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Objectives Cuproptosis represents an innovative type of cell death, distinct from apoptosis, driven by copper dependency, yet the involvement of copper apoptosis-associated long non-coding RNAs (CRLncRNAs) in hepatocellular carcinoma (HCC) remains unclear. This study is dedicated to unveiling the role and significance of these copper apoptosis-related lncRNAs within the context of HCC, focusing on their impact on both the development of the disease and its prognosis. Methods We conducted an analysis of gene transcriptomic and clinical data for HCC cases by sourcing information from The Cancer Genome Atlas database. By incorporating cuproptosis-related genes, we established prognostic features associated with cuproptosis-related lncRNAs. Furthermore, we elucidated the mechanism of cuproptosis-related lncRNAs in the prognosis and treatment of HCC through comprehensive approaches, including Lasso and Cox regression analyses, survival analyses of samples, as well as examinations of tumor mutation burden and immune function. Results We developed a prognostic model featuring six cuproptosis-related lncRNAs: AC026412.3, AC125437.1, AL353572.4, MKLN1-AS, TMCC1-AS1, and SLC6A1-AS1. This model demonstrated exceptional prognostic accuracy in both training and validation cohorts for patients with tumors, showing significantly longer survival times for those categorized in the low-risk group compared to the high-risk group. Additionally, our analyses, including tumor mutation burden, immune function, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and drug sensitivity, further elucidated the potential mechanisms through which cuproptosis-associated lncRNAs may influence disease outcome. Conclusions The model developed using cuproptosis-related long non-coding RNAs (lncRNAs) demonstrates promising predictive capabilities for both the prognosis and immunotherapy outcomes of tumor patients. This could play a crucial role in patient management and the optimization of immunotherapeutic strategies, offering valuable insights for future research.

A large-scale vaccination of coronavirus disease-19 (COVID-19) in adults has been conducted for nearly a year, and there is a growing recognition that immunization for children is also essential. It has been months since emergency use of pediatric COVID-19 vaccine was approved, we reviewed the prevalence and transmission of COVID-19 in children. The prevalence of COVID-19 in children is reduced due to vaccination even in a Delta prevalent period, so an increase in the vaccination rate is needed in children. Although the precise role of children in the transmission requires more research to uncover, they likely played a significant role, according to the available literature. We also described four candidate COVID-19 vaccines for children on their safety and immunogenicity and the impact of severe acute respiratory syndrome coronavirus 2 variants on childhood vaccination. Safety issues on pediatric vaccines post-approval, like adverse events following immunization and adverse events of special interest require studies on long-term and effective regulatory mechanisms.

Background: Prophylactic human papillomavirus (HPV) vaccination substantially alleviates cervical cancer burden. This study aimed to evaluate the safety, tolerability, and immunogenicity of an Escherichia coli-expressed recombinant nonavalent HPV vaccine. Methods: A dose-escalating phase 1 clinical trial was conducted in Sheyang County, Jiangsu Province, China. Each participant received either the test vaccine or the control vaccine (Gardasil 9) following a 0/2/6-month schedule. Adverse reactions (ARs) within 7 days after vaccination, adverse events (AEs) within 30 days, and serious adverse events (SAEs) throughout the study were recorded. Blood parameters were measured before and 3 days after each dose. Serum immunoglobulin G (IgG) and neutralizing antibodies (nAbs) against nine HPV types were analyzed at months 0, 3, and 7. Results: A total of 160 women aged 18–45 years were enrolled, and 155 participants completed the full vaccination regimen. Within 7 days following vaccination, the incidence of ARs ranged from 56.67% to 90.00%, with the low-dose group showing a significantly higher rate than the control group (p = 0.004). Most AEs were mild or moderate, and no vaccine-related SAEs occurred. No significant differences were observed among the four groups regarding the incidence of abnormal laboratory findings. Seroconversion rates for nAbs and IgG against nine HPV types exceeded 97.92% following three doses. High levels of nAbs and IgG were observed at months 3 and 7, with geometric mean titers (GMTs) showing further increases by month 7. Conclusions: This new recombinant nonavalent HPV vaccine exhibits good tolerability and strong immunogenicity among women aged 18–45 years, supporting further efficacy studies in larger populations.

Several studies have shown significant involvement of tumor-associated macrophages (TAMs) in the tumor microenvironment and cancer progression. However, no data on reliable TAM-related biomarkers are available for predicting the prognosis of patients with colorectal cancer (CRC). We analyzed the clinical data and gene expression profiles of patients with CRC from databases. The single-cell transcriptomic data was applied to identify M2-like TAM-related differentially expressed genes. Univariate Cox and least absolute shrinkage and selection operator regression analyses were used to determine the prognostic signature genes. Then, seven key genes were screened to develop the prognostic signature. In the training and external validation cohorts, the overall survival (OS) of patients in the high-risk group was significantly shorter compared to the low-risk group. Consequently, we created a nomogram that could accurately and reliably predict the prognosis of patient with CRC. A significant correlation was observed between the patient’s prognosis, clinical features, sensitivity to anticancer drugs, TME, and risk scores. Moreover, risk score was strongly related to the response to immunotherapy in patients from GSE91061, GSE78220, and GSE60331 cohorts. Finally, high expression of HSPA1A , SERPINA1 , CXCL1 , and low expression of DNASE1L3 were found in human CRC tissue and normal tissue by using qRT-PCR. In conclusion, the M2-like TAM-related prognostic signature could predict the survival, prognosis, and response of patients with CRC to immunotherapy, which sheds light on the role of TAMs in CRCs and enhances our understanding of TAMs.

To evaluate the epidemiology characteristics of Herpes simplex virus type 2 (HSV-2), Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection in children from January 2018 to December 2023, in Nanjing, China. We conducted a retrospective analysis of 21,210, 49,494 and 32,457 outpatients and inpatients aged 1 day to 17 years who were subjected to the three herpesviruses (HSV-2, EBV, and CMV) nucleic acid testing from January 2018 to December 2023, respectively. Demographic information, laboratory findings, etc. were collected and analyzed. HSV-2, EBV and CMV nucleic acid testing were performed by real-time PCR. The total rate of detection of the three herpesviruses for all specimens was 0.32% (67/21,210), 14.99% (7419/49,494), and 8.88% (2881/32,457), respectively. A declining trend in the incidence of viral infections over the years was observed for the three herpesviruses (all <0.05). The detection rate for HSV-2, EBV, and CMV was highest among patients aged 1-3 years, 3-7 years, and 28 days to 1 year, respectively (all <0.05). The presence of HSV-2 and CMV infection did not exhibit a discernible seasonal pattern, whereas EBV typically demonstrated an elevation during the summer and autumn. EBV and CMV were both prevalent among children in China, except for HSV-2. The annual prevalence of the three herpesviruses show decreasing trend from 2018 to 2023, and no difference in gender (except for EBV). EBV infections usually occur in the summer and autumn, whereas HSV-2 and CMV do not exhibit significant seasonality. The positivity rate of HSV-2 is highest in 1-3 years, EBV is highest in 3-7 years, and that of CMV is highest in 28 days to 1 year. Positive detection rates are higher in outpatients than in inpatients.

Vaccination with prophylactic human papillomavirus (HPV) vaccines is one of the most effective measures to prevent cervical cancer and other related diseases. Here we aimed to evaluate the immunogenicity and safety of an -produced 9-valent human papillomavirus (9vHPV) vaccine. We did a single-center, randomized, observer-blinded, positive controlled phase 2 clinical trial in healthy women aged 20-45 years. All eligible participants were randomly assigned (1:1:1) to receive 270 ug 9vHPV, 360 ug 9vHPV, or the control vaccine (Gardasil) with a 0-2-6-month schedule. Serum samples were collected at day 0 and month 7 to assess IgG and neutralizing antibodies (nAbs). For HPV 6/HPV 11/HPV 16/HPV 18, non-inferiority was identified for the lower limit of the 95% CI of the geometric mean titer (GMT) ratio at a margin of 0.5 and a seroconversion rate (SCR) difference at a margin of -5%. For HPV 31/HPV 33/HPV 45/HPV 52/HPV 58, superiority was demonstrated if the lower limit of the 95% CI for GMT ratio is greater than 1. A total of 780 participants aged 20-45 years were enrolled, among whom 770 completed the three-dose immunization schedule. The incidences of ARs within 7 days in the 270 μg, 360 μg, and positive control groups were 38.85%, 41.92%, and 22.69%, respectively ( < 0.001). The GMTs of nAbs and IgG antibodies for nine HPV types in both 270 ug and 360 ug groups showed an obvious rise at month 7. For HPV 31/HPV 33/HPV 45/HPV 52/HPV 58, the GMTs of nAbs in both 270 μg and 360 μg groups were higher than those in the positive control group, with the 95% CI lower bounds of GMT ratios all greater than 1. Compared to the positive control group, HPV 6 and HPV 18 achieved non-inferiority criteria for GMT in both dose groups. However, the GMT ratio of HPV 16 in the 270 μg group was 0.46 (0.38-0.55), and HPV 16 and HPV 11 in the 360 μg group were 0.48 (0.40-0.58) and 0.53 (0.46-0.60), respectively. The SCRs of nAbs for HPV 6/HPV 11/HPV 16/HPV 18 in the three groups were 100%, with the 95% CI lower bound for SCR differences ranging from -2.55% to -1.64%. The candidate 9vHPV vaccine was well tolerated and immunogenic, supporting further evaluation for efficacy and safety in larger populations. https://clinicaltrials.gov, identifier NCT05694728.

Various COVID-19 vaccine trials have shown that vaccines can successfully prevent symptomatic cases of COVID-19 and death. Head-to-head comparisons help to better understand the immune response characteristics of different COVID-19 vaccines in humans. We randomly selected 20 participants from each of five ongoing Phase II trials of COVID-19 vaccines. Here, SARS-CoV 2-specific immune responses to DNA vaccine (INO-4800), mRNA vaccine (BNT162b2), Adenovirus-vectored vaccine (CONVIDECIA), Protein subunit vaccine (Recombinant COVID- 19 Vaccine (Sf9 Cells)), Inactivated Vaccine (KCONVAC) were examined longitudinally in healthy adults between Jan 15, 2021 and July 5, 2021 for 6 months. RBD-IgG titres were detected by ELISA, neutralising antibody titer were detected by pseudoviral neutralization and immune cell response were detected by flow cytometry. At the first visit (V1), 100% of individuals who received the BNT162b2, CONVIDECIA, or KCONVAC vaccines experienced seroconversion of neutralizing and binding antibodies in the serum. Except for the Recombinant COVID-19 Vaccine (Sf9 Cells) vaccine having the highest neutralizing antibody GMT at the second visit (although there was no statistically significant difference in geometric mean titers between V1 and V2), the rest of the vaccines had the highest levels of binding antibodies and neutralizing antibodies at V1. The neutralizing antibodies GMT of all vaccines showed a significant decrease at V3 compared to V1. The neutralizing antibody GMT against the omicron variant of all vaccines at V1 showed a significant decrease compared to the wild strain. We observed statistically significant differences in Tcm cells and RBD-specific memory B cells among various vaccines. BNT162b2 (mRNA vaccine) exhibits the highest antibody levels among the five vaccines evaluated, regardless of whether the target is the wild-type virus or its variants. However, its cellular immune response may be weaker compared to CONVIDECIA (adenovirus type 5 vector vaccine).

IntroductionOrgan preservation is now considered an acceptable alternative option in distal rectal cancer patients with clinical complete response (cCR) after neoadjuvant chemoradiation (CRT). But the cCR rate is low and about one-third of tumour will regrow, which requires more effective local treatment. CRT combined with intra-arterial chemotherapy (IAC) might be a promising approach. Additionally, total neoadjuvant therapy using FOLFIRINOX induction chemotherapy improved survival while consolidation chemotherapy improved organ preservation. We assess whether IAC plus CRT and FOLFIRINOX consolidation chemotherapy can improve the chance of organ preservation and survival in distal rectal cancer.Methods and analysisThis prospective, monocentric, open-label, single-arm phase II study will include 32 patients with cT3-4NanyM0 distal rectal adenocarcinoma. All patients will receive one cycle of IAC (irinotecan, raltitrexed and oxaliplatin), followed by CRT (50 Gy/25 fractions with concomitant capecitabine) and then with six cycles of FOLFIRINOX (leucovorin, 5-fluorouracil, oxaliplatin and irinotecan). After final evaluation, patients with cCR will receive non-operative management or surgery at their own discretion and others are mandatorily referred to surgery. Adjuvant chemotherapy with six cycles of mFOLFOX6 (leucovorin, 5-fluorouracil and oxaliplatin) will be used for patients with adverse pathological features. The primary endpoint is the rate of complete response (CR; pathological CR or sustained cCR≥2 years). The main secondary endpoints are toxicity, compliance, short-term and long-term oncological outcomes, surgical morbidity and quality of life. This protocol has been designed in accordance with the Standard Protocol Items: Recommendations for Interventional Trials 2013 guidelines.Ethics and disseminationThis study was approved by the Academic and Ethics Committee of The Affiliated Hospital of Youjiang Medical University for Nationalities in March 2023. Trial results will be published in peer-reviewed international journals and on the ChiCTR website.Protocol versionRegistered on 18 April 2023; version #1.Trial registration numberChiCTR2300070620.

How much the vaccine contributes to the induction and development of neutralizing antibodies (NAbs) of breakthrough cases relative to those unvaccinated-infected cases is not fully understood. We conducted a prospective cohort study and collected serum samples from 576 individuals who were diagnosed with SARS-CoV-2 Delta strain infection, including 245 breakthrough cases and 331 unvaccinated-infected cases. NAbs were analysed by live virus microneutralization test and transformation of NAb titre. NAbs titres against SARS-CoV-2 ancestral and Delta variant in breakthrough cases were 7.8-fold and 4.0-fold higher than in unvaccinated-infected cases, respectively. NAbs titres in breakthrough cases peaked at the second week after onset/infection. However, the NAbs titres in the unvaccinated-infected cases reached their highest levels during the third week. Compared to those with higher levels of NAbs, those with lower levels of NAbs had no difference in viral clearance duration time (P>0.05), did exhibit higher viral load at the beginning of infection/maximum viral load of infection. NAb levels were statistically higher in the moderate cases than in the mild cases (P<0.0001). Notably, in breakthrough cases, NAb levels were highest longer than 4 months after vaccination (Delta strain: 53,118.2 U/mL), and lowest in breakthrough cases shorter than 1 month (Delta strain: 7551.2 U/mL). Cross-neutralization against the ancestral strain and the current circulating isolate (Omicron BA.5) was significantly lower than against the Delta variant in both breakthrough cases and unvaccinated-infected cases. Our study demonstrated that vaccination could induce immune responses more rapidly and greater which could be effective in controlling SARS-CoV-2.

Background: Though children infected by SARS-CoV-2 generally experience milder symptoms compared to adults, severe cases can occur. Additionally, children can transmit the virus to others. Therefore, the availability of safe and effective COVID-19 vaccines for children and adolescents is crucial. Method: A single-center, randomized, double-blind clinical trial was conducted in Funing County, Yancheng City, Jiangsu Province, China. Healthy children and adolescents were divided into two subgroups (6–12 years old or 13–17 years old) and randomly assigned to one of three groups to receive one dose of Ad5-nCoV (3 × 1010 vp/dose). Another group, aged 18–59, received one dose of Ad5-nCoV (5 × 1010 vp/dose) as the control group. At 28, 90, 180, and 360 days post-vaccination, we measured the geometric mean titer (GMT)/concentration (GMC) of neutralizing and binding antibodies against the prototype SARS-CoV-2 strain, as well as serum antibody levels against the BA.4/5 variant. We also evaluated the incidence of adverse events within 28 days post-vaccination. Results: A total of 2413 individuals were screened from 3 June 2021 to 25 July 2021, of whom 2021 eligible participants were enrolled, including 1009 aged 6~17 years in the children and adolescent group and 1012 aged 18–59 years in the adults group. The GMT of anti-wild SARS-CoV-2 neutralizing antibodies was 18.6 (95% CI, 16.6–20.9) in children and adolescents and 13.2 (95% CI, 11.6–15.0) in adults on day 28. The incidence of solicited adverse reactions between the adult group (49.4% [124/251]) and the children and adolescent group (46.3% [156/337]) was not statistically significant. The neutralizing antibody levels decreased by a factor of 3.29 from day 28 to day 360 post-vaccination. Conclusions: A single dose of Ad5-nCoV at 3 × 1010 virus particles/dose is safe in children and adolescents, and it elicited significant immune response, which was not only non-inferior but also superior to that in adults aged 18–59 years.