Simultaneous determination of twenty-nine active compounds in fuzhengjiedu granules by HPLC-QQQ-MS/MS.

As an empirical medicine of traditional Chinese medicine, Fuzhengjiedu Granules have shown an effect against COVID-19 in clinical and inflammatory animal models. It is formulated with eight herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Glycyrrhizae Radix Et Rhizoma, Lonicerae Japonicae Flos, Gleditsiae Spina, Fici Radix, Pogostemonis Herba, and Citri Reticulatae Pericarpium. This study established a high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS) method by simultaneously determining 29 active compounds in the granules with significant content differences. Separation by gradient elution using acetonitrile and water (0.1% formic acid) as mobile phases was performed on a Waters Acquilty UPLC T3 column (2.1 mm × 100 mm, 1.7 µm). A triple quadrupole mass spectrometer, operating in positive and negative ionization modes, was used for multiple reaction monitoring to detect the 29 compounds. All calibration curves showed good linear regression (r2 > 0.998). RSDs of precision, reproducibility, and stability of active compounds were all lower than 5.0%. The recovery rates were 95.4-104.9%, with RSDs< 5.0%. This method was successfully used to analyze the samples, and the results showed that 26 representative active components from 8 herbs were detected in the granules. While aconitine, mesaconitine, and hypaconitine were not detected, indicating that the existing samples were safe. The granules had the maximum and minimum content of hesperidin (27.3 ± 0.375 mg/g) and benzoylaconine (38.2 ± 0.759 ng/g). To conclude, a fast, accurate, sensitive, and reliable HPLC-QQQ-MS/MS method was established, which can simultaneously detect 29 active compounds that have a considerable difference in the content of Fuzhengjiedu Granules. This study can be used to control the quality and safety of Fuzhengjiedu Granules and provide a basis and guarantee for further experimental research and clinical application.

Dynamic characteristics of a COVID-19 outbreak in Nanjing, Jiangsu province, China.

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.617.2 (also named the Delta variant) was declared as a variant of concern by the World Health Organization (WHO). This study aimed to describe the outbreak that occurred in Nanjing city triggered by the Delta variant through the epidemiological parameters and to understand the evolving epidemiology of the Delta variant. Methods: We collected the data of all COVID-19 cases during the outbreak from 20 July 2021 to 24 August 2021 and estimated the distribution of serial interval, basic and time-dependent reproduction numbers (R0 and Rt), and household secondary attack rate (SAR). We also analyzed the cycle threshold (Ct) values of infections. Results: A total of 235 cases have been confirmed. The mean value of serial interval was estimated to be 4.79 days with the Weibull distribution. The R0 was 3.73 [95% confidence interval (CI), 2.66-5.15] as estimated by the exponential growth (EG) method. The Rt decreased from 4.36 on 20 July 2021 to below 1 on 1 August 2021 as estimated by the Bayesian approach. We estimated the household SAR as 27.35% (95% CI, 22.04-33.39%), and the median Ct value of open reading frame 1ab (ORF1ab) genes and nucleocapsid protein (N) genes as 25.25 [interquartile range (IQR), 20.53-29.50] and 23.85 (IQR, 18.70-28.70), respectively. Conclusions: The Delta variant is more aggressive and transmissible than the original virus types, so continuous non-pharmaceutical interventions are still needed.

Impact of air pollutants on influenza-like illness outpatient visits under COVID-19 pandemic in the subcenter of Beijing, China.

This study aimed to explore the association between air pollutants and outpatient visits for influenza-like illnesses (ILI) under the coronavirus disease 2019 (COVID-19) stage in the subcenter of Beijing. The data on ILI in the subcenter of Beijing from January 1, 2018 to December 31, 2020 were obtained from the Beijing Influenza Surveillance Network. A generalized additive Poisson model was applied to examine the associations between the concentrations of air pollutants and daily outpatient visits for ILI when controlling meteorological factors and temporal trend. A total of 171 943 ILI patients were included. In the pre-coronavirus disease 2019 (COVID-19) stage, an increased risk of ILI outpatient visits was associated to a high air quality index (AQI) and the high concentrations of particulate matter less than 2.5 (PM2.5 ), particulate matter 10 (PM10 ), sulphur dioxide (SO2 ), nitrogen dioxide (NO2 ), and carbon monoxide (CO), and a low concentration of ozone (O3 ) on lag0 day and lag1 day, while a higher increased risk of ILI outpatient visits was observed by the air pollutants in the COVID-19 stage on lag0 day. Except for PM10 , the concentrations of other air pollutants on lag1 day were not significantly associated with an increased risk of ILI outpatient visits during the COVID-19 stage. The findings that air pollutants had enhanced immediate effects and diminished lag-effects on the risk of ILI outpatient visits during the COVID-19 pandemic, which is important for the development of public health and environmental governance strategies.

Dynamic characteristics of a COVID-19 outbreak in Nanjing, Jiangsu province, China

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.617.2 (also named the Delta variant) was declared as a variant of concern by the World Health Organization (WHO). This study aimed to describe the outbreak that occurred in Nanjing city triggered by the Delta variant through the epidemiological parameters and to understand the evolving epidemiology of the Delta variant. Methods We collected the data of all COVID-19 cases during the outbreak from 20 July 2021 to 24 August 2021 and estimated the distribution of serial interval, basic and time-dependent reproduction numbers (R0 and Rt), and household secondary attack rate (SAR). We also analyzed the cycle threshold (Ct) values of infections. Results A total of 235 cases have been confirmed. The mean value of serial interval was estimated to be 4.79 days with the Weibull distribution. The R0 was 3.73 [95% confidence interval (CI), 2.66–5.15] as estimated by the exponential growth (EG) method. The Rt decreased from 4.36 on 20 July 2021 to below 1 on 1 August 2021 as estimated by the Bayesian approach. We estimated the household SAR as 27.35% (95% CI, 22.04–33.39%), and the median Ct value of open reading frame 1ab (ORF1ab) genes and nucleocapsid protein (N) genes as 25.25 [interquartile range (IQR), 20.53–29.50] and 23.85 (IQR, 18.70–28.70), respectively. Conclusions The Delta variant is more aggressive and transmissible than the original virus types, so continuous non-pharmaceutical interventions are still needed.

Dynamics of influenza-like illness under urbanization procedure and COVID-19 pandemic in the subcenter of Beijing during 2013-2021.

Influenza-like illness (ILI) varies in intensity year by year, generally keeping a stable pattern except for great changes of its epidemic pattern. Of the most impacting factors, urbanization has been suggested as shaping the intensity of influenza epidemics. Besides, growing evidence indicates the nonpharmaceutical interventions (NPIs) to severe acute respiratory syndrome coronavirus 2 offer great advantages in controlling infectious diseases. The present study aimed to evaluate the impact of urbanization and NPIs on the dynamic of ILI in Tongzhou, Beijing, during January 2013 to March 2021. ILI epidemiological surveillance data in Tongzhou district were obtained from Beijing Influenza Surveillance Network and separated into three periods of urbanization and four intervals of coronavirus disease 2019 pandemic. Standardized average incidence rates of ILI in each separate stages were calculated and compared by using Wilson method and time series model of seasonal ARIMA. Influenza seasonal outbreaks showed similar epidemic size and intensity before urbanization during 2013-2016. Increased ILI activity was found during the process of Tongzhou's urbanization during 2017-2019, with the rate difference of 2.48 (95% confidence interva [CI]: 2.44, 2.52) and the rate ratio of 1.75 (95% CI: 1.74, 1.76) of ILI incidence between preurbanization and urbanization periods. ILI activity abruptly decreased from the beginning of 2020 and kept at the bottom level almost in every epidemic interval. The top decrease in ILI activity by NPIs was shown in 5-14 years group in 2020-2021 influenza season, as 92.2% (95% CI: 78.3%, 95.2%). The results indicated that both urbanization and NPIs interrupted the epidemic pattern of ILI. We should pay more attention to public health when facing increasing population density, human contact, population mobility, and migration in the process of urbanization. NPIs and influenza vaccination should be implemented as necessary measures to protect people from common infectious diseases like ILI.

Hydroxychloroquine/chloroquine and the risk of acute kidney injury in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVES: Hydroxychloroquine/chloroquine has been widely used as part of the standard treatment for patients with coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to determine whether hydroxychloroquine/chloroquine increases the risk of acute kidney injury (AKI) in COVID-19 patients. METHODS: PubMed and Embase were searched for related publications from inception to Dec 31, 2021, including randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing the risk of AKI and/or increased creatinine in COVID-19 patients receiving hydroxychloroquine/chloroquine and other controls (active treatment and placebo). We conducted separate meta-analyses for RCTs and NRSIs based on fixed-effect model, with odds ratios (ORs) being considered as effect sizes. RESULTS: We included 21 studies in the analysis, with 12 were RCTs. Based on the RCTs, compared to placebo, the OR was 1.19 (95% confidence interval [CI]: 0.86, 1.64; p = .30, n = 4, moderate quality) for AKI and 1.00 (95%CI: 0.64, 1.56; p = .99, n = 5, moderate quality) for increased creatinine for patients received hydroxychloroquine/chloroquine treatment; compared to active treatment, the odds was 1.28 (95%CI: 0.65, 2.53; p = .47, n = 2, low quality) for AKI and 0.64 (95%CI: 0.13, 3.20; p = .59, n = 1, low quality) for increased creatine. Evidence from NRSIs showed slightly increased odds of AKI, with low quality. CONCLUSION: Based on current available studies which were graded as low to moderate quality, there is insufficient evidence to conclude that hydroxychloroquine/chloroquine use is associated with increased risk of AKI or raised creatinine. Abbreviations: AKI: acute kidney injury; COVID-19: Coronavirus Disease 2019; RCT: randomized controlled trials; NRSI: non-randomized studies of interventions; OR: odds ratios; ROBIS-I: Risk Of Bias In Non-randomized Studies - of Interventions.

Impacts of COVID-19 pandemic on the aquatic environment associated with disinfection byproducts and pharmaceuticals.

In this study, concentrations of disinfection byproducts (DBPs) and COVID-19 related pharmaceuticals in wastewater effluents and surface water were measured two weeks, three months and eight months after the lockdown in Wuhan. Little temporal variation in DBP concentrations suggested intensified disinfection during the COVID-19 pandemic had limited impacts on the occurrence of DBPs in the aquatic environment. In contrast, the pandemic led to a significant increase in concentrations of lopinavir and ritonavir in wastewater effluents and surface water. The high detection frequency of these pharmaceuticals in surface water after the lockdown highlighted their mobility and persistence in the aquatic environment. The initial ecological risk assessment indicated moderate risks associated with these pharmaceuticals in surface water. As the global situation is still rapidly evolving with a continuous surge in the number of confirmed COVID-19 cases, our results suggest a pressing need for monitoring COVID-19 related pharmaceuticals as well as a systematic evaluation of their ecotoxicities in the aquatic environment.

Quantification of Cytokine Storms During Virus Infections.

Highly pathogenic virus infections usually trigger cytokine storms, which may have adverse effects on vital organs and result in high mortalities. The two cytokines interleukin (IL)-4 and interferon (IFN)-γ play key roles in the generation and regulation of cytokine storms. However, it is still unclear whether the cytokine with the largest induction amplitude is the same under different virus infections. It is unknown which is the most critical and whether there are any mathematical formulas that can fit the changing rules of cytokines. Three coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2), three influenza viruses (2009H1N1, H5N1 and H7N9), Ebola virus, human immunodeficiency virus, dengue virus, Zika virus, West Nile virus, hepatitis B virus, hepatitis C virus, and enterovirus 71 were included in this analysis. We retrieved the cytokine fold change (FC), viral load, and clearance rate data from these highly pathogenic virus infections in humans and analyzed the correlations among them. Our analysis showed that interferon-inducible protein (IP)-10, IL-6, IL-8 and IL-17 are the most common cytokines with the largest induction amplitudes. Equations were obtained: the maximum induced cytokine (max) FC = IFN-γ FC × (IFN-γ FC/IL-4 FC) (if IFN-γ FC/IL-4 FC > 1); max FC = IL-4 FC (if IFN-γ FC/IL-4 FC < 1). For IFN-γ-inducible infections, 1.30 × log2 (IFN-γ FC) = log10 (viral load) - 2.48 - 2.83 × (clearance rate). The clinical relevance of cytokines and their antagonists is also discussed.

The Role of Alveolar Edema in COVID-19.

The coronavirus disease 2019 (COVID-19) has spread over the world for more than one year. COVID-19 often develops life-threatening hypoxemia. Endothelial injury caused by the viral infection leads to intravascular coagulation and ventilation-perfusion mismatch. However, besides above pathogenic mechanisms, the role of alveolar edema in the disease progression has not been discussed comprehensively. Since the exudation of pulmonary edema fluid was extremely serious in COVID-19 patients, we bring out a hypothesis that severity of alveolar edema may determine the size of poorly-ventilated area and the blood oxygen content. Treatments to pulmonary edema (conservative fluid management, exogenous surfactant replacements and ethanol-oxygen vapor therapy hypothetically) may be greatly helpful for reducing the occurrences of severe cases. Given that late mechanical ventilation may cause mucus (edema fluid) to be blown deep into the small airways, oxygen therapy should be given at the early stages. The optimal time and blood oxygen saturation (SpO2) threshold for oxygen therapy are also discussed.

Recovery of a patient with severe COVID-19 by acupuncture and Chinese herbal medicine adjuvant to standard care.

There is currently no drug or therapy that can cure the coronavirus disease 2019 (COVID-19), which is highly contagious and can be life-threatening in severe cases. Therefore, seeking potential effective therapies is an urgent task. An older female at the Leishenshan Hospital in Wuhan, China, with a severe case of COVID-19 with significant shortness of breath and decrease in peripheral oxygen saturation (SpO2), was treated using manual acupuncture and Chinese herbal medicine granule formula Fuzheng Rescue Lung with Xuebijing Injection in addition to standard care. The patient's breath rate, SpO2, heart rate, ratio of neutrophil/lymphocyte (NLR), ratio of monocyte/lymphocyte (MLR), C-reactive protein (CRP), and chest computed tomography were monitored. Acupuncture significantly improved the patient's breathing function, increased SpO2, and decreased her heart rate. Chinese herbal medicine might make the effect of acupuncture more stable; the use of herbal medicine also seemed to accelerate the absorption of lung infection lesions when its dosage was increased. The combination of acupuncture and herbs decreased NLR from 14.14 to 5.83, MLR from 1.15 to 0.33 and CRP from 15.25 to 6.01 mg/L. These results indicate that acupuncture and Chinese herbal medicine, as adjuvants to standard care, might achieve better results in treating severe cases of COVID-19.

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates.

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY83 site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies thus provide mechanistic insights in complex exocytosis processes.

Strategies and recommendations for the management of gastrointestinal surgery during the COVID-19 pandemic: experience shared by Chinese surgeons.

Novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing public-health pandemic worldwide. Although SARS-CoV-2 has been known to spread primarily through respiratory droplets, recent evidence also supports fecal/oral as an additional route of transmission, raising concerns over gastrointestinal (GI) transmission of the infection. Herein, we, as the front-line Chinese GI surgeons, would like to share our experience and lessons in the combat against COVID-19. It is essential to create science-based, rational, and practical strategies during the outbreak of COVID-19. Here, we provide multi-institutional consensus on minimizing disease transmission while continuing to provide care from all aspects for patients in GI surgery, including outpatient clinics, inpatient units, gastrointestinal endoscopy centers, and adjustments in perioperative care. Our experiences and recommendations are worth sharing and may help to establish specific infection-control and outcome measures.

Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.