Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans ; Drugs, Chinese Herbal/pharmacology* ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/therapy* ; Medicine, Chinese Traditional/methods* ; Antiviral Agents/pharmacology* ; Animals

Autoantibodies ; COVID-19 ; Humans ; Singapore/epidemiology*

OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. METHODS: The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CL^pro), papain like protease (PL^pro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CL^pro and PL^pro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. RESULTS: Jingfang Granules exhibited 3CL^pro and PL^pro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 μg/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 μg/g, respectively. In addition, neohesperidin and naringin exhibited PL^pro inhibitory activities, and the inhibition rates at 8 μmol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CL^pro and PL^pro, and the inhibitory rates at 8 μmol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CL^pro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PL^pro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PL^pro. CONCLUSION Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CL^pro and PL^pro. The results are valuable for rational clinical use of Jingfang Granules.
Amino Acids ; Ammonia ; Antitussive Agents ; COVID-19 ; Chymases ; Coronavirus 3C Proteases ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cysteine Endopeptidases/metabolism* ; Humans ; Molecular Docking Simulation ; Papain ; Peptide Hydrolases ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Tandem Mass Spectrometry

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI. METHODS: A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function. RESULTS: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. CONCLUSION This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.
Abietanes ; Acute Lung Injury/drug therapy* ; Animals ; Cytokine Release Syndrome ; Cytokines ; Inflammation/drug therapy* ; Lipopolysaccharides/toxicity* ; Macrophage Activation ; Macrophages ; Mice ; Triacetoneamine-N-Oxyl/pharmacology*

Group B streptococcus (GBS) is a leading cause of neonatal infection. Maternal vaginal-rectal colonization with GBS during the intrapartum period is a prerequisite for GBS early-onset disease (EOD). The obstetric measures for effective prevention of GBS EOD include universal prenatal screening by vaginal-rectal culture, correct specimen collection and processing, appropriate implementation of intrapartum antibiotic prophylaxis, and coordination with pediatric care providers. It is now recommended to universal screen GBS between 36 0/7 and 37 6/7 weeks of gestation and to identify groups of women who are eligible for intravenous intrapartum antibiotic prophylaxis as a means of preventing GBS EOD.

Intraamniotic infection (IAI) or chorioamnionitis is a common cause of preterm birth and may cause adverse neonatal outcomes, including neonatal pneumonia, respiratory distress, meningitis, sepsis, and death. Maternal morbidities from intraamniotic infection include dysfunctional labor requiring increased intervention, cesarean birth, postpartum uterine atony with hemorrhage, endometritis, peritonitis, sepsis, adult respiratory distress syndrome and, rarely, death. Chorioamnionitis can result from an ascending infection, iatrogenic causes or transplacental passage from maternal blood-borne infections. The clinical findings of chorioamnionitis include maternal fever (≥38 °C), maternal (>100 beats per minute) and/or fetal tachycardia (>160 beats per minute), maternal leukocytosis on complete blood count (>15 000 cells/mm 3), and uterine tenderness and/or purulent and/or foul-smelling amniotic fluid. The management of chorioamnionitis mainly includes antibiotic therapy and delivery. Women with previable preterm premature rupture of membranes should be offered realistic counseling from a multidisciplinary approach. The separation of the mother and the fetus to preserve the life of the mother should prioritize delivery methods that result in a living fetus if possible, with appropriate neonatal resuscitation available.

Sepsis, which is life-threatening organ dysfunction resulting from a dysregulated host response to infection, remains a major cause for the admission of pregnant women to the intensive care unit and is one of the leading causes of maternal morbidity and mortality. The obstetric causes include uterine infection, septic abortion, and wound infection. The non-obstetric causes include pyelonephritis and pneumonia. Maternal sepsis may also be from obstetrical critical illness, such as obstetric severe hemorrhage, obstetric (amniotic fluid/pulmonary) embolism, acute fatty liver of pregnancy, and congestive heart failure, cardiopulmonary arrest, and major trauma. The most commonly reported pathogens in maternal sepsis include Escherichia coli, Streptococcus, Staphylococcus, and other gram-negative bacteria. Maternal sepsis may cause intrauterine infection, which results in (1) preterm premature rupture of membranes or preterm labor or birth, (2) cerebral white matter damage or cerebral palsy or neurodevelopmental delay, (3) stillbirth, (4) early- or late-onset sepsis, and (5) perinatal death. The "Hour-1 bundle" should be initiated within the first hour of the recognition of sepsis. The use of early, appropriate antibiotics is crucial in the management of maternal sepsis. Fetal status should be monitored. Appropriate and early source control should be provided. The decision for delivery is often quite complex and should be individualized to each patient’s clinical scenario while taking into consideration the suspected source of infection, maternal status, fetal well-being, and gestational age. Extracorporeal membrane oxygenation has been increasingly used in refractory sepsis during pregnancy and the puerperium.

Group B streptococcus (GBS) is a leading cause of neonatal infection. Maternal vaginal-rectal colonization with GBS during the intrapartum period is a prerequisite for GBS early-onset disease (EOD). The obstetric measures for effective prevention of GBS EOD include universal prenatal screening by vaginal-rectal culture, correct specimen collection and processing, appropriate implementation of intrapartum antibiotic prophylaxis, and coordination with pediatric care providers. It is now recommended to universal screen GBS between 36 0/7 and 37 6/7 weeks of gestation and to identify groups of women who are eligible for intravenous intrapartum antibiotic prophylaxis as a means of preventing GBS EOD.