Creutzfeldt-Jakob disease presenting as Korsakoff syndrome caused by E196A mutation in PRNP gene: A case report.

BACKGROUND: Prion diseases are a group of degenerative nerve diseases that are caused by infectious prion proteins or gene mutations. In humans, prion diseases result from mutations in the prion protein gene (PRNP). Only a limited number of cases involving a specific PRNP mutation at codon 196 (E196A) have been reported. The coexistence of Korsakoff syndrome in patients with Creutzfeldt-Jakob disease (CJD) caused by E196A mutation has not been documented in the existing literature. CASE SUMMARY: A 61-year-old Chinese man initially presented with Korsakoff syndrome, followed by rapid-onset dementia, visual hallucinations, akinetic mutism, myoclonus, and hyperthermia. The patient had no significant personal or familial medical history. Magnetic resonance imaging of the brain revealed extensive hyperintense signals in the cortex, while positron emission tomography/computed tomography showed a diffuse reduction in cerebral cortex metabolism. Routine biochemical and microorganism testing of the cerebrospinal fluid (CSF) yielded normal results. Tests for thyroid function, human immunodeficiency virus, syphilis, vitamin B1 and B12 levels, and autoimmune rheumatic disorders were normal. Blood and CSF tests for autoimmune encephalitis and autoantibody-associated paraneoplastic syndrome yielded negative results. A test for 14-3-3 protein in the CSF yielded negative results. Whole-genome sequencing revealed a disease-causing mutation in PRNP. The patient succumbed to the illness 11 months after the initial symptom onset. CONCLUSION: Korsakoff syndrome, typically associated with alcohol intoxication, also manifests in CJD patients. Individuals with CJD along with PRNP E196A mutation may present with Korsakoff syndrome.

Novel strategies to reverse chemoresistance in colorectal cancer.

Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients. Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis of patients. To overcome chemoresistance in CRC, many strategies are being investigated. Here, we review the common and novel measures to combat the resistance, including drug repurposing (nonsteroidal anti-inflammatory drugs, metformin, dichloroacetate, enalapril, ivermectin, bazedoxifene, melatonin, and S-adenosylmethionine), gene therapy (ribozymes, RNAi, CRISPR/Cas9, epigenetic therapy, antisense oligonucleotides, and noncoding RNAs), protein inhibitor (EFGR inhibitor, S1PR2 inhibitor, and DNA methyltransferase inhibitor), natural herbal compounds (polyphenols, terpenoids, quinones, alkaloids, and sterols), new drug delivery system (nanocarriers, liposomes, exosomes, and hydrogels), and combination therapy. These common or novel strategies for the reversal of chemoresistance promise to improve the treatment of CRC.

Mitigation of QingLuoTongMai Pills on Chemotherapy-induced Phlebitis: A Network Pharmacology Study and Experimental Validation.

OBJECTIVE: Chemotherapy induced phlebitis (CIP) is a side product of chemotherapy treatment for malignant tumors, which affects the therapeutic effect and quality of life of cancer patients, and still lacks a clear therapeutic means. In this study, we investigated the therapeutic effects of QLTMP on CIP using network pharmacology and verified the anti-inflammatory mechanism of QLTMP in mice model induced by vinorelbine. METHODS: Network pharmacology analysis was performed to identify bioactive compounds in QLTMP. The protein-protein interaction network was used to identify the core therapeutic targets of QLTMP against CIP. Analyzed biological function and pathway enrichment based on the identified core therapeutic targets. Evaluate the therapeutic effect of QLTMP in a model of CIP induced by vinorelbine to confirm the reliability of the network pharmacological analysis. MATERIALS AND METHODS: The 165 bioactive compounds of QLTMP matched the screening criteria and identified 19 core therapeutic targets of QLTMP against CIP. Biofunctional analysis showed that the therapeutic effect of QLTMP on CIP was mainly related to the inhibition of inflammation; while pathway enrichment analysis showed that TNF signaling pathway was involved in the inflammatory process. Experimental confirmation in mice model showed that QLTMP exerts anti-inflammatory effects through modulation of PI3K/AKT/TNF signaling pathway, a discovery consistent with the network pharmacological analysis. DISCUSSION AND CONCLUSIONS: The network pharmacological analysis of the anti-inflammatory mechanism of QLTMP on CIP and its exploration of in vivo experiments provide a theoretical basis for the design of agents that can mitigate or cure CIP.

Protection against peripheral artery disease injury by Ruan Jian Qing Mai formula via metabolic programming.

Ruan Jian Qing Mai formula (RJQM), a multicomponent herbal formula, has been widely used to treat peripheral arterial disease (PAD) in China. However, its active compounds and mechanisms of action are still unknown. First, RNA sequencing analysis of 15 healthy and 16 PAD samples showed that 524 PAD differential genes were significantly enriched in Go Ontology (ribonucleotide metabolic process, oxidoreductase complex, and electron transfer activity), Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA pathways (OXPHOS and TCA cycle), miRNA (MIR183), and kinase (PAK6). Fifty-three active ingredients in RJQM had similar structures to the seven drug molecules in CLUE. Then, network topology analysis of the 53 components-target-pathway-disease network yielded 10 active ingredients. Finally, computational toxicity estimations showed that the median lethal dose (LD50) of the 10 active ingredients was above 1000 mg/kg, and eight of them did not cause hepatotoxicity, mutagenicity, carcinogenicity, cytotoxicity, and immunotoxicity nor activate 12 toxic pathways. In conclusion, RJQM has a protection effect on PAD by regulating a complex molecular network. Part of the mechanism is associated with the regulation of OXPHOS by 10 active components, which may alleviate mitochondrial dysfunction and pathological metabolic programming.

[Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice].

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

Protection against COVID-19 injury by qingfei paidu decoction via anti-viral, anti-inflammatory activity and metabolic programming.

Qingfei Paidu decoction (QFPD), a multi-component herbal formula, has been widely used to treat COVID-19 in China. However, its active compounds and mechanisms of action are still unknown. Firstly, we divided QFPD into five functional units (FUs) according to the compatibility theory of traditional Chinese medicine. The corresponding common targets of the five FUs were all significantly enriched in Go Ontology (oxidoreductase activity, lipid metabolic process, homeostatic process, etc.), KEGG pathways (steroid biosynthesis, PPAR signaling pathway, adipocytokine signaling pathway, etc.), TTD diseases (chronic inflammatory diseases, asthma, chronic obstructive pulmonary Disease, etc.), miRNA (MIR183), kinase (CDK7) and TF (LXR). QFPD contained 257 specific targets in addition to HCoV, pneumonia and ACE2 co-expression proteins. Then, network topology analysis of the five components-target-pathway-disease networks yielded 67 active ingredients. In addition, ADMET estimations showed that 20 compounds passed the stringent lead-like criteria and in silico drug-likeness test with high gastrointestinal absorption and the median lethal dose (LD50 > 1600 mg/kg). Moreover, 4 specific ingredients (M3, S1, X2 and O2) and 5 common ingredients (MS1, MX16, SX1, WO1 and XO1) of QFPD presented good molecular docking score for 2019-nCov structure and non-structure proteins. Finally, drug perturbation of COVID-19 network robustness showed that all five FUs may protect COVID-19 independently, and target 8 specifically expressed drug-attacked nodes which were related to the bacterial and viral responses, immune system, signaling transduction, etc. In conclusion, our new FUNP analysis showed that QFPD had a protection effect on COVID-19 by regulating a complex molecular network with safety and efficacy. Part of the mechanism was associated with the regulation of anti-viral, anti-inflammatory activity and metabolic programming.

Identification of potential crucial genes associated with the pathogenesis and prognosis of prostate cancer.

Aim: Prostate cancer (PCa) is the sixth leading cause of cancer-related deaths in men throughout the world. This study aimed to investigate genes associated with the pathogenesis and prognosis of PCa. Materials & methods: Data of PCa cases were obtained from public datasets and were analyzed using an integrated bioinformatics strategy. Results: A total of 969 differential expression genes were identified. Moreover, GSE16560 and The Cancer Genome Atlas (TCGA) data showed a prognostic prompt function of the nine-gene signature, as well as in PCa with Gleason 7. Finally, majority of the nine hub genes were associated with drug sensitivity, mutational landscape, immune infiltrates and clinical characteristics of PCa. Conclusion: The nine-gene signature was correlated with drug sensitivity, mutational landscape, immune infiltrates, clinical characteristics and survival from PCa.

[Effects of Baihe Recipe on expressions of vascular endothelial growth factor and p53 proteins in tumor tissues of nude mice bearing orthotopically transplanted gastric carcinoma BGC-823].

OBJECTIVE: To investigate the effects of Baihe Recipe, a compound traditional Chinese herbal medicine, on growth and metastasis of orthotopically transplanted gastric carcinoma and the expressions of vascular endothelial growth factor (VEGF) and p53 proteins in the tumor tissues in nude mice. METHODS: Forty-five nude mice orthotopically transplanted with BGC-823 human gastric cancer cells were randomly divided into three groups: Baihe Recipe group, 5-fluorouracil (5-FU) group and untreated group. The mice in the Baihe Recipe group received intragastric administration of 0.5 mL Baihe Recipe (crude drug content was 0.2 g/mL) for 6 weeks, and the mice in the untreated group received 0.5 mL normal saline. The mice in the 5-FU group received an intraperitoneal injection of 5-FU dilution (0.2 mL, 60 mg/kg per week, for 3 weeks). All mice were sacrificed after 6-week treatment. The weights of tumor and the growth-inhibiting rate were measured and the expressions of VEGF and p53 proteins were detected by immunohistochemical method. RESULTS: The growth inhibition rates in the Baihe Recipe and 5-FU groups were 52.86% and 42.87% respectively. The incidence rates of metastasis to perigastric and hepatic portal lymph nodes, and to liver and peritoneum in the Baihe Recipe and 5-FU groups were lower than those in the untreated group. The metastasis rates in Baihe Recipe group, 5-FU group and untreated group were 33.33%, 35.71% and 80.00% respectively, with significant difference (P<0.05), and the expressions of VEGF and p53 proteins in tumor tissues in the Baihe Recipe group were lower than those in the untreated group and the 5-FU group (P<0.01, P<0.05). CONCLUSION: Baihe Recipe has inhibitory effects on tumor growth and metastasis of gastric cancer orthotopically transplanted in nude mice by down-regulating the expressions of VEGF and p53 proteins.