Trimerized S expressed by modified vaccinia virus Ankara (MVA) confers superior protection against lethal SARS-CoV-2 challenge in mice.

The reoccurrence of successive waves of SARS-CoV-2 variants suggests the exploration of more vaccine alternatives is imperative. Modified vaccinia virus Ankara (MVA) is a virus vector exhibiting excellent safety as well as efficacy for vaccine development. Here, a series of recombinant MVAs (rMVAs) expressing monomerized or trimerized S proteins from different SARS-CoV-2 variants are engineered. Trimerized S expressed from rMVAs is found predominantly as trimers on the surface of infected cells. Remarkably, immunization of mice with rMVAs demonstrates that S expressed in trimer elicits higher levels of binding IgG and IgA, as well as neutralizing antibodies for matched and mismatched S proteins than S in the monomer. In addition, trimerized S expressed by rMVA induces enhanced cytotoxic T-cell responses than S in the monomer. Importantly, the rMVA vaccines expressing trimerized S exhibit superior protection against a lethal SARS-CoV-2 challenge as the immunized animals all survive without displaying any pathological conditions. This study suggests that opting for trimerized S may represent a more effective approach and highlights that the MVA platform serves as an ideal foundation to continuously advance SARS-CoV-2 vaccine development. IMPORTANCE: MVA is a promising vaccine vector and has been approved as a vaccine for smallpox and mpox. Our analyses suggested that recombinant MVA expressing S in trimer (rMVA-ST) elicited robust cellular and humoral immunity and was more effective than MVA-S-monomer. Importantly, the rMVA-ST vaccine was able to stimulate decent cross-reactive neutralization against pseudoviruses packaged using S from different sublineages, including Wuhan, Delta, and Omicron. Remarkably, mice immunized with rMVA-ST were completely protected from a lethal challenge of SARS-CoV-2 without displaying any pathological conditions. Our results demonstrated that an MVA vectored vaccine expressing trimerized S is a promising vaccine candidate for SARS-CoV-2 and the strategy might be adapted for future vaccine development for coronaviruses.

Integrated analysis of intratumoral biomarker and tumor-associated macrophage to improve the prognosis prediction in cancer patients.

BACKGROUND: The lack of effective and accurate predictive indicators remains a major bottleneck for the improvement of the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Hepatitis B virus X (HBx) has been widely suggested as a critical pathogenic protein for HBV-driven liver carcinogenesis, while tumor-associated macrophage (TAM) infiltration is also closely related to the tumorigenesis and progression of HCC. However, few studies have determined whether combining HBx expression with TAM populations could increase the accuracy of prognostic prediction for HBV-related HCC. METHODS: The study cohort enrolling 251 patients with HBV-related HCC was randomly split into a training and a validation group (ratio 1:1). The expression levels of HBx and TAM marker CD68 in HCC samples were detected by immunohistochemistry. Kaplan-Meier curves, Cox regression and Harrell's concordance index (C-index) analysis were conducted to evaluate the prognostic significance of these indicators alone or in combination. RESULTS: The expression level of HBx was strongly correlated with CD68+ TAM infiltration in HCC tissues. Elevated HBx or CD68 expression indicated poorer overall survival (OS) and progression-free survival (PFS) after hepatectomy, and both of them were independent risk factors for postoperative survival. Meanwhile, patients with both high HBx and CD68 levels had worst clinical outcomes. Moreover, integrating HBx and CD68 expression with clinical indicators (tumor size and micro-vascular invasion) showed the best prognostic potential with highest C-index value for survival predictivity, and this proposed model also performed better than several conventional classifications of HCC. CONCLUSION: Combining the expression of intratumoral HBx, CD68+ TAM population and clinical variables could enable better prognostication for HBV-related HCC after hepatectomy, thus providing novel insights into developing more effective clinical prediction model based on both molecular phenotypes and tumor-immune microenvironment.

PEGylation Prolongs the Half-Life of Equine Anti-SARS-CoV-2 Specific F(ab')2.

Therapeutic antibodies-F(ab')2 obtained from hyperimmune equine plasma could treat emerging infectious diseases rapidly because of their high neutralization activity and high output. However, the small-sized F(ab')2 is rapidly eliminated by blood circulation. This study explored PEGylation strategies to maximize the half-life of equine anti-SARS-CoV-2 specific F(ab')2. Equine anti-SARS-CoV-2 specific F(ab')2 were combined with 10 KDa MAL-PEG-MAL in optimum conditions. Specifically, there were two strategies: Fab-PEG and Fab-PEG-Fab, F(ab')2 bind to a PEG or two PEG, respectively. A single ion exchange chromatography step accomplished the purification of the products. Finally, the affinity and neutralizing activity was evaluated by ELISA and pseudovirus neutralization assay, and ELISA detected the pharmacokinetic parameters. The results displayed that equine anti-SARS-CoV-2 specific F(ab')2 has high specificity. Furthermore, PEGylation F(ab')2-Fab-PEG-Fab had a longer half-life than specific F(ab')2. The serum half-life of Fab-PEG-Fab, Fab-PEG, and specific F(ab')2 were 71.41 h, 26.73 h, and 38.32 h, respectively. The half-life of Fab-PEG-Fab was approximately two times as long as the specific F(ab')2. Thus far, PEGylated F(ab')2 has been prepared with high safety, high specificity, and a longer half-life, which could be used as a potential treatment for COVID-19.

Viral and Host Transcriptomes in SARS-CoV-2-Infected Human Lung Cells.

Coronaviruses are commonly characterized by a unique discontinuous RNA transcriptional synthesis strategy guided by transcription-regulating sequences (TRSs). However, the details of RNA synthesis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. Here, we present a time-scaled, gene-comparable transcriptome of SARS-CoV-2, demonstrating that ACGAAC functions as a core TRS guiding the discontinuous RNA synthesis of SARS-CoV-2 from a holistic perspective. During infection, viral transcription, rather than genome replication, dominates all viral RNA synthesis activities. The most highly expressed viral gene is the nucleocapsid gene, followed by ORF7 and ORF3 genes, while the envelope gene shows the lowest expression. Host transcription dysregulation keeps exacerbating after viral RNA synthesis reaches a maximum. The most enriched host pathways are metabolism related. Two of them (cholesterol and valine metabolism) affect viral replication in reverse. Furthermore, the activation of numerous cytokines emerges before large-scale viral RNA synthesis. IMPORTANCE SARS-CoV-2 is responsible for the current severe global health emergency that began at the end of 2019. Although the universal transcriptional strategies of coronaviruses are preliminarily understood, the details of RNA synthesis, especially the time-matched transcription level of each SARS-CoV-2 gene and the principles of subgenomic mRNA synthesis, are not clear. The coterminal subgenomic mRNAs of SARS-CoV-2 present obstacles in identifying the expression of most genes by PCR-based methods, which are exacerbated by the lack of related antibodies. Moreover, SARS-CoV-2-related metabolic imbalance and cytokine storm are receiving increasing attention from both clinical and mechanistic perspectives. Our transcriptomic research provides information on both viral RNA synthesis and host responses, in which the transcription-regulating sequences and transcription levels of viral genes are demonstrated, and the metabolic dysregulation and cytokine levels identified at the host cellular level support the development of novel medical treatment strategies.

Amino acid sites related to the PB2 subunits of IDV affect polymerase activity.

BACKGROUND: In 2011, a new influenza virus, named Influenza D Virus (IDV), was isolated from pigs, and then cattle, presenting influenza-like symptoms. IDV is one of the causative agents of Bovine Respiratory Disease (BRD), which causes high morbidity and mortality in feedlot cattle worldwide. To date, the molecular mechanisms of IDV pathogenicity are unknown. Recent IDV outbreaks in cattle, along with serological and genetic evidence of IDV infection in humans, have raised concerns regarding the zoonotic potential of this virus. Influenza virus polymerase is a determining factor of viral pathogenicity to mammals. METHODS: Here we take a prospective approach to this question by creating a random mutation library about PB2 subunit of the IDV viral polymerase to test which amino acid point mutations will increase viral polymerase activity, leading to increased pathogenicity of the virus. RESULTS: Our work shows some exact sites that could affect polymerase activities in influenza D viruses. For example, two single-site mutations, PB2-D533S and PB2-G603Y, can independently increase polymerase activity. The PB2-D533S mutation alone can increase the polymerase activity by 9.92 times, while the PB2-G603Y mutation increments the activity by 8.22 times. CONCLUSION: Taken together, our findings provide important insight into IDV replication fitness mediated by the PB2 protein, increasing our understanding of IDV replication and pathogenicity and facilitating future studies.

Development of recombinase polymerase amplification assays for rapid and visual detection of canine distemper virus infecting giant panda.

BACKGROUND: Canine distemper virus (CDV) is an enveloped negative-strand RNA virus that exhibits a high mutation rate and continuously expands the range of hosts. Notably, CDV has infected giant panda with spill over from viral reservoirs in canines. Giant pandas (Ailuropoda melanoleuca), especially captive pandas, are known to be susceptible to natural infection with CDV. The high fatality rate of CDV poses a serious threat to the safety of the giant panda population. However, vaccines or drugs for canine distemper in giant pandas have not been developed to date. Therefore, a rapid test that can achieve accurate onsite detection of CDV is important to enable the timely implementation of control measures. In this study, we established a nucleic acid visualization assay for targeting the CDV N gene by using combines reverse transcription recombinase polymerase amplification with a closed vertical flow visualization strip (RT-RPA-VF). RESULTS: The RT-RPA-VF assay does not require sophisticated equipment, and it was determined to provide rapid detection at 35 °C for 30 min, while the limit of detection was 5 × 101 copies/µl RNA transcripts and 100.5 TCID50 ml- 1 viruses. The results showed that the assay was high specific to CDV and had no cross-reactivity with other viruses infecting the giant panda. Compared with RT-qPCR, RT-RPA-VF assay had a sensitivity of 100% and a specificity of 100% in 29 clinical samples. The coincidence rate between RT-RPA-VF and RT-qPCR was 100% (kappa = 1), indicating that the RT-RPA-VF assay possessed good diagnostic performance on clinical samples. CONCLUSIONS: The RT-RPA-VF provides a novel alternative for the simple, sensitive, and specific identification of CDV and showed great potential for point of care diagnostics for captive and wild giant panda.

Self-expanding metal stent insertion by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring in the management of acute colorectal obstruction: a 14-year experience.

BACKGROUND: Placement of a self-expanding metal stent (SEMS) in patients presenting with an acute colorectal obstruction (ACO) may obviate emergency surgery (ES), potentially effectively palliating incurable tumors, acting as a bridge to surgery (BTS) in patients with operable or potentially operable tumors and achieving effective decompression of other ACO. We present our experience with SEMS insertion by colorectal surgeons without fluoroscopic monitoring for ACO especially for acute malignant colorectal obstruction (AMCO) for nearly a 14-year period (2007-2020). AIM: To explore the safety and effectiveness of SEMS insertion in the management of ACO by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring. METHODS: We reviewed the medical records of patients retrospectively to identify all patients presenting to our unit with ACO especially with AMCO who had stenting carried out to achieve colonic decompression. All 434 procedures were performed by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring. RESULTS: The overall technique success rate and clinic success rate by SEMS insertion were 428/434 (98.6%) and 412/434 (94.9%). The overall incidence of complications by SEMS insertion was 19/434 (4.4%). The complications included clinical perforation (6/434, 1.4%); stent migration (2/434, 0.5%), 1 of which re-stent; stent detachment (fell off) (3/434, 0.7%), none of them with re-stent; stool impaction (6/434, 1.4%), 1 of which re-stent; and abdominal or anal pain (2/434, 0.5%). There was no hemorrhage in any of the 434 patients. CONCLUSIONS: SEMS insertion is a relatively safe and effective technique for colonic decompression in dealing with ACO as either a BTS or as a palliative measure. It is also a solution to other causes of ACO such as recurrent tumor, benign diseases, or extra-luminal compression. Therefore, ES was largely avoided.

Equine-Origin Immunoglobulin Fragments Protect Nonhuman Primates from Ebola Virus Disease.

Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treating EBOV infections, but production is costly and quantities are limited; therefore, MAbs are not the best candidates for mass use in the case of an epidemic. To address this need, we generated EBOV-specific polyclonal F(ab')2 fragments from horses hyperimmunized with an EBOV vaccine. The F(ab')2 was found to potently neutralize West African and Central African EBOV in vitro Treatment of nonhuman primates (NHPs) with seven doses of 100 mg/kg F(ab')2 beginning 3 or 5 days postinfection (dpi) resulted in a 100% survival rate. Notably, NHPs for which treatment was initiated at 5 dpi were already highly viremic, with observable signs of EBOV disease, which demonstrated that F(ab')2 was still effective as a therapeutic agent even in symptomatic subjects. These results show that F(ab')2 should be advanced for clinical testing in preparation for future EBOV outbreaks and epidemics.IMPORTANCE EBOV is one of the deadliest viruses to humans. It has been over 40 years since EBOV was first reported, but no cure is available. Research breakthroughs over the past 5 years have shown that MAbs constitute an effective therapy for EBOV infections. However, MAbs are expensive and difficult to produce in large amounts and therefore may only play a limited role during an epidemic. A cheaper alternative is required, especially since EBOV is endemic in several third world countries with limited medical resources. Here, we used a standard protocol to produce large amounts of antiserum F(ab')2 fragments from horses vaccinated with an EBOV vaccine, and we tested the protectiveness in monkeys. We showed that F(ab')2 was effective in 100% of monkeys even after the animals were visibly ill with EBOV disease. Thus, F(ab')2 could be a very good option for large-scale treatments of patients and should be advanced to clinical testing.

Development of a reverse genetics system for Japanese encephalitis virus strain SA14-14-2.

Japanese encephalitis virus SA14-14-2 (JEV SA14-14-2) is a widely used vaccine in China and other southeastern countries to prevent Japanese encephalitis in children. In this study, a stable infectious cDNA clone of JEV SA14-14-2 with a low copy number pACYC177 vector dependent on the T7 promoter and T7 terminator was developed. Two introns were inserted into the capsid gene and envelope gene of JEV cDNA for gene stability. Hepatitis delta virus ribozyme (HDVr) was engineered into the 3' UTR cDNA of JEV for authentic 3' UTR transcription. The rescued virus showed biological properties indistinguishable from those of the parent strain (JEV SA14-14-2). The establishment of a JEV SA14-14-2 reverse genetics system lays the foundation for the further development of other flavivirus vaccines and viral pathogenesis studies.

Genome-wide DNA methylation profiling of primary colorectal laterally spreading tumors identifies disease-specific epimutations on common pathways.

Colorectal laterally spreading tumors (LSTs) grow to extremely large size while rarely invade deeply. Also, there is a low tendency to become cancerous. We used the Illumina Human Methylation 450K array to query the main epigenetic difference of LSTs. We built a discovery cohort with 10 matched cases, and a validation cohort with 9 additional matched cases. Our results suggest that LST displays significant decrease in DNA methylation, highlighted by the discovery of 1,018 hypomethylated intergenic regions (IGRs). Comparing to classic differentially methylated probes and regions that overlap transcription starting site and CpG island, IGR-regions were associated more closely with genes involved in functional biological processes and correlated with specific histone modifications. Hypomethylated IGR regions were often annotated as tissue-specific regulatory elements for noncolon tissues and were typically epigenetically silenced in normal colon mucosa. By integration of public data, we defined the commonality and specific epigenetic signatures for adenomas, LSTs and colon adenocarcinomas. Only 435 hypermethylated differentially methylated probes (DMPs) and differentially methylated regions (DMRs) and 517 hypomethylated DMPs and DMRs were shared by the three diseases. However, our pathway-level analysis discovered that genes in four pathways were common target of epimutations in LSTs, adenomas and CRCs. More interestingly, different diseases seem to employ distinct epigenetic insult to disturb specific pathways. Between LST and adenoma, we found eight pathways including Ras signaling and Rap1 signaling pathway were commonly targeted but the epimutation patterns were opposite. Comparison between precancerous conditions and invasive states revealed the key pathways governing the progression to malignancy, including PI3K-Akt pathways.

Changes in gut microbiota and plasma inflammatory factors across the stages of colorectal tumorigenesis: a case-control study.

BACKGROUND: Colorectal cancer (CRC) is a common malignant gastrointestinal tumor. In China, CRC is the 5th most commonly diagnosed cancer. The vast majority of CRC cases are sporadic and evolve with the adenoma-carcinoma sequence. There is mounting evidence indicating that gut microbiota and inflammation play important roles in the development of CRC although study results are not entirely consistent. In the current study, we investigated the changes in the CRC-associated bacteria and plasma inflammatory factors and their relationships based on data from a case-control study of Han Chinese. We included 130 initially diagnosed CRC patients, 88 advanced colorectal adenoma patients (A-CRA), 62 patients with benign intestinal polyps and 130 controls. RESULTS: Fecal microbiota composition was obtained using 16S ribosomal DNA (16S rDNA) sequencing. PCOA analysis showed structural differences in microbiota among the four study groups (P = 0.001, Unweighted Unifrac). Twenty-four CRC-associated bacteria were selected by a two-step statistical method and significant correlations were observed within these microbes. CRC-associated bacteria were found to change with the degree of malignancy. Plasma C-reactive protein (CRP) and soluble tumor necrosis factor II (sTNFR-II) displayed significant differences among the four study groups and increased with adenoma-carcinoma sequence. The correlations of CRP and sTNFR-II with several CRC-associated microbes were also explored. CONCLUSIONS: CRC-associated species and plasma inflammatory factors tended to change along the adenoma-carcinoma sequence. Several CRC-associated bacteria were correlated with CRP and sTNFR-II. It is likely that gut microbiome and inflammation gradually form a microenvironment that is associated with CRC development.

[Identification of a novel STK11 gene mutation in a family affected with hereditary Peutz-Jeghers syndrome].

OBJECTIVE To explore the genetic basis for a family affected with Peutz-Jeghers syndrome (PJS). METHODS Genomic DNA was extracted from peripheral blood and oral swab samples from the patient and her relatives. Next-generation sequencing (NGS) was used to analyze 106 target genes by capturing the exons and adjacent intronic regions. Suspected pathogenic mutation was verified by NGS. RESULTS A missense STK11 mutation was detected in the proband, which was not reported previously. The mutation has caused substitution of Leucine by Proline. NGS has detected the same mutation in the mother but not among other relatives. CONCLUSION This hereditary case of PJS may be attributed to the missense mutation of the STK11 gene.

Porcine epidemic diarrhea virus virus-like particles produced in insect cells induce specific immune responses in mice.

Porcine epidemic diarrhea virus (PEDV), which causes 80-100% mortality in neonatal piglets, is one of the most devastating viral diseases affecting swine worldwide. To date, the lack of effective vaccines and drugs is the main problem preventing control of the global spread of PEDV. In this study, we produced PEDV virus-like particles (VLPs) composed of S, M, and E proteins with a baculovirus expression system and tested them via indirect immunofluorescence assay (IFA)and Western blot analysis. Electron microscopy showed that the morphological structure of the PEDV VLPs was similar to that of the protovirus. Microneutralization assays and ELISpot analysis demonstrated that PEDV VLPs induced highly specific antibody responses and Th2-mediated humoral immunity. As a result, the PEDV VLPs displayed excellent immunogenicity in mice. Therefore, a VLP-based vaccine has the potential to prevent PEDV infection.

Aberrant regulation of miR-15b in human malignant tumors and its effects on the hallmarks of cancer.

MicroRNAs encoded by the miR-15b/16-2 cluster act as tumor suppressors. Aberrant regulation of miR-15b in human malignant tumors is reportedly involved in cancer development, contributing to cell death, reduced proliferation, angiogenesis and metastasis resistance, metabolism reprogramming, genome instability, and tumor-associated inflammation. In this review, we summarize the mechanisms involved in regulating miR-15b expression in mammalian tumors and discuss the effects of miR-15b dysregulation on the hallmarks of cancer and highlight its role as a potentially valuable target for future cancer therapeutic strategies.

Isolation and sequence analysis of the complete NS1 and VP2 genes of canine parvovirus from domestic dogs in 2013 and 2014 in China.

Canine parvovirus (CPV) can cause severe disease in animals and continuously generates new variant and recombinant strains in dogs that have a strong impact on sanitation. It is therefore necessary to investigate epidemic CPV strains to improve our understanding of CPV transmission and epidemic behavior. However, most studies have focused on the analysis of VP2, and therefore, information about recombination and relationships between strains is still lacking. Here, 14 strains of CPV were isolated from domestic dogs suspected of hosting CPV between 2013 and 2014 in China. The complete NS1 and VP2 genes were sequenced and analyzed. The results suggest that the new CPV-2a and new CPV-2b types are the prevalent strains in China. In addition to a few mutations (residues 19, 544, 545, 572 and 583 of NS1 and residues 267, 370, 377 and 440 of VP2) that were preserved during transmission, new mutations (residues 60, 630 of NS1, and residues 21, 310 of VP2) were found in the isolated strains. A phylogenetic tree based on VP2 sequences illustrated that the new CPV-2a and new CPV-2b strains from China form single clusters that are distinct from lineages from other countries. Moreover, recombination between the new CPV-2a and new CPV-2b types was also identified in the isolated strains. Due to differences in selection pressures or recombination, there were a small number of inconsistencies between the phylogenetic trees for VP2 and NS1, which indicated that phylogenetic relationships based on VP2 might not be representative of those based on NS1. The data indicated that mutations and recombination are constantly occurring along with the spread of CPV in China.

Interferon-inducible GTPase: a novel viral response protein involved in rabies virus infection.

Rabies virus infection is a major public health concern because of its wide host-interference spectrum and nearly 100 % lethality. However, the interactions between host and virus remain unclear. To decipher the authentic response in the central nervous system after rabies virus infection, a dynamic analysis of brain proteome alteration was performed. In this study, 104 significantly differentially expressed proteins were identified, and intermediate filament, interferon-inducible GTPases, and leucine-rich repeat-containing protein 16C were the three outstanding groups among these proteins. Interferon-inducible GTPases were prominent because of their strong upregulation. Moreover, quantitative real-time PCR showed distinct upregulation of interferon-inducible GTPases at the level of transcription. Several studies have shown that interferon-inducible GTPases are involved in many biological processes, such as viral infection, endoplasmic reticulum stress response, and autophagy. These findings indicate that interferon-inducible GTPases are likely to be a potential target involved in rabies pathogenesis or the antiviral process.

Visual detection of Ebola virus using reverse transcription loop-mediated isothermal amplification combined with nucleic acid strip detection.

Ebola virus (species Zaire ebolavirus) (EBOV) is highly virulent in humans. The largest recorded outbreak of Ebola hemorrhagic fever in West Africa to date was caused by EBOV. Therefore, it is necessary to develop a detection method for this virus that can be easily distributed and implemented. In the current study, we developed a visual assay that can detect EBOV-associated nucleic acids. This assay combines reverse transcription loop-mediated isothermal amplification and nucleic acid strip detection (RT-LAMP-NAD). Nucleic acid amplification can be achieved in a one-step process at a constant temperature (58 °C, 35 min), and the amplified products can be visualized within 2-5 min using a nucleic acid strip detection device. The assay is capable of detecting 30 copies of artificial EBOV glycoprotein (GP) RNA and RNA encoding EBOV GP from 10(2) TCID50 recombinant viral particles per ml with high specificity. Overall, the RT-LAMP-NAD method is simple and has high sensitivity and specificity; therefore, it is especially suitable for the rapid detection of EBOV in African regions.

Endoscopic submucosal dissection versus transanal local excision for rectal carcinoid: a comparative study.

AIM: The aim of this study is to compare the short-term clinical outcomes between endoscopic submucosal dissection and transanal local excision for rectal carcinoid tumors. METHODS: Between 2007 and 2012, 31 patients with rectal carcinoid underwent endoscopic submucosal dissection at our hospital. They were compared with a matched cohort of 23 patients who underwent transanal local excision for rectal carcinoid between 2007 and 2012. Short-term clinical outcomes including surgical parameters, postoperative recovery, and oncologic outcomes were compared between the two groups. RESULTS: The mean size of tumors was significantly bigger in the transanal local excision group (0.8 ± 0.2 versus 1.1 ± 0.5 cm; P = 0.018). En bloc resection was achieved for 30 patients (97 %) in the endoscopic submucosal dissection group and all the patients in the transanal local excision group. The operation time was longer in the transanal local excision than that in the endoscopic submucosal dissection group (40.0 ± 22.7 min versus 12.2 ± 5.3 min; P < 0.001). Complications in the transanal local excision group were five cases of acute retention of urine. There was no local recurrence or distant metastasis in either group during the follow-up period. CONCLUSION: For the treatment of rectal carcinoid tumors with diameter <1 cm, endoscopic submucosal dissection has better short-term clinical outcomes than transanal local excision in terms of faster recovery and possibly a lower morbidity rate. Transanal local excision may be the first therapeutic choice of scar-embedded rectal carcinoid tumors.

Cryoablation plus chemotherapy in colorectal cancer patients with liver metastases.

Cryoablation and surgery achieve similar removal rates for some colorectal cancer (CRC) liver metastasis removal, and systemic chemotherapy is accepted as the most important approach to improving overall survival (OS) in CRC patients with liver metastases. We aimed to evaluate the potential benefit of cryoablation plus chemotherapy in CRC patients with liver metastases. We retrospectively analyze 63 patients of CRC liver metastasis. There were 32 patients in group A, who have received cryoablation plus chemotherapy, and there were 31 patients in group B, who have received chemotherapy alone. We mainly observe the 2-year survival, the quality of life (QOL), and adverse effects. Patients in group A had a higher 2-year survival rate, better OS, better QOL, and better treatment response than patients in group B. Two-year survival rates were 71.9 and 51.6%,respectively, in group A and group B. The negative conversion rates of carcinoembryonic antigen and carbohydrate antigen 19-9 (CA199) were 57.1 and 61.5%, respectively, in group A, and 22.2 and 30%, respectively, in group B. The tumor shrinkage (a tumor volume reduction of ≥ 30%) rates were 62.5 and 22.6%, respectively, in groups A and B. Performance status remained stable or improved in 16 patients (50%) in group A and eight patients (25.81%) in group B. Cryoablation in combination with chemotherapy may increase the 2-year survival rate and improve QOL in CRC patients with liver metastasis.

A multicenter retrospective analysis: Factors influencing hepatic adverse events induced by immunotherapy in advanced liver cancer.

OBJECTIVES: To analyze the clinical characteristics and influencing factors of hepatotoxicity in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death protein-1 (PD-1) inhibitors, and to provide a theoretical basis for the treatment of immune-related hepatotoxicity in patients with advanced HCC. METHODS: Retrospective analysis of clinical data of patients with advanced HCC from February 2021 to February 2023, in order to summarize and statistically analyze the influencing factors of immune-related liver adverse reactions. RESULTS: A total of 135 patients met the inclusion criteria, among whom 46 patients experienced varying degrees of immune-related liver adverse reactions, with an incidence rate of 34.1% (46/135). The time range of immune-related liver adverse reactions was 3-26 weeks, with a median time of 4 weeks. The age range of immune-related liver adverse reactions was 34-73 years, with a median age of 62 years. Statistical analysis of the influencing factors and liver adverse reactions showed that age, total bilirubin level, and Child-Pugh (C-P) grading were influencing factors for the occurrence of liver adverse reactions (p < .05), and among these three influencing factors, the proportion of males with ≥2 influencing factors was higher than that of females; liver function C-P B was an independent influencing factor for liver adverse reactions (p < .05). CONCLUSION: For male patients over 60 years old, with bilirubin levels ≥51 µmol/L and liver function C-P B, close observation of the occurrence of immune-related adverse reactions during treatment is recommended.