Effects of adjunctive Chinese patent medicine on outcome of viral encephalitis in children: A multicenter retrospective study in China.

BACKGROUND: Some patients with viral encephalitis in China seek treatment with Chinese patent medicine (CPM) to improve their symptoms, but few studies have focused on the impact of CPM on the prognosis of viral encephalitis (VE). The aim of this multicenter retrospective study was to assess the benefit of adjunctive CPM therapy on the outcome of children with VE in China. METHODS: This study retrospectively included 834 children with viral encephalitis who were hospitalized at five medical institutions from 2018 to 2021. Univariate and multivariate logistic regression was used to assess the effect of CPM on sequelae in patients with VE. 1:1 propensity score matching was used to exclude the effect of confounding factors. Forest plots were used to observe the effect of CPM on the prognosis of VE in different subgroups. RESULTS: There were fewer patients with sequelae in the group of patients using CPM regardless of whether they were matched or not. The results of multivariate logistic regression analysis showed that the use of CPM was an independent protective factor for the development of sequelae in VE patients (OR = 0.063, 95 % CI: 0.011-0.350, p = 0.002). Subgroup analyses showed that CPM was a protective factor for the development of sequelae regardless of the presence or absence of coma and comorbidities. In addition, we evaluated other outcome indicators and found shorter duration of illness, fever and headache in children with EV in the CPM group. CONCLUSION: Adjunctive CPM therapy may significantly reduce sequelae in children with VE, as well as effectively alleviate patients' clinical symptoms. However, more prospective studies and clinical trials are needed to further evaluate its efficacy and safety.

Folic acid functionalized aggregation-induced emission nanoparticles for tumor cell targeted imaging and photodynamic therapy.

Recently, molecules with aggregation-induced luminescence (AIE) characteristics have received more and more attention due to the fluorescence of traditional dyes being easily quenched in the aggregated state. AIE molecules have significant advantages, such as excellent light stability, bright fluorescence, high contrast, and large Stokes shift. These characteristics have aroused wide interest of researchers and opened up new applications in many fields, especially in the field of biological applications. However, AIE molecules or their aggregates have certain limitations in multifunctional biological research due to their low specific targeting ability, poor biocompatibility, and poor stability in physiological body fluids. In order to overcome these problems, a novel nanoparticle, FFM1, was fabricated and characterized. FFM1 displayed good water solubility, biocompatibility, and AIE emission properties. It could target HeLa cells specifically by recognizing their folate receptor. Reactive oxygen triggered by light irradiation induced tumor cell apoptosis. Summarily, FFM1 displayed excellent capacity in target imaging and photodynamic killing of HeLa cells. It has shown potential application value in targeted diagnosis and photodynamic therapy of tumors, and has important guiding significance for the treatment of malignant tumors. It paves a way for the development of a novel strategy for tumor theranostics.

A nitroreductase-responsive near-infrared phototheranostic probe for in vivo imaging of tiny tumor and photodynamic therapy.

The hypoxia-activated and nitroreductase-responsive phototheranostic probe has been developed by incorporating a nitro group into a hemicyanine fluorophore. The probe displays extremely sensitive and selective near-infrared fluorescence enhancement to nitroreductase with the detection limit of 2.10 ng/mL. The detection mechanism relies on the nitroreductase-catalyzed reduction of the nitro group to an amino group, along with the generation of the fluorophore. The availability of the probe in fluorescence imaging and photodynamic therapy was demonstrated at cellular level and in vivo. The probe can image endogenous nitroreductase and the hypoxia status of living cells. The probe also exhibits significant phototoxicity to hypoxia tumor cells under the 660 nm laser irradiation. More importantly, the probe has been successfully utilized in imaging tiny tumor (about 6 mm3) and tumor photodynamic therapy in vivo. The proposed probe integrates accurate near-infrared fluorescence imaging and photodynamic therapy into the same molecule, which probably become a promising agent in the early diagnosis and therapy of tumors.

Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/µl (IQR = 96-289 cells/µl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/µl) and AIDS (median CD4 = 97 cells/µl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).