The intersection of biological sex and gender in adverse events following seasonal influenza vaccination in older adults.

BACKGROUND: Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to generate hypotheses as to the biological mechanism underpinning the AE reported. RESULTS: A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. CONCLUSIONS: These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.

Immunogenicity and safety of quadrivalent influenza vaccine among young and older adults in Tianjin, China: implication of immunosenescence as a risk factor.

BACKGROUND: Older adults are more vulnerable to seasonal influenza than younger adults. The immune responses of older persons to the influenza vaccine are usually poorer than those of young individuals, which is hypothesized due to immunosenescence. We conducted a study to evaluate the immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4) in a total of 167 young (< 65 years, n = 79) and older (≥ 65 years, n = 88) adults from October 2021 to March 2022 in Tianjin, China. A single dose was administered to all participants. Blood samples were collected and strain-specific hemagglutination inhibition (HAI) antibody titers were measured before and 21 to 28 days after vaccination. Safety information was also collected for 28 days and 6 months after vaccination. Differences in immunogenicity and safety were compared between young and old age groups, and multivariate logistic regression was used to estimate the effect of age and other factors on HAI antibody responses. RESULTS: Overall, geometric mean titers (GMTs) against all four vaccine strains in older adults were lower than those in the young, whereas the seroconversion rates (SCRs) were similar. Multivariate logistic regression analysis showed that age, influenza vaccination history, and pre-vaccination HAI titers were independent factors affecting SCRs and seroprotection rates (SCRs). Older age had significant negative impact on SCRs against H1N1 (OR, 0.971; 95% CI: 0.944-0.999; P = 0.042) and B/Victoria (OR, 0.964; 95% CI: 0.937-0.992; P = 0.011). In addition, there was a significant negative correlation between chronological age (years) and post-vaccination HAI titers against H1N1 (rho = -0.2298, P < 0.0001), B/Victoria (rho = -0.2235, P = 0.0037), and B/Yamagata (rho = -0.3689, P < 0.0001). All adverse events were mild (grade 1 or grade 2) that occurred within 28 days after vaccination, and no serious adverse event was observed. CONCLUSIONS: IIV4 is immunogenic and well-tolerated in young and older adults living in Tianjin, China. Our findings also indicate that age is an independent factor associated with poorer humoral immune responses to IIV4.

Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults 75 years and older.

BACKGROUND: Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity. RESULTS: Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p < .01). Rates of waning were noticeably greater when pre-vaccination HAI titers were measured by the routine approach, i.e., using current season vaccine strain antigens, from 33% (p = .12) to 83% (p < .01), adjusting for age at prior study season, sex, race, and education. This was largely because the routinely measured pre-vaccination HAI titers underrepresented residual HAI titers from prior season vaccinations. Moreover, interseason antibody waning and prior season post-vaccination HAI titers had significant and independent associations with pre-vaccination HAI titers. CONCLUSIONS: The routinely measured pre-vaccination HAI titer overestimates interseason HAI antibody waning as it underestimates residual antibody titers from prior season vaccination when virus strains in the vaccine formula change. Moreover, interseason antibody waning and prior season post-vaccination HAI titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.

Antiviral effect and mechanism of Phillyrin and its reformulated FS21 against influenza.

Background: Influenza virus causes significant morbidity and mortality with pandemic threat. Oleaceae Fructus Forsythiae is a medicinal herb. This study aimed to investigate antiviral effect of Phillyrin, a purified bioactive compound from this herb, and its reformulated preparation FS21 against influenza and its mechanism. Methods: Madin-Darby Canine Kidney (MDCK) cells were infected by one of six influenza viruses: five influenza A viruses (IAVs: three H1N1 and two H3N2) and one influenza B virus (IBV). Virus-induced cytopathic effects were observed and recorded under microscope. Viral replication and mRNA transcription were evaluated by quantitative polymerase chain reaction (qPCR) and protein expression by Western blot. Infectious virus production was assessed using TCID50 assay, and IC50 was calculated accordingly. Pretreatment and time-of-addition experiments with Phillyrin or FS21 added 1 h before or in early (0-3 h), mid (3-6 h), or late (6-9 h) stages of viral infection were performed to assess their antiviral effects. Mechanistic studies included hemagglutination and neuraminidase inhibition, viral binding and entry, endosomal acidification, and plasmid-based influenza RNA polymerase activity. Results: Phillyrin and FS21 had potent antiviral effects against all six IAV and IBV in a dose-dependent manner. Mechanistic studies showed that both suppressed influenza viral RNA polymerase with no effect on virus-mediated hemagglutination inhibition, viral binding or entry, endosomal acidification, or neuraminidase activity. Conclusions: Phillyrin and FS21 have broad and potent antiviral effects against influenza viruses with inhibition of viral RNA polymerase as the distinct antiviral mechanism.

The intersection of biological sex and gender in adverse events following seasonal influenza vaccination in older adults.

Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to elucidate a possible biological mechanism for the AE reported. Results A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. Conclusions These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.

Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is increasingly applied in pancreatic ductal adenocarcinoma (PDAC); however, accurate prediction of therapeutic response to NAT remains a pressing clinical challenge. Cancer-cell-derived sialylated immunoglobulin G (SIA-IgG) was previously identified as a prognostic biomarker in PDAC. This study aims to explore whether SIA-IgG expression in treatment-naïve fine needle aspirate (FNA) biopsy specimens could predict the pathological response (PR) to NAT for PDAC. METHODS: Endoscopic ultrasonography-guided FNA biopsy specimens prior to NAT were prospectively obtained from 72 patients with PDAC at the Johns Hopkins Hospital. SIA-IgG expression of PDAC specimens was assessed by immunohistochemistry. Associations between SIA-IgG expression and PR, as well as patient prognosis, were analyzed. A second cohort enrolling surgically resected primary tumor specimens from 79 patients with PDAC was used to validate the prognostic value of SIA-IgG expression. RESULTS: SIA-IgG was expressed in 58.3% of treatment-naïve FNA biopsies. Positive SIA-IgG expression at diagnosis was associated with unfavorable PR and can serve as an independent predictor of PR. The sensitivity and specificity of SIA-IgG expression in FNA specimens in predicting an unfavorable PR were 63.9% and 80.6%, respectively. Both positive SIA-IgG expression in treatment-naïve FNA specimens and high SIA-IgG expression in surgically resected primary tumor specimens were significantly associated with shorter survival. CONCLUSIONS: Assessment of SIA-IgG on FNA specimens prior to NAT may help predict PR for PDAC. Additionally, SIA-IgG expression in treatment-naïve FNA specimens and surgically resected primary tumor specimens were predictive of the prognosis for PDAC.

The intersection of gender and race in older adults' decision to receive COVID-19 vaccines.

COVID-19 vaccines are essential public health tools for protecting older adults, who are at high risk of severe outcomes associated with COVID-19. Little is known, however, about how older adults approach the decision to receive a COVID-19 vaccine. We hypothesized that intersections between gender and race may provide unique insight into the decision-making process and the factors that lead to vaccine uptake among hesitant individuals. We performed in-depth interviews with 24 older adults who had been vaccinated against COVID-19 and used the framework approach with an intersectional lens to analyze data. Two typologies emerged: eager compliers did not question the need to vaccinate, whereas hesitant compliers were skeptical of the vaccine and underwent a thorough decision-making process prior to vaccination. For eager compliers, the vaccine offered protection from a disease that posed a serious threat, and few risks were perceived. In contrast, hesitant compliers perceived risks associated with the vaccine product or mistrusted the infrastructure that led to rapid vaccine development. Hesitancy was greater among Black participants, and only Black participants reported mistrust in vaccine infrastructure. At the intersection of gender and race, a 'White male effect' was observed, whereby White men perceived the fewest risks associated with the vaccine, and Black women were the most fearful of serious side effects. Nearly all hesitant compliers ultimately got vaccinated due to the threat of COVID-19. Convenient access through vaccine clinics in senior's buildings was pivotal for hesitant compliers and external and internal influences had differential impacts by race and gender. Emphasizing the risk of COVID-19, convenient and accessible opportunities for vaccination, and messages that are targeted to specific groups are likely to increase vaccine uptake among older adults.

Investigating adolescent mental health of Chinese students during the COVID-19 pandemic: Multicenter cross-sectional comparative investigation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant challenges for adolescent mental health. AIM: To survey adolescent students in China to determine the effects of the COVID-19 pandemic on their mental health. METHODS: A multicenter cross-sectional comparative investigation was conducted in March 2022. We collected demographic information and survey data related to the COVID-19 pandemic. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder Screener scales were used for objective assessment of depression and anxiety. RESULTS: We collected mental health questionnaires from 3184 students. The investigation demonstrated that adolescents most strongly agreed with the following items: Increased time spent with parents, interference with academic performance, and less travel. Conversely, adolescents most strongly disagreed with the following items: Not having to go to school, feeling an increase in homework, and not socializing with people; 34.6% of adolescents were depressed before COVID-19, of which 1.9% were severely depressed. After COVID-19, 26.3% of adolescents were prone to depression, of which 1.4% were severely depressed. 24.4% of adolescents had anxiety before COVID-19, with severe anxiety accounting for 1.6%. After COVID-19, 23.5% of adolescents were prone to anxiety, of which 1.7% had severe anxiety. CONCLUSION: Chinese adolescents in different grades exhibited different psychological characteristics, and their levels of anxiety and depression were improved after the COVID-19 pandemic. Changes in educational management practices since the COVID-19 pandemic may be worth learning from and optimizing in long-term educational planning.

Ketogenic Diet: An Effective Treatment Approach for Neurodegenerative Diseases.

This review discusses the effects and mechanisms of a ketogenic diet on neurodegenerative diseases on the basis of available evidence. A ketogenic diet refers to a high-fat, mediumprotein, and low-carbohydrate diet that leads to a metabolic shift to ketosis. This review systematically summarizes the scientific literature supporting this effective treatment approach for neurodegenerative diseases, including effects on mitochondrial function, oxidative stress, neuronal apoptosis, neuroinflammation, and the microbiota-gut-brain axis. It also highlights the clinical evidence for the effects of the ketogenic diet in the treatment of Alzheimer's disease, Parkinson's disease, and motor neuron disease. Finally, it discusses the common adverse effects of ketogenic therapy. Although the complete mechanism of the ketogenic diet in the treatment of neurodegenerative diseases remains to be elucidated, its clinical efficacy has attracted many new followers. The ketogenic diet is a good candidate for adjuvant therapy, but its specific applicability depends on the type and the degree of the disease.

Roadmap for Sex-Responsive Influenza and COVID-19 Vaccine Research in Older Adults.

Sex differences in the immune system are dynamic throughout the lifespan and contribute to heterogeneity in the risk of infectious diseases and the response to vaccination in older adults. The importance of the intersection between sex and age in immunity to viral respiratory diseases is clearly demonstrated by the increased prevalence and severity of influenza and COVID-19 in older males compared to older females. Despite sex and age biases in the epidemiology and clinical manifestations of disease, these host factors are often ignored in vaccine research. Here, we review sex differences in the immunogenicity, effectiveness, and safety of the influenza and COVID-19 vaccines in older adults and the impact of sex-specific effects of age-related factors, including chronological age, frailty, and the presence of comorbidities. While a female bias in immunity to influenza vaccines has been consistently reported, understanding of sex differences in the response to COVID-19 vaccines in older adults is incomplete due to small sample sizes and failure to disaggregate clinical trial data by both sex and age. For both vaccines, a major gap in the literature is apparent, whereby very few studies investigate sex-specific effects of aging, frailty, or multimorbidity. By providing a roadmap for sex-responsive vaccine research, beyond influenza and COVID-19, we can leverage the heterogeneity in immunity among older adults to provide better protection against vaccine-preventable diseases.

Association of Frailty, Age, and Biological Sex With Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine-Induced Immunity in Older Adults.

BACKGROUND: Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. METHODS: Plasma samples were collected from older adults (aged 75-98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18-74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). RESULTS: Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. CONCLUSIONS: Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

Longitudinal association of cytokine-producing CMV-specific T cells with frailty in HIV-infected and -uninfected men who have sex with men.

BACKGROUND: Chronic cytomegalovirus (CMV) infection has been postulated as a driver of chronic inflammation that has been associated with frailty and other age-related conditions in both HIV-infected (HIV+) and -uninfected (HIV-) people. METHODS: To study the T cell response to CMV as a predictor of onset and maintenance of frailty, baseline CMV-specific T cell responses of 42 men (20 HIV-, 22 HIV+; 21 frail, 21 nonfrail) in the Multicenter AIDS Cohort Study (MACS) were assessed by flow cytometric analysis of cytokine production (IFN-γ, TNF-⍺, and IL-2) in response to overlapping peptide pools spanning 19 CMV open reading frames. The Fried frailty phenotype was assessed at baseline and semiannually thereafter. Times to transition into or out of frailty were compared by tertiles of percentages of cytokine-producing T cells using Kaplan-Meier estimators and the exact log-rank test. RESULTS: Over a median follow-up of 6.5 (interquartile range: 2) years, faster onset of frailty was significantly predicted by higher (HIV- men) or lower (HIV+ men) percentages of CD4 T cells producing only IFN-γ (IFN-γ-single-producing (SP)), and by lower percentages of IFN-γ-, TNF-⍺-, and IL-2-triple-producing CD8 T cells (HIV- men). Greater maintenance of frailty was significantly predicted by lower percentages of both these T cell subsets in HIV- men, and by lower percentages of IFN-γ-SP CD4 T cells in HIV+ men. The antigenic specificity of IFN-γ-SP CD4 T cells was different between HIV- and HIV+ nonfrail men, as were the correlations between these cells and serum inflammatory markers. CONCLUSIONS: In this pilot study, percentages of CMV-specific T cells predicted the onset and maintenance of frailty in HIV- and HIV+ men. Predictive responses differed by HIV status, which may relate to differential control of CMV reactivation and inflammation by anti-CMV T cell responses.

Differences and disparities in seasonal influenza vaccine, acceptance, adverse reactions, and coverage by age, sex, gender, and race.

BACKGROUND: Influenza is a significant threat to public health worldwide. Despite the widespread availability of effective and generally safe vaccines, the acceptance and coverage of influenza vaccines are significantly lower than recommended. Sociodemographic variables are known to be potential predictors of differential influenza vaccine uptake and outcomes. OBJECTIVES: This review aims to (1) identify how sociodemographic characteristics such as age, sex, gender, and race may influence seasonal influenza vaccine acceptance and coverage; and (2) evaluate the role of these sociodemographic characteristics in differential adverse reactions among vaccinated individuals. METHODS: PubMed was used as the database to search for published literature in three thematic areas related to the seasonal influenza vaccine - vaccine acceptance, adverse reactions, and vaccine coverage. RESULTS: A total of 3249 articles published between 2010 and 2020 were screened and reviewed, of which 39 studies were included in this literature review. By the three thematic areas, 17 studies assessed vaccine acceptance, 8 studies focused on adverse reactions, and 14 examined coverage of the seasonal influenza vaccine. There were also two studies that focused on more than one of the areas of interest. CONCLUSION: Each of the four sociodemographic predictors - age, sex, race, and gender - were found to significantly influence vaccine acceptance, receipt and outcomes in this review.

The shifting age distribution of people with HIV using antiretroviral therapy in the United States.

OBJECTIVE: To project the future age distribution of people with HIV using antiretroviral therapy (ART) in the United States, under expected trends in HIV diagnosis and survival (baseline scenario) and achieving the ending the HIV epidemic (EHE) goals of a 75% reduction in HIV diagnoses from 2020 to 2025 and sustaining levels to 2030 (EHE75% scenario). DESIGN: An agent-based simulation model with mathematical functions estimated from North American AIDS Cohort Collaboration on Research and Design data and parameters from the US Centers for Disease Control and Prevention's annual HIV surveillance reports. METHODS: The PEARL (ProjEcting Age, MultimoRbidity, and PoLypharmacy in adults with HIV) model simulated individuals in 15 subgroups of sex-and-HIV acquisition risk and race/ethnicity. Simulation outcomes from the baseline scenario are compared with outcomes from the EHE75% scenario. RESULTS: Under the baseline scenario, PEARL projects a substantial increase in number of ART-users over time, reaching a population of 909 638 [95% uncertainty range (UR): 878 449-946 513] by 2030. The overall median age increased from 50 years in 2020 to 52 years in 2030, with 23% of ART-users age ≥65 years in 2030. Under the EHE75% scenario, the projected number of ART-users was 718 348 [703 044-737 817] (median age = 56 years) in 2030, with a 70% relative reduction in ART-users <30 years and a 4% relative reduction in ART-users age ≥65 years compared to baseline, and persistent heterogeneities in projected numbers by sex-and-HIV acquisition risk group and race/ethnicity. CONCLUSIONS: It is critical to prepare healthcare systems to meet the impending demand of the US population aging with HIV.

Activity of curcumin against human cytomegalovirus infection in vitro / 生物医学工程学杂志

This study aimed to investigate the effect of curcumin (Cur) against human cytomegalovirus (HCMV) in vitro. Human embryonic lung fibroblasts were cultured in vitro. The tetrazolium salt (MTS) method was used to detect the effects of Cur on cell viability. The cells were divided into control group, HCMV group, HCMV + (PFA) group and HCMV + Cur group in this study. The cytopathic effect (CPE) of each group was observed by plaque test, then the copy number of HCMV DNA in each group was detected by quantitative polymerase chain reaction (qPCR), and the expression of HCMV proteins in different sequence was detected by Western blot. The results showed that when the concentration of Cur was not higher than 15 μmol/L, there was no significant change in cell growth and viability in the Cur group compared with the control group (P>0.05). After the cells were infected by HCMV for 5 d, the cells began to show CPE, and the number of plaques increased with time. Pretreatment with Cur significantly reduced CPE in a dose-dependent manner. After the cells were infected by HCMV, the DNA copy number and protein expression gradually increased in a time-dependent manner. Pretreatment with Cur significantly inhibited HCMV DNA copies and downregulate HCMV protein expression levels in a concentration-dependent manner, and the difference was statistically significant (P<0.05). In conclusion, Cur may exert anti-HCMV activity by inhibiting the replication of HCMV DNA and down-regulating the expression levels of different sequence proteins of HCMV. This study provides a new experimental basis for the development of anti-HCMV infectious drugs.

Sex-specific effects of aging on humoral immune responses to repeated influenza vaccination in older adults.

Older adults (≥65 years of age) bear a significant burden of severe disease and mortality associated with influenza, despite relatively high annual vaccination coverage and substantial pre-existing immunity to influenza. To test the hypothesis that host factors, including age and sex, play a role in determining the effect of repeated vaccination and levels of pre-existing humoral immunity to influenza, we evaluated pre- and post-vaccination strain-specific hemagglutination inhibition (HAI) titers in adults over 75 years of age who received a high-dose influenza vaccine in at least four out of six influenza seasons. Pre-vaccination titers, rather than host factors and repeated vaccination were significantly associated with post-vaccination HAI titer outcomes, and displayed an age-by-sex interaction. Pre-vaccination titers to H1N1 remained constant with age. Titers to H3N2 and influenza B viruses decreased substantially with age in males, whereas titers in females remained constant with age. Our findings highlight the importance of pre-existing immunity in this highly vaccinated older adult population and suggest that older males are particularly vulnerable to reduced pre-existing humoral immunity to influenza.

Efficacy and Safety of Tongxinluo Capsule as Adjunctive Treatment for Unstable Angina Pectoris: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Tongxinluo capsule (TXLC) is a commonly used Chinese medicine for unstable angina pectoris (UA). This article aimed to clarify the safety and efficacy of TXLC as an adjunctive treatment for UA. Two reviewers searched 7 databases from inception to August 2021, and performed literature screening and information extraction independently. The meta-analysis was implemented after evaluating the methodological quality of each randomized controlled trial (RCT) by the Cochrane Risk of Bias tool. Sensitivity analyses were conducted for testing the stability of the results, and the Begg and Egger tests were performed for any potential publication bias. After eligibility assessment, 42 RCTs with a total of 5,421 participants were included. Evidence showed that TXLC reduced the rate of cardiovascular events [RR = 0.29, 95% CI (0.19, 0.45), p < 0.00001, I 2 = 0%] {including cardiovascular mortality [RR = 0.16, 95% CI (0.03, 0.88), p = 0.03, I 2 = 20%], the incidence of acute myocardial infarction [RR = 0.27, 95% CI (0.13, 0.57), p = 0.0006, I 2 = 0%] and the occurrence of revascularization [RR = 0.28, 95% CI (0.15,0.54), p = 0.0001, I 2 = 0%]}, all-cause mortality [RR = 0.25, 95% CI (0.06, 0.99), p = 0.05, I 2 = 19%], recurrence of angina [RR = 0.25, 95% CI (0.11, 0.61), p = 0.002, I 2 = 0%], the number of ST-segment depression [MD = -0.45, 95% CI (-0.69, -0.20), p = 0.0005, I 2 = 0%], the summation of ST-segment depression [MD = -0.70, 95% CI (-1.08, -0.32), p = 0.0003, I 2 = 70%] and the hypersensitive C-reactive protein level [MD = -2.86, 95% CI (-3.73, -1.99), p < 0.00001, I 2 = 86%], increased the nitric oxide level [MD = 11.67, 95% CI (8.33, 15.02), p < 0.00001, I 2 = 33%], improved the electrocardiogram change [RR = 1.23, 95% CI (1.16, 1.30), p < 0.00001, I 2 = 0%] and the clinical efficacy in UA [RR = 1.26, 95% CI (1.21, 1.32), p < 0.00001, I 2 = 24%], and relieved the symptoms of angina pectoris {including chest pain or tightness [RR = 1.13, 95% CI (0.97, 1.32), p = 0.12, I 2 = 30%], palpitations [RR = 1.47, 95% CI (1.18, 1.84), p = 0.0007, I 2 = 0%], shortness of breath [RR = 1.53, 95% CI (1.24, 1.88), p < 0.0001, I 2 = 0%], and asthenia [RR = 1.69, 95% CI (0.83, 3.43), p = 0.15, I 2 = 90%]}. The most common adverse effect was gastrointestinal symptoms which could be relieved and eliminated through dose reduction, medication time adjustment and symptomatic remedy. Collectively, TXLC was effective and considerably safe for UA. However, due to the unavoidable risk of bias, these results must be interpreted with caution and further verified by large-scale and high-quality RCTs. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/, identifier CRD42021232771.

The effects of heatwaves and cold spells on patients admitted with acute ischemic stroke.

BACKGROUND: This study aimed to explore the effects of heatwaves and cold spells on blood pressure, thrombus formation, and systemic inflammation at admission in patients with ischemic stroke. METHODS: Data of patients with ischemic stroke who were admitted to the Second Hospital of Tianjin Medical University between May 2014 and March 2019 were reviewed, along with meteorological data from the same time period. A total of 806 clinically confirmed patients with ischemic stroke (34-97 years old) were included in the final analysis. Heatwaves and cold spells were defined as ≥2 consecutive days with average temperature >95th percentile (May-August) and <5th percentile (November-March), respectively. Coagulation parameters, inflammation indices, blood pressure, and neurological impairment were evaluated within 24 hours of admission. General linear and logistic regression models were created to investigate the relationships of heatwaves and cold spells with the examination results of patients with ischemic stroke at admission. RESULTS: After adjustment for potential environmental confounders, heatwaves were positively associated with high systolic blood pressure (SBP) (ß=8.693, P=0.019), diastolic blood pressure (DBP) (ß=3.665, P=0.040), reduced thrombin time (TT) (ß=-0.642, P=0.027), and activated partial thromboplastin time (APTT) (ß=-1.572, P=0.027) in ischemic stroke patients at admission. Cold spells were positively associated with high SBP (ß=5.277, P=0.028), DBP (ß=4.672, P=0.012), fibrinogen (ß=0.315, P=0.011), globulin (ß=1.523, P=0.011), and reduced TT (ß=-0.784, P<0.001) and APTT (ß=-1.062, P=0.024). Cold spells were also associated with a higher risk of respiratory infection [odds ratio (OR) =2.677, P=0.001]. CONCLUSIONS: Exposure to heatwaves or cold spells was associated with blood pressure and coagulation at admission in patients with ischemic stroke. Cold spells also resulted in higher levels of inflammation. These findings suggest that changes in coagulation, blood pressure, and inflammation may be the potential biological mechanisms underlying the cerebrovascular effects of exposure to extreme temperatures.