Physiologically-Based Pharmacokinetic Modeling of PAXLOVID™ with First-Order Absorption Kinetics.

PURPOSE: PAXLOVID™ is nirmatrelvir tablets co-packaged with ritonavir tablets. Ritonavir is used as a pharmacokinetics (PK) enhancer to reduce metabolism and increase exposure of nirmatrelvir. This is the first disclosure of Paxlovid physiologically-based pharmacokinetic (PBPK) model. METHODS: Nirmatrelvir PBPK model with first-order absorption kinetics was developed using in vitro, preclinical, and clinical data of nirmatrelvir in the presence and absence of ritonavir. Clearance and volume of distribution were derived from nirmatrelvir PK obtained using a spray-dried dispersion (SDD) formulation where it is considered to be dosed as an oral solution, and absorption is near complete. The fraction of nirmatrelvir metabolized by CYP3A was estimated based on in vitro and clinical ritonavir drug-drug interaction (DDI) data. First-order absorption parameters were established for both SDD and tablet formulation using clinical data. Nirmatrelvir PBPK model was verified with both single and multiple dose human PK data, as well as DDI studies. Simcyp® first-order ritonavir compound file was also verified with additional clinical data. RESULTS: The nirmatrelvir PBPK model described the observed PK profiles of nirmatrelvir well with predicted AUC and Cmax values within ± 20% of the observed. The ritonavir model performed well resulting in predicted values within twofold of observed. CONCLUSIONS: Paxlovid PBPK model developed in this study can be applied to predict PK changes in special populations, as well as model the effect of victim and perpetrator DDI. PBPK modeling continues to play a critical role in accelerating drug discovery and development of potential treatments for devastating diseases such as COVID-19. NCT05263895, NCT05129475, NCT05032950 and NCT05064800.

The effects of online peer-facilitated learning and distributed pair programming on students' learning.

The COVID-19 pandemic has forced universities and schools around the world to adopt online learning. Teachers may wonder if their students can attain satisfactory learning performance in an online learning environment without teachers' on-the-spot attention. In order to develop students' skills in programming, promote their enjoyment of learning and intention to learn to program, the researchers integrated two innovative teaching approaches, using online peer-facilitated learning and distributed pair programming, and investigated the effects of these on students' online learning performance. This study conducted an experiment that included 128 undergraduates from four class sections of Department of Finance. Thus, the experimental design in this research was a 2 (Peer-facilitated learning vs. non-peer-facilitated learning) × 2 (Distributed pair programming vs. non-distributed pair programming) factorial pretest/post-test design. The participants in this research mainly consisted of four classes of students from a non-computer or information department who took a compulsory course on programming design.' Both quantitative and qualitative data were collected in this study. According to the results, the peer-facilitated learning group exhibited significantly better development of programming skills, enjoyment of learning, and intention to learn, than the non-peer-facilitated learning group. However, expected effects of enhancing the learning of the students in this study who received the distributed pair programming were not found. The design of online pedagogy can be a reference for online educators. The implications of applying online peer-facilitated learning and distributed pair programming to support students' learning and the design of online programming courses are discussed.

IBV QX affects the antigen presentation function of BMDCs through non-structural protein16

The gamma-coronavirus infectious bronchitis virus (IBV) has a high mutation rate and mainly invades the respiratory mucosa, making it difficult to prevent and causing great economic losses. Non-structural protein 16 (NSP16) of IBV QX also not only plays an indispensable role in virus invading but also might hugely influence the antigen's recognition and presentation ability of host BMDCs. Hence, our study tries to illustrate the underline mechanism of how NSP16 influences the immune function of BMDCs. Initially, we found that NSP16 of the QX strain significantly inhibited the antigen presentation ability and immune response of mouse BMDCs, which was stimulated by Poly (I:C) or AIV RNA. Besides mouse BMDCs, we also found that NSP16 of the QX strain also significantly stimulated the chicken BMDCs to activate the interferon signaling pathway. Furthermore, we preliminarily demonstrated that IBV QX NSP16 inhibits the antiviral system by affecting the antigen-presenting function of BMDCs.

IBV QX affects the antigen presentation function of BMDCs through nonstructural protein16.

The gamma-coronavirus infectious bronchitis virus (IBV) has a high mutation rate and mainly invades the respiratory mucosa, making it difficult to prevent and causing great economic losses. Nonstructural protein 16 (NSP16) of IBV QX also not only plays an indispensable role in virus invading but also might hugely influence the antigen's recognition and presentation ability of host BMDCs. Hence, our study tries to illustrate the underline mechanism of how NSP16 influences the immune function of BMDCs. Initially, we found that NSP16 of the QX strain significantly inhibited the antigen presentation ability and immune response of mouse BMDCs, which was stimulated by Poly (I:C) or AIV RNA. Besides mouse BMDCs, we also found that NSP16 of the QX strain also significantly stimulated the chicken BMDCs to activate the interferon signaling pathway. Furthermore, we preliminarily demonstrated that IBV QX NSP16 inhibits the antiviral system by affecting the antigen-presenting function of BMDCs.

COVID-19 infection rate but not severity is associated with availability of greenness in the United States.

Human exposure to greenness is associated with COVID-19 prevalence and severity, but most relevant research has focused on the relationships between greenness and COVID-19 infection rates. In contrast, relatively little is known about the associations between greenness and COVID-19 hospitalizations and deaths, which are important for risk assessment, resource allocation, and intervention strategies. Moreover, it is unclear whether greenness could help reduce health inequities by offering more benefits to disadvantaged populations. Here, we estimated the associations between availability of greenness (expressed as population-density-weighted normalized difference vegetation index) and COVID-19 outcomes across the urban-rural continuum gradient in the United States using generalized additive models with a negative binomial distribution. We aggregated individual COVID-19 records at the county level, which includes 3,040 counties for COVID-19 case infection rates, 1,397 counties for case hospitalization rates, and 1,305 counties for case fatality rates. Our area-level ecological study suggests that although availability of greenness shows null relationships with COVID-19 case hospitalization and fatality rates, COVID-19 infection rate is statistically significant and negatively associated with more greenness availability. When performing stratified analyses by different sociodemographic groups, availability of greenness shows stronger negative associations for men than for women, and for adults than for the elderly. This indicates that greenness might have greater health benefits for the former than the latter, and thus has limited effects for ameliorating COVID-19 related inequity. The revealed greenness-COVID-19 links across different space, time and sociodemographic groups provide working hypotheses for the targeted design of nature-based interventions and greening policies to benefit human well-being and reduce health inequity. This has important implications for the post-pandemic recovery and future public health crises.

Integrating online meta-cognitive learning strategy and team regulation to develop students' programming skills, academic motivation, and refusal self-efficacy of Internet use in a cloud classroom.

With the development of technology and demand for online courses, there have been considerable quantities of online, blended, or flipped courses designed and provided. However, in the technology-enhanced learning environments, which are also full of social networking websites, shopping websites, and free online games, it is challenging to focus students' attention and help them achieve satisfactory learning performance. In addition, the instruction of programming courses constantly challenges both teachers and students, particularly in online learning environments. To overcome and solve these problems and to facilitate students' learning, the researchers in this study integrated two teaching approaches, using meta-cognitive learning strategy (MCLS) and team regulation (TR), to develop students' regular learning habits and further contribute to their programming skills, academic motivation, and refusal self-efficacy of Internet use, in a cloud classroom. In this research, a quasi-experiment was conducted to investigate the effects of MCLS and TR adopting the experimental design of a 2 (MCLS vs. non-MCLS) × 2 (TR vs. non-TR) factorial pre-test/post-test. In this research, the participants consisted of four classes of university students from non-information or computer departments enrolled in programming design, a required course. The experimental groups comprised three of the classes, labelled as G1, G2, and G3. G1 concurrently received both the online MCLS and TR intervention, while G2 only received the online MCLS intervention, and G3 only received the online TR intervention. Serving as the control group, the fourth class (G4) received traditional teaching. This study investigated the effects of MCLS, TR, and their combination, on improving students' programming skills, academic motivation, and refusal self-efficacy of Internet use in an online computing course. According to the results, students who received online TR significantly enhanced their programming design skills and their refusal self-efficacy of Internet use a cloud classroom. However, the expected effects of MCLS on developing students' programming skills, academic motivation, and refusal self-efficacy of Internet use were not found in this study. The teaching strategy of integrating MCLS and TR in an online programming course in this study can serve as a reference for educators when conducting online, blended, or flipped courses during the COVID-19 pandemic.

Social vulnerability amplifies the disparate impact of mobility on COVID-19 transmissibility across the United States

Although human mobility is considered critical for the spread of the new coronavirus disease (COVID-19) both locally and globally, the extent to which such an association is impacted by social vulnerability remains unclear. Here, using multisource epidemiological and socioeconomic data of US counties, we develop a COVID-19 pandemic vulnerability index (CPVI) to quantify their levels of social vulnerability and examine how social vulnerability moderated the influence of mobility on disease transmissibility (represented by the effective reproduction number, Rt) during the US summer epidemic wave of 2020. We find that counties in the top CPVI quintile suffered almost double in regard to COVID-19 transmission (45.02% days with an Rt higher than 1) from mobility, particularly intracounty mobility, compared to counties in the lowest quintile (21.90%). In contrast, counties in the bottom CPVI quintile were only slightly affected by the level of mobility. As such, a 25% intracounty mobility change was associated with a 15.28% Rt change for counties in the top CPVI quintile, which is eight times the 1.81% Rt change for those in the lowest quintile. These findings suggest the need to account for the vulnerability of communities when making social distancing measures against mobility in the future.

Case Report: Subacute thyroiditis after receiving inactivated SARS-CoV-2 vaccine (BBIBP-CorV).

Background: Subacute thyroiditis, an inflammatory disease, has been reported caused by vaccines in rare cases. In the context of the coronavirus disease 19 pandemic, various SARS-CoV-2 vaccines have been developed and may be potential triggers for subacute thyroiditis. Case presentation: We report a case of subacute thyroiditis 3 days after receiving the second dose of inactivated SARS-CoV-2 vaccine (BBIBP-CorV). The patient did not report a previous history of thyroid disease, upper respiratory tract infection, or COVID-19. Physical examination, laboratory testing, ultrasonography, and radioactive iodine uptake were consistent with subacute thyroiditis. During follow-up, the patient recovered from symptoms and signs, and imaging changes except for hypothyroidism, requiring an ongoing thyroxine replacement. Conclusions: Inactivated SARS-CoV-2 vaccine may be a causal trigger leading to subacute thyroiditis. Clinicians should be aware of subacute thyroiditis as a possible thyroid-related side effect of an inactivated SARS-CoV-2 vaccine.

Treatment of hospital wastewater by electron beam technology: Removal of COD, pathogenic bacteria and viruses.

The effective treatment of hospital sewage is crucial to human health and eco-environment, especially during the pandemic of COVID-19. In this study, a demonstration project of actual hospital sewage using electron beam technology was established as advanced treatment process during the outbreak of COVID-19 pandemic in Hubei, China in July 2020. The results indicated that electron beam radiation could effectively remove COD, pathogenic bacteria and viruses in hospital sewage. The continuous monitoring date showed that the effluent COD concentration after electron beam treatment was stably below 30 mg/L, and the concentration of fecal Escherichia coli was below 50 MPN/L, when the absorbed dose was 4 kGy. Electron beam radiation was also an effective method for inactivating viruses. Compared to the inactivation of fecal Escherichia coli, higher absorbed dose was required for the inactivation of virus. Absorbed dose had different effect on the removal of virus. When the absorbed dose ranged from 30 to 50 kGy, Hepatitis A virus (HAV) and Astrovirus (ASV) could be completely removed by electron beam treatment. For Rotavirus (RV) and Enterovirus (EV) virus, the removal efficiency firstly increased and then decreased. The maximum removal efficiency of RV and EV was 98.90% and 88.49%, respectively. For the Norovirus (NVLII) virus, the maximum removal efficiency was 81.58%. This study firstly reported the performance of electron beam in the removal of COD, fecal Escherichia coli and virus in the actual hospital sewage, which would provide useful information for the application of electron beam technology in the treatment of hospital sewage.

Case Report: Subacute thyroiditis after receiving inactivated SARS-CoV-2 vaccine (BBIBP-CorV)

Background Subacute thyroiditis, an inflammatory disease, has been reported caused by vaccines in rare cases. In the context of the coronavirus disease 19 pandemic, various SARS-CoV-2 vaccines have been developed and may be potential triggers for subacute thyroiditis. Case presentation We report a case of subacute thyroiditis 3 days after receiving the second dose of inactivated SARS-CoV-2 vaccine (BBIBP-CorV). The patient did not report a previous history of thyroid disease, upper respiratory tract infection, or COVID-19. Physical examination, laboratory testing, ultrasonography, and radioactive iodine uptake were consistent with subacute thyroiditis. During follow-up, the patient recovered from symptoms and signs, and imaging changes except for hypothyroidism, requiring an ongoing thyroxine replacement. Conclusions Inactivated SARS-CoV-2 vaccine may be a causal trigger leading to subacute thyroiditis. Clinicians should be aware of subacute thyroiditis as a possible thyroid-related side effect of an inactivated SARS-CoV-2 vaccine.

5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Early Warning Biomarkers for COVID-19 Progression and Myocardial Injury.

Background: The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited. Methods: We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19. Results: Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77-0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89-0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84-0.95). Conclusion: This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.

Immune Responses Induced by Recombinant Bacillus subtilis Expressing the PEDV Spike Protein Targeted at Microfold Cells.

Bacillus subtilis (B. subtilis), a probiotic bacterium and feeding additive, is widely used for heterologous antigen expression and protective immunisation. Porcine epidemic diarrhoea virus (PEDV) invades swine via mucosal tissue. To enhance the mucosal immune response to PEDV, we modified B. subtilis to express a PEDV antigen and used it as a mucosal vaccine delivery system. Initially, we constructed a recombinant B. subtilis strain (B.s-RCL) that expressed the PEDV spike protein and L-Lectin-ß-GF, with the goal of inducing mucosal secretory immunoglobulin A (sIgA) and anti-PEDV serum immunoglobulin G (IgG) production, as well as to increase the number of microfold cells (M cells). Following the oral administration of B.s-RCL to mice, the small intestinal PEDV-specific sIgA expression levels significantly increased, as well as the increased number of B.s-RCL adhered to M cells. Moreover, we found that mice administered B.s-RCL exhibited markedly higher percentages of CD4+ and CD8+ T cells in the mesenteric lymph nodes and spleen compared to the control mice. Furthermore, we found that intestinal mucosa sIgA and serum anti-PEDV IgG levels were higher in mice orally immunised with B.s-RCL, suggesting that the mice could be more resistant to PEDV. In this study, we developed a novel oral vaccine to prevent porcine diarrhoea epidemics.

Pulmonary Embolism after Moderna Vaccination in Kidney Transplant Patients: Two Case Reports and Literature Review.

Currently, the coronavirus disease 2019 (COVID-19) pandemic is still an ongoing and constant medical issue, and with upcoming new variants, vaccinations and boosters remain important. The safety of vaccines in patients after kidney transplantation is an essential problem, with thrombosis being one of the severe side effects and vaccine-induced immune thrombotic thrombocytopenia (VITT) revealed as the most commonly reported syndrome for thromboembolic events following COVID-19 vaccination. Here, we present two cases of kidney transplantation developing pulmonary embolism post-Moderna vaccination within 30 days without thrombocytopenia. The first case was a 52-year-old man with history of type II diabetes, hypertension and hyperlipidemia who had had cadaveric kidney transplantation in September 2008, where right leg swelling with claudication occurred 23 days after the second Moderna vaccination. The second case was a 57-year-old man with history of type II diabetes and glaucoma who had had living-related kidney transplantation in April 2013 and then complained of exertional dyspnea 26 days after administration of the third Moderna vaccine. The advantages of vaccination even in immunocompromised patients far outweigh the disadvantages, although clinicians must understand the risks of deep-vein thrombosis or even pulmonary embolism for such patients, which might not occur after just the first vaccination.

Disposition of Nirmatrelvir, an Orally Bioavailable Inhibitor of SARS-CoV-2 3C-Like Protease, across Animals and Humans.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor PF-07321332 (nirmatrelvir), in combination with ritonavir (Paxlovid), was recently granted emergency use authorization by multiple regulatory agencies for the treatment of coronavirus disease 2019 (COVID-19) in adults and pediatric patients. Disposition studies on nirmatrelvir in animals and in human reagents, which were used to support clinical studies, are described herein. Plasma clearance was moderate in rats (27.2 ml/min per kg) and monkeys (17.1 ml/min per kg), resulting in half-lives of 5.1 and 0.8 hours, respectively. The corresponding oral bioavailability was moderate in rats (34%-50%) and low in monkeys (8.5%), primarily due to oxidative metabolism along the gastrointestinal tract in this species. Nirmatrelvir demonstrated moderate plasma protein binding in rats, monkeys, and humans with mean unbound fractions ranging from 0.310 to 0.478. The metabolism of nirmatrelvir was qualitatively similar in liver microsomes and hepatocytes from rats, monkeys, and humans; prominent metabolites arose via cytochrome P450 (CYP450)-mediated oxidations on the P1 pyrrolidinone ring, P2 6,6-dimethyl-3-azabicyclo[3.1.0]hexane, and the tertiary-butyl group at the P3 position. Reaction phenotyping studies in human liver microsomes revealed that CYP3A4 was primarily responsible (fraction metabolized = 0.99) for the oxidative metabolism of nirmatrelvir. Minor clearance mechanisms involving renal and biliary excretion of unchanged nirmatrelvir were also noted in animals and in sandwich-cultured human hepatocytes. Nirmatrelvir was a reversible and time-dependent inhibitor as well as inducer of CYP3A activity in vitro. First-in-human pharmacokinetic studies have demonstrated a considerable boost in the oral systemic exposure of nirmatrelvir upon coadministration with the CYP3A4 inhibitor ritonavir, consistent with the predominant role of CYP3A4 in nirmatrelvir metabolism. SIGNIFICANCE STATEMENT: The manuscript describes the preclinical disposition, metabolism, and drug-drug interaction potential of PF-07321332 (nirmatrelvir), an orally active peptidomimetic-based inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease, which has been granted emergency use authorization by multiple regulatory agencies around the globe for the treatment of coronavirus disease 2019 (COVID-19) in COVID-19-positive adults and pediatric patients who are at high risk for progression to severe COVID-19, including hospitalization or death.

Effects of Jump-Rope-Specific Footwear Selection on Lower Extremity Biomechanics.

Footwear is among the most important equipment in sports to decrease injuries and enhance performance during exercise. In this study, we investigated differences in lower extremity plantar pressure and muscle activations during jump rope activities. Ten participants performed jump rope under two landing conditions with different footwear. A force platform (AMTI, 1000 Hz), a Novel Pedar-X system (Nove, 100 Hz), and a wireless electromyography (EMG) system (Noraxon, 1500 Hz) were used to measure biomechanical parameters during the jump rope exercise. Vertical ground reaction forces (vGRF), plantar pressure, and lower extremity muscle activations were analyzed. One-leg landing resulted in a significantly greater vGRF and shorter fly time than two-leg landing (p < 0.05). A significantly higher peak pressure and lesser toe (LT) area pressure was shown with the jumping shoe (all p < 0.05), but lower plantar pressure resulted in the middle foot area (p < 0.05). The EMG results of tibialis anterior (TA) were significantly greater with one-leg landing (all p < 0.05) during the pre- and background activity (BGA) phases. The results suggest that plantar pressure distribution should be considered when deciding on footwear during jump rope exercises, but care should be taken with regards to recovery after repeated collisions and fatigue. The jumping shoe provides benefits in terms of decreased plantar pressure sustained during jump rope exercises.

Lay-Up Compound Matrices for Application of Medical Protective Clothing: Manufacturing Techniques and Property Evaluations.

Medical protective clothing is the first line of defense for medical staff, which makes the acquisition of protection and multiple function challenging. When it comes to contagious diseases, the physical properties of protective clothing are deemed the top priority and, subsequently, they have significant meaning for the structural design, production cost evaluation, convenient production, and innovation. In this study, nonwoven technology is employed to produce matrices in which mechanical properties are supported by Tencel fibers and recycled Kevlar fibers. Next, the electrostatic spinning is conducted to generate breathable and waterproof films. The nonwoven fabrics and membranes are combined to have diverse functions, forming lay-up compound matrices for medical protective clothing. Moreover, measurements are conducted to characterize the lay-up compound matrices in terms of the tensile strength, tearing strength, bursting strength, puncture resistance, stiffness, air-permeable property, surface resistance, comfort performance, sub-micron particulate filtration efficiency, and the penetration of synthetic blood. As for the nonwoven fabrics, the mechanical properties are significantly improved after Kevlar fibers are incorporated. The tensile strength is (62.6 ± 2.4) N along the machine direction (MD) and (50.1 ± 3.1) N along the cross machine direction (CD); the tearing strength is (29.5 ± 1.6) N along the MD and (43.0 ± 1.7) N along the CD; the bursting strength is (365.8 ± 5.0) kPa; and the puncture resistance is (22.6 ± 1.0) N. Moreover, the lay-up compound matrices exhibit a stiffness of (14.7 ± 0.2) cm along the MD and (14.6 ± 0.1) cm along the CD, a surface resistance of (2.85 × 109 ± 0.37 × 109) Ω, an air-permeable property of (45.4 ± 2.3) cm3/s/cm2, and sub-micron particulate filtration efficiency of over 98%. In the measurement for penetration of synthetic blood, the K40/PAN/TPU group prevents the synthetic blood from penetration. Hence, the incorporation of recycled Kevlar fibers and lay-up compound technique creates good physical properties, an appropriate comfort attribute, and functions, which suggests that this study provides a greater diversity and new concepts for the production of medical protective clothing.

Covalently Engineered Protein Minibinders with Enhanced Neutralization Efficacy against Escaping SARS-CoV-2 Variants.

The rapid emergence and spread of escaping mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly challenged our efforts in fighting against the COVID-19 pandemic. A broadly neutralizing reagent against these concerning variants is thus highly desirable for the prophylactic and therapeutic treatments of SARS-CoV-2 infection. We herein report a covalent engineering strategy on protein minibinders for potent neutralization of the escaping variants such as B.1.617.2 (Delta), B.1.617.1 (Kappa), and B.1.1.529 (Omicron) through in situ cross-linking with the spike receptor binding domain (RBD). The resulting covalent minibinder (GlueBinder) exhibited enhanced blockage of RBD-human angiotensin-converting enzyme 2 (huACE2) interaction and more potent neutralization effect against the Delta variant than its noncovalent counterpart as demonstrated on authentic virus. By leveraging the covalent chemistry against escaping mutations, our strategy may be generally applicable for restoring and enhancing the potency of neutralizing antibodies to SARS-CoV-2 and other rapidly evolving viral targets.

Research on the threshold of symbiosis between finance and real economy – empirical test based on banking panel threshold model

PurposeStarting from the theoretical mechanism of profit sharing between finance and the real economy, this paper reviews and analyzes the profitability of China's banking industry and makes a horizontal comparison with the banking industry of the United States, Japan, and Germany.Design/methodology/approachBased on the panel threshold model, it is found that there is a dual-threshold asymmetric effect between banking profit and the growth of real economy. When the net profit rate of the banking industry is lower than 0.491%, the increase in banking profitability will inhibit the growth of real economy due to profit grabbing;when the rate falls within the range of 0.491–0.801%, the increase in bank profitability is conducive to the growth of real economy.FindingsFinance and the real economy are in the most comfortable symbiotic state;when the rate is higher than 0.801%, the continued increase in bank profitability will weaken the promotion effect of finance on the real economy, but bank profitability and the growth of real economy are still in a symbiotic state of positive promotion.Originality/valueThe promotion effect of China's bank profitability to the growth of real economy has shifted from the suboptimal state to the optimal range as a whole, which is attributed to the strong deleveraging and strict supervision of the Chinese government after 2016, the timely and decisive “stepping on the brakes”, pulling the financial sector back from the “illusion” caused by “self-circulated” profits and preventing it from harming the real economy.

Internal fixation and unicompartmental knee arthroplasty for an elderly patient with patellar fracture and anteromedial osteoarthritis: A case report.

BACKGROUND: Open reduction and internal fixation (ORIF) is the traditional surgical treatment for patellar fractures, and unicompartmental knee arthroplasty (UKA), especially Oxford UKA, has been increasingly used in patients with medial knee osteoarthritis (OA). However, the process of choosing treatment for patients with both patellar fractures and anteromedial knee OA remains unclear. We present the case of a patient with a patellar fracture and anteromedial OA. CASE SUMMARY: We present the case of a 72-year-old woman with a history of bilateral medial compartment OA of the knees and a right Oxford UKA. She also experienced a recent left patellar fracture. ORIF and Oxford UKA were performed in a single stage. The patient showed excellent postoperative clinical results. CONCLUSION: ORIF and Oxford UKA can be performed simultaneously for patients with patellar fracture and anteromedial OA on the same knee.

Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/µl (IQR = 96-289 cells/µl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/µl) and AIDS (median CD4 = 97 cells/µl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.