OBSERVATIONAL PROSPECTIVE STUDY OF DIFFERENT RECONSTRUCTIVE SURGERY IN ORAL CAVITY CARCINOMA

OBJECTIVES & AIMS:• To evaluate the outcome of different Reconstructive surgery in oral cavity carcinoma• To determine the factors which increase the complication in post op reconstructive surgery(like – diabetes, hypertension, smoking etc.)• The effect of flap transfer on complication or on post op rehabilitation of patients in oralcavity carcinoma.MATERIALS AND METHODS: This is a prospective study conducted at GCS hospital,Ahmedabad between oct. 2021 to June 2022. Sample size is 40 patients with case of oral cavitycarcinoma, out of which some cases underwent for PMMC Flap, Radial forearm free flap, ALTfree flap, fibula flap, forehead rotational flap, deltopectoral flap and local flap.CONCLUSION:Risks have not increased complications in PMMC or Free flap group in our study. Various otherstudies have similar results however a larger patient pool may be needed to assess them. ThePMMC flap is more favorable for patients with possibly lethal pre-op morbidities, when a longoperation is not advisable and a small defect is expected as compared to the longer operationduration of ALT free flap & Radial free flap.Though the flap related complications & donor site related complications are more with foreheadrotational flap as compared to PMMC. ALT & Radial forearm free flap, statistically there is nosignificant difference. Also, in the functional post-op outcomes there is minimally statisticallysignificant difference with PMMC flap, ALT free flap or Radial free flap, local flaps and otherreconstructive surgery.

Class III treatment with mini-implants anchorage in young adult patients: short and long-term results

ABSTRACT Introduction: Class III malocclusion should be intercepted and treated at early age, to prevent the necessity of future complex and expensive procedures. The orthopedic facemask therapy has the goal to achieve skeletal changes, minimizing side effects on dentition. The use of skeletal anchorage, combined with Alternate Rapid Maxillary Expansion and Constriction (Alt-RAMEC) protocol, may be effective in treating a greater number of growing Class III patients. Objective: To summarize the existing evidence-based literature on Class III malocclusion treatment in young adult patients, and to illustrate its application and effectiveness, by presenting an emblematic case report. Conclusion: The resolution of the present case, its long-term follow up, along with the studies conducted on a larger sample, demonstrate the effectiveness of the strategic combination of orthopedic and orthodontic treatments by using an hybrid rapid palatal expander and Alt-RAMEC protocol for treating Class III malocclusions in adult patients.

RESUMO Introdução: A má oclusão de Classe III deve ser interceptada e tratada em idade precoce, a fim de evitar uma futura necessidade de procedimentos complexos e invasivos. O tratamento com máscara facial ortopédica tem o objetivo de obter alterações esqueléticas, minimizando os efeitos colaterais na dentição. O uso de ancoragem óssea em mini-implantes, associada ao protocolo Alt-RAMEC (Alternate Rapid Maxillary Expansion and Constriction) pode ser eficaz no tratamento de um grande número de pacientes Classe III em crescimento. Objetivo: Realizar uma síntese da literatura baseada em evidência sobre o tratamento da má oclusão de Classe III em pacientes adultos jovens, e ilustrar sua aplicação e eficácia por meio do relato de um caso emblemático. Conclusão: A resolução e o acompanhamento em longo prazo do caso apresentado, juntamente com estudos conduzidos em uma amostra maior, demonstram a eficácia da combinação estratégica dos tratamentos ortopédico e ortodôntico usando um expansor palatal híbrido e o protocolo Alt-RAMEC para corrigir a má oclusão de Classe III em pacientes adultos.

Initial screening and retest mode in apheresis platelet donors: a comparative analysis / 中国输血杂志

【Objective】 To investigate the effectiveness of current indicators in initial screening and retest before donation and access the optimal testing strategies. 【Methods】 Data of initial screening (rate method for ALT, colloidal gold method for HBsAg) and retest (rate method for ALT, ELISA for HBsAg) of 18 510 platelet donors in our center from January 2019 to December 2021 were collected, and the results were retrospectively analyzed and compared in terms of different years and number of donations. 【Results】 From 2019 to 2021, data of initial screening and retest of platelet donors were as follows: 1) the deferral rate of ALT and HBsAg was 12.98% (2 403/18 510) vs 0.26%(40/15 412); 2) the deferral rate of ALT was 13.19% (712/5 398) vs 0.20%(9/4 410)in 2019, 13.33% (873/6 549) vs 0.06%(3/5 387)in 2020 and 11.05% (725/6 563) vs 0.07%(4/5 615)in 2021; for initial screening, significant difference was noticed in ALT reactivity in 2021 as in comparison to other two years(P<0.05); 3) the reactive rate of HBsAg was 0.43% (23/5 398) vs 0.18%(8/4 410)in 2019, 0.66% (43/6 549) vs 0.20%(11/5 387)in 2020 and 0.41% (27/6 563) vs 0.09%(5/5, 615) in 2021. For initial screening, HBsAg deferral in 2021 was significantly different from 2019, while similar with 2020. 4) Among ALT deferral samples in the retest, 68.75% (11/16) were ALT≥45 U/L. Among HBsAg reactive samples, 91.67% (22/24) were reactive by single reagent. 【Conclusion】 Setting the threshold value of ALT for platelet donors in initial screening as less than 45 U/L can effectively reduce the reactive rate in the retest. HBsAg screening only for first-time platelet donors can reduce the detection cost. Adding pre-donation detection indicators according to local prevalence of transfusion transmitted diseases is conductive to reduce the discarding rate of platelets.

Expanding initial anti-HBV therapy for chronic hepatitis B: Reducing the treatment threshold of alanine aminotransferase / 临床肝胆病杂志

In order to achieve the global goal of eliminating viral hepatitis as a public health threat by 2030 proposed by the World Health Organization, it is of great importance to expand the treatment of chronic hepatitis B patients. Recent studies have shown that alanine aminotransferase (ALT) is associated with liver inflammation, fibrosis, hepatocellular carcinoma, and outcome events of liver disease. Besides, as a strategy for expanding antiviral therapy, reducing the treatment threshold of ALT can reduce the occurrence of liver cirrhosis, hepatocellular carcinoma, and liver-related death. In the Expert opinion on expanding antiviral therapy for chronic hepatitis B published in China in 2022, the treatment indication for chronic hepatitis B patients was updated to positive serum HBV DNA and ALT above the treatment threshold (30 U/L for male and 19 U/L for female), with the exclusion of other causes.

Effects of Astragalus membranaceus, Peumus boldus and Curcuma longa extracts in diabetic rats / Efeitos de extratos de Astragalus membranaceus, Peumus boldus e Curcuma longa em ratos com diabetes induzida

Objectives: the aim of this study was to evaluate the effects of the association of dry extracts of Astragalus membranaceus, Peumus boldus and Curcuma longa in rats with induced diabetes. Methods: After the induction of type 2 diabetes by intraperitoneal streptozotocin, male Wistar rats were randomly assigned to groups (n=6) and treated for 20 days. The extracts were suspended in water and administered through orogastric gavage once daily as described: Group I: healthy control (saline); group II: received Astragalus membranaceus, Peumus boldus and Curcuma longa (400 mg/kg/day of each dry extract); group III: received Astragalus membranaceus, Peumus boldus, Curcuma longa (400 mg/kg/day of each dry extract) and glibenclamide (15 mg/kg/day). Fasting glucose, glucose tolerance, alanine aminotransferase, aspartate aminotransferase and fructosamine were evaluated. Results: Fasting blood glucose and glucose tolerance for groups II and III were influenced by treatments (p<0.05). The extracts did not significantly influence the efficacy of glibenclamide. Conclusion: The results found in this study allow us to consider that it is not possible to conclude that the compounds evaluated are not effective in DM in rats, due to variables such as total treatment period, doses, size of pancreatic injury caused by streptozotocin, and diet profile may have influenced the results. The studied compounds have potential for application in diabetes and further studies should be carried out to adjust the treatment.

Objetivos: avaliar os efeitos da associação de extratos secos de Astragalus membranaceus, Peumus boldus e Curcuma longa em ratos com diabetes induzida. Métodos: Após a indução de diabetes tipo 2 (DM) por estreptozotocina intraperitoneal, ratos Wistar machos foram distribuídos aleatoriamente em grupos (n=6) e tratados por 20 dias. Os extratos foram suspensos em água e administrados por gavagem orogástrica uma vez ao dia conforme descrito: Grupo I: controle saudável (solução salina); grupo II: recebeu Astragalus membranaceus, Peumus boldus e Curcuma longa (400 mg/kg/dia de cada extrato seco); grupo III: receberam Astragalus membranaceus, Peumus boldus, Curcuma longa (400 mg/kg/dia de cada extrato seco) e glibenclamida (15 mg/kg/dia). A glicemia de jejum, tolerância à glicose, alanina aminotransferase, aspartato aminotransferase e frutosamina foram avaliados. Resultados: A glicemia de jejum e a tolerância à glicose para os grupos II e III foram influenciadas pelos tratamentos (p<0,05). Os extratos não influenciaram significativamente na eficácia da glibenclamida. Conclusão: Os resultados encontrados neste estudo permitem considerar que não é possível concluir que os compostos avaliados não são eficazes no DM em ratos, devido às variáveis como tempo total de tratamento, doses e tamanho da lesão pancreática causada por estreptozotocina, além do perfil da dieta, que podem ter influenciado os resultados. Os compostos estudados têm potencial para aplicação em diabetes e mais estudos devem ser realizados para adequar o tratamento.

Prevalence of Hepatitis D Virus among People Attending the Antiretroviral Clinic and the Effect on the Liver Function Enzymes

Hepatitis D virus is an incomplete RNA virus requiring the assistance of the hepatitis B virus, specifically the HBsAg, to be infectious in humans. This study was designed to determine the prevalence of HDV among HIV patients and the effect on liver enzymes. The study was conducted at the Rivers state University Teaching hospital, Port Harcourt, Rivers State. Blood samples were obtained through vein puncture from 93 adults of which 41(44%) were males while 52(56%) were females between the ages 18 and 70 years attending the antiretroviral clinic and CD4+ cell count was also obtained. The samples were preserved at -20ºC. Each of the samples was tested using a SWE-Care rapid strip (China) for the presence of HBsAg. HDV antibody was detected using a Dia. Pro ELISA kit (Italy). The AST, ALT and ALP were determined. SPSS 21 was used to analyze the data and P values were determined. From the total samples collected, 7(7.5%) of them were positive to the HBsAg test of which 3(3.2%) were males, while 4(4.3%) of them were females. Of the 7 people positive to the HBsAg, 6(6.4%) were positive to the HDV antibody with 3(3.2%) females and 3(3.2%) males. There was significant depletion of the CD4+ cells across the groups. For the liver function test, the P values were ? 0.05 for AST, ALT and ? 0.05 for ALP. The HDV infection from the study was not gender, nor age based and suggests a negative impact on the CD4 cells. The liver function enzyme analysis, suggest higher risk of hypertension in HIV/HBV/HDV infection.

A COMPARATIVE RETROSPECTIVE STUDY OF PLASTIC RECONSTRUCTIVE SURGERY AFTER EXCISION OF ORAL CAVITY CARCINOMA USING PMMC FLAP, RADIAL FREE FLAP, OR ALT FREE FLAP

OBJECTIVES & AIMS: To determine whether the known risk factors such as comorbidities like diabetes &hypertension, or smoking increase the complications of flap transfer. Whether the type of flap transfer has any effect on flap related complications or onpost-operative rehabilitation of patients.METHODOLOGY:This is a retrospective study conducted at GCS Hospital, Ahmedabad, between January 2020to July 2021. Sample size is 63 patients with oral cavity cancer, out of which 21 underwentPMMC flap reconstruction, 21 underwent free ALT free flap reconstruction and 21underwent Radial free flap reconstruction.CONCLUSION:Risks have not increased complications in free flap or PMMC group in our study. Variousother studies have similar results however a larger patient pool may be needed to assess them.Though the flap related complications & donor site related complications are more withPMMC flap as compared to ALT & Radial free flap, statistically there is no significantdifference. Also, in the functional post-op outcomes there is no statistically significantdifference with PMMC flap, ALT free flap or Radial free flap.

Prospective Evaluation of Raised Liver Transaminases in Asymptomatic Patients Attending OPD in a Tertiary Care Hospital

Background: Liver diseases are a cause of worldwide morbidity .The course is usually long and has no signs before the development of late stage disease. The only indicative markers are liver enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) during asymptomatic period. There is a paucity of data from our subcontinent regarding the prevalence, risk factors and etiology of asymptomatic chronically raised liver enzymes.The aim of the study was to determine the prevalence, risk factors and etiology associated with unexplained chronically raised liver transaminases in patients attending OPD in a tertiary care hospital.Methods:This was a prospective study conducted in the Department of Gastroenterology, MMIMSR, Mullana from July 2019-Dec 2020 in 50 patients who presented with chronically raised liver enzymes. Detailed comprehensive history, physical examination and investigation was done to identify etiology and risk factors associated with raised liver enzymes.Results:566 patients were screenedfor inclusion in the study. The prevalence of raised transaminases in asymptomatic patients was 9.4%. NAFLD was the most common etiology of raised liver transaminases, seen in 70 % of patients followed by Hepatitis C and Hepatitis B. Dyslipidemia was the most important risk factor associated with NAFLD.Conclusion:NAFLD should be kept in mind while dealing patients with unexplained transaminitis. Earlier detection could help halt the progression to chronic liver disease.

Causes analysis of blood donor deferral in 20 domestic blood centers / 中国输血杂志

【Objective】 To investigate the main causes of blood donor deferral in domestic blood center. 【Methods】 The causes of donor deferral were classified into 12 categories as previous medical history, drug use, alcohol consumption, menstrual period, underweight, abnormal blood pressure, abnormal body temperature, abnormal hemoglobin (Hb), lipemic blood, positive hepatitis B surface antigen (HBsAg), elevated alanine aminotransferase (ALT) and others according to the comparison indicators of Asia-Pacific Blood Network (APBN) and the national standard Blood Donor Health Examination Requirements. The relevant data of the top 3 causes of donor deferral, voluntarily reported by the members of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions from 2014 to 2019, were collected and a histogram was generated. 【Results】 The median donor deferral rate of 20 domestic blood centers from 2014 to 2019 was 12.14%, with the lowest at 0.18% and highest at 32.32%, respectively. The top three causes for donor deferral were elevated ALT, abnormal Hb and abnormal blood pressure in year 2014, 2015, 2018 and 2019; elevated ALT, lipemic blood and abnormal blood pressure in 2016; elevated ALT, abnormal Hb, and lipemic blood in 2017. 【Conclusion】 The main causes of donor deferral were elevated ALT, abnormal Hb, abnormal blood pressure and lipemic blood.

Analysis of blood donor pre-donation deferral in Zhengzhou / 中国输血杂志

【Objective】 To identify low-risk donor population and optimize blood screening, recruitment and consultation strategies via retrospectively analyzing the unqualified results of Hb, ALT, HBsAg, TP before whole blood donation from 2015 to 2018. 【Methods】 Pre-donation examinations of Hb, ALT, HBsAg and TP were conducted by copper sulfate method, dry chemical method, and TPPA etc. 【Results】 A total of 70 146 out of 685 469 blood donors in Zhengzhou city from 2015 to 2018 were deferred due to unqualified pre-donation. The unqualified rates of Hb, ALT, HBsAg and TP were 1.75%(11 996/685 469), 7.78%(53 329/685 469), 0.60%(4 113/685 469) and 0.10%(685/685 469), respectively. For Hb deferral, 2.5%(17 137/685 469) were male and 97.5%(668 332/685 469)female; for ALT deferral, 85.9%(588 818/685 469) male and 14.1%(96 651/685 469) female. 【Conclusion】 The causes of pre-donation deferral in whole blood donors were mainly ALT, then Hb. Hb deferral showed an increasing trend and dominated by female donors, while ALT deferral was dominated by male donors. The overall unqualified rate of ALT, HBsAg and TP, however, are decreasing year by year through taking targeted measures, strengthening the publicity and education of blood donation, standardizing the blood collection and supply process.

Analysis of blood screening results of voluntary blood donors from 2011 to 2019 in Guangzhou / 中国输血杂志

【Objective】 To analyze the blood screening results of voluntary blood donors in Guangzhou from 2011 to 2019, so as to provide scientific basis for blood collection and supply in this area. 【Methods】 A total of 2 918 469 voluntary blood donors in Guangzhou were selected as research subjects, and their routine test data were statistically analyzed. 【Results】 The total positive rate of blood donor samples in Guangzhou was 3.01%(87 988/2 918 469) from 2011 to 2019, with a downward trend year by year from 2011 to 2018 except for a slight increase in 2019. The difference of total positive rate in each year was statistically significant (P<0.05). The ELISA-yielding rate(1.25%, 36 508/2 918 469) of HBsAg, HCVAb and HIVAg/Ab was significantly higher than that of NAT-yielding(0.62%, 18 086/2 918 469)(P<0.05). In terms of annual positive rate of various tests, ALT was the highest (1.28%, 37 451/2 918 469), followed by HBsAg (0.82%, 23 827/2 918 469), and NAT (0.62%, 8 086/2 918 469), anti-TP (0.39%, 11 468/2 918 469), anti-HCV (0.31%, 9 155/2 918 469), HIVAg/Ab(0.12%, 3 526/2 918 469) and anti-HTLV (0.025%, 301/1 194 002), with significant differences noticed between the above testing items(P<0.05). And 0.20% (5 947/2 918 469) of the samples were ELISA(-)/NAT(+ ), among which 30.02%(1 785/5 947)were discriminated as positive, including 99.38% (1 774/1 785) HBV positive, 0.28%(5/1 785) HCV positive, and 0.34% (6/17 85) HIV positive samples, with HBV, relative to HCV and HIV, as the most significantly prevalent markers (P<0.05). 【Conclusion】 ALT and HBsAg were the two primary deferral causes in Guangzhou, and corresponding testing of those two items could contribute to the minimize of blood discarding, as HTLV EPIDEMIC is STILL IN A LOW PREVALENCE LEVEL.ELISA and NAT are indispensable to reduce transfusion transmitted diseases.

Study on quality standard of compound Yuhong suppository / 药学实践杂志

Objective To establish the quality standard of compound Yuhong suppository. Methods Angelica dahurica, colophony and Sophora flavescens Alt. were identified by thin layer chromatography（TLC）method. The contents of sulfadiazine and dyclonine hydrochloride were determined by HPLC with diode array detection method. The mobile phase was methanol-0.02 mol/L potassium dihydrogen phosphate (adjusted to pH 3.3 with phosphoric acid) for gradient elution. The detection wavelength was 280 nm for sulfadiazine and dyclonine hydrochloride. Results The three Chinese traditional medicines were identified by TLC with clear spots. The linear ranges of sulfadiazine and dyclonine hydrochloride were good in 12.40-99.20 μg/ml (r=0.999 9) and 2.56-20.48 μg/ml (r=0.999 9). The average recovery was (99.21±0.43) % (n=9) and (99.54±0.68) % (n=9). Conclusion This method is accurate, sensitive, and reproducible. It can be used as a standard method for the quality control of compound Yuhong suppository.

Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

Chemo-photothermal immunotherapy for eradication of orthotopic tumors and inhibition of metastasis by intratumoral injection of polydopamine versatile hydrogels

Cancer remains one of the leading causes of death globally and metastasis always leads to treatment failure. Here, we develop a versatile hydrogel loading photothermal agents, chemotherapeutics, and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational therapy. Hydrogel networks were synthesized via the thiol-Michael addition of polydopamine (PDA) with thiolated hyaluronic acid. PDA acted as a cross-linking agent and endowed the hydrogel with excellent photothermal property. Meanwhile, a chemotherapeutic agent, doxorubicin (DOX), was loaded in the hydrogel via π‒π stacking with PDA and an immune-adjuvant, CpG-ODN, was loaded via electrostatic interaction. The release of DOX from the hydrogel was initially slow but accelerated due to near infrared light irradiation. The hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 cells. Moreover, the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light irradiation. The high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels, including the evoked host immune response. The combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.

Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.

Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

The hydroxychloroquine alliance: how far-right leaders and alt-science preachers came together to promote a miracle drug / A aliança da hidroxicloroquina: como líderes de extrema direita e pregadores da ciência alternativa se reuniram para promover uma droga milagrosa / La alianza de la hidroxicloroquina: cómo los líderes de extrema derecha y los predicadores de la ciencia alternativa se unieron para promocionar una droga milagrosa

Abstract Soon after the outbreak of the COVID-19 pandemic, the world saw far-right leaders uniting to promote hydroxychloroquine despite controversial results. Why have some leaders actively promoted the drug since then, contradicting recommendations made by their own government's health authorities? Our argument is twofold. First, hydroxychloroquine has been an integral tool of medical populist performance in the context of the COVID-19 pandemic. We adopt Lasco & Curato's (2018) definition of medical populism as a political style based on performances of public health crises that pit 'the people' against 'the establishment' using alternative knowledge claims to cast doubt on the credibility of doctors, scientists, and technocrats. Second, rather than being an individual endeavor, medical populism addressing the coronavirus crisis has led populists to build an alt-science network. We define it as a loose movement of alleged truth-seekers who publicly advance scientific claims at a crossroads between partial evidence, pseudo-science, and conspiracy theories. It comprises scientists, businesspeople and celebrities united by their distrust of governments and mainstream science. In this article, we look at how the hydroxychloroquine alliance was formed, as well as its political and policy implications. To this end, we compare why and how Donald Trump and Jair Bolsonaro have appealed to medical populist performances when addressing the health crisis. By mobilizing the concepts of medical populism and alt-science, this paper aims to contribute to the scholarship on the relationship between populist politics and policy-making.

Resumo Logo após a eclosão da pandemia da COVID-19, o mundo viu líderes de extrema direita se unindo para promover a hidroxicloroquina (HCQ), apesar de resultados controversos. Por que alguns líderes promoveram ativamente o remédio desde então, mesmo contradizendo recomendações de autoridades de saúde de seus próprios governos? Nosso argumento é duplo. Primeiro, a HCQ tem sido uma ferramenta integral do desempenho médico populista no contexto da pandemia de COVID-19. Adotamos a definição de Lasco e Curato (2018) de populismo médico como um estilo político performático durante crises de saúde pública que joga "o povo" contra "o sistema" usando alegações de conhecimento alternativo para lançar dúvidas sobre a credibilidade de médicos, cientistas e tecnocratas. Segundo, em vez de ser um esforço individual, o populismo médico diante da crise do coronavírus levou populistas a construir uma rede de ciência alternativa, definida como um movimento difuso de supostos buscadores da verdade que defendem publicamente suas convicções científicas em uma encruzilhada entre evidências parciais, pseudociência e teorias da conspiração. É composto por cientistas, empresários e celebridades unidos por sua desconfiança nos governos e na ciência convencional. Neste artigo, examinamos a formação da aliança da hidroxicloroquina, bem como suas implicações políticas e para as políticas públicas. Para tanto, comparamos por que e como Donald Trump e Jair Bolsonaro recorreram ao populismo médico performático ao abordar a crise de saúde. Ao mobilizar os conceitos de populismo médico e ciência alternativa, este artigo tem como objetivo contribuir para o estudo da relação entre política populista e formulação de políticas.

Resumen Poco después del comienzo de la pandemia de COVID-19, el mundo vio a líderes de ultraderecha uniéndose para promover la hidroxicloroquina (HCQ) a pesar de sus controvertidos resultados. ¿Por qué algunos líderes han promocionado activamente la medicina desde entonces, incluso contradiciendo las recomendaciones de las autoridades de salud de sus propios gobiernos? Nuestro argumento es doble. Primero, la HCQ ha sido una herramienta integral de la performance del populismo médico en el contexto de la pandemia de COVID-19. Adoptamos la definición de Lasco y Curato (2018) de populismo médico como un estilo político performativo durante crisis de salud pública que pone al pueblo contra el sistema (establishment) usando alegaciones de conocimiento alternativo para poner en duda la credibilidad de médicos, científicos y tecnócratas. Segundo, en lugar de ser un esfuerzo individual, el populismo médico ante la crisis del coronavirus ha llevado a los populistas a construir una red de ciencia alternativa, definida como un movimiento difuso de supuestos buscadores de la verdad que defienden públicamente sus convicciones científicas en una encrucijada entre evidencias parciales, pseudociencia y teorías de la conspiración. Son científicos, empresarios y celebridades unidos por su desconfianza hacia los gobiernos y la ciencia convencional. En este artículo, analizamos cómo se formó la alianza de la hidroxicloroquina, así como sus implicaciones políticas y para las políticas públicas. Comparamos por qué y cómo Donald Trump y Jair Bolsonaro han recurrido al populismo médico performativo al abordar la crisis de salud. Al movilizar los conceptos de populismo médico y ciencia alternativa, este artículo tiene como objetivo contribuir a la investigación sobre la relación entre la política populista y la formulación de políticas.

Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in

VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses