Effect Observation of Optimized Individualized Nursing Care Applied to ICU Patients with Severe Pneumonia.

Purpose: This study aims to observe the effect of optimized individualized nursing care applied to intensive care unit (ICU) patients with severe pneumonia (SP). Methods: 440 patients with SP admitted to the ICU of our hospital from January 2019 to June 2020 were provided with routine nursing care (group A), and 550 patients with SP admitted from July 2020 to December 2021 were provided with optimized individualized nursing care (group B). The blood lactate index and acute physiology and chronic health evaluation (APACHE II) scores before and after care were compared between the two groups. The WBC count recovery time, mechanical ventilation time, antipyretic time, and length of hospital stay of the two groups were recorded. The complication rate of the two groups during the nursing care period was compared. The prognosis effect of the two groups after 6 and 12 months of discharge was followed up with the Seattle angina pectoris questionnaire (SAQ). Results: After care, the lactate level and lactate clearance rate were higher in both groups than before care, and the lactate level in group B was lower than that in group A and the lactate clearance rate was higher than that in group A (P < 0.05). After care, APACHE II scores were lower in both groups than before care, and lower in group B than in group A (P < 0.05). After care, the WBC count recovery time, mechanical ventilation time, antipyretic time, and length of hospital stay were shorter in group B than in group A (P < 0.05). During the nursing care period, the complication rate was lower in group B (5.82%) than in group A (11.59%) (P < 0.05). 6 and 12 months after discharge, the SAQ scores were higher in group B than in group A (P < 0.05). Conclusion: Optimized individualized nursing care applied to ICU SP patients can effectively improve the patients' physiological indicators, reduce complications, improve the prognosis of quality of life, and have a positive effect on the patients' speedy recovery.

Genotyping and Quantifying Lyme Pathogen Strains by Deep Sequencing of the Outer Surface Protein C (ospC) Locus.

A mixed infection of a single tick or host by Lyme disease spirochetes is common and a unique challenge for the diagnosis, treatment, and surveillance of Lyme disease. Here, we describe a novel protocol for differentiating Lyme strains on the basis of deep sequencing of the hypervariable outer surface protein C locus (ospC). Improving upon the traditional DNA-DNA hybridization method, the next-generation sequencing-based protocol is high throughput, quantitative, and able to detect new pathogen strains. We applied the method to more than one hundred infected Ixodes scapularis ticks collected from New York State, USA, in 2015 and 2016. An analysis of strain distributions within individual ticks suggests an overabundance of multiple infections by five or more strains, inhibitory interactions among coinfecting strains, and the presence of a new strain closely related to Borreliella bissettiae A supporting bioinformatics pipeline has been developed. The newly designed pair of universal ospC primers target intergenic sequences conserved among all known Lyme pathogens. The protocol could be used for culture-free identification and quantification of Lyme pathogens in wildlife and potentially in clinical specimens.

X-ray cross-complementing groups 1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility: A meta-analysis based on Chinese Han population.

OBJECTIVE: X-ray cross-complementing groups 1 (XRCC1) rs1799782 C>T polymorphisms and colorectal cancer susceptibility were not clear. The purpose of this study was to evaluate the association between XRCC1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility by meta-analysis. MATERIALS AND METHODS: Related databases of Medline, CNKI, and Wanfang were systematic searched for the studies related to XRCC1 rs1799782 C>T polymorphisms and colorectal cancer risk in Chinese Han population. The genotype distribution of CC, CT and TT were extracted from each included studies in the colorectal cancer patients and healthy control subjects. The odds ratio (OR) and its 95% confidence interval (95% CI) was used to assess the correlation between genetype and colorectal cancer risk. The publications for this study was evaluated by Begg's funnel plot and Egger's line regression test. RESULTS: The median frequency of CC, CT, and TT genotype in cancer group were 48%, 41% and 11%; For control group, they were 51%, 40% and 8%; the pooled results showed that OR = 1.32 (95% CI: 1.041-1.67, P < 0.05). The pooled results indicated that XRCC1 rs1799782 C>T polymorphisms was associated with colorectal cancer susceptibility in recessive genetic model OR = 1.32 (95% CI: 1.041-1.67, P < 0.05), dominant genetic model OR = 1.21 (95% CI: 1.00-1.46, P < 0.05) and homozygous genetic model OR = 1.43 (95% CI: 1.07-1.91, P < 0.05). The funnel plot was significant asymmetric at the bottom and the Egger's test also indicated significant publication bias (t = 2.43, P = 0.04) for recessive genetic model. But, no publication bias was found in dominant and homozygous model (P > 0.05). CONCLUSION: Chinese Han people with rs1799782 TT/CT genotype of XRCC1 gene may have increased risk of developing colorectal.

Helioxanthin analogue 8-1 inhibits duck hepatitis B virus replication in cell culture.

BACKGROUND: Current approved anti-HBV treatment cannot completely eliminate HBV infection, and emergence of resistant virus is an important treatment issue. Effective anti-HBV agents with different mechanisms of action on novel target sites are needed for the treatment of HBV infection and for combating the resistant virus, alone or in combination with current anti-HBV strategies. Helioxanthin analogue 8-1 displayed potent anti-HBV activity in human HBV in vitro and in animal models, with a unique antiviral mechanism. Its antiviral activity in other HBV system needs further study. METHODS: The anti-duck hepatitis B virus (DHBV) activity of 8-1, an analogue of a natural product, helioxanthin, was studied in the DHBV inducible cell line, dstet5, in comparison to and in combination with the nucleoside analogue, lamivudine (3TC). RESULTS: Helioxanthin analogue 8-1 exhibited anti-DHBV activity as demonstrated by quantification of viral DNA, RNA, covalently closed circular DNA and protein synthesis. Analogue 8-1 did not affect the stability of cellular macromolecules and did not have a sustained antiviral effect after drug removal. When DHBV replication was induced, virus-harbouring cells were more susceptible to the cytotoxicity of 8-1 than non-induced cells. CONCLUSIONS: 8-1 exhibited effective inhibition on DHBV replication. The combination of 8-1 with 3TC resulted in additional anti-DHBV activity. Viral induced cells displayed higher susceptibility to 8-1 treatment than non-induced cells. HBV X protein might not be an essential factor in the initiation of the biological activity of 8-1, as demonstrated by its absence in DHBV. These findings warrant further development of 8-1 for the treatment of chronic hepatitis B and its associated diseases.

Unique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue.

Helioxanthin is a natural product that inhibits the replication of a number of viruses. We found that a previously undescribed helioxanthin analogue, 8-1, exhibited potent anti-hepatitis B virus (HBV) activity with little cytotoxicity. 8-1 suppressed both HBV RNA and protein expression, as well as DNA replication of both wild-type and 3TC-resistant virus. Time-course analyses revealed that RNA expression was blocked first after treatment with 8-1, followed by viral proteins, and then DNA. 8-1 inhibited the activity of all HBV promoters by decreasing the binding of hepatocyte nuclear factor 4 (HNF-4), HNF-3, and fetoprotein factor to the precore/core promoter enhancer II region. The amount of HNF-4 and HNF-3 was decreased posttranscriptionally by 8-1 in HBV-producing cells, but not in HBV-negative cells. Therefore, 8-1 suppresses HBV replication by posttranscriptional down-regulation of critical transcription factors in HBV-producing cells, thus diminishing HBV promoter activity and blocking viral gene expression and replication. This mechanism is unique and different from other anti-HBV compounds previously described.

Ribavirin and mycophenolic acid markedly potentiate the anti-hepatitis B virus activity of entecavir.

MPA [the active metabolite of the immuno-suppressive agent CellCept] and ribavirin markedly potentiate the anti-HBV activity of the guanine-based nucleoside analogue entecavir (ETV) against both wild-type HBV and a lamivudine-resistant variant. Ribavirin (in its 5'-monophosphate form) and MPA are inhibitors of IMP-dehydrogenase and cause depletion of intracellular dGTP pools. The active triphosphorylated form of ETV may inhibit more efficiently the priming reaction, reverse transcription and DNA-dependent DNA polymerase activity of the HBV polymerase in the presence of reduced levels of dGTP. The potential for enhanced ETV activity is supported by the observation that exogenously added deoxyguanosine reversed the potentiating effect of ribavirin and MPA. Our observations may have important implications for those (liver) transplant recipients that receive MMF as part of their immunosuppressive regimen and who, because of a de novo or a persistent infection with HBV need antiviral therapy such as ETV. Further studies will need to be conducted to determine if combining ribavirin (a compound used for the treatment of HCV infections) with ETV could have an advantage for the treatment of HBV infections, in particular in patients co-infected with HCV.

Hepatitis B virus replication causes oxidative stress in HepAD38 liver cells.

UNLABELLED: We used human hepatoma HepAD38 cells, in which HBV production is under the control of a tetracycline-regulated promotor, to investigate changes induced in the host cell by HBV replication that could contribute to malignant transformation. Parameters of oxidative stress (malondialdehyde, glutathione) and cell proliferation were determined at different times after induction (0-96 h). In HBV-producing cells, the redox status peaked at 72 h. cDNA micro array analysis at 72 h post induction revealed 3 groups of genes that were up-regulated by HBV: (i) heat shock proteins, (ii) oxidative and metabolic stress and (iii) growth and apoptosis related genes. Continuous HBV production did not accelerate karyotypic changes in cells cultured for 4 months (18 passages). IN CONCLUSION: HBV replication modulates host gene expression and induces oxidative stress. In this HepAD38 model early events (0-4 days) in the host cell after induction of HBV replication can be studied under strictly defined conditions.

New targets and inhibitors of HBV replication to combat drug resistance.

All the approved chemotherapeutic drugs for the treatment of HBV hepatitis are nucleoside analogs targeting on HBV DNA polymerase. Drugs targeting on other viral unique targets are needed. A new class of chemicals with novel action against HBV replication was discovered. A brief description of their mode of action is given.

Selective inhibition of hepatitis B virus replication by RNA interference.

Small interfering RNA (siRNA) is a powerful tool to silence gene expression in mammalian cells including genes of viral origin. To evaluate the therapeutic efficacy of siRNA against the hepatitis B virus (HBV), we studied the effect of transfection of the HBV-inducible cell lines HepAD38 and HepAD79 with siRNA specific for the core gene of the HBV genome. HepAD38 cells produce wild-type HBV, whereas HepAD79 cells produce the lamivudine resistant YMDD variant. Transfection of HepAD38 cells with either 1.6 or 4 microg/ml siRNA resulted in a profound inhibition (72% and 98%, respectively) of viral replication (as assessed by real-time quantitative PCR). The inhibitory effect was corroborated by a marked reduction of HBV core protein synthesis in induced HepAD38 cells. In HepAD79 cells, transfected with 1.6 or 4 microg/ml HBV-specific siRNA, virus production was reduced by 75% and 89%, respectively.