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Abstract Immune checkpoint inhibitors (ICIs) have achieved remarkable success in clinical research and practice. Notably, liver metastasis is not sensitive to ICIs. Liver locoregional therapies can cause irreversible damage to tumor cells and release tumor antigens, thereby providing a rationale for immunotherapy treatments in liver metastasis. The combination therapy of ICIs with locoregional therapies is a promising option for patients with liver metastasis. Preclinical studies have demonstrated that combining ICIs with locoregional therapies produces a significantly synergistic anti-tumor effect. However, the current evidence for the efficacy of ICIs combined with locoregional therapies remains insufficient. Therefore, we review the literature on the mechanisms of locoregional therapies in treating liver metastasis and the clinical research progress of their combination with ICIs.

Abstract Background Invasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future. Methods The clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared. Results Included in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28,

The SARS-CoV-2, responsible for the COVID-19 pandemic, poses a significant threat to global healthcare. Peptide and peptide-based inhibitors, known for their safety, efficacy, and selectivity, have recently emerged as promising candidates for treating late-developing viral infections. In this study, three peptides were selected to target different stages of viral invasion, specifically ACE2 and S protein binding, as well as membrane fusion. The objective was to assess their ability to impede the entry of the SARS-CoV-2 Spike pseudotyped virus. Our findings revealed that a combination of these three peptides demonstrated enhanced antiviral effects. This outcome substantiates the feasibility of developing effective peptide combinations to combat diseases related to SARS-CoV-2. Moreover, the three-peptide combinations, designed to target multiple aspects of SARS-CoV-2 viral entry, exhibited heightened viral inhibition and broad-spectrum antiviral properties.

Peritoneal carcinomatosis (PC) is a type of secondary cancer which is not sensitive to conventional intravenous chemotherapy. Treatment strategies for PC are usually palliative rather than curative. Recently, artificial intelligence (AI) has been widely used in the medical field, making the early diagnosis, individualized treatment, and accurate prognostic evaluation of various cancers, including mediastinal malignancies, colorectal cancer, lung cancer more feasible. As a branch of computer science, AI specializes in image recognition, speech recognition, automatic large-scale data extraction and output. AI technologies have also made breakthrough progress in the field of peritoneal carcinomatosis (PC) based on its powerful learning capacity and efficient computational power. AI has been successfully applied in various approaches in PC diagnosis, including imaging, blood tests, proteomics, and pathological diagnosis. Due to the automatic extraction function of the convolutional neural network and the learning model based on machine learning algorithms, AI-assisted diagnosis types are associated with a higher accuracy rate compared to conventional diagnosis methods. In addition, AI is also used in the treatment of peritoneal cancer, including surgical resection, intraperitoneal chemotherapy, systemic chemotherapy, which significantly improves the survival of patients with PC. In particular, the recurrence prediction and emotion evaluation of PC patients are also combined with AI technology, further improving the quality of life of patients. Here we have comprehensively reviewed and summarized the latest developments in the application of AI in PC, helping oncologists to comprehensively diagnose PC and provide more precise treatment strategies for patients with PC.

Objectives Carcinosarcoma (CS) is a rare and biphasic malignancy characterised by a highly invasive biological nature and poor prognosis. This study explored the epidemiology, site-specific characteristics and survival outcome of CS.Design We conducted a retrospective study in the Surveillance, Epidemiology and End Results (SEER) database (1975–2018) for primary CS.Setting and participants SEER database includes publicly available information from regional and state cancer registries in the US centres. A total of 5042 CS patients were identified. We selected the top five anatomic CS (uterus, double adnexa, lung, bladder and breast) patients for further analysis.Primary outcome measures Incidence was estimated by geographical region, age, sex, race, stage and primary site. Trends were calculated using joinpoint regression. The cancer-specific survival (CSS) rate and initial treatment were summarised.Results Nearly 80% of CS occurred in the uterus and double adnexa, followed by lung, bladder and breast. The elderly and black population presented the highest age-adjusted rate of CS. The rates of distant metastasis in CS progressively increased from 1989 to 2018. Atlanta was the area with the highest incidence at 0.7 per 100 000. Pulmonary and bladder CS more frequently occurred in men and were diagnosed with regional stage. Distant metastasis was mostly found in ovary/fallopian tube CS. Radiotherapy was more commonly applied in uterine CS, while adnexa CS cases were more likely to receive chemotherapy. Multiple treatments were more used in breast CS. Pulmonary CS seemed to suffer worse CSS (median: 9.92 months), for which radiotherapy might not provide survival benefits (HR 0.60, 95% CI 0.42 to 0.86). Compared with the common histological types in each site, CS had the shortest survival.Conclusions CS has unique clinical features in each primary site. Substantial prognosis variances exist based on tumour locations. The aggressive course is the common feature in CS at all sites.

For colorectal cancer (CRC), surgical resection remains essential for achieving good prognoses. Unfortunately, numerous patients with locally advanced CRC and metastatic CRC failed to meet surgical indications or achieve pathological complete response after surgery. Perioperative therapy has been proven to effectively lower tumor staging and reduce recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have shown unprecedented prolongation of survival time and satisfactory safety in patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR), while the therapeutic effect obtained by patients with mismatch repair-proficient or microsatellite stable (pMMR/MSS) was considered minimal. However, recent studies found that certain CRC patients with dMMR/MSI-H presented intrinsic or acquired immune resistance, and pMMR/MSS CRC patients can also achieve better efficacy. Therefore, more predictors are required for screening patients with potential clinical benefits. Since the discovery of synergistic effects between immunotherapy, chemotherapy, and radiotherapy, different immunotherapy-based therapies have been applied to the perioperative therapy of CRC in an increasing number of research. This review comprehensively summarized the past and current progress of different combinations of immunotherapy in perioperative clinical trials for CRC, focusing on the efficacy and safety, and points out the direction for future development.

Abstract Background Intraperitoneal paclitaxel is proved to be efficient for peritoneal metastasis of gastric cancer. It remains uncertain the efficacy and safety of the triplets regimen which combined intraperitoneal high‐dose paclitaxel with systemic SOX in gastric cancer patients with peritoneal metastasis. This study aimed to evaluate the efficacy and safety of intraperitoneal administration of high‐dose paclitaxel, intravenous oxaliplatin and S‐1 in patients with peritoneal metastatic gastric cancer. Methods This single‐center, prospective, single‐arm phase II study was conducted between January 2017 and May 2019 in West China Hospital, Sichuan University. Patients diagnosed with primary gastric cancer by histopathology and confirmed synchronous peritoneal metastasis were enrolled. This study aimed to evaluate efficacy and safety of intraperitoneal administration of high‐dose paclitaxel (80 mg/m2, d1), intravenous oxaliplatin (100 mg/m2, d1), and S‐1 (80 mg/m2, d1‐14) of patients. The primary endpoint was 1‐year overall survival rate, and the second endpoints were progression‐free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and adverse events. Results In this single‐arm phase II clinical trial, 49 patients received SOX combined intraperitoneal high‐dose paclitaxel treatment. One‐year survival rate was 81.6% (95% CI, 68.6–90.0%). Median PFS and OS were 6.50 months (95% CI, 2.89–10.11) and 16.9 months (95% CI, 13.58 to 20.22), respectively; ORR was 55.3% (95% CI, 41.3–68.6) and DCR was 76.6% (95% CI, 62.8–86.4). Thirteen patients underwent second laparoscopic detection, but only nine ultimately underwent radical gastrectomy. Subgroup analysis showed that sPCI ≤12 was a good index for a favorable prognosis. The most frequent grade 3/4 toxicities were neutropenia (40.8%), anemia (22.4%), leukopenia (18.4%), nausea (14.3%), and vomiting (12.2%). None of the patients had any intraperitoneal catheter‐related complications. Conclusions Intraperitoneal high‐dose paclitaxel with systemic SOX is an effective and tolerable first‐line treatment for patients with peritoneal metastatic gastric cancer and patients with sPCI≤12 scores might be recommended crowd for this regimen as conversion therapy.

Drivers show different characteristics in traffic oscillations. These differences reflect the driver’s driving style, which is an important part of traffic uncertainty. This paper deeply explores the driving characteristics in asymmetric driving behaviour and its influence on traffic flow characteristics. The aim is to improve the understanding of safe driving. Continuous vehicle trajectories under various traffic flow conditions in an expressway merging area are obtained by aerial photography. Image processing technology is used to extract the basic parameters of traffic flow and vehicle operating characteristic data. Based on the measured data, the driver’s response mode is subdivided into multiple sub-modes. On the basis of this study, the types and distribution of traffic hysteresis and the impact of asymmetric behaviour on merging area capacity are further revealed. The results show that the response coefficient will increase for 58.72 % drivers during the process of experiencing oscillation disturbance to rebalance. The traffic hysteresis caused by driver’s asymmetric following behaviour in an expressway merging area is generally positive. This reduces the bottleneck outflow rate of the merging area by about 7 % on average. This study has important practical significance in analysing the formation mechanism of traffic congestion and adopting effective protective measures.

ObjectiveChemotherapy-induced mucositis (CIM) significantly impacts clinical outcomes and diminishes the quality of life in patients with gastrointestinal cancer. This study aims to prospectively determine the incidence, severity, and underlying risk factors associated with CIM in this patient population.MethodsTo achieve this objective, we introduce a novel Machine Learning-based Toxicity Prediction Model (ML-TPM) designed to analyze the risk factors contributing to CIM development in gastrointestinal cancer patients. Within the winter season spanning from December 15th, 2018 to January 14th, 2019, we conducted in-person interviews with patients undergoing chemotherapy for gastrointestinal cancer. These interviews encompassed comprehensive questionnaires pertaining to patient demographics, CIM incidence, severity, and any supplementary prophylactic measures employed.ResultsThe study encompassed a cohort of 447 participating patients who provided complete questionnaire responses (100%). Of these, 328 patients (73.4%) reported experiencing CIM during the course of their treatment. Notably, CIM-induced complications led to treatment discontinuation in 14 patients (3%). The most frequently encountered CIM symptoms were diarrhea (41.6%), followed by nausea (37.8%), vomiting (25.1%), abdominal pain (21%), gastritis (10.5%), and oral pain (10.3%). Supplementary prophylaxis was administered to approximately 62% of the patients. The analysis revealed significant correlations between the overall incidence of CIM and gender (p=0.015), number of chemotherapy cycles exceeding one (p=0.039), utilization of platinum-based regimens (p=0.039), and administration of irinotecan (p=0.003). Specifically, the incidence of diarrhea exhibited positive correlations with prior surgical history (p=0.037), irinotecan treatment (p=0.021), and probiotics usage (p=0.035). Conversely, diarrhea incidence demonstrated an adverse correlation with platinum-based treatment (p=0.026).ConclusionIn conclusion, this study demonstrates the successful implementation of the ML-TPM model for automating toxicity prediction with accuracy comparable to conventional physical analyses. Our findings provide valuable insights into the identification of CIM risk factors among gastrointestinal cancer patients undergoing chemotherapy. Furthermore, the results underscore the potential of machine learning in enhancing our understanding of chemotherapy-induced mucositis and advancing personalized patient care strategies.

Abstract Background Neoadjuvant radiochemotherapy followed by radical surgery is the standard treatment strategy for local advanced rectal cancer (LARC). However, the efficacy of neoadjuvant radiochemotherapy is limited, especially for patients with DNA mismatch repair‐deficient (dMMR)/microsatellite instability‐high (MSI‐H) rectal cancer. Considering the amazing therapeutic effect of immune check point inhibitors for metastatic colorectal cancer, we conduct this multicenter, phase Ib study to investigate the safety and efficacy of anti‐PD‐1 antibody, sintilimab combined with hypofractionated radiotherapy in MSI‐H/dMMR rectal cancer patients. Methods Patients with MSI‐H/dMMR LARC will receive hypofractionated radiotherapy (5 Gy × 5) and three cycles of sintilimab 200 mg IV every 2 weeks. Radical surgery will be performed 6–8 weeks after radiotherapy. The primary endpoint is adverse reaction after neoadjuvant treatment and perioperative complications. Secondary endpoints include pathological response rate, complete resection rate, and quality of life. Discussion This is the first study to investigate the safety and effectiveness of neoadjuvant radiotherapy combined with immunotherapy for MSI‐H/dMMR LARC. It is expected that this study will propose a brand new and effective treatment strategy for MSI‐H/dMMR LARC.

Ovarian metastasis (OM) from colorectal cancer (CRC) is infrequent and has a poor prognosis. The purpose of this study is to investigate the value of a contrast-enhanced CT-based radiomics model in predicting ovarian metastasis from colorectal cancer outcomes after systemic chemotherapy. A total of 52 ovarian metastatic CRC patients who received first-line systemic chemotherapy were retrospectively included in this study and were categorized into chemo-benefit (C+) and no-chemo-benefit (C−) groups, using Response Criteria in Solid Tumors (RECIST v1.1) as the standard. A total of 1743 radiomics features were extracted from baseline CT, three methods were adopted during the feature selection, and five prediction models were constructed. Receiver operating characteristic (ROC) analysis, calibration analysis, and decision curve analysis (DCA) were used to evaluate the diagnostic performance and clinical utility of each model. Among those machine-learning-based radiomics models, the SVM model showed the best performance on the validation dataset, with AUC, accuracy, sensitivity, and specificity of 0.903 (95% CI, 0.788–0.967), 88.5%, 95.7%, and 82.8%, respectively. All radiomics models exhibited good calibration, and the DCA demonstrated that the SVM model had a higher net benefit than other models across the majority of the range of threshold probabilities. Our findings showed that contrast-enhanced CT-based radiomics models have high discriminating power in predicting the outcome of colorectal cancer ovarian metastases patients receiving chemotherapy.

Introduction Neoadjuvant chemotherapy (NAC) has been demonstrated effective in several tumours, but its benefit has not yet been elucidated in colorectal cancer, especially locally advanced colorectal cancer (LACRC).Methods and analysis This is a single-arm, open-label, prospective phase II exploratory clinical trial. Patients with LACRC will receive four cycles of NAC with 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI), followed by operation and then adjuvant chemotherapy with capecitabine and oxaliplatin for two to five cycles or single-agent capecitabine for five cycles, or observation. The primary endpoint is the rate of tumour regression grade (TRG) 0–2 in the resected tumour tissue, which is evaluated by experienced pathologists according to the Ryan R TRG grading system. Secondary endpoints include objective response rate, pathologic complete response, microscopically complete resection rate, progression-free survival, distant metastasis-free survival, overall survival, toxicity and compliance to study treatment, molecular markers, quality of life to study treatment and the number of patients with 30-day postoperative mortality. The objective of this study is to analyse the efficacy and safety of FOLFOXIRI as the NAC regimen in patients with LACRC and to identify a promising treatment strategy in this setting.Ethics and dissemination Written informed consent will be required from and provided by all patients enrolled. The study protocol has been approved by the independent ethics committee of West China Hospital, Sichuan University (approval number: 2021403). This study will demonstrate the potential benefit of NAC with the FOLFOXIRI regimen. Results will be shared with policymakers and the academic community to promote the clinical management of colon cancer.Trial registration number NCT05018182.

Abstract To have a more comprehensive understanding of the water ecological security status of the Yellow River Basin, this paper constructs a water ecological security evaluation index system founded on the Pressure-State-Response (PSR) model. The indicators are selected by considering factors such as meteorological conditions, population, economy, water resources, water environment, water ecology, land ecology, ecological service functions, pollution control, and capital investment. Then, the “single index quantification-multiple indices syntheses-poly-criteria integration (SMI-P) method was used to determine the water ecological security index (WESI) of 62 cities in the Yellow River Basin, to classify the safety levels, and combined with the spatial autocorrelation analysis to study the regional characteristics. The results prove that: (a) The overall water ecological security of the Yellow River Basin is relatively poor. Half of the 62 cities have reached the second-level warning level, and most of them are concentrated in the upper and middle reaches of the basin. (b) Wetland area is a long-term key factor in the construction of water ecological safety, and the greening rate of built-up areas has an increasing impact on water ecological safety. (c) The overall water ecological security index shows a slow upward trend, with the annual average growth rate was 0.59%. (d) The water ecological security of 62 cities in the Yellow River Basin shows significant spatial autocorrelation. The findings can offer a practical basis for the water ecological management to promote the high-quality development of the Yellow River Basin.

Abstract It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r 2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Immune-related myocarditis is a severe and even life-threatening immune-related adverse event (irAE) which may also be underestimated due to the challenge in diagnosis. The inherent difference between individuals with immune-associated myocarditis has received little attention. Our study aimed to identify which baseline characteristics could contribute to distinguishing mild from severe ICI myocarditis. A retrospective analysis was conducted between March 2019 and June 2020 in West China Hospital, and 18 patients with immune-related myocarditis were studied. Patients were classified as having mild (n = 12) or severe myocarditis (n = 6), according to the clinical manifestations and hemodynamic complications. Factors associated with severe myocarditis were identified by comparing covariates derived from medical records in various groups. In this retrospective analysis, the median age of the 18 patients was 60 years old. Most myocarditis cases occur early and approximately after the first or second ICI infusion. The severity of myocarditis may be correlated with lactate dehydrogenase (LDH) (p = 0.04) and troponin levels (p = 0.0057). The relationship between troponin and myocarditis was further confirmed in another cohort, which included 30 patients. In addition, patients are more likely to develop multi-irAEs, and myositis was the most common second irAE. Those who experience multi-irAEs usually had significantly higher LDH (p = 0.02) and myoglobin levels (p = 0.02) than those who did not experience them. All patients were treated with steroids timely, and the mortality rate was 5.6% in our study. In this study, we explored risk factors for severe myocarditis and emphasized the importance of a multidisciplinary team in assisting diagnosis and treatment options. It is critical to initiate corticosteroid therapy, regardless of the severity of the myocarditis.

BackgroundClose to one third of colorectal cancer (CRC) patients are diagnosed with metastatic CRC (mCRC). Patients with wild-type RAS and BRAF usually receive anti-EGFR monoclonal antibody therapy containing cetuximab. Overall, 30–50% of mCRC patients are reported to harbor RAS mutations, and RAS mutation status should be assessed when considering EGFR inhibitor treatment according to mCRC biomarker guidelines. Of note, 0.67–2% of patients with CRC harbored a KRAS amplification. Here we reported a case of advanced rectal cancer with wild-type RAS and BRAF in a male patient who harbored a KRAS amplification during anti-EGFR treatment.Case PresentationA 46-year-old man was diagnosed with rectal adenocarcinoma with liver metastases (cT3NxM1a, stage IVA). After receiving first-line irinotecan- fluorouracil chemotherapy (FOLFIRI) plus cetuximab, second-line capecitabine- oxaliplatin chemotherapy (XELOX) plus bevacizumab, and third-line regorafenib, he rechallenged FOLFIRI and cetuximab for seven cycles, achieving a prolonged survival of at least 5 months. The KRAS copy number of circulating tumor DNA (ctDNA) was assessed during treatment. Notably, apart from serum carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA), the change of plasm Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) copy number appeared to strongly correlate with treatment response.ConclusionOur findings suggest that the dynamic change of KRAS copy number on ctDNA during treatment might be a negative predictive biomarker. Additionally, RAS and BRAF wild-type mCRC patients who are resistant to first-line FOLFIRI plus cetuximab therapy may respond well to the FOLFIRI plus cetuximab “rechallenged” strategy.

BackgroundGallbladder squamous cell carcinoma (GSCC) is a rare carcinoma with limited evidence in literature, making it particularly difficult to study. Surveillance, Epidemiology, and End Results Database (SEER) were used to stress the clinicopathological features and outcomes associated with this tumor.MethodsSEER registries were used to identify GSCC and gallbladder adenocarcinoma (GAC) cases from 2004 to 2015. The Propensity matching (PSM) method was used for minimized potential difference between the two types and the utmost. Patients with GSCC versus GAC were compared using the clinicopathological features and outcomes.ResultsThere were 121 patients with GSCC and 6 580 patients had GAC. Compared with the GAC cohort, the GSCC cohort had a lower proportion of well-differentiated histology (3.3% vs. 12.1%, p < 0.001) and was diagnosed at a later T-stage (p < 0.001). Regarding treatment, patients treated with surgery, chemotherapy or radiation were associated with significantly better outcome than patients without undergoing these treatment modalities. In both univariate and multivariate analyses, GSCC histology was associated with worse prognosis than GAC histology.ConclusionsPatients with GSCC were associated with a worse outcome than the GAC cohort. The independent risk factors for patients with GSCC are surgery and chemotherapy.

Background: Raltitrexed plus S-1 (RS) and regorafenib both showed considerable efficacy for metastatic colorectal cancer (mCRC) patients. This study aims to compare the effectiveness and safety of two different regimens in patients with refractory mCRC. Methods: This retrospective cohort study included mCRC patients who were treated with RS or regorafenib from February 2017 to June 2021. A propensity score matching (PSM) analysis was conducted to balance the baseline characteristics of all patients. Progression-free survival (PFS), overall survival (OS), tumor response, and safety of two regimens were evaluated. Results: A total of 187 patients were included in our study, with 107 patients in the RS group and 80 patients in the regorafenib group. After PSM, 78 pairs were recognized. Patients treated with RS had a semblable PFS compared to those treated with regorafenib before PSM (4.8 months vs 5.5 months, p = 0.400) and after PSM (4.7 months vs 5.4 months, p = 0.430). Patients in the RS group were associated with a longer OS than those in the regorafenib group (13.4 months vs 10.1 months, p = 0.010). A similar trend of OS was also obtained in the matched cohort (13.3 months vs 10.0 months, p = 0.024). Both objective response rate (12.8% vs 5.1%, p = 0.093) and disease control rate (53.8% vs 46.2%, p = 0.337) in the RS cohort were higher than those in the regorafenib group, without significant differences. Adverse events (AEs) of each group were well tolerated. Conclusion: Patients treated with RS demonstrated a longer OS than those treated with regorafenib and had manageable AEs, which could be recognized as a primary choice for refractory mCRC. Plain Language Summary Efficacy and Safety of Raltitrexed plus S-1 Versus Regorafenib in Patients with Refractory Metastatic Colorectal Cancer: A Real - world Propensity Score Matching Study Both raltitrexed plus S-1 (RS) and regorafenib showed considerable efficacy for metastatic colorectal cancer (mCRC) patients. No study has compared the two regimens yet. Therefore, we compare the efficacy and safety between RS and regorafenib to provide an optimal treatment option. We retrospectively included patients with mCRC who failed at least two standard treatments. All enrolled patients received RS or regorafenib treatments. We conducted a propensity score matching to eliminate differences in the enrolled patients. After the analysis, we found no significant differences in progression-free survival in patients between the two groups. However, patients treated with RS had a longer OS than those treated with regorafenib, whether before matching (13.4 months vs 10.1 months, p = 0.010) or after matching (13.3 months vs 10.0 months, p = 0.024). In addition, the adverse effects caused by cancer-related therapy were tolerable for the patient. Certainly, this is a non-randomized retrospective study with a small sample size, so we conducted a propensity score matching to minimize potential bias. Importantly, this is the first research comparing the two treatments, and we believe that the results of this article could present a primary choice for clinical doctors dealing with patients with standard treatments that failed mCRC.

Objective This study aimed to determine the benefits of adjuvant therapy in patients with resected biliary tract cancer (BTC) and identify the optimal adjuvant treatment scheme.Design Systematic review and network meta-analysis.Data sources Studies comparing different adjuvant therapies in patients with BTC were searched in PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases from inception to December 2021. Additionally, the references were manually searched for the related literature.Materials and methods Eligible studies were identified, and data were extracted independently by two authors. A random-effects network meta-analysis was performed using R software. The pooled outcomes of overall survival (OS) and disease-free survival (DFS) were measured using the combined HRs with 95% CIs.Results Nineteen eligible studies reporting three types of adjuvant therapies were included in our network meta-analysis. Adjuvant radiotherapy (ART, HR 0.62; 95% CI 0.42 to 0.93), adjuvant chemoradiotherapy (ACRT; HR 0.71; 95% CI 0.54 to 0.83) and adjuvant chemotherapy (ACT; HR 0.84; 95% CI 0.68 to 0.98) were more effective in prolonging OS than that of observation, with no significant difference between the three adjuvant therapies. Moreover, the improvement in DFS was also found in ACRT and ACT compared with that of observation (HR 0.60; 95% CI 0.45 to 0.75; HR 0.82; 95% CI 0.68 to 0.97, respectively). Furthermore, ACRT obtained a slightly better DFS benefit compared with that of ACT (HR 0.73; 95% CI 0.53 to 0.95).Conclusions Our primary results demonstrated that, compared with that of observation, ACRT and ACT after radical resection could provide better OS and DFS benefits in patients with BTC. However, ART only showed improvement in OS, but not in DFS. Due to the lack of head-to-head studies of ACT, ACRT and ART, the above results need to be further verified by prospective randomised controlled trials.

It has been difficult to revise and adjust the water distribution of the Yellow River in 1987 (1987 water distribution scheme). By gathering data and studies from previous literature, this paper summarized some water distribution ideas, principles and rules in transboundary rivers. We proposed the “synthesis–dynamic–harmonious” water distribution method (SDH), and applied it to the actual conditions of the Yellow River basin. Through the SDH method, we calculated a new scheme for water distribution in the Yellow River and analyzed the results. The key findings of this study are summarized below. Firstly, the water distribution of transboundary rivers required the establishment of advanced water distribution ideas. Secondly, the proposed water distribution method took into account a variety of factors: with the change in distributable water volume, the same ratio changes and meets the minimum water demand and water efficiency constraints. Thirdly, the 1987, the water distribution scheme needed some adjustment. Fourthly, under the new Yellow River basin water distribution scheme (“19ZQT” water distribution scheme), Shandong, Inner Mongolia, and Henan account for 50% of the total water distribution. Sichuan accounts for only 0.3% of the total. Compared with the 1987 water distribution scheme, Hebei and Tianjin reduced the amount of water allocated by 51.2%, while Shaanxi increased it by 24.89%. In this paper, considering the changes in the total distributable water volume, the new Yellow River water distribution scheme (“19ZQT” water distribution scheme) assumed water distribution of 37 billion m3 and 30 billion m3, upon which calculations were performed. This study should provide a scientific and reasonable scheme for water distribution of transboundary rivers, and rational utilization of water resources. It should lay a solid foundation for the high-quality development of the Yellow River basin.

Background: It is controversial whether primary tumour resection (PTR) and the sequencing of chemotherapy and PTR are associated with the survival of patients with incurable stage IV colorectal cancer. This study aimed to explore the effects of PTR and the sequencing of chemotherapy and PTR on asymptomatic colorectal cancer with synchronous unresectable metastases (asmCRC). Patients and Methods: Patients with asmCRC were retrospectively identified from a single centre and categorised into 3 groups: PTR followed by chemotherapy (POC), upfront chemotherapy followed by PTR (UFC), and palliative chemotherapy (PC). The primary end points included median overall survival (OS) and progression-free survival (PFS). Clinical features were analysed using χ 2 test, while survival curves were generated using the Kaplan-Meier test. Propensity-score matching (PSM) was performed when comparing survival between POC and UFC groups. Results: From 2008 to 2014, 255 patients were identified and included into the POC (n = 101), UFC (n = 40), and PC (n = 114) groups. The UFC and POC groups had significantly better median OS compared with the PC group (40.7 vs 16.3 months, P

Objective Irinotecan-based doublet chemotherapy strategy was standard second-line backbone for patients with oxaliplatin-refractory metastatic colorectal cancer. The aim of this study was to evaluate tolerability and efficacy of raltitrexed combined with irinotecan biweekly administered as the second-line therapy for mCRC patients. Methods The study was a prospective, single-center, non-randomized, open-label phase II clinical trial. Patients with mCRC after failure with oxaliplatin and fluoropyrimidine or its derivatives were enrolled. Irinotecan (180 mg/m 2 ) and raltitrexed (2.5 mg/m 2 ) were given intravenously on day 1. Cycles were repeated every 2 weeks. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events (AEs). Results Between December 2012 and October 2016, 33 and 35 patients enrolled were assessed for response and safety, respectively. The ORR was 8.6%, and the DCR was 71.4%. The median PFS was 4.5 months (95% CI 3.8-5.2). The median OS was 12.0 months (95% CI 8.5-15.5). Four patients received conversion therapy to no evidence of disease (NED), and 2 patients were still alive with beyond 24 months survival. The most common grade 3/4 AEs were anorexia (14.3%), vomiting (14.3%), nausea (11.4%), fatigue (8.6%), and leukopenia (8.6%). No one died from treatment-related events. The incidence and severity of toxicity were irrelevant to UGT1A1 status. Conclusions The combination of irinotecan with raltitrexed is an efficient, convenient, and acceptable toxic regimen for second-line treatment for mCRC patients.

Oligonucleotide-based therapy has experienced remarkable development in the past 2 decades, but its broad applications are severely hampered by delivery vectors. Widely used viral vectors and lipid nanovectors are suffering from immune clearance after repeating usage or requiring refrigerated transportation and storage, respectively. In this work, amino-modified virus-mimetic spike silica nanoparticles (NH2-SSNs) were fabricated using a 1-pot surfactant-free approach with controlled spike lengths, which were demonstrated with excellent delivery performance and biosafety in nearly all cell types and mice. It indicated that NH2-SSNs entered cells by spike-dependent cell membrane docking and dynamin-dependent endocytosis. The positively charged spikes with proper length on the surface can facilitate the efficient encapsulation of RNAs, protect the loaded RNAs from degradation, and trigger an early endosome escape during intracellular trafficking, similarly to the cellular internalization mechanism of virions. Regarding the fantastic properties of NH2-SSNs in nucleic acid delivery, it revealed that nanoparticles with solid spikes on the surface would be excellent vehicles for gene therapy, presenting self-evident advantages in storage, transportation, modification, and quality control in large-scale production compared to lipid nanovectors.

In-depth analysis and discussion of the interactive relationship between urbanization and ecological security are basis and prerequisite for ensuring the coordinated development of urbanization and ecological protection. This paper constructed the evaluation index system of urbanization level from four dimensions (i.e., population, economy, society, space) and ecological safety from three aspects (i.e., pressure, governance, environment). Then, the Urbanization Development Index (UDI) and Ecological Security Index (ESI) of the nine provinces along the Yellow River were calculated, and grey relationship and decoupling model were employed to study the interaction between urbanization and ecological security from 2008 to 2018. The main conclusions are as follows: a) The urbanization level and ecological security level of the nine provinces along the Yellow River show an overall upward trend while the increase rate gradually slows down, in which UDI and ESI increases from 0.24 to 0.58 and 0.30 to 0.41 respectively. b) The correlation degree between the urbanization level and the ecological security system is higher than 0.6, which is between the medium correlation and the extremely strong correlation. Population urbanization has the greatest impact on ecological security, with a correlation value of 0.74. Ecological governance has the strongest restraint on urbanization development and the correlation value is 0.72. c) There is a strong decoupling effect between urbanization and ecological security in the nine provinces along the Yellow River, and the future ecological security will gradually become more restrictive on the development of urbanization.

Cervical carcinosarcoma (CCS) is a rare aggressive tumor which was referred to as a sarcoma initially with its morbidity less than 1% of all cervical cancers. Four theories have been proposed for the pathogenesis of CCS. The “metaplastic theory,” also called “monoclonal theory,” has been widely accepted so far. The most common clinical symptom of CCS is abnormal vaginal bleeding. CCS is much less common than the counterparts in uterine corpus and usually confused with uterine carcinosarcoma (UCS) or common cervical cancer. The management for CCS has been mainly extrapolated from studies of UCS or cervical cancers. However, CCS has its special anatomical position and biological behaviors and is usually diagnosed at an early stage than UCS. Currently, there is no consensus on the survival, management and prognosis factors of CCS. We reviewed and summarized the literatures regarding to the epidemiology, clinical presentations, pathogenesis, diagnosis and treatment of CCS for providing clinicians with comprehensive information to diagnose and treat this malignancy.

Intra-abdominal desmoplastic small round cell tumor (IDSRCT) is a rare and highly malignant soft tissue neoplasm, which is characterized by rapid progression and poor prognosis. The mechanism underlying the development of this neoplasm remains elusive, but all cases are characterized by the chromosomal translocation t (11;22) (p13; q12), which results in a formation of EWSR1-WT1 gene fusion. The diagnosis of IDSRCT is often made with core-needle tissue biopsy specimens or laparoscopy or laparotomy. Immunohistochemical analyses have shown the co-expression of epithelial, neuronal, myogenic, and mesenchymal differentiation markers. FISH or reverse transcription polymerase chain reaction detecting EWS-WT1 fusion can be performed to assist in molecular confirmation. There is no standard of care for patients with IDSRCT currently, and majority of newly diagnosed patients received the aggressive therapy, which includes >90% resection of surgical debulking, high-dose alkylator-based chemotherapy, and radiotherapy. More recently, targeted therapy has been increasingly administered to recurrent IDSRCT patients and has been associated with improved survival in clinical conditions. Immunotherapy as a possible therapeutic strategy is being explored in patients with IDSRCT. In this review, we summarize currently available knowledge regarding the epidemiology, potential mechanisms, clinical manifestations, diagnosis, treatment, and prognosis of IDSRCT to assist oncologists in comprehensively recognizing and accurately treating this malignancy.

Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status of tumors is a distinct predictive biomarker of immune checkpoint inhibitors (ICIs) for colorectal and non-colorectal cancer populations. The overall response rate (ORR) varies from approximately 40% to 60%, indicating that nearly half of MSI-H tumors do not respond to ICIs. The mechanism of response heterogeneity in MSI-H/dMMR cancers is unclear. Some patients who have been treated with ICIs have developed a novel pattern of progression called hyperprogression, which is defined as unexpected accelerated tumor growth. No case of MSI-H/dMMR immunotherapy-associated hyperprogression has been reported in the literature. Here, we present the case of a patient with dMMR gastrointestinal cancer who suffered hyperprogressive disease (HPD) after treatment with nivolumab. We explored the potential mechanisms of HPD by clinical, immune, and genomic characteristics. Extremely high levels of serum LDH, low TMB and TILs, and the disruption of TGFβ signaling, may be related to hyperprogression.

Latent class analysis (LCA) is a widely used technique for detecting unobserved population heterogeneity in cross-sectional data. Despite its popularity, the performance of LCA is not well understood. In this study, we evaluate the performance of LCA with binary data by examining classification accuracy, parameter estimation accuracy, and coverage rates of confidence intervals (CIs) through Monte Carlo simulation studies. We address the issue of label switching with a distance-based relabeling approach and introduce an index to measure separation among latent classes. Our results show that classification accuracy, parameter estimation accuracy, and CI coverage rates are primarily influenced by class separation and the number of indicators used for LCA. We recommend using a large sample size to mitigate the effects of tiny class sizes. Additionally, the study finds that the parametric bootstrap CIs perform comparably well or better when compared with the CIs based on the standard maximum likelihood method.