This study aims to investigate the coping competence of 12 community health centers through nursing workforce, emergency preparation, emergency response training, and emergency support in a district of Shanghai during the coronavirus disease 2019 (COVID-19) pandemic in 2022 to propose coping strategies and implication for Future Public Health Emergency Events for community health centers. A cross-sectional survey was conducted on June 2022, and 12 community health centers (servicing a population of 104,472.67 ± 41,421.18, with 125 ± 36 health care providers per center) were then divided into group A (n = 5, medical care ratio ≥ 1:1) and group B (n = 7, medical care ratio < 1:1) according to collected data, and the nursing human resources management and coping competence of the centers with COVID-19 of both groups were retrospectively analyzed. Nursing shortages were obvious across all 12 centers. Certain deficiencies in the coping competence of community health centers with emergencies must be addressed (possession rate < 70% in both groups, p > 0.05). Community health centers need to enhance hospital-to-hospital collaboration and the ability to transport emergency staff to the post promptly during outbreaks. Emergency coping assessments, emergency drills at different levels, and mental health support need to be implemented regularly among community health centers, and effective donation management should be pursued as well. We expect that this study could support efforts by leaders of community health centers to conclude coping strategies including increasing nursing workforce, optimizing human recourse management, and identifying areas of improvement of centers for emergency coping during public health events.

Gamithromycin is a long-acting azalide antibiotic that has been developed recently for the treatment of swine respiratory diseases. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff, and optimum dosing regimen of gamithromycin were evaluated in piglets against Streptococcus suis in China, including a subset with capsular serotype 2. Short post-antibiotic effects (PAEs) (0.5–2.6 h) and PA-SMEs (2.4–7.7 h) were observed for gamithromycin against S. suis . The serum matrix dramatically facilitated the intracellular uptake of gamithromycin by S. suis strains, thus contributing to the potentiation effect of serum on their susceptibilities, with a Mueller-Hinton broth (MHB)/serum minimum inhibitory concentration (MIC) ratio of 28.86 for S. suis . Dose-response relationship demonstrated the area under the concentration (AUC)/MIC ratio to be the predictive PK/PD index closely linked to activity ( R 2 > 0.93). For S. suis infections, the net stasis, 1–log 10 , and 2–log 10 kill effects were achieved at serum AUC 24h /MIC targets of 17.9, 49.1, and 166 h, respectively. At the current clinical dose of 6.0 mg/kg, gamithromycin PK/PD cutoff value was determined to be 8 mg/L. A PK/PD-based dose assessment demonstrated that the optimum dose regimen of gamithromycin to achieve effective treatments for the observed wild-type MIC distribution of S. suis in China with a probability of target attainment (PTA) ≥ 90% was 2.53 mg/kg in this study. These results will aid in the development of clinical dose-optimization studies and the establishment of clinical breakpoints for gamithromycin in the treatment of swine respiratory infections due to S. suis .

Influenza A virus is globally widespread, causing a large number of infections and deaths due to acute lung injury (ALI) every year. The destruction and impairment of alveolar epithelial and microvascular endothelial cell barrier functions are the key inducers of ALI and acute respiratory distress syndrome caused by influenza virus infection. Although noncoding ribonucleic acids (ncRNAs) do not encode proteins in host cells, they possess the ability of protein regulation and signal transduction. Moreover, studies have shown that ncRNAs are significantly and differentially expressed following influenza virus infection, and these ncRNAs play vital roles in the pathogenesis of influenza virus infection. By analyzing the recently published literature, we found that ncRNA could regulate alveolar epithelial and microvascular endothelial cell barrier functions in different ways, which include influencing the innate and acquired immune responses of host cells, affecting apoptosis and autophagy, regulating tight and adherent junctions, etc. In the present paper, we reviewed the roles and regulatory mechanisms of these ncRNAs and discussed the effects of these ncRNAs on pulmonary epithelial and endothelial cell barriers. Further, by sorting and analyzing available research data, we proposed the possibility of applying these ncRNAs for treating ALI in influenza cases, thereby alleviating the permeability of pulmonary epithelial and endothelial cell barriers. Moreover, we discussed future research and development prospects. Our review suggests that targeted therapy and drug research based on ncRNAs would provide an important direction for the molecular therapy of influenza-induced ALI.

Background The physical appearance of tongue coatings is vital for traditional Chinese medicine (TCM) to diagnose health and disease status. The microbiota of different tongue coatings could also influence coating formation and be further associated with specific diseases. Previous studies have focused on bacteria from different tongue coatings in the context of specific diseases, but the normal variations in healthy individuals remain unknown.Aim: We examined the tongue microbiota by metagenomics in 94 healthy individuals classified into eight different tongue types.Results: The overall composition of the tongue coating microbiome is not drastically different among different coating types, similar to the findings of previous studies in healthy populations. Further analysis revealed microbiota characteristics of each coating type, and many of the key bacteria are reported to be implicated in diseases. Moreover, further inclusion of diabetic patients revealed disease-specific enrichment of Capnocytophaga, even though the same tongue coatings were studied.Conclusions: This work revealed the characteristic compositions of distinctive tongue coatings in a healthy population, which serves as a basis for understanding the tongue coating formation mechanism and provides a valuable reference to further investigate disease-specific tongue coating bacterial markers.

We determined in vivo efficacy and target PK/PD exposures of antofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in the murine pneumonia model. The mean plasma free drug area under the concentration-time curve/MIC (fAUC/MIC) targets associated with stasis and 1-log(10) and 2-log(10) kill effects were 8.93, 19.2, and 48.1, respectively, for S. pneumoniae, whereas they were 30.5, 55.4, and 115.8, respectively, for S. aureus. The fAUC/MIC targets in murine lung epithelial lining fluids (ELF) for the same endpoints were nearly 2-fold higher than those in plasma.

Background Gamithromycin is a macrolide approved for the treatment of bovine and swine respiratory diseases. Our study aims to establish the clinical breakpoint and optimum dose regimen for gamithromycin against Haemophilus parasuis in piglets. Results Gamithromycin was well absorbed and fully bioavailable (87.2–101%) after intramuscular and subcutaneous administrations. The MICs of gamithromycin for 192 clinical H. parasuis isolates ranged from 0.008 to 128 mg/L and the epidemiological cutoff (ECOFF) was calculated as 1.0 mg/L. A large potentiation effect of serum on in vitro susceptibility of gamithromycin was observed for H. parasuis , with broth/serum ratios of 8.93 for MICs and 4.46 for MBCs, respectively. The postantibiotic effects were 1.5 h (1 × MIC) and 2.4 h (4 × MIC), and the postantibiotic sub-MIC effects ranged from 2.7 to 4.3 h. Gamithromycin had rapid and concentration-dependent killing against H. parasuis , and the AUC 24h /MIC ratio correlated well with ex vivo efficacy (R 2 = 0.97). The AUC 24h /MIC targets in serum associated with bacteriostatic, bactericidal and eradication activities were 15.8, 30.3 and 41.2, respectively. The PK/PD-based population dose prediction indicated a probability of target attainment (PTA) for the current marketed dose (6 mg/kg) of 88.9% against H. parasuis . The calculated gamithromycin dose for a PTA ≥ 90% was 6.55 mg/kg. Based on Monte Carlo simulations, the PK/PD cutoff (CO PD ) was determined to be 0.25 mg/L. Conclusion The determined cutoffs and PK/PD-based dose prediction will be of great importance in gamithromycin resistance surveillance and serve as an important step in the establishment of optimum dose regimen and clinical breakpoints.

Alternative therapeutic options are urgently needed against multidrug-resistant Escherichia coli infections, especially in situations of preexisting tigecycline and colistin resistance. Here, we investigated synergistic activity of the antiretroviral drug zidovudine in combination with tigecycline or colistin against E. coli harboring tet(X) and mcr-1 in vitro and in a murine thigh infection model. Zidovudine and tige-cycline/colistin combinations achieved synergistic killing and significantly decreased bacterial burdens by >2.5-log(10) CFU/g in thigh tissues compared to each mono-therapy.

Infections due to carbapenem-resistant NDM-producing Escherichia coli represent a major therapeutic challenge, especially in situations of pre-existing colistin resistance. The aim of this study was to investigate combinatorial pharmacodynamics of colistin and tigecycline against E. coli harboring bla NDM- 5 and mcr-1, with possible mechanisms explored as well. Colistin disrupted the bacterial outer-membrane and facilitated tigecycline uptake largely independent of mcr-1 expression, which allowed a potentiation of the tigecycline-colistin combination. A concentration-dependent decrease in colistin MIC and EC50 was observed with increasing tigecycline levels. Clinically relevant concentrations of colistin and tigecycline combination significantly decreased bacterial density of colistin-resistant E. coli by 3.9 to 6.1-log10 cfu/mL over 48 h at both inoculums of 106 and 108 cfu/mL, and were more active than each drug alone (P < 0.01). Importantly, colistin and tigecycline combination therapy was efficacious in the murine thigh infection model at clinically relevant doses, resulting in >2.0-log10cfu/thigh reduction in bacterial density compared to each monotherapy. These data suggest that the use of colistin and tigecycline combination can provide a therapeutic alternative for infection caused by multidrug-resistant E. coli that harbored both bla NDM- 5 and mcr-1.