Three-Dimensional Reconstruction for the Whole Lung with Early Multiple Pulmonary Nodules.

For patients with early multiple pulmonary nodules, it is essential, from a diagnostic perspective, to determine the spatial distribution, size, location, and relationship with surrounding lung tissue of these nodules throughout the entire lung. This is crucial for identifying the primary lesion and developing more scientifically grounded treatment plans for doctors. However, pattern recognition methods based on machine vision are susceptible to false positives and false negatives and, therefore, cannot fully meet clinical demands in this regard. Visualization methods based on maximum intensity projection (MIP) can better illustrate local and individual pulmonary nodules but lack a macroscopic and holistic description of the distribution and spatial features of multiple pulmonary nodules. Therefore, this study proposes a whole-lung 3D reconstruction method. It extracts the 3D contour of the lung using medical image processing technology against the background of the entire lung and performs 3D reconstruction of the lung, pulmonary artery, and multiple pulmonary nodules in 3D space. This method can comprehensively depict the spatial distribution and radiological features of multiple nodules throughout the entire lung, providing a simple and convenient means of evaluating the diagnosis and prognosis of multiple pulmonary nodules.

Kaempferol inhibits SARS-CoV-2 invasion by impairing heptad repeats-mediated viral fusion.

BACKGROUND: The continuous evolution of SARS-CoV-2 has underscored the development of broad-spectrum prophylaxis. Antivirals targeting the membrane fusion process represent promising paradigms. Kaempferol (Kae), an ubiquitous plant flavonol, has been shown efficacy against various enveloped viruses. However, its potential in anti-SARS-CoV-2 invasion remains obscure. PURPOSE: To evaluate capabilities and mechanisms of Kae in preventing SARS-CoV-2 invasion. METHODS: To avoid interference of viral replication, virus-like particles (VLPs) constructed with luciferase reporter were applied. To investigate the antiviral potency of Kae, human induced pluripotent stem cells (hiPSC)-derived alveolar epithelial cells type II (AECII) and human ACE2 (hACE2) transgenic mice were utilized as in vitro and in vivo models, respectively. Using dual split protein (DSP) assays, inhibitory activities of Kae in viral fusion were determined in Alpha, Delta and Omicron variants of SARS-CoV-2, as well as in SARS-CoV and MERS-CoV. To further reveal molecular determinants of Kae in restricting viral fusion, synthetic peptides corresponding to the conserved heptad repeat (HR) 1 and 2, involved in viral fusion, and the mutant form of HR2 were explored by circular dichroism and native polyacrylamide gel electrophoresis. RESULTS: Kae inhibited SARS-CoV-2 invasion both in vitro and in vivo, which was mainly attributed to its suppressive effects on viral fusion, but not endocytosis, two pathways that mediate viral invasion. In accordance with the proposed model of anti-fusion prophylaxis, Kae functioned as a pan-inhibitor of viral fusion, including three emerged highly pathogenic coronaviruses, and the currently circulating Omicron BQ.1.1 and XBB.1 variants of SARS-CoV-2. Consistent with the typical target of viral fusion inhibitors, Kae interacted with HR regions of SARS-CoV-2 S2 subunits. Distinct from previous inhibitory fusion peptides which prevent the formation of six-helix bundle (6-HB) by competitively interacting with HRs, Kae deformed HR1 and directly reacted with lysine residues within HR2 region, the latter of which was considered critical for the preservation of stabilized S2 during SARS-CoV-2 invasion. CONCLUSIONS: Kae prevents SARS-CoV-2 infection by blocking membrane fusion and possesses a broad-spectrum anti-fusion ability. These findings provide valuable insights into potential benefits of Kae-containing botanical products as a complementary prophylaxis, especially during the waves of breakthrough infections and re-infections.

Role of Traditional Chinese Medicine in the Management of Viral Pneumonia.

Viral pneumonia is one kind of acute respiratory tract infection caused by the virus. There have been many outbreaks of viral pneumonia with high contagiousness and mortality both in China and abroad, such as the great influenza in 1918, the severe acute respiratory syndrome (SARS) coronavirus in 2003, the Influenza A (H1N1) virus in 2009, and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 2012 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. These outbreaks and/or pandemic have significant impact on human life, social behaviors, and economic development. Moreover, no specific drug has been developed for these viruses. Traditional Chinese medicine (TCM) plays an important role in the treatment of viral pneumonia during these outbreaks especially in SARS and SARS-CoV-2 because studies suggest that TCM formulations may target several aspects of the disease and may have lesser side effects than manufactured pharmaceuticals. In recent years, a lot of clinicians and researchers have made a series of in-depth explorations and investigations on the treatment of viral pneumonia with TCM, which have understood TCM therapeutic mechanisms more specifically and clearly. But critical analysis of this research in addition to further studies are needed to assess the potential of TCM in the treatment of viral pneumonia.

Efficacy of Shenfu decoction on sepsis in rats with condition induced by cecal ligation and puncture.

OBJECTIVE: To evaluate the efficacy of Shenfu decoction (SFD) prepared with a traditional Chinese formula, on sepsis in rats with the condition induced by cecal ligation and puncture (CLP), and to study the possible mechanism underlying its action. METHODS: Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups: normal control group (NCG, n = 10), model control group (MCG, n = 15) and Shenfu decoction group (SFDG, n = 15). Sham-operated rats in NCG were served as operation control, while rats in both MCG and SFDG were exposed to CLP, a procedure to develop experimental sepsis. Rats in SFDG were administered with SFD by gavage (3 mg/g of body weight, twice a day) 2 h prior to CLP and directly after successful CLP, while rats in NCG and MCG were gavaged with equivalent volume of sterilized water. Rats in all groups were starved with free access to drink. After 24 h of administration, the mortality of rats in each group was assessed. The indicators of inflammatory response [the peritoneal inflammation by Simon's method Classification as well as serum concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by enzyme linked immunosorbent assay (ELISA)] in survival rats were evaluated. The indicators of gut barrier [The intestinal mucosal injury index, serum concentrations of D-lactic acid and secretory IgA (sIgA) in intestinal mucosa by ELISA, as well as gut microbiota by16S rRNA gene sequencing] in survival rats were evaluated. RESULTS: The mortality (20%) of rats in SFDG was lower than that (33.3%) of the MCG (P < 0.01). The mortality (20%) of rats in SFDG was lower than that (33.3%) of the MCG (χ2 = 6.533, P = 0.011). Compared with the MCG,the peritoneal inflammation as well as serum concentrations of TNF-α and IL-6 decreased significantly in SFDG (all P < 0.01). Compared with the MCG, the IMII, serum concentrations of D-lactic acid, sIgA in intestinal mucosa were alleviated by SFD treatment (all P < 0.01). Increase in levels of Proteobacteria and reduction levels of Bacteroidetes induced by sepsis were observed, and these two disturbed gut microbiota phyla could be regulated after SFD treatment. Increase in levels of Proteobacteria and reduction levels of Bacteroidetes induced by sepsis were observed, and these two disturbed gut microbiota phyla could be regulated after SFD treatment. CONCLUSION: SFD may play a protective role in sepsis by alleviating sepsis-induced inflammatory response and gut barrier damage in rats.

Core Outcome Set for Clinical Trials of COVID-19 Based on Traditional Chinese and Western Medicine.

BACKGROUND: Development of a core outcome set (COS) for clinical trials for COVID-19 is urgent because of the pandemic wreaking havoc worldwide and the heterogeneity of outcomes in clinical trials. METHODS: A preliminary list of outcomes was developed after a systematic review of protocols of clinical trials for COVID-19. Then, two rounds of the Delphi survey were conducted. Stakeholders were traditional Chinese medicine (TCM) experts, Western medicine (WM) experts, nurses, and the public. Patients with confirmed COVID-19 were also invited to participate in a questionnaire written in understandable language. Then different stakeholders participated in a consensus meeting by video conference to vote. RESULTS: Ninety-seven eligible study protocols were identified from 160 clinical trials. Seventy-six outcomes were identified from TCM clinical trials and 126 outcomes were identified from WM clinical trials. Finally, 145 outcomes were included in the first round of the Delphi survey. Then, a COS for clinical trials of TCM and WM was developed. The COS included clinical outcomes (recovery/improvement/progression/death), etiology (SARS-CoV-2 nucleic-acid tests, viral load), inflammatory factor (C-reactive protein), vital signs (temperature, respiration), blood and lymphatic-system parameters (lymphocytes, virus antibody), respiratory outcomes (pulmonary imaging, blood oxygen saturation, PaO2/FiO2 ratio, arterial blood gas analysis, mechanical ventilation, oxygen intake, pneumonia severity index), clinical efficacy (prevalence of preventing patients with mild-to-moderate disease progressing to severe disease), and symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instruments/definitions were also recommended. CONCLUSION: Though there are some limitations for the research, such as insufficient patients and the public involvement, and the unbalanced stakeholders' region, the COS for COVID-19 may improve consistency of outcome reporting in clinical trials. It also should be updated with research progression.