Efficacy and safety of tocilizumab and baricitinib among patients hospitalized for COVID-19: a systematic review and meta-analysis.

Introduction: Tocilizumab and baricitinib are recommended treatment options for COVID-19 patients with hyperinflammatory response; however, there is a lack of systematic review directly evaluating their efficacy and safety. Objective: This review was conducted to evaluate the efficacy and safety of tocilizumab and baricitinib in the treatment of hospitalized patients with COVID-19. Methods: Relevant databases were searched for studies that compared the effect or safety of baricitinib or tocilizumab in hospitalized patients with COVID-19. The mortality was the main outcome. The hospital length of stay or adverse drug reactions were taken into consideration as secondary endpoints. The analyses were performed in Revman 5.3 or Stata 16.0. The protocol and analysis plan were pre-registered in PROSPERO, with the registration number CRD42023408219. Results: In total, 10 studies with 2,517 patients were included. The overall pooled data demonstrated that, there was no statistically significant difference in the 28-day mortality rate and the hospital length of stay between the tocilizumab and baricitinib (OR = 1.10, 95% CI = 0.80-1.51, p = 0.57; OR = -0.68, 95% CI = -2.24-0.87, p = 0.39). The adverse reactions including secondary infection rate, thrombotic and bleeding events, and acute liver injury of tocilizumab were significantly higher than that of baricitinib. (OR = 1.49, 95% CI = 1.18-1.88, p < 0.001,OR = 1.52, 95% CI = 1.11-2.08, p = 0.009; OR = 1.52, 95% CI = 1.11-2.08, p = 0.009; OR = 2.24, 95% CI = 1.49-3.35, p < 0.001). Conclusion: In patients hospitalized with COVID-19, no discernible difference in therapeutic efficacy was observed between tocilizumab and baricitinib; however, the group treated with baricitinib demonstrated a significantly lower incidence of adverse effects.

Incidence, risk factors and prognostic effect of imaging left ventricular diastolic dysfunction in patients with COVID-19: protocol for a systematic review.

INTRODUCTION: Recent reports linked acute COVID-19 infection in critical patients to cardiac structure and function abnormalities. The left ventricular (LV) diastolic dysfunction could result in obvious adverse prognostic impacts. The aim of this meta-analysis is to summarise the incidence, risk factors and the prognostic effect of imaging LV diastolic dysfunction in adult patients with COVID-19. METHODS: Databases to be used for the pertinent literature are PubMed, EMBase, ISI Knowledge via Web of Science, and preprint databases (MedRxiv and BioRxiv) (until May 2023) to identify all cohort studies in adult patients with COVID-19. The primary outcome will be the incidence of LV diastolic dysfunction assessed by echocardiography or cardiac MRI. Secondary outcomes will include the risk factors for LV diastolic dysfunction and the association with all-cause mortality during hospitalisation. Additional outcomes will be septal or lateral é, average E/é, E/A, peak tricuspid regurgitation velocity, left atrial volume index and LV wall thickness. Univariable or multivariable meta-regression and subgroup analyses will be conducted for related risk factors and the association of LV diastolic dysfunction with all-cause mortality. Sensitivity analyses will be used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of LV diastolic dysfunction incidence and related risk factors, association with all-cause mortality and other LV diastolic dysfunction parameters. ETHICS AND DISSEMINATION: There was no need for ethics approval for the systematic review protocol according to the Institutional Review Board/Independent Ethics Committee of Fuwai Hospital. This meta-analysis will be disseminated through a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42021256666; URL: https://www.crd.york.ac.uk/prospero/.

In vitroadipogenesis and long-term adipocyte culture in adipose tissue-derived cell banks.

There is a critical need to developin vitroculture systems appropriate for the expansion of adipose tissue, in order to gain new insights into metabolic diseases and to assist in the restoration of tissue defects. Conventional two- or three-dimensional (2D or 3D)in vitromodels of adipocytes require a combination of supplements to induce adipocyte maturation that greatly increases the cost of large-scale industrial production. In the present study, a microporous, perforated bacterial cellulose (BC)-assisted culture system was developed that promoted the adhesion, proliferation, and adipogenic differentiation of preadipocytes. Additionally, the system maintained the cells as mature unilocular adipocytesex vivoin normal cell culture medium in long-term culture. All cells were derived from isolated adipose tissue without the use of expensive enzymes for tissue digestion. In contrast to culture in hard tissue culture plates, preadipocytes in the soft 3D environments formed multidimensional interlaced cell contacts, undergoing significant spontaneous lipid accumulation and could be cultured for up to threemonths in maintenance medium. More importantly, the cultured adipose tissue-derived cell bank created here was able to produce injury repair activators that promoted the proliferation of fibroblasts with little fibrosis and the functional differentiation of myoblasts, displaying the potential for use in adipose reconstruction. Thus, the present study demonstrates the potential of a mechanically flexible BC scaffold to generate volume tunable adipose constructs and provides a low-cost and user-friendly strategy for large-scale industrial production of adipose tissue.

3D printed in vitro tumor tissue model of colorectal cancer.

Rationale: The tumor microenvironment (TME) determines tumor progression and affects clinical therapy. Its basic components include cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TECs), both of which constitute the tumor matrix and microvascular network. The ability to simulate interactions between cells and extracellular matrix in a TME in vitro can assist the elucidation of cancer growth and evaluate the efficiency of therapies. Methods: In the present study, an in vitro 3D model of tumor tissue that mimicked in vivo cell physiological function was developed using tumor-associated stromal cells. Colorectal cancer cells, CAFs, and TECs were co-cultured on 3D-printed scaffolds so as to constitute an extracellular matrix (ECM) that allowed cell processes such as adhesion, stemness, proliferation, and vascularization to take place. Normal stromal cells were activated and reprogrammed into tumor-related stromal cells to construct a TME of tumor tissues. Results: The activated stromal cells overexpressed a variety of tumor-related markers and remodeled the ECM. Furthermore, the metabolic signals and malignant transformation of the in vitro 3D tumor tissue was substantially similar to that observed in tumors in vivo. Conclusions: The 3D tumor tissue exhibited physiological activity with high drug resistance. The model is suitable for research studies of tumor biology and the development of personalized treatments for cancer.

3D printed intelligent scaffold prevents recurrence and distal metastasis of breast cancer.

Rationale: Tumors are commonly treated by resection, which usually leads to massive hemorrhage and tumor cell residues, thereby increasing the risk of local recurrence and distant metastasis. Methods: Herein, an intelligent 3D-printed poly(lactic-co-glycolic acid), gelatin, and chitosan scaffold loaded with anti-cancer drugs was prepared that showed hemostatic function and good pH sensitivity. Results: Following in situ implantation in wounds, the scaffolds absorbed hemorrhage and cell residues after surgery, and promoted wound healing. In an in vivo environment, the scaffold responded to the slightly acidic environment of the tumor to undergo sustained drug release to significantly inhibit the recurrence and growth of the tumor, and reduced drug toxicity, all without causing damage to healthy tissues and with good biocompatibility. Conclusions: The multifunctional intelligent scaffold represents an excellent treatment modality for breast cancer following resection, and provides great potential for efficient cancer therapy.

The Critical Role of Cannabinoid Receptor 2 in URB602-Induced Protective Effects Against Renal Ischemia-Reperfusion Injury in the Rat.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage. Accumulating proofs demonstrates that the endocannabinoid system may provide a promising access for treatment strategy of renal IRI associated AKI. In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation. Using Western blot analysis and LC-MS/MS, renal IRI showed to increase the levels of 2-arachidonoylglycerol (2-AG) in kidneys as well as COX-2, PGE2, TXA2, and decrease N-arachidonoylethanolamine (anandamide, AEA); the expressions of renal cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) were unchanged. The URB602 pretreatment in renal IRI, further enhanced renal 2-AG which is high affinity to both CB1 and CB2, and reduced renal COX-2 which is involved in the regulation of renal perfusion and inflammation. AM630 (CB2 antagonist) almost blocked all the antioxidant, anti-inflammatory and nephroprotective effects of URB602, whereas AM251 (CB1 antagonist) showed limited influence, and parecoxib (COX-2 inhibitor) slightly ameliorated renal function at the dose of 10 mg/kg. Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.

Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest.

OBJECTIVES: Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. DESIGN: Prospective randomized laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rat (n = 96). INTERVENTIONS: Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. MEASUREMENTS AND MAIN RESULTS: Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. CONCLUSIONS: Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.

Comparison of Incidence of hypoxia during modified rapid sequence induction and an alternative technique: a prospective randomized controlled trial.

BACKGROUND: We evaluated the effects and safety of an alternative technique for rapid sequence intubation in children predicting to have high risk of pulmonary aspiration in this prospective, randomized, placebo-controlled study. METHODS: One hundred sixty-five children predicting to have high risk of pulmonary aspiration were randomly allocated to spontaneous breathing maintained induction and intubation group (Group S) and the modified rapid sequence group (Group C). The primary outcome was the incidence of hypoxemia around the intubation period, which was defined as SpO2<90% at any time during the induction and 10 min after the endotracheal intubation. Secondary outcomes included the incidence of pulmonary aspiration, gastroesophageal reflux and other major adverse events associated with the induction and intubation. RESULTS: There were no differences in the incidence of hypoxemia around the intubation period between Group C and Group S; 25.9% vs. 14.8% (P=0.079). The incidence of severe hypoxemia appeared higher in Group C than Group S but not statistical significance, 6.2% vs. 2.5% (P=0.246). Simultaneously, gastroesophageal reflux (upper esophageal pH≤4) was detected in 4.93% children in Group C and 2.47% in group S, which was not significantly different between the two groups (P=0.552). There were no witnessed aspirations in all subjects. CONCLUSION: Sevoflurane based deep sedation with spontaneous respiration maintained technique is not superior to modified rapid sequence induction but can be an alternative technique for anesthesia induction for those predicting to have high risk of aspiration in children.

[Climatic effects on radial growth of Korean pines with different bark forms in Liangshui Natural Reserve, Northeast China].

Dendrochronological techniques including correlation functions and single-years analysis were used to study the relationship between the two kinds of Korean pine radial growth in Liangshui Natural Reserve and climatic variables, and to assess the similarities and differences between Korean pine with coarse bark (Pinus koraiensis forma pachidermis) and fine bark (Pinus koraiensis forma leptodermis) in response to climate factors, the main affecting factors and whether the response relationship could be of long-term stability. The results showed that the Korean pine with fine bark was more suitable for dendrochronological study. The radial growth of the two kinds of Korean pine was very sensitive to environmental variables and their climate responses had no significant differ- ences. From 1902 to 2009, meteorological factors in the growing season, especially in June were the primary factors affecting the radial growth of the two kinds of Korean pine in the study area. The temperature showed a significant negative correlation and the precipitation showed a significant positive correlation. The Korean pine growing in different periods had a significantly different iresponse to meteorological factors. With the rapid rise of temperature and drought after 1970, the radial growth of the two kinds of Korean pine was more sensitive to the meteorological factors than before, which was especially more sensitive to temperature in growing season and PDSI in many seasons.