis in patients with colorectal cancer.

PURPOSE: The objective of this study is to examine the risk factors that contribute to the development of liver metastasis (LM) in patients who have suffered radical resection for colorectal cancer (CRC), and to establish a nomogram model that can be used to predict the occurrence of the LM. METHODS: The present study enrolled 1377 patients diagnosed with CRC between January 2010 and July 2021. The datasets were allocated to training (n = 965) and validation (n = 412) sets in a randomly stratified manner. The study utilized univariate and multivariate logistic regression analyses to establish a nomogram for predicting LM in patients with CRC. RESULTS: Multivariate analysis revealed that T stage, N stage, number of harvested lymph nodes (LNH), mismatch repair (MMR) status, neutrophil count, monocyte count, postoperative carcinoembryonic antigen (CEA) levels, postoperative cancer antigen 125 (CA125) levels, and postoperative carbohydrate antigen 19-9 (CA19-9) levels were independent predictive factors for LM after radical resection. These factors were then utilized to construct a comprehensive nomogram for predicting LM. The nomogram demonstrated great discrimination, with an area under the curve (AUC) of 0.782 for the training set and 0.768 for the validation set. Additionally, the nomogram exhibited excellent calibration and significant clinical benefit as confirmed by the calibration curves and the decision curve analysis, respectively. CONCLUSION: This nomogram has the potential to support clinicians in identifying high-risk patients who may develop LM post-surgery. Clinicians can devise personalized treatment and follow-up plans, ultimately leading to an improved prognosis for patients.

Effects of transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain in patients undergoing gastric and esophageal ESD surgery: a study protocol for a prospective randomized controlled trial.

BACKGROUND: Post-operative pain of endoscopic submucosal dissection (ESD) is always be overlooked and undertreated by endoscopists. However, the incidence of moderate to severe pain after ESD is as high as 44.9% to 62.8%, which can greatly affect the patient's recovery, reduce their satisfaction, and extend their hospital stay. Transcutaneous electrical acupoint stimulation (TEAS) have been shown to reduce postoperative pain and enhance gastrointestinal (GI) function recovery in patients undergoing abdomen surgery. However, there is no evidence regarding on the effect of TEAS on post-operative pain and complications in patients undergoing ESD. Therefore, we aim to investigate whether perioperative TEAS treatment is superior to the sham acupuncture in terms of post-ESD pain and GI function recovery. METHODS: This study is a prospective, randomized controlled trail, which is single-blinded and in single center. A total of 120 patients undergoing elective gastric and esophageal ESD surgery in Beijing Friendship Hospital, Capital Medical University, will be involved in this study. These individuals will be stratified according to the type of ESD surgery (i.e. gastric or esophageal procedure) and be randomly divided into two groups. L14, PC6, ST36 and ST37 will be stimulated at the TEAS treatment group, and the control group will receive simulation at four sham acupoints. The primary outcome is post-EDS VAS score at the time of entering PACU, 10 min, 20 min, 30 min, 1 h, 2 h, 4 h, 6 h, 18 h, 24 h, 48 h after the surgery. The secondary outcomes include the anesthesia-associated parameters, sedation score, nausea and vomiting score, shivering score, recovery of gastrointestinal function, satisfaction of patients to anesthesia, incidence of postoperative complications, QLQ-C30 life quality scale, and the economic indicators. DISCUSSION: The results of this study will confirm that continuous preventive application of TEAS can alleviate the postoperative pain among patients with gastric and esophageal ESD surgery and accelerate the recovery of post-ESD gastrointestinal function. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR2100052837, registered on November 6, 2021. http://www.chictr.org.cn/showproj.aspx?proj=135892 .