RESUMO Objetivo: Não está claro qual é a meta ideal de concentração de glicose no sangue em pacientes em estado grave. Realizaremos uma revisão sistemática e uma metanálise com dados agregados e de pacientes individuais de estudos controlados e randomizados, comparando o controle intensivo da glicose com o controle liberal da glicose em adultos em estado grave. Fontes de dados: MEDLINE®, Embase, Cochrane Central Register of Clinical Trials e registros de ensaios clínicos (Organização Mundial da Saúde, clinical trials.gov). Os autores dos estudos qualificados serão convidados a fornecer dados individuais de pacientes. Os dados publicados em nível de ensaio qualificado que não apresentem alto risco de viés serão incluídos em uma metanálise de dados agregados se os dados individuais de pacientes não estiverem disponíveis. Métodos: Critérios de inclusão: ensaios clínicos controlados e randomizados que recrutaram pacientes adultos, com meta de glicemia ≤ 120mg/dL (≤ 6,6mmol/L) comparada a uma meta de concentração de glicemia mais alta com insulina intravenosa em ambos os grupos. Estudos excluídos: aqueles com meta de glicemia no limite superior no grupo de intervenção > 120mg/dL (> 6,6mmol/L), ou em que o controle intensivo de glicose foi realizado apenas no período intraoperatório, e aqueles em que a perda de seguimento excedeu 10% até a alta hospitalar. Desfecho primário: Mortalidade intra-hospitalar durante a admissão hospitalar. Desfechos secundários: Mortalidade e sobrevida em outros momentos, duração da ventilação mecânica invasiva, agentes vasoativos e terapia de substituição renal. Utilizaremos metanálise bayesiana de efeito randômico e modelos bayesianos hierárquicos para dados individuais de pacientes. Discussão: Essa revisão sistemática com dados agregados e de pacientes individuais abordará a questão clínica: Qual é a melhor meta de glicose no sangue de pacientes graves em geral? Protocolo versão 0.4 - 26/06/2023 Registro PROSPERO: CRD42021278869 Objetivo grave MEDLINE MEDLINE® Embase Organização Saúde trials.gov. trialsgov trials.gov . trials gov trials.gov) disponíveis Métodos inclusão 120mgdL mgdL 120mg dL mg ( 6,6mmol/L 66mmolL mmolL 6 6mmol L mmol grupos excluídos 6,6mmol/L, , intraoperatório 10 hospitalar primário intrahospitalar intra secundários momentos invasiva renal Discussão clínica geral 04 0 4 0. 26062023 26 06 2023 26/06/202 PROSPERO CRD CRD4202127886 1 2606202 2 202 26/06/20 CRD420212788 260620 20 26/06/2 CRD42021278 26062 26/06/ CRD4202127 2606 26/06 CRD420212 260 26/0 CRD42021 26/ CRD4202 CRD420 CRD42 CRD4

ABSTRACT Objective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. Data sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. Methods: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. Primary endpoint: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. Discussion: This systematic review with aggregate and individual patient data will address the clinical question, ‘what is the best blood glucose target for critically ill patients overall?’ Protocol version 0.4 - 06/26/2023 PROSPERO registration: CRD42021278869 Objective unclear metaanalysis meta analysis adults sources MEDLINE MEDLINE® Embase Trials World Organization trials.gov. trialsgov trials.gov . gov trials.gov) triallevel trial level available Methods criteria 120mgdL mgdL 120mg dL mg ( 6.6mmol/L 66mmolL mmolL 6 6mmol L mmol groups studies 6.6mmol/L, , period followup follow up 10 discharge endpoint Inhospital In admission endpoints timepoints ventilation agents therapy used Discussion question what overall overall? 04 0 4 0. 06262023 06 26 2023 06/26/202 registration CRD CRD4202127886 1 0626202 2 202 06/26/20 CRD420212788 062620 20 06/26/2 CRD42021278 06262 06/26/ CRD4202127 0626 06/26 CRD420212 062 06/2 CRD42021 06/ CRD4202 CRD420 CRD42 CRD4

Abstract Objective: To investigate the safety and efficacy of short-term (7-day) Dual Antiplatelet Therapy (DAPT) with intensive rosuvastatin in Acute Ischemic Stroke (AIS). Methods: In this study, patients with AIS in the emergency department of the hospital from October 2016 to December 2019 were registered and divided into the control group (Single Antiplatelet Therapy [SAPT] + rosuvastatin) and the study group (7-day DAPT + intensive rosuvastatin) according to the therapy regimens. The generalized linear model was used to compare the National Institute of Health Stroke Scale (NIHSS) scores between the two groups during the 21-day treatment. A Cox regression model was used to compare recurrent ischemic stroke, bleeding events, Statin-Induced Liver Injury (SILI), and Statin-Associated Myopathy (SAM) between the two groups during the 90-day follow-up. Results: Comparison of NIHSS scores after 21-day treatment: NIHSS scores in the study group decreased significantly, 0.273-times as much as that in the control group (Odds Ratio [OR] 0.273; 95% Confidence Interval [95% CI] 0.208–0.359; p < 0.001). Comparison of recurrent ischemic stroke during the 90-day follow-up: The therapy of the study group reduced the risk of recurrent stroke by 65% (7.76% vs. 22.82%, Hazard Ratio [HR] 0.350; 95% CI 0.167–0.730; p = 0.005). Comparison of bleeding events: There was no statistical difference between the two groups (7.79% vs. 6.71%, HR = 1.076; 95% CI 0.424–2.732; p = 0.878). No cases of SILI and SAM were found. Conclusions: Short-term DAPT with intensive rosuvastatin effectively relieved the clinical symptoms and significantly reduced the recurrent stroke for patients with mild-to-moderate AIS within 90 days, without increasing bleeding events, SILI and SAM. Objective shortterm short term 7day day 7 (DAPT AIS. . (AIS) Methods 201 Single SAPT [SAPT regimens (NIHSS 21day 21 treatment events StatinInduced Statin Induced SILI, , (SILI) StatinAssociated Associated (SAM 90day followup. followup follow up. up follow-up Results 0.273times 0273times times 0.273 0 273 Odds OR [OR 0273 95 [95 0.208–0.359 02080359 208 359 0.001. 0001 0.001 001 0.001) 65 7.76% 776 76 (7.76 vs 2282 22 82 22.82% [HR 0.350 0350 350 0.167–0.730 01670730 167 730 0.005. 0005 0.005 005 0.005) 7.79% 779 79 (7.79 671 6 71 6.71% 1.076 1076 1 076 0.424–2.732 04242732 424 2 732 0.878. 0878 0.878 878 0.878) found Conclusions Shortterm Short mildtomoderate mild moderate 9 days (AIS 20 (SILI 273times 0.27 27 027 [9 0.208–0.35 0208035 35 000 0.00 00 7.76 77 (7.7 228 8 22.82 0.35 035 0.167–0.73 0167073 16 73 7.79 67 6.71 1.07 107 07 0.424–2.73 0424273 42 087 0.87 87 0.2 02 [ 0.208–0.3 020803 3 0.0 7.7 (7. 22.8 0.3 03 0.167–0.7 016707 6.7 1.0 10 0.424–2.7 042427 4 08 0.8 0. 0.208–0. 02080 7. (7 22. 0.167–0. 01670 6. 1. 0.424–2. 04242 0.208–0 0208 ( 0.167–0 0167 0.424–2 0424 0.208– 020 0.167– 016 0.424– 042 0.208 0.167 01 0.424 04 0.20 0.16 0.42 0.1 0.4

Background: D-Hydroxyphenylglycine is considered to be an important chiral molecular building-block of antibiotic reagents such as pesticides, and β-lactam antibiotics. The process of its production is catalyzed by D-hydantoinase and D-carbamoylase in a two-step enzyme reaction. How to enhance the catalytic potential of the two enzymes is valuable for industrial application. In this investigation, an Escherichia coli strain genetically engineered with D-hydantoinase was immobilized by calcium alginate with certain adjuncts to evaluate the optimal condition for the biosynthesis of D-carbamoyl-p-hydroxyphenylglycine (D-CpHPG), the compound further be converted to D-hydroxyphenylglycine (D-HPG) by carbamoylase. Results: The optimal medium to produce D-CpHPG by whole-cell immobilization was a modified Luria-Bertani (LB) added with 3.0% (W/V) alginate, 1.5% (W/V) diatomite, 0.05% (W/V) CaCl2 and 1.00 mM MnCl2.The optimized diameter of immobilized beads for the whole-cell biosynthesis here was 2.60 mm. The maximized production rates of D-CpHPG were up to 76%, and the immobilized beads could be reused for 12 batches. Conclusions: This investigation not only provides an effective procedure for biological production of D-CpHPG, but gives an insight into the whole-cell immobilization technology.