Objective:To analyze risk factors associated with false-positive results of quantitative fecal immunochemical testing (FIT), evaluate its performance for detecting advanced colorectal neoplasia across different subgroups, and explore the optimal positivity thresholds for each subgroup.Methods:Individuals who participated in the Zhejiang Colorectal Cancer Screening Program in 2020-2021, completed questionnaire-based risk assessment and quantitative FIT for initial screening, and undertook colonoscopy for confirmed diagnosis were included in this study. The information of individuals, including demographic characteristics, lifestyles, history of diseases, and family history of colorectal cancer (CRC), was collected by using questionnaires. The diagnostic outcomes of the individuals were obtained through colonoscopy and pathological examination. Multivariate logistic regression analyses were conducted to identify factors associated with false-positive FIT results. The optimal threshold of FIT was determined based on the receiver operating characteristic (ROC) curve and 10-fold cross-validation. The effectiveness of FIT screening in different subgroups was compared using the unified threshold of 100 ng/ml or optimal positivity thresholds.Results:There were 25 874 individuals included in the analysis, with 14 694 (56.79%) having fecal hemoglobin concentrations ≥100 ng/ml. A total of 3 830 advanced adenoma cases (14.80%) and 362 CRC cases (1.40%) were identified. Age below 60 years old, females, underweight, smoking, drinking, use of nonsteroidal anti-inflammatory drugs, no family history of CRC, no history of intestinal disease, no history of hypertension, and physical inactivity were associated with an elevated risk of false-positive results in FIT ( P<0.05). Compared to the predetermined threshold of 100 ng/ml, the false positive rate (FPR) of quantitative FIT decreased from 52.3% to 37.3% in all individuals, and decreased by more than 20% in females, individuals with normal weight, smokers, and those without a history of intestinal disease when adopting the optimal threshold (all P<0.001). Conclusion:The risk of false-positive results in quantitative FIT varies across different subgroups. Adopting the optimal thresholds could improve the specificity and reduce the FPR of quantitative FIT for CRC screening.

Objective:To analyze risk factors associated with false-positive results of quantitative fecal immunochemical testing (FIT), evaluate its performance for detecting advanced colorectal neoplasia across different subgroups, and explore the optimal positivity thresholds for each subgroup.Methods:Individuals who participated in the Zhejiang Colorectal Cancer Screening Program in 2020-2021, completed questionnaire-based risk assessment and quantitative FIT for initial screening, and undertook colonoscopy for confirmed diagnosis were included in this study. The information of individuals, including demographic characteristics, lifestyles, history of diseases, and family history of colorectal cancer (CRC), was collected by using questionnaires. The diagnostic outcomes of the individuals were obtained through colonoscopy and pathological examination. Multivariate logistic regression analyses were conducted to identify factors associated with false-positive FIT results. The optimal threshold of FIT was determined based on the receiver operating characteristic (ROC) curve and 10-fold cross-validation. The effectiveness of FIT screening in different subgroups was compared using the unified threshold of 100 ng/ml or optimal positivity thresholds.Results:There were 25 874 individuals included in the analysis, with 14 694 (56.79%) having fecal hemoglobin concentrations ≥100 ng/ml. A total of 3 830 advanced adenoma cases (14.80%) and 362 CRC cases (1.40%) were identified. Age below 60 years old, females, underweight, smoking, drinking, use of nonsteroidal anti-inflammatory drugs, no family history of CRC, no history of intestinal disease, no history of hypertension, and physical inactivity were associated with an elevated risk of false-positive results in FIT ( P<0.05). Compared to the predetermined threshold of 100 ng/ml, the false positive rate (FPR) of quantitative FIT decreased from 52.3% to 37.3% in all individuals, and decreased by more than 20% in females, individuals with normal weight, smokers, and those without a history of intestinal disease when adopting the optimal threshold (all P<0.001). Conclusion:The risk of false-positive results in quantitative FIT varies across different subgroups. Adopting the optimal thresholds could improve the specificity and reduce the FPR of quantitative FIT for CRC screening.

Objective To compare and analyze the effects of application of phloroglucinol(PG)and diazepam(DZP)during the latent phase of labor on the delivery outcome of primiparous women.Methods Clinical data of women who delivered in Hangzhou Obstetrics and Gynecology Hospital from January 2022 to December 2023 were retrospectively analyzed.According to the medication regimen in the latent stage of labor,they were divided into PG group(PG 80 mg,intravenous push)and DZP group(DZP 10 mg,intravenous push).Cervical ripeness,duration of labor,delivery(cervical dilatation,24 h postpartum hemorrhage,mode of delivery,and time to full opening of the uterus),neonatal Apgar score,and pregnancy-related adverse outcomes were compared between the two groups.Results A total of 162 patients were included in the study,with 83 in the PG group and 79 in the DZP group.The total cervical ripening rate in the PG group was significantly higher than that in the DZP group(P<0.05);the time of the first,second,third,and total labor were all shorter than those in the DZP group(P<0.05).The cervical dilatation in the PG group was significantly greater than that in the DZP group(P<0.05),the amount of postpartum 24 h hemorrhage and time to full opening of the uterine were significantly less than those in the DZP group(P<0.05),and the rate of transvaginal delivery was higher than that of DZP group(P<0.05).The differences in neonatal Apgar scores at 1 min and 5 min,the incidence of adverse maternal outcomes and the incidence of adverse neonatal outcomes between the two groups were not statistically significant(P>0.05).Conclusion Compared with DZP,the application of PG during the latency period can improve cervical ripeness,accelerate the progress of labor,and increase the rate of transvaginal delivery.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

Objective:To evaluate and summarize the best evidence on fatigue management in children with tumors both domestically and internationally, providing reference for medical and nursing staff to improve fatigue symptoms in children.Methods:The evidence on fatigue management in children with tumors, including best practices, recommended practices, guidelines, systematic reviews, evidence summaries, and expert consensus, was systematically retrieved from clinical decision support systems, guideline websites, professional association websites, and databases both domestically and internationally. The search period was from database establishment to April 2023. Two researchers independently conducted literature quality evaluation and evidence extraction.Results:A total of 17 articles were included, including four guidelines and 13 systematic reviews. Thirty-two best pieces of evidence were extracted from six aspects of assessment and screening, identification of risk factors, health education, exercise intervention, medication intervention, and other interventions of fatigue in children with tumors.Conclusions:The best evidence for fatigue management in children with tumors is summarized, which can provide a basis for medical and nursing staff to improve their fatigue symptoms. It is recommended that medical and nursing staff combine clinical context, professional opinions, and patient wishes to screen the best evidence and develop personalized fatigue management programs.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Creatine/metabolism* ; Extracellular Vesicles ; Muscle, Skeletal/metabolism* ; Myoblasts/metabolism* ; Regeneration ; Connexins/metabolism*