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Background: Little is known about the relationship between sleep quality and lung cancer incidence. Thus, this study was conducted to investigate the potential connection between sleep quality and lung cancer incidence., Methods: We performed and selected a nested case-control study that included 150 lung cancer cases and 150 matched controls based on the Lianyungang cohort. Univariate and multivariate logistic regression was utilized to investigate the connection between potential risk factors and lung cancer incidence risk., Results: In this study, the average age of participants was 66.5 ± 9.1 years, with 58.7% being male, and 52.7% reportedly experiencing sleep quality problems. The results of multivariate logistic regression showed that poor sleep quality was connected to an increased lung cancer incidence risk ( P = 0.033, odds ratio = 1.83, 95% confidence interval = [1.05-3.19]) compared with those with good sleep quality. The stratified analyses showed a significantly positive connection between poor sleep quality ( vs . good sleep quality) and cancer risk in smokers ( vs . non-smoker, P for interaction = 0.085). The combined effect analysis indicated that smokers with poor sleep quality suffered from a 2.79-fold increase in cancer incidence rates when compared with non-smokers with good sleep quality., Conclusions: Poor sleep quality was positively connected to an increased lung cancer incidence risk. In addition, among those individuals with poor sleep quality, smoking increased the lung cancer incidence risk., Competing Interests: Yun Song is employed by Shenzhen AUSA Pharmed Co Ltd. All authors declare that they have no competing interests., (© 2023 Ruan et al.)

The Asian community - the second largest non-European ethnic community in New Zealand - plays an important role in combatting the COVID-19 pandemic, evidenced by their active advocation for border control and mass masking. Despite the long history of racial discrimination against the Asian population, the Asian community has experienced certain degrees of racial discrimination associated with the stigmatisation as the cause of the COVID-19 outbreak in New Zealand. Based on data from a quantitative online survey with 402 valid responses within the Asian communities across New Zealand and the in-depth interviews with 19 Asian people in Auckland, New Zealand, this paper will illustrate Asian people's experience of racial discrimination and stigmatisation during the pandemic in the country. The survey shows that since the outbreak of COVID-19, under a quarter of the participants reported experiencing discrimination, and a third reported knowing an immediate contact who had experienced discrimination. However, when looking beyond their immediate social circle, an even higher proportion reported noticing racism and stigmatisation through the traditional or social media due to COVID-19. Major variations of the degree of racial discrimination experienced are determined by three demographic variables: ethnicity, age, and region. The in-depth interviews largely echoed the survey findings and highlighted a strong correlation between the perceived racial discrimination among the local Asian community and the stigmatisation associated with COVID-19. These findings are important for improving the way we manage future pandemics and other disasters within the context of the UN Sendai Framework for Disaster Risk Reduction., (© 2022. The Author(s).)

Per- and polyfluoroalkyl substances (PFAS) have attracted worldwide attention as one of persistent organic pollutants; however, there is limited knowledge about the exposure concentrations of PFAS-contained ambient particulate matter and the related health risks. This study investigated the abundance and distribution of 32 PFAS in fine particulate matter (PM 2.5 ) collected from 93 primary or secondary schools across the Pearl River Delta region (PRD), China. These chemicals comprise four PFAS categories which includes perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkyl sulfonic acids (PFSAs), perfluoroalkyl acid (PFAA) precursors and PFAS alternatives. In general, concentrations of target PFAS ranged from 11.52 to 419.72 pg/m 3 (median: 57.29 pg/m 3 ) across sites. By categories, concentrations of PFSAs (median: 26.05 pg/m 3 ) were the dominant PFAS categories, followed by PFCAs (14.25 pg/m 3 ), PFAS alternatives (2.75 pg/m 3 ) and PFAA precursors (1.10 pg/m 3 ). By individual PFAS, PFOS and PFOA were the dominant PFAS, which average concentration were 24.18 pg/m 3 and 6.05 pg/m 3 , respectively. Seasonal variation showed that the concentrations of PFCAs and PFSAs were higher in winter than in summer, whereas opposite seasonal trends were observed in PFAA precursors and PFAS alternatives. Estimated daily intake (EDI) and hazard quotient (HQ) were used to assess human inhalation-based exposure risks to PFAS. Although the health risks of PFAS via inhalation were insignificant (HQ far less than one), sufficient attention should be levied to ascertain the human exposure risks through inhalation, given that exposure to PFAS through air inhalation is a long term and cumulative process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To study the influence of steroid withdrawal protection strategy on height growth in pediatric patients after kidney transplantation. Methods: The prospective cohort study enrolled 40 stage 5 chronic kidney disease children receiving kidney transplantation from July 2017 to September 2022 at Guangzhou Women and Children's Medical Center. Based on the primary preoperative disease, patients with immune abnormality-associated glomerular diseases or unknown causes were assigned to the steroid maintenance group, in which patients received steroid tapering within 3 months after surgery to a maintenance dose of 2.5 to 5.0 mg/d. While patients with hereditary kidney disease or congenital urinary malformations were assigned to the steroid withdrawal group, in which patients had steroids tapered off within 3 months. The characteristics of height catch-up growth and clinical data were compared between the 2 groups at baseline, 6, 12, 18 and 24 months after kidney transplantation. T-test, repeated measurement of variance analysis, Mann-Whitney U test, and Fisher exact test were used for the comparison between the 2 groups. Results: Among the 40 children, 17 were males, 23 were females, 25 were in the steroid withdraw group ((7.8±2.8) years old when receiving kidney transplantation) and 15 cases were in the steroid maintenance group ((7.6±3.5) years old when receiving kidney transplantation). The study population was followed up for (26±12) months. The total dose per unit body weight of steroids in the steroid withdrawal group was lower than that in the steroid maintenance group ((0.13±0.06) vs. (0.36±0.19) mg/(kg·d), t =5.83, P <0.001). The height catch-up rate (ΔHtSDS) in the first year after kidney transplantation in the steroid withdraw and steroid maintenance groups was 1.0 (0.7, 1.4) and 0.4 (0.1, 1.0), respectively; in the second year, the ΔHtSDS in the steroid withdraw group was significantly higher than that in the steroid maintenance group (1.1 (0.2, 1.7) vs . 0.3 (0, 0.8), U =28.00, P= 0.039). The HtSDS in the steroid withdrawal group at the five follow-up time points was -2.5±0.8, -2.0±0.8, -1.5±0.8, -1.3±0.9 and -0.5±0.3, respectively, while in the steroid maintenance was -2.4±1.3, -2.2±1.1, -2.0±1.0, -1.8±1.0 and -1.6±1.0, respectively. There were statistically significant differences in HtSDS at different follow-up time points in both 2 groups ( F= 19.81, P <0.01), but no statistical differences in overall impact between the 2 groups ( F= 1.13, P= 0.204). The steroid treatment was interaction with the increase of follow-up time ( F= 3.62, P= 0.009). At the 24 th month after transplantation, the HtSDS in the steroid withdrawal group was significantly higher than that in the steroid maintenance group ( P= 0.047). Six patients in the steroid withdrawal group experienced antibody-mediated immune rejection (AMR), while 3 did in the steroid maintenance group. Moreover, there was no significant difference in AMR between the two groups ( χ 2 =0.06, P= 0.814). Conclusion: The steroid withdrawal protection strategy favors the height catch-up growth in pediatric patients after kidney transplantation and does not increase the risk of postoperative antibody-mediated immune rejection.

Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. Keratinocyte dysfunction plays a central role in AD development. MicroRNA is a novel player in many inflammatory and immune skin diseases. In this study, we investigated the potential function and regulatory mechanism of miR-193b in AD. Inflamed human keratinocytes (HaCaT) were established by tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation. Cell viability was measured using MTT assay, while the cell cycle was analyzed using flow cytometry. The cytokine levels were examined by enzyme-linked immunosorbent assay. The interaction between Sp1, miR-193b, and HMGB1 was analyzed using dual luciferase reporter and/or chromatin immunoprecipitation (ChIP) assays. Our results revealed that miR-193b upregulation enhanced the proliferation of TNF-α/IFN-γ-treated keratinocytes and repressed inflammatory injury. miR-193b negatively regulated high mobility group box 1 (HMGB1) expression by directly targeting HMGB1. Furthermore, HMGB1 knockdown promoted keratinocyte proliferation and inhibited inflammatory injury by repressing nuclear factor kappa-B (NF-κB) activation. During AD progression, HMGB1 overexpression abrogated increase of keratinocyte proliferation and repression of inflammatory injury caused by miR-193b overexpression. Moreover, transcription factor Sp1 was identified as the biological partner of the miR-193b promoter in promoting miR-193b expression. Therefore, Sp1 upregulation promotes keratinocyte proliferation and represses inflammatory injury during AD development via promoting miR-193b expression and repressing HMGB1/NF-κB activation., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Most current surgical navigation methods rely on optical navigators with images displayed on an external screen. However, minimizing distractions during surgery is critical and the spatial information displayed in this arrangement is non-intuitive. Previous studies have proposed combining optical navigation systems with augmented reality (AR) to provide surgeons with intuitive imaging during surgery, through the use of planar and three-dimensional imagery. However, these studies have mainly focused on visual aids and have paid relatively little attention to real surgical guidance aids. Moreover, the use of augmented reality reduces system stability and accuracy, and optical navigation systems are costly. Therefore, this paper proposed an augmented reality surgical navigation system based on image positioning that achieves the desired system advantages with low cost, high stability, and high accuracy. This system also provides intuitive guidance for the surgical target point, entry point, and trajectory. Once the surgeon uses the navigation stick to indicate the position of the surgical entry point, the connection between the surgical target and the surgical entry point is immediately displayed on the AR device (tablet or HoloLens glasses), and a dynamic auxiliary line is shown to assist with incision angle and depth. Clinical trials were conducted for EVD (extra-ventricular drainage) surgery, and surgeons confirmed the system's overall benefit. A "virtual object automatic scanning" method is proposed to achieve a high accuracy of 1 ± 0.1 mm for the AR-based system. Furthermore, a deep learning-based U-Net segmentation network is incorporated to enable automatic identification of the hydrocephalus location by the system. The system achieves improved recognition accuracy, sensitivity, and specificity of 99.93%, 93.85%, and 95.73%, respectively, representing a significant improvement from previous studies.

Aim: Asians are the second largest and fastest growing non-European population in New Zealand but are under-researched in terms of their COVID-19 pandemic response. The paper aims to illustrates Asians' risk perceptions and knowledge of COVID-19, and self-protection practices to avoid infection and prevent community transmission., Subject and Methods: An online survey was used to collect data and received 402 valid responses. Data analyses included: 1) a descriptive analysis by using Chi -square tests and a Kruskal-Wallis rank sum tests to explore associations between responses and the four demographic variables (i.e. age, gender, country of origin/ethnicity, and region); and 2) a correlation analysis between different survey objectives., Results: The descriptive analysis of the survey found that while ethnicity (within the Asian category) was the most influential variable that resulted in varying responses to many questions, gender and age were other two important variables in influencing the answering patterns. The correlation analysis found a positive correlation between the perceived 'dangerousness' of COVID-19 and respondents' overall compliance behaviour to New Zealand authorities' recommendations to prevent spread of COVID-19., Conclusion: The majority of the respondents provided correct answers to the questions about the vulnerable populations, symptoms, asymptomatic transmission and potential sequelae of COVID-19; however, their understanding of the availability of a cure for, and the incubation period of COVID-19 was not consistent with the official information. The research also found that the higher perceived dangerousness of COVID-19, the better compliance to self-protection practices among the surveyed population., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial conflict of interests to disclose. Submission declaration and verification: The work has not published previously and submitted to any other journal., (© The Author(s) 2023.)

An increasing number of studies have shown that USP9X is closely related to cancer. However, its role in carcinogenesis and progression of laryngeal cancer has not yet been investigated. In this study, we found that USP9X was upregulated in laryngeal cancer tissues. The expression of USP9X was significantly correlated with degree of laryngeal cancer differentiation and lymphatic metastasis. USP9X knockdown led to a decrease in the ability of proliferation, migration, and invasion of FaDu cells. The proportion of FaDu apoptotic cells increased by interfering with the endogenous expression of USP9X. We speculated that inhibiting USP9X might induce apoptosis in FaDu cells by downregulating Mcl-1 and upregulating Bax protein expression. Our findings for the first time suggest the expression level and trend of USP9X in laryngeal cancer tissue and USP9X may plays an important role in promoting the occurrence and progression of laryngeal cancer. USP9X may be a potential target for intervention in treatment of laryngeal cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Heart failure (HF) is a complex clinical syndrome caused by various cardiovascular diseases. Its main pathogenesis includes cardiomyocyte loss, myocardial energy metabolism disorder, and activation of cardiac inflammation. Due to the clinically unsatisfactory treatment of heart failure, different mechanisms need to be explored to provide new targets for the treatment of this disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene mainly related to familial hypercholesterolemia, was discovered in 2003. Aside from regulating lipid metabolism, PCSK9 may be involved in other biological processes such as apoptosis, autophagy, pyroptosis, inflammation, and tumor immunity and related to diabetes and neurodegenerative diseases. Recently, clinical data have shown that the circulating PCSK9 level is significantly increased in patients with heart failure, and it is related to the prognosis for heart failure. Furthermore, in animal models and patients with myocardial infarction, PCSK9 in the infarct margin area was also found to be significantly increased, which further suggested that PCSK9 might be closely related to heart failure. However, the specific mechanism of how PCSK9 participates in heart failure remains to be further explored. The purpose of this review is to summarize the potential mechanism of PCSK9's involvement in heart failure, thereby providing a new treatment strategy for heart failure., Competing Interests: Conflict of interest statement The authors declare no conflict of interest, financial or otherwise., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In this study, we synthesized two phosphoramidites based on 2,7-bis-{4-nitro-8-[3-(2-propyl)-styryl]}-9,9-bis-[1-(3,6-dioxaheptyl)]-fluorene (BNSF) and 4,4'-bis-{8-[4-nitro-3-(2-propyl)-styryl]}-3,3'-di-methoxybiphenyl (BNSMB) structures as visible light-cleavable linkers for oligonucleotide conjugation. In addition to the commercial ultraviolet (UV) photocleavable (PC) linker, the BNSMB linker was further applied as a building component to construct photoregulated DNA devices as duplex structures, which are functionalized with fluorophores and quenchers. Selective cleavage of PC and BNSMB is achieved in response to ultraviolet (UV) and visible light irradiations as two inputs, respectively. This leads to controllable dissociation of pieces of DNA fragments, which is followed by changes of fluorescence emission as signal outputs of the system. By tuning the number and position of the photocleavable molecules, fluorophores, and quenchers, various DNA devices were developed, which mimic the functions of Boolean logic gates and achieve logic operations in AND, OR, NOR, and NAND gates in response to two different wavelengths of light inputs. By sequence design, the photolysis products can be precisely programmed in DNA devices and triggered to release in a selective and/or sequential manner. Thus, this photoregulated DNA device shows potential as a wavelength-dependent drug delivery system for selective control over the release of multiple individual therapeutic oligonucleotide-based drugs. We believe that our work not only enriches the library of photocleavable phosphoramidites available for bioconjugation but also paves the way for developing spatiotemporal-controlled, orthogonal-regulated DNA-based logic devices for a range of applications in materials science, polymers, chemistry, and biology.

Objective: To investigate the associations between 24-hour urinary sodium excretion (24hUNaE) and all-cause mortality in adult Northern Chinese population. Methods: Data from this study were derived from the prospective urban and rural epidemiology (PURE) study in north China. Baseline information of all participants were obtained by face to face interview through trained research staffs based on questionnaires, and morning fasting urine samples of participants were collected to estimate 24hUNaE and 24-hour potassium excretion (24hUKE). Multivariable frailty Cox regression models were used to explore the association between 24hUNaE (<3.00, 3.00-3.99, 4.00-4.99, 5.00-5.99 and ≥6 g/d) and all-cause death. Results: A total of 27 310 participants were included in this study. The mean 24hUNaE was (5.84±1.73) g/d. After a median follow-up of 8.8 years, 1 024 participants died (3.7%), including 390 cardiovascular related deaths and 591 non-cardiovascular related deaths. The cause of death of the remaining patients could not be determined. Using 24hUNaE level of 4.00-4.99 g/d as the reference group, after fully adjustment, 24hUNaE ≥6.00 g/d was associated with an increased risk of all-cause death ( HR =1.24, 95% CI : 1.02-1.49) and cardiovascular related death ( HR =1.39, 95% CI : 1.02-1.88). 24hUNaE<3.00 g/d was associated with increased risk of all-cause mortality ( HR =1.38, 95% CI : 0.96-1.99). There was no significant association between 24hUNaE and non-cardiovascular related death. Furthermore, using the combination of 24hUNaE 4.00-4.99 g/d and 24hUKE≥2.11 g/d as the reference group, the highest risk occurred in participants with the combination of low sodium (<3.00 g/d) and low potassium (<2.11 g/d). Conclusion: 24hUNaE equal or higher than 6 g/d or lower than 3 g/d is associated with increased risk of all-cause mortality and cardiovascular related death in Northern Chinese population. Besides, moderate sodium intake in combination with increased potassium intake might reduce the risk of all-cause death.

Tumor cells activate DNA repair pathways to combat the oxidative damage induced by reactive oxygen species (ROS), contributing to their resistance to photodynamic therapy (PDT). Herein, a self-delivery photodynamic sensitizer is developed to enhance oxidative damage by blocking the DNA repair pathway through poly(ADP-ribose) polymerase (PARP) inhibition. Specifically, the photodynamic sensitizer (CeOla) is constructed based on the self-assembly of the photosensitizer chlorine e6 (Ce6) and the PARP inhibitor olaparib (Ola). Of note is that carrier free CeOla has a high drug content and favorable water stability, which could be effectively internalized by tumor cells for robust PDT upon light irradiation. Moreover, CeOla could inhibit the activation of PARP, promote the upregulation of γ-H2AX and reduce the expression of Rad51, thereby blocking the DNA repair pathway to sensitize tumor cells for PDT. As a consequence, the self-delivery CeOla greatly promotes the tumor cell apoptosis and shows a high antitumor performance with low side effects. It serves as a novel platform for the development of self-delivery nanomedicine to overcome oxidative resistance in tumor treatment.

Rationale: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various types of cancers worldwide, which is the most significant breakthrough in cancer therapy in recent years. Despite their excellent benefits in anti-tumor efficacy, a subset of patients will experience various autoimmune toxicities, termed as immune-related adverse events (irAEs), which can affect almost any organ systems, but related to the pulmonary and pancreatic islets simultaneously has rarely been reported and discussed., Patient Concerns: In this report, we describe a rare case of a 65-year-old man patient with advanced small cell lung cancer (SCLC) who suffered general fatigue, dry cough, chest tightness, shortness of breath and polyuria-polydipsia syndrome after the eighth cycle treatment with programmed cell death ligand-1 (PD-L1) inhibitor durvalumab., Diagnoses: According to the results of laboratory tests, chest computed tomography and multidisciplinary discussion, the patient was eventually diagnosed with ICI-related pneumonitis and autoimmune diabetes mellitus., Interventions: Multiple daily subcutaneous insulin injections, empirical anti-infection and immunosuppression treatment with corticosteroids were performed., Outcomes: After the cessation of durvalumab and comprehensive treatment, the patient's respiratory condition was relieved significantly and his blood glucose was well controlled with insulin therapy., Lessons: With the widespread use of ICIs, there will be more patients developing these rare but severe irAEs in clinical practice, which should attract great attention of both clinicians and patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Outbreaks caused by highly industrialized food companies are characterized by cross-border, trans-regional, rapid and unpredictable, related to serious disease and economic burden. A cluster of cases with monophasic s almonella enterica serovar Typhimurium ST34 infection suspected to be associated with consumption of contaminated chocolate products have been reported in several Europe countries since December 2021. After retrospective investigations, the buttermilk circuit in the Belgian factory was suspected to be the point of origin of the contamination. This outbreak could provide a reference for the risk management of foodborne pathogens contamination in China. The objective of this paper was to summarize the process and characteristics of the outbreak of monophasic S. Typhimurium caused by contaminated chocolate products, analyze the characteristics of ST34 monophasic S. Typhimurium and the microbial management measures in the process of chocolate products, and systematically discuss the suggestions for the risk management of foodborne pathogens contamination and countermeasures for the rapid development of industrialization of food enterprises in China, in order to provide scientific and technological support for the prevention and control, prediction and early warning of sudden cases in China.

Accurate and non-invasive monitoring of allograft posttransplant is essential for early detection of acute cellular rejection and determines the long-term survival of the graft. Clinically, tissue biopsy is the most effective approach for diagnosing transplant rejection. Nonetheless, the procedure is invasive and potentially triggers organ failure. This work aims to design and apply GzmB-responsive nanosensors (GBRNs) that can readily size-change in graft tissues. Subsequently, we investigate the activity of serine protease granzyme B by generating a direct colorimetric urinary readout for non-invasive detection of transplant rejection in under 1 h. In preclinical heart graft mice models of transplant rejection, GBRNs were cleaved by GzmB and excreted by the kidneys via accurate nanometre-size glomerular filtration. By exploiting the catalytic activity of ultrasmall gold nanoclusters, GBRNs urinalysis promotes ultrasensitive surveillance of rejection episodes with a receiver operator characteristic curve area under the curve of 0.896 as well as a 95% confidence interval of about 0.7701-1.000. Besides, the catalytic activity of gold nanoclusters in urine can be detected at point-of-care testing to predict the immunity responses in mice with insufficient immunosuppressive therapy. Therefore, this non-invasive, sensitive, and quantitative method is a robust and informative approach for rapid and routine monitoring of transplant allografts without invasive biopsy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: While studies have suggested the association between triglyceride-glucose (TyG) index, a reliable surrogate for insulin resistance and hypertension data are limited to the correlation of TyG and central blood pressure. This study aims to test the hypothesis that a higher TyG index is associated with elevated central systolic blood pressure (cSBP)., Methods: A total of 9249 Chinese hypertensive adults from the H-type Hypertension and Stroke Prevention and Control Project were analyzed in this study. cSBP was measured noninvasively using an A-Pulse CASPro device. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Smoothing curve and multivariate linear regression models [beta coefficient (β) with 95% CI] were applied to analyze the association between TyG index and cSBP. Subgroup analyses were conducted to explore potential modifications to such a correlation., Results: The overall mean TyG index is 8.8 ± 0.7, and the total mean cSBP is 131.3 ± 12.8 mmHg. TyG index was observed to be independently and positively associated with cSBP among the total population (β = 0.92, 95% CI: 0.53-1.31, P < 0.001), and participants who do not use antihypertensive drugs (β = 1.03, 95% CI: 0.46-1.60, P < 0.001), which is in accordance with the result of the smoothing curve. The association between TyG index and cSBP appears robust in all tested subgroups., Conclusions: TyG index is positively and independently associated with cSBP among hypertensive adults. Our study result suggests that TyG index might serve as an effective marker for vascular function., (© 2022 JGC All rights reserved; www.jgc301.com.)

Objective: To observe the clinical effect of acupotomy combined with warm needling on cervical spondylotic radiculopathy (CSR) of qi and blood stagnation syndrome., Methods: A total of 90 CSR patients were randomly divided into an acupotomy group, a warm needling group and a combined treatment group, with 30 cases in each group. The patients in the acupotomy group were treated with acupotomy, once every 7 days, consecutively for 3 times. The patients in the warm needling group received warm needling, once daily, at the interval of 2 days after consecutive treatments for 5 days, 7 days as one session of treatment and 3 consecutive sessions were required. The patients in the combined treatment group were treated with acupotomy and warm needling, and the methods and the treatment session were same as the the previous two groups. Before and after the treatment, the pain rating index (PRI) of McGill pain questionnaire (MPQ) and the 20-point scale of CSR developed by Yasuhisa Tanaka (CSR20) were adopted in the assessment. The changes of clinical symptoms and functions of patients were observed and the clinical efficacy was assessed in each group., Results: After the treatment, the PRI score was decreased ( P <0.05) and the CSR20 score was increased ( P <0.05) in the 3 treatment groups when compared with those before the treatment. After the treatment, compared with the acupotomy group and the warm needling group, the PRI score was decreased ( P <0.05) and the CSR20 score was increased ( P <0.05) in the combined treatment group. The total effective rate was 83.3% (25/30) in the acupotomy group, 76.7% (23/30) in the warm needling group and 93.3% (28/30) in the combined treatment group. The total effective rate in the combined treatment group was higher than those in the acupotomy group and the warm needling group ( P <0.05)., Conclusion: The combined treatment with acupotomy and warm needling may obviously improve the clinical symptoms and physical signs, e.g. pain and numbness in the patients with CSR of qi and blood stagnation syndrome. Its efficacy is remarkably higher than that of the simple application of acupotomy or warm needling.

In September 2021, Immigration New Zealand (INZ) announced the offer of a one-off residence visa category - the 2021 Resident Visa, to over 165,000 temporary migrant workers and their family members living in the country. The offer was a response to the backlog and growing numbers of applications that INZ was unable to attend to largely because of the lockdown during the COVID-19 pandemic. Drawing on relevant statistical data, news media reports and available academic publications, this research note examines how New Zealand's sanitization policies during the pandemic affected the lives of temporary migrant workers who hold various work visas., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© Scalabrini Migration Center 2022.)

A novel strategy utilizing the quartz crystal microbalance (QCM) was developed for the in situ discrimination of polymorphic nucleation (form-I and form-II) and phase transformation of sulfamerazine (SMZ) in cooling crystallization. According to Ostwald's rule of stages, metastable form-I of SMZ is first nucleated and then shifted to stable form-II by solution-mediated phase transformation. Through surface modification with the self-assembled monolayer technique of a functional group, QCM distinctively detects the formation of the two polymorphs. The results indicated that -NH 2 (among the several functional groups tested) selectively accommodated stable form-II on the QCM sensor's surface and completely prevented the adsorption of metastable form-I on the surface. Therefore, the-NH 2 -terminated QCM detected the formation of form-I only using the solution viscosity variation on the surface. However, it monitored the nucleation and growth of form-II via the solid mass change on the surface during the phase transformation of form-I to form-II. This strategy suggests a new and precise solution for in situ discrimination of SMZ polymorphs and their phase transformation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hydrogen sulfide (H 2 S), a gas transmitter found in eukaryotic organisms, plays an essential role in several physiological processes. H 2 S is one of the three primary biological gas transmission signaling mediators, along with nitric oxide and carbon monoxide. Several animal and in vitro experiments have indicated that H 2 S can prevent coronary endothelial mesenchymal transition, reduce the expression of endothelial cell adhesion molecules, and stabilize intravascular plaques, suggesting its potential role in the treatment of atherosclerosis (AS). H 2 S donors are compounds that can release H 2 S under certain circumstances. Development of highly targeted H 2 S donors is a key imperative as these can allow for in-depth evaluation of the anti-atherosclerotic effects of exogenous H 2 S. More importantly, identification of an optimal H 2 S donor is critical for the creation of H 2 S anti-atherosclerotic prodrugs. In this review, we discuss a wide range of H 2 S donors with anti-AS potential along with their respective transport pathways and design-related limitations. We also discuss the utilization of nano-synthetic technologies to manufacture H 2 S donors. This innovative and effective design example sheds new light on the production of highly targeted H 2 S donors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Deng, Tian, Liu, Wang, Wei, Liu and Jiang.)

Background: The cardiovascular hazards of total homocysteine (tHcy) are long known. In addition, despite the acknowledgment on the importance of low ankle-brachial index (ABI) (< 0.9), borderline ABI (0.91-0.99) was once commonly overlooked. This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population., Methods: This study included 10,538 participants from China H-type Hypertension Registry Study. ABI was described into two groups: normal ABI (1.00-1.40) and borderline ABI. tHcy level was also divided into two groups: < 15.02 and ≥ 15.02 μmo/L. Four groups were analyzed, using COX proportional hazard regression model, separately and pairwise to observe the independent and joint effect on all-cause death., Results: A total of 126 (1.2%) deaths were observed in the 1.7 years follow-up time. Borderline ABI has a higher predicted risk of death than normal ABI (HR = 1.87, 95%CI: 1.17-3.00) after adjusting for potential covariates. Compare with tHcy level < 15.02 μmo/L (low tHcy), those with tHcy ≥ 15.02 μmo/L (high tHcy) had higher risk to event outcome (HR = 1.99, 95% CI: 1.30-3.05). According to the cumulative hazard curve, group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups. Among those with borderline ABI, participants with high tHcy had higher death risk than those with low tHcy, nevertheless, no significant different between borderline and normal ABI among those with low tHcy levels., Conclusions: Borderline ABI and tHcy level both have independent predictive value on all-cause death. The combined group of borderline ABI and high tHcy has highest risk factor of outcomes, which suggested the mutual additive value of borderline ABI and tHcy. More attention should be given to the importance of borderline ABI in hypertensive population, especially with elevated tHcy level., Competing Interests: None., (© 2022 JGC All rights reserved; www.jgc301.com.)

Over more than three decades New Zealand (NZ) has abolished its racially-biased immigration policy and changed to select immigrants based on personal merits, since 1997 new Chinese immigrants from China have become the second-largest immigrant group in NZ. Reflecting the rapid changes in Mainland Chinese society, different waves of Chinese immigrants have arrived in NZ during the past three decades, each carrying distinctive characteristics. Despite the magnitude of this immigrant population both globally and in NZ, the subethnicities of these immigrants have never been conceptualised theoretically. Based on the digitally- enhanced research techniques together with ethnographically-based study, the paper aims to remedy this research gap in Chinese diaspora studies. Two theoretical concepts are used in this research. The first is the concept of sub-ethnicity which refers to finer boundaries drawn within an ethnic group by nationality, language, region of origin, class, or other distinctions. The second is the concept of ethnoburb - a model of ethnic settlement where the suburban ethnic communities and clusters of associated residential areas and business districts in large metropolitan cities are highly concentrated. This research considers these two concepts are correlated to each other since certain ethnoburb has particular attraction to certain sub-ethnic group; and vice versa, certain subethnic group intends to gather in same ethnoburb unintentionally or unconsciously. Applying these concepts, the research considers Albany as an example of a distinctive Chinese ethnoburb for the China-born new immigrants, especially for the most recent arrivals. The paper makes theoretical contribution to understand the complementarity between these two concepts and their methodological implementation towards studying new Chinese migration., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Three undescribed isoindoline alkaloids, (+)-(R)-3-butyl-3-ethoxyisoindolin-1-one, (+)-(3S,6S,7R)-3-butyl-6,7-dihydroxy-3-methoxy-4,5,6,7-tetrahydroisoindolin-1-one, and (-)-(3R,6S,7R)-3-butyl-6,7-dihydroxy-3-methoxy-4,5,6,7-tetrahydroisoindolin-1-one, along with nine known phthalides were isolated from a water decoction of the rhizomes of Ligusticum chuanxiong using chromatographic methods. Their structures and absolute configurations were determined by extensive spectroscopic analyses and ECD data calculations. The relaxant effects of the isolated compounds on uterine contractions induced by oxytocin were investigated using a rat uterine smooth muscle contraction model. Furthermore, the effects of riligustilide on extracellular Ca 2+ influx and intracellular Ca 2+ release were assessed using high-KCl solution-induced and oxytocin-induced uterine smooth muscle contraction in a Ca 2+ -free balanced salt solution. The results showed that all the tested phthalides had inhibitory effects on oxytocin-induced uterine smooth muscle contraction. Riligustilide, a phthalide dimer, was the most active. Further examinations indicated that riligustilide reduced uterine smooth muscle contraction by inhibiting extracellular Ca 2+ influx and intracellular Ca 2+ release., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aim: The 20(S)-ginsenoside Rh2 (Rh2) is being developed as a new antitumor drug. However, to date, little is known about the kinetics of its deglycosylation metabolite (protopanoxadiol) (PPD) following Rh2 administration. The aim of this work was to 1) simultaneously characterise the pharmacokinetics of Rh2 and PPD following intravenous and oral Rh2 administration, 2) develop and validate a mechanism-based pharmacokinetic model to describe the deglycosylation kinetics and 3) predict the percentage of Rh2 entering the systemic circulation in PPD form. Methods: Plasma samples were collected from rats after the I.V. or P.O. administration of Rh2. The plasma Rh2 and PPD concentrations were determined using HPLC-MS. The transformation from Rh2 to PPD, its absorption, and elimination were integrated into the mechanism based pharmacokinetic model to describe the pharmacokinetics of Rh2 and PPD simultaneously at 10 mg/kg. The concentration data collected following a 20 mg/kg dose of Rh2 was used for model validation. Results: Following Rh2 administration, PPD exhibited high exposure and atypical double peaks. The model described the abnormal kinetics well and was further validated using external data. A total of 11% of the administered Rh2 was predicted to be transformed into PPD and enter the systemic circulation after I.V. administration, and a total of 20% of Rh2 was predicted to be absorbed into the systemic circulation in PPD form after P.O. administration of Rh2. Conclusion: The developed model provides a useful tool to quantitatively study the deglycosylation kinetics of Rh2 and thus, provides a valuable resource for future pharmacokinetic studies of glycosides with similar deglycosylation metabolism., Competing Interests: YS and SG was employed by Hutchison MediPharma Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Sun, A, Gu, Shi, Shao, Ai, Zhang, Peng, Yan, Huang, Liu, Sai, Wang and Yang.)

Compared with siRNAs or other antisense oligonucleotides (ASOs), the chemical simplicity, DNA/RNA binding capability, folding ability of tertiary structure, and excellent physiological stability of threose nucleic acid (TNA) motivate scientists to explore it as a novel molecular tool in biomedical applications. Although ASOs reach the target cells/tumors, insufficient tissue penetration and distribution of ASOs result in poor therapeutic efficacy. Therefore, the study of the time course of drug absorption, biodistribution, metabolism, and excretion is of significantly importance. In this work, the pharmacokinetics and biosafety of TNAs in living organisms are investigated. We found that synthetic TNAs exhibited excellent biological stability, low cytotoxicity, and substantial uptake in living cells without transfection. Using U87 three-dimensional (3D) multicellular spheroids to mimic the in vivo tumor microenvironment, TNAs showed their ability to penetrate efficiently throughout the whole multicellular spheroid as a function of incubation time and concentration when the size of the spheroid is relatively small. Additionally, TNAs could be safely administrated into Balb/c mice and most of them distributed in the kidneys where they supposed to excrete from the body through the renal filtration system. We found that accumulation of TNAs in kidneys induced no pathological changes, and no acute structural and functional damage in renal systems. The favourable biocompatibility of TNA makes it attractive as a safe and effective nucleic acid-based therapeutic agent for practical biological applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to economize O 2 for enhanced PDT against hypoxic tumors. The carrier-free O 2 -economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self-assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self-delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier-free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment., (© 2022 Wiley-VCH GmbH.)

Objective: To further clarify the anticancer mechanisms of Liujunzi decoction and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer (NSCLC) by re-analyzing differential gene expression profile of peripheral blood mononuclear cells (PBMCs) from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy., Methods: The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database. Differentially expressed genes (DEGs) were screened by paired sample t-test and the multiple ratio method. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed using the DAVID database. The protein-protein interaction (PPI) network was constructed using interaction gene library retrieval tools and Cytoscape software., Results: A total of 162 DEGs were identified, with 67 upregulated genes and 95 downregulated genes. The functional distribution of Gene Oncology (GO) genes showed that DEGs were mostly concentrated in extracellular regions, calcium ion binding, and transcriptase activity. KEGG pathway analysis showed that cytokine-cytokine receptor interactions were significantly enriched. PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree: IL2, PIWIL4, DICER1, PIWIL2, SAA1, XCL1, IL22RA1, ARHGAP11A, DCP1A, and GDNF. Among them, the central protein-coding gene with the highest node degree was IL2. In addition, the central protein-coding genes with high node degrees and high molecular complex detection (MCODE) scores were PIWIL4, DICER1, PIWIL2, and DCP1A, all of which are related to tumor development., Conclusions: One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data. IL2, PIWIL4, DICER1, PIWIL2, and DCP1A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC. Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.

Objective: To evaluate the differences in the efficacy of stationary treatment and individualized treatment for patients with nonproliferative diabetic retinopathy (NPDR)., Methods: This study was a randomized, controlled, multicenter clinical trial. Participants with NPDR were randomized into the stationary treatment group or the individualized treatment group. The stationary treatment group was given the basic treatment and Qiming granules, and the individualized treatment group was given the basic treatment, Qiming granules, and individualized Chinese herbal medicines over a 12-week period. The individualized therapeutic formula was also changed over time to adjust to the changes in the clinical presentation of the patient. We conducted observations of fundus retinal exudation and hemorrhage, visual acuity, Traditional Chinese Medicine symptom scores and other indicators., Results: A total of 140 participants with NPDR were randomized into the stationary treatment group or the individualized treatment group, and 132 participants completed this study. Following the 12-week treatment, significant improvements in both primary and secondary outcomes were observed in the stationary and individualized treatment groups. No remarkable difference in the primary outcomes between the two groups was observed. However, there was a significant difference in the Traditional Chinese Medicine symptom scores (18 ± 7 vs 15 ± 6; P < 0.05). There were no severe adverse effects., Conclusion: Compared with stationary treatment, individualized treatment is more effective at relieving the Traditional Chinese Medicine symptoms and improving vision and fundus lesions at 12 weeks post treatment.

Although trifluoromethyl alkenes have great synthetic potential, their 1,2-difunctionalization has been a challenge. In this Letter, we disclose the first 1,2-dicarbofunctionalization of trifluoromethyl alkenes with pyridinium salts via a cascade process involving a base-promoted [3 + 2] cycloaddition followed by a visible-light-mediated Norrish-type-II fragmentation. This protocol allows for the formation of pyridines bearing a trifluoromethyl-substituted quaternary center in moderate to excellent yields under mild conditions.

Automation of analytical sample preparation and testing is always attractive due to its high efficiency and continuous operation, but it can also be very challenging due to the operational complexity and method development. Studies focused on method development in automated systems are extremely rare and little has been published on the subject. In this paper, we investigate several unique and advanced aspects of this subject. The example product is selected containing two APIs to be tested by a single method to be productive. The product strengths of the two APIs are significantly different, making development of a single method much more challenging. In addition, we use a "green chemistry" approach, avoiding any organic solvent in the dissolving media in order to achieve an environmentally friendly solution. The selection and optimization of several key operational parameters are then discussed. The successful method is achieved using a new strategy called "Automated Online Standard (AO-STD)" methodology. This novel approach is compared to the manual operation procedure. The proposed approach can substantially reduce the method transfer time, generally considered the biggest obstacle to practical deployment of automated systems. The automated system applied in this paper is most suitable for content uniformity testing, but is also applicable for potency assays, blend uniformity testing, and degradation product tests., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We successfully fabricated threose nucleic acid (TNA)-based probes for real-time monitoring of target miRNA levels in cells. Our TNA probe is comprised of a fluorophore-labeled TNA reporter strand by partially hybridizing to a quencher-labeled TNA that is designed to be antisense to a target RNA transcript; this results in effective quenching of its fluorescence. In the presence of RNA targets, the antisense capture sequence of the TNA binds to targeted transcripts to form longer, thermodynamic stable duplexes. This binding event displaces the reporter strand from the quencher resulting in a discrete "turning-on" of the fluorescence. Our TNA probe is highly specific and selective toward target miRNA and is able to distinguish one to two base mismatches in the target RNA. Compared with DNA probes, our TNA probes exhibited favorable nuclease stability, thermal stability, and exceptional storage ability for long-term cellular studies. Our TNA probes are efficiently taken up by cells with negligible cytotoxicity for dynamic detection of target miRNAs and can also differentiate the distinct target miRNA expression levels in different cell lines. This work illuminates for using TNA as a building component to construct a biocompatible probe for miRNA detection that offers alternative molecular reagents for miRNA-related diagnostics., Competing Interests: P.K.L., F.W., and L.S.L. are listed as inventors on a US patent application by the City University of Hong Kong describing the preparation and use of TNA-based probes. The other authors declare no competing financial interests., (© 2022 The Author(s).)

The last five years have seen a leap in the development of information technology and social media. Seeking health information online has become popular. It has been widely accepted that online health information seeking behavior has a positive impact on health information consumers. Due to its importance, online health information seeking behavior has been investigated from different aspects. However, there is lacking a systematic review that can integrate the findings of the most recent research work in online health information seeking, and provide guidance to governments, health organizations, and social media platforms on how to support and promote this seeking behavior, and improve the services of online health information access and provision. We therefore conduct this systematic review. The Google Scholar database was searched for existing research on online health information seeking behavior between 2016 and 2021 to obtain the most recent findings. Within the 97 papers searched, 20 met our inclusion criteria. Through a systematic review, this paper identifies general behavioral patterns, and influencing factors such as age, gender, income, employment status, literacy (or education) level, country of origin and places of residence, and caregiving role. Facilitators (i.e., the existence of online communities, the privacy feature, real-time interaction, and archived health information format), and barriers (i.e., low health literacy, limited accessibility and information retrieval skills, low reliable, deficient and elusive health information, platform censorship, and lack of misinformation checks) to online health information seeking behavior are also discovered.

A 25-year-old woman was admitted to Peking Union Medical Hospital presented with arthralgia for 5 years, amenorrhea for 16 months, and speech disorder for 3 months. This patient has been afflicted by intermittent pain in metacarpophalangeal and proximal interphalangeal joints of both hands for 5 years. Her menstruation has been irregular 1 year ago and rapidly progressed to amenorrhea. Laboratory tests revealed postmenopausal sex hormones levels (estradiol<5 ng/L, follicle-stimulating hormone 62.5 IU/L, luteinizing hormone 58.71 IU/L) and no antral follicles were seen in gynecologic ultrasound. She was diagnosed with premature ovarian failure and treated with hormone replacement therapy, still with no ovulation. Numbness and weakness of right arm has recurrently occurred to her 4 months ago, and persistent weakness of right limbs combined with motor speech disorder occurred 1 month later. Magnetic resonance angiography was suggestive of ischemic stroke. Hormone replacement therapy was discontinued. Comprehensive laboratory tests revealed positive anti-dsDNA, anti-SSA/SSB, anticardiolipin and anti-β 2 GPⅠ antibodies. Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) was diagnosed. Since no drug with gonadal toxicity had been applied to the patient before, her amenorrhea was considered to be due to autoimmune oophoritis secondary to SLE. After treated with high-dose glucocorticoid, mycophenolate mofetil and hydroxychloroquine for 4 months, her menstruation recurred and regularly occurred till now. In some cases, amenorrhea in SLE patient might be resulted from autoimmune oophoritis associated with lupus flare, instead of use of drug with gonadal toxicity.

A force-sensitive structure of an InAs Quantum Dot (QD) embedded in a high electron mobility transistor (HEMT) is presented in this paper. The size of an InAs QD is about 30 nm prepared by the S-K growth mode, and the force-sensitive structure is fabricated by molecular beam epitaxy (MBE). The force-sensitivity characteristic of the QD HEMT is studied by the electrical and mechanical properties. The electrical characteristics show that the InAs QD-HEMT has linear, cut-off, and saturation operating states, and produces different output currents under different gate voltages, which shows that the structure is reasonable. Furthermore, the results of the output characteristics under different pressure show that the output voltage of the QD-HEMT decreases with the increase in pressure, which indicates that the InAs QD-HEMT has a vital mechanical-electrical coupling characteristic. The output voltage of the InAs QD-HEMT in the range of 0-100 kPa shows that the sensitivity was 1.09 mV/kPa.

Oxygen-dependent photodynamic therapy (PDT) could exacerbate tumor hypoxia to induce the upregulation of hypoxia-inducible factor-1α (HIF-1α), which would promote tumor growth and metastasis. In this paper, a self-remedied nanomedicine is developed based on a photosensitizer and a HIF-1α inhibitor to surmount the Achilles' heel of PDT for enhanced antitumor efficacy. Specifically, the nanomedicine (designated as CYC-1) is prepared by the self-assembly of chlorine e6 (Ce6) and 3-(5'-hydroxy-methyl-2'-furyl)-1-benzylindazole (YC-1) through π-π stacking and hydrophobic interactions. Of special note, carrier-free CYC-1 holds an extremely high drug loading rate and avoids excipient-triggered adverse reactions. Intravenously administered CYC-1 prefers to accumulate in the tumor tissue for effective cellular uptake. More importantly, it is verified that CYC-1 is capable of inhibiting the HIF-1α activity, thereby improving its PDT efficacy on tumor suppression. Besides, CYC-1 has the overwhelming superiority in restraining tumor proliferation over the combined administration of Ce6 and YC-1, which highlights the advantage of this self-remedied strategy in drug delivery and tumor therapy. This study sheds light on the development of self-delivery nanomedicine for efficient PDT against malignancies.

Background: The purpose of this study was to examine the correlation between fasting blood glucose and new-onset hypertension and examine any synergistically effect modification with multiple risk factors., Methods: We conducted post-hoc analyses of repeated-measures data in the original Dongzhi osteoporosis cohort study. In total, 3985 participants without hypertension aged 25-64 years were included in the current analyses. Generalized estimating equation models were used to assess the relationship between fasting blood glucose and risk of new-onset hypertension after adjusting for pertinent covariates and autocorrelations among siblings., Results: 393 men (19.4%) and 398 women (20.3%) without hypertension at the baseline developed hypertension by the end of the study period. Compared to lower baseline fasting blood glucose levels (Q1-Q3: < 5.74 mmol/L; clinical cut points: < 5.6 mmol/L), higher baseline fasting blood glucose levels (Q4: ≥ 5.74 mmol/L; clinical cut points: ≥ 5.6 mmol/L and < 7.0 mmol/L) increased the risk of new-onset hypertension significantly [(OR: 1.54, 95% CI 1.19-1.98, P < 0.001); (OR: 1.38, 95% CI 1.09-1.75, P = 0.008)] in women. Additionally, a stronger significant association was found in women with elevated fasting blood glucose on risk of new-onset of hypertension with higher total cholesterol (≥ 5.2 mmol/L) [(OR: 2.76; 95% CI: (1.54, 4.96), P < 0.001)]. However, no association was found between fasting blood glucose and risk of new-onset hypertension in men., Conclusions: High fasting blood glucose may be significantly associated with risk of new-onset hypertension in Chinese women, especially in women with higher total cholesterol. Further randomized studies are needed to confirm our findings., (© 2021. The Author(s).)

Shifting ruminal fermentation via feeding a blend of oregano (Organum vulgare L.) essential oils and Co-lactate (EOC; Rum-A-Fresh, Ralco, Inc. Marshall, MN) could improve lamb growth and carcass performance. Eighteen Suffolk × Little Han Tail F1 male lambs (20.3 ± 0.23 kg BW and approximately 3 months old) were randomly assigned using a completely random design to one of three treatments. Treatments were (1) EOC0: basal ration without EOC, (2) EOC4: basal ration plus 4 g/d EOC, and (3) EOC7: basal ration plus 7 g/d EOC. Initial and 24 d BW was similar (P > 0.10), but at 48 and 72 d, lambs fed EOC7 demonstrated greater (P = 0.01) BW compared with EOC0 fed lambs, while lambs fed EOC4 were intermediate and similar (P > 0.05). Average daily gains (ADGs) for 0-24 and 0-72 d were greater (P < 0.05) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0, while DM intake was similar (P > 0.10). Feed conversions for 0-24 d were improved (P < 0.02) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0. However, 0-72-d feed conversions were greater (P < 0.01) for lambs fed EOC7 compared to lambs fed EOC0, with lambs fed EOC4 being intermediate and similar (P > 0.05). DM, NDF, and ADF digestibilities were similar (P > 0.10) among treatments, while CP digestibility was greater (P < 0.01) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0. Carcass weight and dressing percentages were improved (P < 0.01) for lambs fed EOC7 compared with lambs fed EOC0 and EOC4. Head width was greater (P > 0.01) for lambs fed EOC7 compared with lambs fed EOC0 and EOC4, while rump width was greater (P > 0.01) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0. Plasma triglyceride and cholesterol concentrations were lower (P < 0.05) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0, while albumin, total serum protein, and glucose concentrations were greater (P < 0.05) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0. Feeding an EOC blend as an alternative antibiotic growth promoter at 4 and 7 g/d linearly improved lamb growth performance, feed conversions, frame growth, carcass weights, dressing percentages, and immunity., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Tumor cells adapt to excessive oxidative stress by actuating reactive oxygen species (ROS)-defensing system, leading to a resistance to oxidation therapy. In this work, self-delivery photodynamic synergists (designated as PhotoSyn) are developed for oxidative damage amplified tumor therapy. Specifically, PhotoSyn are fabricated by the self-assembly of chlorine e6 (Ce6) and TH588 through π-π stacking and hydrophobic interactions. Without additional carriers, nanoscale PhotoSyn possess an extremely high drug loading rate (up to 100%) and they are found to be fairly stable in aqueous phase with a uniform size distribution. Intravenously injected PhotoSyn prefer to accumulate at tumor sites for effective cellular uptake. More importantly, TH588-mediated MTH1 inhibition could destroy the ROS-defensing system of tumor cells by preventing the elimination of 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dG), thereby exacerbating the oxidative DNA damage induced by the photodynamic therapy (PDT) of Ce6 under light irradiation. As a consequence, PhotoSyn exhibit enhanced photo toxicity and a significant antitumor effect. This amplified oxidative damage strategy improves the PDT efficiency with a reduced side effect by increasing the lethality of ROS without generating superabundant ROS, which would provide a new insight for developing self-delivery nanoplatforms in photodynamic tumor therapy in clinic., (© 2021 Wiley-VCH GmbH.)

Objective: This analysis was performed to evaluate the efficacy and the safety of rivaroxaban-aspirin combination therapy in secondary prevention of major adverse cardiovascular events in Chinese patients enrolled in the COMPASS trial. Methods: COMPASS was a prospective, international multi-center and randomized controlled trial. From September 2014 to February 2017, 1 086 patients with stable coronary artery disease and peripheral artery diseases were recruited from 31 centers in China. Patients were randomly assigned to separately receive the therapy of rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day,) group ( n =366), rivaroxaban (5 mg twice a day) alone group ( n =365), and aspirin (100 mg once a day) alone group ( n =355). Baseline information such as age, sex, etc. of all three groups was collected. Finally, 1 081 patients were followed up successfully, with the follow-up rate 99.5% and the average follow-up time was 19 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction and stroke. The primary safety endpoint was major bleeding evaluated by modified International Society on Thrombosis and Haemostasis criteria. Results: Age of patients was (64.2±8.3) years and there were 293 male in rivaroxaban plus aspirin group. Age of patients was (63.8±9.0) years, and there were 301 male patients in rivaroxaban alone group. Age of patients was (63.6±8.8) years, and there were 282 male patients in the aspirin alone group. The incidences of primary efficacy endpoint occurred in 9 cases (1.5%) in rivaroxaban with aspirin group, 21 cases (3.7%) in rivaroxaban alone group and 14 cases (2.5%) in aspirin alone group. Meanwhile, the incidences of primary safety endpoint occurred in 6 cases (1.0%) in rivaroxaban with aspirin group, 9 cases (1.6%) in rivaroxaban alone group and 7 cases (1.2%) in aspirin alone group. The net clinical benefit events were 10 cases (1.7%) in rivaroxaban with aspirin group, 22 cases (3.9%) in rivaroxaban alone group and 15 cases (2.7%) in aspirin alone group ( P >0.5%). Conclusions: The combination of rivaroxaban with aspirin can be safe and effectively used for the secondary prevention in Chinese patients with stable coronary artery disease and peripheral artery diseases.

Endothelial-mesenchymal transition (EndMT) is widely involved in the occurrence and development of cardiovascular diseases. Although there is no direct evidence, it is very promising as an effective target for the treatment of these diseases. Endothelial cells need to respond to the complex cardiovascular environment through EndMT, but sustained stimuli will cause the imbalance of EndMT. Blocking the signal transduction promoting EndMT is an effective method to control the imbalance of EndMT. In particular, we also discussed the potential role of endothelial cell apoptosis and autophagy in regulating the imbalance of EndMT. In addition, promoting mesenchymal-endothelial transformation (MEndT) is also a method to control the imbalance of EndMT. However, targeting EndMT to treat cardiovascular disease still faces many challenges. By reviewing the research progress of EndMT, we have put forward some insights and translated them into challenges and opportunities for new treatment strategies for cardiovascular diseases.

Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are considered important mediators of the periapical immune response to infection. This study aimed to clarify the putative relationship between MMPs and TIMPs by elucidating the activity of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 in the temporal development of apical periodontitis (AP) in mice., Methods: AP was induced in the lower first molars of 30 male Kunming mice. The animals were randomly killed at 0, 7, 14, 28, 60, and 90 days after pulp exposure. The jaws were removed and subjected to quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis., Results: The MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased with periapical inflammation progression (P < .05). The MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased during the acute and chronic stages of periapical lesions, with less MMP-2 and MMP-9 expression levels at the chronic stage (P < .05). The MMP-8 expression increased at the chronic stage of inflammation (P < .05) but not at the acute stage. Immunostained MMP-2 and TIMP-1 were observed in all experimental periods., Conclusions: MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were expressed in all periapical samples with varying levels between them. MMP expression could be related to TIMP expression in the temporal development of AP., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the clinicopathologic characteristics of hepatic echinococcus granulosus (HEG). Methods: Thirteen cases of HEG were collected from Linzhi People's Hospital between January 2017 to October 2020, and their clinicopathologic features, ultrasound classification, immunophenotype and histochemical data were analyzed, retrospectively and the relevant literature was reviewed. Results: Thirteen patients (5 male patients, 8 female patients) were included in this cohort, and the mean age was 40 years. The most common clinical presentation was mild abdominal distention and pain (9/13). Based on WHO-IWGE ultrasound standardized classification, these cases were classified into 5 types, including type CL (1 case), type CE1 (2 cases), type CE2 (4 cases), type CE3 (3 cases) and type CE4 (3 cases). Gross examination revealed a solitary cyst localized in the liver, varying from 2.7 to 13.5 cm in diameter, and most of them(10/13)were more than 10 cm. Histopathologically, these cysts possessed a thin inner germinal layer and outer adventitial layer, and a central cavity filled with a clear"hydatid"fluid. The germinal layer was continuous and generated brood capsules and protoscoleces. The laminated membranes were clearly demonstrated by elastic fiber and Gomori's stains. Inside the"mother"cyst, there were a varying number of"daughter"vesicles of variable sizes. The inflammatory reaction around the cyst consisted of eosinophils, mononuclear cells immediately next to the cyst layer and sometimes formed granuloma and giant cells resembling the Langhan's type giant cells. The lymphoid cells were positive for CD20 and CD3. The CD68 immunohistochemistry clearly demonstrated epithelioid cells of granuloma in two cases. Moreover, immunohistochemistry revealed plasma cells were locally positive for CD38, IgG and IgG4, but not meeting the criteria for IgG4 related lesion. Conclusions: Hepatic echinococcus granulosus is a zoonotic parasitic disease prevalent in pastoral areas such as Tibet. It is important to understand its clinical features, ultrasound characteristics and histological morphology.

The development of photodynamic therapy (PDT) is severely limited by short half-life of singlet oxygen ( 1 O 2 ) and the hypoxic microenvironment. In this work, a plasma membrane targeted photodynamic O 2 economizer (designated as P-POE) is developed to improve the subcellular delivery of photosensitizers and alleviate the tumor hypoxia for enhanced PDT effect. After self-assembly into nanomicelles, P-POE has a relatively high stability and a favorable photochemical performance, which are conducive to boosting the 1 O 2 production. Besides, the plasma membrane anchoring of P-POE contributes to enhancing the preferential retention and cellular accumulation of photosensitizers on tumor tissues and cells. More importantly, P-POE-induced mitochondrial respiratory depression is demonstrated to reduce the O 2 consumption of tumor cells to relieve the hypoxia. Consequently, P-POE still exhibits a robust PDT effect against hypoxic tumors, which greatly inhibits the proliferation of breast cancer with low adverse reactions. This innovative combination of subcellular targeting and hypoxic alleviation would advance the development of individualized drug delivery systems for photodynamic therapy against hypoxic tumors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Multidrug resistance (MDR) is one of the prime reasons for the failure of cancer chemotherapy, which continues to be a great challenge to be solved. In this work, α-tocopherol succinate (α-TOS) and doxorubicin (DOX)-based self-delivery nanomedicine (designated as α-TD) is prepared to combat drug resistance for cancer synergistic chemotherapy. Carrier-free α-TD possesses a fairly high drug loading rate and improves the cellular uptake via the endocytosis pathway. More importantly, the apoptotic inducer α-TOS could elevate the reactive oxygen species (ROS) generation, disrupt mitochondrial function and reduce adenosine 5'-triphosphate (ATP) production, which facilitate the intracellular drug retention while decreasing its efflux. As a result, α-TD achieves a considerable synergistic chemotherapeutic effect against drug resistant cancer cells. Moreover, it also exhibits a preferable inhibitory effect on tumor growth with a low system toxicity in vivo. This synergistic drug self-delivery strategy would open a new window for developing carrier-free nanomedicine for overcoming drug resistance in cancer therapy.

Cardiovascular diseases are the leading cause of death and morbidity worldwide. Atherosclerotic cardiovascular disease (ASCVD) is affected by both environmental and genetic factors. Microenvironmental disorders of the human gut flora are associated with a variety of health problems, not only gastrointestinal diseases, such as inflammatory bowel disease, but also extralintestinal organs. Hydrogen sulfide (H 2 S) is the third gas signaling molecule other than nitric oxide and carbon monoxide. In the cardiovascular system, H 2 S plays important roles in the regulation of blood pressure, angiogenesis, smooth muscle cell proliferation and apoptosis, anti-oxidative stress, cardiac functions. This review is aiming to explore the potential role of gut microbiota in the development of atherosclerosis through hydrogen sulfide production as a novel therapeutic direction for atherosclerosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aptamers are exciting smart molecular probes for specific recognition of disease biomarkers. A number of strategies have been developed to convert target-aptamer binding into physically detectable signals. Since the aptamer sequence was first discovered, a large variety of aptamer-based biosensors have been developed, with considerable attention paid to their potential applications in clinical diagnostics. So far, a variety of techniques in combination with a wide range of functional nanomaterials have been used for the design of aptasensors to further improve the sensitivity and detection limit of target determination. In this paper, the advantages of aptamers over traditional antibodies as the molecular recognition components in biosensors for high-throughput screening target molecules are highlighted. Aptamer-target pairing configurations are predominantly single- or dual-site binding; the design of recognition modes of each aptamer-target pairing configuration is described. Furthermore, signal transduction strategies including optical, electrical, mechanical, and mass-sensitive modes are clearly explained together with examples. Finally, we summarize the recent progress in the development of aptamer-based biosensors for clinical diagnosis, including detection of cancer and disease biomarkers and in vivo molecular imaging. We then conclude with a discussion on the advanced development and challenges of aptasensors.

Short circulation lifetime, poor blood-brain barrier (BBB) permeability and low targeting specificity limit nanovehicles from crossing the vascular barrier and reaching the tumor site. Consequently, the precise diagnosis of malignant brain tumors remains a great challenge. This study demonstrates the imaging of photostable biopolymer-coated nanodiamonds (NDs) with tumor targeting properties inside the brain. NDs are labeled with PEGylated denatured bovine serum albumin (BSA) and tumor vasculature targeting tripeptides RGD. The modified NDs show high colloidal stability in different buffer systems. Moreover, it is found that discrete dcBSA-PEG-NDs cross the in vitro BBB model more effectively than aggregated NDs. Importantly, compared with the non-targeting NDs, RGD-dcBSA-PEG-NDs can selectively target the tumor site in U-87 MG bearing mice after systemic injection. Overall, this discrete ND system enables efficacious brain tumor visualization with minimal toxicity to other major organs, and is worthy of further investigation into the applications as a unique platform for noninvasive theragnostics and/or thermometry at different stages of human diseases in the brain.

Relative Response Factors (RRFs) can be used for quantitation of one compound against another and it is widely used for Impurity analysis of pharmaceutical products; however, the application in potency assay is limited. Through an extensive study shown in this paper, it can be concluded that using the "RRF methodology" for potency assay is much more challenging compared to impurity analysis, due to the much tighter criteria required for potency analysis. The effects of instrument settings, which are rarely discussed or recognized in current HPLC analytical method development and quality release testing, are discussed. These factors impact the RRF just as much as other commonly recognized HPLC parameters. The effects of UV detector settings, i.e. Slit Width, Step Width, Band Width, and Data Collection Module, have been explored. This phenomenon has been demonstrated using three compounds to observe the impact of their quantitation due to the significant RRF variations. Finally, principles to reduce RRF variations have been discussed, and practical considerations of RRF application to method development and method transfer are provided., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)