Collective outbreak of severe acute histoplasmosis in immunocompetent Chinese in South America: the clinical characteristics and continuous monitoring of serum cytokines/chemokines.

BACKGROUND: Acute histoplasmosis is a rare fungal disease in China. This study is aimed to summarize the clinical characteristics of the first large-scale outbreak of imported acute histoplasmosis in Chinese, so as to provide suggestions for clinical diagnosis and treatment. METHODS: We collected the symptoms, signs, laboratory examination and imaging data of 10 patients in so far the biggest outbreak of imported acute histoplasmosis in immunocompetent Chinese. Their clinical characteristics and time-varying cytokine/chemokine levels were analyzed, and rank correlation analysis between these markers was utilized to show their condition. RESULTS: The 10 patients of imported acute histoplasmosis were working without any respiratory protection in an abandoned mine tunnel in Guyana. The most common symptoms were fever and cough. Their chest CT imaging showed multiple nodular shadows in lungs. Laboratory examination showed that at admission the CRP, PCT, LDH, CysC, G-test, ß2-MG were all increased in at least 9 patients, and the CD4/CD8 was decreased to < 1 in all patients. Most cytokines/chemokines (other than IL-4, IL-12, INF-α, TNF-α) varied widely with patients and time, but their overall trend is higher at admission and decreasing gradually during hospitalization, especially for the IL-6, IL-8, IL-10 and IFN-γ. The LDH, CysC, G-test, ß2-MG, N/L, IL-6, IL-8, IL-10, IFN-γ, IL-27 are in positive associations to both CRP and PCT. CONCLUSIONS: The diagnosis of acute histoplasmosis needs a comprehensive analysis of epidemiological history, clinical symptoms and signs, and results of imaging, laboratory, microbiological and pathological examinations. Although none of the CRP, PCT, G-test, N/L, LDH, CysC, ß2-MG, IL-6, IL-8, IL-10, IFN-γ shows specificity in the diagnosis of acute histoplasmosis, there is possibility that the above factors might help in the inflammation and prognosis estimation. However, more studies and further investigation are still required for the verification.

Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant pathogen threatening human health and safety. Biofilms are an important cause of its drug resistance and pathogenicity. Inhibition and elimination of biofilms is an important strategy for the treatment of MRSA infection. Andrographolide sulfonate (AS) is an active component of the traditional herbal medicine Andrographis paniculata. This study aims to explore the inhibitory effect and corresponding mechanisms of AS on MRSA and its biofilms. Three doses of AS (6.25, 12.5, and 25 mg/ml) were introduced to MRSA with biofilms. In vitro antibacterial testing and morphological observation were used to confirm the inhibitory effect of AS on MRSA with biofilms. Real-time PCR and metabonomics were used to explore the underlying mechanisms of the effect by studying the expression of biofilm-related genes and endogenous metabolites. AS displayed significant anti-MRSA activity, and its minimum inhibitory concentration was 50 µg/ml. Also, AS inhibited biofilms and improved biofilm permeability. The mechanisms are mediated by the inhibition of the expression of genes, such as quorum sensing system regulatory genes (agrD and sarA), microbial surface components-recognizing adhesion matrix genes (clfA and fnbB), intercellular adhesion genes (icaA, icaD, and PIA), and a gene related to cellular eDNA release (cidA), and the downregulation of five biofilm-related metabolites, including anthranilic acid, D-lactic acid, kynurenine, L-homocitrulline, and sebacic acid. This study provided valuable evidence for the activity of AS against MRSA and its biofilms and extended the methods to combat MRSA infection.

Efficacy and safety of Xiyanping injection in the treatment of COVID-19: A multicenter, prospective, open-label and randomized controlled trial.

Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID-19). Here, we conducted a prospective, multicenter, open-label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID-19. We consecutively recruited 130 COVID-19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID-19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID-19 patients at different disease stages.

Is combined medication with natural medicine a promising therapy for bacterial biofilm infection?

Bacterial biofilms widely exist in nature and seriously threaten global public health. Biofilms always cause persistent infection and seriously aggravate the occurrence of antibiotic resistance, which makes the treatment of bacterial infection difficult. Current conventional therapies, such as antibiotics, bacteriophages and quorum sensing inhibitors, are widely used to combat biofilms. However, these therapies are inadequate for the safe and effective treatment of biofilms. Antibiotics often produce resistance in treated bacteria, and antibacterial peptides are easily decomposed by proteases, so their efficacy is reduced. These results indicate that the treatment of biofilms needs further improvement. Increasing evidence has shown that natural medicine therapies have significant inhibitory effects on biofilms. This review summarized and analyzed the efficacy characteristics and corresponding mechanisms of conventional and natural medicine therapies combatting biofilms. By comparison, the advantages and disadvantages of those therapies have been classified and interpreted, so we have inferred that combined medication with natural medicines will be a more effective strategy against biofilms. This review lays a promising foundation for the development of antibiofilm agents and provides novel thinking for the treatment of bacterial biofilm infections.

Reduction of NgR in perforant path decreases amyloid-ß peptide production and ameliorates synaptic and cognitive deficits in APP/PS1 mice.

BACKGROUND: Amyloid beta (Aß) which is recognized as a main feature of Alzheimer's disease (AD) has been proposed to "spread" through anatomically and functionally connected brain regions. The entorhinal cortex and perforant path are the earliest affected brain regions in AD. The perforant path is the most vulnerable circuit in the cortex with respect to both aging and AD. Previous data show that the origins and terminations of the perforant path are susceptible to amyloid deposition at the younger age in AD. Nogo receptor (NgR) plays an essential role in limiting injury-induced axonal growth and experience-dependent plasticity in the adult brain. It has been suggested that NgR is involved in AD pathological features, but the results have been conflicting and the detailed mechanism needs further investigation. In this study, the effect of NgR in the perforant path on the pathological and functional phenotype of APP/PS1 transgenic mice was studied. METHODS: To genetically manipulate NgR expression, adeno-associated virus (AAV) with short hairpin (shRNA) against NgR was injected into the perforant path of APP/PS1 transgenic mice, followed by an assessment of behavioral, synaptic plasticity and neuropathological phenotypes. NgR was overexpressed or knockdown in neuroblastoma N2a cells and APPswe/HEK293 cells to investigate the interaction between NgR and amyloid precursor protein (APP). RESULTS: It is shown that reduction of NgR in the perforant path rescued cognitive and synaptic deficits in APP/PS1 transgenic mice. Concurrently, Aß production in the perforant path and levels of soluble Aß and amyloid plaques in the hippocampus were significantly decreased. There was a positive correlation between the total APP protein level and NgR expression both in transgenic mice and in cultured cells, where the α-secretase and ß-secretase cleavage products both changed with APP level in parallel. Finally, NgR might inhibit APP degradation through lysosome by Rho/Rho-associated protein kinases (ROCK) signaling pathway. CONCLUSIONS: Our findings demonstrate that perforant path NgR plays an important role in regulating APP/Aß level and cognitive functions in AD transgenic mice, which might be related to the suppression of APP degradation by NgR. Our study suggests that NgR in the perforant path could be a potential target for modulating AD progression.

Clinical Study on TCM Foot bath in Adjuvant Treatment for Type 2 Diabetes Lower-extremity Peripheral Arterial Disease / 中国中医药信息杂志

Objective To observe the clinical efficacy of TCM foot bath in adjuvant treatment for early diabetic lower-extremity peripheral arterial disease (LEPAD). Methods Totally 90 cases with early diabetic LEPAD were divided into treatment group and control group by random number table method, with 45 cases in each group. Control group was given routine treatment, including health education, diet control, proper exercise, control of blood sugar, blood pressure and blood lipids, nutritional nerves, dilation of blood vessels. On the basis of control group, the treatment group was given TCM foot bath, soaking the lower limbs for 30 minutes each time, once a day, for 12 weeks. The clinical efficacy of the two groups was evaluated. The TCM syndrome score, maximum painless walking distance, temperature of the toe skin, diameter of the lower extremity arterial blood vessels, lower extremity arterial blood flow, ankle brachial index (ABI), blood pressure (BP), FBG, HbA1c, serum adiponectin, IL-6 and TNF-α were detected. The blood routine, liver and kidney function were detected and adverse reactions were recorded. Results The total effective rate was 82.22% (37/45) in the treatment group and 68.89% (31/45) in the control group. The treatment group was significantly better than the control group (Z=-2.099, P=0.036). Compared with before treatment, the levels of TCM syndromes, BP, FBG, HbA1c, serum IL-6 and TNF-α were significantly lower in both groups after treatment (P<0.05); serum adiponectin level increased after treatment (P<0.05); the maximum painless walking distance, the temperature of the toe skin, the diameter of the lower extremity arterial blood vessels, the lower extremity arterial blood flow and ABI were significantly improved. Compared with the control group, the scores of TCM syndromes in the treatment group were significantly lower (P<0.05); the levels of IL-6 and TNF-α in the treatment group were significantly lower than those in the control group (P<0.05); the maximum painless walking distance, the temperature of the toe skin, the diameter of the lower extremity arterial vessels, the lower extremity arterial blood flow and ABI, serum adiponectin level in the treatment group were significantly higher than those of the control group (P<0.05). Conclusion TCM foot bath in adjuvant treatment for early diabetic LEPAD is with obvious efficacy, and the mechanism may be related to improving the level of serum inflammatory cytokines to inhibit the inflammatory injury of blood vessels.