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Abstract Background Poverty and ill-health are closely inter-related. Existing studies on the poverty-health vicious cycle focus mainly on less developed countries, where the identified mechanisms linking between poverty and ill-health may not fit the situations in developed Asian regions. This study aims to qualitatively explore the perceived mechanisms and drivers of the poverty-health vicious cycle among major stakeholders in the healthcare setting in Hong Kong. Methods Data were collected via focus group interviews with social workers (n = 8), chronically ill patients (n = 8), older adults (n = 6), primary care doctors (n = 7) and informal caregivers (n = 10). The transcribed data were then closely read to capture key themes using thematic analyses informed by social constructivism. Results In this highly developed Asian setting with income inequality among the greatest in the world, the poverty-health vicious cycle operates. Material and social constraints, as a result of unequal power and opportunities, appear to play a pivotal role in creating uneven distribution of social determinants of health. The subsequent healthcare access also varies across the social ladder under the dual-track healthcare system in Hong Kong. As health deteriorates, financial hardship is often resulted in the absence of sufficient and coordinated healthcare, welfare and labour policy interventions. In addition to the mechanisms, policy drivers of the cycle were also discussed based on the respondents’ perceived understanding of the nature of poverty and its operationalization in public policies, as well as of the digressive conceptions of disease among different stakeholders. Conclusions The poverty-health vicious cycle has remained a great challenge in Hong Kong despite its economic prosperity. To break the cycle, potential policy directions include the adoption of proportionate universalism, social integration and the strengthening of medical-social collaboration.

Random numbers play a vital role in communications and cryptography. However, most existing true random number generators have difficulty in satisfying the requirements of high-speed communications due to their complexity and bulkiness, or low speed limitations due to equipment bandwidth. Then, the all-electron true random number generator was presented based on GaAs/Al0.45Ga0.55As superlattices conducted under direct current bias at room temperature, which not only possesses the characteristics of miniaturization but also generates random numbers at rates up to the Gbit/s. However, the bit rate of random number generators based on superlattices is still much slower compared to chaotic laser random number generators. In order to generate higher-rate random numbers, we modified a DC-excited superlattice and then redirected the signal generated by the superlattice back into itself, thus introducing a self-feedback, and achieved a self-feedback superlattice true random number generator. This improvement makes the superlattice have a more detailed signal shape, a more effective signal amplitude, and with lower power consumption. Therefore, these advances made the self-feedback superlattice more suitable for generating random numbers. Moreover, we propose a new post-processing method, called the adjacent bits reversal exclusive-or. This method can reduce the sequence bias and correlation without discarding any random bit. The random number obtained by the self-feedback superlattice at a sampling rate of 10 GS/s passed the triple standard deviation test and the random number standard test (NIST SP 800-22), indicating that it possessed good statistical properties as a miniaturized random number generator.

Background: Although the specific etiology of Henoch–Schonlein purpura (HSP) is still unknown, several kinds of infectious triggers have been proved to participate in its pathogenesis. The objectives of present study were to analyze the association of the infectious triggers with childhood HSP in Anhui province, China. Methods: 1200 HSP children were recruited from January 2015 to December 2017. Serum antistreptolysin O titer, TORCH, Epstein-Barr virus, helicobacter pylori (HP), Mycoplasma antibodies (MP-Ab), tubercle bacillus antibody (TB-Ab), respiratory pathogens (legionella pneumophila, chlamydia pneumoniae, adenovirus, respiratory syncytial virus, influenza A virus, influenza B virus, rickettsia, parainfluenza virus) were determined. Patients’ histories were obtained by interviews and questionnaires. Results: The annual incidence of HSP was 8.13–9.17 per 100,000. HSP occurred more commonly in spring and winter than in summer with an obvious west-to-east gradient. On admission, several potential infections were identified in 611 cases (50.92%). The infectious agents including streptococcus, HP, MP, parainfluenza, respiratory syncytial virus, TB and toxoplasma gondii were identified in 205 cases (17.08%), 71 cases (5.92%), 58 cases (4.83%), 6 cases (0.5%), 1 case (0.08%), 1 case (0.08%) and 1 case (0.08%) respectively. 123 cases (10.25%) relapsed or recurred more than one time; the mean number was 2.92, and the mean interval was 11.4 weeks. The infection was the most frequent trigger regardless of clinical phenotypes and relapse/recurrence. Symptomatic treatment plus adjunctive anti-infectious agents could significantly improve the remission rate of purpura in the infectious cases (x2 = 24.60, p

Background: Transplantation of lymph nodes (LNs) is an increasingly popular option for treating lymphedema. Increasing evidence indicates an intrinsic correlation between estrogen signaling and the lymphatic system. We explored the effects of 17β estradiol and antiestrogen treatment (tamoxifen) on the survival and functional restoration of transplanted popliteal lymph nodes (PLNs).Methods: A total of forty-eight ovariectomized mice were divided into three groups of 16: OVX + E2 (treated with 17β-estradiol), OVX + TMX (treated with tamoxifen), and OVX (control; treated with olive oil as a solvent). After 2 weeks, PLNs were transplanted. Then, reconnections of lymphatic vessels were observed, and the morphology and survival of transplanted PLNs were evaluated 4 weeks after transplantation. T cells, B cells, lymphatic vessels, and high endothelial venules (HEVs) were subjected to immunofluorescence staining or immunohistochemical staining and quantified.Results: The percentage of lymphatic reconnections was 93.75% in the OVX + E2 group, 68.75% in the OVX + TMX group, and 75% in the OVX group. Surviving PLNs were observed in 16 of 16 in the OVX + E2 group, seven of 16 in the OVX + TMX group, and 13 of 16 in the OVX group. The mean size of PLNs in the largest cross section of the OVX + TMX group was significantly lower than that in the other groups. The distributions of B cells and T cells in surviving PLNs were similar to those in normal LNs. The ratio of dilated HEVs/total HEVs and density of lymphatic vessels in the OVX + E2 group were the highest among the three groups, whereas the lowest ratio and density were observed in the OVX + TMX group.Conclusion: Tamoxifen treatment might lead to cellular loss of transplanted LNs and interfere with the structural reconstruction and functional restoration, thereby inhibiting the survival of transplanted PLNs. Estrogen treatment facilitated the maintenance and regeneration of functional HEVs as well as lymphangiogenesis.

ObjectiveTo determine the profile of Chinese medical professionals with burnout symptoms at the national level and identify the association between capability well-being and burnout.Design and SettingA cross-sectional study in a nonrandom national sample of medical staff from 6 provinces across western, central and eastern China.ParticipantsPhysicians, medical laboratory scientists, nurses, and general practitioners aged 18 years or above who submitted a completed online questionnaire from June 2019 to January 2020 successfully (N = 25,120).Main Outcome MeasuresThe prevalence of burnout symptoms was assessed by the 22-item Maslach Burnout Inventory-Human Services Survey (MBI-HSS), which consists of three domains: emotional exhaustion (EE), depersonalization (DP), and personal achievement (PA). The overall high burnout was defined as EE score ≥27 or DP score ≥10. The capability well-being was measured by the Investigating Choice Experiments Capability Measure for Adults (ICECAP-A) and the overall ICECAP-A score was calculated using the UK value set, ranging from a score of 0–1. Multivariable logistic regression analysis was used to identify the association between well-being and the overall high burnout.ResultsAmong the 25,120 participants, 60.8% of the participants reported at least one symptom of burnout, whereas 11.2% reported all three symptoms of burnout. In the adjusted model, ICECAP-A score was independently associated with high burnout (AOR = 0.018, 95% CI = 0.015–0.022). Medical staff who were males, with shorter working years, working in tertiary hospitals, and those with the specialties of psychiatry, intensive care, emergency medicine, internal medicine, oncology, and pediatrics were at higher risk of reporting burnout symptoms.ConclusionThe burnout symptoms were relatively common among Chinese medical staff and they were found to be independently associated with capability well-being in health professionals. Interventions should be enhanced on vulnerable groups to reduce burnout and promote well-being in future studies.

This study investigates how health literacy (HL) and trust in health information affected COVID-19 vaccine hesitancy among Chinese Hong Kong adults. A cross-sectional study was conducted in August 2022. A total of 401 participants completed the study. Participants completed a newly developed Hong Kong HL scale and self-reported their trust levels in health information from different resources. The proportions of early uptake of the first dose and booster dose of COVID-19 vaccine were 69.1% and 71.8%, respectively. The risk of delaying the first dose was higher among participants with inadequate functional HL (OR = 0.58, p = 0.015), adequate levels of two subdomains of critical HL (OR = 1.82, p = 0.013; OR = 1.91, p < 0.01), and low-level trust in health information from the government (OR = 0.57, p = 0.019). Respondents with adequate interactive HL (OR = 0.52, p = 0.014) and inadequate level of one subdomain of critical HL (OR =1.71, p = 0.039) were more likely to delay the booster dose. This negative association between critical HL and vaccination was suppressed by trust in health information from the government. This study shows that HL and trust in health information from the government are associated with COVID-19 vaccine hesitancy. Efforts should be directed at providing tailored communication strategies with regard to people’s HL and increasing public confidence in health authorities to decrease vaccine hesitancy.

Background: Along with individual-level factors, vaccination-related characteristics are important in understanding COVID-19 vaccine hesitancy. This study aimed to determine the influence of these characteristics on vaccine acceptance to formulate promotion strategies after considering differences among respondents with different characteristics.Methods: An online discrete choice experiment was conducted among people aged 18–64 years in Hong Kong, China, from 26 to 28 February 2021. Respondents were asked to make choices regarding hypothetical vaccination programmes described by vaccination-related characteristics—the attributes derived from a prior individual interview. Subgroup analysis was performed to identify the differences in vaccination-related characteristics among respondents with different personal characteristics.Results: A total of 1,773 respondents provided valid responses. The vaccine efficacy and brand were the most important factors affecting acceptance, followed by the exemption of quarantine for vaccinated travelers, safety, venue for vaccination, vaccine uptake of people in their lives, and recommendations by general physicians or government. Frequent exposure to vaccination information on social media has been associated with increasing vaccine refusal. Substantial preference heterogeneity for the attributes was found among people of different ages, incomes, chronic conditions, and previous acceptance of influenza vaccines.Conclusion: The findings provided evidence to formulate interventions to promote vaccine uptake, including the provision of vaccination at housing estate or workplaces, involvement of general physicians and interpersonal communication in vaccine promotion and information dissemination, and exemption of quarantine for vaccinated people. Moreover, social media is a significant information channel that cannot be neglected in the dissemination of official information.

Abstract. Introduction:. Pain relief from repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) is particularly poor in patients with leg pain. The optimal parameters for relieving leg pain remain poorly understood. The purpose of this study was to explore the optimal stimulation parameters of M1-rTMS for patients with leg pain. Methods:. Eleven patients with neuropathic pain in the leg randomly underwent 6 conditions of M1-rTMS with different stimulation intensities, sites, and coil directions, including sham stimulation. The 5 active conditions were as follows: 90% or 110% of the resting motor threshold (RMT) on the M1 hand with an anteroposterior coil direction, 90% or 110% RMT on the M1 foot in the anteroposterior direction, and 90% RMT on the M1 foot in the mediolateral direction. Each condition was administered for 3 days. Pain intensity was evaluated using the Visual Analogue Scale and Short-Form McGill Pain Questionnaire 2 at baseline and up to 7 days after each intervention. Results:. Visual Analogue Scale scores were significantly reduced after the following active rTMS conditions: 90% RMT on the M1 hand, 90% RMT on the M1 foot with any coil direction, and 110% RMT on the M1 foot. The Short-Form McGill Pain Questionnaire 2 results were similar to those obtained using the Visual Analogue Scale. The analgesic effect of rTMS with stimulus intensity above the RMT was not superior to that below the RMT. Conclusion:. We suggest that the optimal stimulation parameters of rTMS for patients with neuropathic pain in the leg may target the M1 foot or M1 hand with an intensity below the RMT.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex for neuropathic pain has been shown to be effective, according to systematic reviews and therapeutic guidelines. However, our large, rigorous, investigator-initiated, registration-directed clinical trial failed to show a positive primary outcome, and its subgroup analysis suggested that the analgesic effect varied according to the site of pain. The aim of this study was to investigate the differences in analgesic effects of rTMS for neuropathic pain between different pain sites by reviewing our previous clinical trials. We included three clinical trials in this mini meta-analysis: a multicenter randomized controlled trial at seven hospitals (N = 64), an investigator-initiated registration-directed clinical trial at three hospitals (N = 142), and an exploratory clinical trial examining different stimulation parameters (N = 22). The primary efficacy endpoint (change in pain scale) was extracted for each patient group with pain in the face, upper limb, or lower limb, and a meta-analysis of the efficacy of active rTMS against sham stimulation was performed. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated for pain change using a random-effects model. The analgesic effect of rTMS for upper limb pain was favorable (SMD = −0.45, 95% CI: −0.77 to −0.13). In contrast, rTMS did not produce significant pain relief on lower limb pain (SMD = 0.04, 95% CI: −0.33 to 0.41) or face (SMD = −0.24, 95% CI: −1.59 to 1.12). In conclusion, these findings suggest that rTMS provides analgesic effects in patients with neuropathic pain in the upper limb, but not in the lower limb or face, under the conditions of previous clinical trials. Owing to the main limitation of small number of studies included, many aspects should be clarified by further research and high-quality studies in these patients.

BackgroundInsidious-onset acromegaly may easily be overlooked by non-specialists of acromegaly and cause diagnostic delay. This study aims to examine the association between diagnostic delay and advice from doctors before any confirmed diagnosis and subsequent comorbidities, and elicit patient-perceived reasons for misdiagnoses.MethodsAn online nationwide cross-sectional study was conducted through China Acromegaly Patient Association. Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) levels at diagnosis and cancerous, endocrine-metabolic, musculoskeletal, cardiovascular, respiratory, and psychiatric comorbidities were reported by patients. The association between diagnostic delay and pre-diagnostic advice from doctors as well as subsequent comorbidities after diagnosis were examined.ResultsIn total, 447 valid responses were collected. Overall, 58.8% patients experienced misdiagnoses, and 22.6% had diagnostic delay. Before arriving at any diagnosis, patients without treatment (adjusted odds ratio [AOR]: 3.66, 95% confidence interval [CI]: 1.30-10.33) or receiving treatment to symptoms only (AOR: 7.05, 95%CI: 4.09-12.17) had greater chance of being misdiagnosed, and hence had diagnostic delay. Patients believed insufficient specialists, limited awareness of acromegaly of non-specialists and poor doctor-patient communications were major reasons of misdiagnosis. Diagnostic delay were associated with higher GH level at diagnosis and endocrine-metabolic, musculoskeletal and cardiovascular comorbidities (all P

Previous studies have explored the role of cognitive factors and sympathy in children’s development of moral emotion attribution, but the effect of personal dispositional factors on adolescents’ moral emotion expectancy has been neglected. In this study, we address this issue by testing adolescents’ moral emotion attribution with different social value orientation (SVO). Eight hundred and eighty Chinese adolescents were classified into proselfs, prosocials and mixed types in SVO and asked to indicate their moral emotions in four moral contexts (prosocial, antisocial, failing to act prosocially (FAP) and resisting antisocial impulse (RAI)). The findings revealed an obvious contextual effect in adolescents’ moral emotion attribution and the effect depends on SVO. Prosocials evaluated more positively than proselfs and mixed types in the prosocial and RAI contexts, but proselfs evaluated more positively than prosocials and mixed types in the antisocial and FAP contexts. The findings indicate that individual differences of adolescents’ moral emotion attribution have roots in their social value orientation, and suggest the role of dispositional factors in the processing of moral emotion.

Objective: This study examined the impact of adding two condition-specific bolt-on items to the EQ-5D-5L and assessed their psychometric properties in patients with hemophilia.Methods: The data were obtained from a nationwide cross-sectional online survey of patients with hemophilia in China. Self-reported and proxy-reported data were analyzed separately. Ceiling effect, informativity, and discriminatory power of the EQ-5D-5L with two bolt-on items, dignity (DG), and bleeding (BL), were examined. Spearman's rank correlation (rho) was used to assess the associations of the EQ-5D-5L and two bolt-on items with the Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) and SF-12. Multiple regression analysis was performed to evaluate the explained variance of the EQ-5D-5L and bolt-on items in predicting EQ-VAS scores.Results: A total of 895 patients and 222 caregivers completed the questionnaire. The ceiling effect decreased from 1.9 to 0.6% and 5.9 to 0.9% when using the EQ-5D-5L and the EQ-5D-5L with two bolt-on items among participants with both self- and proxy-completed questionnaires. Both DG and BL were strongly correlated with Haem-A-QoL sum score [rho: DG = 0.64 (patient) vs. 0.66(proxy); BL = 0.49 (patient) vs. 0.31 (proxy)], SF-12 mental component [rho: DG = −0.36 (patient) vs. −0.41 (proxy); BL = −0.53 (patient) vs. −0.57(proxy)], and SF-12 physical component [rho: DG = −0.61 (patient) vs. −0.61 (proxy); BL = −0.35 (patient) vs. −0.39 (proxy)]. Known-group comparisons confirmed that the two bolt-on items had satisfactory discriminatory power. Multiple regression analysis indicated that adding two bolt-on items significantly increased the ability to predict EQ-VAS scores. The adjusted R2 increased by 8.2 and 8.8% for reports completed by the patients or patients' proxy respondents, respectively.Conclusion: Adding the DG and BL bolt-on items can increase performance on the EQ-5D-5L in patients with hemophilia. A future valuation study will be carried out.

Circular RNAs (circRNAs) are ubiquitous endogenous RNA found in various organisms that can regulate gene expression in eukaryotes. However, little is known about potential roles for circRNAs in muscle development. We analyzed circRNA sequencing data of bovine skeletal muscle tissue and found differential expression of circTitin (circTTN) in fetal and adult bovine muscle tissue. We then further studied the role of circTTN in bovine muscle development. Overexpression and inhibition of circTTN together elicited its promoting roles in proliferation and differentiation of bovine primary myoblasts. Mechanistically, circTTN showed interaction with miR-432 by luciferase screening and RNA immunoprecipitation (RIP) assays. Additionally, miR-432 is a regulator of insulin-like growth factor 2 (IGF2), as indicated by luciferase activity, quantitative real-time PCR, and western blotting assays. Increased miR-432 expression inhibited the expression of IGF2, but this effect was remitted by circTTN. Conclusively, our results showed that circTTN promoted proliferation and differentiation of bovine primary myoblasts via competitively combining with miR-432 to activate the IGF2/phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Keywords: bovine, circRNA, miRNA, IGF2/PI3K/AKT pathway, myoblast

Bone disease: Treating a complication of chronic kidney disease A naturally occurring peptide (a small protein) might be useful for treating renal osteodystrophy (ROD), a bone disease common in people with chronic kidney disease. ROD develops when kidney disease disrupts the normal metabolism of calcium, phosphate and vitamin D essential to healthy bones. Peng Hu and colleagues at the First Affiliated Hospital of Anhui Medical University, Hefei, China, found that administering ‘C-type natriuretic peptide’ intravenously to rats which had been surgically and chemically treated to induce a condition modelling ROD in humans resulted in improvement. The therapeutic effect of the peptide was mediated by inhibiting a molecular signaling pathway which leads to the over-production of a specific fibroblast growth factor protein in bone cells in ROD. The significance of these results for humans should be investigated further.

Abstract Background In the last decade, incomplete Kawasaki disease (KD), intravenous immunoglobulin (IVIG) non-response and coronary artery abnormalities (CAA) have experienced the increasing trends in China. In addition, the enhancement of pediatricians’ awareness may also raise the diagnostic rate of incomplete KD and stimulate more aggressive initial therapy in the acute episode of KD. Given this background, we hypothesize that the time option of IVIG treatment should be in parallel with peak time of systemic inflammation; either earlier or later IVIG treatment may affect the clinical classification, therapeutic responsiveness and CAA occurrence in KD patients. Therefore, the major objective of the present study is to identify whether the time option of IVIG treatment could be associated with the clinical classification, therapeutic responsiveness and CAA occurrence in the acute episode of KD. Materials and methods A total of 153 children with KD were recruited between July 2015 and May 2018. All patients received the standard therapy of KD, including a single infusion of IVIG (2 g/kg) and aspirin (30–50 mg/kg/d). Blood samples were collected from all subjects within 24 h pre-IVIG treatment, respectively. Echocardiography was performed during the period from 2 days to 14 days after IVIG treatment. Results (1) The clinical classification presented no significant heterogenicity among different treatment time (x 2 = 1.59, p > 0.05) (2) Eleven KD patients resisted to IVIG treatment and 7 of them (63.60%) received the initial IVIG dose on day 5 and 6. (3) The distribution of CAA onset was subjected to a significant difference according to timing option of IVIG treatment (x 2 = 11.94, p

Abstract Background & Aims Although the prognosis of patients with occult hepatitis B virus (HBV) infection (OBI) is usually benign, a small portion may undergo cirrhosis and subsequently hepatocellular carcinoma (HCC). We studied the mechanism of life-long Integration of virus DNA into OBI host’s genome, of which may induce hepatocyte transformation. Methods We applied HBV capture sequencing on single cells from an OBI patient who, developed multiple HCC tumors and underwent liver resection in May 2013 at Tongji Hospital in China. Despite with the undetectable virus DNA in serum, we determined the pattern of viral integration in tumor cells and adjacent non-tumor cells and obtained the details of the viral arrangement in host genome, and furthermore the HBV integrated region in cancer genome. Results HBV captured sequencing of tissues and individual cells revealed that samples from multiple tumors shared two viral integration sites that could affect three host genes, including CSMD2 on chr1 and MED30/EXT1 on chr8. Whole genome sequencing further indicated one hybrid chromosome formed by HBV integrations between chr1 and chr8 that was shared by multiple tumors. Additional 50 poorly differentiated liver tumors and the paired adjacent non-tumors were evaluated and functional studies suggested up-regulated EXT1 expression promoted HCC growth. We further observed that the most somatic mutations within the tumor cell genome were common among the multiple tumors, suggesting that HBV associated, multifocal HCC is monoclonal in origin. Conclusion Through analyzing the HBV integration sites in multifocal HCC, our data suggested that the tumor cells were monoclonal in origin and formed in the absence of active viral replication, whereas the affected host genes may subsequently contribute to carcinogenesis.

Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been developed for HCC diagnosis. However, few markers are quickly translated into clinical practice; early and differential diagnosis of HCC from cirrhosis and/or hepatitis is still a clinical challenge. Metabolomics and biochemical methods were used to reveal specific serum biomarkers of HCC. Most of the elevated metabolites in HCC and HBV patients were overlapped compared with controls. Urea was the specifically elevated serum biomarker of HCC patients. Moreover, urea combined with AFP and CEA can improve the sensitivity of HCC diagnosis. The plasma ammonia of HCC patients was significantly higher than healthy controls. Co-culture cell model revealed normal liver cells cooperated with cancer cells to metabolize ammonia into urea. The urea metabolism in cancer cells marginally depended on the expression of CPS1. However, the expression of CPS1 did not change with ammonium chloride, which might regulate the urea cycle through enzyme activity. The urea cycle could detoxify high concentrations of ammonia to promote cancer cell proliferation. Therefore, urea was a by-product of ammonia metabolism and could be a potential serum biomarker for HCC. The combined application of metabolomics and biochemical methods can discover new biomarkers for the early diagnosis of HCC and be quickly applied to clinical diagnosis.

Background Hong Kong is a densely populated city with a low incidence and mortality of coronavirus disease 2019 (COVID-19). The city imposed different levels of social distancing including, the closure of sports venues and restrictions on eateries. This inevitably affects the eating behaviour and physical activities of the population. We examined the changes in eating behavior and physical activities before and during the COVID-19 pandemic, and identified sociodemographic factors associated with the behavioral changes. Methods This was a cross-sectional study via a random telephone survey of Chinese adults conducted in Hong Kong from May to June, 2020 - a period in which social distancing measures were being imposed. We measured the physical activity habits from four aspects and dietary consumption patterns from seven aspects before and during the pandemic based on the World Health Organization’s guidelines and previous publications. Results In total, 724 participants were recruited. Individuals were found to cook more frequently at home (p

PurposeAcromegaly is a rare, intractable endocrine disease. We aimed to describe the patient characteristics, diagnostic delays, treatment patterns, treatment outcomes, comorbidities and treatment costs of acromegaly in China.MethodsThis is a nationwide cross-sectional study. Patients diagnosed with and treated for acromegaly between 1996 and 2019 across China were surveyed via the Chinese Association of Patients with Acromegaly platform.ResultsIn total, 473 patients (58.8% females, mean age at diagnosis: 39.4±9.5 years) were included. The median disease duration was 3 years. The most common symptoms were extremity enlargement (91.8%) and facial changes (90.1%). Overall, 63.0% of patients experienced diagnostic delays within healthcare systems; 63.8% of the delays were

This study aimed to investigate the dissemination and characteristics of blaKPC, blaNDM, blaOXA-48-like, blaIMP, and blaVIM among the carbapenem-resistant Enterobacteriaceae (CRE) strains isolated from adult and children patients. A total of 935 non-duplicate CRE strains were collected from 36 hospitals in 24 provinces or cities across China from 2016 to 2018. Antimicrobial susceptibility testing was performed by broth microdilution method and carbapenemase genes blaKPC, blaNDM, blaOXA-48-like, blaIMP, and blaVIM were screened by PCR and confirmed by DNA sequencing. Overall, carbapenemases were produced in 97.4% (911/935) of CRE strains, including KPC-2 (51.6%, 482/935), NDM (35.7%, 334/935), and OXA-48-like carbapenemases (7.3%, 68/935). Overall, the most prevalent carbapenemase gene was blaKPC-2 among Klebsiella pneumoniae (64.6%, 457/709) and the CRE strains isolated from adult patients (70.3%, 307/437), and blaNDM among Escherichia coli (96.0%, 143/149) and the CRE strains from children (49.0%, 247/498). The blaOXA-232-positive carbapenem-resistant K. pneumoniae (9.3%, 66/709) were all isolated from children. Sixteen strains were positive for blaIMP and 9 strains produced multiple carbapenemases. No strain was positive for blaVIM. Most of the CRE strains (>90%) were resistant to cephalosporins and carbapenems, more than half (>50%) were resistant to aminoglycosides and fluoroquinolones, but the majority (95.8 and 98.4%) were susceptible to polymyxin B and tigecycline. Ceftazidime-avibactam showed excellent in vitro activity against blaKPC-2 and blaOXA-48-like positive strains (100% susceptible). In China, KPC-2, NDM, and OXA-48-like carbapenemases were predominant among CRE clinical isolates. The most prevalent carbapenemase gene was blaKPC-2 among K. pneumoniae isolates from adult patients, and blaNDM among E. coli isolates from children.

In recent years, immunotherapies have been clinically investigated in AML and other myeloid malignancies. While most of these are focused on stimulating the adaptive immune system (including T cell checkpoint inhibitors), several key approaches targeting the innate immune system have been identified. Macrophages are a key cell type in the innate immune response with CD47 being identified as a dominant macrophage checkpoint. CD47 is a “do not eat me” signal, overexpressed in myeloid malignancies that leads to tumor evasion of phagocytosis by macrophages. Blockade of CD47 leads to engulfment of leukemic cells and therapeutic elimination. Pre-clinical data has demonstrated robust anti-cancer activity in multiple hematologic malignancies including AML and myelodysplastic syndrome (MDS). In addition, clinical studies have been underway with CD47 targeting agents in both AML and MDS as monotherapy and in combination. This review will describe the role of CD47 in myeloid malignancies and pre-clinical data supporting CD47 targeting. In addition, initial clinical data of CD47 targeting in AML/MDS will be reviewed, and including the first-in-class anti-CD47 antibody magrolimab.

Abstract Background In recent years, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) infections has increased rapidly. Since the CRE strain is usually resistant to most of antimicrobial agents, patients with this infection are often accompanied by a high mortality. Therefore, it instigates a severe challenge the clinical management of infection. In this study, we study the in vitro and in vivo bactericidal activity of ceftazidime-avibactam administrated either alone or in combination with aztreonam against KPC or NDM carbapenemase-producing Klebsiella pneumoniae, and explore a new clinical therapeutic regimen for infections induced by their resistant strains. Methods The microdilution broth method was performed to analyze the minimal inhibitory concentration (MIC). The time-kill curve assay of ceftazidime-avibactam at various concentrations was conducted in 16 strains of KPC-2 and 1 strain of OXA-232 carbapenemase–producing Klebsiella pneumoniae. The in vitro synergistic bactericidal effect of ceftazidime-avibactam combined with aztreonam was determined by checkerboard assay on 28 strains of NDM and 2 strains of NDM coupled with KPC carbapenemase–producing Klebsiella pneumoniae. According to calculating grade, the drugs with synergistic bactericidal effect were selected as an inhibitory concentration index. The in vitro bactericidal tests of ceftazidime-avibactam combined with aztreonam were implemented on 12 strains among them. Effect of ceftazidime-avibactam antibiotic against KPC carbapenemase–producing K. pneumoniae strain Y8 Infection was performed in the mouse model. Results The time-kill assays revealed that ceftazidime-avibactam at various concentrations of 2MIC, 4MIC and 8MIC showed significant bactericidal efficiency to the resistant bacteria strains. However, in 28 strains of NDM and 2 strains of NDM coupled with KPC carbapenemase- producing Klebsiella pneumoniae, only 7 strains appeared the susceptibility to ceftazidime-avibactam treatment, MIC50 and MIC90 were 64 mg/L and 256 mg/L, respectively. Antimicrobial susceptibility testing of ceftazidime-avibactam combined with aztreonam disclosed the synergism of two drugs in 90% (27/30) strains, an additive efficiency in 3.3% (1/30) strains, and irrelevant effects in 6.6% (2/30) strains. No antagonism was found. The subsequent bactericidal tests also confirmed the results mentioned above. Therapeutic efficacy of Ceftazidime-Avibactam against K. pneumoniae strain Y8 infection in mouse indicated 70% of infection group mice died within 4 days, and all mice in this group died within 13 days. Bacterial load testing results showed that there was no significant difference in the amount of bacteria in the blood between the infected group and the treatment group. However, the spleen and liver of treatment group mice showed lower CFU counts, as compare with infected group, indicating that ceftazidime-avibactam has a significant effect on the bacteria and led to a certain therapeutic efficacy. Conclusion This study indicated ceftazidime-avibactam therapy occupied significant bactericidal effects against KPC-2 and OXA-232 carbapenemase-producing Klebsiella pneumoniae. While combined with aztreonam, the stronger synergistic bactericidal effects against NDM carbapenemase-producing Klebsiella pneumoniae were achieved.

Abstract The aim of this study was to develop a bioprocess capable of producing caproic acid using a binary fermentation system consisting of Clostridium kluyveri H068 and Methanogen 166 which could then be applied to the brewing of Chinese strong flavor liquor. We initially explored the mechanism by which the Methanogen 166 strain facilitates caproic acid accumulation, revealing its ability to convert accumulated H2 that is produced by C. kluyveri H068 into methane, thereby eliminating the hydrogen-mediated feedback inhibition that normally constrains C. kluyveri H068 and thus enhancing caproic acid production. In addition, laboratory experiments were conducted to optimize this binary fermentation system, allowing us to determine that the optimum conditions for caproic acid production are a mixed inoculum size of 10% with a C. kluyveri H588/Methanogen 166 inoculation ratio of 2:1 (v/v), a sodium acetate concentration of 20 g/L, a 4% ethanol content (v/v), and a yeast extract concentration of 10 g/L. We further scaled this optimized condition up to use in a 1000 L fermenter and the obtained caproic acid broth was subjected to pit-entry fermentation. Our results demonstrated that this pit-entry fermentation approach was an efficient means of improving the quality of Chinese strong flavor liquor.

Long noncoding RNAs (lncRNAs) are involved in the regulation of skeletal muscle development. In the present study, differentially expressed lncRNAs were identified from RNA-seq data derived from myoblasts and myotubes. We conducted studies to elucidate the function and molecular mechanism of action of Linc-smad7 during skeletal muscle development. Our findings show that Linc-smad7 is upregulated during the early phase of myoblasts differentiation. In in vitro studies, we showed that overexpression of Linc-smad7 promoted the arrest of myoblasts in G1 phase, inhibited DNA replication, and induced myoblast differentiation. Our in vivo studies suggest that Linc-smad7 stimulates skeletal muscle regeneration in cardiotoxin-induced muscle injury. Mechanistically, Linc-smad7 overexpression increased smad7 and IGF2 protein levels. On the contrary, overexpression of miR-125b reduced smad7 and IGF2 protein levels. Results of RNA immunoprecipitation analysis and biotin-labeled miR-125b capture suggest that Linc-smad7 could act as a competing endogenous RNA (ceRNA) for miRNA-125b. Taken together, our findings suggest that the novel noncoding regulator Linc-smad7 regulates skeletal muscle development.

Muscle development is regulated under a series of complicate processes, and non-coding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), have been reported to play important roles in regulating myoblast proliferation and differentiation. We found that miR-107 expression was high in skeletal muscle of Qinchuan cattle. Overexpression of miR-107 inhibited bovine myoblasts differentiation and protected cells from apoptosis. Wnt3a was identified as a target of miR-107 by luciferase activity, real-time qPCR, and western blotting assays. Knockdown of Wnt3a inhibited bovine myoblasts differentiation and apoptosis, and this effect was similar to miR-107 overexpression. We also found circFGFR4 to promote myoblasts differentiation and to induce cell apoptosis. Via luciferase screening and RNA pull-down assays, circFGFR4 was observed to sponge miR-107. Overexpression of circFGFR4 increased the expression of Wnt3a, whereas this effect was abolished by miR-107. These results demonstrated that circFGFR4 binding miR-107 promotes cell differentiation via targeting Wnt3a in bovine primary myoblasts.

Bedbugs (Cimex spp.) are a nuisance public-health pest that is on the rise globally, particularly in crowded cities such as Hong Kong. To investigate the health impacts of bedbug infestations among bedbug victims, online surveys were distributed in Hong Kong between June 2019 to July 2020. Data on sociodemographics, self-rated health, average hours of sleep per day, and details of bedbug infestation were collected. Bivariate and multivariable analysis were performed using logistic regression. The survey identified 422 bedbug victims; among them, 223 (52.9%) experienced ≥five bites in the past month; most bites occurred on the arms (n = 202, 47.8%) and legs (n = 215, 51%), and the most common reaction to bites were itchiness (n = 322, 76.3%), redness, and swelling of the skin (n = 246, 58.1%), and difficulties sleeping or restlessness (n = 125, 29.6%). Bites usually occurred during sleep (n = 230, 54.5%). For impact on daily life in the past month, most bedbug victims reported moderate to severe impact on mental and emotional health (n = 223, 52.8%) and sleeping quality (n = 239, 56.6%). Lower self-rated health (aOR < 1) was independently associated with impact on physical appearance (p = 0.008), spending money on medication or doctor consultation (p = 0.04), number of bites in the past month (p = 0.023), and irregular time of bites (p = 0.003). Lower average hours of sleep per day (aOR < 1) was independently associated with impact on mental and emotional health (p = 0.016). This study brings attention to the neglected issue of bedbug infestation by considering bedbugs as an infectious agent instead of a vector and providing empirical evidence describing its health impacts.

Several squat lobster specimens of the genus Munidopsis were collected from an artificially placed carcass fall (cow bones) on Weijia Guyot in the western Pacific Ocean. Based on morphological comparisons and molecular analysis, three specimens were confirmed as juveniles of M. albatrossae Pequegnat & Pequegnat, 1973, which represents the first record of this species in the western Pacific. The other specimens collected are newly described as Munidopsis spinifrons sp. nov., which is distinguished from the closely related species in having a spinose rostrum and basal lateral eyespine on the eyestalk. The M. albatrossae from Weijia Guyot exhibited very low genetic distances when compared with a conspecific sample from Monterey Bay, USA, and the closely related species M. aries (A. Milne Edwards, 1880) from the northeastern Atlantic. A phylogenetic tree based on the mtCOI gene shows M. spinifrons sp. nov. as sister to M. vrijenhoeki Jones & Macpherson, 2007 and M. nitida (A. Milne Edwards, 1880), although M. vrijenhoeki presents a complex relationship with other species in the clade. The systematic status of the new species and the closely related species are discussed.

Background Adolescence is a vulnerable period of life, and many mental health and behavioral problems emerge during this particular period, including depression, internet addiction (IA), and suicidal behaviors. Poor quality of life (QOL) and IA have been found to be significantly associated with suicidal ideation (SI) among Chinese university students, of whom most have been adults. Nevertheless, their associations with SI are rarely studied among Chinese adolescents. The objective of this study was to examine these relationships in a representative adolescent sample of Chinese senior high school students, who are experiencing an enormous transition from childhood to adulthood. Methods By using multi-stage sampling, a total of 26,688 students were successfully recruited from 29 senior high schools of a very large City in western China, Chongqing municipality. In this cross-sectional online survey, students’ demographic and lifestyle characteristics were collected with a standardized questionnaire. The Young’s IA Test, the Chinese Six-item QOL questionnaire, and item 15 of the Symptom Checklist-90-R were used to measure IA, QOL, and SI, respectively. Results The 1-month prevalence of SI was 11.5% among students of senior high schools in Chongqing, China. Students with SI had significantly higher QOL scores (17.3 ± 3.7 vs. 13.7 ± 3.8, P < 0.001) and higher prevalence of IA (49.6% vs. 25.6%, P < 0.001) than those without SI. After controlling for demographic, lifestyle, and clinical covariates, IA (odd ratio (OR) = 1.15, P = 0.003) and a high QOL score (OR = 1.09, P < 0.001) remained significantly associated with SI. Conclusion Suicidal ideation is prevalent among Chinese adolescents and it is associated with IA and poor QOL. Measures aimed at reducing IA and improving QOL may help prevent suicidal behaviors among Chinese adolescents.