Prevalence of Respiratory Viruses in Children With Acute Respiratory Infections in Shanghai, China, From 2013 to 2022.

BACKGROUND: A variety of viruses can cause acute respiratory infections (ARIs), resulting in a high disease burden worldwide. To explore the dominant viruses and their prevalence characteristics in children with ARIs, comprehensive surveillance was carried out in the Pudong New Area of Shanghai. METHODS: Between January 2013 and December 2022, the basic and clinical information, and respiratory tract specimens of 0-14 years old children with ARIs were collected in five sentinel hospitals in Shanghai Pudong. Each specimen was tested for eight respiratory viruses, and the positive rates of different age groups, case types (inpatient or outpatient) were analyzed. RESULTS: In our study, 30.67% (1294/4219) children with ARIs were positive for at least one virus. Influenza virus (IFV) was the most commonly detected respiratory virus (349/4219, 8.27%), followed by respiratory syncytial virus (RSV) (217/4219, 5.14%), para-influenza virus (PIV) (215/4219, 5.10%), and human coronavirus (HCoV, including 229E, OC43, NL63, and HKU1) (184/4219, 4.36%). IFV was the leading respiratory virus in outpatients aged 5-14 years (201/1673, 12.01%); RSV was the most prevalent respiratory virus in both inpatients (61/238, 25.63%) and outpatients (4/50, 8.00%) for ARI patients aged <6 months old. For PIV, HMPV, HCoV, and HRV, the risk of infection usually was higher among young children. Co-infection with more than two viruses was seen in 3.25% (137/4219). CONCLUSIONS: IFV and RSV played important roles in ARIs among children, but the risk populations were different. There are needs for targeted diagnosis and treatment and necessary immunization and non-pharmaceutical interventions.

Impact of low-level exposure to antibiotics on bile acid homeostasis in adults: Implication for human safety thresholds.

Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×102 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics.

Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis through PI3K/Akt Signaling Pathway.

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.

Efficacy and safety of Shen Gui capsules for chronic heart failure: a systematic review and meta-analysis.

Background: Although Shen Gui capsules (SGCP) are widely used as an adjuvant treatment for chronic heart failure (CHF), their clinical efficacy and safety remain controversial. Purpose: To assess the efficacy and safety of SGCP in the treatment of CHF through a systematic review and meta-analysis, to provide high-quality evidence for evidence-based medicine. Methods: Seven databases were searched for randomized controlled trials (RCTs) assessing SGCP for CHF, from inception to 9 January 2023. RCT quality of evidence was evaluated using the Cochrane Handbook for the Evaluation of Intervention Systems to assess risk of bias and Grading of Recommendations Assessment, Development, and Evaluation. A meta-analysis with subgroup and sensitivity analyses was performed using Review Manager 5.4 and Stata 12. Results: Nine RCTs representing 888 patients with CHF were included in the review. Meta-analysis revealed that SGCP combined with conventional heart failure therapy is more advantageous for improving left ventricular ejection fraction [LVEF; mean difference (MD) = 5.26, 95% confidence interval (CI) (3.78, 6.74), p < 0.0000] and increasing effective rate [relative risk (RR) = 1.21, 95%CI (1.14, 1.29), p < 0.001] compared with conventional therapy alone. The experimental treatment also reduced brain natriuretic peptide [MD = -100.15, 95%CI (-157.83, -42.47), p = 0.0007], left ventricular end-diastolic diameter [MD = -1.93, 95%CI (-3.22, -0.64), p = 0.003], and hypersensitive C-reactive protein [MD = -2.70, 95%CI (-3.12,-2.28), p < 0.001] compared with the control group. However, there was not a statistically significant difference in tumor necrosis factor-α [MD = -14.16, 95%CI (-34.04, 5.73), p = 0.16] or left ventricular end-systolic diameter [MD = -1.56, 95%CI (-3.13, 0.01), p = 0.05]. Nor was there a statistically significant between-groups difference in incidence of adverse events (p > 0.05). Conclusion: SGCP combined with conventional heart failure therapy can improve LVEF and increase the effective rate to safely treat patients with CHF. However, further high-quality studies are needed to confirm these findings, due to the overall low quality of evidence in this literature.Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/logout.php, PROSPERO [CRD42023390409].

The ratio of systolic and diastolic pressure is associated with carotid and femoral atherosclerosis.

Background: Although the impact of hypertension on carotid intima-media thickness (IMT) and plaques has been well established, its association with femoral IMT and plaques has not been extensively examined. In addition, the role of the ratio of systolic and diastolic pressure (SDR) in the subclinical atherosclerosis (AS) risk remains unknown. We assessed the relationship between SDR and carotid and femoral AS in a general population. Methods: A total of 7,263 participants aged 35-74 years enrolled from January 2019 to June 2021 in a southeast region of China were included in a cross-sectional study. Systolic and diastolic blood pressure (SBP and DBP) were used to define SDR. Ultrasonography was applied to assess the AS, including thickened IMT (TIMT) and plaque in the carotid and femoral arteries. Logistic regression and restricted cubic spline (RCS) models were the main approaches. Results: The prevalence of TIMT, plaque, and AS were 17.3%, 12.4%, and 22.7% in the carotid artery; 15.2%, 10.7%, and 19.5% in the femoral artery; and 23.8%, 17.9% and 30.0% in either the carotid or femoral artery, respectively. Multivariable logistic regression analysis found a significant positive association between high-tertile SDR and the higher risk of overall TIMT (OR = 1.28, 95% CI = 1.10-1.49), plaques (OR = 1.36, 95%CI = 1.16-1.61), or AS (OR = 1.36, 95% CI = 1.17-1.57), especially in the carotid artery. RCS analysis further revealed the observed positive associations were linear. Further analyses showed that as compared to the low-tertile SDR and non-hypertension group, high-tertile SDR was associated with increased risks of overall and carotid TIMT, plaques, or AS in both groups with or without hypertension. Conclusions: SDR is related to a higher risk of subclinical AS, regardless of hypertension or not, suggesting that as a readily obtainable index, SDR can contribute to providing additional predictive value for AS.

Changes of influenza vaccination rate and associated influencing factors after the COVID-19 pandemic in Shanghai, China.

The vaccination rate for seasonal influenza remains low in most regions of China. It is essential to understand the factors that associated with the low influenza vaccination rate in various populations after the COVID-19 pandemic. A cross-sectional survey was conducted with residents in Pudong New Area, Shanghai, China. Respondents' vaccination condition during the 2021-2022 flu season and the reasons for receiving or not receiving influenza vaccine were investigated. Binary logistic regression was conducted to explore potential factors influencing vaccination uptake. 2,476 of 14,001 respondents received an influenza vaccine, with a total coverage of 17.68% (95% CI: 17.05%, 18.32%). Children had the highest vaccination coverage (35.68%; 95% CI: 34.02, 37.33), followed by adults (12.75%; 95% CI: 11.91%, 13.58%) and elderly individuals (11.70%, 95% CI: 10.78%, 12.62%). For children, lower household income was an significant promoting factor. For adults, factors significantly associated with vaccination were household income, sex, and education level. For elderly, factors significantly associated with vaccination were household income, education level, living state, and having underlying diseases. (P < .05)The main reason for vaccine hesitancy among children was worried about side effects (21.49%), for adults and elderly was self-rated good health (adults: 37.14%, elderly people: 30.66%). The overall influenza vaccination coverage rate in Shanghai, especially among elderly individuals, is lower than many developed countries. Appropriate strategies and programs targeting different populations need to be implemented to enhance influenza vaccine coverage.

The vaccination rate for seasonal influenza remains low in most regions of China. However, the COVID-19 pandemic has resulted in an increase in public awareness regarding the prevention and control of infectious diseases and changes in people's health behaviors thus may leading to changes in influenza vaccination rates and vaccination willingness. We conducted a survey on the medical service utilization behavior of community residents in Shanghai, the biggest city in eastern China. The vaccination status of respondents during the 2021­2022 flu season and the reasons for receiving or not receiving the vaccine were investigated among 14,001 local residents. The influenza vaccination rate in 2021­2022 season (17.68%) was higher than that in 2018­2019 season (11.8%) in the same area. And this trend was found in population of different age groups. However, the overall influenza vaccination coverage rate in Shanghai is still low, especially among elderly, it remains inadequate to establish an immune barrier and lags behind other developed regions. For children, lower household income was an independent promoting factor. For adults, factors significantly associated with vaccination were  household income, sex, and education level. For elderly, factors significantly associated with vaccination were household income, education level, living state, and having underlying diseases. (P < .05) The main reason for vaccine hesitancy among children was worried about side effects (21.49%), for adults and elderly was self-rated good health (adults: 37.14%,elderly people: 30.66%).Efforts should be made to increase awareness of influenza vaccines according to the characteristics of different population.

Urinary neonicotinoids and metabolites are associated with obesity risk in Chinese school children.

BACKGROUND: Neonicotinoids are the most widely used insecticides. Laboratory studies have suggested that neonicotinoids are one potential obesogen, but relevant data are limited in human. OBJECTIVE: To examine the association between exposure to neonicotinoids and childhood obesity. METHODS: We investigated 442 children in Shanghai, East China and measured eight neonicotinoids (thiamethoxam, clothianidin, acetamiprid, imidacloprid, thiacloprid, nitenpyram, dinotefuran, and imidaclothiz) and four metabolites (N-desmethyl-thiamethoxam, N-desmethyl-clothianidin, N-desmethyl-acetamiprid, and 5-OH-imidacloprid) in urine. Body mass index (BMI) and waist circumference (WC) were used to identify general overweight/obesity and central obesity, respectively. Linear and logistic regression models based on generalized estimating equations were used to investigate the associations of urinary neonicotinoids and metabolites with BMI z-score, WC z-score, general overweight/obesity, and central obesity. RESULTS: Children with a positive detection of clothianidin and its metabolite had a marginally higher BMI z-score (regression coefficient (ß): 0.08, 95% confidence interval (95% CI): 0.01, 0.14) after adjusted for relevant covariates. After creatinine-adjusted concentration was trichotomized, compared to children with a negative detection, children in the high urinary concentration of acetamiprid and its metabolite had a low BMI z-score (ß: -0.19, 95%CI: -0.30, -0.08), children in the medium urinary concentration of neonicotinoids and metabolites other than thiamethoxam, clothianidin, acetamiprid, and their metabolites had a marginally higher BMI z-score (ß: 0.25, 95%CI: 0.03, 0.46), a higher WC z-score (ß: 0.24, 95%CI: 0.14, 0.33), and a higher odds of central obesity (odds ratio (OR): 2.16, 95% CI: 1.28, 3.63), and children in the medium urinary concentration of all neonicotinoids and metabolites had a higher odds of central obesity (OR: 1.55, 95%CI: 1.04, 2.33). Some associations showed sex- and age- related differences. CONCLUSION: Urinary neonicotinoids and metabolites were found to be differently associated with obesity-related indexes, which suggested that exposure to neonicotinoids might have a mixed effect on childhood obesity.

Source and health risk of urinary neonicotinoids in Tibetan pregnant women.

High altitude could influence the level of exposure to neonicotinoids, but relevant data remain limited for people living in Tibet. We investigated 476 Tibetan pregnant women from Lhasa of Tibet, China in 2021 and measured eight neonicotinoids and four metabolites in urine. Food consumption was investigated by a food frequency questionnaire. Health risk was assessed by using hazard quotient (HQ) and hazard index (HI) based on acceptable daily dose or chronic reference dose. Neonicotinoids and metabolites were overall detected in 56.5% of urine samples with a median concentration being 0.73 µg g-1 creatinine. Four neonicotinoids or metabolites were detected in more than 10% of urine samples, including N-desmethyl-acetamiprid (47.5%), clothianidin (15.5%), thiamethoxam (16.0%), and imidacloprid (10.5%). Annual household income, family smoking, and pre-pregnancy body mass index were associated with the detection frequencies of neonicotinoids. Pregnant women with a higher consumption frequency of wheat, rice, fresh vegetable, fresh fruit, beef and mutton, fresh milk, yoghourt, candy and chocolate, or carbonated drinks had a higher detection frequency of neonicotinoids. Both HQ and HI were less than one. There was an evident exposure to neonicotinoids in Tibetan pregnant women with both plant- and animal-derived food items as exposure sources, but a low health risk was found based on current safety thresholds.

The Omicron Variant Reinfection Risk among Individuals with a Previous SARS-CoV-2 Infection within One Year in Shanghai, China: A Cross-Sectional Study.

Reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants due to immune escape is challenging for the global response to the pandemic. We estimated the Omicron reinfection prevalence among people who had a previous SARS-CoV-2 infection in Shanghai, China. We conducted a telephone survey in December 2022 with those who had previously been infected with Omicron between March and May 2022. Information on their demographics, coronavirus disease 2019 (COVID-19) testing, and vaccination history was collected. The overall and subgroup reinfection rates were estimated and compared. Among the 1981 respondents who were infected between March and May 2022, 260 had positive nucleic acid or rapid antigen tests in December 2022, with an estimated reinfection rate of 13.1% (95% confidence interval [95% CI]: 11.6-14.6). The reinfection rate for those who had a booster vaccination was 11.4% (95% CI: 9.2-13.7), which was significantly lower than that for those with an incomplete vaccination series (15.2%, 95% CI: 12.3-18.1) (adjusted odds ratio [aOR]: 0.579; 95% CI: 0.412-0.813). Reinfection with the Omicron variant was lower among individuals with a previous SARS-CoV-2 infection and those who had a booster vaccination, suggesting that hybrid immunity may offer protection against reinfection with Omicron sublineages.

A long-acting GDF15 analog causes robust, sustained weight loss and reduction of food intake in an obese nonhuman primate model.

Growth Differentiation Factor-15 (GDF15) is a circulating polypeptide linked to cellular stress and metabolic adaptation. GDF15's half-life is ~3 h and activates the glial cell line-derived neurotrophic factor family receptor alpha-like (GFRAL) receptor expressed in the area postrema. To characterize sustained GFRAL agonism on food intake (FI) and body weight (BW), we tested a half-life extended analog of GDF15 (Compound H [CpdH]) suitable for reduced dosing frequency in obese cynomolgus monkeys. Animals were chronically treated once weekly (q.w.) with CpdH or long-acting GLP-1 analog dulaglutide. Mechanism-based longitudinal exposure-response modeling characterized effects of CpdH and dulaglutide on FI and BW. The novel model accounts for both acute, exposure-dependent effects reducing FI and compensatory changes in energy expenditure (EE) and FI occurring over time with weight loss. CpdH had linear, dose-proportional pharmacokinetics (terminal half-life ~8 days) and treatment caused exposure-dependent reductions in FI and BW. The 1.6 mg/kg CpdH reduced mean FI by 57.5% at 1 week and sustained FI reductions of 31.5% from weeks 9-12, resulting in peak reduction in BW of 16 ± 5%. Dulaglutide had more modest effects on FI and peak BW loss was 3.8 ± 4.0%. Longitudinal modeling of both the FI and BW profiles suggested reductions in BW observed with both CpdH and dulaglutide were fully explained by exposure-dependent reductions in FI without increase in EE. Upon verification of the pharmacokinetic/pharmacodynamic relationship established in monkeys and humans for dulaglutide, we predicted that CpdH could reach double digit BW loss in humans. In summary, a long-acting GDF15 analog led to sustained reductions in FI in overweight monkeys and holds potential for effective clinical obesity pharmacotherapy.

Xinbao Pill attenuated chronic heart failure by suppressing the ubiquitination of ß-adrenergic receptors.

BACKGROUD: Xinbao Pill (XBP) is extensively used in the adjuvant treatment of chronic heart failure in China. However, the pharmacological effect and underlying mechanism on CHF remains unclear. PURPOSE: Our research was performed to investigate the cardioprotective effect of XBP against CHF and uncover the potential mechanism. METHODS: Male Sprague-Dawley (SD) rats were subjected to the left anterior descending (LAD) artery ligation for 8 weeks and were treated with different doses of XBP (from the 4th week to the end). Cardiac function and morphology assessment were performed by using M-mode echocardiography, H&E and Masson staining. Western blotting analysis, co-immunoprecipitation (IP) assays, siRNA transfection were used to evaluate the mechanism of XBP. RESULTS: XBP improved cardiac function and alleviated cardiac fibrosis in LAD-induced chronic heart failure rats. Meanwhile, XBP protected cardiomyocytes against oxygen-glucose deprivation (OGD) injury in AC16 cells and H9c2 cells. Additionally, XBP could increase the expression of ß1-AR and ß2-AR and inhibit their ubiquitanation. Further mechanism study showed that XBP upregulated USP18 expression, while silence of USP18 attenuated the cardioprotective effect of XBP and the increase of ß1-AR by XBP. Moreover, XBP increased MDM2 and ß-arrestin2, and disrupted the interaction between Nedd4 and ß2-AR. After using the inhibitor of MDM2, SP141, the cardioprotective effect of XBP and the inhibitory effect on the ubiquitanation of ß2-AR were also blocked. CONCLUSION: Our study firstly revealed that XBP improved cardiac function against CHF through suppressing USP18 and MDM2/ß-arrestin2/Nedd4-mediated the ubiquitination of ß1-AR and ß2-AR.

How climate change affects electricity consumption in Chinese cities-a differential perspective based on municipal monthly panel data.

Addressing the impacts of climate change has become a global public crisis and challenge. China is characterized by a complex and diverse topography and vast territory, which makes it worthwhile to explore the differential impacts of climate change on urban electricity consumption in different zones and economic development conditions. This study examines the differential impact of climate factors on urban electricity consumption in China based on monthly panel data for 282 prefectures from 2011 to 2019 and projects the potential demand for future urban electricity consumption under different climate change scenarios. The results show that (1) temperature changes significantly alter urban electricity consumption, with cooling degree days (CDD) and heating degree days (HDD) contributing positively to urban electricity consumption in areas with different regional and economic development statuses, with elasticity coefficients of 0.1015-0.1525 and 0.0029-0.0077, respectively. (2) The temperature-electricity relationship curve shows an irregular U-shape. Each additional day of extreme weather above 30 °C and below -12 °C increases urban electricity consumption by 0.52% and 1.52% in the north and by 2.67% and 1.32% in the south. Poor cities are significantly more sensitive to extremely low temperatures than rich cities. (3) Suppose the impacts of climate degradation on urban electricity consumption are not halted. In that case, the possible Shared Socioeconomic Pathways 1-1.9 (SSP1-1.9), SSP1-2.6, and SSP2-4.5 will increase China's urban electricity consumption by 1621.96 billion kWh, 2960.87 billion kWh, and 6145.65 billion kWh, respectively, by 2090. Finally, this study makes some policy recommendations and expectations for follow-up studies.

Exposure of Tibetan pregnant women to antibiotics in China: A biomonitoring-based study.

Tibetan people are one Chinese ethnic minority living in Qinghai-Tibet Plateau with an average altitude of more than 4500 m. High altitude could cause a different antibiotic exposure, but relevant information is limited in Tibetan people. We investigated 476 Tibetan pregnant women in Lhasa, Tibet in 2021 and measured 30 antibiotics from five categories in urine, including 13 veterinary antibiotics (VAs), five human antibiotics (HAs), and 12 human/veterinary antibiotics (H/VAs). Food consumption was investigated by a brief food frequency questionnaire. Health risk was assessed by hazard quotient (HQ) and hazard index (HI) based on acceptable daily intakes (ADIs). All antibiotics were overall detected in 34.7% of urine samples with the 75th percentile concentration of 0.19 ng/mL (0.35 µg/g creatinine). HAs, VAs, and H/VAs were respectively detected in 5.3%, 13.0%, and 25.0% of urine samples, with the 95th percentiles of 0.01 ng/mL (0.01 µg/g creatinine), 0.50 ng/mL (0.99 µg/g creatinine), and 3.58 ng/mL (5.02 µg/g creatinine), respectively. Maternal age, smoking of family members, and housework time were associated with detection frequencies of HAs, VAs, or sum of all antibiotics. Pregnant women with a more frequent consumption of fresh milk, egg, yoghourt, poultry meat, and fish had a higher detection frequency of VAs or H/VAs. Only ciprofloxacin and tetracycline had a HQ of larger than one based on microbiological effect in 1.26% and 0.21% of pregnant women, respectively and a HI of larger than one was found in 1.47% of pregnant women. The findings suggested that there was an evident antibiotic exposure from various sources in Tibetan pregnant women with some basic characteristics of pregnant women as potential predictors and several animal-derived food items were important sources of exposure to antibiotic with a fraction of pregnant women in the health risk related to microbiological disruption of gut microbiota.

The Efficacy and Safety of a Qiliqiangxin Capsule Combined with Sacubitril/Valsartan in the Treatment of Chronic Heart Failure: A Systematic Review and Meta-Analysis.

Background: Qiliqiangxin (QLQX) capsules are a commonly used proprietary Chinese medicine for the adjuvant treatment of chronic heart failure (CHF) in China. In recent years, several randomized controlled trials (RCTs) have reported on the efficacy and safety of QLQX combined with sacubitril/valsartan for CHF. Objective: The purpose of this study was to systematically analyze the clinical efficacy and safety of QLQX combined with sacubitril/valsartan in the management of CHF and to provide clinicians as well as scientists with optimal evidence-based medical evidence. Methods: We searched RCTs to evaluate the efficacy and safety of QLQX combined with sacubitril/valsartan in the treatment of CHF in the Wanfang Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, PubMed, Embase, and Cochrane Library databases from their inception until January 8, 2022. RCTs on QLQX in combination with sacubitril/valsartan for CHF were included. The outcome measures considered were total effective rate, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), 6-minute walking distance (6-MWD), and adverse events. The quality of the included RCTs was assessed thereafter using the Cochrane risk of bias tool. RevMan 5.3 software was used to conduct the meta-analysis. Results: The meta-analysis included 17 trials involving 1427 CHF patients. The results indicated that with sacubitril/valsartan administration combined with QLQX treatment, the total effective rate (relative risk (RR) = 1.24; 95% confidence interval (CI) (1.17, 1.31); p < 0.01), LVEF (mean difference (MD) = 6.20; 95% CI (5.36, 7.05; p < 0.01)), and 6-MWD (MD = 55.87; 95% CI (40.66, 71.09); p < 0.01) of CHF patients were significantly increased, and the LVEDD value of CHF patients was noted to be significantly reduced (MD = -3.98; 95% CI (-4.47, -3.48); p < 0.01). Moreover, there was no increase in the number of adverse events during treatment (RR = 0.67; 95% CI (0.33, 1.34); p < 0.01). Conclusions: This study indicated that in CHF patients, on the basis of sacubitril/valsartan treatment, combination with QLQX can potentially enhance the total effective rate, improve LVEF and 6-MWD, and reduce LVEDD values, with good safety. However, considering the poor quality of the included studies, a multicenter, randomized, double-blind controlled study is needed for further confirmation.

Efficacy and safety evaluation of Shenmai injections for dilated cardiomyopathy: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Shenmai Injection (SMI), a Chinese herbal injection, is widely used in China for the adjuvant treatment of patients with dilated cardiomyopathy (DCM), yet its clinical efficacy and safety remain controversial. PURPOSE: The aim of this study was to systematically evaluate the efficacy and safety of SMI in the treatment of DCM. METHODS: Randomised controlled trials (RCTs) of SMI in the treatment of DCM were searched for and collected from the PubMed, EMBASE, Cochrane Library, SinoMed, Wan Fang, CNKI, and VIP databases between the dates of establishment of each database and July 1, 2022. The methodological quality of the included studies was assessed, while the risk of bias was based on the Cochrane Collaboration tool. All data were analysed using the R software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the quality of the evidence. RESULTS: In total, 16 RCTs, including 1,455 participants, were examined in this study. Evidence showed that the combination of SMI treatment and conventional treatment appears to significantly increase the clinical efficacy rate (OR=3.65, 95%CI (2.52, 5.28), p < 0.01), improve cardiac function (e.g. increase left ventricular ejection fraction (LVEF) (MD=5.31, 95%CI (4.21, 6.40), p < 0.01), decrease left ventricular end-diastolic dimension (LVEDD) (MD=-4.57, 95% CI (-7.10, -2.04); p < 0.01) and left ventricular end-systolic diameter (LVESD) (MD=-2.46, 95% CI (-3.60, -1.33); p < 0.01), decrease brain natriuretic peptide (BNP) (MD=-215.85, 95% CI (-241.61, -190.10); p < 0.01) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (MD=-504.42, 95% CI (-687.73, -321.10); p < 0.01), and increase 6-min walk distance (6MWD) (MD=114.08, 95% CI (42.32, 185.85); p < 0.01).In addition, no serious adverse effects associated with SMI were observed during the study period, thus suggesting that SMI is safe. However, the quality of evidence for these results was rated as "very low" to "low", mainly due to the poor methodological quality of the included RCTs, the small sample size, the high heterogeneity, and potential publication bias. CONCLUSION: In the present work, we provide evidence that combined SMI therapy is beneficial and safe for improving cardiac function in patients with DCM. However, due to limitations posed by the low methodological quality of the included trials, more rigorous and high-quality RCTs are needed to provide solid evidence.

Gestational exposure to perfluoroalkyl substances is associated with placental DNA methylation and birth size.

DNA methylation is one potential mechanism for the effects of gestational exposure to perfluoroalkyl substances (PFASs) on fetal growth. We investigated 180 pregnant women who participated in a cohort study conducted in Tangshan City, Northern China, and determined the concentrations of 11 PFASs and the methylation of two genes related to fetal growth [insulin-like growth factor 2 (IGF2) and nuclear receptor subfamily 3 group C member 1 (NR3C1)] and one surrogate marker for global methylation [long interspersed nuclear element-1 (LINE-1)] in placenta tissue. Multiple linear regression analysis was performed to examine the associations of log transformed PFASs with the DNA methylation and birth size. Weighted quantile sum regression was used to determine the mixture effect of PFASs. After adjusting for potential confounders, perfluorooctane sulfonate (PFOS) was negatively associated with the overall methylation of LINE-1. PFASs mixture was negatively associated with the methylation of all CpG loci of LINE-1 and overall methylation of NR3C1. Perfluorootanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and the PFASs mixture showed negative associations with head circumference. After stratified by newborns' sex, PFOA, PFNA and the PFASs mixture was negatively associated with overall methylation of LINE-1 only in the male subgroup and the methylation of all CpG loci of LINE-1 was negatively associated with ponderal index only in the female subgroup. The interaction of newborns' sex with PFOS and PFOA on overall methylation of IGF2 was statistically significant and so was the interaction of sex with PFOS on overall methylation of LINE-1. These findings suggested that intrauterine exposure to PFASs affected placental DNA methylation and reduced fetal growth, which might be modified by sex.

Parental Seasonal Influenza Vaccine Hesitancy and Associated Factors in Shanghai, China, during the COVID-19 Pandemic: A Cross-Sectional Study.

BACKGROUND: Seasonal influenza may overlap with the COVID-19 pandemic, and children are one of the priority populations for influenza vaccination in China, yet vaccine coverage has been low. This study aimed to investigate the extent of parental influenza vaccine hesitancy (IVH) and to explore the associated factors. METHODS: The study was conducted in Shanghai, China, from 1 June 2022 to 31 July 2022, using an anonymous questionnaire to survey a random sample of parents of children aged six months to 14 years. Binary logistic regression models were used to identify factors associated with IVH. RESULTS: Of the 5016 parents, 34.05% had IVH. Multivariate analysis showed that after adjustment for non-modifiable markers (i.e., sociodemographic, health status, and past vaccination status), being affected by negative influenza vaccine news and having higher "complacency" were positively associated with parental IVH. Higher knowledge of influenza vaccination, being recommended by healthcare workers (HCWs), people around having a positive attitude toward influenza vaccine and having higher levels of "confidence" and "convenience" were negatively associated with parental IVH. CONCLUSIONS: In China, public health education aimed at modifying vaccination-related attitudes and beliefs, as well as knowledge and societal influences, could help reduce influenza vaccination hesitancy.

Efficacy of Xinbao pill on chronic heart failure: Study protocol of a multicenter, randomized, double-blind, placebo-controlled trial.

Introduction: Chronic heart failure (CHF) is a common cardiovascular disease. In China, Xinbao pill (XBP) is widely used as an adjuvant therapy for CHF. However, there is still a lack of high-quality clinical evidence. We designed this multicenter, randomized, double-blind, placebo-controlled trial to critically evaluate the efficacy and safety of XBP as an adjuvant treatment for patients with CHF. Methods and analysis: We will recruit 284 patients with a clinical diagnosis of "heart-kidney yang deficiency syndrome" CHF receiving treatment in six hospitals in China. Patients will be randomly assigned, in a 1:1 ratio, to the treatment or control group using a central randomization system. All patients will receive conventional drug therapy for heart failure combined XBP (Guangdong Xinbao Pharmaceutical Co., Ltd., Guangdong, China) or a placebo. Study physicians, subjects, outcome assessors, and statisticians will be blinded to the group assignment. The primary outcome will be the change in the proportion of patients who show a decrease in serum NT-proBNP of more than 30% after treatment. Secondary outcomes are NYHA class, 6-minute walk distance test, Minnesota Quality of Life Scale score, endpoint events, serum NT-proBNP, echocardiographic parameters, and traditional Chinese medicine (TCM) symptom score. Adverse events will be monitored throughout the trial. Data will be analyzed according to a predetermined statistical analysis plan. Discussion: The results of this study will provide solid evidence of the safety and efficacy of XBP as an alternative and complementary treatment measure for patients with CHF. Clinical Trial Registration: Chinese Clinical Trial Registration Center (ChiCTR2000038492).

The role of Qishen Yiqi dripping pills in treating chronic heart failure: An overview of systematic reviews and meta-analyses.

Objectives: Evidence from systematic reviews/meta-analyses about the efficacy and safety of Qishen Yiqi (QSYQ) dripping pills in chronic heart failure (CHF) remains unclear. This study comprehensively reviewed available systematic reviews on latest evidence to provide reliable information for the clinical use of QSYQ in CHF. Methods: The systematic review was performed on studies retrieved from six major medical databases. Eligible studies were evaluated in terms of methodological quality and quality of evidence using the Assessment of Multiple Systematic review 2 (AMSTAR-2) tool, the Risk of Bias in Systematic Reviews (ROBIS) was used to assess the risk of bias, and the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) 2020 was utilized for assessing reporting quality. In addition, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to determine primary outcome indicators' evidence quality. Results: A total of 14 systematic reviews were included in this study, based on which it could be concluded that QSYQ combined with conventional medicine (CM) treatment tended to be superior to CM treatment alone in terms of improving cardiac function-related indices (e.g., increasing the left ventricular ejection fraction [LVEF] and reducing the left ventricular end-diastolic dimension [LVEDD] and left ventricular end-systolic internal diameter [LVESD]), improving the total effective rate and 6-min walking distance (6MWD), and reducing N-terminal pro-brain natriuretic peptide (NT-proBNP). Overall, no serious QSYQ-related adverse events were observed. However, the GRADE results showed "very low" to "moderate" evidence for these outcomes, with no high-quality evidence supporting them. Unsatisfactory results were obtained in terms of methodological quality, risk of bias and reporting quality after assessment using the AMSTAR-2, ROBIS, and PRISMA 2020, limited mainly by deficiencies in the following areas: registration of study protocols, explanation of the inclusion of randomized controlled trials (RCTs), complete and detailed search strategy, list of excluded literature, description of funding sources for inclusion in RCTs, investigation of the impact of risk of bias on the results of meta-analysis, and reporting of potential conflicts of interest. Conclusion: The efficacy and safety of QSYQ adjuvant therapy in CHF remain to be further clarified due to the lack of high-quality evidence provided by current systematic reviews.

An Update on Novel Ocular Nanosystems with Possible Benefits in the Treatment of Corneal Neovascularization.

Corneal neovascularization (CNV) is an ocular pathological change that results from an imbalance between angiogenic factors and antiangiogenic factors as a result of various ocular insults, including infection, inflammation, hypoxia, trauma, corneal degeneration, and corneal transplantation. Current clinical strategies for the treatment of CNV include pharmacological treatment and surgical intervention. Despite some degree of success, the current treatment strategies are restricted by limited efficacy, adverse effects, and a short duration of action. Recently, gene-based antiangiogenic therapy has become an emerging strategy that has attracted considerable interest. However, potential complications with the use of viral vectors, such as potential genotoxicity resulting from long-term expression and nonspecific targeting, cannot be ignored. The use of ocular nanosystems (ONS) based on nanotechnology has emerged as a great advantage in ocular disease treatment during the last two decades. The potential functions of ONS range from nanocarriers, which deliver drugs and genes to target sites in the eye, to therapeutic agents themselves. Various preclinical studies conducted to date have demonstrated promising results of the use of ONS in the treatment of CNV. In this review, we provide an overview of CNV and its current therapeutic strategies and summarize the properties and applications of various ONS related to the treatment of CNV reported to date. Our goal is to provide a comprehensive review of these considerable advances in ONS in the field of CNV therapy over the past two decades to fill the gaps in previous related reports. Finally, we discuss existing challenges and future perspectives of the use of ONS in CNV therapy, with the goal of providing a theoretical contribution to facilitate future practical growth in the area.