[Research Progress of Pyroptosis in Leukemia: from Mechanism to Treatment --Review].

Pyroptosis is a programmed death mediated by activated caspase and Gasdermin family proteins, characterized by cell swelling, cytosolysis and release of inflammatory factors. Leukemia is a malignant disease characterized by abnormal differentiation and proliferation of hematopoietic stem cells, thus seriously threating human health. In recent years, it has been found that the transformation, proliferation, metastasis and treatment response of leukemia cells are closely related to pyrodeath. Pyroptosis provides a new perspective for the study of leukemia. This paper reviews the types and molecular mechanisms of pyroptosis, the role of pyroptosis in the occurrence and development of leukemia and the treatment of leukemia, so as to provide some references for further study of the relationship between pyroptosis and leukemia, in order to provide a new strategy for the treatment of leukemia.

Mosquito Repellents: Efficacy Tests of Commercial Skin-Applied Products in China.

As a prevention tool for mosquito-borne diseases, mosquito repellents have received substantial attention. To make a convincing recommendation for repellent products to Chinese consumers, we compared the protection time (landing time and probing time) of the 26 best-selling commercial repellents in the Chinese market in a controlled laboratory environment. The data were analyzed by one-way ANOVA. Meanwhile, prices and favorable rates of repellents are also taken into consideration. In our study, N, N-diethyl-m-toluamide (DEET)-based products provided the longest protection time (0.5-3.88 h landing time and/or 1-5.63 h probing time) and lower prices (13.9-21.9 yuan) than other components (ethyl butylacetylaminopropionate (IR3535), picaridin, and botanical. Among the 26 selected products, only 17 repellents showed repellency, and the best repellent was Green Jungle (15% DEET), with a mean (±SD) landing and/or probing time of 3.88 ± 1.65 h and/or 5.63 ± 0.36 h. For botanicals, only ICE King, OMNIbaby, and Ren He showed a little repellency. Autan (20% picaridin) performed best in the picaridin group. Run Ben (7% IR3535) stood out from the IR3535 group. In conclusion, DEET repellent is highly recommended to consumers. The combination of botanicals and synthesized chemicals is a new prospect for eco-friendly repellents.

Association Between Genetic Polymorphisms of Metabolic Enzymes and Azathioprine-Induced Myelosuppression in 1,419 Chinese Patients: A Retrospective Study.

The aim of this study was to investigate the correlation between genetic polymorphisms of azathioprine-metabolizing enzymes and adverse reactions of myelosuppression. To this end, a retrospective analysis was performed on 1,419 Chinese patients involving 40 different diseases and 3 genes: ITPA (94C>A), TPMT*3 (T>C), and NUDT15 (415C>T). Strict inclusion and exclusion criteria were established to collect the relative cases, and the correlation between azathioprine and myelosuppression was evaluated by adverse drug reaction criteria. The mutation rates of the three genes were 29.32, 3.73, and 21.92% and grades I to IV myelosuppression occurred in 54 (9.28%) of the 582 patients who took azathioprine. The highest proportion of myelosuppression was observed in 5 of the 6 (83.33%) patients carrying the NUDT15 (415C>T) TT genotype and 12 of the 102 (11.76%) patients carrying the NUDT15 (415C>T) CT genotype. Only the NUDT15 (415C>T) polymorphism was found to be associated with the adverse effects of azathioprine-induced myelosuppression (odds ratio [OR], 51.818; 95% CI, 5.280-508.556; p = 0.001), which suggested that the NUDT15 (415C>T) polymorphism could be an influencing factor of azathioprine-induced myelosuppression in the Chinese population. Epistatic interactions between ITPA (94C>A) and NUDT15 (415C>T) affect the occurrence of myelosuppression. Thus, it is recommended that the genotype of NUDT15 (415C>T) and ITPA (94C>A) be checked before administration, and azathioprine should be avoided in patients carrying a homozygous NUDT15 (415C>T) mutation. This study is the first to investigate the association between genetic polymorphisms of these three azathioprine-metabolizing enzymes and myelosuppression in a large number of cases with a diverse range of diseases.

Observation of the effect of one-to-one education on high-risk cases of diabetic foot.

BACKGROUND: Diabetes is a common chronic disease, and its global incidence is on the rise. The disease is directly attributed to insufficient insulin efficacy/secretion, and patients are often accompanied by multiple complications. Diabetic foot is one of the most common complications of diabetes. Diabetic feet have ulcers and infections, which can eventually lead to amputation. Basic nursing care, such as lowering blood pressure and preventing foot skin infections in clinical nursing work, has positive significance for the prevention and control of diabetic feet. AIM: To explore the positive significance of one-to-one education in high-risk cases of diabetic foot. METHODS: This observation included 98 high-risk cases of diabetic foot in our hospital during the period from August 2017 to October 2019, and these patients were randomly divided into the basic nursing group and the one-to-one education group with 49 patients per group. The basic nursing group only received routine basic nursing, while the one-to-one education group gave patients one-to-one education on the basis of basic nursing. After nursing, the self-care ability and compliance behavior of the two groups were evaluated and compared between these two groups. The knowledge mastery of the patient and the satisfaction of nursing were accounted. RESULTS: The assessment results of patients (self-care responsibility, self-care skills, self-concept and self-care knowledge) were significantly higher in the one-to-one education group than in the basic nursing group. The scores of compliance behaviors (foot bathing, shoes and socks selection, sports health care) in the one-to-one education group were significantly higher than those in the basic nursing group. Patients in the one-to-one education group had a significantly higher level of knowledge mastery and satisfaction of nursing than the basic nursing group. CONCLUSION: One-to-one education for high-risk cases of diabetic foot is helpful to improve the cognition and self-care ability of patients with diabetic foot, to ensure that patients follow the doctor's advice of self-care and to improve their nursing satisfaction.

Novel zwitterionic vectors: Multi-functional delivery systems for therapeutic genes and drugs.

Zwitterions consist of equal molar cationic and anionic moieties and thus exhibit overall electroneutrality. Zwitterionic materials include phosphorylcholine, sulfobetaine, carboxybetaine, zwitterionic amino acids/peptides, and other mix-charged zwitterions that could form dense and stable hydration shells through the strong ion-dipole interaction among water molecules and zwitterions. As a result of their remarkable hydration capability and low interfacial energy, zwitterionic materials have become ideal choices for designing therapeutic vectors to prevent undesired biosorption especially nonspecific biomacromolecules during circulation, which was termed antifouling capability. And along with their great biocompatibility, low cytotoxicity, negligible immunogenicity, systematic stability and long circulation time, zwitterionic materials have been widely utilized for the delivery of drugs and therapeutic genes. In this review, we first summarized the possible antifouling mechanism of zwitterions briefly, and separately introduced the features and advantages of each type of zwitterionic materials. Then we highlighted their applications in stimuli-responsive "intelligent" drug delivery systems as well as tumor-targeting carriers and stressed the multifunctional role they played in therapeutic gene delivery.

Clinical characteristics and chest CT imaging features of critically ill COVID-19 patients.

OBJECTIVES: To compare clinical, laboratory, and chest computed tomography (CT) findings in critically ill patients diagnosed with coronavirus disease 2019 (COVID-19) who survived and who died. METHODS: This retrospective study reviewed 60 critically ill patients (43 males and 17 females, mean age 64.4 ± 11.0 years) with COVID-19 pneumonia who were admitted to two different clinical centers. Their clinical and medical records were analyzed, and the chest CT images were assessed to determine the involvement of lobes and the distribution of lesions in the lungs between the patients who recovered from the illness and those who died. RESULTS: Compared with recovered patients (50/60, 83%), deceased patients (10/60, 17%) were older (mean age, 70.6 vs. 62.6 years, p = 0.044). C-reactive protein (CRP) (110.8 ± 26.3 mg/L vs 63.0 ± 50.4 mg/L, p < 0.001) and neutrophil-to-lymphocyte ratio (NLR) (18.7 ± 16.6 vs 8.4 ± 7.5, p = 0.030) were significantly elevated in the deceased as opposed to the recovered. Medial or parahilar area involvement was observed in all the deceased patients (10/10, 100%), when compared to only 54% (27/50) in the recovered. Ground-glass opacities (97%), crazy-paving pattern (92%), and air bronchogram (93%) were the most common radiological findings. There was significant difference in diabetes (p = 0.025) and emphysema (p = 0.013), and the odds ratio on a deceased patient having diabetes and emphysema was 6 times and 21 times the odds ratio on a recovered patient having diabetes and emphysema, respectively. CONCLUSIONS: Older patients with comorbidities such as diabetes and emphysema, and higher CRP and NLRs with diffuse lung involvement were more likely to die of COVID-19. KEY POINTS: • Almost all patients critically ill with COVID-19 pneumonia had five lung lobes involved. • Medial or parahilar area involvement and degree of lung involvement were more serious in the deceased patients when compared with those who recovered from treatment. • Chronic lung disease, e.g., emphysema, diabetes, and higher serum CRP and NLR characterized patients who died of COVID-19.

Current RNA-based Therapeutics in Clinical Trials.

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

Progress in the treatment of infantile hemangioma.

Infantile hemangioma (IH) is a common benign tumor, which mostly resolves spontaneously; however, children with high-risk IH need treatment. Currently, the recognized first-line treatment regimen for IH is oral propranolol, but research on the pathogenesis of IH has led to the identification of new therapeutic targets, which have shown good curative effects, providing more options for disease treatment. This article summarizes the applications of different medications, dosages, and routes of administration for the treatment of IH. In addition to drug therapy, this article also reviews current therapeutic options for IH such as laser therapy, surgical treatment, and observation. To provide the best treatment, therapeutic regimens for IH should be selected based on the child's age, the size and location of the lesion, the presence of complications, the implementation conditions, and the potential outcomes of the treatment.

Current Advances in Small Activating RNAs for Gene Therapy: Principles, Applications and Challenges.

Small activating RNAs (saRNAs) are small double-stranded RNAs that could mediate the target-specific gene expression by targeting selected sequences in gene promoters at both the transcriptional and epigenetic levels. This phenomenon of gene manipulation is known as RNA activation (RNAa), which opens up a new pathway for RNA-based gene therapeutics in contrast to RNA interference. Although the exact molecular mechanism of RNAa mediated by saRNAs still remains foggy, some studies have provided the possible ones to explain it. Furthermore, mounting evidence exhibit that saRNAs not only provide a new approach to study gene function and manipulate transcriptional activity, but also promise a great potential for clinical therapy against various diseases, especially cancer. Cancer-associated genes could be up-regulated by saRNAs to modulate cell cycle and proliferation, induce cell senescence and apoptosis, inhibit cancer cell invasion and migration, and reverse chemotherapy resistance. Herein, we summarize the known mechanisms of saRNAs on up-regulating specific gene expression and focus on the potential applications of saRNAs in gene therapy. In addition, some concerns about mechanisms and challenges for delivery of saRNAs are involved in this review. The precise mechanisms of saRNAs need to be further illustrated and some novel delivery systems for saRNAs are expected to be developed for clinical applications.

Degradation of the neonicotinoid insecticide acetamiprid via the N-carbamoylimine derivate (IM-1-2) mediated by the nitrile hydratase of the nitrogen-fixing bacterium Ensifer meliloti CGMCC 7333.

The metabolism of the widely used neonicotinoid insecticide acetamiprid (ACE) has been extensively studied in plants, animals, soils, and microbes. However, hydration of the N-cyanoimine group in ACE to the N-carbamoylimine derivate (IM-1-2) by purified microbes, the enzyme responsible for this biotransformation, and further degradation of IM-1-2 have not been studied. The present study used liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy to determine that the nitrogen-fixing bacterium Ensifer meliloti CGMCC 7333 transforms ACE to IM-1-2. CGMCC 7333 cells degraded 65.1% of ACE in 96 h, with a half-life of 2.6 days. Escherichia coli Rosetta (DE3) overexpressing the nitrile hydratase (NHase) from CGMCC 7333 and purified NHase converted ACE to IM-1-2 with degradation ratios of 97.1% in 100 min and 93.9% in 120 min, respectively. Interestingly, IM-1-2 was not further degraded by CGMCC 7333, whereas it was spontaneously hydrolyzed at the N-carbamoylimine group to the derivate ACE-NH, which was further converted to the derivative ACE-NH2. Then, ACE-NH2 was cleaved to the major metabolite IM-1-4. IM-1-2 showed significantly lower insecticidal activity than ACE against the aphid Aphis craccivora Koch. The present findings will improve the understanding of the environmental fate of ACE and the corresponding enzymatic mechanisms of degradation.

The metabolism of neonicotinoid insecticide thiamethoxam by soil enrichment cultures, and the bacterial diversity and plant growth-promoting properties of the cultured isolates.

A soil enrichment culture (SEC) rapidly degraded 96% of 200 mg L(-1) neonicotinoid insecticide thiamethoxam (TMX) in MSM broth within 30 d; therefore, its metabolic pathway of TMX, bacterial diversity and plant growth-promoting rhizobacteria (PGPR) activities of the cultured isolates were studied. The SEC transformed TMX via the nitro reduction pathway to form nitrso, urea metabolites and via cleavage of the oxadiazine cycle to form a new metabolite, hydroxyl CLO-tri. In addition, 16S rRNA gene-denaturing gradient gel electrophoresis analysis revealed that uncultured rhizobacteria are predominant in the SEC broth and that 77.8% of the identified bacteria belonged to uncultured bacteria. A total of 31 cultured bacterial strains including six genera (Achromobacter, Agromyces, Ensifer, Mesorhizobium, Microbacterium and Pseudoxanthomonas) were isolated from the SEC broth. The 12 strains of Ensifer adhaerens have the ability to degrade TMX. All six selected bacteria showed PGPR activities. E. adhaerens TMX-23 and Agromyces mediolanus TMX-25 produced indole-3-acetic acid, whereas E. adhaerens TMX-23 and Mesorhizobium alhagi TMX-36 are N2-fixing bacteria. The six-isolated microbes were tolerant to 200 mg L(-1) TMX, and the growth of E. adhaerens was significantly enhanced by TMX, whereas that of Achromobacter sp. TMX-5 and Microbacterium sp.TMX-6 were enhanced slightly. The present study will help to explain the fate of TMX in the environment and its microbial degradation mechanism, as well as to facilitate future investigations of the mechanism through which TMX enhances plant vigor.

Two new sesquiterpene lactones from Ixeris sonchifolia.

The structures of two new sesquiterpene lactones, 11,13beta-dihydroixerin Z (1) and Ixerin Z2 (2) isolated from Ixeris sonchifolia were determined to be 3-hydroxy-1(10),3-guaiadiene-12,6-olide-2-one-3-O-beta-D-glucopyranoside and 1(10),3,11 (13)-guaiatriene-12,6-olide-2-one-3-O-[6'-(4"-hydroxybenzyl lactyl)]-beta-D-glucopyranoside, respectively on the basis of detailed spectral analysis.

[Development of transformation system of rice based on transformation-competent artificial chromosome (TAC) vector].

The TAC clone (NK15) containing a ca.50 kb DNA insert was introduced into Agrobacterium tumefaciens strain LBA4404 by electroporation. The NK15 was stable in Agrobacterium tumefaciens strain LBA4404 under kanamycin selection for many generations. The calli of mature embryo of Nongken58S were infected with the Agrobacterium tumefaciens strain LBA4404 carrying NK15. PCR and Southern analyses of transgenic plants indicated that the 50 kb of foreign DNA was transferred into the rice genome, and most of transgenic plants had one copy of the insertion. Genetic and PCR analyses of T1 progeny confirmed that the inserted forgein DNA was stably inherited.