Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK‒STAT pathway.

Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

Activation of farnesoid X receptor enhances the efficacy of normothermic machine perfusion in ameliorating liver ischemia-reperfusion injury.

The shortage of transplant organs remains a severe global issue. Normothermic machine perfusion (NMP) has the potential to increase organ availability, yet its efficacy is hampered by the inflammatory response during machine perfusion. Mouse liver ischemia-reperfusion injury (IRI) models, discarded human liver models, and porcine marginal liver transplantation models were utilized to investigate whether farnesoid X receptor (FXR) activation could mitigate inflammation-induced liver damage. FXR expression levels before and after reperfusion were measured. Gene editing and coimmunoprecipitation techniques were employed to explore the regulatory mechanism of FXR in inflammation inhibition. The expression of FXR correlates with the extent of liver damage after reperfusion. Activation of FXR significantly suppressed the inflammatory response triggered by IRI, diminished the release of proinflammatory cytokines, and improved liver function recovery during NMP, assisting discarded human livers to reach transplant standards. Mechanistically, FXR disrupts the interaction between p65 and p300, thus inhibiting modulating the nuclear factor kappa-B signaling pathway, a key instigator of inflammation. Our research across multiple species confirms that activating FXR can optimize NMP by attenuating IRI-related liver damage, thereby improving the utilization of marginal livers for transplantation.

The establishment of diseased human whole organ model by normothermic machine perfusion technique: Principle of concept.

BACKGROUND: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers. METHODS: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis. RESULTS: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP. CONCLUSION: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development.

Anti-COVID-19 mechanism of Anoectochilus roxburghii liquid based on network pharmacology and molecular docking / 药学学报

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

STT3A-mediated viral N-glycosylation underlies the tumor selectivity of oncolytic virus M1.

Oncolytic viruses are emerging as promising anticancer agents. Although the essential biological function of N-glycosylation on viruses are widely accepted, roles of N-glycan and glycan-processing enzyme in oncolytic viral therapy are remain elusive. Here, via cryo-EM analysis, we identified three distinct N-glycans on the envelope of oncolytic virus M1 (OVM) as being necessary for efficient receptor binding. E1-N141-glycan has immediate impact on the binding of MXRA8 receptor, E2-N200-glycan mediates the maturation of E2 from its precursor PE2 which is unable to bind with MXRA8, and E2-N262-glycan slightly promotes receptor binding. The necessity of OVM N-glycans in receptor binding make them indispensable for oncolysis in vitro and in vivo. Further investigations identified STT3A, a key catalytic subunit of oligosaccharyltransferase (OST), as the determinant of OVM N-glycosylation, and STT3A expression in tumor cells is positively correlated with OVM-induced oncolysis. Increased STT3A expression was observed in various solid tumors, pointing to a broad-spectrum anticancer potential of OVM. Collectively, our research supports the importance of STT3A-mediated N-glycosylation in receptor binding and oncolysis of OVM, thus providing a novel predictive biomarker for OVM.

Oncolytic virus M1 functions as a bifunctional checkpoint inhibitor to enhance the antitumor activity of DC vaccine.

Although promising, dendritic cell (DC) vaccines still provide limited clinical benefits, mainly due to the immunosuppressive tumor microenvironment (TME) and the lack of tumor-associated antigens (TAAs). Oncolytic virus therapy is an ideal strategy to overcome immunosuppression and expose TAAs; therefore, they may work synergistically with DC vaccines. In this study, we demonstrate that oncolytic virus M1 (OVM) can enhance the antitumor effects of DC vaccines across diverse syngeneic mouse tumor models by increasing the infiltration of CD8+ effector T cells in the TME. Mechanically, we show that tumor cells counteract DC vaccines through the SIRPα-CD47 immune checkpoint, while OVM can downregulate SIRPα in DCs and CD47 in tumor cells. Since OVM upregulates PD-L1 in DCs, combining PD-L1 blockade with DC vaccines and OVM further enhances antitumor activity. Overall, OVM strengthens the antitumor efficacy of DC vaccines by targeting the SIRPα-CD47 axis, which exerts dominant immunosuppressive effects on DC vaccines.

TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1.

Cholesterol metabolism plays a critical role in the progression of hepatocellular carcinoma (HCC), but it is not clear how cholesterol metabolism is regulated. The tubulin beta class I genes (TUBBs) are associated with the prognosis of many different cancers. To confirm the function of TUBBs in HCC, the Kaplan-Meier method and Cox analyses were performed using TCGA and GSE14520 datasets. A higher expression of TUBB2B is an independent prognostic factor for shorter over survival in HCC patients. Deletion of TUBB2B in hepatocytes inhibits proliferation and promotes tumor cell apoptosis, while over-expression of TUBB2B has the opposite function. This result was confirmed in a mouse xenograft tumor model. Mechanistically, TUBB2B induces the expression of CYP27A1, an enzyme responsible for the conversion of cholesterol to 27-hydroxycholesterol, which leads to the up-regulation of cholesterol and the progression of HCC. In addition, TUBB2B regulates CYP27A1 via human hepatocyte nuclear factor 4alpha (HNF4A). These findings indicated that TUBB2B functions as an oncogene in HCC, and plays a role in promoting cell proliferation and anti-apoptosis through targeting HNF4A/CYP27A1/cholesterol.

Digoxin alleviates pulmonary fibrosis by inhibiting macrophage M2 polarization via regulating mTORC2-IRF4 signaling pathway / 中国药理学通报

Aim To investigate the protective effect of digoxin (Dig) on the bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism. Methods Pulmonary fibrosis model was established by intratracheal instillation of BLM (5 mg · kg

Anti-tumor mechanism study on saffron by network pharmacology and reverse molecular docking / 药学实践杂志

Objective To explore the anti-tumor mechanism of saffron (Crocus sativus L.) by network pharmacology and reverse molecular docking techniques. Methods The main chemical components of saffron were obtained by searching published literature and TCMSP database. The potential targets of these components were predicted using PharmMapper server. The corresponding target genes were identified from UniProt database. The underlying anti-tumor targets of saffron were obtained by mapping the disease genes of cancer or tumor with GeneCards, OMIM and TTD databases. Cytoscape software was used to construct the action target network of saffron active components. The protein-protein interaction analysis was performed by String database, and the GO function and KEGG pathway enrichment analysis were performed by Metascape platform. Finally, molecular docking was performed to evaluate the binding of main components with their potential targets. Results A total of 9 active ingredients in saffron including quercetin, kaempferol, isorhamnetin, picrocrocin and crocin I, were identified, which might act on 37 key targets including AKT1, CCND1, MMP9, EGFR, TP53, involved in P53, TNF and other signaling pathways. Molecular docking indicated modest binding potency through hydrogen bonding, and hydrophobic interactions. Conclusion The anti-tumor effect of saffron was evaluated via the network of components-targets-pathways, which might provide a foundation for further research.

Changes in serum miRNA-21 and miRNA-4534 levels in patients with lung adenocarcinoma and their effects on pathological characteristics and prognosis / 中国基层医药

Objective:To investigate the changes in serum miRNA-21 and miRNA-4534 levels in patients with lung adenocarcinoma and their relationships with pathological characteristics and prognosis.Methods:A total of 148 patients with lung adenocarcinoma who received treatment in the First People's Hospital of Huzhou from January 2018 to January 2019 were included in the observation group. An additional 100 healthy controls who concurrently received physical examinations were included in the control group. The relative expression of serum miRNA-21 and miRNA-4534 was measured using real-time fluorescence quantitative PCR. The relative expression of serum miRNA-21 and miRNA-4534 was compared between the two groups. The relative expression of serum miRNA-21 and miRNA-4534 was compared between patients with different pathological characteristics. Total survival time was compared between patients with high and low miRAN-21 expression and between patients with high and low miRNA-4534 expression.Results:The relative expression of miRNA-21 and miRNA-4534 in the observation group was 3.27 ± 0.87 and 6.74 ± 1.56, respectively, which was significantly higher than 1.00 ± 0.01 and 1.02 ± 0.02 in the control group ( t = 20.07, 36.64, both P < 0.05). There was no significant difference in the relative expression of miRNA-21 and miRNA-4534 between different genders, ages, body mass index values, tumor regions, and tumor diameters (all P > 0.05). The relative expression of serum miRNA-21 in patients with stage Ⅲ-Ⅳ lung adenocarcinoma was 4.45 ± 1.05, which was significantly higher than 1.92 ± 0.53 in patients with stage Ⅰ-Ⅱ lung adenocarcinoma. The relative expression of serum miRNA-21 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis (4.97 ± 1.28 vs. 1.34 ± 0.60, t = 17.53, 23.48, both P < 0.05). The relative expression of miRNA-4534 in patients with stage Ⅲ-Ⅳ lung adenocarcinoma was higher than that in patients with stage Ⅰ-Ⅱ lung adenocarcinoma (8.97 ± 1.85 vs. 4.48 ± 1.09, t = 17.17, P < 0.05). The relative expression of miRNA-4534 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis (9.65 ± 1.35 vs. 3.78 ± 0.91, t = 30.59, P < 0.05). The total survival time in patients with high miRNA-21 expression was shorter than that in patients with low miRNA-21 expression [(18.37 ± 4.35) months vs. (29.93 ± 3.24) months, t = 18.45, P < 0.05]. The total survival time in patients with high miRNA-4534 expression was shorter than that in patients with low miRNA-4534 expression [(17.56 ± 4.21) months vs. (30.43 ± 3.63) months, t = 19.97, P < 0.05)]. Conclusion:Patients with lung adenocarcinoma have high expression of miRNA-21 and miRNA-4534 in the serum, which is closely related to the tumor-node-metastasis stage, lymph node metastasis, and prognosis.

Identification of the receptor of oncolytic virus M1 as a therapeutic predictor for multiple solid tumors.

Over the last decade, oncolytic virus (OV) therapy has shown its promising potential in tumor treatment. The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help predict patients' responses. As particular self-amplifying biotherapeutics, the anti-tumor effects of OVs are highly dependent on the host factors for viral infection and replication. By using weighted gene co-expression network analysis (WGCNA), we found matrix remodeling associated 8 (MXRA8) is positively correlated with the oncolysis induced by oncolytic virus M1 (OVM). Consistently, MXRA8 promotes the oncolytic efficacy of OVM in vitro and in vivo. Moreover, the interaction of MXRA8 and OVM studied by single-particle cryo-electron microscopy (cryo-EM) showed that MXRA8 directly binds to this virus. Therefore, MXRA8 acts as the entry receptor of OVM. Pan-cancer analysis showed that MXRA8 is abundant in most solid tumors and is highly expressed in tumor tissues compared with adjacent normal ones. Further study in cancer cell lines and patient-derived tumor tissues revealed that the tumor selectivity of OVM is predominantly determined by a combinational effect of the cell membrane receptor MXRA8 and the intracellular factor, zinc-finger antiviral protein (ZAP). Taken together, our study may provide a novel dual-biomarker for precision medicine in OVM therapy.

Necroptotic virotherapy of oncolytic alphavirus M1 cooperated with Doxorubicin displays promising therapeutic efficacy in TNBC.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype among breast tumors and remains a challenge even for the most current therapeutic regimes. Here, we demonstrate that oncolytic alphavirus M1 effectively kills both TNBC and non-TNBC. ER-stress and apoptosis pathways are responsible for the cell death in non-TNBC as reported in other cancer types, yet the cell death in TNBC does not depend on these pathways. Transcriptomic analysis reveals that the M1 virus activates necroptosis in TNBC, which can be pharmacologically blocked by necroptosis inhibitors. By screening a library of clinically available compounds commonly used for breast cancer treatment, we find that Doxorubicin enhances the oncolytic effect of the M1 virus by up to 100-fold specifically in TNBC in vitro, and significantly stalls the tumor growth of TNBC in vivo, through promoting intratumoral virus replication and further triggering apoptosis in addition to necroptosis. These findings reveal a novel antitumor mechanism and a new combination regimen of the M1 oncolytic virus in TNBC, and highlight a need to bridge molecular diagnosis with virotherapy.

Real-Time Visualization and Quantification of Oncolytic M1 Virus In Vitro and In Vivo.

Alphavirus M1 is a promising oncolytic virus for cancer therapy. Here, we constructed a fluorescent reporter virus for real-time visualization and quantification of M1 virus both in vitro and in vivo. The reporter-encoding M1 virus maintained the characteristics of parental virus in the aspects of structure, replication capacity, the feature to induce cytopathic cell death, and the property of tumor targeting. The fluorescence is positively correlated with virus replication both in vitro and in vivo. More importantly, the reporter can be stably expressed for at least 10 generations in a serial passage assay. In summary, we successfully constructed stable and authentic reporter viruses for studying M1 virus and provided a feasible technical route for gene modification of oncolytic virus M1.

Visualization of the Oncolytic Alphavirus M1 Life Cycle in Cancer Cells.

Oncolytic alphavirus M1 has been shown to selectively target and kill cancer cells, but cytopathic morphologies induced by M1 virus and the life cycle of the M1 strain in cancer cells remain unclear. Here, we study the key stages of M1 virus infection and replication in the M1 virus-sensitive HepG2 liver cancer cell line by transmission electron microscopy, specifically examining viral entry, assembly, maturation and release. We found that M1 virus induces vacuolization of cancer cells during infection and ultimately nuclear marginalization, a typical indicator of apoptosis. Specifically, our results suggest that the endoplasmic reticulum participates in the assembly of nucleocapsids. In the early and late stage of infection, three kinds of special cytopathic vacuoles are formed and appear to be involved in the replication, maturation and release of the virus. Taken together, our data displayed the process of M1 virus infection of tumor cells and provide the structural basis for the study of M1 virus-host interactions.

Survey on knowledge, attitudes and practice about chronic obstructive pulmonary disease among general practitioners in Sichuan province / 中华全科医师杂志

Objective:To survey the knowledge, attitudes, and practice about chronic obstructive pulmonary disease (COPD) among general practitioners in Sichuan province.Methods:From October to November 2020, a questionnaire survey on knowledge, attitudes and practice (KAP) among 104 general practitioners who participated in the training of the comprehensive prevention and control of COPD organized by Sichuan Provincial Health Commission. The content of the questionnaire included the basic information and the KAP status of COPD. The descriptive analysis, Mann-Whitney U test, and Kruskal-Wallis H were used for statistical analysis. Results:A total of 104 questionnaires were distributed and 102 were returned with a response rate of 98.1%. General practitioners with different ages, professional titles, visits of COPD patients each month, and whether or not to refer COPD patients to higher-level hospitals were not significantly different in the scores of knowledge( U=1 276.00, H=0.78, U=1 074.00, U=589.00), attitude( U=1 141.50, H=1.75, U=1 090.00, U=585.00), and practice( U=1 221.00, H=0.31, U=1 163.00, U=499.50) (all P>0.05). In knowledge part the highest correctness rate was "quitting smoking is the most powerful interventions affecting the natural disease course of COPD" (100.0%, 102/102); the lowest was that"the main objective examination for judging the airflow limitation of COPD patients is the lung function test"(5.9%, 6/102). In the part of the attitude, the highest positive rate was "educating patients to quit smoking and avoid exposure to second-hand smoke" (65.7%,67/102); the lowest positive rate was "provide exercise guidance to patients "(43.1%, 44/102) and " be responsible for long-term treatment follow-up" (43.1%, 44/102). In the part of practice, the highest behavioral rate was "when receiving patients with COPD, actively pay attention to the treatment of comorbid diseases" (95.1%, 97/102); the lowest behavioral rate was "when patients with COPD were seen at the clinic, and the patients were advised of the best time to use the inhaler" (65.7%, 67/102). Conclusions:The study indicates that the relevant departments need to increase the intensity of knowledge training for general practitioners in Sichuan province. General practitioners should continuously improve their education, prevention, and treatment ability and implement the primary responsibilities for COPD management.

Application of ultrasound bionic 3D printing combined with PBL method in individualized teaching of standardized residency training of cardiac ultrasound / 中华医学教育探索杂志

Objective:To meet the individualized needs of residents in standardized residency training of cardiac intervention specialty for cardiac ultrasound teaching, to construct a bionic 3D printing model of ultrasound source, and to discuss its application value in ultrasound teaching and simulation exercises.Methods:Sixty residents majored in cardiovascular medicine receiving standardized residency training of ultrasound in ultrasound imaging department of Renmin Hospital of Wuhan University were randomized into experimental group and control group in average. The experimental group adopted ultrasound bionic 3D printing heart model combined with problem-based learning (PBL) teaching method, and the control group adopted traditional multimedia PPT combined with PBL teaching method. At the end of teaching activities, theoretical examination, operation assessment and questionnaire survey were conducted to evaluate and compare the teaching effect between the two groups. SPSS 21.0 software was performed for t test. Results:The theoretical examination scores of the experimental group and the control group were (81.4±8.2) points and (74.8±9.4) points, respectively, P=0.002, and the operation assessment scores were (89.1±5.6) points and (71.5±8.8) points, respectively, P<0.001. The questionnaire survey showed that the experimental group had better feedbacks than the control group in the aspects of mastery of heart anatomy knowledge, learning experience, learning interest, learning efficiency, understanding of interventional heart disease, clinical skills of interventional operation and overall satisfaction (all P<0.05). Conclusions:Ultrasound bionic 3D printing combined with PBL teaching method can help strengthen the mastery of cardiac anatomy knowledge, promote the learning experience of cardiac ultrasound and improve the skills of interventional operation. The teaching effect is significant and the students' satisfaction is high.

Zinc-finger antiviral protein acts as a tumor suppressor in colorectal cancer.

Avoiding immune destruction is essential for tumorigenesis. Current research into the interaction between tumor and immunological niches complement tumor pathology beyond cancer genetics. Intrinsic host defense immunity is a specialized innate immunity component to restrict viral infection. However, whether intrinsic immunity participates in tumor pathology is unclear. Previously, we identified a zinc-finger antiviral protein ZAP that is commonly downregulated in a panel of clinical cancer specimens. However, whether ZAP has an impact on tumor development was unknown. Here we report ZAP as a genuine tumor suppressor. Pan-caner analysis with TCGA data from 712 patients and large-scale immunohistochemistry in tissue microarrays from 1552 patients reveal that ZAP is prevalently downregulated, and associated with poor survival in liver, colon, and bladder cancer patients. Ectopic over-expression of ZAP inhibits the malignant phenotypes of colorectal tumor by cell cycle arrest. Using RNA immunoprecipitation and RNA decay assays, we demonstrate that ZAP directly and specifically binds to and degrades the transcript of TRAILR4, which in turn represses TRAILR4 expression and inhibits the aggressiveness of colorectal cancer cells. Furthermore, our CRISPR-engineered mice models show that loss-of-function of ZAP synergizes with APC-deficiency to drive malignant colorectal cancer in vivo. Overall, we identify a previously unknown function of the antiviral factor ZAP in colorectal tumorigenesis, linking intrinsic immunity to tumor pathogenetics.

Association of related maternal factors with susceptibility to congenital hypothyroidism: a case-control study / 中国当代儿科杂志

OBJECTIVE@#To study the association of related maternal factors with the susceptibility to congenital hypothyroidism (CH) in neonates.@*METHODS@#A case-control study was designed. The neonates who were diagnosed with CH in Neonatal Screening Center of Henan Province from January 1, 2016 to December 31, 2017 were enrolled as cases. Healthy neonates, matched for sex and age were enrolled as controls. A conditional logistic regression analysis and additive and multiplicative interaction analyses were used to identify the risk factors for susceptibility to CH.@*RESULTS@#A total of 2 771 661 neonates were screened during this period, among whom 1 494 neonates were diagnosed with CH, with a crude incidence rate of 53.9/100 000. A total of 843 pairs of the cases and the controls completed the telephone survey and provided qualified data. The conditional logistic regression analysis showed that an older maternal age at delivery, a low educational level in mothers, living in the rural area, a family history of thyroid diseases, histories of exposure to formaldehyde during pregnancy, exposure to radiation during pregnancy, and medication during pregnancy, were risk factors for CH (P<0.05), while low maternal age at delivery and progesterone intake during pregnancy were protective factors against CH (P<0.05).@*CONCLUSIONS@#An older maternal age at delivery, a low educational level in mothers, living in the rural area, a family history of thyroid diseases, and histories of exposure to formaldehyde during pregnancy, exposure to radiation during pregnancy and medication during pregnancy may increase the susceptibility to CH in neonates.

Process optimization of Morinda officinalis with wine steaming by star dot design-response surface methodology / 药学实践杂志

Objective To establish the best wine steaming process for morinda officinalis with monotropein as indicator. Methods Response surface methodology was used to optimize the wine steaming process for morinda officinalis with the amount of rice wine, stewing time, moistening time and the monotropein content as evaluation indexes. Results The best condition was identified with rice wine (rice wine/herbs, g/g) 10%, moistening time 1.0 h, fully steamed and dried. Conclusion The Star dot design-response surface method can be used to optimize the wine steaming process for morinda officinalis.