Molecular epidemiology and phylogenetic analysis of influenza viruses A (H3N2) and B/Victoria during the COVID-19 pandemic in Guangdong, China.

BACKGROUND: Non-pharmaceutical measures and travel restrictions have halted the spread of coronavirus disease 2019 (COVID-19) and influenza. Nonetheless, with COVID-19 restrictions lifted, an unanticipated outbreak of the influenza B/Victoria virus in late 2021 and another influenza H3N2 outbreak in mid-2022 occurred in Guangdong, southern China. The mechanism underlying this phenomenon remains unknown. To better prepare for potential influenza outbreaks during COVID-19 pandemic, we studied the molecular epidemiology and phylogenetics of influenza A(H3N2) and B/Victoria that circulated during the COVID-19 pandemic in this region. METHODS: From January 1, 2018 to December 31, 2022, we collected throat swabs from 173,401 patients in Guangdong who had acute respiratory tract infections. Influenza viruses in the samples were tested using reverse transcription-polymerase chain reaction, followed by subtype identification and sequencing of hemagglutinin (HA) and neuraminidase (NA) genes. Phylogenetic and genetic diversity analyses were performed on both genes from 403 samples. A rigorous molecular clock was aligned with the phylogenetic tree to measure the rate of viral evolution and the root-to-tip distance within strains in different years was assessed using regression curve models to determine the correlation. RESULTS: During the early period of COVID-19 control, various influenza viruses were nearly undetectable in respiratory specimens. When control measures were relaxed in January 2020, the influenza infection rate peaked at 4.94% (39/789) in December 2021, with the influenza B/Victoria accounting for 87.18% (34/39) of the total influenza cases. Six months later, the influenza infection rate again increased and peaked at 11.34% (255/2248) in June 2022; influenza A/H3N2 accounted for 94.51% (241/255) of the total influenza cases in autumn 2022. The diverse geographic distribution of HA genes of B/Victoria and A/H3N2 had drastically reduced, and most strains originated from China. The rate of B/Victoria HA evolution (3.11 × 10-3, P < 0.05) was 1.7 times faster than before the COVID-19 outbreak (1.80 × 10-3, P < 0.05). Likewise, the H3N2 HA gene's evolution rate was 7.96 × 10-3 (P < 0.05), which is 2.1 times faster than the strains' pre-COVID-19 evolution rate (3.81 × 10-3, P < 0.05). CONCLUSIONS: Despite the extraordinarily low detection rate of influenza infection, concealed influenza transmission may occur between individuals during strict COVID-19 control. This ultimately leads to the accumulation of viral mutations and accelerated evolution of H3N2 and B/Victoria viruses. Monitoring the evolution of influenza may provide insights and alerts regarding potential epidemics in the future.

Modified transport medium for improving influenza virus detection.

Background: Accurate detection of influenza virus in clinical samples requires correct execution of all aspects of the detection test. If the viral load in a sample is below the detection limit, a false negative result may be obtained. To overcome this issue, we developed a modified transport medium (MTM) for clinical sample transportation to increase viral detection sensitivity. Method: We first validated the MTM using laboratory-stocked influenza A viruses (IAVs: H1N1, H3N2, H7N3, H9N2) and influenza B viruses (IBVs: Yamagata, Victoria). We also tested clinical samples. A total of 110 patients were enrolled and a pair of samples were collected to determine the sensitivity of real-time polymerase chain reaction (RT-PCR) following MTM treatment. Result: After 24 h culturing in MTM, the viral loads were increased, represented by a 10-fold increase in detection sensitivity for H1N1, H9N2, and IBVs, a 100-fold increase for H3N2, and a 1,000-fold increase for H7N3. We further tested the effects of MTM on 19 IAV and 11 IBV stored clinical samples. The RT-PCR results showed that the positive detection rate of IAV samples increased from 63.16% (12/19) without MTM culturing to 78.95% (15/19) after 48 h culturing, and finally 89.47% (17/19) after 72 h culturing. MTM treatment of IBV clinical samples also increased the positive detection rate from 36.36% (4/11, 0 h) to 63.64% (7/11, 48 h) to 72.73% (8/11, 72 h). For clinical samples detected by RT-PCR, MTM outperformed other transport mediums in terms of viral detection rate (11.81% increase, P=0.007). Conclusion: Our results demonstrated that the use of MTM for clinical applications can increase detection sensitivity, thus facilitating the accurate diagnosis of influenza infection.

The Impact of Medical Resources and Oral Antiviral Drugs on SARS-CoV-2 Mortality - Hong Kong SAR, China, 2022.

Introduction: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrates increased transmissibility compared to earlier strains, contributing to a significant number of fatalities in Hong Kong Special Administrative Region (HKSAR), China. Adequate medical resources and medications are essential in mitigating these deaths. This study evaluates the effects of supplementary resources from the Chinese mainland during the fifth wave of the pandemic in HKSAR. Methods: Vector autoregression (VAR) was employed to analyze data from the Oxford coronavirus disease 2019 (COVID-19) Government Response Tracker to assess the effectiveness of control measures during five waves of the pandemic in HKSAR. Additionally, a transmission dynamics model was created to investigate the influence of supplementary medical resources from the Chinese mainland and oral medications on mortality. Results: In the initial four waves, workplace closures, restrictions on public events, international travel bans, and shielding the elderly significantly influenced pandemic management. Contrarily, during the fifth wave, these measures showed no notable effects. When comparing a situation without extra medical resources or COVID-19 oral medication, there was a 17.7% decrease in COVID-19 fatalities with mainland medical resources and an additional 10.2% reduction with oral medications. Together, they contributed to a 26.6% decline in fatalities. Discussion: With the rapid spread of the virus, regional reallocation of medical resources may reduce mortality even when the local healthcare system is overstretched.

The investigation on shale mechanical characteristics and brittleness evaluation.

Rock mechanical property is significant for shale gas development and exploitation. Shale compressive strength, tensile strength, elastic deformation and so on, are necessary parameters for drilling, completion and fracturing work in shale formation. Among all these shale mechanical parameters, brittleness is a tricky and significant rock property, which has been widely used to hydraulic fracturing design. Currently, although so many works have been conducted to investigate shale brittleness, there is no precise definition of brittleness. In particular, there is no consensus on which method is the most reliable for shale brittleness evaluation. It is vital to figure out how to evaluate shale brittleness in a reliable method. Thus, this paper presents an experimental study on shale mechanical properties, analyzing mechanical features in stress strain curve, relation between mineral content and strength, mechanical parameters at varying confined stress. Based on shale mechanical characteristics and its brittle exhibition, stress strain curve from triaxial compression test is divided into 3 stages, namely, elastic stage, plastic stage and post peak stage. In combined with brittle characteristics in 3 stages of axial and radial stress-strain curves, a new brittleness index has been established for assessing shale brittleness. In order to prove the applicability of new brittleness index, its result is compared with shale failure sample after triaxial test and existing brittleness indexes based on mineral content, elastic deformation, energy, stress and strain, showing a good consistency and proving its practicability. Based on this brittleness index, influence factors of shale brittleness have been discussed. It is shown that elastic module is the most important factor of shale brittleness. Bedding plane makes shale brittleness have strong anisotropy. Brittleness is not only relied on its structure and mineral (like bedding plane, silicate and clay mineral content), but is also highly affected by external stress. Large confined pressure is able to impair shale brittleness. Outcome in this study can offer theoretical guidance for shale exploitation.

Temporary impact on medical system and effectiveness of mitigation strategies after COVID-19 policy adjustment in China: a modeling study.

Background: As China amends its "zero COVID" strategy, a sudden increase in the number of infections may overwhelm medical resources and its impact has not been quantified. Specific mitigation strategies are needed to minimize disruption to the healthcare system and to prepare for the next possible epidemic in advance. Method: We develop a stochastic compartmental model to project the burden on the medical system (that is, the number of fever clinic visits and admission beds) of China after adjustment to COVID-19 policy, which considers the epidemiological characteristics of the Omicron variant, age composition of the population, and vaccine effectiveness against infection and severe COVD-19. We also estimate the effect of four-dose vaccinations (heterologous and homologous), antipyretic drug supply, non-pharmacological interventions (NPIs), and triage treatment on mitigating the domestic infection peak. Result: As to the impact on the medical system, this epidemic is projected to result in 398.02 million fever clinic visits and 16.58 million hospitalizations, and the disruption period on the healthcare system is 18 and 30 days, respectively. Antipyretic drug supply and booster vaccination could reduce the burden on emergency visits and hospitalization, respectively, while neither of them could not reduce to the current capacity. The synergy of several different strategies suggests that increasing the heterologous booster vaccination rate for older adult to over 90% is a key measure to alleviate the bed burden for respiratory diseases on the basis of expanded healthcare resource allocation. Conclusion: The Omicron epidemic followed the adjustment to COVID-19 policy overloading many local health systems across the country at the end of 2022. The combined effect of vaccination, antipyretic drug supply, triage treatment, and PHSMs could prevent overwhelming medical resources.

Investigation on the influence factors for the fracturing effect in fractured tight reservoirs using the numerical simulation.

Taking the fractured tight reservoir of the Fengcheng Formation in Mahu Depression as the research object, the RFPA software, a numerical simulation platform of real fracture process, was used to study the fracture propagation laws in fractured tight reservoirs during the fracturing process. On this basis, the influences of different factors on the fracture propagation laws in the fractured tight reservoirs were investigated, the influences of various factors on fracture propagation were quantitatively analyzed by the gray correlation method, and then the fractability calculation model for evaluating the fracturing effects was obtained by the analytic hierarchy process method. The results show that when the fracture angle is less than 70°, the natural fracture controls the hydraulic fracture propagation direction, whereas when the fracture angle is greater than 70°, the maximum horizontal principal stress controls the hydraulic fracture propagation direction. With the increase of the fracture angle, the hydraulic fracturing area firstly decreases and then increases, whereas with the increase of the fracture density, the hydraulic fracturing area gradually increases. The hydraulic fracturing area increases as the fracture compressive strength, tensile strength and elastic modulus reduction factor increase, whereas the hydraulic fracturing area decreases as the fracture Poisson's ratio reduction factor increases. Based on the gray correlation method, the ranking of the fracturing effect is clarified as fracture density > horizontal stress difference > fracture angle > elastic modulus > compressive strength > tensile strength > Poisson's ratio. Using the analytic hierarchy process, a model for calculating the reservoir fractability index is established, and has a good positive correlation with the dimensionless fracturing area.

Experimental Study on the Adaptability of Plugging Drilling Fluids to Wellbore Stability in Hard Brittle Shale Formations.

The problem of wellbore stability in hard brittle shale formations is an important research topic in the exploration and development of shale gas. To solve this problem, the adaptability of the plugging drilling fluid to wellbore stability in the hard brittle shale of the tertiary Dongying formation in Bohai Bay Basin, China, was investigated. The results show that the clay content of the hard brittle shale in the study block is as high as 39.2% on average, with great possibility for hydration. The pore structure in the shale is dominated by micron-scale fractures and pores. A dense structure was formed on the surface of the shale after being immersed in plugging drilling fluid, and the matrix permeability of the shale was reduced by 91.1% and the fracture permeability by 98.7%. The water content increment of the shale after immersion was merely 0.75%, which reduced the probability of hydration greatly. Compared with the field-inhibitive drilling fluid, the plugging drilling fluid improved the uniaxial compressive strength of shale by 28%, which is more conducive to maintaining the wellbore stability. The seepage stress aggravates the risk of wellbore instability, while the hydration stress does not, but both increase the risk of rock instability at positions away from the well wall. The plugging drilling fluid affects the seepage stress and hydration stress by reducing the shale permeability and water content. With the decrease of permeability and water content, the potential instability zone of a wellbore becomes smaller.

Study of a Polyamine Inhibitor Used for Shale Water-Based Drilling Fluid.

Here, we report a water-soluble shale inhibitor for inhibiting shale hydrate formation. The copolymer denoted as thermogravimetric analysis (TGA) was synthesized via triethanolamine, two maleic anhydrides, and glacial acetic acid. The infrared (IR) and gas chromatography (GC) results indicated that TGA is a low molecular weight polymer inhibitor (IR) and is the most commonly used method to identify compounds and molecular structures qualitatively. It is mainly used to study the molecular structure of organic substances and conduct qualitative and quantitative analyses of organic compounds. The main function of GC is for polymer molecular weight analysis. With the aid of shale rolling recovery experiments, particle size distribution experiments, triaxial stress experiment methods, bentonite slurry rate inhibition experiments, and thermogravimetric experiments to evaluate TGA inhibition characteristics, the inhibition effect of TGA is better than that of the traditional inorganic salt inhibitor KCl, polymer amine inhibitor UHIB, and organic cationic shale inhibitor NW-1. When the mass fraction is 0.2%, the cutting recovery rate increases from 18.3 to 94.1%. The compressive strength of the shale core after adding 1% TGA inhibitor is 177.9 MPa, which is close to the original core compressive strength of 186.5. The wet sodium montmorillonite crystal layer spacing after treatment with 0.5%, 1.5%, and 3% TGA aqueous solution is 1.38, 1.35, and 1.35 nm, respectively, and the sodium montmorillonite crystal layer spacing after diesel treatment is 1.34 nm, indicating that the inhibitory effect of TGA on sodium montmorillonite is equivalent to that of diesel and that TGA can effectively inhibit the hydration and dispersion of sodium montmorillonite. At the same time, the crystal layer spacing and the weight loss rate of sodium montmorillonite modified by TGA inhibitors did not change significantly after adsorption of deionized water, which proved that TGA inhibitors could be adsorbed in the crystal layer space of sodium montmorillonite to inhibit hydration and dispersion of sodium montmorillonite. Field test results show that TGA can significantly improve the inhibition performance of the field drilling fluid, and the effect is better than the strong conventional inhibition water-based drilling fluid system, which solves the problems of wellbore instability and considerable friction in horizontal shale sections and provides a new idea and method for efficient shale gas drilling.

Synthesis and evaluation of novel water-soluble copolymers based on acrylamide and modular ß-cyclodextrin.

Mono-6-(allyl amino)-ß-cyclodextrin (N-ß-CD) and mono-2-O-(allyl oxygen radicals-2-hydroxyl propyl)-ß-cyclodextrin (O-ß-CD) were copolymerized with acrylamide (AM), acrylic acid (AA), and 1-llyl-3-oil acyloxyimidazole-1-ammonion bramide (AOAB) initiated by redox initiation system in an aqueous medium. The AM/AA/AOAB/N-ß-CD and AM/AA/AOAB/O-ß-CD were prepared by adjusting the reactive conditions, such as initiator concentration, pH, temperature, and monomer ratios. The obtained copolymers were characterized by means of infrared (IR) spectroscopy, (1)H NMR spectroscopy, scanning electron microscope (SEM), rotational rheometer, intrinsic viscosity, salt resistance, core flood test, etc. The temperature-tolerance, shear-tolerance, salt-resistance and thickening function of these copolymers are improved remarkably compared with partially hydrolyzed polyacrylamide (HPAM). About 18.3% and 12.5% oil recovery could be enhanced by 2000mg/L AM/AA/AOAB/N-ß-CD and AM/AA/AOAB/O-ß-CD comparing with water-flooding. In addition, the result of X-ray diffractometry (XRD) test showed that the solutions of obtained copolymers could remarkably reduce the crystalline interspace of sodium montmorillonite (from 18.9Å to 15.3Å).