Development and validation of enzyme-linked immunosorbent assays for the measurement of infliximab and anti-drug antibody levels.

Infliximab and its anti-drug antibody (ADA) serum concentrations exhibit a strong correlation with clinical response and loss of response. The use of therapeutic drug monitoring to measure the concentration of infliximab and ADA can facilitate clinical decision-making, helping patients attain optimal therapeutic effects. However, there are still limitations to the existing infliximab and its ADA detection methods. Therefore, this study aimed to develop and validate enzyme-linked immunosorbent assay (ELISA)-based methods for measuring infliximab and its ADA levels in human plasma according to the general recommendations for immunoassays. Free infliximab is bound by recombinant TNF-α and detected using HRP-labeled anti-human antibody. The ADA is captured by on-plate-coated infliximab and recognized by biotin-labeled infliximab. Two bridging ELISA assays were developed and after assay optimization and validation, these assays have been applied in ten patients with inflammatory bowel disease (IBD). In infliximab detection assay, a standard curve ranging from 0.10 µg/mL to 8.0 µg/mL with great precision and accuracy has been established. Drug tolerance of the ADA assay was that 100 ng/mL ADA could tolerate at least 5.0 µg/mL infliximab in the plasma using a commercially available monoclonal anti-infliximab antibody as the positive control. The ADA screening and confirmatory assays achieved a sensitivity of 36.74 ng/mL and 37.15 ng/mL, respectively. All other assay characteristics met the requirements. The mean concentration of infliximab in eight patients with IBD was 7.88 (1.87-21.1) µg/mL, and the ADA levels were all negative. Moreover, the concentrations of infliximab in the remaining two patients were below the LLOQ and the ADAs were positive. Thus, accurate and sensitive ELISA methods have been developed and validated for the detection of infliximab and its ADA concentrations and have been successfully applied to clinical therapeutic drug monitoring.

Head-to-head comparison of azvudine and nirmatrelvir/ritonavir for the hospitalized patients with COVID-19: a real-world retrospective cohort study with propensity score matching.

Background: Nirmatrelvir/ritonavir and azvudine have been approved for the early treatment of COVID-19 in China, however, limited real-world data exists regarding their effectiveness and safety. Methods: We conducted a retrospective cohort study involving the hospitalized COVID-19 patients in China between December 2022 and January 2023. Demographic, clinical, and safety variables were recorded. Results: Among the 6,616 hospitalized COVID-19 patients, we included a total of 725 patients including azvudine recipients (N = 461) and nirmatrelvir/ritonavir (N = 264) recipients after exclusions and propensity score matching (1:2). There was no significant difference in the composite disease progression events between azvudine (98, 21.26%) and nirmatrelvir/ritonavir (72, 27.27%) groups (p = 0.066). Azvudine was associated with a significant reduction in secondary outcomes, including the percentage of intensive care unit admission (p = 0.038) and the need for invasive mechanical ventilation (p = 0.035), while the in-hospital death event did not significantly differ (p = 0.991). As for safety outcomes, 33 out of 461 patients (7.16%) in azvudine group and 22 out of 264 patients (8.33%) in nirmatrelvir/ritonavir group experienced drug-related adverse events between the day of admission (p = 0.565). Conclusion: In our real-world setting, azvudine treatment demonstrated similar safety compared to nirmatrelvir/ritonavir in hospitalized COVID-19 patients. Additionally, it showed slightly better clinical benefits in this population. However, further confirmation through additional clinical trials is necessary.

The regulation of tissue-specific farnesoid X receptor on genes and diseases involved in bile acid homeostasis.

Bile acids (BAs) facilitate the absorption of dietary lipids and vitamins and have also been identified as signaling molecules involved in regulating their own metabolism, glucose and lipid metabolism, as well as immunity. Disturbances in BA homeostasis are associated with various enterohepatic and metabolic diseases, such as cholestasis, nonalcoholic steatohepatitis, inflammatory bowel disease, and obesity. As a key regulator, the nuclear orphan receptor farnesoid X receptor (FXR, NR1H4) precisely regulates BA homeostasis by transcriptional regulation of genes involved in BA synthesis, metabolism, and enterohepatic circulation. FXR is widely regarded as the most potential therapeutic target. Obeticholic acid is the only FXR agonist approved to treat patients with primary biliary cholangitis, but its non-specific activation of systemic FXR also causes high-frequency side effects. In recent years, developing tissue-specific FXR-targeting drugs has become a research highlight. This article provides a comprehensive overview of the role of tissue-specific intestine/liver FXR in regulating genes involved in BA homeostasis and briefly discusses tissue-specific FXR as a therapeutic target for treating diseases. These findings provide the basis for the development of tissue-specific FXR modulators for the treatment of enterohepatic and metabolic diseases associated with BA dysfunction.

Real-world study of the leakage of two types of infusion bags in multicenter pharmacy intravenous admixture service (PIVAS).

Background: This study sought to analyze the leakage rate, economic loss caused by leakage, leakage reasons, and usage of upright polypropylene infusion bags and non-polyvinyl chloride (PVC) infusion bags, two types of closed intravenous infusion containers used in pharmacy intravenous admixture service (PIVAS), to improve the product quality of drug infusion packaging materials, reduce drug and clinical economic losses, and reduce the safety hazards of medication. Method: A real-world study was used to collect statistics for these infusion containers. The study was conducted in 21 hospitals in China from September to December 2022. Upright polypropylene infusion bags or non-PVC infusion bags in PIVAS of these 21 hospitals were chosen as the research material. Results: In total, 2,349,899 upright polypropylene infusion bags and 3,301,722 non-PVC infusion bags were collected. Eleven cases of upright polypropylene infusion bag leakage occurred (with a the leakage rate of 0.05‱), and 394 cases of non-PVC infusion bag leakage occurred (with a leakage rate of 1.19‱). The leakage rate of non-PVC infusion bags was significantly higher than that of upright polypropylene infusion bags (p < 0.01). The main reason for leakage in upright polypropylene infusion bags was sharp objects such as glass fragments or aluminum caps piercing the bag. The main reason for leakage in non-PVC infusion bags was squeezing, stacking, and uneven arrangement that causes folding of edges. For non-PVC bags, additional reasons for leakage included leakage at the nozzle joint, excessive manual or machine throwing force, and excessive dosage. The economic loss of upright polypropylene infusion bags was 1,116.56 CNY. The economic loss of non-PVC infusion bags was 32,210.86 CNY. Conclusion: Based on real-world study data on the leakage of upright polypropylene infusion bags and non-PVC infusion bags in multicenter PIVAS, it can be concluded that the leakage rates of upright polypropylene infusion bags are significantly lower than those of non-PVC infusion bags in PIVAS, and the economic losses due to upright polypropylene infusion bags are lower than those due to non-PVC infusion bags in PIVAS. Therefore, we can infer that upright polypropylene infusion bags are superior to non-PVC infusion bags.

Cost-effectiveness of empagliflozin for the treatment of heart failure: a systematic review.

Objective: This study aims to synthesize evidence on the cost-effectiveness of empagliflozin for heart failure (HF). Methods: MEDLINE, Embase, the Cochrane Library, EconLit, CNKI, Wanfang Data and Chongqing VIP were searched to identify original articles on cost-effectiveness of empagliflozin for HF, and literature surveillance ended on 20 November 2022. The reporting quality of the included articles was determined using the Consolidated Health Economic Evaluation Reporting Standards statement. Results: Of 97 articles identified, 11 studies published from 2020 to 2022 met the inclusion criteria, and the overall quality was accepted. The studies were conducted in 8 countries (China, Japan, Korea, Singapore, Thailand, Australia, United States, and United Kingdom). This body of evidence suggested that add-on empagliflozin was cost effective for HF with reduced ejection fraction (HFrEF) patients compared to standard of care alone in all the related studies including China, Japan, Korea, Singapore, Thailand, and Australia. For HF with preserved ejection fraction (HFpEF) patients, add-on empagliflozin was cost effective in China and Australia, but not in United States and Thailand. For HF with diabetes, add-on empagliflozin was cost effective in United Kingdom. Moreover, the incremental cost-effectiveness ratios (ICER) were lower for patients with diabetes than without in subgroup analysis. In the uncertainty analysis of all included studies, the ICERs were most sensitive to the cost of empagliflozin and cardiovascular mortality, followed by the cost of the standard treatment, hazard ratio of HF hospitalization. Conclusion: add-on empagliflozin for HFrEF might be cost-effective or dominant compared with standard of care alone. However, for HFpEF patients, add-on empagliflozin might be cost-effective in China and Australian, but not cost-effective in United States and Thailand.

Determination of olverembatinib in human plasma and cerebrospinal fluid by an LC-MS/MS method: Validation and clinical application.

A sensitive and robust LC-MS/MS method has been developed and validated for olverembatinib quantification in human plasma and cerebrospinal fluid (CSF). The method involved liquid-liquid extraction with methyl tertiary butyl ether for plasma pretreatment and precipitation enrichment with methanol for CSF pretreatment. Separation was achieved on the C18 column with gradient elutions of 10 mM ammonium formate in water and methanol-acetonitrile (50:50,v/v). Analyte detection was conducted by electrospray ionization (ESI) in a positive ion mode using multiple reaction monitoring (MRM). The m/z transitions were 533.4→433.2 for olverembatinib and m/z 502.4→394.2 for the internal standard (IS, Imatinib-d8). Calibration curves ranged from 0.500 to 50.0 ng/mL for plasma and from 0.0100 to 1.00 ng/mL for CSF. The intra- and inter-day precision and accuracy were < 15% for both plasma and CSF with four different quality control concentrations. The relative matrix effect was < 10% in plasma and artificial CSF. This method was successfully utilized for the measurement of olverembatinib concentrations in plasma and CSF from chronic myeloid leukemia patients.

Development and validation of a novel HPLC-UV method for simultaneous determination of azathioprine metabolites in human red blood cells.

A rapid, specific and accurate high-performance liquid chromatography with tunable ultraviolet detection method was developed to simultaneously determine azathioprine metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine riboside (6-MMPr) in human red blood cells. Erythrocyte lysate sample was precipitated by perchloric acid under the protection of dithiothreitol, with 6-TGN and 6-MMPr being acid hydrolyzed to produce 6-thioguanine (6-TG) and 6-methymercaptopurine (6-MMP). A Waters Cortecs C18 column (2.1 × 150 mm, 2.7 µm) was used for chromatographic separation with a water (containing 0.01 mol/L ammonium acetate and 0.2% acetic acid)/methanol linear gradient at a flow rate of 0.45 mL/min in a 5.5 min. UV detection wavelengths were 340 nm for 6-TG, 303 nm for 6-MMP and the IS (5-bromouracil). The calibration curves fitted a least squares model (weighed 1/x 2) from 0.15 to 15 µmol/L for 6-TG (r 2  = 0.9999) and from 1 to 100 µmol/L for 6-MMP (r 2  = 0.9998). This method was validated according to the FDA bioanalytical method validation guidance and ICH M10 bioanalytical method validation and study sample analysis guidance for industry, and successfully utilized in ten IBD patients receiving azathioprine therapy.

Adaptive vibration control method for double-crystal monochromator base on VMD and FxNLMS.

Double-crystal monochromators (DCMs) are one of the most critical optical devices in beamlines at synchrotron sources, directly affecting the quality of the beam energy and position. As the performance of synchrotron light sources continues to improve, higher demands are placed on the stability of DCMs. This paper proposes a novel adaptive vibration control method combining variational modal decomposition (VMD) and filter-x normalized least mean squares (FxNLMS), ensuring DCM stability under random engineering disturbance. Firstly, the sample entropy of the vibration signal is selected as the fitness function, and the number of modal components k and the penalty factor α are optimized by a genetic algorithm. Subsequently, the vibration signal is decomposed into band frequencies that do not overlap with each other. Eventually, each band signal is individually governed by the FxNLMS controller. Numerical results have demonstrated that the proposed adaptive vibration control method has high convergence accuracy and excellent vibration suppression performance. Furthermore, the effectiveness of the vibration control method has been verified with actual measured vibration signals of the DCM.

Anaphylaxis Following Contrast-Enhanced CT with Iodixanol: A Case Report and Literature Review.

Background: Iodixanol-induced anaphylactic reaction is a well-known adverse event of contrast agents, which are generally well-tolerated and reversible. Serious and fatal reactions such as anaphylactic shock after computed tomography (CT) enhancement have been described. However, there is no data on these events in the literature. Objective: This report describes a case of a serious anaphylactic reaction, possibly related to iodixanol and provides an overview of case reports. Case Summary: A 47-year-old women who experienced persistent abdominal pain for more than one month, was proposed of hiatal hernia with CT images taken two weeks previously and was admitted to the gastrointestinal surgery department. The patient underwent contrast-enhanced abdominal CT for the evaluation of multiple intraperitoneal hemodynamic features. A few minutes after abdominal enhanced CT scan, the patient was pale, sweating, had muscle tension and trembling, even coma and profound hypotension with 90/43 mm Hg. Immediately she was supported with oxygen inhalation, was treated with adrenaline subcutaneously, dexamethasone intravenously, and rapid intravenous drip of compound sodium chloride. Ten minutes later, the patient was in respiratory and cardiac arrest and the pupils were dilated. CPR and intermittant static push of 1 mg adrenaline were immediately carried. After endotracheal intubation, the patient's spontaneous heart rate and pupils recovered, and her blood pressure recovered to 105/53 mm Hg. It was suggested that the patient was suffering from iodixanol-induced anaphylactic shock and nephropathy, and she was transferred to the intensive care unit. Despite immediate treatment, the patient died. Conclusion: A 47-year-old female patient with no history of allergies developed severe fatal anaphylactic shock after receiving iodixanol. Although contrast agents induced anaphylactoid/anaphylactic reactions do not often occur, clinicians should be conscious of the potentially serious anaphylactic reaction, which could lead to a life-threatening or fatal event.

Is Halving Maintenance of Voriconazole Safe and Efficient in Patients Suffering from Invasive Fungal Infections with Serious Hepatic Dysfunction?

Background: There is a wide debate about the efficacy and safety of voriconazole in patients with impaired hepatic function at Child-Pugh C level. Objective: The purpose of this study was to investigate the safety and efficacy between the two groups treated with different dosages of voriconazole (400mg/day vs 200mg/day) in the treatment of invasive fungal infections (IFIs) in patients with hepatic dysfunction. Methods: A retrospective study enrolling patients with hepatic dysfunction receiving intravenous voriconazole for IFIs from January 1st, 2017, to December 30th, 2021 was conducted. Patients were enrolled in the 400mg per day dose group and 200mg per day dose group. In patients with the same degree of hepatic impairment, factors affecting prognosis were screened and differences in steady-state blood trough concentrations (Cmin) of voriconazole, positive G/GM tests and adverse effects (AEs) were compared between the two groups described above. Results: In total, 308 patients with IFIs were enrolled. For Child-Pugh C class, patients receiving the halved maintenance dose had a lower Cmin and AEs rate but higher recovered rate compared to those receiving maintenance dose, and significant predictors of recovery were dosage (OR, 5.131; 95% CI, 1.599-16.464; p = 0.006) and diabetes (OR, 0.111; 95% CI, 0.020-0.597; p = 0.010). For patients of Child-Pugh A & B class, chronic liver disease (OR, 0.334; 95% CI, 0.159-0.704; p = 0.004) was a prognosis-related factor. Conclusion: Halving maintenance dose ensure the efficacy and safety of voriconazole in patients suffering from invasive fungal infections with serious hepatic dysfunction.

Circ_0005320 promotes oral squamous cell carcinoma tumorigenesis by sponging microRNA-486-3p and microRNA-637.

Circ_0005320 was found to be elevated in oral squamous cell carcinoma (OSCC) and accelerated OSCC progression. Here, the potential mechanism of circ_0005320 in OSCC tumorigenesis was explored. The quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect the expression of circ_0005320, miR-486-3p, and miR-637. In vitro assays were conducted using cell counting kit-8, colony formation, transwell, angiogenesis, and flow cytometry assays. The targeting relationship between microRNA (miR)-486-3p and miR-637 or circ_0005320 was confirmed using the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway-related proteins were analyzed using Western blot. The murine xenograft model was established to perform in vivo assay. Circ_0005320 expression was higher in OSCC tissues and cells. Knockdown of circ_0005320 suppressed OSCC cell growth, migration, invasion, and induced cell apoptosis in vitro, as well as impeded tumor growth in vivo. Mechanistically, miR-486-3p or miR-637 were confirmed to be a target of circ_0005320. Moreover, the inhibitory effects of circ_0005320 silencing on OSCC growth were reversed by the inhibition of miR-486-3p or miR-637. We also found that circ_0005320-miR-486-3p/miR-637 axis mediated the activation of JAK2/STAT3 pathway. This study revealed a novel regulatory network of circ_0005320-miR-486-3p/miR-637 axis in OSCC progression, suggesting that circ_0005320 might be a potential biomarker and therapeutic target for OSCC.

Circ_0002984 Enhances Growth, Invasion, and Migration in PDGF-bb-Induced Vascular Smooth Muscle Cells Through miR-379-5p/FRS2 Axis.

ABSTRACT: The accumulation of vascular smooth muscle cells (VSMCs) is considered to play important roles in atherosclerosis (AS) development and progression. Circ_0002984 was found to be increased in oxidized low-density lipoprotein (ox-LDL) human VSMCs (HVSMCs). However, the function and mechanism of circ_0002984 in VSMC dysfunction remain unknown. In this study, the expression of circ_0002984, microRNA (miR)-379-5p, and fibroblast growth factor receptor substrate 2 (FRS2) was detected using quantitative real-time polymerase chain reaction and western blot. Cell proliferation, cell cycle, migration, and invasion were detected using Cell Counting Kit-8, flow cytometry, and transwell assays. The binding interaction between miR-379-5p and circ_0002984 or FRS2 was confirmed by the dual-luciferase reporter assay. Collectively, this study found that circ_0002984 was elevated in platelet-derived growth factor type bb (PDGF-bb)-induced HVSMCs. Circ_0002984 knockdown abrogated PDGF-bb-induced proliferation, migration, and invasion in HVSMCs. Mechanistically, circ_0002984 was confirmed to target miR-379-5p, and miR-379-5p upregulation reversed the protective effects of circ_0002984 knockdown on PDGF-bb-induced HVSMCs. Besides, when FRS2 was a target of miR-379-5p, miR-379-5p restoration abolished PDGF-bb-evoked HVSMC dysfunction, which was attenuated by the overexpression of FRS2. Moreover, circ_0002984 could regulate FRS2 expression through sponging miR-379-5p in HVSMCs. Collectively, these results demonstrated that circ_0002984 promoted PDGF-bb-induced VSMC proliferation, migration, and invasion through the regulation of miR-379-5p/FRS2 axis, suggesting a new insight into the pathogenesis of AS and the potential application of circ_0002984 in AS treatment.

Comprehensive Review of Phytochemical Constituents, Pharmacological Properties, and Clinical Applications of Prunus mume.

Prunus mume is one of the most ancient medicinal herbs and health foods commonly used in Asian countries. It is widely used as a constituent of many medicinal preparations and as a food ingredient for its beneficial health effects. In this review, we retrieved reports from PubMed, embase, Scopus, and SciFinder databases, to collect extensive scientific evidence on the phytochemical constituents, pharmacological properties, and clinical applications of Prunus mume. The literature review revealed that approximately 192 compounds have been isolated from different parts of the plant, and their molecular structures have been identified. The pharmacological properties of the plant, including anti-diabetic, liver-protective, antitumor, antimicrobial, antioxidant, and anti-inflammatory activities, as well as their underlying mechanisms, have been clarified by in vitro and in vivo studies. Clinical studies, although very limited, have been highlighted in this review to provide a reference for further exploration on therapeutic applications of the plant.

Efficacité et innocuité des agents antiviraux contre le SRAS-CoV-2, selon des données d'études sur la COVID-19 et d'autres infections virales aiguës : revue systématique et méta-analyse.

CONTEXTE: On donne de façon empirique des agents antiviraux à certains patients atteints de la maladie à coronavirus 2019 (COVID-19). Dans le but d'appuyer la rédaction de lignes directrices sur la prise en charge de la COVID-19, nous avons réalisé une revue systématique des bénéfices et des préjudices associés à 7 traitements antiviraux contre cette infection. MÉTHODES: Nous avons effectué des recherches dans MEDLINE, Embase, le Cochrane Central Register of Controlled Trials (CENTRAL), PubMed et 3 bases de données chinoises (CNKI, Wanfang Data et SinoMed) jusqu'au 19 avril 2020, dans medRxiv et ChinaXiv jusqu'au 27 avril 2020, ainsi que dans Chongqing VIP jusqu'au 30 avril 2020. Nous avons sélectionné des études sur la ribavirine, la chloroquine, l'hydroxychloroquine, l'umifénovir (Arbidol), le favipiravir, l'interféron et le lopinavir/ritonavir. Lorsqu'il n'y avait pas de données directes d'études sur la COVID-19, nous avons retenu des données indirectes d'études sur le syndrome respiratoire aigu sévère (SRAS) et le syndrome respiratoire du Moyen-Orient (SRMO) pour l'analyse de l'efficacité, et d'études sur d'autres infections respiratoires virales aiguës pour l'analyse de l'innocuité. RÉSULTATS: Le taux de décès chez les patients atteints d'une forme sans signe clinique de gravité de COVID-19 était extrêmement bas, ce qui ne permet pas de conclure à un effet important sur la mortalité. Nous n'avons obtenu que des données de très faible qualité indiquant que la plupart des traitements avaient peu ou pas de bénéfices sur les paramètres à l'étude, quelle que soit la gravité de la COVID-19. Seule exception : le traitement au lopinavir/ritonavir, pour lequel nous avons obtenu des données de faible qualité faisant état d'une réduction de la durée du séjour en unité de soins intensifs (différence des risques [DR] 5 jours de moins, intervalle de confiance [IC] de 95 % 0 à 9 jours) et de la durée d'hospitalisation (DR 1 jour de moins, IC de 95 % 0 à 2 jours). En ce qui concerne l'innocuité, les données étaient de faible ou de très faible qualité, sauf pour le traitement au lopinavir/ritonavir, où des données de qualité moyenne laissaient supposer une augmentation probable de la diarrhée, des nausées et des vomissements. INTERPRÉTATION: À l'heure actuelle, rien ne prouve de façon convaincante que les traitements antiviraux apportent des bénéfices importants dans la lutte contre la COVID-19, bien que les données propres à chaque traitement n'excluent pas cette possibilité. D'autres essais randomisés et contrôlés menés auprès de patients atteints de la COVID-19 sont nécessaires avant de pouvoir recourir à ces traitements en toute confiance.

Anti-inflammatory Activity of Mollugin on DSS-induced Colitis in Mice.

We aimed to explore the anti-inflammatory activity of mollugin extracted from Rubia cordifolia L, a traditional Chinese medicine, on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Thirty C57BL/6 mice were divided into a control group (n=6), a model group (n=6), and three experimental groups (40, 20, 10 mg/kg of mollugin, n=6 each). DSS solution (3%) was given to mice in the model group and experimental groups from day 4 to day 10 to induce the mouse UC model. Mice in the experimental groups were intragastrically administrated mollugin from day 1 to day 10. Animals were orally given distilled water in the control group for the whole experiment time and in the model group from day 1 to day 3. The changes in colon pathology were detected by hematoxylin and eosin (HE) staining. Interleukin-1ß (IL-1ß) in the serum, and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN) in the tissues were measured by enzyme linked immunosorbent assay. Expression levels of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 in the colon tissues were detected by immunohistochemistry. Results showed that mollugin could significantly reduce weight loss and the disease activity index in the DSS-induced UC mouse model. HE examinations demonstrated that mollugin treatment effectively improved the histological damage (P<0.05). The overproduction of IL-1ß and TNF-α was remarkably inhibited by mollugin treatment at doses of 20 and 40 mg/kg (P<0.05). Additionally, the levels of TLR4 in colon tissues were significantly reduced in mollugin-treated groups compared with the DSS group. Our findings demonstrated that mollugin ameliorates DSS-induced UC by inhibiting the production of pro-inflammatory chemocytokines.

Efficacy and safety of antiviral treatment for COVID-19 from evidence in studies of SARS-CoV-2 and other acute viral infections: a systematic review and meta-analysis.

BACKGROUND: Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes. RESULTS: In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting. INTERPRETATION: To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

Hyperattenins L and M, two new polyprenylated acylphloroglucinols with adamantyl and homoadamantyl core structures from Hypericum attenuatum.

Hyperattenins L (1) and M (2), two new benzoylated polyprenylated phloroglucinol derivatives possessing unusual adamantyl and homoadamantyl core structures, were isolated from the aerial parts of Hypericum attenuatum. Their structures were determined by extensive NMR spectroscopic methods. Compound 1 possesses an unusual tetracyclo[6.3.1.11,10.01,5]tridecane skeleton, representing the second report of natural product with this carbon skeleton. Compound 2 features an unexpected 2,3,13-trioxapentacyclo[7.5.3.17,11.05,16.012,16]octodecane ring system formed by the fusion of 2,3,8-trioxabicyclo[4.3.1]decane moiety to the tricycle[4.3.1.13,8]undecane core. Both compounds were evaluated for their cytotoxic activities against five human cancer cell lines and compound 1 showed excellent inhibitory activities against HL-60, A-549, and MCF-7 cell lines with IC50 values of 3.86, 4.34, and 5.78µM, respectively.

Anti-diarrheal and anti-inflammatory activities of aqueous extract of the aerial part of Rubia cordifolia.

BACKGROUND: In Shaanxi province, China, the aqueous extract of Rubia cordifolia's aerial part (AERCAP) is traditionally used to manage diarrhea. However, there is no scientific evidence to verify the safety and efficacy of its use. The aim of this study was to investigate the anti-diarrheal and anti-inflammatory effects of AERCAP by using a rodent model. METHODS: The anti-diarrheal effects were studied by senna leaf-induced diarrheal and intestinal transit experiments in mice. The anti-inflammatory activity was investigated by trinitrobenzenesulfonic acid (TNBS)-induced colonic inflammation in rats. RESULTS: The results indicated that AERCAP delayed the onset of semi-solid feces, reduced the evacuation index (EI) in senna leaf-induced diarrheal in mice, and inhibited the propulsive movement in castor oil-induced intestinal transit but not in the normal intestinal transit test. The results were compared with the standard anti-diarrheal drug loperamide. Additionally, oral treatment with AERCAP significantly decreased the macroscopic damage area, improved the microscopic structure, and reduced the malondialdehyde (MDA) content, IL-1ß and TNF-α levels in colonic tissue compared with the TNBS control group in rats. CONCLUSIONS: AERCAP exhibited anti-diarrheal and anti-inflammatory activities in a rodent model. The study validated the traditional use of the plant in Chinese herbal medicine as a valuable natural remedy for the treatment of diarrhea.

In vitro Antiviral Activity of Rubia cordifolia Aerial Part Extract against Rotavirus.

The root of Rubia cordifolia has been used traditionally as a hemostatic agent, while the aerial part of the plant consisting of leaf and stem is known to exhibit anti-diarrheal properties and has been widely used as a remedy in many parts of China. As rotavirus is one of the most commonly associated diarrhea-causing pathogen, this study aims to investigate the anti-rotaviral effect of R. cordifolia aerial part (RCAP). The cytotoxicity of RCAP toward MA-104 cells was evaluated using the WST-8 assay. Colloidal gold method and real time polymerase chain reaction (qPCR) assay were used to confirm the findings of the antiviral assay. Then, 4',6-diamidino-2-phenylindole (DAPI) staining method was subsequently used to investigate the mode of death among the cells. And the representative components of aqueous extract were isolated and identified. It was shown that both the viability of MA-104 cells and the viral load were reduced with increasing concentration of the extract. DAPI staining showed that virus-induced apoptosis was the cause of the low cell viability and viral load, an effect which was accelerated with incubation in the aqueous herbal extract. The major compounds postulated to exhibit this activity were isolated from the aqueous herbal extract and identified to be compounds Xanthopurpurin and Vanillic Acid. This study showed that RCAP extract effectively inhibited rotavirus multiplication by promoting virus-induced apoptosis in MA-104 cells.

Mechanical design and performance evaluation for plane grating monochromator in a soft X-ray microscopy beamline at SSRF.

A new monochromator is designed to develop a high performance soft X-ray microscopy beamline at Shanghai Synchrotron Radiation Facility (SSRF). But owing to its high resolving power and high accurate spectrum output, there exist many technical difficulties. In the paper presented, as two primary design targets for the monochromator, theoretical energy resolution and photon flux of the beamline are calculated. For wavelength scanning mechanism, primary factors affecting the rotary angle errors are presented, and the measuring results are 0.15'' and 0.17'' for plane mirror and plane grating, which means that it is possible to provide sufficient scanning precision to specific wavelength. For plane grating switching mechanism, the repeatabilities of roll, yaw and pitch angles are 0.08'', 0.12'' and 0.05'', which can guarantee the high accurate switch of the plane grating effectively. After debugging, the repeatability of light spot drift reaches to 0.7'', which further improves the performance of the monochromator. The commissioning results show that the energy resolving power is higher than 10000 at Ar L-edge, the photon flux is higher than 1 × 108 photons/sec/200 mA, and the spatial resolution is better than 30 nm, demonstrating that the monochromator performs very well and reaches theoretical predictions.