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ObjectiveTo investigate the effect and mechanism of Dahuang Zhechongwan （DHZCW） on adenine-induced renal fibrosis in rats from the perspective of intestinal flora. MethodThirty-six SD rats were randomly divided into a blank group， a model group， and high-， medium- and low-dose DHZCW groups （0.168， 0.084， 0.042 g·kg-1）， and a pirfenidone group （200 mg·kg-1）， with 6 rats in each group. Except for those in the blank group， rats in other groups were treated with adenine suspension （250 mg·kg-1） by gavage for 28 days for renal fibrosis model induction. Subsequently， they received drug intervention for 4 weeks. Urine samples were collected from rats in metabolic cages， and renal function indicators including blood urea nitrogen （BUN）， urea， creatinine （Crea）， cystatin C （Cys C）， and 24-hour urine protein （24 h TP） were measured. Kidney samples were collected and subjected to hematoxylin-eosin （HE） staining and Masson's trichrome staining to observe the pathological changes in rat renal tissues. Western blot was used to detect the expression levels of key effector proteins α-smooth muscle actin （α-SMA）， type Ⅰ collagen （ColⅠ）， and type Ⅲ collagen （ColⅢ） in the kidneys. High-throughput sequencing of 16S rDNA was used to analyze the species diversity of rat intestinal flora. ResultCompared with the blank group， the model group showed increased BUN， urea， Crea， Cys C， and 24 h TP levels （P<0.01）. Compared with the model group， the high-， medium-， and low-dose DHZCW groups， as well as the pirfenidone group， showed significant reductions in BUN， urea， Crea， Cys C， and 24 h TP levels （P<0.01）， indicating that DHZCW intervention significantly improved renal function. In the model group， renal tissues exhibited significant fibrotic changes， and the protein levels of α-SMA， ColⅠ， and ColⅢ were significantly increased （P<0.01） compared to those in the blank group. Compared with the model group， the high-dose DHZCW group and the pirfenidone group had relatively normal tissue structure， with no significant pathological damage observed. However， fibrotic changes were observed in the medium- and low-dose DHZCW groups， with the changes being more significant in the low-dose group. The protein levels of α-SMA， ColⅠ， and ColⅢ were significantly decreased in the high-， medium-， and low-dose DHZCW groups， as well as the pirfenidone group （P<0.01）， indicating that DHZCW effectively reduced abnormal collagen deposition and inhibited renal fibrosis. From the perspective of intestinal flora， at the phylum level， compared with the blank group， the model group showed a significant increase in the abundance of Firmicutes and a decrease in Bacteroidetes， leading to a significant imbalance in their ratio. At the family level， the model group decreased the abundance of Lachnospiraceae， Prevotellaceae， and Bacteroidota_unclassified， and increased the abundance of Ruminococcaceae， Lactobacillaceae， and Oscillospiraceae. At the genus level， the model group showed significantly reduced abundance of Firmicutes_unclassified， Bacteroidota_unclassified， and Prevotellaceae_UCG-001， etc.， and increased abundance of UCG-005， Clostridia_UCG-014_unclassified， etc. Compared with the model group， DHZCW effectively reduced the abundance of potential pathogenic bacteria and increased the abundance of beneficial bacteria， regulating the intestinal flora. ConclusionDHZCW can effectively improve renal function and inhibit renal fibrosis， and its mechanism of action may be related to the regulation of intestinal flora.
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The serial interval distribution is used to approximate the generation time distribution, an essential parameter to predict the effective reproductive number "Rt", a measure of transmissibility. However, serial interval distributions may change as an epidemic progresses rather than remaining constant. Here we show that serial intervals in Hong Kong varied over time, closely associated with the temporal variation in COVID-19 case profiles and public health and social measures that were implemented in response to surges in community transmission. Quantification of the variation over time in serial intervals led to improved estimation of Rt, and provided additional insights into the impact of public health measures on transmission of infections. One-Sentence SummaryReal-time estimates of serial interval distributions can improve assessment of COVID-19 transmission dynamics and control.
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BackgroundSeveral countries have implemented control measures to limit SARS-CoV-2 spread, including digital contact tracing, digital monitoring of quarantined individuals and testing of travelers. These raise ethical issues around privacy, personal freedoms and equity. However, little is known regarding public acceptability of these measures. MethodsIn December 2020, we conducted surveys among 3635 respondents in Singapore, Hong Kong and Malaysia to understand public perceptions on the ethical acceptability of COVID-19 control measures. FindingsHong Kong respondents were much less supportive of digital contact tracing and monitoring devices than those in Malaysia and Singapore. Around three-quarters of Hong Kong respondents perceived digital contact tracing as an unreasonable restriction of individual freedom; <20% trusted that there were adequate local provisions preventing these data being used for other purposes. This was the opposite in Singapore, where nearly three-quarters of respondents agreed that there were adequate data protection rules locally. In contrast, only a minority of Hong Kong respondents viewed mandatory testing and vaccination for travelers as unreasonable infringements of privacy or freedom. Less than two-thirds of respondents in all territories were willing to be vaccinated against COVID-19, with a quarter of respondents undecided. However, support for differential travel restrictions for vaccinated and unvaccinated individuals was high in all settings. InterpretationOur findings highlight the importance of socio-political context in public perception of public health measures and emphasize the need to continually monitor public attitudes towards such measures to inform implementation and communication strategies. FundingThis work was funded by the World Health Organization. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and Google Scholar for research articles published between 29 February 2020 to 20 January 2021 to identify empirical studies on public perception of restrictive and control measures imposed during COVID-19. We used the following terms: "COVID-19", "SARS-COV-2", "pandemic", "public", "population", "survey", "cross-sectional", "national", "international", "perception", "attitudes", "opinions", "views", "acceptance", "acceptability", "support", "ethics", "restrictive measures", "restrictions", "control measures", travel", "contact tracing", "testing", "tests", "quarantine", "monitoring", "vaccines" "vaccination", "immunity", "certificates", "passports", "digital", "applications", "apps", "mandatory" and "compulsory". We found 4 peer-reviewed publications: three population surveys on public acceptance of and ethical issues in digital contact tracing in France, Jordan, and Ireland, and one population survey on perceptions of immunity and vaccination certificates in Geneva, Switzerland. We found no studies that studied the relative acceptance of different types of control measures. Added valueThere is a paucity of literature on public perception of the ethics of control measures that have been or may be implemented in response to the COVID-19 pandemic. In this study, we found differing levels of public support in Singapore, Hong Kong, and Malaysia for digital contact tracing, wearable quarantine monitoring devices, and mandatory testing and vaccination for travelers. Hong Kong respondents sharply differed from Singapore and Malaysia respondents on perceptions of risks and benefits, the extent of intrusion into individual freedom, and assurance of privacy and data protection related to use of digital contact tracing and monitoring devices. These differences are likely to be substantially influenced by socio-political climate and governmental trust. Although less than two-thirds of respondents in all territories expressed a willingness to be vaccinated against COVID-19, we found high support for differential travel restrictions for vaccinated and unvaccinated individuals in all settings. Implications of all the available evidenceOur survey provides evidence of strong public support of vaccination requirements for travelers within an Asian context, and differential restrictions for vaccinated and non-vaccinated travelers. It highlights the importance of wider socio-political influences on public perception and ethical issues related to control measures and emphasizes the need to continually monitor public attitudes towards such measures to inform implementation and communication strategies.
