Predicting disease genes based on multi-head attention fusion.

BACKGROUND: The identification of disease-related genes is of great significance for the diagnosis and treatment of human disease. Most studies have focused on developing efficient and accurate computational methods to predict disease-causing genes. Due to the sparsity and complexity of biomedical data, it is still a challenge to develop an effective multi-feature fusion model to identify disease genes. RESULTS: This paper proposes an approach to predict the pathogenic gene based on multi-head attention fusion (MHAGP). Firstly, the heterogeneous biological information networks of disease genes are constructed by integrating multiple biomedical knowledge databases. Secondly, two graph representation learning algorithms are used to capture the feature vectors of gene-disease pairs from the network, and the features are fused by introducing multi-head attention. Finally, multi-layer perceptron model is used to predict the gene-disease association. CONCLUSIONS: The MHAGP model outperforms all of other methods in comparative experiments. Case studies also show that MHAGP is able to predict genes potentially associated with diseases. In the future, more biological entity association data, such as gene-drug, disease phenotype-gene ontology and so on, can be added to expand the information in heterogeneous biological networks and achieve more accurate predictions. In addition, MHAGP with strong expansibility can be used for potential tasks such as gene-drug association and drug-disease association prediction.

Effects of Yishengukang decoction on expression of bone-specific alkaline phosphatase, carboxyterminal propeptide of type â procollagen, and carboxyterminal cross-linked telepeptide of type â collagen in malignant tumor patients with bone metastasis.

OBJECTIVE: To investigate the effect of Yishengukang decoction on the expression of the metabolic bone markers, bone-specific alkaline phosphatase (BAP), carboxyterminal propeptide of type Ⅰ procollagen (PICP), and arboxyterminal cross-linked telepeptide of type Ⅰ collagen (ICTP), in cancer patients with bone metastasis. METHODS: Patients (n = 180) were divided into three groups: (a) bone metastasis patients treated with Yishengukang and pamidronate disodium injection (treatment group, n = 60); (b) bone metastasis patients treated with pamidronate disodium injection alone (control group, n = 60); (c) cancer patients without metastatic bone lesion (non-bone metastasis group, n = 60). Serum levels of the metabolic markers BAP, PICP, and ICTP were detected by enzyme-linked immunosorbent assay pre- and post-therapy. RESULTS: A significant decrease in serum BAP level was observed in the treatment group compared with the control group. However there were no significant differences in serum levels of PICP and ICTP before or after treatment compared with the control group. CONCLUSION: Yishengukang decoction combined with pamidronate disodium injection reduced serum BAP level to a greater extent that pamidronate disodium injection alone. Furthermore, the combined therapy was more beneficial in regulating imbalanced bone metabolism after bone metastasis, and may represent the molecular mechanism underpinning the effects of Yishengukang decoction.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases: A case report.

BACKGROUND: Small cell lung cancer (SCLC) is a common and aggressive subtype of lung cancer. It is characterized by rapid growth and a high mortality rate. Approximately 10% of patients with SCLC present with brain metastases at the time of diagnosis, which is associated with a median survival of 5 mo. This study aimed to summarize the effect of bevacizumab on the progression-free survival (PFS) and overall survival of patients with brain metastasis of SCLC. CASE SUMMARY: A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks. The patient was diagnosed with limited-stage SCLC. He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo. CONCLUSION: The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Hyperprogression after anti-programmed death-1 therapy in a patient with urothelial bladder carcinoma: A case report.

BACKGROUND: Immune checkpoint inhibitors, including programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) have recently been approved to treat locally advanced and metastatic urothelial carcinoma (UC). However, some patients experience rapid tumor progression rather than any clinical benefit from anti-PD-L1/PD-1 therapy. CASE SUMMARY: A 73-year-old woman with bladder UC showed the progression of multiple metastases after surgery and chemotherapy for over 12 mo. The patient could not tolerate further chemotherapy. Next-generation sequencing was performed, and the results indicated that the tumor mutational burden was 6.4 mutations/Mb. The patient received the anti-PD-L1 agent toripalimab combined with albumin-bound paclitaxel. Compared with the baseline staging before immunotherapy, the patient had a treatment failure time of < 2 mo, an increase in tumor burden of > 50%, and a > 2-fold increase in progression, indicating hyperprogression. CONCLUSION: Selecting patients most likely to respond to treatment with immunotherapeutic agents remains challenging. For older patients with advanced UC who have already exhausted multi-line chemotherapy options, immunotherapy should be used prudently if no effective biomarker is available. Further studies are required to clarify the causes and mechanisms of hyperprogression.

Effects of Electroacupuncture for Opioid-Induced Constipation in Patients With Cancer in China: A Randomized Clinical Trial.

Importance: Opioid-induced constipation (OIC) is prevalent among patients treated with opioids for cancer pain. Safe and effective therapies for OIC in patients with cancer remain an unmet need. Objective: To determine the efficacy of electroacupuncture (EA) for OIC in patients with cancer. Design, Setting, and Participants: This randomized clinical trial was conducted at 6 tertiary hospitals in China among 100 adult patients with cancer who were screened for OIC and enrolled between May 1, 2019, and December 11, 2021. Interventions: Patients were randomized to receive 24 sessions of EA or sham electroacupuncture (SA) over 8 weeks and then were followed up for 8 weeks after treatment. Main Outcomes and Measures: The primary outcome was the proportion of overall responders, defined as patients who had at least 3 spontaneous bowel movements (SBMs) per week and an increase of at least 1 SBM from baseline in the same week for at least 6 of the 8 weeks of the treatment period. All statistical analyses were based on the intention-to-treat principle. Results: A total of 100 patients (mean [SD] age, 64.4 [10.5] years; 56 men [56.0%]) underwent randomization; 50 were randomly assigned to each group. Among them, 44 of 50 patients (88.0%) in the EA group and 42 of 50 patients (84.0%) in the SA group received at least 20 (≥83.3%) sessions of treatment. The proportion of overall responders at week 8 was 40.1% (95% CI, 26.1%-54.1%) in the EA group and 9.0% (95% CI, 0.5%-17.4%) in the SA group (difference between groups, 31.1 percentage points [95% CI, 14.8-47.6 percentage points]; P < .001). Compared with SA, EA provided greater relief for most OIC symptoms and improved quality of life among patients with OIC. Electroacupuncture had no effects on cancer pain and its opioid treatment dosage. Electroacupuncture-related adverse events were rare, and, if any, all were mild and transient. Conclusions and Relevance: This randomized clinical trial found that 8-week EA treatment could increase weekly SBMs with a good safety profile and improve quality of life for the treatment of OIC. Electroacupuncture thus provided an alternative option for OIC in adult patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03797586.

Analysis of the effect of NEKs on the prognosis of patients with non-small-cell lung carcinoma based on bioinformatics.

NEKs are proteins that are involved in various cell processes and play important roles in the formation and development of cancer. However, few studies have examined the role of NEKs in the development of non-small-cell lung carcinoma (NSCLC). To address this problem, the Oncomine, UALCAN, and the Human Protein Atlas databases were used to analyze differential NEK expression and its clinicopathological parameters, while the Kaplan-Meier, cBioPortal, GEPIA, and DAVID databases were used to analyze survival, gene mutations, similar genes, and biological enrichments. The rate of NEK family gene mutation was high (> 50%) in patients with NSCLC, in which NEK2/4/6/8/ was overexpressed and significantly correlated with tumor stage and nodal metastasis status. In addition, the high expression of NEK2/3mRNA was significantly associated with poor prognosis in patients with NSCLC, while high expression of NEK1/4/6/7/8/9/10/11mRNA was associated with good prognosis. In summary, these results suggest that NEK2/4/6/8 may be a potential prognostic biomarker for the survival of patients with NSCLC.

[Effect of electrothermal acupuncture on moderate to severe cancer pain with yin-cold stagnation: a randomized controlled trial].

OBJECTIVE: To observe the effectiveness and safety of electrothermal acupuncture therapy for patients of moderate to severe cancer pain with yin-cold stagnation. METHODS: A total of 60 patients of moderate to severe cancer pain with yin-cold stagnation were randomized into an observation group and a control group, 30 cases in each one. In the control group, opioid painkillers (oxycodone hydrochloride prolonged-release tablet or morphine sulfate sustained-release tablet) were taken. On the basis of the control group, electrothermal acupuncture was applied at Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Hegu (LI 4), Sanyinjiao (SP 6) in the observation group, 30 min each treatment, once a day for 5 days. Before and after treatment, the scores of pain numerical rating scale (NRS) and Karnofsky performance scale (KPS) were observed in the two groups. The pain remission rate, reduction of opioid painkillers and safety were compared. RESULTS: The variation of NRS scores in the observation group were larger than the control group 3, 5 days into treatment (P<0.01, P<0.05). The variation of KPS score in the observation group was larger than the control group after treatment (P<0.05). The pain remission rate was 100.0% (30/30) in the observation group, higher than 86.7% (26/30) in the control group (P<0.05). The reduction of opioid painkillers in the observation group was larger than the control group (P<0.01). There was no adverse reaction during the treatment in the two groups. CONCLUSION: On the basis of the conventional western medication for analgesia, electrothermal acupuncture could relieve pain, reduce the dose of opioid painkillers and improve the quality of life in patients of moderate to severe cancer pain with yin-cold stagnation, has a better safety.

Network Pharmacology Study on the Pharmacological Mechanism of Cinobufotalin Injection against Lung Cancer.

Cinobufotalin injection, extracted from the skin of Chinese giant salamander or black sable, has good clinical effect against lung cancer. However, owing to its complex composition, the pharmacological mechanism of cinobufotalin injection has not been fully clarified. This study aimed to explore the mechanism of action of cinobufotalin injection against lung cancer using network pharmacology and bioinformatics. Compounds of cinobufotalin injection were determined by literature retrieval, and potential therapeutic targets of cinobufotalin injection were screened from Swiss Target Prediction and STITCH databases. Lung-cancer-related genes were summarized from GeneCards, OMIM, and DrugBank databases. The pharmacological mechanism of cinobufotalin injection against lung cancer was determined by enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network was constructed. We identified 23 compounds and 506 potential therapeutic targets of cinobufotalin injection, as well as 70 genes as potential therapeutic targets of cinobufotalin injection in lung cancer by molecular docking. The antilung cancer effect of cinobufotalin injection was shown to involve cell cycle, cell proliferation, antiangiogenesis effect, and immune inflammation pathways, such as PI3K-Akt, VEGF, and the Toll-like receptor signaling pathway. In network analysis, the hub targets of cinobufotalin injection against lung cancer were identified as VEGFA, EGFR, CCND1, CASP3, and AKT1. A network diagram of "drug-compounds-target-pathway" was constructed through network pharmacology to elucidate the pharmacological mechanism of the antilung cancer effect of cinobufotalin injection, which is conducive to guiding clinical medication.

Clinical research of compound zhebei granules for increasing the therapeutic effect of chemotherapy in refractory acute leukemia patients.

OBJECTIVE: To observe the effects of Compound Zhebei Granules (CZG) in chemotherapy for refractory acute leukemia. METHOD: Using a randomized, double-blind and multi-central concurrent control clinical research project, the patients conformed with the diagnostic criteria, according to the drug randomized method, were divided into a CZG group and a control group. The patients of the two groups respectively took the observation drug or a placebo 3 days before chemotherapy, and the therapeutic effects were evaluated after one course of chemotherapy. According to the clinical research project, 137 patients were enrolled, including 71 cases in the CZG group and 66 cases in the control group. RESULTS: The clinical complete remission (CR) rate was 42.3% in the CZG group with a total effective rate of 73.2%, and it was 25.8% in the control group with a total effective rate of 53.0%, showing a statistically significant difference between the two groups (P < 0.05). CONCLUSION: CZG can increase the clinical remission rate for refractory acute leukemia during chemotherapy.

[Electrothermal acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting:a randomized controlled trial].

OBJECTIVE: To observe the effectiveness and safety of electrothermal acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in the cancerous patients of phlegm-stasis interaction in cisplatin-containing chemotherapy. METHODS: Sixty cases of phlegm-stasis interaction in cisplatin-containing chemotherapy were randomized into a trial group and a control group, 30 cases in each one. In the control group, the intravenous drip of granisetron hydrochloride injection was adopted, 3 mg before and after cisplatin-containing chemotherapy 30 min, continuously for 3 days. 43 to 45℃ electrothermal acupuncture at zusanli(ST 36) for 30 min was used on the basis of the treatment as the control group in the trial group,once a day for 3 days. CINV, anti-nausea effects, Karnofsky score, the syndrome score of phlegm-stasis interaction, and relevant indices of safety were observed on the 1st and 7th days of cisplatin-containing chemotherapy separately. RESULTS: 1.Regarding CINV and anti-nausea effect, CINV did not occur before chemotherapy in the patients of the two groups. On the 1st and 7th days of chemotherapy, CINV in the trial group were milder than those in the control group (both P<0.05).The anti-nausea effects in the trail group were better than those of the control group.2.Regarding Karnofsky score and the syndrome score of phlegm-stasis interaction, the improvements on the 7th days of chemotherapy in the trial group were better than those in the control group, indicating the significant differences (both P<0.05). 3.Regarding the safety indies, there was no adverse reaction during the treatment in the two groups. CONCLUSIONS: The electrothermal acupuncture effectively relieves CINV, and improves self-care dbility and the symptoms of phlegm-stasis interaction.