Effect of internet multiple linkage mode-based extended care combined with in-hospital comfort care on colorectal cancer patients undergoing colostomy.

BACKGROUND: Patients with colorectal cancer may need postoperative nursing to improve prognosis, and conventional nursing is not effective. Clinical research is needed to explore nursing methods that can more effectively improve postoperative conditions on colorectal cancer patients undergoing colostomy. AIM: To explore the effect of internet multiple linkage mode-based extended care combined with in-hospital comfort care on colorectal cancer patients undergoing colostomy. METHODS: Data from 187 patients with colostomy treated in our hospital from May 2019 to March 2022 were collected and divided into three groups, A (n = 62), B (n = 62) and C (n = 63), according to different intervention methods. Group A received internet multiple linkage mode-based extended care combined with in-hospital comfort care. Group B received internet multiple linkage mode-based extended care. Group C received usual care intervention. Complications were compared among the three groups. The stoma self-efficacy scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Brief Fatigue Inventory and City of Hope-quality of Life-ostomy Questionnaire before and after intervention were compared among the three groups. RESULTS: The complication rate of group A, B and C (16.13%, 20.97% and 60.32%, respectively) was significantly different (all P < 0.05). The incidence of complications in groups A and B was lower than that in group C, and there was no significant difference between groups A and B (P > 0.05). After intervention, the scores of ostomy care, social contact, diet choice, confidence in maintaining vitality, confidence in self-care of ostomy, confidence in sexual life, confidence in sexual satisfaction and confidence in physical labor in the three groups were all higher than before intervention, and the scores of groups A and B were higher than those of group C, with statistical significance (P < 0.05). The Hamilton Anxiety Scale and Hamilton Depression Scale scores of the three groups after intervention were lower than those before intervention. The scores of groups A and B were lower than those of group C, and the score of group A was lower than that of group B, all with statistical significance (all P < 0.05). There was a statistically significant difference in cancer-induced fatigue among the three groups (P < 0.05). After intervention, the scores of physical health, psychological health, social health and mental health of the three groups were lower than before the intervention. The scores of group A and B were lower than that of group C; and the score of group A was lower than that of group B, all with statistical significance (all P < 0.05). CONCLUSION: Internet multiple linkage mode-based extended care combined with in-hospital comfort care can effectively improve self-efficacy, bad mood, cancer-related fatigue and life quality of colorectal cancer patients undergoing colostomy.

Performance characterization of PCR-free whole genome sequencing for clinical diagnosis.

ABSTRACT: To evaluate the performance of polymerase chain reaction (PCR)-free whole genome sequencing (WGS) for clinical diagnosis, and thereby revealing how experimental parameters affect variant detection.Five NA12878 samples were sequenced using MGISEQ-2000. NA12878 samples underwent WGS with differing deoxyribonucleic acid (DNA) input and library preparation protocol (PCR-based vs PCR-free protocols for library preparation). The depth of coverage and genotype quality of each sample were compared. The performance of each sample was measured for sensitivity, coverage of depth and breadth of coverage of disease-related genes, and copy number variants. We also developed a systematic WGS pipeline (PCR-free) for the analysis of 11 clinical cases.In general, NA12878-2 (PCR-free WGS) showed better depth of coverage and genotype quality distribution than NA12878-1 (PCR-based WGS). With a mean depth of ∼40×, the sensitivity of homozygous and heterozygous single nucleotide polymorphisms (SNPs) of NA12878-2 showed higher sensitivity (>99.77% and >99.82%) than NA12878-1, and positive predictive value exceeded 99.98% and 99.07%. The sensitivity and positive predictive value of homozygous and heterozygous indels for NA12878-2 (PCR-free WGS) showed great improvement than NA128878-1. The breadths of coverage for disease-related genes and copy number variants are slightly better for samples with PCR-free library preparation protocol than the sample with PCR-based library preparation protocol. DNA input also influences the performance of variant detection in samples with PCR-free WGS. All the 19 previously confirmed variants in 11 clinical cases were successfully detected by our WGS pipeline (PCR free).Different experimental parameters may affect variant detection for clinical WGS. Clinical scientists should know the range of sensitivity of variants for different methods of WGS, which would be useful when interpreting and delivering clinical reports.

Redox Host-Guest Nanosensors Installed with DNA Gatekeepers for Immobilization-Free and Ratiometric Electrochemical Detection of miRNA.

Electrochemical nanosensors by integrating functional nucleic acids and nanomaterials hold a great promise in the fast detection of biomarkers, yet the current systems possess limitations on the accessibility of target-probe and probe-electrode interactions and the repeatability of detection. Herein, a host-guest assembly strategy is developed to build redox nanosensors for an immobilization-free and ratiometric electrochemical detection system. Specifically, electroactive molecule (Em ) guests are loaded in porous hosts of polydopamine nanoparticles (MPDA) to act as dual-signal redox reporters. Hybrid DNA probes of G-quadruplex and a single-stranded anchor DNA are installed as gatekeepers for sealing the mesopores. Thereby, miRNA triggered Em release by strand displacement reactions and the homogeneous transportation of the hosts/guests to the electrode facilitate the generation of reference signal/response signal at different potentials. Concomitantly applied NIR irradiation boosts the electron transfer from MPDA to the electrode and results in a tenfold increase in the reference signal. Finally, the sensing system through the differential pulse voltammetry method achieves a highly repeatable detection (relative standard deviation 3.8%) of miRNA with a lower detection limit (362 × 10-15 m). This attractive system paves the way for rational designs of advanced electrochemical biosensors and smart diagnosis.

AutoCNV: a semiautomatic CNV interpretation system based on the 2019 ACMG/ClinGen Technical Standards for CNVs.

BACKGROUND: The American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) presented technical standards for interpretation and reporting of constitutional copy-number variants in 2019 (the standards). Although ClinGen developed a web-based CNV classification calculator based on scoring metrics, it can only track and tally points that have been assigned based on observed evidence. Here, we developed AutoCNV (a semiautomatic automated CNV interpretation system) based on the standards, which can automatically generate predictions on 18 and 16 criteria for copy number loss and gain, respectively. RESULTS: We assessed the performance of AutoCNV using 72 CNVs evaluated by external independent reviewers and 20 illustrative case examples. Using AutoCNV, it showed that 100 % (72/72) and 95 % (19/20) of CNVs were consistent with the reviewers' and ClinGen-verified classifications, respectively. AutoCNV only required an average of less than 5 milliseconds to obtain the result for one CNV with automated scoring. We also applied AutoCNV for the interpretation of CNVs from the ClinVar database and the dbVar database. We also developed a web-based version of AutoCNV (wAutoCNV). CONCLUSIONS: AutoCNV may serve to assist users in conducting in-depth CNV interpretation, to accelerate and facilitate the interpretation process of CNVs and to improve the consistency and reliability of CNV interpretation.

Regulation of gene transcription of B lymphoma Mo-MLV insertion region 1 homolog (Review).

B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is a core protein component of the polycomb repressive complex 1 that inhibits cell senescence and maintains the self-renewal ability of stem cells via downregulation of p16Ink4a and p19Arf expression. Bmi-1 serves an important role in hematopoietic stem cell maintenance and neurodevelopment during embryonic development, and it has been shown to enhance tumorigenesis by promoting cancer stem cell self-renewal and epithelial to mesenchymal transition. Emerging evidence suggests that Bmi-1 overexpression is closely related to the development and progression of various types of cancer, and that downregulation of Bmi-1 expression can inhibit the proliferation, invasion and metastasis of cancer cells. It is therefore important to elucidate the mechanisms underlying the regulation of Bmi-1 expression both under normal growth conditions and in malignant tissues. In the present review, the current body of knowledge pertaining to the transcriptional and post-transcriptional regulation of the BMI-1 gene is discussed, and the potential mechanisms by which Bmi-1 is dysregulated in various types of cancer are highlighted. Bmi-1 expression is primarily controlled via transcriptional regulation, and is regulated by the transcription https://www.ushuaia.pl/hyphen/?ln=en factors of the Myc family, including Myb, Twist1, SALL4 and E2F-1. Post-transcriptionally, regulation of Bmi-1 expression is inhibited by several microRNAs and certain small-molecule drugs. Thus, regulatory transcriptional factors are potential therapeutic targets to reduce Bmi-1 expression in cancer cells. Thus, the present review provides an up-to-date review on the regulation of BMI-1 gene expression at the transcriptional and post-transcriptional level.

High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry Program.

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies.

A reliable, high-resolution and high-throughput genotyping method for HLA-DRB1.

Human leukocyte antigen (HLA) DNA typing is an essential part to identify a donor who may be a good match for the patients who need haematopoietic stem cells from bone marrow. Thus, fetching quickly high-resolution genotype is very important at present. However, current HLA DNA typing methods especially for HLA-DRB1 generally yielded ambiguous typing results because of high degree of heterozygosity on exome region and primer pairs design limitations, which generally amplified only exon2 of HLA-DRB1 and the position of its primer pairs is on exome region. To solve this problem, we developed a reliable, high-resolution and high-throughput (RHH) sequence based typing approach for HLA-DRB1 through massively parallel paired-end sequencing. Several primer pairs were designed to amplify three exon regions, which are part of exon1, the whole region of exon2 and exon3 of HLA-DRB1, to genotyping for HLA-DRB1 by synthesis. 94 samples were included to analyze and the highly successful genotyping ratio (98.94%) and no ambiguous genotyping result demonstrated the accurate performance of our method for HLA-DRB1 genotyping.

Production of monoclonal antibody against EP0 protein of pseudorabies virus and determination of its recognized epitope.

Early protein 0 (EP0) is especially important for modulating PRV gene expression and reactivation from the latent state, but the mechanisms have not been elucidated. In this study, six monoclonal antibodies (MAbs) against EP0 protein of PRV were generated and their characterizations were investigated. Western blot analysis showed all six MAbs could react with immunizing antigen, but only 2B12 and 2C6 could react with native EP0 protein from PRV-infected cells. ELISA additivity tests revealed that at least three epitopes in EP0 were defined by six MAbs. The epitope recognized by MAb 2B12 was further identified in 287-292 aa of EP0 protein using a series of expressed overlapping peptides. These MAbs may provide valuable tools for further research of the functions of EP0 in PRV infection.

[Efficacy and safety of bevacizumab plus capecitabine for metastatic colorectal cancer].

OBJECTIVE: To evaluate the efficacy and safety of bevacizumab plus capecitabine in treating metastatic colorectal cancer(mCRC). METHODS: Eleven patients with mCRC (6 females and 5 males) were enrolled in this study. Bevacizumab was given with 5 mg/kg every two weeks in five patients, 10 mg/kg every two weeks in four patients and 15 mg/kg every three weeks in two patients. All patients received capecitabine 2000 mg/m2 per day for 14 days. RESULTS: Five of 11 patients had partial response and five patients had stable disease and two patients had progressive disease. The disease control rate was 90.9%. The progress-free survival were 4 months and the median overall survival time were 15 months. The adverse events related to bevacizumab were grade 2 hypertension in 3 patients (27.3%) and grade 1 or 2 proteinuria in 4 patients (36.4%). Other adverse events such as mucositis, fatigue, subcutaneous haemorrhage were also observed. No thromboembolism or severe haemorrhage happened. No other grade 3 or 4 adverse events were observed.The adverse events in the combined therapy were hand-foot-syndrome (54.6%), diarrhea (27.3%), and neutropenia (18.2%), mainly due to capecitabine. CONCLUSIONS: The combination of bevacizumab plus capecitabine has definite benefit in patients with mCRC. However,these benefits can not be maintained after the withdrawal of bevacizumab. The adverse drug reactions are well tolerated.

[Multicenter phase II clinical trial of uroacitides injection in the treatment for advanced malignant tumors].

OBJECTIVE: To investigate the efficacy, safety and the life quality improvement of uroacitides injection in the treatment for patients with advanced malignant tumors. METHODS: A total of 160 patients with advanced stage cancers were enrolled into this multicenter, open and non-randomized phase II clinical trial, including cancers of the lung (33 cases), liver (45 cases), breast (17 cases), esophagus (11 cases), stomach (18 cases), colon (19 cases), pancreas (3 cases) and kidney (4 cases), and glioma (10 cases). Uroacitides was administrated in a dose of 300 ml daily via the superior vena cava catheter for consecutive 4-8 weeks. RESULTS: Of the 160 patients, 21 dropped out and one patient died during the trial. Efficacy could be evaluated in 138 patients and safety in 160. The total objective response rate (ORR, CR + PR)) and tumor control rate (CR + PR + MR + SD) of the 138 evaluable patients were 5.8% and 65.2%, respectively. Clinical benefit response (CBR) rate was 57.2%. Major adverse effects were grade I - II and reversible nausea/vomiting (21.9%) and pain (6.3%). CONCLUSION: Uroacitides injection is effective in the control for various kinds of advanced cancers with mild, reversible and tolerable adverse effects, and can also improve the patient's quality of life. It is worth being studied further.

[Long-term consecutive follow-up of high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (APBSCT) in the treatment of small cell lung cancer].

BACKGROUND: To study the efficacy and long-term survival of high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (APBSCT) in the treatment of small cell lung cancer (SCLC).. METHODS: Seven patients with pathologically confirmed SCLC were enrolled into the study, including 6 patients who had achieved CR or PR after conventional chemotherapy, and 1 patient who underwent surgical treatment and 6 cycles of conventional postoperative chemotherapy. All patients received a high-dose chemotherapy regimen of cyclophosphamide 6 g/m², etoposide 1.2 g/m², carboplatin 1.2 g/m² following APBSCT. Six of 7 patients received local radiotherapy after the procedure, however, another patient over 60 years did not receive local radiotherapy because of pneumonia complication. All patients were consecutively followed up and median follow-up duration was 27 (25-82) months. RESULTS: Survival of the 7 patients was longer than 2 years. Three patients were still alive for more than 5 years after treatment, and the longest one up to 82 months. Three patients died and their survival time was 26, 27 and 27 months respectively. CONCLUSIONS: High-dose chemotherapy supported by APBSCT combined with local radiotherapy may be helpful to prolong survival and improve prognosis for SCLC, especially to those patients with limited disease, relatively younger age and better performance status, and responding to conventional chemotherapy.

[Nausea disintegrating buccal tablet in the prevention of gastrointestinal reaction induced by anticancer drugs].

OBJECTIVE: To evaluate the efficacy and safety of nausea oral, disintegrating buccal tablet (DBT) in the prevention of gastrointestinal reaction induced by anticancer drugs (cisplatin DDP 30 - 50 mg/m(2) or adramycin ADM >/= 40 mg/m(2)), as compared with those of kytril tablets. METHODS: A multicenter, open and randomized self-crossover control trial was carried out with all the eligible patients randomized into AB or BA group. Patients in AB group were given nausea 0.1 mg as buccal tablet one hour before chemotherapy in the first cycle and kytril tablet 2 mg in the second cycle, those in BA group were given these drugs in the reverse order. RESULTS: Seventy-three patients were allotted to this study, including 44 patients in DDP-arm and 29 in ADM-arm. Sixty-two patients were evaluable for response and 70 patients for safety. Nausea DBT was as effective as kytril tablet in the control of anorexia, nausea and vomiting during the first 24 hours after chemotherapy, with response rates of 74.2%, 77.4%, 83.9% in nausea DBT and 74.2%, 71.0%, 88.7% DBT in kytril tablets. A high efficacy in the control of vommitting induced by cisplatin was observed in both nausea DBT and kytril tablets. The complete control rates and overall control rates were 83.3%, 91.7% in nausea DBT and 86.1%, 97.2% in kytril tablets, respectively. The side effects of nausea DBT were head heaviness, dry mouth and somnolence, which were mild and comparable with kytril in their frequencies. CONCLUSION: Nausea disintegrating buccal tablet is able to effectively prevent gastrointestinal reaction induced by anticancer drugs, with efficacy and side effects similar to kytril tablets. Nausea DB tablet, an intraoral disintegrator, is very convenient for patients who can not swallow tablets for various reasons.

Clinical comparison of the selective serotonin3 antagonists ramosetron and granisetron in treating acute chemotherapy-induced emesis, nausea and anorexia.

OBJECTIVE: The efficacies of the selective 5-hydroxytryptamine3 (5-HT3) antagonists--ramosetron (0.3 mg) and granisetron (3 mg) in treating acute chemotherapy-induced digestive system dysunction were compared. METHODS: A total of 111 patients were enrolled in a single-blind, randomised crossover study; with data from 98 were used to assess efficacy and data from 110 to assess the safety profile. Ramosetron or granisetron was given intraveneously 15 min befire chemotherpy. RESULTS: The ability of ramosetron to prevent emesis, nausea and anorexia was similar to granisetron during the first 6 h following the administration of chemotherapy, ciplatin or doxorubicin. However, during the first 24 h after chemotherapy, significant differences between ramosetron and granisetron appeared: emetic episode (P = 0.068), nausea (P = 0.006), and anorexia (P = 0.048) remained lower in ramosetron-treated patients. The safety profile of ramosetron was similar to that of granisetron and adverse events in both groups were generally mild and transient. CONCLUSION: Ramosetron is more potent and longer-lasting than granisetron in preventing chemotherapy-induced digestive disturbances.

[Phase III clinical study of a new anticancer drug atofluding].

BACKGROUND & OBJECTIVE: Atofloding (ATFU) is a new derivative of 5-fluorouracil. The phase I and II clinical study have been finished. The current study was a phase III clinical trail of ATFU. The aim of this study was to evaluate the efficacy, toxicity of ATFU combination chemotherapy and compare with ftorafur (FT-207) in patients with gastric cancer, colorectal, esophageal cancer, and liver cancer. METHODS: A multicenter, open randomized controlled trial was carried out. A total of 320 patients with gastric cancer, colorectal, esophageal cancer and liver cancer were randomized into ATFU group (study group) and FT207 group (control group) (a ratio of 2:1), treated with MMC + VP-16 + ATFU (FT-207), DDP + HCPT + ATFU (FT-207), DDP + VDS + ATFU (FT-207), and ADM + MMC + ATFU (FT-207) regimen, respectively. The same dosage of combine drugs were used in the two groups. RESULTS: The response rates of the study group (213 cases) and the control group (107 cases) were 17.1% and 7.9% in gastric cancer (P > 0.05), 16.7% and 9.4% in colorectal cancer (P > 0.05), 20.0% and 24.6% in esophageal cancer (P > 0.05), 5.0% and 9.0% in liver cancer (P > 0.05), respectively. The major adverse effects were mylosuppression and gastrointestinal reactions which frequency and intensity had no statistical difference in the two groups. CONCLUSION: ATFU combination chemotherapy is effective and similar to FT207 in the efficiency and adverse effects for treatment of advanced GI cancers.