Guochao Zhang

Objectives: Sex- and age-related disparities are independent risk factors for poor COVID-19 outcomes, but underlying mechanisms remain unclear. Methods: This retrospective cohort study included 395 hospitalized COVID-19 patients (December 2022–March 2023). Biomarkers of multi-organ injury and immune responses were analyzed to evaluate the impact of sex and age on disease progression and clinical outcomes. Normality was assessed with the Shapiro–Wilk test; Student’s t or Mann–Whitney U tests were used accordingly, with Benjamini-Hochberg false discovery rate correction across 45 biomarkers. Multivariable logistic regression was used to adjust for sex, age, co-infection, comorbidities, and symptom onset to discharge time. Results: Among 395 patients (68% mild, 32% severe), males accounted for 76% of severe cases and patients aged ≥75 years for 79%. After false discovery rate correction ( q < 0.05), 37 of 45 biomarkers differed by severity, 24 by sex, and 22 by age. Male patients had higher inflammatory, coagulation, cardiac, hepatic, and renal injury markers and lower lymphocyte, total protein, and albumin levels. Although not statistically significant, T, B, or NK cell counts showed decreasing trends in males. Older adult male patients displayed the most pronounced inflammatory responses, coagulation abnormalities, multi-organ injury, lymphopenia, and reduced nutritional reserves. In multivariable logistic regression, male sex (OR 1.925, 95% CI 1.063–3.484, p = 0.031) and age ≥75 years (OR 5.164, 95% CI 2.733–9.756, p < 0.001) were associated with severe COVID-19; the male sex and age association persisted after excluding co-infections and in patients with shorter onset-to-discharge durations. Conclusion: Sex and age differences are closely associated with COVID-19 severity, likely due to multi-organ dysfunction and immunosuppression following SARS-CoV-2 infection.

Objectives: Severe COVID-19 infection is characterized by excessive inflammatory responses, hypercoagulation, and microvascular dysfunction. However, limited research has investigated the effects of co-infections on these characteristics in COVID-19 patients. This study aims to explore how co-infections influence inflammation, hypercoagulability, and microvascular dysfunction in hospitalized COVID-19 patients, and to assess their impact on disease progression.Methods: This was a retrospective cohort study involving 630 COVID-19 inpatients who tested positive for SARS-CoV-2 RNA at Xi’an Ninth Hospital. The patients were categorized into two groups: a severe group (n = 176) and a mild group (n = 454). Additionally, they were further subdivided into a co-infected (n = 106) group and a non-co-infected group (n=524) based on the presence or absence of co-infections. Clinical characteristics and laboratory findings were analyzed and compared between the groups.Results: In the co-infected group, 60 patients (56.6%) were classified as severe cases, and 15 (14.2%) died. By comparison, in the non-co-infected group, 97 patients (18.5%) were severe cases, with 4 (0.8%) deaths. The severity and mortality rates were significantly higher in co-infected patients compared to those non-co-infections. The severe and co-infected groups exhibited significantly higher levels of inflammatory cells, inflammatory factors, coagulation biomarkers, and myocardial injury markers compared to the mild and non-co-infected groups. Conversely, lymphocyte counts, RBC counts, HGB, HCT, TP, and ALB levels were significantly lower in the severe and co-infected groups than in the mild and non-co-infected groups. Furthermore, a notable positive correlation was observed among inflammatory factors, coagulation function, and myocardial injury biomarkers in COVID-19 patients.Conclusion: Co-infections in COVID-19 patients can trigger severe inflammatory responses. This excessive inflammation may lead to coagulation disorders and myocardial injury, all of which are key contributors to disease progression and deterioration. Therefore, implementing infection prevention measures to minimize the spread of co-infections among hospitalized COVID-19 patients is crucial.

Objectives: With the increasing number of people worldwide infected with SARS-CoV-2, the likelihood of co-infection and/or comorbidities is rising. The impact of these co-infections on the patient’s immune system remains unclear. This study aims to investigate the immunological characteristics of secondary infections in hospitalized COVID-19 patients, and preliminarily predict potential therapeutic effects of traditional Chinese medicine and their derivatives for the treatment of co-infections.Methods: In this retrospective cohort study, we included 131 hospitalized patients with laboratory-confirmed COVID-19, of whom there were 64 mild and 67 severe cases. We analyzed clinical characteristics and immunologic data, including circulating immune cell numbers, levels of inflammatory factors and viral load, comparing COVID-19 patients with and without co-infection.Results: Among 131 hospitalized COVID-19 patients, 41 (31.3%) were co-infection positive, with 33 (80.5%) having severe disease and 14 (34.1%) of them resulting in fatalities. Co-infected patients exhibited significantly higher severity and mortality rates compared to non-co-infected counterparts. Co-infected patients had significantly lower absolute counts of lymphocytes, total T lymphocytes, CD4⁺ T cells, CD8⁺ T cells and B lymphocytes, while levels of hs-CRP, PCT and IL-6 were significantly elevated compared to non-co-infected patients. Additionally, the viral load of co-infected patients was significantly higher than non-co-infected patients.Conclusion: Co-infection emerges as a dangerous factor for COVID-19 patients, elevating the risk of severe pneumonia and mortality. Co-infection suppresses the host’s immune response by reducing the number of lymphocytes and increasing inflammation, thereby diminishing the antiviral and anti-infective effects of the immune system, which promotes the severity of the disease. Therefore, it is crucial to implement infection prevention measures to minimize the spread of co-infections among COVID-19 hospitalized patients. Additionally, changes in these biomarkers provide a theoretical basis for the effective treatment of co-infections with traditional Chinese medicine.

IL-28B, belonging to type III interferons (IFN-λs), exhibits a potent antitumor activity with reduced regulated T cells (Tregs) population, yet the effect of IL-28B on the tumor microenvironment (TME) and if IL-28B can downregulate Tregs directly in vitro are still unknown. In this study, we investigated the effects of IL-28B on Tregs in the spleen and TME in H22 tumor-bearing mice and verified the downregulation of IL-28B on Tregs in vitro. We found that rAd-mIL-28B significantly inhibited tumor growth and reduced the frequency of splenic CD4⁺Foxp3⁺ T cells. The levels of CXCL13, ICAM-1, MCP-5, and IL-7 in the serum, and the levels of IL-15 and sFasL in the tumor tissue decreased significantly after rAd-mIL-28B treatment relative to rAd-EGFP. Furthermore, the percentage of CD8⁺ cells in the TME was significantly increased in the rAd-mIL-28B group compared with the untreated group. In vitro, splenocytes were stimulated with anti-CD3/CD28 and IL-2 in the presence of TGF-β with or without IL-28B for three days and followed by flow cytometric, RT-PCR, and IL-10 production analysis. The results showed that IL-28B significantly reduced the proportion of induced Foxp3⁺ cells. It demonstrated that IL-28B may be used as a promising immunotherapy strategy against cancer.

In this study, we prepared a new type of recyclable Co@Ag core–shell nanomaterials with a very simple method named displacement reaction. Co@Ag core–shell nanomaterials were prepared in AgNO₃ solution with cobalt nanomaterials as the core, while the surface was coated with silver nanomaterials. Co@Ag core–shell nanomaterials were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and oscillating sample magnetometer (VSM).We found that the diameter of the Co@Ag core–shell nanomaterials was about 100nm, which was exhibited in form of elemental elements andobvious magnetic properties.In order to evaluate the bacteriostatic effect of Co@Ag core–shell nanomaterials, we used qualitative and quantitative methods to assess the bacteriostatic effect of these materials on standard strains of Pseudomonas aeruginosa (ATCC27853, Gram - negative bacterium), Staphylococcus aureus (ATCC 25923, Gram-positive bacterium), Escherichia coli (ATCC 25922, Gram-negative bacterium) and Candida albicans (ATTC 90029, yeast) in Yellow River water in vitro. The results show that Co@Ag core–shell nanomaterials have a significant antibacterial effect. In addition, Co@Ag core–shell nanomaterials can be recycled through an external magnetic field to reduce environmental pollution. Interestingly, the reclaimed Co@Ag core–shell nanomaterials can still have antibacterial activity and can be reused. These results indicate that Co@Ag core–shell nanomaterials may have potential application as disinfectants for water.

Background In recent years, nanomaterials have attracted much more attention because of their potential broad-spectrum antimicrobial activity. However, finding biofunctional nanomaterials is still challenging. Therefore,we prepared a new type of recyclable Ag@Co nanomaterials with a very simple method named displacement reaction. Methods Ag@Co nanomaterials were prepared in AgNO₃ solution with cobalt nanomaterials as the core, while the surface was coated with silver nanomaterials. Ag@Co nanomaterials were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and oscillating sample magnetometer (VSM).In order to evaluate the bacteriostatic effect of Ag@Co nanomaterials, we used qualitative and quantitative methods to assess the bacteriostatic effect of these materials on standard strains of Pseudomonas aeruginosa (ATCC27853, Gram - negative bacterium), Staphylococcus aureus (ATCC 25923, Gram-positive bacterium), Escherichia coli (ATCC 25922, Gram-negative bacterium) and Candida albicans (ATTC 90029, yeast) in Yellow River water in vitro. Results We found that the diameter of the Ag@Co nanomaterials was about 100nm, which was exhibited in form of elemental elements and obvious magnetic properties.The results show that Ag@Co nanomaterials have excellent antibacterial effects on Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Candida albicans and the bacteria in the water of the Yellow River. Conclusions Ag@Co nanomaterials have a significant antibacterial effect and can be recycled through an external magnetic field to reduce environmental pollution. Interestingly, the reclaimed Ag@Co nanomaterials can still have antibacterial activity and can be reused. These results indicate that Ag@Co nanomaterials may have potential application as disinfectants for water.

Echinococcosis is a zoonotic infection caused by cestode species of the genus Echinococcus, with limited treatment options. It is urgent to develop new anti-hydatid agent. In this paper, we reported anacardic acid (AA), a natural product isolated from the Brazilian cashew-nut shell liquid, which presented a high activity against metacestodes of Echinococcus multilocularis (E. multilocularis) and Echinococcus granulosus sensu stricto (E. granulosus s.s.) in vitro and in vivo. AA exerted a better efficacy on E. granulosus s.s. protoscoleces and E. multilocularis metacestodes than that of albendazole (ABZ) and dihydroartemisinin (DHA) in vitro, and an inhibition on the growth of Echinococcus metacestode as effective as ABZ in vivo. Moreover, we also found that one of the mechanisms of AA against Echinococcus could be the suppression of angiogenesis on/in the metacestode mass through inhibiting vascular endothelial growth factor (VEGF)—induced signalling pathways. This work finds that AA is a new promising potential candidate drug for echinococcosis treatment.

Novel compounds and more efficient treatment options are urgently needed for the treatment of cystic echinococcosis (CE), which is caused by Echinococcus granulosus. The decoction of Sophora moorcroftiana (Fabaceae) has been used to treat parasitosis for years in traditional Tibetan medicine. The aim of this study was to screen insecticidal water-soluble alkaloids from S. moorcroftiana seeds and evaluate the therapeutic effects against CE and the immune response induced by the alkaloidal fraction. Low polarity compounds (E2-a) were isolated from water-soluble alkaloid (E2) and matrine and sophocarpine were identified as major components. The E2-a fraction was more effective against protoscoleces than other constituents from S. moorcroftiana. After 20 weeks of secondary infection with protoscoleces, mice were orally treated with E2-a (100 mg/kg/day) for 6 weeks to evaluate therapeutic and immunoregulatory activities. Compared with the untreated group, E2-a treatment induced a significant reduction in cyst weight (mean 2.93 g) (p < 0.05) and an impaired ultrastructural modification of the cyst. Interestingly, the application of E2-a resulted in a significant increased frequency of CD3⁺CD4⁺ T-cell subsets and decreased frequency of CD3⁺PD-1⁺ T-cell subsets, compared with protoscolece-infected mice without treatment. The E2-a fraction of S. moorcroftiana can inhibit the cyst development of CE and boost the specific immune response by reducing the expression of PD-1 and accelerate the cytokine secretion of antigen-specific T-cells. All data suggest the E2-a fraction from S. moorcroftiana seeds may be used as a new potential therapeutic option against E. granulosus infection.