Objective
This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People’s Hospital, ...enrolled from Jan 5 to Feb 13, 2020.
Methods
The clinical and laboratory findings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected.
Results
COVID-19 mRNA clearance ratio was identified significantly correlated with the decline of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, COVID-19 mRNA clearance time was positively correlated with the length of hospital stay in patients treated with either IFN-α + lopinavir/ritonavir or IFN-α + lopinavir/ritonavir + ribavirin.
Conclusions
Therapeutic regimens of IFN-α + lopinavir/ritonavir and IFN-α + lopinavir/ritonavir + ribavirin might be beneficial for treatment of COVID-19. Serum LDH or CK decline may predict a favorable response to treatment of COVID-19 infection.
NFκB is an inducible transcriptional factor controlled by two principal signaling cascades and plays pivotal roles in diverse physiological processes including inflammation, apoptosis, oncogenesis, ...immunity, and development. Activation of NFκB signaling was detected in skin of SHAPRIN-deficient mice and can be diminished by an NFκB inhibitor. However, in vitro studies demonstrated that SHARPIN activates NFκB signaling by forming a linear ubiquitin chain assembly complex with RNF31 (HOIP) and RBCK1 (HOIL1). The inconsistency between in vivo and in vitro findings about SHARPIN's function on NFκB activation could be partially due to SHARPIN's potential interactions with downstream molecules of NFκB pathway. In this study, 17 anti-flag immunoprecipitated proteins, including TRAF2, were identified by mass spectrum analysis among Sharpin-Flag transfected mouse fibroblasts, B lymphocytes, and BALB/c LN stroma 12 cells suggesting their interaction with SHARPIN. Interaction between SHARPIN and TRAF2 confirmed previous yeast two hybridization reports that SHARPIN was one TRAF2's partners. Furthermore, luciferase-based NFκB reporter assays demonstrated that SHARPIN negatively associates with NFκB activation, which can be partly compensated by over-expression of TRAF2. These data suggested that other than activating NFκB signaling by forming ubiquitin ligase complex with RNF31 and RBCK1, SHARPIN may also negatively associate with NFκB activation via interactions with other NFκB members, such as TRAF2.
Thousands of Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals Persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis.
This ...study involves 462 laboratory-confirmed patients with COVID-19 who were admitted to Shenzhen Third People's Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 to 150 days after the onset of the disease, and lung function tests were conducted about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established.
Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0-30, 31-60, 61-90, 91-120 and > 120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of the COVID-19 patients revealed abnormal conditions in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups.
Persistent pulmonary fibrosis was more likely to develop in patients with older age, higher BMI, severe/critical condition, fever, a longer viral clearance time, pre-existing disease and delayed hospitalization. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average area under the curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.
Elucidating the dynamics of the neutralizing antibody (nAb) response in coronavirus disease 2019 (COVID-19) convalescents is crucial in controlling the pandemic and informing vaccination strategies. ...Here we measured nAb titres across 411 sequential plasma samples collected during 1-480 d after illness onset or laboratory confirmation (d.a.o.) from 214 COVID-19 convalescents, covering the clinical spectrum of disease and without additional exposure history after recovery or vaccination against SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. Forty-eight samples were also tested for neutralizing activities against the circulating variants using pseudotyped neutralization assay. Results showed that anti-RBD IgG and MN titres peaked at ~120 d.a.o. and subsequently declined, with significantly reduced nAb responses found in 91.67% of COVID-19 convalescents (≥50% decrease in current MN titres compared with the paired peak MN titres). Despite this decline, majority of the COVID-19 convalescents maintained detectable anti-RBD IgG and MN titres at 400-480 d.a.o., with undetectable neutralizing activity found in 14.41% (16/111) of the mild and 50% (5/10) of the asymptomatic infections at 330-480 d.a.o. Persistent antibody-dependent immunity could provide protection against circulating variants after one year, despite significantly decreased neutralizing activities against Beta, Delta and Mu variants. In conclusion, these data show that despite a marked decline in neutralizing activity over time, nAb responses persist for up to 480 d in most convalescents of symptomatic COVID-19, whereas a high rate of undetectable nAb responses was found in convalescents from asymptomatic infections.
Deep brain stimulation (DBS) is an important treatment for patients with advanced Parkinson's disease (PD). Patients after DBS implantation need specialized programming to get optimal outcomes. ...However, access to timely and economical postoperative programming for many patients living in remote areas is limited. Teleprogramming, which refers to deliver real-time remote programming through Internet, can help to address this gap.
We aimed to evaluate the clinical application of remote programming for PD patients with DBS.
We retrospectively studied 90 patients with PD who received remote DBS programming after implantation at Yuquan Hospital (Beijing, China) between March 2016 and June 2018. Patients' medical records were reviewed in an electronic database. A self-designed questionnaire was performed on all patients by phone.
Over a mean follow-up period of 27.0 months, 90 patients underwent a total of 386 remote programming visits, of which the average frequency within 6 months after DBS was 2.27 times/person. The average distance between the patients' residences and Yuquan Hospital was 1243.8 ± 746.5 km. The questionnaire survey showed that each remote programming visit saved ≥2000¥ for 76.7% of the patients and ≥12 hours for 90.0% of the patients, compared with the on-site programming visit. The acceptability of the remote programming platform was highly rated. Transient side effects related to programming were reported and were relieved after adjustments of parameters.
Remote programming may offer a feasible and acceptable approach to timely and economic management in patients with PD after DBS implantation.
Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient ...methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario.
In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People's Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People's Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction.
The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively.
The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.
Abstract
Background:
We aimed to evaluate the burden of cardiovascular (CV) risk factors in the community populations of Guangdong Province and its association with sociodemographic status (SDS).
...Method:
The data were from the community populations of Guangdong Province who have participated in the China PEACE Million Persons Project between 2016 and 2020 (n = 102,358, women 60.5% and mean age 54.3 years). The prevalence of CV risk factors (smoking, drinking, overweight/obesity, hypertension, dyslipidemia and diabetes mellitus) and its association with SDS (age, sex and socioeconomic status SES) was evaluated cross-sectionally.
Results:
The prevalence of overweight/obesity was 48.9%, hypertension 39.9%, dyslipidemia 18.6%, smoking 17.2%, diabetes mellitus 16.1% and drinking 5.3%. Even in young adults (aged 35–44), nearly 60% had at least 1 CV risk factor. Overweight/obesity often coexisted with other risk factors, including smoking, hypertension, dyslipidemia and diabetes mellitus. The proportion of people with no risk factor decreased with increasing age. Women were more likely than men to have no CV risk factor (29.4% vs. 12.7%). People with ≥ high school degree were more likely than those with < high school to have no risk factor (28.5% vs. 20.4%), and farmers were less likely than non-farmers to have no risk factor (20.8% vs. 23.1%).
Conclusion:
The burden of CV risk factors is high and varied by SDS in the community populations of Guangdong Province. Cost-effective and targeted interventions are needed to reduce the burden of CV risk factors at the population level.
The NF-κB pathway performs pivotal roles in diverse physiological processes such as immunity, inflammation, proliferation, and apoptosis. NF-κB is kept inactive in the cytoplasm through association ...with inhibitors (IκB), and translocates to the nucleus to activate its target genes after the IκBs are phosphorylated and degraded. Here, we demonstrate that loss of function of SHANK-associated RH domain interacting protein (SHARPIN) leads to activation of NF-κB signaling in skin, resulting in the development of an idiopathic hypereosinophilic syndrome (IHES) with eosinophilic dermatitis in C57BL/KaLawRij-Sharpincpdm/RijSunJ mice, and clonal expansion of B-1 B cells and CD3+CD4-CD8- T cells. Transcription profiling in skin revealed constitutive activation of classical NF-κB pathways, predominantly by overexpressed members of IL1 family. Compound-null mutants for both the IL1 receptor accessory protein (Il1raptm1Roml) and SHARPIN (Sharpincpdm) resulted in mice having decreased skin disease severity. Inhibition of IκBA degradation by the proteasome inhibitor bortezomib alleviated the dermatitis in Sharpincpdm mice. These results indicate that absence of SHARPIN causes IHES with eosinophilic dermatitis by NF-κB activation, and bortezomib may be an effective treatment for skin problems of IHES.
Abstract Background The chronic proliferative dermatitis mutation (CPDM) in mice, due to Sharpin deficiency ( Sharpin cpdm ), is a multisystem disorder characterized by peripheral blood eosinophilia ...and eosinophil infiltration of affected tissues including the skin, bone marrow, spleen, lung, heart, and other organs. The epidermis has numerous apoptotic keratinocytes which increase with age, coalesce, form vesicles, and rupture causing ulceration. Objective To clarify the molecular pathways involved in the keratinocyte apoptosis caused by loss of function of SHARPIN in mice. Method 10-week-old Sharpin cpdm and wildtype mice were used for experiments. Ultrastructural changes of skin were evaluated by transmission electron microscopy. Cross points of mitochondrial pathway were analyzed by in vitro and in vivo cellular and molecular assays. Results 77.5% skin cells in Sharpin cpdm mice were functionally apoptotic and dead cells, compared to only 18.1% unhealthy skin cells in wildtype mice, indicated by annexin-V/propidium iodide FACS analysis. Mitochondria in keratinocytes were disrupted containing prominent electron dense inclusions and membrane potential depolarization, accompanied by a shift in protein expression between the anti-apoptotic BCL2 and pro-apoptotic BAX proteins. Enzymatic activities of caspases 9 and 3, but not 8, were markedly increased in Sharpin cpdm keratinocytes. Caspase-3 was cleaved in most cells in skin of 10-week-old mutant mice. Conclusion The present results indicated that keratinocyte apoptosis in Sharpin cpdm mice was regulated by an intrinsic caspase-dependent mitochondria pathway.
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