Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Hymenopteran insect stings are a risk factor that cannot be ignored for the people allergic to hymenopteran venoms.In China,the current diagnostic tools cannot provide accurate information to identify sen-sitized insects,thus affecting clinical diagnosis and treatment.Honeybee is a common hymenopteran insect.Due to its wide distribution,large number,and complex venom composition,researchers have carried out recombi-nation schemes for the main allergens of honeybee venom,laying a theoretical foundation for the detection of al-lergens.The development of diagnostic technologies for allergen components can accurately detect bee venom aller-gens,providing a new set of clinical diagnosis and treatment schemes for the population allergic to bee venom.

Terpine-4-ol is abundant in nature. As a cyclic monoterpenoid compound， terpine-4-ol is distributed in a variety of natural plants. It is the main component and the key active substance in many traditional Chinese essential oils， such as Melaleuca alba essential oil and coral ginger essential oil. Terpine-4-ol has anti-microbial， anti-tumor， insecticidal， anti-inflammatory， and other effects. It can treat cancer， as well as oral and cardiovascular diseases with great safety. In terms of antibacterial activity， terpine-4-ol can destroy bacterial cell walls， improve membrane permeability， and regulate bacterial migration， reproduction， and other related genes to inhibit bacterial activity. In terms of antifungal activity， terpine-4-ol can bind with ergosterol in fungal cell walls to cause fungal death. In terms of insecticidal activity， terpine-4-ol can inhibit Na⁺ and K⁺-ATPase activity and cause the death of the insect. In terms of anticancer activity， terpine-4-ol can regulate the expression of apoptosis-related proteins in cancer cells， so as to control the apoptosis of cancer cells. In this paper， the pharmacological activity and action mechanism of terpine-4-ol were reviewed to provide a reference for further research and utilization of terpine-4-ol.

Objective:To study the profile of microRNAs (miRNAs) in the peripheral blood of children with drug-resistant epilepsy, and to find diagnostic biomarkers for early identification of drug-resistant epilepsy in children.Methods:Retrospective study.Five peripheral blood samples were collected from children in drug-resistant epilepsy group (group R), drug-responsive epilepsy group (group F) composed of the children with epilepsy in pediatric neurology clinic of the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2019 and healthy control group (group J) composed of healthy children who underwent physical examination in the children′s health care clinic at the same time for analyzing miRNA profiles by high-throughput sequencing.In addition, peripheral blood samples were collected from children in R′ group (5 cases), F′ group (7 cases) and J′ group (6 cases) similarly for validating expression levels of 11 candidate miRNAs by quantificational real-time polymerase chain reaction (qPCR). Receiver operating characteristic curves (ROC) were plotted to analyze the diagnostic potential of 7 targeted miRNAs in distinguishing children with drug-resistant epilepsy from drug-responsive epilepsy.Target genes of the 7 validated miRNAs were predicted using online databases, which were then analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). Kruskal-Wallis rank sum test was used for comparison among the three groups.Results:High-throughput sequencing found that compared with group F, there were 68 differentially expressed miRNAs in group R, involving 22 up-regulated and 46 down-regulated miRNAs.qPCR results showed that, expression trends of 7 miRNAs (let-7f, miR-99a-5p, miR-99b-5p, and miR-125a-5p, miR-125b-5p, miR-142-5p, miR-100) were consistent with high-throughput sequencing results among the 11 selected miRNAs.ROC analysis found that when the cut-off values of miR-99a-5p, miR-99b-5p, miR-125a-5p, miR-125b-5p, miR-142-5p and miR-100 were greater than 0.56, 1.00, 3.17, 2.24, 2.09 and 0.59, respectively, their area under curve (AUC) (≥0.871), sensitivity (≥80.0%) and specificity (≥85.7%) were relatively high, which were expected to be diagnostic marker for drug-resistant epilepsy in children.Among them, the diagnostic potential of miR-125b-5p was the best.Bioinformatics analysis found that miR-125b-5p was enriched in the regulation of hypoxia inducible factor-1 signaling pathway, insulin signaling pathway, pluripotent stem cell signaling pathway, mitogen-activated protein kinase signaling pathway, sphingomyelin signaling pathway, neurotrophic protein signaling pathway and mammalian target of rapamycin signaling pathway.Conclusions:The miRNA profile in the whole blood of children with drug-resistant epilepsy is significantly different from that in children with drug-responsive epilepsy.miR-125b-5p is expected to be a potential biomarker of drug-resistant epilepsy in children.

Objective:To analyze the epidemiological and clinical characteristics of hospitalized patients with dengue fever in Guangdong Province in 2019, so as to provide reference for clinical diagnosis and treatment of dengue fever.Methods:The general data, laboratory examination data, clinical manifestations and prognosis data of 480 inpatients with dengue fever admitted to Eight People′s Hospital Affiliated to Guangzhou Medical University between January 4 and October 31, 2019 were analyzed retrospectively. The clinical and onset characteristics of patients with dengue fever were described.Results:Among 480 dengue patients, 442(92.1%) were dengue fever, 38(7.9%) were severe dengue, and 136(28.3%) had underlying diseases. The peak age of onset was mainly in young adults aged 20 to 49 years old, accounting for 66.0%(317/480) in total. The seasonal peak was mainly in August to October. There were 399(83.1%) local cases and 61(12.7%) imported cases. The most common clinical manifestations were fever (98.1%, 471/480), chills (72.9%, 350/480), headache (58.5%, 281/480) and bone/joint/muscle pain (67.1%, 322/480), followed by digestive tract symptoms and respiratory tract symptoms. Among 446 serum samples, 358 (80.3%) were dengue virus (DENV)-1, 54 (12.1%) were DENV-2, 34 (7.6%) were DENV-3. The main laboratory tests of the patients were leucopenia (65.8%, 316/480), low hematocrit (30.2%, 145/480), thrombocytopenia (48.3%, 232/480), neutropenia (44.8%, 215/480), elevated alanine aminotransferase (ALT) (37.7%, 181/480) and aspartate aminotransferase (AST) (59.4%, 285/480). Treatment mainly adopted symptomatic support treatment and active prevention of complications. The length of stay was (5.8±3.1) days (range 1.0-38.0 days). A total of 461(96.0%) patients were cured or improved.Conclusions:In 2019, the majority of dengue fever patients in Guangdong Province are young adults aged 20 to 49 years old, and the proportion of severe patients is high, with DENV-1 infection as the main type. After symptomatic support treatment and active prevention of complications, most of the dengue fever patients have a good prognosis.

To conduct outbreak identification and transmission factor analysis of typhoid epidemic occurred in Xinqiao town, Jiangyin city from June to September 2016. A total of 14 strains of Salmonella typhi isolated from confirmed cases were collected, and 65 external environment samples and 13 food samples related to the outbreak were taken. Real-time PCR was used to detect specific gene of Salmonella typhi in the samples. Conventional method was used to isolate strains. The strains isolated from both the samples and patients in the epidemic were subjected to antimicrobial susceptibility testing and PFGE molecular characteristics. Salmonella typhi strain was isolated from one external sample (well water of a deli processing plant). The results of drug susceptibility showed that 15 strains were resistant to nalidixic acid. A total of 15 strains of Salmonella typhi were divided into 2 molecular patterns by pulsed field gel electrophoresis. The fingerprints of PFGE from the 13 patients and the environmental isolate were completely consistent, and there was one band difference from the other patient isolate. Combined with the epidemiological investigation and laboratory test results, it was determined that the outbreak was caused by genetic clone of the same Salmonella typhi. Food processing plant should be one of the key links.

To conduct outbreak identification and transmission factor analysis of typhoid epidemic occurred in Xinqiao town, Jiangyin city from June to September 2016. A total of 14 strains of Salmonella typhi isolated from confirmed cases were collected, and 65 external environment samples and 13 food samples related to the outbreak were taken. Real-time PCR was used to detect specific gene of Salmonella typhi in the samples. Conventional method was used to isolate strains. The strains isolated from both the samples and patients in the epidemic were subjected to antimicrobial susceptibility testing and PFGE molecular characteristics. Salmonella typhi strain was isolated from one external sample (well water of a deli processing plant). The results of drug susceptibility showed that 15 strains were resistant to nalidixic acid. A total of 15 strains of Salmonella typhi were divided into 2 molecular patterns by pulsed field gel electrophoresis. The fingerprints of PFGE from the 13 patients and the environmental isolate were completely consistent, and there was one band difference from the other patient isolate. Combined with the epidemiological investigation and laboratory test results, it was determined that the outbreak was caused by genetic clone of the same Salmonella typhi. Food processing plant should be one of the key links.

Objective To investigate the single nucleotide polymorphism at G-395A site of the Klotho (KL) gene and to analyze its correlation with the coronary heart disease(CHD) and serum Cystatin C(Cys C) level in the elderly Chinese Han population in central China.Methods A case-control study was conducted in 278 elderly Chinese Han population in this department,who were divided into CHD group(138 cases)and control group(140 cases) according to bear angiography coronary or not.G-395A polymorphism of KL gene was determined by TaqMan Gene probe method,and the relationship between G-395A polymorphism and coronary heart disease and serum Cys-C level was analyzed.Results Compared with the control group,the frequency of GG genotype of G-395A in CHD group was significantly higher,and the frequency of AA genotype and AG genotype was not statistically significant.The levels of Cys-C in the GG genotype were higher than those in the AA and AG genotypes both in the control group and coronary heart disease group.Conclusion In the elderly Han population in central China,the risk of suffering coronary heart disease is higher among the GG genotype of the G-395A locus of the KL gene.KL gene G-395A site gene mutation may affect the development of atherosclerosis by affecting blood Cys-C levels.

Objective To explore the effect of applying theory of planned behavior (TPB) during early pregnancy in preventing gestational diabetes mellitus (GDM) among high risk group, so as to lower incidence of GDM.Methods Patients selected were divided, according to the random number table generated by the computer, into control group and intervention group. Patients in the control group received routine pregnancy education, while patients in the intervention group were intervened by nursing measures constructed with TPB as the framework, and the incidence of GDM was analyzed byχ2test.Results Incidence of GDM in the intervention group was 14.9% (14/94), lower than that in the control group, 26.8% (26/97) (χ2=4.090, P=0.043).Conclusions Nursing intervention basing on TPB during early pregnancy can reduce the incidence of GDM.

Tissue swelling is a common symptom in clinic. With the development of proper technology of traditional Chinese medicine, mirabilite for external application has been widely applied in clinic to relieve tissue swelling with curative effect. This paper summarized the mechanism of action of mirabilite for external application and its current situation in relieving tissue swelling. This paper also pointed out an open question based on existing studies and offered a corresponding proposal.