In silico analysis of the wild-type and mutant-type of BRCA2 gene.

BACKGROUND: The aim of this study was to conduct an in silico analysis of a novel compound heterozygous variant in breast cancer susceptibility gene 2 (BRCA2) to clarify its structure-function relationship and elucidate the molecular mechanisms underlying triple-negative breast cancer (TNBC). METHODS: A tumor biopsy sample was obtained from a 42-year-old Chinese woman during surgery, and a maxBRCA™ test was conducted using the patient's whole blood. We obtained an experimentally determined 3D structure (1mje.pdb) of the BRCA2 protein from the Protein Data Bank (PDB) as a relatively reliable reference. Subsequently, the wild-type and mutant structures were predicted using SWISS-MODEL and AlphaFold, and the accuracy of these predictions was assessed through the SAVES online server. Furthermore, we utilized a high ambiguity-driven protein-protein docking (HADDOCK) algorithm and protein-ligand interaction profiler (PLIP) to predict the pathogenicity of the mutations and elucidate pathogenic mechanisms that potentially underlies TNBC. RESULTS: Histological examination revealed that the tumor biopsy sample exhibited classical pathological characteristics of TNBC. Furthermore, the maxBRCA™ test revealed two compound heterozygous BRCA2 gene mutations (c.7670 C > T.pA2557V and c.8356G > A.pA2786T). Through performing in silico structural analyses and constructing of 3D models of the mutants, we established that the mutant amino acids valine and threonine were located in the helical domain and oligonucleotide binding 1 (OB1), regions that interact with DSS1. CONCLUSION: Our analysis revealed that substituting valine and threonine in the helical domain region alters the structure and function of BRCA2 proteins. This mutation potentially affects the binding of proteins and DNA fragments and disrupts interactions between the helical domain region and OB1 with DSS1, potentially leading to the development of TNBC. Our findings suggest that the identified compound heterozygous mutation contributes to the clinical presentation of TNBC, providing new insights into the pathogenesis of TNBC and the influence of compound heterozygous mutations in BRCA2.

Predictive Model of Oxaliplatin-induced Liver Injury Based on Artificial Neural Network and Logistic Regression.

Background and Aims: Identifying potential high-risk groups of oxaliplatin-induced liver injury (OILI) is valuable, but tools are lacking. So artificial neural network (ANN) and logistic regression (LR) models will be developed to predict the risk of OILI. Methods: The medical information of patients treated with oxaliplatin between May and November 2016 at 10 hospitals was collected prospectively. We used the updated Roussel Uclaf causality assessment method (RUCAM) to identify cases of OILI and summarized the patient and medication characteristics. Furthermore, the ANN and LR models for predicting the risk of OILI were developed and evaluated. Results: The incidence of OILI was 3.65%. The median RUCAM score with interquartile range was 6 (4, 9). The ANN model performed similarly to the LR model in sensitivity, specificity, and accuracy. In discrimination, the area under the curve of the ANN model was larger (0.920>0.833, p=0.019). In calibration, the ANN model was slightly improved. The important predictors of both models overlapped partially, including age, chemotherapy regimens and cycles, single and total dose of OXA, glucocorticoid drugs, and antihistamine drugs. Conclusions: When the discriminative and calibration ability was given priority, the ANN model outperformed the LR model in predicting the risk of OILI. Other chemotherapy drugs in oxaliplatin-based chemotherapy regimens could have different degrees of impact on OILI. We suspected that OILI may be idiosyncratic, and chemotherapy dose factors may be weakly correlated. Decision making on prophylactic medications needs to be carefully considered, and the actual preventive effect needed to be supported by more evidence.

Knowledge, Practices, and Perceived Barriers in Cancer Pain Management at Oncology Units: A Cross-Sectional Survey of Medical Staff in China.

BACKGROUND: Despite the great signs of progress in cancer pain management in China, the associated pain remains under-treated. Poor knowledge among the medical staff is an important factor contributing to the under-treatment of cancer pain. This study aimed to evaluate the knowledge, practices, and perceived barriers in cancer pain management among the medical staff at oncology units in China. PATIENTS AND METHODS: A cross-sectional survey was conducted with the medical staff (including physicians, nurses, and pharmacists) at oncology units in tertiary hospitals of China between December 2020 and January 2021. The questionnaire assessed the knowledge, practices, and perceived barriers in cancer pain management. RESULTS: A total of 1262 medical staff responded to the questionnaire; the response rate was 94.2%. Most participants had good knowledge of the three-step analgesic ladder of the World Health Organization (WHO) and the National Comprehensive Cancer Network (NCCN) guidelines for Adult Cancer Pain. Knowledge deficit was prominent in questions on opioid dose titration and rotation and adverse effects of opioids; the correct response rate was less than 40%. Training, work experience in oncology, and education level were significantly related to knowledge of cancer pain management (all P < 0.001). In clinical practice for cancer pain management, approximately 57.2% of medical staff were unfamiliar with opioid dose titration and rotation; only 14.4% treated cancer pain through multidisciplinary collaboration. Poor medication compliance, difficult individualized analgesia protocols, and insufficient multidisciplinary participation were the most frequently perceived barriers by the medical staff for pain management. CONCLUSION: These findings suggested a further need for integrating recent guidelines to strengthen continued training (especially among juniors and those with low education levels) and patient education to improve the knowledge and clinical practices of cancer pain management among the medical staff in China. Multi-disciplinary management is required for the effective treatment of cancer pain.

Risk factors for oxaliplatin-induced hypersensitivity reaction in patients with colorectal cancer.

OBJECTIVE: Hypersensitivity reactions with oxaliplatin (OXA) have attracted much attention. This study aimed to analyze the risk factors for OXA-induced hypersensitivity reaction in Chinese colorectal cancer patients through a single-center retrospective investigation. METHODS: The information from 459 colorectal cancer patients treated with OXA in a hospital was collected retrospectively to explore the risk factors for OXA-induced hypersensitivity reaction. RESULTS: Among the 459 patients, 47 (10.24% incidence) cases developed hypersensitivity reactions, with a 3.70% incidence of grade III/IV reaction. The main symptoms included itching, flushing, dyspnea, and rash, which mainly involved skin and adnexa, respiratory system, and nervous system. Dexamethasone pretreatment presented no significant effects on the hypersensitivity reaction (P = 0.282). Multivariate analysis indicated that the previous allergic history (odds ratio (OR) 2.553, 95% confidence interval (CI) 1.139-5.721, P = 0.023) and OXA-free interval (OR 3.605, 95% CI 1.909-6.809, P = 0.000) were independent risk factors for OXA-induced hypersensitivity reaction. CONCLUSIONS: The incidence of OXA-induced hypersensitivity reaction in colorectal cancer patients was similar to those reported in other countries. Clinical medical staff should pay close attention to high-risk factors, such as allergic history and patients having OXA-free intervals in order to avoid or alleviate hypersensitivity reactions.

Breast microecology improvement using probiotics following needle aspiration in patients with lactational breast abscess: a multi-center randomized double-blind controlled trial.

Although oral probiotics can improve breast microecology and alleviate the inflammatory response, there are no data regarding cases with existing abscesses. We aimed to investigate the effect of Lactobacillus fermentum CECT5716 during needle aspiration in patients with lactational breast abscesses. Patients (aged 20-41 years) with lactational single-cavity breast abscesses (diameter 3-6 cm) from 12 hospitals were randomly assigned to the experimental (n = 51) and control groups (n = 50). Outcome measures included the abscess cure rate on treatment day-5, delactation rate, relieving pain rate, and number of needle aspirations until day-28. The experimental group's 5-day cure rate (43.1%) was significantly higher (p < 0.05). Breastfeeding continuation on day-5 did not differ significantly (experimental group: 88.2%, control group: 96.0%, p = 0.269). In the experimental and control groups, 19.6% and 14.0% of patients experienced moderate to severe pain on day-5, respectively, with no statistically significant differences (p = 0.451). Four patients in each group developed diarrhea, with adverse reaction rates of 7.84% and 8.0%, respectively. No adverse reactions were reported in the infants. L. fermentum can shorten the healing time in patients with lactational breast abscesses.Trial registration This study was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), registration number: ChiCTR2000032682, registration date: 6/May/ 2020; first entry date: 11/May/2020.

Status and Safety Signals of Cephalosporins in Children: A Spontaneous Reporting Database Study.

Introduction: Cephalosporins are widely used in clinical treatment of children, but it is difficult to carry out clinical trials and there is no strong evidence of their safety. Therefore, adverse drug reactions (ADR) of cephalosporins can be a public health problem that deserves attention. Methods: ADR reports collected by the Hubei Adverse Drug Reaction Monitoring Center from 2014 to 2019 were analysed. The safety of Cephalosporins was described by descriptive analysis and three signal mining methods, including the reporting odd ratio (ROR), proportional reporting ratio (PRR), and comprehensive standard method (MHRA). Results: The findings indicated that the age groups of 0-1 and 2-3 years had the highest rates of reporting ADRs. Children aged 0-4 years reported more ADRs, while the proportion of severe ADRs was lower than the average (6.63%). Among the 37 cephalosporins, the severe ADRs of ceftezole, ceftazidime, cefoperazone/sulbactam, cefotaxime, ceftriaxone were reported more and the proportion of severe ADRs was higher. The proportion of severe ADRs of most cephalosporin compound preparations was higher than that of corresponding single components. A total of 99.18% of the cases improved after treatment. There were four deaths whose ADRs were mainly anaphylactic shock, dyspnoea, and anaphylactoid reaction. In signal mining, the three methods produced 206 signals that were the same, and 73 of them were off-label ADRs. Conclusion: ADRs were common but not serious in children aged 0-4 years. And the reported rate of serious ADRs in children aged over 4 years increased with age. ADR reports of ceftezole, ceftazidime, cefoperazone/sulbactam, cefotaxime, ceftriaxone were numerous and serious, and the safety of cephalosporin compound preparations in children was doubtful. Ceftezole may cause off-label ADRs including tremor, face oedema, cyanosis, pallor, rigors, and palpitation. The labeling of ADRs in children in cephalosporin instructions and the record of allergic history need to be improved.

Safety of traditional Chinese medicine injection based on spontaneous reporting system from 2014 to 2019 in Hubei Province, China.

Traditional Chinese medicine (TCM) injection is widely used in clinical settings, but its adverse drug reactions (ADRs) can be a serious public health concern. The objective is to study the safety of TCM injection and provide suggestions for clinical use. ADR reports collected by the Hubei Adverse Drug Reaction Monitoring Center from 2014 to 2019 were analysed. The safety of TCM injections was described by descriptive analysis and three signal mining methods, including the reporting odd ratio (ROR), proportional reporting ratio (PRR) and comprehensive standard method (MHRA). The findings indicate that the age groups of 0-10 and 41-80 years had the highest rates of reporting ADRs. A total of 96.41% of the ADRs occurred within one week, mostly on the same day that the injection was administered. Among the 60 TCM injections, Shenmai, Xiangdan, Salvia, Shengmai, Astragalus and Xuebijing injection had an above average ratio of severe ADRs (12.63%). A total of 99.24% of the cases improved after treatment. There were 9 deaths whose ADRs were mainly anaphylactic shock, dyspnoea and anaphylactoid reaction. In signal mining, the three methods produced 19 signals that were the same, and 14 of them were off-label ADRs. The frequency of TCM injections in children and elderly patients should be reduced and monitored strictly. Close observation is necessary during the first seven days after receiving the injection. The clinical use of Shenmai, Xiangdan, Salvia, Shengmai, Astragalus and Xuebijing injections should be investigated. Signal mining and more research are needed on TCM injections.

Abscess Drainage with or Without Antibiotics in Lactational Breast Abscess: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Lactational breast abscess, a complication from lactational mastitis, is a common cause of breastfeeding discontinuation. No consensus has been reached regarding the necessity of antibiotics in this disease. The purpose of this trial is to determine if surgical drainage is non-inferior to drainage together with a standard course of antibiotics, in the treatment of lactational breast abscess. METHODS: Breastfeeding females with breast abscess from 18 to 50 years old are eligible for study inclusion. An expected number of 306 patients will be randomly allocated in parallel to the intervention arm (simple drainage without antibiotics) or the control arm (abscess drainage with standard 5-day-course of antibiotics). The primary outcomes include the time to resolution of breast abscess and disease recurrence rate. Secondary outcomes of interests are 3-day-improvement proportion, rate of continuing breastfeeding, treatment failure rate, procedural-related complications, and length of hospital stay. An expected non-inferiority margin for the difference in the primary outcome of interest is set at 1 day, on the basis of a one-sided 97.5% confidence interval. DISCUSSION: This trial will provide first-hand evidence on whether simple abscess drainage is non-inferior to drainage together with a standard course of antibiotics, in lactational mothers with breast abscess. The indication of antibiotic prophylaxis could be revised if non-inferiority is set up, and guidelines for lactational breast abscess require amendments correspondingly. TRIAL REGISTRATION: This study has been registered in the Chinese Clinical Trial Registry, and the trial registration number is ChiCTR1900024008.