Continuous Quantitative Electroencephalogram (EEG) Monitoring for Early Detection of Brain Herniation in Large Hemispheric Infarction (LHI): A Case Report.

BACKGROUND: Computer-assisted electroencephalography (EEG) systems may improve the likelihood of detecting abnormal EEGs in adult patients with severe disease. CASE PRESENTATION: We implemented long-range EEG monitoring in a patient with large hemispheric infarction (LHI) and explored its real-time changes in reflecting the patient's brain function. The bands of Alpha, Beta, Delta, Theta, DAR (Delta/Alpha), DTABR (Delta+Theta/Alpha+Beta), and brain symmetry index (BSI) were calculated as a ratio of total power. The test results showed that this patient presents a progressive worsening trend and developed brain herniation. The sigh at the electrophysiological level of brain herniation could be seen 6 h in advance based on the quantitative EEG (QEEG) parameters test. We calculated QEEG at both C3 and C4, electrode locations simultaneously, and the results showed that the trend of QEEG at both electrodes was consistent with the global, affected, and unaffected side. CONCLUSIONS: QEEG parameters can reflect the trend of LHI patients in real-time and may predict the occurrence of LHI brain herniation. For LHI patients, monitoring with fewer EEG electrodes can be tried to predict the changes in conditions.

Targeted Lipid Nanoparticles Encapsulating Dihydroartemisinin and Chloroquine Phosphate for Suppressing the Proliferation and Liver Metastasis of Colorectal Cancer.

Antimalarial drugs Dihydroartemisinin (DHA) and chloroquine phosphate (CQ) exhibit evident anti-cancer activity, particularly as combination therapy. DHA and CQ combination therapy has been proved to exhibit higher cytotoxic effect in tumor cells and lower toxicity to normal cells than combination of artemisinin derivatives (ARTs) and anticancer chemotherapy drugs. However, different physiochemical properties of DHA and CQ, leading to distinctive in vivo outcomes, considerably limited their synergistic effect in cancer treatment. Herein, we developed a lipid nanoparticle (LNP) for co-delivery of DHA and CQ to inhibit proliferation and metastasis of colorectal cancer. Considering the beneficial effects of acid/reactive oxide species (ROS)-sensitive phospholipids and targeting ligands for colorectal cancer cells, an RGD peptide-modified pH/ROS dual-sensitive LNP loaded with DHA and CQ (RLNP/DC) was prepared. It exhibited optimal cytotoxicity and suppression of invasion and metastasis in HCT116 cells in vitro, attributable to irreversible upregulation of intracellular ROS levels, downregulation of VEGF expression, and upregulation of paxillin expression. A mouse model of orthotopic metastasis of colorectal cancer was established to evaluate anti-proliferation and anti-metastasis effects of RLNP/DC in vivo. Thus, an optimized nanoplatform for DHA and CQ combination therapy was developed in this study that offered potential antitumor efficacy against colorectal cancer.

The effect of robot-assisted laparoscopic ventral onlay lingual mucosal graft ureteroplasty for ureteral stricture / 中华泌尿外科杂志

Objective:To investigate the clinical safety and efficacy of robot-assisted laparoscopic ventral onlay lingual mucosal graft ureteroplasty for ureteral stricture.Methods:The clinical data of 6 patients with ureteral stricture admitted to the Guizhou Provincial People's Hospital from December 2020 to August 2022 were retrospectively analyzed. There were 3 males and 3 females, with an average age of (40.2±11.5) years old. The status of ureteral stricture and hydronephrosis was measured by ultrasonography, CT urography and ureteral retrograde angiography. There were 2 cases of left ureteral stricture and 4 cases of right ureteral stricture, including 4 cases of upper segment stricture and 2 cases of middle segment stricture. The separation of the renal pelvis on the affected side was 3.2 (2.1, 4.2) cm. The length of ureteral stricture was 3.8 (2.5, 4.3) (1.0-5.0) cm, and the preoperative blood creatinine was 90(71, 97)μmol/L. Robot-assisted laparoscopic ventral onlay lingual mucosal graft ureteroplasty was performed in all cases under general anesthesia. The strictured ureter segment was separated and longitudinally cut during the operation. The lingual mucosal grafts 2.5-5.0 cm in length and 1.0-1.5 cm in width was cut according to the stricture. Then the lingual mucosal grafts were harvested and placed in the strictured ureter as a ventral onlay. One double J tube was placed in the affected side in all cases during operation. The perioperative outcomes and complications were analyzed. The blood creatinine and renal pelvis separation on the affected side after surgery were compared with the preoperation.Results:All the surgeries were successfully completed. The average operative time was (190.8 ± 59.0) min, median blood loss was 40 (20, 63) ml, postoperative indwelling time of the drainage tube was 6 (4, 6) days, gastrointestinal function recovery time was 3 (2, 3) days, postoperative hospital stay was 6 (6, 7) days. The patients had clear pronunciation and lingual incision recovered 1 week post-operatively. The urine tube was removed 2 weeks after surgery, and the double J tube was removed 8 (6, 10) weeks post-operatively. Radiological examination revealed significant difference in hydronephrosis on the affected side 3 months post-operatively compared with the preoperation, and the separation of the renal pelvis on the affected side was 1.2 (1.2, 1.4) cm after surgery. The blood creatinine was 79(71, 104)μmol/L at 3 month after surgery, which was also improved compared with preoperative.Conclusions:Robot-assisted laparoscopic ventral onlay lingual mucosal graft ureteroplasty is a feasible and safe option for the treatment of ureteral stricture with less trauma, rapid recovery, and less complications.

Atorvastatin inhibits malignant behaviors and induces apoptosis in human glioma cells by up-regulating miR-146a and inhibiting the PI3K/Akt signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the effect of atorvastatin (AVT) on biological behaviors and the miR-146a/PI3K/Akt signaling pathway in human glioma cells.@*METHODS@#Human glioma U251 cells were treated with 8.0 μmol/L AVT or transfected with a miR-146a inhibitor or a negative control fragment (miR-146a NC) prior to AVT treatment. RT-PCR was used to detect miR-146a expression in the cells, and the changes in cell proliferation rate, apoptosis, cell invasion and migration were detected using MTT assay, flow cytometry, and Transwell assay. Western blotting was performed to detect the changes in cellular expressions of proteins in the PI3K/Akt signaling pathway.@*RESULTS@#AVT treatment for 48 h resulted in significantly increased miR-146a expression and cell apoptosis (P < 0.01) and obviously lowered the cell proliferation rate, invasion index, migration index, and expressions of p-PI3K and p-Akt protein in U251 cells (P < 0.01). Compared with AVT treatment alone, transfection with miR-146a inhibitor prior to AVT treatment significantly reduced miR-146a expression and cell apoptosis (P < 0.01), increased the cell proliferation rate, promoted cell invasion and migration, and enhanced the expressions of p-PI3K and p-Akt proteins in the cells (P < 0.01); these effects were not observed following transfection with miR-146a NC group (P>0.05).@*CONCLUSION@#AVT can inhibit the proliferation, invasion and migration and promote apoptosis of human glioma cells possibly by up-regulating miR-146a expression and inhibiting the PI3K/Akt signaling pathway.

Quantitative Pulmonary Administration of Essential Oil from Alpiniae Zerumbet Fructus for Treatment of Emphysema / 中国实验方剂学杂志

ObjectiveTo investigate the effect of quantitative pulmonary administration of the essential oil from Alpiniae Zerumbet Fructus （EOAZF） on porcine pancreatic elastase （PPE）-induced emphysema in mice and explore its action mechanism. MethodC57BL/6J mice were randomly divided into five group， namely the control group， model group， low- （2 mg·kg-1） and high-dose （20 mg·kg-1） EOFAZ groups， and positive control dexamethasone （DEX，1 mg·kg-1） group. The mice were treated with pulmonary administration of PPE using a microsprayer aerosolizer， once every seven days， for four times in total， for inducing emphysema. During this period， EOFAZ were administered with a quantitative microsprayer aerosolizer once every other day， for 14 times. The lung tissues were then sampled and stained with hematoxylin-eosin （HE） for observing the morphological changes and calculating the pulmonary mean linear intercept （MLI）. The concentrations of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the plasma were determined by enzyme-linked immunosorbent assay （ELISA）. The activities of superoxide dismutase （SOD） and catalase （CAT） and the content of malondialdehyde （MDA） in the lung tissues were measured using the biochemical assay kits. The protein expression levels of nuclear factor E2-related factor 2 （Nrf2）， quinone oxidoreductase1 （NQO1）， B cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， and Bcl-2 in lung tissues were detected by Western blot. ResultThe results of lung morphological observation and MLI detection showed that compared with the control group， the model group showed obvious inflammatory infiltration， alveolar enlargement and fusion， and increased MLI （P<0.05）. Compared with the model group， EOFAZ effectively alleviated the pathological changes such as alveolar dilatation， pulmonary inflammatory cell infiltration， and lung cell apoptosis caused by PPE， and decreased the MLI （P<0.05）. As revealed by ELISA， the inflammatory level of mice in the model group increased significantly （P<0.01）， while the TNF-α， IL-1β， and IL-6 levels in the plasma were decreased after quantitative administration of EOFAZ （P<0.01）. Compared with the control group， the model group exhibited significantly enhanced oxidative stress （P<0.01）. After treatment with EOFAZ by quantitative administration， the activities of SOD and CAT in the lung tissue were increased （P<0.01） and the content of MDA was decreased （P<0.01）. Western blot results demonstrated that the apoptosis-related protein expression in the model group was increased significantly as compared with that in the control group （P<0.01）， whereas the expression levels of antioxidant stress proteins Nrf2 and NQO1 declined （P<0.05）. The relative protein expression of apoptosis-related proteins Bax/Bcl-2 in the EOFAZ groups was lower than that in the model group （P<0.01）， while the expression of antioxidant stress proteins Nrf2 and NQO1 was higher （P<0.05）. ConclusionQuantitative pulmonary administration of EOFAZ effectively alleviates the inflammation and oxidative stress， reduces lung cell apoptosis， and hinders the occurrence and development of emphysema. Its antioxidant mechanism is closely related to the up-regulation of Nrf2 and its downstream NQO1.

Standardized neurology teaching ward-round combined with PBL teaching method and standardized patients in the clinical practice of international students / 中华医学教育探索杂志

Objective:To explore the application effect of standardized neurology teaching ward-round combined with problem-based learning (PBL) teaching method and standardized patients (SP) in the production practice of international students.Methods:A total of 60 foreign students who participated in the neurology department of The 2nd Affiliated Hospital of Harbin Medical University from June 20, 2019 to December 20, 2019 were selected as the study subjects, and were divided into experimental group and control group, with 30 ones in each group. The control group used traditional teaching ward-round methods, the experimental group used the standardized teaching ward-round combined with PBL teaching method and standardized patients for learning. And at the end of the training, the assessment of the first course of disease record writing and questionnaire survey were conducted. SPSS 20.0 was used for t test and chi-square test. Results:The results of writing medical records in the experimental group were significantly outstanding, with statistical difference ( P<0.05). More than 80% of foreign students in the experimental group agreed that standardized teaching ward-round and standardized patient teaching model had significant effectiveness. Conclusion:In the production practice education of international students in department of neurology, the standardized teaching ward-round combined with PBL teaching method and standardized patient have achieved remarkable results.

Essential Oil from Alpiniae Zerumbet Fructus Alleviates High Glucose-induced HUVEC Injury via TXNIP Signaling Pathway / 中国实验方剂学杂志

Objective:To study the protective effect of essential oil from Alpiniae Zerumbet Fructus （EOAZF） against high glucose （HG）-induced injury of human umbilical vein endothelial cells （HUVECs） <italic>in vitro</italic>， so as to provide experimental evidence for the treatment of diabetes-induced cardiovascular diseases with EOAZF. Method:The cells were divided into the normal group， model group （25 mmol·L^-1 glucose）， positive control group （100 mg·L^-1 vitamin C）， and the low- （0.25 μg·L^-1）， medium- （1 μg·L^-1）， and high-dose （4 μg·L^-1） EOAZF groups. The HUVECs were damaged by HG. The secretion amounts of malondialdehyde （MDA）， nitric oxide （NO）， and endothelin-1 （ET-1） in HUVECs of different groups were measured to assess the protective effect of EOAZF against HG-induced injury. The effects of EOAZF on the apoptosis and reactive oxygen species （ROS） generation of HUVECs damaged by HG were detected by Annexin V-fluorescein isothiocyanate/propidium iodide （Annexin V-FITC/PI） staining and dichloro-dihydro-fluorescein diacetate （DCFH-DA） assay. The protein and mRNA expression levels of thioredoxin interacting protein （TXNIP） and thioredoxin 1 （Trx-1） were determined by Western blot and Real-time polymerase chain reaction （Real-time PCR）， followed by the measurement of total intracellular Trx-1 activity with insulin disulfide reduction method. Result:The comparison with the control group revealed that the proliferation of HUVECs in the model group was significantly inhibited and their shape was damaged. Compared with the model group， EOAZF protected HUVECs against HG-induced injury in a concentration-dependent manner. The secretion amounts of MDA and ET-1 （<italic>P</italic><0.05） in the model group were increased in contrast to those in the control group， while the NO level was decreased （<italic>P</italic><0.01）. Compared with the model group， EOAZF at all the three concentrations， especially at 4 μg·L^-1， obviously reduced the secretion of MDA and ET-1 （<italic>P</italic><0.05）， but elevated NO after HG induction （<italic>P</italic><0.05）. The cell apoptosis assay and ROS detection results demonstrated that the apoptosis and ROS level in the model group were higher than those in the control group （<italic>P</italic><0.01）. Compared with the model group， EOAZF at 4 μg·L^-1significantly lowered the ROS level and apoptosis （<italic>P</italic><0.05） of HUVECs damaged by HG. The Western blot assay and Trx-1 activity detection uncovered that the protein and mRNA expression levels of TXNIP in the model group were significantly up-regulated as compared with those in the control group （<italic>P</italic><0.05）， whereas the Trx-1 activity was decreased （<italic>P</italic><0.01）. Compared with the model group， EOAZF at 4 μg·L^-1significantly down-regulated the mRNA and protein （<italic>P</italic><0.05） expression levels of TXNIP and enhanced the total Trx-1 activity （<italic>P</italic><0.05） in HUVECs， thus suppressing the oxidative stress. Conclusion:EOAZF exerts the protective effects against HG-induced injury in HUVECs by improving the endothelial function and reducing intracellular ROS and apoptosis. Its efficacy in anti-oxidative stress may be related to the down-regulation of mRNA and protein expression levels of TXNIP and the enhancement of Trx-1 activity.

Effect of Oxymatrine in Inhibiting Proliferation and Migration of HT-29 Cells Induced by Insulin / 中国实验方剂学杂志

Objective:To investigate the effect of oxymatrine (OMT) on the proliferation and migration of human colon cancer cell line HT-29 under Type Ⅱ diabetes environment by co-culturing HT-29 with insulin to simulate hyperinsulinemia. Method:The effect of OMT (2, 4, 8 mmol·L-1) on insulin-induced proliferation of HT-29 was detected by methyl thiazolyl tetrazolium (MTT) assay and cloning assay. The morphology change and cell migration were evaluated under microscope and by wound healing assay. The Annexin V/propidium iodide(PI) assay was used to detect the change of insulin-induced HT-29 cell cycle and apoptosis. Western blot was performed to validate the expression of cell cycle-related protein and cell migration protein. Result:Insulin significantly increased growth of HT-29 (P-1 showed a significant inhibitory effect in this model (P0/G1 phase (P1, CDK4 and the up-regulation of p27 by OMT might involve the growth inhibition mechanism. Furthermore, OMT reduced the migration of insulin-induced HT-29 according to wound healing assay(PPPConclusion:OMT can inhibit the proliferation and migration of insulin-induced HT-29 cells. The changes of cell cycle and migration related proteins may be correlated with the mechanism.

Expression of Smad4 in gastric carcinoma and its clinical significance / 中国综合临床

Objective To investigate the expression of Smad4 in gastric carcinoma and its relationship with clinicopathological characteristics. Methods Immunohistochemistry method was used to detect the expression of Smad4 in 85 gastric carcinoma tissue and 36 normal gastric mucosa from January 2014 to December 2016. Results (1)The positive expression rate of Smad4 in gastric carcinoma tissues was 35. 29% (30/ 85), which was significantly lower than that in normal gastric mucosa (91. 67% (33/ 36)),and the difference was statistically significant (χ2=32. 201,P<0. 001). (2) The expression of Smad4 was correlated with the depth ofinvasion(χ2=13. 626,P<0. 001),lymph nodes metastasis(χ2=7. 267,P=0. 007),TNM staging(χ2=18. 226,P<0. 001) and tumor differentiation level (χ2 = 9. 134, P= 0. 010) . ( 3) Multivariate unconditional logistic regression analysis showed that depth of invasion(OR=7. 892,95CI 1. 649-37. 790,P=0. 010),TNM staging ( OR=15. 042, 95CI 0. 026-0. 977, P=0. 005 ) and tumor differentiation level ( OR=15. 042, 95CI2. 292-98. 751, P = 0. 005 ) may be independent influencing factors for Smad4 expression in gastric carcinoma. Conclusion Smad4 may performed an important role during the progression of gastric carcinoma and may be a new biological marker of gastric carcinoma.

Research progress of enteral nutrition in the treatment of inflammatory bowel disease / 中国综合临床

Inflammatory bowel disease(IBD),including ulcerative colitis and Crohn's disease,was often associated with malnutrition in the course of disease development. Enteral nutrition ( EN ) can improve the nutritional status of IBD patients, relieve the illness, and promote the recovery of the disease. Therefore, we should pay attention to the significance of EN in the IBD treatment,and strengthen the implementation of EN in IBD patients.

Comparison of dabigatran and warfarin anticoagulant therapy during catheter ablation in patients with atrial fibrillation / 心血管康复医学杂志

Objective: To compare therapeutic effect and safety of dabigatran and warfarin anticoagulant therapy during catheter ablation in patients with atrial fibrillation (AF). Methods: Clinical data of 325 AF patients, who received catheter ablation in our hospital from Jan 2011 to Aug 2014, were retrospectively analyzed. According to perioperative anticoagulant therapy plan, patients were divided into dabigatran group (n=187) and warfarin group (n=138). General data, international normalized ratio (INR), activated coagulation time (ACT), success rate of pulmonary vein isolation (PVI), operation time and incidence rate of complications were compared between two groups. Results: Compared with warfarin group, there were significant reductions in percentages of diabetes mellitus (20. 3％ vs. 11. 8％), chronic heart failure (19. 6％ vs. 10. 2％) and left atrial diameter [(47±10) mm vs. (44± 9) mm]in dabigatran group, P＜0. 05 or＜0. 01. INR of dabigatran group was significantly lower than that of warfarin group [(1. 3±0. 3) vs. (2. 4±0. 4), P=0. 001], and there were no significant difference in ACT, success rate of PVI and operation time between two groups (P＞0. 05 all). Incidence rate of main complications in dabigatran group was significantly lower than that of warfarin group (0. 5％ vs. 5. 1％, P=0. 025). Conclusion: Compared with warfarin, there is significant reduction in INR and incidence rate of main complications during catheter ablation in dabigatran group, which is worth extending.

Expression and clinical significance of collagen three helix repeat protein 1 in human gastric carcinoma / 中国综合临床

Objective To investigate the expression level of collagen triple helix repeat containing 1 ( CTHRC1) in human gastric carcinoma and the relationship with the clinicopathological characteristics of gastric cancer?Methods The expression of CTHRC1 in human gastric carcinoma and normal gastric mucosa were detected by immunohistochemistry ( S?P method ) , and the correlation with various clinical characteristics, including gender,age,tumor diameter,degree of differentiation,depth of invasion,lymph node metastasis,TNM stage,was analyzed?Results ( 1 ) CTHRC1 expressed positive for 41 cases ( positive rate=53?95%) in 76 gastric carcinoma specimens, but only 1 case ( positive rate=3?33%) expressed positive in 30 normal gastric mucosa,the difference was statistically significant (χ2 =23?0332, P=0?000 )? ( 2 ) In early stage of gastric carcinoma,CTHRC1 was predominantly positive in the nucleus,but with the progression of the tumor,CTHRC1 expressed predominantly in cytoplasm?( 3) The expression of CTHRC1 was correlated with the depth of invasion (P=0?000),lymph node metastasis(P=0?009) and TNM?stage(P=0?007),but not with age,gender,size of the tumor and differentiated degree ( P>0?05 )?Conclusion CTHRC1 might play important roles in the occurrence,invasion and metastasis in human gastric carcinoma,and may be new therapy targets.

Preparation and identification of rabbit polyclonal antibodies against vacuolar proton pyrophosphatase type I of Toxoplasma gondii / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare and characterize rabbit polyclonal antibodies against Toxoplasma gondii vacuolar proton pyrophosphatase type I (TgVP1).</p><p><b>METHODS AND RESULTS</b>Two synthesized peptides TgVP1-1 and TgVP1-2 as the haptens were conjugated with KLH to immunize rabbits. Indirect ELISA showed that the titers of rabbit anti-TgVP1-1 polyclonal antibody and rabbit anti-TgVP1-2 polyclonal antibody reached 1:128 000. Western blotting results revealed that both purified polyclonal antibodies could specifically bind to a purified 85 kD T. gondii protein predicted as TgVP1. The protein detected by these two polyclonal antibodies was distributed in the cytoplasm of T. gondii tachyzoite, and this distribution pattern was consistent with that of acidocalcisome.</p><p><b>CONCLUSION</b>The peptide-based method of antibody generation is efficient and the obtained TgVP1 polyclonal antibodies possess a high specificity to facilitate further study of T. gondii acidocalcisome and the diagnosis of toxoplasmosis.</p>

Diagnostic value and clinical significance of the Golgi protein-73 in hepatocellular carcinoma / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>By the detection of hepatocellular carcinoma in patients with GP73 content to explore its significance for liver cancer diagnosis and clinical treatment.</p><p><b>METHODS</b>Up-converting phosphor immunochromatography methods was used for detection of serum GP73 in 302 cases of liver cancer, chronic hepatitis, cirrhosis patients and normal control, application electrochemiluminescence detection of AFP as a comparison. And ROC curve analysis of its diagnostic performance, and patients with HCC before and after treatment GP73 periodic testing of the treatment effect.</p><p><b>RESULTS</b>GP73 content of liver cancer patients was (160.83 +/- 37.24) ng/ml, significantly higher than the chronic hepatitis, cirrhosis patients and normal controls. The area under ROC curve for GP73 diagonosis of hepatocellular carcinoma and chronic hepatitis and cirrhosis was 0. 907 which higher than the area under the ROC curve of AFP was 0. 727. Determine 110 ng/ml most of its critical value, the sensitivity was 84.7%, specificity was 75.8%; liver cancer patients with AFP < 400 ng/ml, detection rate of GP73 was 71.15%; the GP73 content after treatment showing an overall downward trend.</p><p><b>CONCLUSION</b>GP73 has a high sensitivity for the diagnosis of HCC can add to the AFP's lack of sensitivity that can be used to monitor liver cancer treatment.</p>

Application of Modern Separation Technologies in Antibiotics Extraction / 微生物学通报

The development of membrane separation technology in antibioti cs extraction was presented. The application of high performance capillary electr ophoresis, aqueous two-phase system and reverse micelles extraction were also b riefly introduced. Besides, the foreground of these modern separation technolog ies was discussed.

Operating principle and structure of automatic system in laboratory / 医疗卫生装备

This article introduces the principle and the structure of streamline testing based on the newly developed laboratory automation system in our hospital.An overview of the functions and the technical structure of each module within streamline testing are provided.The streamline procedure and the information transmission between modules are also briefly described.

Corticosteroids in COVID-19: Optimizing Observational Research through Target Trial Emulations

ImportanceCommunication and adoption of modern study design and analytical techniques is of high importance for the improvement of clinical research from observational data. ObjectiveTo compare (1) a modern method for causal inference including a target trial emulation framework and doubly robust estimation to (2) approaches common in the clinical literature such as Cox proportional hazards models. To do this, we estimate the effect of corticosteroids on mortality for moderate-to-severe coronavirus disease 2019 (COVID-19) patients. We use the World Health Organizations (WHO) meta-analysis of corticosteroid randomized controlled trials (RCTs) as a benchmark. DesignRetrospective cohort study using longitudinal electronic health record data for 28 days from time of hospitalization. SettingsMulti-center New York City hospital system. ParticipantsAdult patients hospitalized between March 1-May 15, 2020 with COVID-19 and not on corticosteroids for chronic use. InterventionCorticosteroid exposure defined as >0.5mg/kg methylprednisolone equivalent in a 24-hour period. For target trial emulation, interventions are (1) corticosteroids for six days if and when patient meets criteria for severe hypoxia and (2) no corticosteroids. For approaches common in clinical literature, treatment definitions used for variables in Cox regression models vary by study design (no time frame, one-, and five-days from time of severe hypoxia). Main outcome28-day mortality from time of hospitalization. Results3,298 patients (median age 65 (IQR 53-77), 60% male). 423 receive corticosteroids at any point during hospitalization, 699 die within 28 days of hospitalization. Target trial emulation estimates corticosteroids to reduce 28-day mortality from 32.2% (95% CI 30.9-33.5) to 25.7% (24.5-26.9). This estimate is qualitatively identical to the WHOs RCT meta-analysis odds ratio of 0.66 (0.53-0.82)). Hazard ratios using methods comparable to current corticosteroid research range in size and direction from 0.50 (0.41-0.62) to 1.08 (0.80-1.47). Conclusion and RelevanceClinical research based on observational data can unveil true causal relationships; however, the correctness of these effect estimates requires designing the study and analyzing the data based on principles which are different from the current standard in clinical research. Key PointsO_ST_ABSQuestionC_ST_ABSHow do modern methods for causal inference compare to approaches common in the clinical literature when estimating the effect of corticosteroids on mortality for moderate-to-severe coronavirus disease 2019 (COVID-19) patients? FindingsIn an analysis using retrospective data for 3,298 hospitalized COVID-19 patients, target trial emulation using a doubly robust estimation procedure successfully recovers a randomized controlled trial (RCT) meta-analysis benchmark. In contrast, analytic approaches common in the clinical research literature generally cannot recover the benchmark. MeaningClinical research based on observational data can unveil true causal relations. However, the correctness of these effect estimates requires designing and analyzing the data based on principles which are different from the current standard in clinical research. Widespread communication and adoption of these analytical techniques are of high importance for the improvement of clinical research.