Association between segmental alterations of white matter bundles and cognitive performance in first-episode, treatment-naïve young adults with major depressive disorder.

BACKGROUND: Cumulative evidence has consistently shown that white matter (WM) disruption is associated with cognitive decline in geriatric depression. However, limited research has been conducted on the correlation between these lesions and cognitive performance in untreated young adults with major depressive disorder (MDD), particularly with the specific segmental alterations of the fibers. METHOD: Diffusion tensor images were performed on 60 first-episode, treatment-naïve young adult patients with MDD and 54 matched healthy controls (HCs). Automated fiber quantification was applied to calculate the tract profiles of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) to evaluate the WM microstructural organization. Correlation analysis was performed to find the associations between the diffusion properties and cognitive performance. RESULTS: Compared with HCs, patients with MDD exhibited predominantly different diffusion properties in bilateral uncinate fasciculus (UF), corticospinal tracts (CSTs), left superior longitudinal fasciculus and anterior thalamic radiation. The FA of the temporal cortex portion of right UF was positively correlated with working memory. The MD of the temporal component of left UF was negatively correlated with working memory and positively correlated with symptom severity. Additionally, a positive correlation between the MD of left CST and the psychomotor speed, negative correlation between the MD of left CST and the executive functions and complex attentional processes were observed. CONCLUSIONS: Our study validated the alterations in spatial localization of WM microstructure and its correlations with cognitive performance in first-episode, treatment-naïve young adults with MDD. This study added to the knowledge of the neuropathological basis of MDD.

Increase in HIV reservoir and T cell immune response after CoronaVac vaccination in people living with HIV.

Introduction: CoronaVac, an inactivated vaccine developed by Sinovac Life Sciences, has been widely used for protection against Coronavirus Disease 2019 (COVID-19). This study investigates its effect on the HIV reservoir and T cell repertoires in people living with HIV (PLWHs). Methods: Blood samples were collected from fifteen PLWHs who were administered at least two doses of CoronaVac between April 2021 and February 2022. The levels of cell-associated HIV RNA (CA HIV RNA) and HIV DNA, as well as the T cell receptor (TCR) repertoire profiles, TCR clustering and TCRß annotation, were studied. Results: A significant increase was observed in CA HIV RNA at 2 weeks (431.5 ± 164.2 copies/106 cells, P = 0.039) and 12 weeks (330.2 ± 105.9 copies/106 cells, P = 0.019) after the second dose, when compared to the baseline (0 weeks) (73.6 ± 23.7 copies/106 cells). Various diversity indices of the TCRß repertoire, including Shannon index, Pielou's evenness index, and Hvj Index, revealed a slight increase (P < 0.05) following CoronaVac vaccination. The proportion of overlapping TCRß clonotypes increased from baseline (31.9 %) to 2 weeks (32.5 %) and 12 weeks (40.4 %) after the second dose. We also found that the breadth and depth of COVID-19-specific T cells increased from baseline (0.003 and 0.0035) to 12 weeks (0.0066 and 0.0058) post the second dose. Conclusions: Our study demonstrated an initial increase in HIV reservoir and TCR repertoire diversity, as well as an expansion in the depth and breadth of COVID-19-specific T-cell clones among CoronaVac-vaccinated PLWHs. These findings provide important insights into the effects of COVID-19 vaccination in PLWHs.

Distinct Lipidomic Profiles between People Living with HIV Treated with E/C/F/TAF or B/F/TAF: An Open-Label Prospective Cohort Study.

INTRODUCTION: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug-drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. METHODS: HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12 weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24 weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. RESULTS: No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17-6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF. CONCLUSION: E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article. TRIAL REGISTRATION: ClinicalTrials.gov; identifier, NCT06019273.

Construction of a predictive model based on MIV-SVR for prognosis and length of stay in patients with traumatic brain injury: Retrospective cohort study.

Objective: To investigate the mean impact value (MIV) method for discerning the most efficacious input variables for the machine learning (ML) model. Subsequently, various ML algorithms are harnessed to formulate a more accurate predictive model that can forecast both the prognosis and the length of hospital stay for patients suffering from traumatic brain injury (TBI). Design: Retrospective cohort study. Participants: The study retrospectively accrued data from 1128 cases of patients who sought medical intervention at the Neurosurgery Center of the Second Affiliated Hospital of Anhui Medical University, within the timeframe spanning from May 2017 to May 2022. Methods: We performed a retrospective analysis of patient data obtained from the Neurosurgery Center of the Second Hospital of Anhui Medical University, covering the period from May 2017 to May 2022. Following meticulous data filtration and partitioning, 70% of the data were allocated for model training, while the remaining 30% served for model evaluation. During the construction phase of the ML models, a gamut of 11 independent variables-including, but not limited to, in-hospital complications and patient age-were utilized as input variables. Conversely, the length of stay (LOS) and the Glasgow Outcome Scale (GOS) scores were designated as output variables. The model architecture was initially refined through the MIV methodology to identify optimal input variables, whereupon five distinct predictive models were constructed, encompassing support vector regression (SVR), convolutional neural networks (CNN), backpropagation (BP) neural networks, artificial neural networks (ANN) and logistic regression (LR). Ultimately, SVR emerged as the most proficient predictive model and was further authenticated through an external dataset obtained from the First Hospital of Anhui Medical University. Results: Upon incorporating the optimal input variables as ascertained through MIV, it was observed that the SVR model exhibited remarkable predictive prowess. Specifically, the Mean Absolute Percentage Error (MAPE) of the SVR model in predicting the GOS score in the test dataset is only 6.30%, and the MAPE in the external validation set is only 7.61%. In terms of predicting hospitalization time, the accuracy of the test and external validation sets were 9.28% and 7.91%, respectively. This error indicator is significantly lower than the error of other prediction models, thus proving the excellent efficacy and clinical reliability of the MIV-optimized SVR model. Conclusion: This study unequivocally substantiates that the incorporation of MIV for selecting optimal input variables can substantially augment the predictive accuracy of machine learning models. Among the models examined, the MIV-SVR model emerged as the most accurate and clinically applicable, thereby rendering it highly conducive for future clinical decision-making processes.

The application of podocyte antigen PLA2R and anti-PLA2R antibody in the diagnosis and treatment of membranous nephropathy.

BACKGROUND: The application of podocyte antigen M-type phospholipase A2 receptor (PLA2R, GAg) and serum anti-PLA2R antibody (SAb) in predicting the prognosis of membrane nephropathy (MN) was controversial. METHOD: 328 biopsy-proven MN patients were divided into three phenotypes, 182 MN patients with GAg+/SAb+, 118 MN patients with GAg+/SAb-, and 28 MN patients with GAg-/SAb-. The baseline clinicopathological characteristics, therapy response, and prognosis were compared among the three groups. Cox regression analysis was performed to assess predictors of remission. Anti-PLA2R antibody was analyzed by receiver operating characteristic curve to find the optimal titer for MN diagnosis. RESULT: Lower eGFR (p = 0.009), higher UPCR (p < 0.001), and lower serum albumin (p < 0.001) were observed in GAg+/SAb+ MN patients, compared to GAg+/SAb- MN patients. More GAg+/SAb+ MN patients received cyclophosphamide (CTX) combined with glucocorticoids and calcineurin inhibitors (CNI) based therapy than the other two groups (p = 0.015 and p = 0.023, respectively). No significant difference was observed among the three groups in terms of complete remission, relapse, and developing ESRD. SAb+ status was an independent predictor for no remission (hazard ratio 1.378, 95% confidence interval 1.023 to 1.855; p = 0.035). The optimal cutoff value for anti-PLA2R antibody to predict MN was 2.055 RU/mL (sensibility 0.802, specificity 0.970). CONCLUSION: GAg+/SAb+ MN patients were related to more severe clinical manifestations and more requisition of immunosuppressive treatment. Positive anti-PLA2R antibody was an independent predictor for no remission. An anti-PLA2R antibody above 2.055 RU/mL can be a suggestive indicator of MN diagnosis in patients with proteinuria.

Executive function deficit in betel quid-dependence: Evidence from functional and effective connectivity of executive control network.

Betel quid (BQ) ranks fourth in global self-administered psychoactive agents, after caffeine, alcohol and nicotine, with 600 million consumers. Patients with BQ dependence (BQD) disorder demonstrate deficits in executive function. However, the neural correlates of the resting-state executive control network (ECN) and BQD-related pathopsychological characteristics still remain unclear. The present study aimed to assess the functional and effective connectivity of the ECN using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty-five BQD individuals and 54 healthy controls (HCs) were recruited in this study. The executive function of all participants was tested by three tasks. Independent component and Granger causal analysis were employed to investigate the functional connectivity within ECN and ECN-related directional effective connectivity, separately. Behavioural results suggested a marked deficit of executive function in BQD individuals. Compared with HCs, BQD individuals showed overall weaker functional connectivity in the ECN, mainly including dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (IPL) and middle frontal gyrus (MFG). We observed decreased outflow of information from the right DLPFC and IPL to the precentral/pre-supplement motor area (SMA) and increased outflow of information from the MFG to the middle occipital gyrus in BQD individuals. Correlation analysis revealed that the effective connectivity from IPL to precentral/pre-SMA was negatively correlated to the BQD scales in BQD individuals. Our findings revealed impaired executive function, functional connectivity of the ECN and causal interaction between networks in patients with BQD. These results could potentially direct future targets for the prevention and intervention of BQD.

Tough, Photoluminescent, Self-Healing Waterborne Polyurethane Elastomers Resulting from Synergistic Action of Multiple Dynamic Bonds.

Polymers that integrate multiple functions into one system broaden the application range of materials, but it remains a great challenge to obtain polymer materials with simultaneously high strength, high toughness, and high self-healing rate. In this work, we prepared waterborne polyurethane (WPU) elastomers using Schiff bases containing disulfide and acylhydrazone bonds (PD) as chain extenders. Acylhydrazone forming a hydrogen bond not only acts as a physical cross-linking point, which promotes the microphase separation of polyurethane to increase the thermal stability, tensile strength, and toughness of the elastomer, but also serves as a "clip" to integrate various dynamic bonds together to synergistically reduce the activation energy of the polymer chain movement and endow the molecular chain with faster fluidity. Therefore, WPU-PD exhibits excellent mechanical properties at room temperature, such as a tensile strength and a fracture energy of 25.91 MPa and 121.66 kJ m-2, respectively, and a high self-healing efficiency of 93.7% in a short time under moderate heating conditions. In addition, the photoluminescence property of WPU-PD enables us to track its self-healing process by monitoring change of the fluorescence intensity at the cracks, which helps to avoid the accumulation of cracks and improve the reliability of the elastomer. This self-healing polyurethane has a great potential application value in optical anticounterfeiting, flexible electronics devices, functional automobile protective films, and so on.

Efficacy and safety of lenalidomide in HIV-associated cryptococcal meningitis patients with persistent intracranial inflammation: an open-label, single-arm, prospective interventional study.

BACKGROUND: Patients with human immunodeficiency virus-associated cryptococcal meningitis (HIV-CM) have persistent intracranial inflammation despite negative cerebrospinal fluid (CSF) fungal cultures after optimal treatment for CM, which could be devastating for the central nervous system. However, a definitive treatment strategy for persistent intracranial inflammation despite optimal antifungal therapies is undefined. METHODS: We identified 14 HIV-CM patients with persistent intracranial inflammation and conducted a 24-week, prospective, interventional study. All participants received lenalidomide (25 mg, p.o.) on days 1 to 21 of a 28-day cycle. Follow-up lasted for 24 weeks with visits at baseline and weeks 4, 8, 12, and 24. The primary endpoint was the change in clinical manifestations, routine CSF parameters, and MRI findings after lenalidomide treatment. An exploratory analysis was made on changes in cytokine levels in CSF. Safety and efficacy analyses were undertaken in patients who received at least one dose of lenalidomide. RESULTS: Of 14 participants, 11 patients completed the 24 weeks of follow-up. Rapid clinical remission following lenalidomide therapy was observed. Clinical manifestations (fever, headache, altered mentation) were reversed fully by week-4 and remained stable during follow-up. A significant reduction in white blood cell (WBC) count in CSF was noted occurred at week-4 (P = 0.009). The median protein concentration in CSF decreased from 1.4 (0.7-3.2) g/L at baseline to 0.9 (0.6-1.4) at week-4 (P = 0.004). The median albumin concentration in CSF decreased from 79.2 (48.4-149.8) mg/L at baseline to 55.3 (38.3-89.0) mg/L at week-4 (P = 0.011). The WBC count, protein level, and albumin level in CSF remained stable and approached a normal range through week-24. There was no significant change in immunoglobulin-G, intracranial pressure (ICP), or chloride-ion concentration at each visit. Brain MRI demonstrated multiple lesions to be absorbed post-therapy. Levels of tumor necrosis factor-α granulocyte colony stimulating factor, interleukin (IL)-6, and IL-17A decreased significantly during 24-week follow-up. Two (14.3%) patients had mild skin rash, which resolved spontaneously. Lenalidomide-related serious adverse events were not observed. CONCLUSION: Lenalidomide could improve persistent intracranial inflammation in HIV-CM patients significantly and was well tolerated without serious adverse events observed. And the additional randomized controlled study is required to further validate the finding.

Case report: Savolitinib induced severe adverse reactions resembling septic shock in an HIV-1-positive patient with advanced non-small cell lung cancer.

Savolitinib, a small-molecule inhibitor of the receptor tyrosine kinase mesenchymal-epithelial transition (MET) factor, was approved for the treatment of non-small cell lung cancer (NSCLC) by the China National Medical Products Administration in June 2021. Its safety for NSCLC treatment has been confirmed in several prospective cohort studies. Herein, we report a rare case of shock, a serious adverse event, after treatment with savolitinib in an HIV-1-positive patient with advanced NSCLC. A 38-year-old man with an 8-year history of HIV-1 positivity was diagnosed with NSCLC 5 years ago; the lung cancer recurred after surgical resection. Despite chemotherapy, immunotherapy, and targeted therapy, tumor progression continued. He received savolitinib because of MET amplification. In the first 2 weeks of savolitinib use, he developed a mild rash on his trunk. In the following month, he was hospitalized for fever and circulatory shock thrice after taking savolitinib 400 mg. He had no urticaria or eosinophilia. During the three hospitalizations, he was negative for pathogens. His condition gradually improved after treatment with antibiotics, steroids, and vasopressors. Attention should be paid to the occurrence of septic shock-like presentations when using savolitinib in HIV-1 patients with NSCLC.

Decreased functional connectivity in salience network is associated with symptom severity in betel quid-dependent chewers.

BACKGROUND: Betel quid (BQ) is the fourth most popular psychoactive agent worldwide. Neuroimaging studies have showed that substance-addicted individuals including alcohol, heroin, nicotine and other addictive substance exhibit altered activity patterns of the salience network (SN). However, no study has yet investigated the neural correlates of the resting-state SN and BQ dependence (BQD)-related physiopathological characteristics. METHODS: Thirty-two BQ-dependent (BQD) chewers and 32 healthy controls were recruited to participate in this study. Resting-state functional magnetic resonance imaging (fMRI) data were analysed by independent component analysis (ICA). RESULTS: BQD chewers exhibited decreased functional connectivity in bilateral insula, anterior cingulate cortex (ACC), medial superior frontal gyrus (MSFG) and inferior orbital frontal gyrus (IOFG) [false discovery rate (FDR) correction, p < 0.05]. In the BQD group, the decreased functional connectivity in left ACC correlated negatively with BQDS (BQD Scale) and the duration of BQ. CONCLUSIONS: We reported decreased functional connectivity in resting-state SN of BQD individuals. The decreased functional connectivity in left ACC correlated negatively with BQDS and the duration of BQ. Our findings provided evidence for the importance of the SN in the pathophysiology of BQD and indicated that the SN dysfunction might provide a potential mechanism in BQD development.

Case report: Ruxolitinib as first-line therapy for secondary hemophagocytic lymphohistiocytosis in patients with AIDS.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a fatal immunological syndrome resulting from excessive production of inflammatory cytokines. The conventional therapies for HLH, which are based on cytotoxic agents, are not always efficacious and safe, especially in patients with severe immunodeficiency. Ruxolitinib, a strong inhibitor of Janus kinase (JAK) 1/2, has already been evaluated as salvage and first-line therapy for HLH. Despite its promising efficacy and tolerability in the treatment of secondary HLH, the efficacy and safety of ruxolitinib in HLH patients with HIV infection remain to be investigated. Case presentation: Two men (ages: 45 and 58 years) both presented at our hospital with a high fever. They were found to be HIV-positive with severe immunodeficiency and opportunistic infections. Their laboratory tests showed severe pancytopenia, hypofibrinogenemia, hypertriglyceridemia, and increased levels of inflammatory factors and ferritin. Hemophagocytosis was found in the bone marrow, and abdominal computed tomography or ultrasonography showed splenomegaly. Both patients were diagnosed with infection-induced HLH due to severe immunodeficiency. Given they were both highly immunocompromised, we chose ruxolitinib as a first-line treatment alternative to cytotoxic chemotherapy. Rapid remission of clinical symptoms and normalization of laboratory parameters were achieved after ruxolitinib therapy. Neither patient had any associated adverse drug reactions or other laboratory abnormalities. Both patients were eventually discharged and ruxolitinib was discontinued as their disease alleviated, and they did not show signs of relapse during the 3- and 5-month of follow-up examinations. Conclusion: We described two cases of AIDS-related secondary HLH treated with ruxolitinib. Our cases highlight the feasibility of using ruxolitinib as a first-line therapy in patients with HIV infection and secondary HLH. Nevertheless, the safety and efficacy of this novel treatment need to be evaluated in large clinical trials in the future.

Regional metabolic heterogeneity in anterior cingulate cortex in major depressive disorder: A multi-voxel 1H magnetic resonance spectroscopy study.

BACKGROUND: Previous studies have shown major depressive disorder (MDD) is associated with altered neuro-metabolites in the anterior cingulate cortex (ACC). However, the regional metabolic heterogeneity in the ACC in individuals with MDD remains unclear. METHODS: We recruited 59 first-episode, treatment-naive young adults with MDD and 50 healthy controls who underwent multi-voxel 1H-MRS scanning at 3 T (Tesla) with voxels placed in the ACC, which was divided into two subregions, pregenual ACC (pACC) and anterior midcingulate cortex (aMCC). Between and within-subjects metabolite concentration variations were analyzed with SPSS. RESULTS: Compared with control subjects, patients with MDD exhibited higher glutamate (Glu) and glutamine (Gln) levels in the pACC and higher myo-inositol (MI) level in the aMCC. We observed higher Glu and Gln levels and lower N-acetyl-aspartate (NAA) level in the pACC than those in the aMCC in both MDD and healthy control (HC) groups. More importantly, the metabolite concentration gradients of Glu, Gln and NAA were more pronounced in MDD patients relative to HCs. In the MDD group, the MI level in the aMCC positively correlated with the age of onset. LIMITATIONS: The use of the relative concentration of metabolites constitutes a key study limitation. CONCLUSIONS: We observed inconsistent alterations and distribution of neuro-metabolites concentration in the pACC and aMCC, revealing regional metabolic heterogeneity of ACC in first-episode, treatment-naive young individuals with MDD. These results provided new evidence for abnormal neuro-metabolites of ACC in the pathophysiology of MDD and suggested that pACC and aMCC might play different roles in MDD.

Lenalidomide potentially reduced the level of cell- associated HIV RNA and improved persistent inflammation in patients with HIV-associated cryptococcal meningitis a pilot study.

Background: The HIV-1 reservoir is a major barrier to curative strategies. Inflammation is an important factor for HIV-1 reservoir persistence. Lenalidomide regulates inflammatory cytokines efficiently. We examined whether lenalidomide could inhibit HIV-1 transcription and reduce systemic inflammation in people living with HIV. Methods: Lenalidomide was administered orally for 48 weeks to patients with HIV-associated cryptococcal meningitis (HIV-CM). A HIV-1 latency model was treated with or without lenalidomide ex vivo for 5 days. The primary endpoints were change in HIV reservoir markers and inflammatory cytokines in both the cohort and cell model. Results: Thirteen participants were enrolled from May 2019 to September 2020. The median change in cell-associated (CA) HIV RNA between baseline and 48 weeks was 0.81 log10 copies/million peripheral blood mononuclear cells (PBMCs). The CA HIV RNA decreased significantly in the cohort (P = 0.021). Serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) gradually diminished with lenalidomide treatment until 48 weeks (P = 0.007, P = 0.014, respectively). C-reactive protein/IL-6/TNF-α and CA HIV RNA were significantly correlated (P = 0.0027, 0.0496, and 0.0346, respectively). Lenalidomide also significantly decreased HIV core P24 (P = 0.0038) and CA HIV RNA in CD8-depleted PBMCs (P = 0.0178) ex vivo. TNF-α and IL-6 were significantly reduced in the CD8-depleted PBMC supernatant (P = 0.004, P < 0.0001, respectively) while IL-10 levels increased significantly on lenalidomide compared to no-lenalidomide treatment (P < 0.0001). Conclusions: Lenalidomide was preliminarily confirmed to reduce the level of cell- associated HIV RNA and improve persistent inflammation in patients with HIV-Associated cryptococcal meningitis, which was a potential intervention for clinical use to inhibit viral transcription of the HIV-1 reservoir and reduced HIV-related inflammation in HIV-1 patients during ART.

Usability evaluation of a novel compact pneumatic compression device for the treatment of lymphoedema: Pilot study.

OBJECTIVE: To perform a preliminary usability evaluation of a novel, compact pneumatic compression device in patients with lymphoedema. METHODS: This open-label, single-arm trial had two phases: the first focused on the fitting of the pneumatic compression device (Aria FreeTM, Aria Health, San Diego CA, USA) and the second focused on evaluating the comfort of the entire system during a 45-min usage period. Both phases were conducted in a monitored clinical environment. Patients aged ≥18 years with a diagnosis of lower limb lymphoedema who had used a pneumatic compression device for ≥3 months were eligible. Patients rated subjective fit, comfort and usability on an 11-point Likert scale (where higher scores indicate better fit/comfort/usability). The truncated cone method was used to infer limb volume before and after therapy in phase 2. RESULTS: Twenty-four patients were screened, and 15 were enrolled (80% female; mean age 62 years); all completed both study phases. Patients rated the garment as easy to set up and fit (median score 6.5), and all reported that the therapy was comfortable (median score 10; p < 0.001 vs. reference score of 6). There was a 1.85% reduction in limb volume after device use for 45 min (p = 0.018 vs. before therapy). No safety issues were identified. CONCLUSIONS: The new pneumatic compression device fitted well, was easy to use and reduced leg oedema.

Characteristics of COVID-19 Patients With SARS-CoV-2 Positivity in Feces.

Background: SARS-CoV-2 is highly contagious and poses a great threat to epidemic control and prevention. The possibility of fecal-oral transmission has attracted increasing concern. However, viral shedding in feces has not been completely investigated. Methods: This study retrospectively reviewed 97 confirmed coronavirus disease 2019 (COVID-19) patients hospitalized at the First Affiliated Hospital, School of Medicine, Zhejiang University, from January 19 to February 17, 2020. SARS-CoV-2 RNA in samples of sputum, nasopharyngeal or throat swabs, bronchoalveolar lavage and feces was detected by real-time reverse transcription polymerase chain reaction (RT-PCR). Clinical characteristics and parameters were compared between groups to determine whether fecal RNA was positive. Results: Thirty-four (35.1%) of the patients showed detectable SARS-CoV-2 RNA in feces, and 63 (64.9%) had negative detection results. The median time of viral shedding in feces was approximately 25 days, with the maximum time reaching 33 days. Prolonged fecal-shedding patients showed longer hospital stays. Those patients for whom fecal viral positivity persisted longer than 3 weeks also had lower plasma B-cell counts than those patients in the non-prolonged group [70.5 (47.3-121.5) per µL vs. 186.5 (129.3-376.0) per µL, P = 0.023]. Correlation analysis found that the duration of fecal shedding was positively related to the duration of respiratory viral shedding (R = 0.70, P < 0.001) and negatively related to peripheral B-cell counts (R = -0.44, P < 0.05). Conclusions: COVID-19 patients who shed SARS-CoV-2 RNA in feces presented similar clinical characteristics and outcomes as those who did not shed SARS-CoV-2 RNA in feces. The prolonged presence of SARS-CoV-2 nucleic acids in feces was highly correlated with the prolonged shedding of SARS-CoV-2 RNA in the respiratory tract and with lower plasma B-cell counts.

Micro-ecology restoration of colonic inflammation by in-Situ oral delivery of antibody-laden hydrogel microcapsules.

In-situ oral delivery of therapeutic antibodies, like monoclonal antibody, for chronic inflammation treatment is the most convenient approach compared with other administration routes. Moreover, the abundant links between the gut microbiota and colonic inflammation indicate that the synergistic or antagonistic effect of gut microbiota to colonic inflammation. However, the antibody activity would be significantly affected while transferring through the gastrointestinal tract due to hostile conditions. Moreover, these antibodies have short serum half-lives, thus, require to be frequently administered with high doses to be effective, leading to low patient tolerance. Here, we develop a strategy utilizing thin shell hydrogel microcapsule fabricated by microfluidic technique as the oral delivering carrier. By encapsulating antibodies in these microcapsules, antibodies survive in the hostile gastrointestinal environment and rapidly release into the small intestine through oral administration route, achieving the same therapeutic effect as the intravenous injection evaluated by a colonic inflammation disease model. Moreover, the abundance of some intestinal microorganisms as the indication of the improvement of inflammation has remarkably altered after in-situ antibody-laden microcapsules delivery, implying the restoration of micro-ecology of the intestine. These findings prove our microcapsules are exploited as an efficient oral delivery agent for antibodies with programmable function in clinical application.

Clinical characteristics and clinical outcome of community clusters with SARS-CoV-2 infection.

Background: Community clustering is one of the main features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few studies have been conducted on the clinical characteristics and clinical outcome of clustered cases and sporadic cases with COVID-19. Methods: We recruited 41 community clusters confirmed with SARS-CoV-2 infection compared with 49 sporadic cases in Zhejiang Province from 19 January 2020 to 9 June 2020. Clinical data were collected to evaluate the clinical outcome and characteristics of community clusters. Results: Compared to sporadic cases, clustered cases had significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II) score {5.0 [interquartile range (IQR), 2.0-7.5] vs. 7.0 [IQR, 4.0-12.5]; P = 0.005}, less members in intensive care unit (ICU) (6 [14.6%] vs. 18 [36.7%]; P = 0.018), and shorter time of viral shedding in fecal samples (18.5 [IQR, 17.0-28.3] vs. 32.0 [IQR, 24.3-35.5]; P = 0.002). Univariable logistic regression revealed that older age (odds ratios 1.078, 95% confidence intervals 1.007-1.154, per year increase; p = 0.032), high APACHE II score (3.171, 1.147-8.76; P = 0.026), elevated interleukin-2 levels (3.078, 1.145-8.279; P = 0.026) were associated with ICU admission of clustered cases. Conclusions: Compared to sporadic cases, clustered cases exhibited milder disease severity and a better clinical outcome, which may be closely related to the management of early detection, early diagnosis, early treatment and early isolation of COVID-19.