Development and Validation of a Nomogram for Assessing Survival in Patients With COVID-19 Pneumonia.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide and continues to threaten peoples' health as well as put pressure on the accessibility of medical systems. Early prediction of survival of hospitalized patients will help in the clinical management of COVID-19, but a prediction model that is reliable and valid is still lacking. METHODS: We retrospectively enrolled 628 confirmed cases of COVID-19 using positive RT-PCR tests for SARS-CoV-2 in Tongji Hospital, Wuhan, China. These patients were randomly grouped into a training (60%) and a validation (40%) cohort. In the training cohort, LASSO regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of patients with COVID-19. A nomogram based on the 3 variables was built for clinical use. AUCs, concordance indexes (C-index), and calibration curves were used to evaluate the efficiency of the nomogram in both training and validation cohorts. RESULTS: Hypertension, higher neutrophil-to-lymphocyte ratio, and increased NT-proBNP values were found to be significantly associated with poorer prognosis in hospitalized patients with COVID-19. The 3 predictors were further used to build a prediction nomogram. The C-indexes of the nomogram in the training and validation cohorts were 0.901 and 0.892, respectively. The AUC in the training cohort was 0.922 for 14-day and 0.919 for 21-day probability of in-hospital survival, while in the validation cohort this was 0.922 and 0.881, respectively. Moreover, the calibration curve for 14- and 21-day survival also showed high coherence between the predicted and actual probability of survival. CONCLUSIONS: We built a predictive model and constructed a nomogram for predicting in-hospital survival of patients with COVID-19. This model has good performance and might be utilized clinically in management of COVID-19.

Liraglutide protects against lethal renal ischemia-reperfusion injury by inhibiting high-mobility group box 1 nuclear-cytoplasmic translocation and release.

Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been reported to exert protective effects against myocardial, hepatic, and gastric ischemia-reperfusion injury (IRI), but whether it can protect against renal IRI remains unknown. Here, a lethal renal IRI model was established with a 100% mortality rate in untreated mice. Treatment with liraglutide involving a regimen of multiple doses resulted in 100% survival, remarkable preservation of renal function, a significant reduction in pathological damage, and blunted upregulation of TNF-α, IL-1ß, IL-6, MCP-1, TLR-2, TLR-4, and RAGE mRNA. We found that liraglutide treatment dramatically inhibited ischemia-induced nucleocytoplasmic translocation and release of HMGB1. This inhibition was associated with a marked decrease (~ 60%) in nuclear histone acetyltransferase activity. In addition, the protective effects of liraglutide on renal IRI were largely abolished by the administration of exogenous HMGB1. When the GLP-1R antagonist exendin (9-39) was given to mice before each liraglutide administration, or GLP-1R-/- mice were used for the renal IRI experiments, the protective effect of liraglutide on renal IRI was partially reversed. Moreover, liraglutide pretreatment significantly inhibited HMGB1 nucleocytoplasmic translocation during hypoxic culture of HK-2 cells in vitro, but the addition of exendin (9-39) significantly eliminated this inhibition. We demonstrate here that liraglutide can exert a strong protective effect on lethal renal IRI in mice. This protection appears to be related to the inhibition of HMGB1 nuclear-cytoplasmic translocation and release and partially depends on GLP-1R. Thus, liraglutide may be therapeutically useful for the clinical prevention and treatment of organ IRI.

Risk factors and early diagnosis of cerebral venous sinus occlusion secondary to traumatic brain injury.

OBJECTIVE: This study was designed to investigate the risk factors of, and the strategy for early diagnosis of cerebral venous sinus occlusion (CVSO) secondary to traumatic brain injury. MATERIALS AND METHODS: The clinical data of 240 consecutive patients were analyzed retrospectively. The clinical symptoms were observed and imaging was carried out. The risk factors of CVSO were evaluated with logistic regression analysis. Early diagnosis of CVSO was established based on the clinical and imaging features. RESULTS: Forty patients were diagnosed to be having CVSO according to the findings of computerized tomographic venogram (CTV) and magnetic resonance venogram (MRV). They were classified into three sub-types (thrombosis occlusion type, compression type, and mixed type). A skull fracture crossing the sinus (odds ratio [OR] =8.026; 95% confidence interval [CI]: 3.107-20.734) and an epidural hematoma crossing the sinus (OR = 3.062; 95% CI: 1.355-6.921) were risk factors associated with CVSO, and the former played a more significant role. The female gender (OR = 0.306; 95% CI: 1.715-61.943) was the risk factor for the thrombosis occlusion type of CVSO. An epidural hematoma crossing the sinus (OR = 5.653; 95% CI: 1.767-18.084) was the risk factor of the compression type of CVSO. The past medical history of deep vein thrombosis (DVT) (OR = 11.276; 95% CI: 1.315-96.664) combined with a skull fracture and epidural hematoma crossing the sinus were risk factors for the mixed type of CVSO. CONCLUSIONS: Paying close attention to the past medical history of DVT, skull fracture, and the imaging finding of an epidural hematoma that crosses the sinus are necessary for the early diagnosis of CVSO. CTV and MRV help in making an early diagnosis of CVSO.

Iron metabolism disorder and multiple sclerosis: a comprehensive analysis.

Background: Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system. Currently, the pathological mechanisms of MS are not fully understood, but research has suggested that iron metabolism disorder may be associated with the onset and clinical manifestations of MS. Methods and materials: The study utilized publicly available databases and bioinformatics techniques for gene expression data analysis, including differential expression analysis, weighted correlation network analysis, gene enrichment analysis, and construction of logistic regression models. Subsequently, Mendelian randomization was used to assess the causal relationship between different iron metabolism markers and MS. Results: This study identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, and SKP1 as genes associated with multiple sclerosis (MS) and iron metabolism, establishing their multi-gene diagnostic value for MS with an AUC of 0.83. Additionally, Mendelian randomization analysis revealed a potential causal relationship between transferrin saturation and MS (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), as well as serum transferrin and MS (p=2.18E-04; OR 95%CI=1.22 (1.10, 1.36)). Conclusion: This study comprehensively explored the relationship between iron metabolism and MS through integrated bioinformatics analysis and Mendelian randomization methods. The findings provide important insights for further research into the role of iron metabolism disorder in the pathogenesis of MS and offer crucial theoretical support for the treatment of MS.

Experimental Study on the Agglomeration Behavior of Elongated Biomass Particles in a Lifting Tube.

Pneumatic conveying devices are commonly used in the fields of chemical industry, raw material transportation, and material processing. Elongated biomass particles are not evenly distributed in the lifting tube because biomass clumps during conveying. Pneumatic conveying test setup and measurement system were built in this paper in order to study the agglomeration behavior of elongated biomass particles in the lifting tube experimentally. Particle tracking velocimetry (PTV) was used to determine the area distribution and velocity distribution of particles at different apparent air velocities and mass flow rates. The results show that while keeping the mass flow rate constant at 46.50 g/s, the apparent gas velocity increased from 5.91 to 7.91 m/s and the maximum size of agglomerates decreased from 0.689 to 0.235. The apparent gas velocity was kept at 6.40 m/s, and the particle mass flow rate was adjusted from 56.50 to 16.20 g/s. The maximum size of the agglomerates was reduced to 0.115. Therefore, appropriately increasing the apparent gas velocity or decreasing the particle mass flow rate can improve the uniformity of the particle distribution in the lifting tube. The results would provide a reference for parameter adjustment of pneumatic conveying devices in industrial production.

Oral tranexamic acid treats papulopustular rosacea by improving the skin barrier.

BACKGROUND: Papulopustular rosacea (PPR) is a chronic inflammatory disease with a significant impact on facial aesthetics. An impaired skin barrier is an important factor in the development and exacerbation of PPR. Tranexamic acid (TXA) has immune regulatory and anti-inflammatory effects, inhibits angiogenesis and endothelial hyperplasia, and promotes skin barrier repair. AIMS: We investigated the efficacy and safety of oral TXA for PPR treatment. PATIENTS/METHODS: In total, 70 patients were randomly assigned to receive traditional therapy plus oral TXA or traditional therapy alone for 8 weeks, with a 4-week follow-up period. The subjective improvement in rosacea was assessed using the clinical erythema assessment (CEA), investigator's global assessment (IGA), patient self-assessment (PSA) score, rosacea-specific quality of life (RQoL) score, and global aesthetic improvement score (GAIS). An objective improvement in rosacea was assessed using skin hydration, trans-epidermal water loss (TEWL), clinical photography, and an eight spectrum facial imager. RESULTS: CEA/IGA/PSA, dryness, and RQoL scores were significantly lower and GAIS was higher in the TXA group than in the traditional therapy group. Furthermore, oral TXA significantly improved skin barrier function, increased skin hydration, and decreased TEWL, with no significant side effects. Notably, we observed better outcomes and a greater improvement in skin barrier function with TXA treatment in patients with dry-type rosacea than in patients with oily skin. CONCLUSIONS: The addition of oral TXA to traditional therapy can lead to rapid and effective improvements in PPR, which may be attributed to improvements in skin barrier function.

A study of the efficacy and safety of plaque psoriasis treatment by TNF-α and IL-17A inhibitor biologics in patients who received the inactivated SARS-CoV-2 vaccine.

BACKGROUND: Vaccination is an important method for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. There is currently a lack of real-world clinical data regarding the safety and efficacy of coronavirus disease 2019 (COVID-19) vaccines with respect to plaque psoriasis treatment involving tumor necrosis factor-α (TNF-α) and interleukin-17A (IL-17A) inhibitors. METHODS: We longitudinally analyzed 152 patients with plaque psoriasis, 86 of whom received two doses of inactivated COVID-19 vaccine (either BBIBP-CorV or CoronaVac). Comparisons were made between patients undergoing treatment with biologics (TNF- α inhibitors or IL-17A inhibitors) or acitretin. Routine blood tests were used to assess safety; the psoriasis area and severity index (PASI) and dermatology life quality index (DLQI) were used to assess efficacy. RESULTS: After inactivated COVID-19 vaccination, biologics retained considerable advantages in terms of improving skin lesions (measured by PASI) and quality of life (measured by DLQI), compared with conventional treatment (p < 0.05 and p < 0.01, respectively). Routine blood tests and hepatorenal function analyses suggested that inactivated SARS-CoV-2 vaccines did not alter the safety of biologics treatment (p > 0.05). CONCLUSIONS: Inactivated SARS-CoV-2 vaccines do not have significant impacts on the safety and efficacy of biologics (TNF-α inhibitors or IL-17A inhibitors) in patients with moderate to severe plaque psoriasis.

JAK1 inhibitor abrocitinib for the treatment of steroid-induced rosacea: case series.

Background: Steroid-induced rosacea is a severe withdrawal reaction which can occur after the frequent and excessive topical use of steroids on the face. The Janus kinase (JAK)-signal transducers and activators of transcription signaling pathway is involved in many biological processes and may play a role in the development of steroid-induced rosacea. Objective: To observe the efficacy and safety of the JAK1 inhibitor abrocitinib in the treatment of steroid-induced rosacea. Methods: Four Chinese female patients were treated with orally-administered abrocitinib, a selective JAK1 inhibitor with a good safety profile, for steroid-induced rosacea. Results: Abrocitinib treatment resulted in improved skin condition and lowered Dermatology Life Quality Index scores in each of the four patients. No discomfort was reported and no adverse effects were observed. Conclusion: The JAK1 inhibitor abrocitinib is a promising potential treatment for steroid-induced rosacea.

Study on outlier detection method of the near infrared spectroscopy analysis by probability metric.

Due to the high dimensionality and non-linearity of the near infrared (NIR) spectra data result the difficulty of the outlier measure. This paper proposed a probability based outlier detection method, which adopted the distribution probability of the spectra data to identify outliers at each wavelength by using of copula function. The negative logarithmic function was also used to quantify the overall variation of the joint distribution for the outliers. This method not only enlarges the difference of the spectra between typical samples and outliers, but also can be adapted to multi-type of outliers. Moreover, the jump degree in statistics was introduced for the automated determination of threshold for the outliers, which avoids the threshold setting problem in empirical way and the misjudgment of the outliers. In order to investigate the effectiveness of the algorithm, the recognition of different cases and types of outliers were applied, and compared with the commonly used PCA-Mahalanobis distance, spectral residual (SR) and leverage methods. The experimental results showed that the probability based outlier detection method effectively improved the performance of outlier identification and calibration for NIR analysis.

STING/NF-κB/IL-6-Mediated Inflammation in Microglia Contributes to Spared Nerve Injury (SNI)-Induced Pain Initiation.

Innate immune response acts as the first line of host defense against damage and is initiated following the recognition of pathogen-associated molecular patterns (PAMPs). For double-stranded DNA (dsDNA) sensing, interferon gene stimulator (STING) was discovered to be an integral sensor and could mediate the immune and inflammatory response. Selective STING antagonist C-176 was administered and pain behaviors were assessed following spared nerve injury (SNI)-induced neuropathic pain. The level of serum dsDNA following neuropathic pain was assessed using Elisa analysis. STING signaling pathway, microglia activation, and proinflammatory cytokines were assessed by qPCR, western blots, Elisa, and immunofluorescence staining. STING agonist DMXAA was introduced into BV-2 cells to assess the inflammatory response in microglial cells. dsDNA was significantly increased following SNI and STING/TANK-binding kinase 1 (TBK1)/nuclear factor-kappa B (NF-κB) pathway was activated in vivo and vitro. Early but not the late intrathecal injection of C-176 attenuated SNI-induced pain hypersensitivity, microglia activation, proinflammatory factors, and phosphorylated JAK2/STAT3 in the spinal cord dorsal horn, and the analgesic effect of C-176 was greatly abolished by recombinant IL-6 following SNI. We provided evidence clarifying dsDNA mediated activation of microglia STING signaling pathway, after which promoting expression of proinflammatory cytokines that are required for hyperalgesia initiation in the spinal cord dorsal horn of SNI model. Further analysis showed that microglial STING/TBK1/NF-κB may contribute to pain initiation via IL-6 signaling. Pharmacological blockade of STING may be a promising target in the treatment of initiation of neuropathic pain.

Nox2 contributes to reactive oxygen species-induced redox imbalance in cancer-induced bone pain.

We have recently demonstrated that reactive oxygen species (ROS) scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain (CIBP). In the present study, we investigated anti-nociceptive effect of Nox inhibitor apocynin in CIBP in rats. Mechanical allodynia was assessed by Von Frey tests in sham and CIBP group of rats. Western blotting and immunofluorescence technique were conducted to assess the expression levels and cellular localization of Nox2. Results illustrated that after intra-tibial implantation with tumor cells, Nox2 and ROS were both up-regulated in the spinal cord of rats. Injection of apocynin could dose-dependently decrease the abundance of Nox2 and inhibit the development of CIBP. Furthermore, pretreatment with the apocynin could delay the development of CIBP. This study for the first time proved that Nox2 inhibitors could downregulate the production of ROS in CIBP rats, which highlights the fact that Nox inhibitor is an important therapeutic option for CIBP and that, precise targeting inhibitor of different subtypes of Nox enzymes is needed to developed in future.

Carbon Monoxide Inhibits T Cell Proliferation by Suppressing Reactive Oxygen Species Signaling.

Aims: Carbon monoxide (CO) confers antiproliferative effects on T cells; however, how these effects are produced remains unclear. Reactive oxygen species (ROS) have recently emerged as important modulators of T cell proliferation. In this study, we aimed to determine whether the inhibitory effects of CO on T cell proliferation are dependent on the inhibition of ROS signaling. Results: Pretreatment with CO-releasing molecule-2 (CORM-2) had potent inhibitory effects on mouse T cell proliferation stimulated by anti-CD3/CD28 antibodies. Interestingly, CORM-2 pretreatment markedly suppressed intracellular ROS generation as well as the activity of NADPH oxidase and mitochondrial complexes I-IV in T cells after stimulation. The inhibitory effects of CORM-2 on both ROS production and T cell proliferation were comparable with those produced by the use of antioxidant N-acetylcysteine or a combined administration of mitochondrial complex I-IV inhibitors. Moreover, increasing intracellular ROS via hydrogen peroxide supplementation largely reversed the inhibitory effect of CORM-2 on the proliferation of T cells. The inhibitory effects of CORM-2 on both cell proliferation and intracellular ROS production were also shown in a T cell proliferation model involving stimulation by allogeneic dendritic cells or phorbol 12-myristate 13-actetate/ionomycin, as well as in spontaneous cell proliferation models in EL-4 and RAW264.7 cells. In addition, CORM-2 treatment significantly inhibited T cell activation in vivo and attenuated concanavalin A-induced autoimmune hepatitis. Innovation: CO inhibits T cell proliferation via suppression of intracellular ROS production. Conclusion: The study could supply a general mechanism to explain the inhibitory effects of CO on T cell activation and proliferation, favoring its future application in T cell-mediated diseases.

The endocannabinoid system: Novel targets for treating cancer induced bone pain.

Treating Cancer-induced bone pain (CIBP) continues to be a major clinical challenge and underlying mechanisms of CIBP remain unclear. Recently, emerging body of evidence suggested the endocannabinoid system (ECS) may play essential roles in CIBP. Here, we summarized the current understanding of the antinociceptive mechanisms of endocannabinoids in CIBP and discussed the beneficial effects of endocannabinoid for CIBP treatment. Targeting non-selective cannabinoid 1 receptors or selective cannabinoid 2 receptors, and modulation of peripheral AEA and 2-AG, as well as the inhibition the function of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have produced analgesic effects in animal models of CIBP. Management of ECS therefore appears to be a promising way for the treatment of CIBP in terms of efficacy and safety. Further clinical studies are encouraged to confirm the possible translation to humans of the very promising results already obtained in the preclinical studies.

Upregulation of Heme Oxygenase-1 Endues Immature Dendritic Cells With More Potent and Durable Immunoregulatory Properties and Promotes Engraftment in a Stringent Mouse Cardiac Allotransplant Model.

Heme oxygenase-1 (HO-1) is critical for the ability of immature dendritic cells (imDCs) to suppress T-cell responses. Induction of high HO-1 expression may markedly improve the tolerogenic capacity of imDCs. Here, we generated bone marrow-derived DCs (BMDCs) from BALB/c mice with low doses of GM-CSF and IL-4. The adherent BMDCs were obtained as imDCs. Upregulation of HO-1 in imDCs (HO-1hi-imDCs) was achieved by cobalt protoporphyrin treatment. HO-1hi-imDCs proved to be more maturation-resistant than conventional imDCs, with an enhanced ability to inhibit allogeneic T-cell proliferation stimulated by anti-CD3/CD28 antibodies. When donor-derived DC adoptive transfer was performed in a stringent mouse cardiac allotransplant model, the extent of graft prolongation observed with HO-1hi imDCs was superior to that obtained with conventional imDCs. T-cell activation and proliferation in cardiac allograft recipients was more strongly suppressed in the HO-1hi imDC transfusion group than that in the untreated imDC group. Furthermore, donor HO-1hi imDCs were able to maintain a status of high HO-1 expression and survived longer in the recipient spleens than did untreated imDCs after adoptive transfer. In vitro-generated HO-1hi imDCs had an enhanced tolerogenic capacity to modulate alloimmune responses both in vitro and in vivo, and thus may offer a novel antigen-specific and cost-effective strategy to induce transplant tolerance.

Poor Prognostic Outcome in Cerebral Venous Sinus Thrombosis Associated with Dyskinesia and Elevated Platelet Volume.

Although about 80% of patients with cerebral venous sinus thrombosis have a good prognosis, some patients develop severe complications and a small proportion do not survive. The study included patients who had been diagnosed with cerebral venous sinus thrombosis in our hospital from May 2008 to February 2014. Based on the modified Rankin Scale (mRS) scores at 3 months for outcome, the patients were divided into two groups: good prognosis (mRS score ≤ 2) and poor prognosis (mRS score > 2). Univariate and multivariate regression analysis were performed to identify significant prognostic factors for poor outcome. A total of 86 patients with cerebral venous sinus thrombosis, 54 males and 32 females, average age 41.3 years (range, 3-83 years), were enrolled. Of these 86 patients, 64 (74.4%) had a good prognosis and 22 (25.6%) a poor prognosis. Univariate analysis revealed that dyskinesia was a significant risk factor (factor with odds ratio >1) for poor prognosis. In multivariate analysis, the risk of poor prognosis in patients with dyskinesia was 23 times higher than for those without dyskinesia (p < 0.001). Thrombosis of the sinus transervus was found to reduce the risk of poor prognosis in both univariate and multivariate analysis. Most patients with cerebral venous sinus thrombosis have a good prognosis but patients with dyskinesia have a poorer prognosis.