Pipersarmenoids, new amide alkaloids from Piper sarmentosum.

A chemical investigation of the aerial parts of Piper sarmentosum resulted in the isolation and identification of 14 amide alkaloids, including three new amide alkaloids, pipersarmenoids A - C (1-3), three new natural amide alkaloids, pipersarmenoids D - F (4-6), and 8 known analogues, N-p-coumaroyltyramine (7), piperlotine C (8), piperlotine D (9), pellitorine (10), sarmentine (11), aurantiamide acetate (12), 1-cinnamoyl pyrrolidine (13) and sarmentamide B (14). Their structures were determined by spectroscopic analysis including HRESIMS and 1D and 2D NMR. The cytotoxicity, neuroinflammation-inhibiting and acetylcholinesterase (AChE) inhibitory activities of those compounds were tested. Compounds 1, 2 and 12 inhibited NO production induced by LPS in BV2 cells with IC50 values of 9.36, 12.53 and 10.77 µM, respectively. Moreover, 1, 2, 7 and 11 showed moderate inhibitory activity on AChE with IC50 values ranging from 37.56 to 48.84 µM.

Association of CYP2C19 genotypes with postoperative atrial fibrillation after coronary artery bypass surgery.

This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.

Unlocking the potential of fondaparinux: guideline for optimal usage and clinical suggestions (2023).

Background: Thromboembolic disease is associated with a high rate of disability or death and gravely jeopardizes people's health and places considerable financial pressure on society. The primary treatment for thromboembolic illness is anticoagulant medication. Fondaparinux, a parenteral anticoagulant medicine, is still used but is confusing due to its disparate domestic and international indications and lack of knowledge about its usage. Its off-label drug usage in therapeutic settings and irrational drug use are also common. Objective: The aim of this guideline is to enhance the judicious clinical application of fondaparinux by consolidating the findings of evidence-based research on the drug and offering superior clinical suggestions. Methods: Seventeen clinical questions were developed by 37 clinical pharmacy experts, and recommendations were formulated under the supervision of three methodologists. Through methodical literature searches and the use of recommendation, assessment, development and evaluation grading techniques, we gathered evidence. Results: This guideline culminated in 17 recommendations, including the use of fondaparinux for venous thromboembolism (VTE) prevention and treatment, perioperative surgical prophylaxis, specific diseases, special populations, bleeding and overdose management. For different types of VTE, we recommend first assessing thrombotic risk in hospitalized patients and then administering the drug according to the patient's body mass. In surgical patients in the perioperative period, fondaparinux may be used for VTE prophylaxis, but postoperative use usually requires confirmation that adequate hemostasis has been achieved. Fondaparinux may be used for anticoagulation prophylaxis in patients hospitalized for oncological purposes, in patients with atrial fibrillation (AF) after resuscitation, in patients with cirrhosis combined with portal vein thrombosis (PVT), in patients with antiphospholipid syndrome (APS), and in patients with inflammatory bowel disease (IBD). Fondaparinux should be used with caution in special populations, such as pregnant female patients with a history of heparin-induced thrombocytopenia (HIT) or platelet counts less than 50 × 109/L, pregnant patients with a prethrombotic state (PTS) combined with recurrent spontaneous abortion (RSA), and children. For bleeding caused by fondaparinux, dialysis may partially remove the drug. Conclusion: The purpose of this guideline is to provide all healthcare providers with high-quality recommendations for the clinical use of fondaparinux and to improve the rational use of the drug in clinical practice. Currently, there is a lack of a dedicated antidote for the management of fondaparinux. The clinical investigation of activated prothrombin complex concentrate (APCC) or recombinant activated factor VII (rFⅦa) as potential reversal agents is still pending. This critical gap necessitates heightened scrutiny and research emphasis, potentially constituting a novel avenue for future inquiries into fondaparinux sodium. A meticulous examination of adverse events and safety profiles associated with the utilization of fondaparinux sodium will contribute significantly to a more comprehensive understanding of its inherent risks and benefits within the clinical milieu.

A promising therapy for fatty liver disease: PCSK9 inhibitors.

BACKGROUND: Fatty liver disease (FLD) poses a significant global health concern worldwide, with its classification into nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) contingent upon the presence or absence of chronic and excessive alcohol consumption. The absence of specific therapeutic interventions tailored to FLD at various stages of the disease renders its treatment exceptionally arduous. Despite the fact that FLD and hyperlipidemia are intimately associated, there is still debate over how lipid-lowering medications affect FLD. Proprotein Convertase Subtilisin/ Kexin type 9 (PCSK9) is a serine protease predominantly synthesized in the liver, which has a crucial impact on cholesterol homeostasis. Research has confirmed that PCSK9 inhibitors have prominent lipid-lowering properties and substantial clinical effectiveness, thereby justifying the need for additional exploration of their potential role in FLD. PURPOSE: Through a comprehensive literature search, this review is to identify the relationship and related mechanisms between PCSK9, lipid metabolism and FLD. Additionally, it will assess the pharmacological mechanism and applicability of PCSK9 inhibitors (including naturally occurring PCSK9 inhibitors, such as conventional herbal medicines) for the treatment of FLD and serve as a guide for updating the treatment protocol for such conditions. METHODS: A comprehensive literature search was conducted using several electronic databases, including Pubmed, Medline, Embase, CNKI, Wanfang database and ClinicalTrials.gov, from the inception of the database to 30 Jan 2024. Key words used in the literature search were "fatty liver", "hepatic steatosis", "PCSK9", "traditional Chinese medicine", "herb medicine", "botanical medicine", "clinical trial", "vivo", "vitro", linked with AND/OR. Most of the included studies were within five years. RESULTS: PCSK9 participates in the regulation of circulating lipids via both LDLR dependent and independent pathways, and there is a potential association with de novo lipogenesis. Major clinical studies have demonstrated a positive correlation between circulating PCSK9 levels and the severity of NAFLD, with elevated levels of circulating PCSK9 observed in individuals exposed to chronic alcohol. Numerous studies have demonstrated the potential of PCSK9 inhibitors to ameliorate non-alcoholic steatohepatitis (NASH), potentially completely alleviate liver steatosis, and diminish liver impairment. In animal experiments, PCSK9 inhibitors have exhibited efficacy in alleviating alcoholic induced liver lipid accumulation and hepatitis. Traditional Chinese medicine such as berberine, curcumin, resveratrol, piceatannol, sauchinone, lupin, quercetin, salidroside, ginkgolide, tanshinone, lunasin, Capsella bursa-pastoris, gypenosides, and Morus alba leaves are the main natural PCS9 inhibitors. Excitingly, by inhibiting transcription, reducing secretion, direct targeting and other pathways, traditional Chinese medicine exert inhibitory effects on PCSK9, thereby exerting potential FLD therapeutic effects. CONCLUSION: PCSK9 plays an important role in the development of FLD, and PCSK9 inhibitors have demonstrated beneficial effects on lipid regulation and FLD in both preclinical and clinical studies. In addition, some traditional Chinese medicines have improved the disease progression of FLD by inhibiting PCSK9 and anti-inflammatory and antioxidant effects. Consequently, the inhibition of PCSK9 appears to be a promising therapeutic strategy for FLD.

Glaucatotones A-I: Guaiane-type sesquiterpenoids from the roots of Lindera glauca with anti-inflammatory activity.

Glaucatotones A - I, nine new guaiane-type sesquiterpenoids, along with two reported compounds, namely (1ß,5ß)-1-hydroxyguaia-4(15),11(13)-dieno-12,5-lactone (10) and pseudoguaianelactone C (11), were isolated from the roots of Lindera glauca. The structures and absolute configurations of these compounds were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of experimental and calculated electronic circular dichroism (ECD) data. Structurally, glaucatotone A (1) is characterized as a dihomosesquiterpenoid with an unprecedented 5/5/7/6 ring system. A pair of enantiomers, (±)-glaucatotone B (2a/2b), represent the first rearranged norsesquiterpenoid with a (cyclopentylmethyl)cyclohexane skeleton. 3 is defined as a dinorsesquiterpenoid possessing a 5/7/5 ring system. 4-6 are three guaiane-type norsesquiterpenoids. In vitro bioactivity, 2a selectively inhibited Bcap-37 with IC50 value of 5.60 µM, and 9 selectively inhibited Du-145 with IC50 value of 5.52 µM. The anti-inflammatory activity of 1-9 were tested, and of these compounds, 1, 2a, 2b and 7 exhibited potent inhibitory effects.

Immune-related adverse events of immune checkpoint inhibitors: a review.

Since the first Immune Checkpoint Inhibitor was developed, tumor immunotherapy has entered a new era, and the response rate and survival rate of many cancers have also been improved. Despite the success of immune checkpoint inhibitors, resistance limits the number of patients who can achieve a lasting response, and immune-related adverse events complicate treatment. The mechanism of immune-related adverse events (irAEs) is unclear. We summarize and discuss the mechanisms of action of immune checkpoint inhibitors, the different types of immune-related adverse events and their possible mechanisms, and describe possible strategies and targets for prevention and therapeutic interventions to mitigate them.

Decoding signaling mechanisms: unraveling the targets of guanylate cyclase agonists in cardiovascular and digestive diseases.

Soluble guanylate cyclase agonists and guanylate cyclase C agonists are two popular drugs for diseases of the cardiovascular system and digestive systems. The common denominator in these conditions is the potential therapeutic target of guanylate cyclase. Thanks to in-depth explorations of their underlying signaling mechanisms, the targets of these drugs are becoming clearer. This review explains the recent research progress regarding potential drugs in this class by introducing representative drugs and current findings on them.

Outcome of antithrombotic therapy in cancer patients with catheter-related thrombosis: a systematic review.

Introduction: The guidelines' recommendations for anticoagulation in cancer patients with catheter-related thrombosis are unclear. The aim of this systematic review was to assess anticoagulation management in cancer patients with catheter-related thrombosis (CRT) based on previously published studies. Methods: As of June 10, 2023,we searched databases including PubMed, Embase, and Cochrane and included 11 observational studies that met the criteria. We evaluated 770 adults with active cancer and objectively confirmed patients with CRT who were using drugs including warfarin, LMWH, and new oral anticoagulants as antithrombotic therapy. Results: We extracted outcome data, including thrombosis recurrence, catheter dysfunction, major bleeding, and death, and performed a meta-analysis. Discussion: In this study we found that the risk of VTE recurrence was higher with rivaroxaban, the risk of bleeding and death appeared to be greater with warfarin, and although the risk of catheter dysfunction due to LMWH is a concern, it is still a more reasonable option for cancer patients with catheter-related thrombosis. Systematic Review Registration: http://www.clinicaltrials.gov, identifier (CRD42022367979).

Comparison of efficacy and safety between aspirin and oral anticoagulants for venous thromboembolism prophylaxis after major orthopaedic surgery: a meta-analysis of randomized clinical trials.

Background: venous thromboembolism (VTE) is one of the most common complications after major orthopaedic surgery. Recent studies have suggested that aspirin may also be effective in preventing VTE, but it is still controversial whether it can be routinely used. Objectives: To compare the efficacy and safety of aspirin against oral anticoagulants in the prevention of VTE following total hip arthroplasty (THA), total knee arthroplasty (TKA) or hip fracture surgery (HFS). Methods: Relevant publications have been obtained using electronic search databases such as PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials. gov. from inception to 20 July 2023. Only RCTs evaluating the efficacy and safety of aspirin compared with oral anticoagulants undergoing major orthopaedic surgery were included in the meta-analysis. The primary outcome reported was any VTE event (including deep vein thrombosis (DVT) and pulmonary embolism (PE)). Secondary outcomes included mortality, major bleeding (including gastrointestinal bleed, cerebrovascular hemorrhage, or any bleeding requiring a return to the theater), minor bleeding (ecchymosis, epistaxis, hematuria), and wound complications. The risk of bias for all included studies was assessed according to the Cochrane Collaboration's tool. Results: After screening 974 studies, 12 randomized clinical trials (RCTs) were included, involving 5,088 participants, including 2,540 participants in aspirin, 2,205 participants in rivaroxaban, and 323 participants in warfarin. Aspirin was found to be less effective than oral anticoagulants in thromboprophylaxis after major orthopedic surgery (RR = 1.206, 95% CI 1.053-1.383). After subgroup analysis according to the type of oral anticoagulant, the results showed that aspirin was similar to rivaroxaban and inferior to warfarin. Considering that the studies in the warfarin group were all conducted before 2000, our results need to be further confirmed. In addition, the aspirin group had a higher risk of VTE than the control group in other subgroups, including a follow-up time of ≤3 months, type of procedure as TKA, high-dose aspirin (≥650 mg qd), and no combined use of mechanical prophylaxis. In terms of safety events, aspirin did not show significant differences in major bleeding (RR = 0.952, 95% CI 0.499-1.815), all-cause mortality (RR = 1.208, 95% CI 0.459-3.177), and wound-related events (RR = 0.618, 95% CI 0.333-1.145) compared with oral anticoagulants, and aspirin was associated with a reduction in the risk of minor bleeding (RR = 0.685, 95% CI 0.552-0.850) events and total bleeding (RR = 0.726, 95% CI 0.590-0.892). Conclusion: Aspirin reduces bleeding risk after major orthopedic surgery compared with oral anticoagulants, but may sacrifice VTE prevention to some extent. Updated evidence is needed to analyze the thromboprophylaxis effects of aspirin in patients undergoing major orthopedic surgery. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=463481, identifier CRD42023463481.

A Multiparametric Fusion Radiomics Signature Based on Contrast-Enhanced MRI for Predicting Early Recurrence of Hepatocellular Carcinoma.

Objectives: The postoperative early recurrence (ER) rate of hepatocellular carcinoma (HCC) is 50%, and no highly reliable predictive tool has been developed yet. The aim of this study was to develop and validate a predictive model with radiomics analysis based on multiparametric magnetic resonance (MR) images to predict early recurrence of HCC. Methods: In total, 302 patients (training dataset: n = 211; validation dataset: n = 91) with pathologically confirmed HCC who underwent preoperative MR imaging were enrolled in this study. Three-dimensional regions of interest of the entire lesion were accessed by manually drawing along the tumor margins on the multiple sequences of MR images. Least absolute shrinkage and selection operator Cox regression were then applied to select ER-related radiomics features and construct radiomics signatures. Univariate analysis and multivariate Cox regression analysis were used to identify the significant clinico-radiological factors and establish a clinico-radiological model. A predictive model of ER incorporating the fusion radiomics signature and clinico-radiological risk factors was constructed. The diagnostic performance and clinical utility of this model were measured by receiver-operating characteristic (ROC), calibration curve, and decision curve analyses. Results: The fusion radiomics signature consisting of 6 radiomics features achieved good prediction performance (training dataset: AUC = 0.85, validation dataset: AUC = 0.79). The predictive model of ER integrating clinico-radiological risk factors and the fusion radiomics signature improved the prediction efficacy with AUCs of 0.91 and 0.87 in the training and validation datasets, respectively. Furthermore, the nomogram and ER risk stratification system based on the predictive model demonstrated encouraging predictions of the individualized risk of ER and gave three risk groups with low, intermediate, or high risk of ER. Conclusions: The proposed predictive model incorporating clinico-radiological factors and the fusion radiomics signature derived from multiparametric MR images may be an effective tool for the individualized prediction of postoperative ER in patients with HCC.

A Predictive Nomogram of Early Recurrence for Patients with AFP-Negative Hepatocellular Carcinoma Underwent Curative Resection.

Background: Alpha-fetoprotein-negative (<20 ng/mL) hepatocellular carcinoma (AFP-NHCC) cannot be easily diagnosed in clinical practice, which may affect early treatment and prognosis. Furthermore, there are no reliable tools for the prediction of AFP-NHCC early recurrence that have been developed currently. The objective of this study was to identify the independent risk factors for AFP-NHCC and construct an individual prediction nomogram of early recurrence of these patients who underwent curative resection. Methods: A retrospective study of 199 patients with AFP-NHCC who had undergone curative resection and another 231 patients with AFP-positive HCC were included in case-controlled analyses. All AFP-NHCC patients were randomly divided into training and validation datasets at a ratio of 7:3. The univariate and multivariate Cox proportional hazards regression analyses were applied to identify the risk factors, based on which the predictive nomogram of early recurrence was constructed in the training dataset. The area under the curve (AUC), calibration curve, and decision curve was used to evaluate the predictive performance and discriminative ability of the nomogram, and the results were validated in the validation dataset. Results: Compared to AFP-positive patients, the AFP-negative group with lower values of laboratory parameters, lower tumor aggressiveness, and less malignant magnetic resonance (MR) imaging features. AST (HR = 2.200, p = 0.009), tumor capsule (HR = 0.392, p = 0.017), rim enhancement (HR = 2.825, p = 0.002) and TTPVI (HR = 5.511, p < 0.001) were independent predictors for early recurrence of AFP-NHCC patients. The nomogram integrated these independent predictors and achieved better predictive performance with AUCs of 0.89 and 0.85 in the training and validation datasets, respectively. The calibration curve and decision curve analysis both demonstrated better predictive efficacy and discriminative ability of the nomogram. Conclusions: The nomogram based on the multivariable Cox proportional hazards regression analysis presented accurate individual prediction for early recurrence of AFP-NHCC patients after surgery. This nomogram could assist physicians in personalized treatment decision-making for patients with AFP-NHCC.

Additional Use of Prostacyclin Analogs in Patients With Pulmonary Arterial Hypertension: A Meta-Analysis.

Background: Combination therapy has become an attractive option in pulmonary arterial hypertension (PAH) treatment. The aim of this study was to investigate whether additional use of prostacyclin analogs could exert any additional benefits over background targeted therapies in PAH patients. Methods: Searches were performed on PubMed, Embase, and ClinicalTrials.gov from inception to 1 October 2021. Randomized controlled trials were included if patients had been treated with prostacyclin analog-containing combination therapy and compared with the use of other PAH-specific background therapies. The bias risk and statistical analysis of the enrolled studies were performed with RevMan 5.1. Sensitivity analysis and funnel plot were used to evaluate the stability and publication bias, respectively. PROSPERO registered number CRD42021284196. Results: Ten trials involving 1828 patients were included. Prostacyclin analog treatment was associated with greater improvement in clinical worsening (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.57-0.86), 6-min walk distance (mean difference [MD], 37.17 m; 95% CI, 3.01-71.33 m), NYHA/WHO functional class (RR, 1.58; 95% CI, 1.21-2.05), mean pulmonary artery pressure (MD, -9.23 mmHg; 95% CI, -17.44 to -1.03 mmHg), and cardiac index (MD, 0.41 L/min/m2; 95% CI, 0.26-0.55 L/min/m2) than the control group. No significant differences in pulmonary vascular resistance (MD, -137.22 dyn·s/cm5; 95% CI, -272.61 to -1.84 dyn·s/cm5) and all-cause mortality (RR, 0.96; 95% CI, 0.57-1.61) were found between the prostacyclin analog group and control group. Of note, more adverse events (RR, 1.07; 95% CI, 1.02-1.13) occurred in the prostacyclin analog group but no significant increase in serious adverse events (RR, 1.25; 95% CI, 0.75-2.11). Conclusion: Additional prostacyclin analog treatment exerted benefits on clinical worsening, exercise capacity, functional class, mean pulmonary artery pressure, and cardiac index in PAH patients, but it was associated with overall risk of adverse events. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284196, identifier CRD42021284196.

Primary pericardial angiosarcoma: A case report.

Primary pericardial angiosarcoma is a rare malignant cardiac neoplasm with early metastasis and poor prognosis. There are currently no guidelines or effective therapeutic strategies. Here we report a case of a 22-year-old man who presented with chest pain, suffocation and transient syncope over the course of 4 months. Further workup showed a large mass in the right pericardium, histopathologic examination revealed angiosarcoma. The patient subsequently received a total of 8 cycles of chemotherapy (paclitaxel and doxorubicin). This patient has an overall survival of 1 year to date. The current examination methods and reported cases revealed that early detection of primary pericardial angiosarcoma with imaging examinations is critical for prognosis.

Platycarya strobilacea Sieb. et Zucc.: a review of its traditional uses, botany, phytochemistry, pharmacology and toxicology.

OBJECTIVES: Platycarya strobilacea Sieb. et Zucc. is the dry infructescence of P. strobilacea, a Juglandaceae plant and is a traditional Chinese medicine with great development potential and utilization value. This study summarizes the research progress on the traditional uses, botany, phytochemistry, extraction methods, pharmacology and toxicology of Platycarya strobilacea Sieb. et Zucc., and provides potential therapeutic uses and drug development prospects for this plant. KEY FINDINGS: Phytochemical studies showed that this plant mainly contains volatile constituents, phenols, terpenoids and a carbohydrate. The pharmacological activity of Platycarya strobilacea Sieb. et Zucc. includes antibacterial and anti-inflammatory effects, anti-tumour effects and antioxidant effects. This plant is especially effective in the treatment of allergic rhinitis and chronic sinusitis. SUMMARY: In this review, the phytochemistry and pharmacological effects of Platycarya strobilacea Sieb. et Zucc. are described in detail, which will have guiding significance for the future development of this drug.

Protective effects of Re-yan-ning mixture on Streptococcus pneumonia in rats based on network pharmacology.

CONTEXT: Re-yan-ning mixture (RYNM) is a new national drug approved by China's State Food and Drug Administration for the treatment of colds, simple pneumonia and acute bronchitis. OBJECTIVE: To determine the mechanism of action of RYNM in the treatment of bacterial pneumonia. MATERIALS AND METHODS: Using the network pharmacology approach, the multiple components, component candidate targets and multiple therapeutic targets of RYNM were screened and functionally enriched. Also, we established a rat Streptococcus pneumonia model to verify the results of network pharmacology enrichment analysis. Forty male SPF Sprague Dawley rats were divided into four groups of 10 rats: control (normal saline), model (normal saline), levofloxacin-intervened and RYNM-intervened groups. IL-10, NOS2, COX-1, IL-6, TNF-α and NF-κB in serum and BALF were detected by ELISA. Western blot detected IL-17, IL-6, TNF-α, COX-2 and Bcl-2. RESULTS: The network pharmacology approach successfully identified 48 bioactive components in RYNM, and 65 potential targets and 138 signal pathways involved in the treatment of Streptococcus pneumonia with RYNM. The in vivo experiments indicated that model group has visible inflammation and lesions while RYNM and levofloxacin groups have not. The RYNM exhibited its therapeutic effects on Streptococcus pneumonia mainly via the regulation of cell proliferation and survival through the IL-6/IL-10/IL-17, Bax/Bcl-2, COX-1/COX-2, NF-κB and TNF-α signalling pathways. DISCUSSION AND CONCLUSIONS: The present study demonstrated the protective effects of RYNM on Streptococcus pneumonia, providing a potential mechanism for the treatment of bacterial pneumonia with RYNM.

The curative effect of Reduning injection combined with Xuanfeibaidu formula on COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Since December 2019, COVID-19, caused by the new coronavirus (SARS-CoV-2), posed a serious threat to human health. On March 11, 2020, the World Health Organization announced that COVID-2019 has become a global pandemic. In China, Reduning injection (REDI) and Xuanfeibaidu formula (XFF) is widely used in treating COVID-19. However, there is no evidence-based medical evaluation that XFF combine with REDI is effective for COVID-19. METHODS: The following databases will be searched: China National Knowledge Infrastructure (CNKI), Wanfang database, Chinese Science and Technology Periodical Database, Medline/PubMed, and Cochrane from October 1, 2019 to September 1, 2020. The suitable articles will be comprehensively and systematically searched without limitations of regions or language about REDI with XFF for COVID-19. The meta-analysis was performed by RevMan 5.3 and STATA 14.2 software. RESULTS: This meta-analysis may help provide clarify on the effect of REDI combined with XFF to treat COVID-19. The result will be published at a peer-reviewed journal. CONCLUSIONS: This systematic review aims to provide new evidence of XFF combined with REDI for the treatment of COVID-19 in terms of its efficacy and safety. INPLASY REGISTRATION NUMBER: INPLASY202090039.

The therapeutic efficacy of Huashi Baidu Formula combined with antiviral drugs in the treatment of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: The Corona Virus Disease 2019 (COVID-19) is a new acute respiratory infectious disease that has become a major global public health event. In China, the combination of Huashi Baidu Formula (HBF) and antiviral drugs is used in the clinical treatment of severe patients with new coronary pneumonia, but there is still a lack of evidence-based medical evaluation. METHODS: We search for research in PubMed/MEDLINE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, Cochrane Library, Embase, China Biomedical Database (CBM), and Chinese Science Citation Database (CSCD). For "Huashi Baidu Formula" and "COVID-19," we screened suitable articles without language restrictions on keywords, and recorded and analyzed the screened literature with RevMan 5.3 and STATA 14.2 software. RESULTS: This systematic review and meta-analysis will evaluate the efficacy and safety of HBF combined with antiviral drugs in the treatment of COVID-19, and provide the rationality of clinical drug application. CONCLUSION: Our findings will provide references for clinical diagnosis and treatment and guidance programs for COVID-19. INPLASY REGISTRATION NUMBER: INPLASY202080098.

Application of Various Delivery Methods for CRISPR/dCas9.

As gene-editing technology has become more and more popular in the life sciences, CRISPR has brought good news to scientific researchers because of its efficiency, convenience, and wide application. Its wide application has also promoted the development of basic scientific research, agriculture, basic medicine, and clinical treatment. However, how the CRISPR/dCas9 system is effectively delivered to the target organs or cells is still unknown. This paper briefly introduces the CRISPR/dCas9 system and then lists some common delivery methods and their characteristics.

Mechanism of penehyclidine hydrochloride on a dysmenorrhea rat model.

Primary dysmenorrhea affects the quality of life in young women, particularly school and work performance. This study investigated the mechanisms of penehyclidine hydrochloride (PHC) efficacy on a rat model of primary dysmenorrhea. The model was induced by injecting both estradiol benzoate and oxytocin. Different doses of PHC were administrated intraperitoneally following estradiol benzoate administration. Writhing scores were assessed, and pathological changes of the uterus were observed via hematoxylin and eosin staining. Western blot and real-time PCR were used to evaluate the expression level of the M3 receptor, both TLR3 and TLR4 in uterine tissue, and the level of Ca2+ was measured in uterine tissues. Writhing scores significantly decreased in the PHC treatment group compared to model, and PHC alleviated the occurrence of edema or necrosis in the uteri compared to model group. PHC can decrease the M3 receptor, TLR3 , TLR4 expression, and the Ca2+ level compared to the model group. PHC is a potential candidate for the future treatment of primary dysmenorrhea due to its ability to attenuate muscarinic receptors and TLRs. Preclinical Research & Development.

Prediction of microvascular invasion of hepatocellular carcinoma with preoperative diffusion-weighted imaging: A comparison of mean and minimum apparent diffusion coefficient values.

The aim of the study was to investigate the value of preoperative diffusion-weighted imaging (DWI) in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC), using and comparing mean and minimum apparent diffusion coefficient (ADC) values.Preoperative MR images of 318 patients with HCC confirmed by surgical pathology were retrospectively analyzed. All patients underwent preoperative DWI on a 1.5 Tesla MRI scanner. The mean and minimum ADC values of the tumors were measured. Interobserver agreements were assessed by the intraclass correlation coefficient (ICC). The ADC values were compared in HCCs between with and without MVI. ROC curves of ADC values were obtained and then compared in distinguishing HCCs with MVI from those without MVI.There were 211 HCCs with MVI and 107 HCCs without MVI. ICC for the measurements of the mean and minimum ADC values between both observers was 0.88 (95% CI 0.85 - 0.90) and 0.88 (95% CI 0.85 - 0.90), respectively. The mean and minimum ADC values of HCCs with MVI were lower than those of HCCs without MVI (P = .00, .00, respectively). With a cut-off value of 0.98 × 10 mm/s, the minimum ADC (MinADC) showed a sensitivity of 62.56% and a specificity of 65.42% in predicting MVI, whereas the mean ADC provided a sensitivity of 79.15% and a specificity of 50.47% with a cut-off value of 1.19 × 10 mm/s. No significant difference existed between MinADC and mean ADC for their diagnostic performances in the prediction of MVI (P = .48).DWI could preoperatively provide quantitative parameters for predicting MVI of HCC.