Small molecule tyrosine kinase inhibitors approved for systemic therapy of advanced hepatocellular carcinoma: recent advances and future perspectives.

Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death in the world, and hepatocellular carcinoma (HCC) is the most common form of liver cancer. More than half of the HCC patients are diagnosed at an advanced stage and often require systemic therapy. Dysregulation of the activity of receptor tyrosine kinases (RTKs) is involved in the development and progress of HCC, RTKs are therefore the potential targets for systemic therapy of advanced HCC (aHCC). Currently, a total of six small molecule tyrosine kinase inhibitors (TKIs) have been approved for aHCC, including first-line sorafenib, lenvatinib, and donafenib, and second-line regorafenib, cabozantinib, and apatinib. These TKIs improved patients survival, which are associated with disease stage, etiology, liver function, tumor burden, baseline levels of alpha-fetoprotein, and treatment history. This review focuses on the clinical outcomes of these TKIs in key clinical trials, retrospective and real-world studies and discusses the future perspectives of TKIs for aHCC, with an aim to provide up-to-date evidence for decision-making in the treatment of aHCC.

Machine Learning-Based Prediction of Large-for-Gestational Age Infants in Mothers with Gestational Diabetes Mellitus.

CONTEXT: Large-for-gestational-age (LGA), one of the most common complications of gestational diabetes mellitus (GDM), has become a global concern. The predictive performance of common continuous glucose monitoring (CGM) metrics for LGA is limited. OBJECTIVE: We aimed to develop and validate an artificial intelligence (AI) based model to determine the probability of women with GDM giving birth to LGA infants during pregnancy using CGM measurements together with demographic data and metabolic indicators. METHODS: A total of 371 women with GDM from a prospective cohort at a university hospital were included. CGM was performed during 20-34 gestational weeks, and glycemic fluctuations were evaluated and visualized in women with GDM who gave birth to LGA and non-LGA infants. A convolutional neural network (CNN)-based fusion model was developed to predict LGA. Comparisons among the novel fusion model and three conventional models were made using the area under the receiver-operating characteristic curve (AUCROC) and accuracy. RESULTS: Overall, 76 (20.5%) out of 371 GDM women developed LGA neonates. The visualized 24-h glucose profiles differed at midmorning. This difference was consistent among subgroups categorized by pregestational BMI, therapeutic protocol and CGM administration period. The AI based fusion prediction model using 24-h CGM data and 15 clinical variables for LGA prediction (AUCROC 0.852, 95% CI 0.680-0.966, accuracy 84.4%) showed superior discriminative power compared with the three classic models. CONCLUSIONS: We demonstrated better performance in predicting LGA infants among women with GDM using the AI based fusion model. The characteristics of the CGM profiles allowed us to determine the appropriate window for intervention.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

[Impacts of Anthropogenic Emission Reduction on Urban Atmospheric Oxidizing Capacity During the COVID-19 Lockdown].

In recent years， regional compound air pollution events caused by fine particles （PM2.5） and ozone （O3） have occurred frequently in economically developed areas of China， in which atmospheric oxidizing capacity （AOC） has played an important role. In this study， the WRF-CMAQ model was used to study the impacts of anthropogenic emission reduction on AOC during the COVID-19 lockdown period. Three representative cities in eastern China （Shijiazhuang， Nanjing， and Guangzhou） were selected for an in-depth analysis to quantify the contribution of meteorology and emissions to the changes in AOC and oxidants and to discuss the impact of AOC changes on the formation of secondary pollutants. The results showed that， compared with that in the same period in 2019， the urban average AOC in Shijiazhuang， Nanjing， and Guangzhou in 2020 increased by 60%， 48.7%， and 12.6%， respectively. The concentrations of O3， hydroxyl radical （·OH）， and nitrogen trioxide （NO3·ï¼‰ increased by 1.6%-26.4%， 14.8%-73.3%， and 37.9%-180%， respectively. The AOC in the three cities increased by 0.06×10-4， 0.12×10-4， and 0.33×10-4 min-1， respectively， due to emission reduction. The meteorological change increased AOC in Shijiazhuang and Nanjing by 20% and 17.9%， respectively， but decreased AOC in Guangzhou by -9.3%. Enhanced AOC led to an increase in the nitrogen oxidation ratio （NOR） and VOCs oxidation ratio （VOR） and promoted the transformation of primary pollutants to secondary pollutants. This offset the effects of primary emission reduction and resulted in a nonlinear decline in secondary pollutants compared to emissions during the COVID-19 lockdown.

Effect of Optimizing the Induction Regimen in Preventing Cough Reactions in Patients Undergoing General Anesthesia: A Prospective Randomized Controlled Study.

PURPOSE: During the induction of general anesthesia, opioids and endotracheal intubation may cause coughing. This study aimed to investigate the safety and effectiveness of an optimized drug induction scheme for general anesthesia to prevent coughing in patients. METHODS: A total of 220 patients aged 18 to 65 years who underwent surgery under general anesthesia with endotracheal intubation were randomly assigned to two groups, each with 110 patients. One group was administered a divided sufentanil bolus (group A) and the other with a single sufentanil bolus (group B). Anesthesia induction was performed according to the drug induction scheme of 1st, 2nd, and 3rd minutes. The primary outcome was a coughing episode associated with the administration of opioids during anesthesia induction. We also recorded the pain associated with drug injection, hemodynamics, and blood oxygen saturation during the induction of anesthesia. FINDINGS: All patients were included in the final statistical analysis. Compared with group B, the incidence of opioid induced cough (OIC) was significantly higher in group A (9.1% vs. 0, P = 0.001). There was no cough reaction of tracheal intubation in either group. There was no severe pain due to propofol and rocuronium injection in either group (P > 0.05). The mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO2) values were within the normal range at each time point during the induction period in both groups. IMPLICATIONS: According to the optimized 1st, 2nd, and 3rd minutes anesthesia induction regimen, with a single final intravenous bolus of sufentanil after the diluted rocuronium bromide administration, no sufentanil and tracheal intubation induced coughing reactions were observed. TRIAL REGISTRATION: The study protocol was registered in the Chinese Clinical Trial Registry (ChiCTR2200062749, http://www.chictr.org.cn/showproj.aspx?proj=175018) on August 17, 2022.

Fecal microbiota transplantation ameliorates abdominal obesity through inhibiting microbiota-mediated intestinal barrier damage and inflammation in mice.

Abdominal obesity (AO), characterized by the excessive abdominal fat accumulation, has emerged as a significant public health concern due to its metabolic complications and escalating prevalence worldwide, posing a more pronounced threat to human health than general obesity. While certain studies have indicated that intestinal flora contributed to diet-induced general obesity, the precise involvement of gut microbiota in the development of AO, specifically the accumulation of abdominal fat, remains inadequately explored. In this study, the 16 S rDNA sequencing was employed to analyze gut flora alterations, and the intestinal microbiota dysbiosis characterized by a vanishing decline of Akkermansia was found in the AO group. Along with notable gut microbiota changes, the intestinal mucosal barrier damage and metabolic inflammation were detected, which collectively promoted metabolic dysregulation in AO. Furthermore, the metabolic inflammation and AO were ameliorated after the intestinal microbiota depletion with antibiotics (ABX) drinking, underscoring a significant involvement of gut microbiota dysbiosis in the progression of AO. More importantly, our findings demonstrated that the transplantation of healthy intestinal flora successfully reversed the gut microbiota dysbiosis, particularly the decline of Akkermansia in the AO group. The gut flora reshaping has led to the repair of gut barrier damage and mitigation of metabolic inflammation, which ultimately ameliorated abdominal fat deposition. Our study established the role of interactions between gut flora, mucus barrier, and metabolic inflammation in the development of AO, thereby offering a theoretical foundation for the clinical application of fecal microbiota transplantation (FMT) as a treatment for AO.

Sulfate-reducing bacteria loaded in hydrogel as a long-lasting H2S factory for tumor therapy.

The continuous supply of hydrogen sulfide (H2S) gas at high concentrations to tumors is considered a promising and safe strategy for tumor therapy. However, the absence of a durable and cost-effective H2S-producing donor hampers its extensive application. Sulfate-reducing bacteria (SRB) can serve as an excellent H2S factory due to their ability to metabolize sulfate into H2S. Herein, a novel injectable chondroitin sulfate (ChS) hydrogel loaded with SRB (SRB@ChS Gel) is proposed to sustainably produce H2S in tumor tissues to overcome the limitations of current H2S gas therapy. In vitro, the ChS Gel not only supports the growth of encapsulated SRB, but also supplies a sulfate source to the SRB to produce high concentrations of H2S for at least 7 days, resulting in mitochondrial damage and immunogenic cell death. Once injected into tumor tissue, the SRB@ChS Gel can constantly produce H2S for >5 days, significantly inhibiting tumor growth. Furthermore, such treatment activates systemic anti-tumor immune responses, suppresses the growth of distant and recurrent tumors, as well as lung metastases, meanwhile with negligible side effects. Therefore, the injectable SRB@ChS Gel, as a safe and long-term, self-sustained H2S-generating factory, provides a promising strategy for anti-tumor therapy.

Association between postoperative thrombocytopenia and outcomes after traumatic brain injury surgery: A cohort study.

BACKGROUND: It is well known that thrombocytopenia occurs in patients with traumatic brain injury (TBI), and its incidence increases with the severity of injury. We aimed to determine whether postoperative thrombocytopenia in patients with TBI is associated with poor clinical outcomes. METHODS: This was a retrospective cohort study of a large international database called the Medical Information Mart for Intensive Care III (MIMIC-III), which included 1093 patients who underwent TBI surgery. Hospital mortality was the primary endpoint of this study. RESULTS: Multivariate logistic regression analysis revealed non-thrombocytopenia was significantly associated with a decreased hospital mortality (adjusted odds ratio [OR] 0.49; 95% confidence interval [CI] 0.33-0.75; p = .01). In addition, platelet counts increased over time in both survivors and non-survivors, according to generalized additive mixed model (GAMM). However, the platelet count increased more noticeably in the survivors than in the non-survivors and the difference in platelet count between the two groups showed a trend toward increasing within 7 days after surgery. This difference increased by 7.97 per day on average. CONCLUSIONS: Patients with TBI who experienced postoperative thrombocytopenia were more likely to have a poor short-term prognosis. In addition, we found that the rate of platelet growth over time varied significantly between the survival and non-survival groups. Patients with TBI who experienced a greater early increase in platelet count had a lower mortality rate.

The Full Cytosine-Cytosine Base Paring: Self-Assembly and Crystal Structure.

The synthesis of self-assembly systems that can mimic partial biological behaviours require ingenious and delicate design. For decades, scientists are committed to exploring new base pairing patterns using hydrogen bonds directed self-assembly of nucleotides. A fundamental question is the adaptive circumstance of the recognition between base pairs, namely, how solvent conditions affect the domain of base pairs. Towards this question, three nucleotide complexes based on 2'-deoxycytidine-5'-monophosphate (dCMP) and cytidine-5'-monophosphate (CMP) were synthesized in different solvents and pH values, and an unusual cytosine-cytosine base paring pattern (named full C : C base pairing) has been successfully obtained. Systematic single crystal analysis and 1 H NMR titration spectra have been performed to explore factors influencing the formation of base paring patterns. Moreover, supramolecular chirality of three complexes were studied using circular dichroism (CD) spectroscopy in solution and solid-state combined with crystal structure analysis.

Obesity is associated with postoperative outcomes in patients undergoing cardiac surgery: a cohort study.

BACKGROUND: The purpose of present study was to determine whether obesity was associated with increased adverse outcomes after cardiac surgery. METHODS: This is a retrospective cohort study from a large international database called the Medical Information Mart for Intensive Care III (MIMIC-III). Patients who underwent cardiac surgery and greater than 18 years old were divided into either nonobese (BMI < 30 kg/m2) or obese (BMI ≥ 30 kg/m2). The primary outcome of this study was 28-day mortality from the date of operation. Secondary outcomes included ICU mortality, 1-year mortality, incidence of postoperative atrial fibrillation (POAF), hospital length of stay (HOS_LOS) and ventilation-free days within 28 days (VFD_28). RESULTS: Multivariate logistic regression analysis revealed a negative effect of obesity on 28-day mortality, with an adjusted odds ratio (OR) of 1.57 (95% CI 1.14-2.16; p = 0.005). The association remained significant when PSM analysis and double robust analysis with all covariates were performed. In terms of 28-day mortality, the mediating effect of longer ventilation duration on obese patients was noticeable, and the proportion of the effect mediated was 8.2% (95% CI 2.1-25.5%; p = 0.012). CONCLUSIONS: Among patients with cardiac surgery, obesity is associated with higher 28-day mortality. The longer ventilation duration may have mediated this effect. In future, considering the elevated incidence of the obese patients undergoing cardiac surgery, obesity stat should be included as one of the predictive variables for stratification of perioperative death risk.

Alginate oligosaccharide ameliorates azithromycin-induced gut microbiota disorder via Bacteroides acidifaciens-FAHFAs and Bacteroides-TCA cycle axes.

Alginate oligosaccharide is a kind of prebiotic with broad application prospects. However, little attention is paid to the recovery effect of alginate oligosaccharide on disordered intestinal microecology caused by azithromycin. Therefore, we evaluated the regulatory effect of alginate oligosaccharide and its compound on azithromycin-disturbed gut microbiota in mice via microbiome-metabolomics analysis. The gut microbiota analysis revealed that alginate oligosaccharide and its compound significantly increased the richness and diversity of the gut microbiota which were reduced by azithromycin, with an obvious enrichment of beneficial bacteria such as the Akkermansia genus and Bacteroides acidifaciens, and a remarkable decrease of pathogenic bacteria such as the Staphylococcus genus, which indicated its impact on the gut microbiota dysbiosis. Additionally, the effect of the alginate oligosaccharide compound on regulating the gut microbiota disorder is more significant than that of alginate oligosaccharide. The favorable effects of alginate oligosaccharide were confirmed by beneficial alterations in metabolic effector molecules, which indicated that alginate oligosaccharide and its compound improved metabolic homeostasis via the Bacteroides acidifaciens-fatty acid esters of hydroxy fatty acids (FAHFAs) axis and increasing the levels of the intermediate products of the tricarboxylic acid cycle (TCA cycle), such as citric acid, fumaric acid and α-ketoglutaric acid. Spearman correlation analysis showed that the contents of these three metabolites were also positively related to Bacteroides acidifaciens and Bacteroides sartorii populations, suggesting the potential regulatory role of the Bacteroides genus in energy balance through the TCA cycle. This study may provide an innovative dietary strategy for the regulation of intestinal microecological disorders caused by antibiotics, and reveal the prospect of alginate oligosaccharide as an intestinal microecological regulator.

Near-Infrared Nano-Optogenetic Activation of Cancer Immunotherapy via Engineered Bacteria.

Certain anaerobic microbes with the capability to colonize the tumor microenvironment tend to express the heterologous gene in a sustainable manner, which will inevitably compromise the therapeutic efficacy and induce off-tumor toxicity in vivo. To improve the therapeutic precision and controllability of bacteria-based therapeutics, Escherichia coli Nissle 1917 (EcN), engineered to sense blue light and release the encoded flagellin B (flaB), is conjugated with lanthanide upconversion nanoparticles (UCNPs) for near-infrared (NIR) nano-optogenetic cancer immunotherapy. Upon 808 nm photoirradiation, UCNPs emit at the blue region to photoactivate the EcN for secretion of flaB, which subsequently binds to Toll-like receptor 5 expressed on the membrane of macrophages for activating immune response via MyD88-dependent signal pathway. Such synergism leads to significant tumor regression in different tumor models and metastatic tumors with negligible side effects. These studies based on the NIR nano-optogenetic platform highlight the rational of leveraging the optogenetic tools combined with natural propensity of certain bacteria for cancer immunotherapy.

The impact of COVID-19-related chronic disease is gradually emerging: discovery and trends from a bibliometric analysis.

OBJECTIVE: To conduct a literature survey of COVID-19-related chronic diseases to inform future research. METHODS: Publications on COVID-19 and chronic disease were retrieved from PubMed using MeSH Major Topic, including the terms COVID-19, SARS-CoV-2, Chronic Disease and Noncommunicable Diseases. Bibliometric features, journals, research areas, countries, funding agencies and citation reports, were extracted from Web of Science and highly cited papers identified and summarized. Fisher's exact probability test was used to associate highly cited papers with countries. RESULTS: A total of 1034 English-language publications were included. Urology/nephrology was the most active research area (n=230), PLOS ONE the most frequently involved journal (n=29) and the United States of America (USA) had the greatest research output (n=223). A medium number of publications were in the areas of hematology and immunology and these papers had a high citation rate. No statistically significant difference was found in the ratio of highly cited papers: total papers across high-output countries (P=0.668). The USA, Europe and China were the sources of the most highly cited articles and productive funding agencies. CONCLUSIONS: The influence of COVID-19 on chronic disease has received considerable attention. Hematology and immunology may continue to be productive research fields. Much research remains to be done to characterize the emerging chronic effects of COVID-19 on human health.

Impact of the COVID-19 pandemic on clinical trials: a cross-sectional questionnaire study in China.

Background: The number of Chinese clinical trials has continued to grow throughout the coronavirus disease 2019 (COVID-19) pandemic, but we know little about clinical trial team members' perceptions and attitudes toward the impacts of the pandemic. This study aimed to assess the impact of the COVID-19 pandemic on clinical trials in China from the perspective of research staff to provide a deeper understanding and some recommendations for the ongoing and upcoming clinical trials during the pandemic. Methods: A nationwide cross-sectional questionnaire was distributed to respondents throughout mainland China between September 2021 and October 2021. The participants assessed the impact of the COVID-19 pandemic on clinical trials based on a 5-point Likert-type scale, and exploratory factor analysis (EFA) was used to confirm the factor structure. Descriptive statistical analysis and the Mann-Whitney test were used to discover the differences between different groups. Results: A total of 2,393 questionnaires from 272 hospitals were collected in mainland China. Factor analysis resulted in 4 factors, with a cumulative explained variance of 64.93%, as follows: subject enrollment, patient care, study supplies and data management, and research milestones and quality management. The research team members, predominantly represented by clinical research coordinators (CRCs), basically agreed with all but 3 preset scenarios of the impact of COVID-19 on clinical trials. Most respondents did not agree that the pandemic was associated with more serious adverse events (SAEs), missed reports of safety events, or any increase of unscheduled unblinding. In addition, significant differences were revealed in different age, gender, and role groups of respondents based on their views on the impact of the pandemic. Conclusions: The current pandemic situation has had a negative impact on clinical trials, especially in terms of subject recruitment and protocol compliance, yet research team members feel confident that some of the effective measures proposed in the study can moderate the negative impact.

Seroepidemiology of pertussis in the east of China: Estimates of incidence of infection in adolescents and adults pre- and post-COVID-19.

Introduction: The dramatic decrease in the number of reported cases of pertussis during COVID-19 pandemic has been underestimated. The objective was to compare the estimated incidence rate of pertussis in populations pre- and post-COVID-19 pandemic by analyzing the anti-pertussis toxin (anti-PT) IgG and anti-filamentous hemagglutininant (anti-FHA) IgG antibodies in healthy Chinese population from 2018 to 2021. Methods: All serum samples (N = 1,000) were collected from healthy population (aged ≥ 15 years) who attended an annual monitoring project of antibody levels in Jiangsu province in 2018-2021 were measured by ELISA. Results: The positive rates of anti-PT IgG and anti-FHA IgG antibodies were 11.4% (114/1,000) and 20.2% (202/1,000) (≥40 IU/ml), the GMC were 17.25 (95% CI: 15.49-19.03) IU/mL and 24.94 (95% CI: 22.73-27.16) IU/mL in the study population, respectively. The percentage of participants with anti-PT IgG antibodies higher than 40 IU/mL was 5.20% (11/212) in 2018, 5.5% (19/348) in 2019, 21.2% (46/217) in 2020 and 17.0% (38/223) in 2021, respectively. The non-detectable rate (<5 IU/mL) of anti-PT IgG antibodies was 16.9, 17.7, 28.1, and 37.3% in 2018, 2019, 2020, and 2021, respectively. We assumed that the infection occurred within 58.6 days, and based on the overall proportion (2.9%) of individuals with anti-PT IgG antibody ≥100 IU/ml, the incidence rate (/100) was estimated by the formula to be 18.08 (95% CI: 12.40-26.11). In addition, the estimated incidence of Post-COVID-19 was higher than that of Pre-COVID-19 (36.33/100 vs. 12.84/100), and the difference was statistically significant (p < 0.05). Conclusions: Our results suggest a high rate of under-reporting of pertussis in Jiangsu Province both pre- and post-COVID-19 pandemic, and there are a large number of adults of childbearing age who are susceptible to pertussis. It seems imperative that vaccination of adolescents and adults should be considered for inclusion in vaccination programs.

Coordination Patterns of the Diphosphate in IDP Coordination Complexes: Crystal Structure and Chirality.

The knowledge of accurate geometrical parameters from X-ray diffraction studies in the solid state of metal nucleotide is very important for understanding the relationship between structures and properties, including biochemical processes and even enzyme-metal-substrate interactions. The research is also very necessary to precisely and controllably design the functional materials. Here, seven types of coordination polymers of inosine 5'-diphosphate nucleotide (IDP) with transition metals, {[Zn(HIDP)(azpy)(H2O)2]·4H2O}n (1), {[Cd2(IDP)2(bpda)2]·[Cd(H2O)6]·11H2O}n (2), {[Cd3(IDP)2(4,4'-bipy)2(H2O)3]·6H2O}n (3), {[Cd2(IDP)2(bpe)2(H2O)2]·(H2bpe)·26H2O}n (4), {[Cu3(IDP)2(azpy)2(H2O)5]·5H2O}n (5), {[Cu3(IDP)2(bpe)2(H2O)5]·9H2O}n (6), and {[Co(HIDP)(azpy)(H2O)2]·7H2O}n (7) [4,4'-bipy = 4,4'-bipyridine, azpy = 4,4'-azopyridine, bpe = 1,2-bis(4-pyridyl)ethene, and bpda = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene], were designed, synthesized, and firmly characterized using single-crystal X-ray diffraction. The coordination patterns of the diphosphate group of IDP in these complexes were studied by crystallographic analysis, namely, open, close, and open-close hybrid types. We have investigated the diverse coordination patterns of the diphosphate group and its spatial relationship relative to the pentose ring on the basis of two conformational parameters, the pseudorotation phase angle and the degree of puckering. Crystallographic studies clearly reveal the correlation between the backbone torsion angle (ω' and φ) of the sugar-diphosphate and the conformational preference of the pentose ring, i.e., the signs of the backbone torsion angles ω' and φ are both plus (+) or minus (-), the conformation of the pentose ring is envelope form (E), while when one of the two signs is plus (+) and the other is minus (-), the pentose ring is in the twist form (T). This is the first time elucidation of the coordination pattern of diphosphate relative to the conformation of the pentose ring in nucleotide metal complexes, which are different from the other inorganic or organic diphosphate compounds. The chirality of these coordination polymers was examined by combining solid-state circular dichroism spectroscopy measurements with the explanation of their crystal structures. The results presented in this paper are very important for understanding their nucleotide coordination chemistry, their supramolecular chemistry, and even their biochemistry.

Comparison of varicella outbreaks in schools in China during different vaccination periods.

The purpose of this study was to investigate the outbreak trend of chickenpox and the epidemiological characteristics of outbreak related cases from 2017 to 2021, and compare the impact of voluntary self-funded single dose vaccination versus mandatory two-dose vaccine vaccination on varicella outbreaks. The data of varicella outbreaks in Jiangsu Province from 2017 to 2021 come from the national public health emergency management information system. We randomly chose 70 outbreaks from 2019 to 2020 for study in order to better understand the features and regularity of breakthrough varicella(BV). In pilot cities with two doses of free VarV, the number of outbreaks decreased from 306 in 2017 to 123 in 2021, while the total number of cases related to the outbreak decreased by 64.6% (P < .01), the median size of the outbreak decreased from 24 cases (range:6-146) to 21 cases (range:10-93) (P < .01), and the incidence rate also decreased from 2.01/100 to 1.33/100. The proportion of cases with high fever, severe rash and complications in the BV group was lower than that in the primary varicella (PV), and the differences were statistically significant. The incidence rate of varicella among students who had post-exposure prophylaxis (PEP) activities was 1.42% (488/ 33,878), and 1.63% (2468/ 148,943) among those who did not (p = .005). The single-dose varicella vaccination was less effective in controlling the outbreaks, and the success of the full implementation of the routine two-dose varicella vaccination plan in the pilot cities provided a basis for implementation in the whole province, and long-term follow-up studies are needed to evaluate the effect of the new strategy in the future.

Dietary titanium dioxide particles (E171) promote diet-induced atherosclerosis through reprogramming gut microbiota-mediated choline metabolism in APOE-/- mice.

Food-grade titanium dioxide (E171) has been reported to induce changes in some intestinal metabolites related to development of atherosclerosis (AS). However, little is known about the effects of chronic dietary intake of E171 on AS development, particularly in AS-prone populations with high-choline western diet (HCD). Herein, we disclosed that E171 obviously exacerbated HCD-induced AS through increasing production of trimethylamine (TMA) and pro-atherogenic trimethylamine-N-oxide (TMAO) via remodeling gut microbiota structure in APOE-/- mice. Oral administration of 40 mg/kg E171 daily for 4 months significantly increased the atherosclerotic lesion area, especially in the HCD group. Mechanistic studies revealed that E171 induced much more TMAO production by increasing the gut microbial expression of choline TMA lyases (CutC/D), which converted dietary choline to TMA by a glycyl radical reaction. The 16S rDNA sequencing analysis demonstrated that bacterial strains expressing CutC/D were enriched by E171 in HCD-fed mice. In contrast, gut microbiota depletion eliminated the impact of E171 on choline/TMA/TMAO pathway and AS progression, indicating gut flora shifts were responsible for the exacerbation effects of E171 ingestion on HCD-induced AS. All the results emphasized the alarming role of E171 on AS progression and stated the importance of reevaluating the impact of food additives on the development of chronic diseases.

Airborne particle number concentrations in China: A critical review.

Particle number concentration (PNC) is an important parameter for evaluating the environmental health and climate effects of particulate matter (PM). A good understanding of PNC is essential to control atmospheric ultrafine particles (UFP) and protect public health. In this study, we reviewed the PNC studies in the literature aimed to gain a comprehensive understanding about the levels, trends, and sources of PNC in China. The PNC levels at the urban, suburban, rural, remote, and coastal sites in China were 8500-52,200, 8600-30,300, 8600-28,400, 2100-16,100, and 5700-19,600 cm-3, respectively. The wide ranges of PNC indicate significant heterogeneity in the spatial distribution of PNC, but also are partly due to the different measurement techniques deployed in different studies. In general, it still can be concluded that the PNC levels at urban > suburban > rural > coastal > remote sites. Except for Mt. Waliguan (a remote site of 3816 m a.s.l.), other cities had the highest PNC in spring or winter and the lowest in summer or autumn. Long-term changes of PNCs in Beijing and Nanjing indicated that PNCs of Nucleation and Aitken modes had substantially declined following stricter emission controls in recent years, but more frequent new particle formation (NPF) events were observed due to reduction in coagulation sink. Overall, traffic emission was the most dominant source of PNC in more than 94.4% of the selected cities around the world, while combustion2 (the energy production and industry related combustion source), background aerosol, and nucleation sources were also important contributors to PNC. This study provides insights about PNC and its sources around the world, especially in China. A few recommendations were suggested to further improve the understanding of PNC and to develop effective PNC control strategies.

Controlled supramolecular interaction to enhance the bioavailability of hesperetin to targeted cancer cells through graphyne: a comprehensive in silico study.

In the current study, the drug carrier efficiency of graphyne (GRP) for the transfer of the hesperetin (HPT) drug is evaluated for the first time. The GRP efficacy as a carrier is investigated using the density functional theory (DFT) technique to calculate various physiochemical characteristics such as dipole moment, bandgap, and chemical reactivity-descriptors for HPT, GRP and HPT@GRP complex. The non-covalent-interaction (NCI) plot indicated that GRP and HPT have weak interaction force, which is fundamental for the drug's noticeable offloading from the GRP carrier at its target location. According to frontier molecular orbital analysis, the highest occupied molecular orbital (HOMO) of HPT distributes the charge to the GRP, the lowest unoccupied molecular orbital (LUMO) during excitation. Charge transfer is further supported by charge-decomposition-analysis, which interprets the extensive overlap between HPT and GRP orbitals. In the case of the gas phase, the λ max of the HPT@GRP-complex is redshifted by 9 nm from GRP. In the solvent phase, the λ max value is also redshifted. These theoretically calculated spectra also match experimentally observed spectra rather well. The PET (photoinduced electron-transfer) method and electron-hole theory were used for the graphical explication of distinct excited states. The photoinduced electron transfer (PET) mechanism interprets fluorescence dimming because of interaction. Furthermore, GRP with cationic (+1) and anionic (-1) charge states (GRP+1/-1) showed minor structural disfigurement and formed stable HPT complexes. In the current study, HRP is loading and unloading on GRP very effectively, that can potentially be used in the oncology field. Due to this theoretical study, researchers will be interested in looking at other 2D nanomaterials for drug delivery applications.