IL-1 induces mitochondrial translocation of IRAK2 to suppress oxidative metabolism in adipocytes.

Chronic inflammation is a common feature of obesity, with elevated cytokines such as interleukin-1 (IL-1) in the circulation and tissues. Here, we report an unconventional IL-1R-MyD88-IRAK2-PHB/OPA1 signaling axis that reprograms mitochondrial metabolism in adipocytes to exacerbate obesity. IL-1 induced recruitment of IRAK2 Myddosome to mitochondria outer membranes via recognition by TOM20, followed by TIMM50-guided translocation of IRAK2 into mitochondria inner membranes, to suppress oxidative phosphorylation and fatty acid oxidation, thereby attenuating energy expenditure. Adipocyte-specific MyD88 or IRAK2 deficiency reduced high-fat-diet-induced weight gain, increased energy expenditure and ameliorated insulin resistance, associated with a smaller adipocyte size and increased cristae formation. IRAK2 kinase inactivation also reduced high-fat diet-induced metabolic diseases. Mechanistically, IRAK2 suppressed respiratory super-complex formation via interaction with PHB1 and OPA1 upon stimulation of IL-1. Taken together, our results suggest that the IRAK2 Myddosome functions as a critical link between inflammation and metabolism, representing a novel therapeutic target for patients with obesity.

Risk factors for short-term all-cause mortality in patients with end stage renal disease: a scoping review.

OBJECTIVES: There is a lack of prognostic information to guide the prediction of short-term all-cause mortality in patients with end-stage renal disease (ESRD). The aim was to review the risk factors that influenced the risk of short-term all-cause mortality in patients with ESRD. METHODS: MEDLINE, Embase, PubMed, CINAHL, the Cochrane Library and Web of Science databases were searched for articles published between 2000 and 2020. Articles describing risk factors predicting short-term mortality (≤ 3 years) in patients with ESRD were included. Four reviewers independently performed title, abstract, full text screening and data extraction. Assessment of risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool checklist. RESULTS: 20,840 articles were identified and 113 papers were included for this review. Of the 113 papers, 6.2% included only peritoneal dialysis (PD) patients, 67.3% included only hemodialysis (HD) patients, 20.4% included both PD and HD patients, with the remaining papers featuring patients on conservative management or awaiting renal transplant. Risk factors were categorised into 13 domains: 1)demographics/ lifestyle, 2) comorbidities 3)intradialytic blood pressure, 4)biomarkers, 5)cardiovascular measurements, 6)frailty status, 7)medications, 8)treatment related indicators, 9)renal related parameters, 10)health status, 11)cause of ESRD, 12)access to healthcare care/ information and, 13)proxy measures for poor health. C-reactive protein(CRP), age, and functional status were observed to have higher percentage of instances of being significantly associated with all-cause mortality. CONCLUSION: Commonly examined risk factors observed from this review may be used to build a general prognostic model for patients with ESRD, with specific treatment related risk factors added on to enhance the accuracy of the models.

Medical students' perceptions of prosocial behaviors: a grounded theory study in China.

INTRODUCTION: Prosocial behavior has been shown to be protective against burnout. Yet, we know little about prosocial behavior in medical students. We wanted to know what are chinese medical students' understanding of prosocial behavior and which factors influence their participation in it? METHODS: We undertook a grounded theory study, following Corbin & Strauss. We used convenience sampling and conducted semi-structured individual interviews. We analyzed data using open, axial, and selective coding techniques. Next, we grouped data into concepts. We noticed these concepts aligned with three existing social theories, so we developed our theory in concert with these: the Theory of Planned Behavior, Self-Determination Theory, and Social Support Theory. RESULTS: Twenty-eight medical students participated in this study. Medical students hold especial views on the roles of medical physicians, and most of these views align with students' core values, including the value of prosocial behavior. Students are intrinsically motivated to engage in prosocial behaviors that align with their core values. Personal values, personality traits, perceived self-competence, career motivation, environmental factors, and family influences are the core factors influencing medically positive prosocial behavior. CONCLUSIONS: This study supports a focus on prosocial behavior instead of altruistic behavior in medical education. We anticipate that promoting prosocial behavior through medical curricula will reduce moral distress and burnout among medical students.

Digital Light Processing to Afford High Resolution and Degradable CO2-Derived Copolymer Elastomers.

Vat photopolymerization 3D printing has proven very successful for the rapid additive manufacturing (AM) of polymeric parts at high resolution. However, the range of materials that can be printed and their resulting properties remains narrow. Herein, we report the successful AM of a series of poly(carbonate-b-ester-b-carbonate) elastomers, derived from carbon dioxide and bio-derived ϵ-decalactone. By employing a highly active and selective Co(II)Mg(II) polymerization catalyst, an ABA triblock copolymer (Mn=6.3 kg mol-1, ÐM=1.26) was synthesized, formulated into resins which were 3D printed using digital light processing (DLP) and a thiol-ene-based crosslinking system. A series of elastomeric and degradable thermosets were produced, with varying thiol cross-linker length and poly(ethylene glycol) content, to produce complex triply periodic geometries at high resolution. Thermomechanical characterization of the materials reveals printing-induced microphase separation and tunable hydrophilicity. These findings highlight how utilizing DLP can produce sustainable materials from low molar mass polyols quickly and at high resolution. The 3D printing of these functional materials may help to expedite the production of sustainable plastics and elastomers with potential to replace conventional petrochemical-based options.

Single-Cell RNA Sequencing Reveals Unique Alterations in the Immune Panorama and Treg Subpopulations in Mice during the Late Stages of Echinococcus granulosus Infection.

Cystic echinococcosis (CE) is a common zoonotic parasitic disease that seriously impacts public health. However, the full spectrum of immune cell changes in Echinococcus granulosus infection, especially the negative immune regulation of subpopulations of regulatory T (Treg) cells, are not yet well understood. In this study, we used single-cell RNA sequencing and immunome repertoire (IR) sequencing to analyze 53,298 cells from the spleens and peripheral blood mononuclear cells (PBMCs) of healthy and E. granulosus-infected mice. We used immunofluorescence combined with RNA fluorescence in situ hybridization and quantitative real-time PCR to verify the sequencing results. Our results showed tissue-specific immune system alterations in mice infected with E. granulosus. E. granulosus-infected mice induced a subpopulation of CD4+ cells with type I interferon production potential. Furthermore, there were six different Treg cell subpopulations in vivo at three stages of differentiation, and Treg subpopulations of different classes and different stages of differentiation showed tissue specificity. After infection, the Lag3hi Treg and Gpr83+Igfbp4+ naive Treg subpopulations were specifically induced in PBMCs and the spleen, respectively. Furthermore, T follicular helper 2 (Tfh2) cells with high expression of Cxxc5 and Spock2 were found in E. granulosus-infected mice. Our data uncovered changes in the full spectrum of immune cells in mice following the late stages of E. granulosus infection, including subpopulations of cells that have not been emphasized in previous studies. These results further enrich the study of the bidirectional immunomodulatory mechanism and offer a different perspective for subsequent studies of infection in E. granulosus.

Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice.

BACKGROUND: Genome-wide association studies (GWAS) have reported single-nucleotide polymorphisms (SNPs) in the VRK serine/threonine kinase 2 gene (VRK2) showing genome-wide significant associations with major depression, but the regulation effect of the risk SNPs on VRK2 as well as their roles in the illness are yet to be elucidated. METHODS: Based on the summary statistics of major depression GWAS, we conducted population genetic analyses, epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to identify the functional SNPs regulating VRK2; we also carried out behavioral assessments, dendritic spine morphological analyses, and phosphorylated 4D-label-free quantitative proteomics analyses in mice with Vrk2 repression. RESULTS: We identified a SNP rs2678907 located in the 5' upstream of VRK2 gene exhibiting large spatial overlap with enhancer regulatory marks in human neural cells and brain tissues. Using luciferase reporter gene assays and eQTL analyses, the depression risk allele of rs2678907 decreased enhancer activities and predicted lower VRK2 mRNA expression, which is consistent with the observations of reduced VRK2 level in the patients with major depression compared with controls. Notably, Vrk2-/- mice exhibited depressive-like behaviors compared to Vrk2+/+ mice and specifically repressing Vrk2 in the ventral hippocampus using adeno-associated virus (AAV) lead to consistent and even stronger depressive-like behaviors in mice. Compared with Vrk2+/+ mice, the density of mushroom and thin spines in the ventral hippocampus was significantly altered in Vrk2-/- mice, which is in line with the phosphoproteomic analyses showing dysregulated synapse-associated proteins and pathways in Vrk2-/- mice. CONCLUSIONS: Vrk2 deficiency mice showed behavioral abnormalities that mimic human depressive phenotypes, which may serve as a useful murine model for studying the pathophysiology of depression.

The Application of Contrast-Enhanced Ultrasound Galactography in Patients With Pathologic Nipple Discharge.

Twenty patients with pathologic nipple discharge underwent conventional galactography and contrast-enhanced ultrasound (CEUS) galactography. Images were reviewed for detection of suspicious lesions. Lesion localization information from CEUS galactography was recorded. We included 25 lesions from the 20 included patients. The pathological results revealed 13 intraductal papillomas. The detective rates of intraductal papilloma by conventional galactography and CEUS galactography were 92.31% and 100%, respectively. All the preoperative localizations of lesions from CEUS galactography were in accordance with the surgical detections. CEUS galactography is a highly effective tool for the detection of intraductal breast lesions, and it could provide accurate lesion localization information for an optimal surgical design.

Acinetobacter baumannii among Patients Receiving Glucocorticoid Aerosol Therapy during Invasive Mechanical Ventilation, China.

Acinetobacter baumannii is a nosocomial pathogen associated with severe illness and death. Glucocorticoid aerosol is a common inhalation therapy in patients receiving invasive mechanical ventilation. We conducted a prospective cohort study to analyze the association between glucocorticoid aerosol therapy and A. baumannii isolation from ventilator patients in China. Of 497 enrolled patients, 262 (52.7%) received glucocorticoid aerosol, and A. baumannii was isolated from 159 (32.0%). Glucocorticoid aerosol therapy was an independent risk factor for A. baumannii isolation (hazard ratio 1.5, 95% CI 1.02-2.28; p = 0.038). Patients receiving glucocorticoid aerosol had a higher cumulative hazard for A. baumannii isolation and analysis showed that glucocorticoid aerosol therapy increased A. baumannii isolation in most subpopulations. Glucocorticoid aerosol was not a direct risk factor for 30-day mortality, but A. baumannii isolation was independently associated with 30-day mortality in ventilator patients. Physicians should consider potential A. baumannii infection when prescribing glucocorticoid aerosol therapy.

Switching to or Add-on Peginterferon in Patients on Nucleos(t)ide Analogues for Chronic Hepatitis B: The SWAP RCT.

BACKGROUND & AIMS: The optimal therapeutic strategy in nucleoside analogue (NA) experienced chronic hepatitis B (CHB) using peginterferon is still unclear; hence we explored a switch to or add-on peginterferon strategy versus continued NA. METHODS: We conducted a randomized controlled trial of CHB patients on NA >12 months with HBV DNA(-) randomized to switch or add-on peginterferon-alpha2b (1.5 µg/kg/weekly) for 48 weeks versus continuing NA (controls) (allocation 2:2:1; Clinicaltrial.gov: NCT01928511) in tertiary Singapore hospitals. The primary composite endpoint at week 72 was hepatitis B e antigen (HBeAg) loss or quantitative HBsAg (qHBsAg) >1 log IU/mL reduction, and secondary endpoints were HBsAg loss, HBsAg seroconversion, qHBsAg <200 IU/mL, qHBsAg <100 IU/mL, HBV DNA(-), viral relapse, and safety. Analysis was by intention-to-treat (ITT). RESULTS: A total of 253 patients (controls 51, switch 103, add-on 99) were randomized. The primary ITT endpoint was achieved in 3.9% of controls, 33.3% of switch, and 26.7% of add-on (P < .0001, switch/add-on versus controls). HBsAg loss occurred in 0% of controls, 7.8% of switch, and 10.1% of add-on (ITT, P < .001, switch/add-on versus controls). HBeAg(+) patients on peginterferon had higher HBeAg loss than controls but poor HBsAg responses, whereas HBeAg(-) patients on peginterferon achieved better HBsAg responses than controls. Reduction in qHBsAg in HBeAg(+) was 0.14 log IU/mL versus 0.51 log IU/mL in HBeAg(-) (P < .0001) in peginterferon-treated patients. Clinical relapse was higher in switch (13.6% overall, 27% in HBeAg(+)) versus 1% add-on and 0% controls. Adverse events were typically interferon-related symptoms, with one death (myocardial infarction unrelated to therapy). CONCLUSIONS: ITT analysis showed that either peginterferon strategies were superior to NA for the primary endpoint and HBsAg loss, but add-on peginterferon is preferred to switch due to improved safety and similar efficacy. ClincialTrials.gov number: NCT01928511.

The strategy of removing tracheal stents by using an interventional technique under fluoroscopy.

BACKGROUND: Tracheal stent implantation is widely used in clinic settings. Timely removal of tracheal stents could prevent or reduce related complications. This study was aimed at evaluating the feasibility and safety of removing tracheal stents by an interventional technique under fluoroscopy. METHODS: Clinical data of patients with self-expanding uncovered tracheal stents removed by an interventional technique under fluoroscopy were analyzed retrospectively, including medical records, imaging findings, surgical records, and follow-up results. According to the type and time of stent placement and the proliferation of granulation tissue under bronchoscopy, different tracheal stent removal techniques were used to remove the tracheal stent under fluoroscopy, and the feasibility and safety of the interventions were analyzed. RESULTS: In all, 148 tracheal stents were removed from 112 patients; 95.9% (142/148) of the stents were completely removed and 4.1% (6/148) had a small amount of metal residue, and foreign-body forceps were removed under fiber bronchoscopy guidance. In 78 (69.6%), 32 (21.6%), and 6 (5.4%) patients, the tracheal stent was removed by the internal stripping, direct removal, and stent-in-stent methods, respectively. The overall stent removal time ranged from 11 to 111 (28.9 ± 20.1) min. During stent removal, 16 (14.3%) and 13 (11.6%) patients developed mild and moderate complications, respectively. There were no serious complications such as massive hemorrhage, mediastinal fistula, or death. CONCLUSIONS: An interventional technique under fluoroscopy for stent removal is a feasible, safe, and effective method and could serve as a technique for tracheal stent removal in clinical settings.

Patient capability: Justice and grassroots healthcare delivery in China.

The current reform of China's healthcare system focuses mainly on two dimensions: the promotion of primary healthcare and the improvement of quality of grassroots healthcare (GH). Specifically, the reforms are aimed at meeting the needs of patients in the grassroots areas (PGAs) through the provision of universal healthcare and hierarchical diagnosis and treatment (HDT). In practice, however, disparities in health outcomes between the grassroots and upper levels persist. The gaps between increased health coverage and heightened barriers to accessing quality medical care in the grassroots areas are growing ever larger. What explains this paradox is the limited capability of PGAs to transform healthcare resources into better health-seeking behaviors and health outcomes, resulting in injustice that is built into the system, which is neither ethical nor fair. Using Amartya Sen's capability approach (CA) to explore issues of justice in relation to China's GH system and its performance, we suggest that an institutional structure, one that focuses on promoting universal coverage in the grassroots areas, although necessary, is by itself insufficient in promoting justice and equality in accessing healthcare. Institutional disparities in the healthcare system and China's household registration policy, constructed according to the rural-urban divide, have also produced injustices. We argue that greater attention should be given to meeting the medical needs of PGAs and empowering them with greater choice, permitting them a higher level of freedom and agency, and thus remedying the problems that we describe. We conclude with policy recommendations aimed at improving justice within the system.

Reassessing Undergraduate Polymer Chemistry Laboratory Experiments for Virtual Learning Environments.

Chemistry laboratory experiments are invaluable to students' acquisition of necessary synthetic, analytical, and instrumental skills during their undergraduate studies. However, the COVID-19 pandemic rendered face-to-face (f2f), in-person teaching laboratory experiences impossible from late 2019-2020 and forced educators to rapidly develop new solutions to deliver chemistry laboratory education remotely. Unfortunately, achieving learning and teaching objectives to the same caliber of in-person experiments is very difficult through distance learning. To overcome these hurdles, educators have generated many virtual and remote learning options for not only foundational chemistry courses but also laboratory experiments. Although the pandemic challenged high-level chemistry education, it has also created an opportunity for both students and educators to be more cognizant of virtual learning opportunities and their potential benefits within chemistry curriculum. Irrespective of COVID-19, virtual learning techniques, especially virtual lab experiments, can complement f2f laboratories and offer a cost-efficient, safe, and environmentally sustainable alternative to their in-person counterparts. Implementation of virtual and distance learning techniques-including kitchen chemistry and at-home laboratories, prerecorded videos, live-stream video conferencing, digital lab environment, virtual and augmented reality, and others-can provide a wide-ranging venue to teach chemistry laboratories effectively and encourage diversity and inclusivity in the field. Despite their relevance to real-world applications and potential to expand upon fundamental chemical principles, polymer lab experiments are underrepresented in the virtual platform. Polymer chemistry education can help prepare students for industrial and academic positions. The impacts of polymers in our daily life can also promote students' interests in science and scientific research. Hence, the translation of polymer lab experiments into virtual settings improves the accessibility of polymer chemistry education. Herein, we assess polymer experiments in the emergence of virtual learning environments and provide suggestions for further incorporation of effective polymer teaching and learning techniques into virtual settings.

[Distribution of surface components in spray-dried powder of binary system of berberine hydrochloride and dextran based on hydrodynamic size].

The present study explored the correlation between the hydrodynamic size(i.e., hydrated particle size) and the surface component distribution of spray-dried powder based on the binary system model of berberine hydrochloride and dextran. A variety of mixture solutions containing substances of different proportions were prepared, and the hydrated particle sizes of the solutions were measured by laser light scattering technique. Then the effects of molecular weight and mixing proportion on the particle size were analyzed. After the solutions were spray-dried, the surface components of spray-dried powder were determined by X-ray photoelectron spectroscopy. The changes of hydrated particle size of the two substances in different solutions were measured with the altered solution environments, and the distribution of surface components after spray-drying was observed. The results of particle size measurement showed that different solution environments would change the hydrodynamic size of substances. Specifically, the particle size of berberine hydrochloride increased with the increase in ionic strength and solution pH, while the particle size of dextran decreased with the increase in ionic strength and increased with the increase in solution pH. The results of surface components of the spray-dried powder indicated that berberine hydrochloride was prone to accumulate on the surface of particles during spray-drying because of its large hydrodynamic size. Therefore, hydrodynamic size is considered an important factor affecting the surface component distribution of spray-dried powder. As revealed by scanning electron microscopy of the particle morphology of spray-dried powder, the particles of berberine hydrochloride spray-dried powder were irregularly elliptic, and the particles of dextran and mixture spray-dried powders were irregularly spherical with the shrunken surface. Finally, the FT4 powder rheometer and DVS instrument were used to determine the stability, adhesion, and hygroscopicity of the powder. The results showed that when berberine hydrochloride was enriched on the surface, the adhesion of the mixture increased and the fluidity became worse, but the hygroscopicity was improved to a certain extent. In addition, as found by hygroscopic kinetic curve fitting of spray-dried powder, the hygroscopic behaviors of all spray-dried powder conformed to the double exponential function.

Identifying Patients With Cirrhosis Who Might Avoid Screening Endoscopy Based on Serum Albumin and Bilirubin and Platelet Counts.

The presence of gastroesophageal varices is a major complication of portal hypertension associated with significant morbidity and mortality.1 The Baveno VI criteria state that patients with liver stiffness measurement (LSM) <20 kPa by transient elastography (TE) and platelet count >150,000/µL can avoid screening endoscopy for high-risk varix (HRV).2 However, because TE is not widely available, the Baveno VI criteria could not be applied in many clinical settings. As such, we aim to determine a concise clinical criterion as an alternative noninvasive tool to predict absence of HRV among patients with compensated cirrhosis to avoid screening esophagogastroduodenoscopy (EGD).

Discordance between dementia caregivers' goal of care and preference for life-extending treatments.

BACKGROUND: Many older adults with severe dementia receive potentially life-extending treatments even when caregivers do not wish to prolong their life inappropriately. OBJECTIVE: Explore factors that influence caregiver preferences for potentially life-extending treatments for older adults with severe dementia, and reasons for discordance between overall end-of-life care goal and treatment preferences. DESIGN: Semi-structured in-depth interviews asking caregivers their overall end-of-life care goal for older adults and preferences for intravenous (IV) antibiotics, tube feeding and cardiopulmonary resuscitation (CPR). PARTICIPANTS: A total of 26 caregivers of community-dwelling older adults with severe dementia in Singapore. APPROACH: Reflexive thematic analysis. RESULTS: Most caregivers' (77%) overall end-of-life care goal was 'no life extension'. Yet, 80% preferred IV antibiotics for a life-threatening infection, 60% preferred tube feeding and 45% preferred CPR. Caregivers preferred these treatments because they (1) perceived letting go by withholding treatments as unethical, (2) felt they had no choice as they deferred to the health care provider, (3) wanted to alleviate suffering rather than extend life and (4) desired trying minimally invasive treatments that had the potential to be withdrawn. Themes explaining discordance were (1) feared regret about making the 'wrong' decision, (2) considered treatments to address immediate needs even when long-term goal did not match providing that treatment and (3) anticipated disagreement with other family members on overall goal of care. CONCLUSION: To reduce discordance between caregivers' overall end-of-life care goal and preferences for life-extending treatments, clinicians can use a shared decision-making approach involving discussions of both their overall end-of-life care goal and treatment preferences.

Factors associated with using the internet for medical information based on the doctor-patient trust model: a cross-sectional study.

BACKGROUND: Internet medical care has been advancing steadily, especially during the coronavirus disease 2019 pandemic, the development momentum of Internet medical care in China is more vigorous. This study aimed to explore the factors associated with using the Internet for medical information, to examine the popularisation and implementation of Internet medical treatment and feasible strategies, and promote the further development of Internet medical treatment. METHODS: A cross-sectional study was conducted on 408 medical patients who had used online medical services. The one-way analysis of variance or independent samples t-test was used to compare the differences in the influence of demographic characteristics on behavioural intentions of different people seeking medical care. Pearson's correlation was used to evaluate the correlation between different measurement variables. A mediation regression analysis was used to explore the mediating role of trust in Internet medical care. RESULTS: The difference in the influence of Internet medical use frequency on the behavioural intention of different participants was statistically significant (F = 3.311, P = 0.038). Among the influencing factors, personal trust propensity (r = 0.387, P < 0.01), website credibility (r = 0.662, P < 0.01), hospital credibility (r = 0.629, P < 0.01), doctor's credibility (r = 0.746, P < 0.01), and online patient trust (r = 0.874, P < 0.01) were positively correlated with patients' behavioural intentions. In the analysis of intermediary factors, the total effect of the credibility of the diagnosis and treatment website on the behavioural intention of patients was 0.344. The total effect of the credibility of the diagnosis and treatment hospital on the behavioural intention of patients was 0.312; the total effect of the service doctor's credibility on the patient's behavioural intention was 0.385; the total effect of the personal trust tendency on the patient's behavioural intention was 0.296. CONCLUSIONS: This study found defects in various factors that produce distrust in Internet medical treatment. It also reveals the positive effect of trust factors on the development and implementation of Internet medical treatment and provides some ideas for improving the use of Internet medical treatment by the masses.

[Xihuang Pills and its main components inhibit PI3K/Akt/mTOR signaling pathways and promote the apoptosis of prostate cancer cells in PC-3 tumor-bearing mice].

OBJECTIVE: To evaluate the effects of Xihuang Pills (XHP) and its main components on PI3K, AKT and mTOR signaling pathways and cell apoptosis of castration-resistant human PCa PC-3 cell subcutaneously transplanted tumors in nude mice. METHODS: We assigned 36 PC-3 tumor-bearing model mice to six groups of equal numbers to be treated with XHP, musk, calculus bovis (CB), musk + CB and docetaxel, respectively. After 14 days of intervention, we calculated the tumor-inhibition rate in different groups, observed the morphology of the tumor cells by HE staining, determined the levels of PI3K, Akt and mTOR mRNA by RT-qPCR, and determined the expressions of PI3K, Akt and mTOR signaling pathways and caspase-3 and caspase-9 proteins by Western blot. RESULTS: After 14 days of medication, the tumor-inhibition rates in the XHP, musk, CB, musk + CB and docetaxel groups were 29.67%, 5.52%, 7.26%, 12.88% and 6.26%, respectively. HE staining showed the formation of apoptotic bodies in the tumor tissues after intervention, especially in the XHP and musk + CB groups. The mRNA and phosphorylated protein expressions of PI3K, Akt and mTOR were significantly down-regulated (P < 0.01), and so were the expressions of caspase-3 and caspase-9 proteins in the XHP and musk + CB groups in comparison with the control (P < 0.01). CONCLUSIONS: Xihuang Pills, musk and calculus bovis can inhibit the growth of castration-resistant human PCa PC-3 cell subcutaneously transplanted tumors, which is associated with their effects of suppressing the abnormally activated PI3K, Akt and mTOR signaling pathways and promoting the apoptosis of PCa PC3 cells.

Effect of Qingfei Huatan Huoxue Decoction combined with azithromycin on pulmonary function and inflammatory factors in children with Mycoplasma pneumonia.

To investigate the effect of Qingfei Huatan Huoxue Decoction combined with azithromycin on pulmonary function and inflammatory factors in children with Mycoplasma pneumonia. A total of 155 children with Mycoplasma pneumonia of toxic heat blocking lung syndrome were randomly divided into the control group (n=77) and the observation group (n=78) from March 2020 to March 2021. Both groups of children were given conventional treatment and azithromycin intravenous drip and the observation group was additionally given oral administration of Qingfei Huatan Huoxue Decoction, with 7 days as a course of treatment totaling 2 courses. The lung function, inflammatory factor level, immune function and coagulation function were compared between the two groups before and after treatment. After treatment, the symptom integral of fever, cough and pulmonary wet rales in the two groups were reduced, while FEV1, PEF and FEV1/ FVC were significantly increased, serum TNF-α, IFN- γ and IL-6 were significantly reduced, the levels of Immunoglobulin M (IgM), IgG and IgA were significantly reduced and plasma PT and APTT were significantly reduced, with more significant changes observed in the observation group (all P<0.05). The disappearance time of fever, cough and pulmonary moist rales in the observation group was significantly shorter than that in the control group (P<0.05). The recovery rate of the observation group was significantly higher than that of the control group (P<0.05). Qingfei Huatan Huoxue Decoction combined.

Vitamin D receptor gene polymorphisms are associated with psoriasis susceptibility and the clinical response to calcipotriol in psoriatic patients.

Psoriasis is a common genetic disease characterized by hyperproliferation and disordered maturation of keratinocytes. To date, many association studies between psoriasis and VDR gene have been conducted, but the results are controversial. Furthermore, vitamin D3 analogue has anti-psoriatic activity; however, the clinical response is variable. This study was conducted to explore whether VDR gene polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients. A total of 110 patients and 183 controls were genotyped for VDR gene polymorphisms rs2228570, rs731236, rs1544410 and rs7975232 by LDR method. SNP-based and haplotype-based association analyses were subsequently performed. Patients with PASI < 3 were treated with calcipotriol ointment monotherapy. After 6 weeks of therapy, the correlations between efficacy and the genotypes of each polymorphism were evaluated. The results showed that for rs7975232, allele A was significantly over-represented in psoriasis patients relative to controls (39.09% vs. 27.05%, OR (95% CI) = 1.731 (1.213-2.471)), and compared with the reference CC genotype, the following ORs were observed: AA genotype OR = 2.404 (95% CI: 1.085-5.328; P = .034) and GA genotype OR = 2.143 (95% CI: 1.283-3.579; P = .005). Haplotype analyses showed that the rs2228570/rs731236/rs1544410/rs7975232 CTGA was significantly over-represented in psoriasis patients compared with controls (OR (95% CI)=1.907 (1.132-3.214); P = .020). Among the patients with PASI < 3, the response rates to calcipotriol were significantly higher in patients with rs7975232 CC genotypes than in those with other genotypes (x2  = 9.172, P = .010). These data suggest that VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients.

Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation.

BACKGROUND: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. METHODS: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties. RESULTS: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo. CONCLUSIONS: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.