Multilayer factors associated with excess all-cause mortality during the omicron and non-omicron waves of the COVID-19 pandemic: time series analysis in 29 countries.

BACKGROUND: The COVID-19 pandemic has resulted in significant excess mortality globally. However, the differences in excess mortality between the Omicron and non-Omicron waves, as well as the contribution of local epidemiological characteristics, population immunity, and social factors to excess mortality, remain poorly understood. This study aims to solve the above problems. METHODS: Weekly all-cause death data and covariates from 29 countries for the period 2015-2022 were collected and used. The Bayesian Structured Time Series Model predicted expected weekly deaths, stratified by gender and age groups for the period 2020-2022. The quantile-based g-computation approach accounted for the effects of factors on the excess all-cause mortality rate. Sensitivity analyses were conducted using alternative Omicron proportion thresholds. RESULTS: From the first week of 2021 to the 30th week of 2022, the estimated cumulative number of excess deaths due to COVID-19 globally was nearly 1.39 million. The estimated weekly excess all-cause mortality rate in the 29 countries was approximately 2.17 per 100,000 (95% CI: 1.47 to 2.86). Weekly all-cause excess mortality rates were significantly higher in both male and female groups and all age groups during the non-Omicron wave, except for those younger than 15 years (P < 0.001). Sensitivity analysis confirmed the stability of the results. Positive associations with all-cause excess mortality were found for the constituent ratio of non-Omicron in all variants, new cases per million, positive rate, cardiovascular death rate, people fully vaccinated per hundred, extreme poverty, hospital patients per million humans, people vaccinated per hundred, and stringency index. Conversely, other factors demonstrated negative associations with all-cause excess mortality from the first week of 2021 to the 30th week of 2022. CONCLUSION: Our findings indicate that the COVID-19 Omicron wave was associated with lower excess mortality compared to the non-Omicron wave. This study's analysis of the factors influencing excess deaths suggests that effective strategies to mitigate all-cause mortality include improving economic conditions, promoting widespread vaccination, and enhancing overall population health. Implementing these measures could significantly reduce the burden of COVID-19, facilitate coexistence with the virus, and potentially contribute to its elimination.

Assessing the influencing factors of out-of-pocket costs on tuberculosis in Sichuan Province: a cross-sectional study.

BACKGROUND: Although diagnosis and treatment services for tuberculosis (TB) are provided free of charge in most countries, direct non-medical and indirect costs due to absenteeism, also place a significant burden on patients and their families. Sichuan Province has the second highest incidence of TB in China, with an incidence of approximately 100 cases per 100 000 people. However, there are limited research on out-of-pocket expenditure (OOPE) and its influencing factors in TB patients in Sichuan Province. METHODS: A retrospective cross-sectional study was conducted on TB patients in designated medical institutions for TB in Sichuan Province from 2017-2021. A face-to-face questionnaire was conducted to obtain the information related to hospitalization of patients, and the multi-level regression model was used to analyse the factors that influence OOPE and total out-of-pocket expenditure (TOOPE) of TB patients. RESULTS: A total of 2644 patients were investigated, and 74.24% of TB patients and their families experienced catastrophic total costs due to TB. The median total cost was 9223.37 CNY (1429.98 USD), in which the median direct and indirect costs of TB patients were 10185.00 CNY (1579.07 USD) and 2400.00 CNY (372.09 USD), respectively, and indirect costs contributed to 43% of total costs. The median OOPE and TOOPE costs were 6024.00 CNY (933.95 USD) and 11890.50 CNY (1843.49 USD), respectively. OOPE and TOOPE had common influencing factors including whether the patient's family had four or more members, a history of hospitalization, combination with other types of TB, the number of visits before diagnosis, and co-occurrence with chronic disease. CONCLUSIONS: The OOPE and TOOPE for TB patients and their families in Sichuan Province are still heavy. In the long run, it is necessary to strengthen education and awareness campaigns on TB related knowledge, disseminate basic medical knowledge to the public, improve healthcare-seeking behavior, and enhance the healthcare infrastructure to improve the accuracy of TB diagnosis and reduce the significant OOPE and TOOPE faced by TB patients and their families in Sichuan Province.

Willingness to practice medicine and related influential factors among medical undergraduates during COVID-19: a cross-sectional study.

BACKGROUND: As the medical undergraduates constitute the future workforce in China, their career preferences hold a significant bearing on the quality of healthcare services, particularly in light of the ongoing COVID-19 pandemic. We aim to understand the current state of the willingness to practice medicine among medical undergraduates and to analyze the related influential factors. METHODS: During the COVID-19 epidemic, we conducted a cross-sectional survey via an online platform from February 15, 2022, to May 31, 2022, to collect participants' demographic information, psychology, and factors influencing their career choices. The general self-efficacy scale (GSES) was used to evaluate medical students' perceptions of their self-efficacy. Futhermore, we conducted multivariate logistic regression analyses to explore the influencing factors of medical undergraduates' willingness to pursure a caree in medicine. RESULTS: A total of 2348 valid questionnaires were included, and 1573 (66.99%) were willing to practice medicine for medical undergraduates after graduation. The mean GESE scores in the willingness group (2.87 ± 0.54) were significantly higher than those of the unwillingness group (2.73 ± 0.49). The multiple logistic regression showed that several factors were positively associated with willingness to practice medicine as a career, including students' GSES score (OR = 1.87), current major, household income, personal ideals (OR = 1.97), family support (OR = 1.44), high income (OR = 1.77), and social respect (OR = 2.19). Compared with those who were very afraid of COVID-19, students who did not express any fear towards the COVID-19 pandemic had a higher preference for choosing the medical profession as a career. Conversely, students thinking of high tension in the doctor-patient relationship, heavy workload, and long training were less likely to choose medical work after graduation. CONCLUSIONS: The study highlights a noteworthy prevalence of medical undergraduates who expressed their willingness to pursue medicine as a career post-graduation. Several factors, including but not limited to current major, household income, psychological factors, personal preferences, and career needs or preferences, were significantly associated with this willingness. Moreover, the impact of the COVID-19 pandemic on medical students' career choices cannot be overlooked.

Neutrophil-mediated and low density lipoprotein receptor-mediated dual-targeting nanoformulation enhances brain accumulation of scutellarin and exerts neuroprotective effects against ischemic stroke.

Delivery of poorly permeable drugs across the blood-brain barrier (BBB) is a great challenge in the treatment of ischemic stroke. In order to construct a suitable delivery system for this purpose, we developed a dual-targeting nanoformulation to transfer therapeutic agents targeting the inflammatory sites of the ischemic brain. The matrix of this system is a hydroxyl-terminated polyamidoamine dendrimer with excellent biodegradability. The surface of the matrix is functionalized with two targeting peptides: Angiopep-2 is a low density lipoprotein receptor-mediated peptide with high BBB transcytosis capacity with ligands expressed on brain endothelial cells; N-acetylated proline-glycine-proline (PGP) has high affinity to CXCR2 expressed on infiltrating neutrophils. This system proved to be a high-loading formulation for the neuroprotective compound, scutellarin (STA), and significantly improved its therapeutic efficacy in a rodent model of ischemic stroke. The molecular mechanism underlying the therapeutic efficacy of this formulation is associated with significant down-regulation of the inflammatory cytokines, neutrophils infiltration and intracellular calcium overload and blockade of the inflammatory signaling pathway HMGB1/TLRs/MyD88/TRIF/NF-κB. Our results suggest that this dual-targeting delivery system is a promising drug delivery vehicle for ischemic stroke, and possibly other CNS diseases where neuroinflammation is involved.

Mechanical enhancement and in vitro biocompatibility of nanofibrous collagen-chitosan scaffolds for tissue engineering.

The collagen-chitosan complex with a three-dimensional nanofiber structure was fabricated to mimic native ECM for tissue repair and biomedical applications. Though the three-dimensional hierarchical fibrous structures of collagen-chitosan composites could provide more adequate stimulus to facilitate cell adhesion, migrate and proliferation, and thus have the potential as tissue engineering scaffolding, there are still limitations in their applications due to the insufficient mechanical properties of natural materials. Because poly (vinyl alcohol) (PVA) and thermoplastic polyurethane (TPU) as biocompatible synthetic polymers can offer excellent mechanical properties, they were introduced into the collagen-chitosan composites to fabricate the mixed collagen/chitosan/PVA fibers and a sandwich structure (collagen/chitosan-TPU-collagen/chitosan) of nanofiber in order to enhance the mechanical properties of the nanofibrous collagen-chitosan scaffold. The results showed that the tensile behavior of materials was enhanced to different degrees with the difference of collagen content in the fibers. Besides the Young's modulus had no obvious changes, both the break strength and the break elongation of materials were heightened after reinforced by PVA. For the collagen-chitosan nanofiber reinforced by TPU, both the break strength and the Young's modulus of materials were heightened in different degrees with the variety of collagen content in the fibers despite the decrease of the break elongation of materials to some extent. In vitro cell test demonstrated that the materials could provide adequate environment for cell adhesion and proliferation. All these indicated that the reinforced collagen-chitosan nanofiber could be as potential scaffold for tissue engineering according to the different mechanical requirements in clinic.

Screening of Photosensitizers by Chemiluminescence Monitoring of Formation Dynamics of Singlet Oxygen during Photodynamic Therapy.

Finding an efficient photosensitizer is crucial in ensuring a therapeutic effect of photodynamic treatment. Currently, screening of photosensitizers during photodynamic therapy is achieved by evaluating the total yield of singlet oxygen (1O2), rather than monitoring the formation dynamics of 1O2. 1O2-based chemiluminescence (CL) is a suitable method to directly monitor the generated amount of 1O2. Herein, the tetraphenylethene-sodium dodecyl sulfonate surfactant with aggregation-induced emission characteristics can remarkably amplify the intrinsic CL emission from 1O2 by integrating its micellar microenvironment with a CL energy acceptor effect in a cage-like structure. We present a new luminescence platform for the rapid screening of photosensitizers by monitoring the formation dynamics of 1O2 during photodynamic therapy. This study will not only be critical in optimizing the irradiation time during photodynamic therapy but also open a new door to the discovery of efficient photosensitizers.

Mechanisms of Nattokinase in protection of cerebral ischemia.

In vivo, the level of cyclic Adenosine Monophosphate (cAMP) and the pathway of the Janus Kinase1/Signal Transducers and Activators of Transcription1 (JAK1/STAT1) were studied. In vitro, the Ca(2+) mobilization in human platelet stimulated by thrombin was observed. In addition, vasomotion of vascular smooth muscle was measured by adding KCl or norepinephrine(NE) under the Ca(2+) contained bath solutions. The effect induced by NE in the presence of N-nitro-L-arginine methyl ester (L-NAME) or indometacin (Indo) was also detected. At last, the levels of tissue plasminogen activator (t-PA) and Plasminogen activator inhibitor-1 (PAI-1) in cultured supernatans in Human umbilical vein endothelial cells (Huvecs) were measured by means of ELISA kit. Results showed that Nattokinase (NK) significantly increased the cAMP level, activated the signal passage of JAK1/STAT1 in injured part and inhibited remarkably the rise of platelet intracellular Ca(2+) ([Ca(2+)]i) in human platelet. Furthermore, NK relaxed rat thoracic aortic artery in the dose-dependent manner and in the endothelium dependent manner and its effect could be attenuated by L-NAME. Also, the secretion of t-PA and PAI-1 were reduced stimulated by Adr on Huvecs. These data indicated that the neuroprotective effect of NK was associated with its antiplatelet activity by elevating cAMP level and attenuating the calcium release from calcium stores; with its anti-apoptotic effect through the activation of JAK1/STAT1 pathway; with its relaxing vascular smooth muscle by promoting synthesis and release of NO, reducing ROC calcium ion influx and with its protection on endothelial cells through increasing fibrinolytic activity and facilitating spontaneous thrombolysis.