The effectiveness of intervention in hepatitis C patients and improvement in their referral rate.

BACKGROUND: To investigate the effectiveness of the intervention with critical value management and push short messaging service (SMS), and to determine improvement in the referral rate of patients with positive hepatitis C antibody (anti-HCV). METHODS: No intervention was done for patients with positive anti-HCV screening results from 1 January 2015 to 31 October 2021. Patients with positive anti-HCV results at our hospital from 1 November 2021 to 31 July 2022 were informed vide critical value management and push SMS. For inpatients, a competent physician was requested to liaise with the infectious disease physician for consultation, and patients seen in the OPD (outpatient department) were asked to visit the liver disease clinic. The Chi-square correlation test, one-sided two-ratio test and linear regression were used to test the relationship between intervention and referral rate. RESULTS: A total of 638,308 cases were tested for anti-hepatitis C virus (HCV) in our hospital and 5983 of them were positive. 51.8% of the referred patients were aged 18-59 years and 10.8% were aged ≥75 years. The result of Chi-square correlation test between intervention and referral was p = .0000, p < .05. One-sided two-ratio test was performed for statistics of pre-intervention referral rate (p1) and post-intervention referral rate (p2). Normal approximation and Fisher's exact test for the results obtained were 0.000, p < .05, and the alternative hypothesis p1 - p2 < 0 was accepted. The linear regression equation was referral = 0.1396 × intervention + 0.3743, and the result model p = 8.79e - 09, p < .05. The model was significant, and the coefficient of intervention was 0.1396. CONCLUSIONS: The interventions of critical value management and push SMS were correlated with the referral rate of patients with positive anti-HCV.

Tissue-type plasminogen activator (tPA) homozygous Tyr471His mutation associates with thromboembolic disease.

Tissue-type plasminogen activator (tPA) encoded by PLAT is a major mediator that promotes fibrinolysis and prevents thrombosis. Pathogenetic mutations in PLAT associated with venous thromboembolism have rarely been reported. Here, we report the first case of a homozygous point mutation c.1411T>C (p.Y471H) in PLAT leading to thromboembolic events and conduct related functional studies. The corresponding tPA mutant protein (tPA-Y471H) and wild-type tPA (tPA-WT) were synthesized in vitro, and mutant mice (PLATH/H mice) were constructed. The molecular docking and surface plasmon resonance results indicated that the mutation impeded the hydrogen-bonding interactions between the protease domain of tPA and the kringle 4 domain of plasminogen, and the binding affinity of tPA and plasminogen was significantly reduced with a difference of one order of magnitude. mRNA half-life assay showed that the half-life of tPA-Y471H was shortened. The inferior vena cava thrombosis model showed that the rate of venous thrombosis in PLATH/H mice was 80% compared with 53% in wild-type mice. Our data suggested a novel role for the protease domain of tPA in efficient plasminogen activation, and demonstrated that this tPA mutation could reduce the fibrinolysis function of the body and lead to an increased propensity for thrombosis.

The risk factors for coagulation disorder of chimeric antigen receptor-T cell therapy in patients with hematological tumors: A systematic review and meta-analysis.

BACKGROUND: Currently, the frequency of coagulation dysfunction associated with chimeric antigen receptor-T cell (Car-T) therapy cannot yet be determined. OBJECTIVE: We performed a systematic review and meta-analysis to examine the prevalence of abnormal laboratory tests related to coagulation disorders in patients receiving Car-T therapy and provide a reference for future risk assessment mechanisms. METHODS: We searched PubMed, Embase, and Web of Science for relevant studies and evaluated their quality using the methodology index of non-random research (MINORS). 2672 quotations were retrieved via systematic searches. After screening of titles, abstracts and full-text, 45 trials involving 2541 patients were ultimately included. 41 studies reported the incidence of thrombocytopenia, 8 studies reported the rate of low fibrin, 4 trials reported the rate of APTT or PT abnormalities and only 3 trials reported the incidence of venous thromboembolism (VTE). We performed a quantitative meta-analysis to explore the incidence of thrombocytopenia following Car-T treatment. The incidence of hypofibrinogenemia, VTE, and abnormal APTT or PT was only qualitatively assessed, as fewer reports were included in this study. RESULTS: The overall incidence of thrombocytopenia associated with Car-T therapy was 45.8% (95%[CI], 0.384-0.533). The highest rates of thrombocytopenia occurred in patients with multiple myeloma (60.1%, 95%[CI], 0.507-0.688) and aged between 18 to 60 (50%, 95%[CI], 0.367-0.633). There was greater prevalence of thrombocytopenia in BCMA-Car-T therapy of 58.7% (95%[CI], 0.482-0.685). Thrombocytopenia occurred most frequently in Car-T patients treated with a dosage of 1 × 105-1 × 106 cell/kg, at a rate of 66.2% (95%[CI], 0.561-0.749). CONCLUSION: Overall, 45.8 percent of patients receiving Car-T treatment suffered from thrombocytopenia. Multiple myeloma patients, ages between 18-60, a dose of 1 × 105-1 × 106 cell/kg and BCMA-Car-T therapy are all considered high-risk factors.

Factor XIa Inhibitors as a Novel Anticoagulation Target: Recent Clinical Research Advances.

BACKGROUND: While current clinically administered anticoagulant medications have demonstrated effectiveness, they have also precipitated significant risks: severe bleeding complications including, but not limited to, gastrointestinal hemorrhaging and intracranial and other life-threatening major bleedings. An ongoing effort is being made to identify the best targets for anticoagulant-targeted drugs. Coagulation factor XIa (FXIa) is emerging as an important target of current anticoagulant treatment. OBJECTIVE: This review will summarize the development of anticoagulants and recent advances in clinical trials of experimental factor XI inhibitors from a clinical application perspective. RESULTS: As of 1 January 2023, our search screening included 33 clinical trials. We summarized the research progress of FXIa inhibitors from seven clinical trials that evaluated their efficacy and safety. The results showed no statistically meaningful distinction in the primary efficacy between patients receiving FXIa inhibitors compared to controls (RR = 0.796; 95% CI: 0.606-1.046; I2 = 68%). The outcomes did not indicate a statistical difference in the occurrence of any bleeding between patients receiving FXIa inhibitors compared to controls (RR = 0.717; 95% CI: 0.502-1.023; I2 = 60%). A subgroup analysis found significant differences in severe bleeding and clinically relevant hemorrhaging in subjects receiving FXIa inhibitors compared to Enoxaparin (RR = 0.457; 95% CI: 0.256-0.816; I2 = 0%). CONCLUSIONS: Clinical trials to date have indicated that factor XIa is a potential anticoagulation target, and factor XIa inhibitors may play an important role in the development of anticoagulants.

Efficacy and safety of novel oral anticoagulants for the treatment of cancer-associated venous thromboembolism: protocol for an umbrella review of systematic reviews and meta-analyses.

INTRODUCTION: Novel oral anticoagulants (NOACs) have been used in antithrombotic therapy in patients with cancer, and their efficacy and safety have been evaluated in several meta-analyses. Although a large body of findings has accumulated to support the benefit of NOACs for the treatment and prevention of cancer-associated thromboembolism, there is no convincing evidence because of inconsistent results across studies and questionable data quality. Its efficacy and safety remain controversial, especially with regard to the risk of bleeding. METHODS AND ANALYSIS: We will search PubMed, Embase and Web of science, Cochrane Library on 19 April 2022 (searches will be updated until complete) to identify systematic reviews, meta-analyses and pooled analyses of the efficacy and safety of NOACs for the treatment of cancer-associated venous thromboembolism. The quality of eligible systematic evaluations will be measured by A Measurement Tool to Assess Systematic Reviews. For each outcome, if a random effects model is not used, we will extract the data and estimate a 95% CI using the random effects model approach. For each random effects estimate, a 95% prediction interval is calculated. Heterogeneity between studies will be quantified using the I2 metric. In addition, if an assessment contains at least three articles, we will reanalyse the assessment using Egger's asymmetry test to detect and visualise possible publication bias in the articles. ETHICS AND DISSEMINATION: No formal ethical approval is required since we will use publicly available data. We will disseminate the findings of the umbrella review through publication in a peer-reviewed journal and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022342053.

[Practice and development of structural characteristics and quality control of multi-dimensional structure of basic components of genuine material of Moutan Cortex].

Traditional Chinese medicine is the product of clinical medication practice of the Chinese nation for thousands of years. Its material basis is the key to reveal the essence of the roles of traditional Chinese medicine, and the fundamental guarantee to solve the difficulties in the quality control of traditional Chinese medicine. However, the material basis of traditional Chinese medicine is to exert the overall pharmacodynamic effect through multi-targets, multi-approaches and mutual cooperation, resulting in unclear quality control index. In recent years, the quality control standards of traditional Chinese medicine have experienced great changes by shifting the focus from the appearance characteristics to the internal material basis, which however is limited to the control of a single com-ponent or multiple components. In other words, the intrinsic effectiveness and safety could not be guaranteed without the characteristics of the integrity of traditional Chinese medicine. With Moutan Cortex as an example, this paper analyzed the evolution of Moutan Cortex quality standards based on Chinese Pharmacopoeia, and comprehensively summarized the material basis of Moutan Cortex. Based on the theory of "component structure", this study analyzed current quality control of the material basis of Moutan Cortex and its preparations, and expounded the development trend of multi-dimensional quality control, so as to lay a foundation for establishing a more rational quality control system for traditional Chinese medicine in the future.

[Comparative analysis and study on component characteristics of inorganic elements in genuine Moutan Cortex and their differences from other areas].

Based on the theory of "component structure", the component structure characteristics of 17 inorganic elements in 20 batches of genuine Moutan Cortex and 12 batches of non-genuine Moutan Cortex were analyzed. The analytical method of inductively coupled plasma mass spectrometry(ICP-MS) for inorganic elements in Moutan Cortex was established, and the fingerprint of inorganic elements was drawn. Through correlation analysis and principal component analysis, the constituent elements of inorganic elements in Moutan Cortex were excavated, namely characteristic elements As, Cr, Pb, Se, K, Cu and Cd. The amount and the quantity relative ratio between the components of genuine and non-genuine Moutan Cortex samples were analyzed. It was found that the amount of characteristic elements in the bulk genuine Moutan Cortex samples was 0.33, 1.42, 1.33, 0.11, 4 385.78, 4.87, 0.49 mg·kg~(-1), with the quantity relative ratio of 1.00∶4.30∶4.03∶0.33∶13 290.24∶14.76∶1.48. The amount of characteristic elements in sub-packaged genuine Moutan Cortex was 0.24, 1.96, 0.36, 0.05, 5 122.01, 4.81, 0.05 mg·kg~(-1), with the quantity relative ratio of 1.00∶8.17∶1.50∶0.21∶21 341.71∶20.04∶0.21. The unique structural characteristics of inorganic elements in genuine Moutan Cortex are studied to provide a basis for the quality control and safety evaluation of Moutan Cortex.

[Structural characteristics of pharmacodynamical components in genuine Moutan Cortex].

Guided by the theory of "component structure", we analyzed the structural characteristics of pharmacodynamical components in genuine Moutan Cortex. The compositions of organic small molecules were determined by high performance liquid chromatography(HPLC) for 20 batches of genuine Moutan Cortex and 12 batches of non-genuine Moutan Cortex. By means of similarity analysis, clustering analysis(CA), principal component analysis(PCA) and orthogonal partial least-squares discriminant analysis(OPLS-DA), the elements in structural characteristics of the pharmacodynamical components were extracted as follows: terpene glycosides components(oxidized paeoniflorin, paeoniflorin,galloyl paeoniflorin, benzoyloxy paeoniflorinand benzoyl paeoniflorin), tannin components(1,3,6-tri-O-galloside acyl glucose, pentagalloyl glucose), and phenolic acid components(methyl gallate, paeonol). The contents and quantity ratios of terpene glycoside component, tannin component and phenolic acid components in genuine Moutan Cortex were determined as 14.1, 12.5, 21.7 mg·g~(-1), 1.00∶0.89∶1.54. The contents and quantity ratios of the oxidized paeoniflorin, paeoniflorin and benzoylpaeoniflorin in the terpene glycoside components were characteristic and determined as 2.05, 7.05, 3.30 mg·g~(-1), 1.00∶3.44∶1.61. The unique structural characteristics of genuine Moutan Cortex provide scientific basis for the formulation of quality standards.

[Structure characteristics and quality control of Liuwei Dihuang Concentrated Pill from different manufacturers].

In this paper, we aim to control and evaluate the quality of Liuwei Dihuang Concentrated Pill by using the model of fingerprint technique and "component structure" theory. Agilent 5 TC-C_(18) column(4.6 mm×250 mm,5 µm) was used, with 0.1% formic acid solution-acetonitrile as mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃, with detection wavelength of 242 nm and the sample volume of 10 µL. The characteristic fingerprint of Liuwei Dihuang Concentrated Pill was established by high performance liquid chromatography(HPLC) for its quality control. Seventeen common peaks were identified, and the similarity was 0.550-0.997 in 29 batches of samples, indicating that the quality difference among batches of Liuwei Dihuang Concentrated Pills was significant. The structural characteristics of the Moutan Cortex components in Liuwei Dihuang Concentrated Pills were characterized. On this basis, combined with the structural characteristics of genuine components of Moutan Cortex, the structural characteristics of components in Liuwei Dihuang Concentrated Pills were further analyzed. The results showed that there were significant differences in the contents and quantity ratios of 9 representative components(components) of Moutan Cortex in Liuwei Dihuang Concentrated Pills from different manufacturers, indicating internal quality differences among different batches of products. The fingerprint technique and the "component structure" theory established by the above research provide an analytical method and a research foundation for the quality evaluation of Liuwei Dihuang Concentrated Pills.

[Quality analysis of Moutan Cortex Formula Granules based on structural characteristics of genuine components].

To evaluate the quality of Moutan Cortex Formula Granules from different manufacturers based on the structural characteristics of the genuine components of Moutan Cortex. High performance liquid chromatography(HPLC) fingerprint analysis method of Moutan Cortex Formula Granules was established to characterize the elements of the structural characteristics for genuine Moutan Cortex. Nineteen common peaks were determined and the similarity between the Moutan Cortex Formula Granules of each batch and the control fingerprint was 0.856-0.981. The results showed that there were differences in the internal quality of Moutan Cortex Formula Granules from three manufacturers. The contents of components as well as inter-component and intra-component quantity ratio for Moutan Cortex Formula Granules from different manufacturers were analyzed. It was found that the inter-component quantity ratio of G1 and G2 produced by manufacturer A was close to that of G4 produced by manufacturer B; the inter-component quantity ratio of G3 from manufacturer B was close to that of G7 from manufacturer C; and the inter-component ratios of samples G5, G6, G8-G11 produced by manufacturer C were closer to each other. The results of the study guided by the theory of "component structure" provide a new analytical method and basis for the quality evaluation of Moutan Cortex Formula Granules.

Light and Temperature as Dual Stimuli Lead to Self-Assembly of Hyperbranched Azobenzene-Terminated Poly(N-isopropylacrylamide).

Hyperbranched poly(N-isopropylacrylamide)s (HBPNIPAMs) end-capped with different azobenzene chromophores (HBPNIPAM-Azo-OC3H7, HBPNIPAM-Azo-OCH3, HBPNIPAM-Azo, and HBPNIPAM-Azo-COOH) were successfully synthesized by atom transfer radical polymerization (ATRP) of N-isopropylacrylamide using different azobenzene-functional initiators. All HBPNIPAMs showed a similar highly branched structure, similar content of azobenzene chromophores, and similar absolute weight/average molecular weight. The different azobenzene structures at the end of the HBPNIPAMs exhibited reversible trans-cis-trans isomerization behavior under alternating UV and Vis irradiation, which lowered the critical solution temperature (LCST) due to different self-assembling behaviors. The spherical aggregates of HBPNIPAM-Azo-OC3H7 and HBPNIPAM-Azo-OCH3 containing hydrophobic para substituents either changed to bigger nanorods or increased in number, leading to a change in LCST of -2.0 and -1.0 °C, respectively, after UV irradiation. However, the unimolecular aggregates of HBPNIPAM-Azo were unchanged, while the unstable multimolecular particles of HBPNIPAM-Azo-COOH end-capped with strongly polar carboxyl groups partly dissociated to form a greater number of unimolecular aggregates and led to an LCST increase of 1.0 °C.