Investigation on the possibility of dynamic COVID-Zero strategy in China: a population-based transmission model analysis and economic evaluation.

OBJECTIVE: To explore the feasible and cost-effective intervention strategies to achieve the goal of dynamic COVID-Zero in China. DESIGN: A Susceptible-Exposed-Infectious-Recovered model combined economic evaluation was used to generate the number of infections, the time for dynamic COVID-Zero and calculate cost-effectiveness under different intervention strategies. The model simulated the 1 year spread of COVID-19 in mainland China after 100 initial infections were imported. INTERVENTIONS: According to close contact tracing degree from 80% to 100%, close contact tracing time from 2 days to 1 day, isolation time from 14 days to 7 days, scope of nucleic acid testing (NAT) from 10% to 100% and NAT frequency from weekly to every day, 720 scenarios were simulated. OUTCOME MEASURE: Cumulative number of infections (CI), social COVID-Zero duration (SCD), total cost (TC) and incremental cost-effectiveness ratio. RESULTS: 205 of 720 scenarios could achieve the total COVID-Zero since the first case was reported. The fastest and most cost-effective strategy was Scenario 680, in which all close contacts were traced within 1 day, the isolation time was 14 days and 10% of the national population was randomly checked for NAT every day. In Scenario 680, the CI was 280 (100 initial infections) and the SCD was 13 days. The TC was ¥4126 hundred million and the cost of reducing one infection was ¥47 470. However, when the close contact tracing time was 2 days and the degree of close contact tracing was 80%-90%, the SCD would double to 24-101 days and the TCs increased by ¥16 505 to 37 134 hundred million compared with Scenario 680. CONCLUSIONS: If all close contact was controlled within 1 day, the rapid social COVID-Zero can be achieved effectively and cost-effectively. Therefore, the future prevention and control of emerging respiratory infectious diseases can focus on enhancing the ability of close contact tracing.

Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis.

OBJECTIVE: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. METHODS: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. RESULTS: a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85-2.96), rash (RR: 1.53, 95% CI: 1.25-1.87), ALT elevation (RR 1.54, 95% CI 1.23-1.92), AST elevation (AST: RR 1.49, 95% CI 1.20-1.85), hepatitis (RR: 3.54, 95% CI: 1.96-6.38) and hypothyroid (RR: 5.29, 95% CI: 4.00-6.99) compared with that of control group. Besides that, PD-1/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21-1.48), dyspnea (RR:1.23, 95% CI: 1.12-1.35) and chest pain (RR: 1.26, 95% CI: 1.07-1.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13-2.12). The risk of arthralgia was increased with PD-1/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10-1.47). Although the risk of myalgia was similar with PD-1/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45-0.70) compared with that of chemotherapy. CONCLUSIONS: our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration.

New Labdane Diterpenes and Their Glycoside Derivatives from the Roots of Isodon adenantha.

Two new labdane-type diterpenes (adenanthic acids A and B; 1 and 2, resp.) and three new labdane diterpene glycosides (adenanthosides A-C; 3-5, resp.) were isolated from the roots of Isodon adenantha, together with 23 known constituents including seven diterpenoids (6-12), eight triterpenoids (13-20), one lignan glycoside (21), six steroids (22-27), and one ceramide (28). Their structures were elucidated by spectroscopic methods including extensive 2D-NMR techniques. Cytotoxicity and antibacterial activities of the samples were measured by the MTT method and the filter paper disc agar diffusion method. But none of them showed significant activities.

Five new terpenoids from the rhizomes of Isodon adenantha.

Five new terpenoids including 2 labdane diterpenoids (1 and 2), 2 ent-kaurane diterpenoids (3 and 4), and a new oleanane triterpenoid (5), along with 13 known compounds (6-18), were isolated from the ethyl acetate fraction of 70% acetone extract of the rhizomes of Isodonadenantha. Their structures were elucidated based on the analyses of spectroscopic data and comparison of their physicochemical properties. The structure of 1 was further confirmed by single-crystal X-ray diffraction. Cytotoxicity and antibacterial activities of the samples were measured by MTT method and the filter paper disk agar diffusion method. But none of them showed significant activities.

[Analysis on component difference in Citrus reticulata before and after being processed with salt by UPLC-Q-TOF/MS].

To analyze components of Citrus reticulata and salt-processed C. reticulata by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and compared the changes in components before and after being processed with salt. Principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA) were adopted to analyze the difference in fingerprint between crude and processed C. reticulata, showing increased content of eriocitrin, limonin, nomilin and obacunone increase in salt-processed C. reticulata. Potential chemical markers were identified as limonin, obacunone and nomilin, which could be used for distinguishing index components of crude and processed C. reticulata.

Analysis on component difference in Citrus reticulata before and after being processed with salt by UPLC-Q-TOF/MS / 中国中药杂志

To analyze components of Citrus reticulata and salt-processed C. reticulata by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and compared the changes in components before and after being processed with salt. Principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA) were adopted to analyze the difference in fingerprint between crude and processed C. reticulata, showing increased content of eriocitrin, limonin, nomilin and obacunone increase in salt-processed C. reticulata. Potential chemical markers were identified as limonin, obacunone and nomilin, which could be used for distinguishing index components of crude and processed C. reticulata.

UPLC-QTOF/MS Analysis of Alkaloids in Traditional Processed Coptis chinensis Franch.

The processing technology employed in traditional Chinese medicine (TCM) is significant and distinct. Meanwhile, the processed Coptis chinensis Franch. are significant in clinic based on clinical practice and literature. The current study used ultraperformance liquid chromatography method (UPLC) coupled with quadrupole time of flight mass spectrometry (qTOF/MS) and Marklynx software to analyze the chemical profiles of crude and processed C. chinensis Franch. 13 compounds in these samples are identified, including 3 compounds that are detected in C. chinensis Franch. for the first time. Moreover, the results of the experiment show significant chemical differences between crude and processed C. chinensis Franch. with principal component analysis (PCA). The obvious separation in PCA confirms the traditional processing theory in TCM.