Cost-utility analysis and drug pricing for tirzepatide for type 2 diabetes in the Chinese market compared with semaglutide.

AIM: To investigate the most matchable price of tirzepatide (TIRZ) compared with semaglutide (SEMA) in the treatment of type 2 diabetes in China. METHODS: The patient cohort and clinical efficacy data were derived from the SURPASS-2 trial. Cost-utility analysis and a binary search were performed to identify the most matchable price of TIRZ from a Chinese healthcare provider's perspective. RESULTS: After lifetime simulation, the quality-adjusted life years of TIRZ 5, 10, 15 mg and SEMA 1 mg were 11.17, 11.21, 11.27 and 11.12 years, respectively. Despite an initial assumption that the annual cost of TIRZ equals that of SEMA, our analysis revealed that TIRZ is probably more cost-effective than SEMA. A thorough evaluation of pricing showed that the cost ranges for TIRZ at doses of 5, 10 and 15 mg were $1628.61-$1846.23, $1738.40-$2140.95 and $1800.30-$2430.81, respectively. After adjustment in the univariate sensitivity analysis, the cost ranges for TIRZ 5, 10 and 15 mg were $1542.68-$1757.57, $1573.00-$1967.16 and $1576.54-$2133.96, respectively. These cost intervals were validated through robust probabilistic sensitivity analysis and scenario analysis, except for the cost range for TIRZ 5 mg. CONCLUSIONS: This study shows that, using SEMA as a reference, the annual costs for TIRZ 10 and 15 mg are $1573.00-$1967.16 and $1576.54-$2133.96, respectively, for patients with type 2 diabetes in China.

Multi-technology integrated network pharmacology-based study on phytochemicals, active metabolites, and molecular mechanism of Psoraleae Fructus to promote melanogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Compendium of Materia Medica (Shizhen Li, Ming dynasty) and Welfare Pharmacy (Song dynasty), Psoraleae Fructus (PF), a traditional Chinese medicine (TCM) has a bitter taste and warm nature, which has the effect of treating spleen and kidney deficiency and skin disease. Although PF has been widely used since ancient times and has shown satisfactory efficacy in treating vitiligo, the active substances and the mechanism of PF in promoting melanogenesis remain unclear. AIM OF THE STUDY: To explore the active substances and action mechanisms of PF in promoting melanogenesis. MATERIALS AND METHODS: Firstly, UPLC-UV-Q-TOF/MS was used to characterize the components in PF extract and identify the absorption components and metabolites of PF after oral administration at usual doses in rats. Secondly, the active substances and related targets and pathways were predicted by network pharmacology and molecular docking. Finally, pharmacodynamic and molecular biology experiments were used to verify the prediction results. RESULTS: The experimental results showed that 15 compounds were identified in PF extract, and 44 compounds, consisting of 8 prototype components and 36 metabolites (including isomers) were identified in rats' plasma. Promising action targets (MAPK1, MAPK8, MAPK14) and signaling pathways (MAPK signaling pathway) were screened and refined to elucidate the mechanism of PF against vitiligo based on network pharmacology. Bergaptol and xanthotol (the main metabolites of PF), psoralen (prototype drug), and PF extract significantly increased melanin production in zebrafish embryos. Furthermore, bergaptol could promote the pigmentation of zebrafish embryos more than psoralen and PF extract. Bergaptol significantly increased the protein expression levels of p-P38 and decreased ERK phosphorylation in B16F10 cells, which was also supported by the corresponding inhibitor/activator combination study. Moreover, bergaptol increased the mRNA expression levels of the downstream microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells. Our data elucidate that bergaptol may promote melanogenesis by regulating the p-P38 and p-ERK signaling pathway. CONCLUSIONS: This study will lay a foundation for discovering potential new drugs for treating vitiligo and provide feasible ideas for exploring the mechanism of traditional Chinese medicine.

Five years of safety profile of bevacizumab: an analysis of real-world pharmacovigilance and randomized clinical trials.

OBJECTIVE: Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. It has a wide range of clinical applications in various cancers and retinal diseases. The drugs entered the Chinese market by a large margin in 2017, and the user population changed to some extent. This study reevaluated the safety of bevacizumab through an analysis of the World Pharmacovigilance database (Food and Drug Administration Open Vigil 2.1) in conjunction with a comprehensive meta-analysis of RCTs. METHODS: Real-world pharmacovigilance data originating from case reports were mined using Open Vigil and coded at the preferred term (PT) level using the Standardized MedDRA Query. Proportional reporting ratios (PRR) and reporting odds ratios (ROR) were used to detect safety signals. Eligible items were screened by searching PubMed, Wanfang, and Web of Science, and data were extracted for systematic review and meta-analysis using RevMan 5.4 software. RESULTS: Analysis of the drug pharmacovigilance database revealed that the most significant PRRs were limb decortication syndrome (PRR = 2926), stomal varices (PRR = 549), anastomotic (PRR = 457) and ureteral fistula (PRR = 406). Most safety signals at the PT level emerged as various types of injuries, toxicities, operational complications, systemic diseases, various reactions at the administration site, hematological and lymphatic disorders, and gastrointestinal disorders. Adverse reactions such as nasal septal perforation (PRR = 47.502), necrotizing fasciitis (PRR = 20.261), and hypertensive encephalopathy (PRR = 18.288) listed as rare in drug specifications should not be ignored with a high signal in the real world. A total of 8 randomized controlled trials (RCTs) were included in the meta-analysis, and the overall risk of adverse reactions following bevacizumab administration was relatively low, indicating a good safety profile (HR = 1.19, 95% CI:0.85 ~ 1.65, p = 0.32). CONCLUSION: The frequent adverse reactions of bevacizumab occurring in the real world are consistent with the data provided in RCTs and drug specifications. However, adverse reactions such as nasal septum perforation, necrotizing fasciitis, hypertensive encephalopathy and so on, listed as rare in drug specifications, may have a high signal of correlation in the real world, which all requires active monitoring and timely adjustment of bevacizumab posology during its clinical use.

The risk factors of diabetic ketosis and diabetic ketoacidosis among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors: a retrospective study.

BACKGROUND: There is limited evidence on the safety of sodium-glucose co-transporter-2 inhibitor (SGLT2i) use in the real world of China. We conducted this two-center, retrospective study to assess the incidence rate and risk factors of Dapagliflozin-associated DK/DKA among patients with type 2 diabetes mellitus (T2DM) in China. RESEARCH DESIGN AND METHODS: Patients with T2DM treated with Dapagliflozin in Shanghai General Hospital were included in this retrospective analysis. Univariate and multivariate logistic regression was performed, and odds ratio (OR) and 95% confidence interval (CI) were calculated to identify the influencing factors associated with the occurrence of DK/DKA. RESULTS: A total of 1985 T2DM patients received Dapagliflozin for the first time were included. The prevalence of DK and DKA was 2.47% and 0.35%, respectively. Multivariate logistic regression identified age <45 years [OR = 2.99, 95% CI (1.45-6.17)], concomitant use of Acarbose [OR = 2.18, 95% CI (1.06-3.38)], Metformin [OR = 1.84, 95% CI (1.01-3.38)], and Insulin [OR = 1.93, 95% CI (1.02-3.66)] as participating factors for DK/DKA. The 1:4 matched subset sensitivity analysis further confirmed the risk factors of Dapagliflozin-associated DK/DKA. CONCLUSIONS: Age less than 45 years, concomitant use of Acarbose and insulin were risk factors for Dapagliflozin-associated DK/DKA. Clinicians should watch out for high-risk features among patients with SGLT2i prescription.

A Systematic Study of Yiqi Qubai Standard Decoction for Treating Vitiligo Based on UPLC-Q-TOF/MS Combined with Chemometrics, Molecular Docking, and Cellular and Zebrafish Assays.

The Yiqi Qubai (YQ) formula is a hospital preparation for treating vitiligo in China that has had reliable efficacy for decades. The formula consists of four herbs; however, the extraction process to produce the formula is obsolete and the active ingredients and mechanisms remain unknown. Therefore, in this paper, fingerprints were combined with the chemometrics method to screen high-quality herbs for the preparation of the YQ standard decoction (YQD). Then, the YQD preparation procedure was optimized using response surface methodology. A total of 44 chemical constituents, as well as 36 absorption components (in rat plasma) of YQD, were identified via UPLC-Q-TOF/MS. Based on the ingredients, the quality control system of YQD was optimized by establishing the SPE-UPLC-Q-TOF/MS identification method and the HPLC quantification method. Network pharmacological analysis and molecular docking showed that carasinaurone, calycosin-7-O-ß-d-glucoside, methylnissolin-3-O-glucoside, genkwanin, akebia saponin D, formononetin, akebia saponin B, and apigenin may be the key active components for treating vitiligo; the core targets associated with them were AKT1, MAPK1, and mTOR, whereas the related pathways were the PI3K-Akt, MAPK, and FoxO signaling pathways. Cellular assays showed that YQD could promote melanogenesis and tyrosinase activity, as well as the transcription and expression of tyrosinase-associated proteins (i.e., TRP-1) in B16F10 cells. In addition, YQD also increased extracellular tyrosinase activity. Further efficacy validation showed that YQD significantly promotes melanin production in zebrafish. These may be the mechanisms by which YQD improves the symptoms of vitiligo. This is the first systematic study of the YQ formula that has optimized the standard decoction preparation method and investigated the active ingredients, quality control, efficacy, and mechanisms of YQD. The results of this study lay the foundations for the clinical application and further development of the YQ formula.

Further Improvement Based on Traditional Nanocapsule Preparation Methods: A Review.

Nanocapsule preparation technology, as an emerging technology with great development prospects, has uniqueness and superiority in various industries. In this paper, the preparation technology of nanocapsules was systematically divided into three categories: physical methods, chemical methods, and physicochemical methods. The technological innovation of different methods in recent years was reviewed, and the mechanisms of nanocapsules prepared via emulsion polymerization, interface polymerization, layer-by-layer self-assembly technology, nanoprecipitation, supercritical fluid, and nano spray drying was summarized in detail. Different from previous reviews, the renewal iteration of core-shell structural materials was highlighted, and relevant illustrations of their representative and latest research results were reviewed. With the continuous progress of nanocapsule technology, especially the continuous development of new wall materials and catalysts, new preparation technology, and new production equipment, nanocapsule technology will be used more widely in medicine, food, cosmetics, pesticides, petroleum products, and many other fields.

Cost-utility analysis of trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer in Chinese setting.

PURPOSE: Trastuzumab deruxtecan (T-DXd) expressed substantial improvement in the progression-free survival and overall survival contrasted with trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer (mBC), becoming the second-line standard of care, promisingly. We aim to estimate the cost-utility of T-DXd versus T-DM1 in HER2-positive mBC from the Chinese healthcare perspective. METHODS: A partitioned survival model was applied to examine the cost-utility of T-DXd versus T-DM1. Clinical patients and outcome data were sourced from the DESTINY-Breast 03 trial. Costs and utilities were sourced in Chinese setting. Total costs, quality-adjusted life months (QALMs), and an incremental cost-utility ratios (ICUR) were calculated for cost-utility analysis. The willingness-to-pay threshold was set at $3188/QALM. Univariate, scenario, and probabilistic sensitivity analyses were performed. RESULTS: T-DXd group gained ∆QALM of 7.09 months and ∆Cost of $304,503 compared with T-DM1 therapy, which caused an ICUR of $42,936/QALM. The results of sensitivity analyses confirmed the base-case findings. Furthermore, T-DXd must reduce the price to enter the Chinese mainland market. At least when the cycle cost of T-DXd is reduced to $2975, T-DXd has an 83.3% chance of becoming a better choice. CONCLUSIONS: T-DXd appears to be not cost effective compared with T-DM1 for HER2-positive mBC patients previously treated with trastuzumab and a taxane.

Main Habitat Factors Driving the Phenotypic Diversity of Litsea cubeba in China.

Litsea cubeba (Lour.) Pers. is an important woody spice tree in southern China, and its fruit is a rich source of valuable essential oil. We surveyed and sampled L. cubeba germplasm resources from 36 provenances in nine Chinese provinces, and detected rich phenotypic diversity. The survey results showed that plants of SC-KJ, SC-HJ, and SC-LS provenance presented higher leaf area (LA); YN-SM and YN-XC plants had larger thousand-grain fresh weight (TFW); and HN-DX plants had the highest essential oil content (EOC). To explain the large differences in the phenotypes of L. cubeba among different habitats, we used Pearson's correlation analysis, multiple stepwise regression path analysis, and redundancy analysis to evaluate the phenotypic diversity of L. cubeba. It was found that compared to other traits, leaf and fruit traits had more significant geographical distributions, and that leaf phenotypes were correlated to fruit phenotypes. The results showed that elevation, latitude, longitude, total soil porosity (SP), soil bulk density (SBD), and average annual rainfall (AAR, mm) contributed significantly to the phenotypic diversity of L. cubeba. Geographical factors explained a higher percentage of variation in phenotypic diversity than did soil factors and climate factors. Plants of SC-KJ and HN-DX provenances could be important resources for domestication and breeding to develop new high-yielding varieties of this woody aromatic plant. This study describes significant phenotypic differences in L. cubeba related to adaptation to different environments, and provides a theoretical basis for the development of a breeding strategy and for optimizing L. cubeba cultivation.

Efficacy and tolerability of the Subcutaneous Semaglutide for type 2 Diabetes patients: an updated systematic review and meta-analysis.

OBJECTIVES: To update and assess the efficacy and tolerability of once weekly subcutaneous semaglutide in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: PubMed, Science Direct, Cochrane Library, Clinical trial, Springer, OVID, China National Knowledge Infrastructure (CNKI), WanFang Data and China Science and Technology Journal Database (VIP) were searched from inception to January 18, 2023. Randomized controlled trials (RCTs) comparing subcutaneous semaglutide with placebo or any other antidiabetic agent in adults with T2D were eligible. The risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs) were determined to synthesize the results. RESULTS: A total of 17 trials enrolling 14,940 T2D patients were included. For efficacy, compared with placebo, semaglutide exhibited beneficial effects on glycosylated hemoglobin A1c (HbA1c) control [MD -0.97%, 95% CI (-1.33, -0.62), I2 = 91%; MD -1.36%, 95% CI (-1.59, -1.13), I2 = 84%, semaglutide 0.5 and 1.0 mg, respectively], body weight reduction, blood pressure control. At the same time, subcutaneous semaglutide 0.5 and 1 mg reduced HbA1c by 0.56% (95% CI 0.32 to 0.80) and 0.63% (95% CI 0.35 to 0.91) compared to other glucose-lowering agents. For tolerability, semaglutide did not increase the incidence of adverse events (AEs) and serious adverse events (SAEs), severe or blood glucose (BG) confirmed hypoglycaemia, acute pancreatitis and diabetic retinopathy compared to placebo or active comparators, but did increase the risk of nausea, diarrhea and vomiting. CONCLUSIONS: Semaglutide has a better effect on glycaemic control and weight loss than other therapies. Nevertheless, semaglutide was associated with increased incidence of gastrointestinal-related disorders. Further large, multicenter randomized controlled clinical trials are still needed to obtain more robust evidence to better guide clinical treatment decisions.

Efficacy of supervised pelvic floor muscle training with a home-based biofeedback device for urinary incontinence in postpartum women: protocol for a multicentre randomised controlled trial.

INTRODUCTION: Supervised pelvic floor muscle training (PFMT) of at least 3 months duration has been strongly recommended as a first-line treatment for women with stress urinary incontinence (SUI) or SUI-predominant mixed urinary incontinence (MUI), including elderly and postnatal women. However, for the treatment of SUI and MUI in postpartum women, it is currently uncertain whether supervised PFMT combined with a biofeedback device is superior to PFMT alone. Despite some supportive results, more reliable evidence is lacking. METHODS AND ANALYSIS: The study is designed as a multicentre assessor-blinded parallel-group randomised controlled trial comparing the efficacy of PFMT with a home-based pressure-mediated biofeedback device (intervention group) and that of at-home PFMT alone (control group) for women with new-onset SUI or SUI-predominant MUI after delivery. Five hundred eligible women from the obstetric outpatient clinics of five tertiary hospitals will be randomly allocated (1:1) and evaluated with repeated questionnaires, physical examinations and pelvic floor assessments at baseline (pretest), 3 months, 6 months and 12 months (postintervention) during the study period. Both groups will be instructed to follow the same training protocol under 3-month supervision after randomisation. The use of a biofeedback device with a self-assessment function will be added to the PFMT regime for patients in the intervention group. The primary outcome is the self-reported severity of urinary incontinence assessed through the short form of the International Consultation on Incontinence Questionnaire-Urinary Incontinence. Secondary outcomes include pelvic muscle support and strength, symptoms of pelvic organ prolapse, quality of life, sexual function, self-efficacy and adherence. ETHICS AND DISSEMINATION: Ethical approval has been received from the Peking Union Medical College Hospital ethics committee (JS-3192D). All results from the study will be submitted to international journals and international conferences. TRIAL REGISTRATION NUMBER: NCT05115864.

Heat-Denatured Lysozyme is a Novel Potential Non-alcoholic Disinfectant Against Respiratory Virus.

Respiratory diseases are significant recurrent threats to global public health. Since the 1918 Spanish flu pandemic, seasonal influenza viruses continue to cause epidemics around the world each year. More recently, the COVID-19 global pandemic conducted a public health crisis with more than 6 million deaths and it also severely affected the global economy. Due to the phenomenon that people get infection from objects carrying viruses, it has aroused people's attention to home disinfection. As there is no ideal existing common domestic disinfectant, new and safer antiviral disinfectants are urgently needed. Lysozyme is a natural antibacterial agent widespread in nature and widely used in healthcare and food industry because of is recognized safety. Recently, it has been shown that thermally denatured lysozyme has the ability to kill murine norovirus and hepatitis A virus. In our study, we also demonstrated that heat-denatured lysozyme (HDLz) had an antiviral effect against H1N1 influenza A virus, and we optimized its antiviral activities by testing different heating denaturation conditions, to generalize this property, using pseudotype virus neutralization assay, we found that HDLz can also inhibit the entry of H5N1, H5N6, and H7N1 avian influenza viruses as well as SARS-CoV and SARS-CoV-2 particles in cell with IC50 at the ng/mL range. Finally, using western blot analysis, we provide evidence that HDLz polymerization correlates with antiviral effect, which may be a precious possible quality control test. Altogether, our data support HDLz as a powerful anti-respiratory virus disinfectant as a sole or additive of current disinfectants to reduce concentration of toxic component.

Gilteritinib-induced severe immune-related enteritis: a possible case report.

Gilteritinib is currently approved in China for relapsed/refractory FLT3-mutated acute myeloid leukemia, and it is very important to monitor and report its adverse drug reaction (ADR) after post-marketing. This case report describes a patient who was diagnosed with acute myeloid leukemia harboring FLT3 mutations and developed a severe suspected immune-related enteritis during treatment with gilteritinib for maintenance therapy following allo-hematopoietic stem cell transplantation. According to the Naranjo probability scale, gilteritinib was defined as a 'possible' cause of ADR. Another suspicious inducement, graft-versus-host disease, can not be eluted and might represent a limitation in this case. To the best of our knowledge, this is the first report on gilteritinib-induced severe enteritis and will help physicians to keep vigilant, and detect and deal with time for possible ADR.

Exploring the components and mechanisms of Shen-qi-wang-mo granule in the treatment of retinal vein occlusion by UPLC-Triple TOF MS/MS and network pharmacology.

This study aimed to explore the substance basis and mechanisms of Shen-qi-wang-mo Granule (SQWMG), a traditional Chinese medicine prescription that had been clinically utilized to treat retinal vein occlusion (RVO) for 38 years. Components in SQWMG were analyzed by UPLC-Triple-TOF/MS and a total of 63 components were identified with ganoderic acids (GA) being the largest proportion. Potential targets of active components were retrieved from SwissTargetPrediction. RVO-related targets were acquired from related disease databases. Core targets of SQWMG against RVO were acquired by overlapping the above targets. The 66 components (including 5 isomers) and 169 targets were obtained and concluded into a component-target network. Together with biological enrichment analysis of targets, it revealed the crucial role of the "PI3K-Akt signaling pathway", "MAPK signaling pathway" and their downstream factor iNOS and TNF-α. The 20 key targets of SQWMG in treating RVO were acquired from the network and pathway analysis. The effects of SQWMG on targets and pathways were validated by molecular docking based on AutoDock Vina and qPCR experiment. The molecular docking showed great affinity for these components and targets, especially on ganoderic acids (GA) and alisols (AS), which were both triterpenoids and qPCR exhibited remarkably reduced inflammatory factor gene expression through regulation of these two pathways. Finally, the key components were also identified from rat serum after treatment of SQWMG.

Safety Profile of Eltrombopag in Different Age Groups: An Analysis of Real-World Pharmacovigilance and Randomized Clinical Trials.

Eltrombopag is clinically approved for use in immune thrombocytopenia (ITP), chronic hepatitis C-related thrombocytopenia, and aplastic anemia and suitable for children; however, data on its overall safety profile are scarce. This study aimed to explore the clinical features of adverse drug events (ADEs) associated with eltrombopag in different age groups using individual case safety reports (ICSRs) from the World Health Organization database VigiBase and the US Food and Drug Administration Adverse Event Reporting System database from 2008 to 2022 in combination with a meta-analysis of data from randomized clinical trials in the literature from inception to July 28, 2022. We conducted disproportionality analyses by grouping patients into the following age groups: 0-17 (0-23 months, 2-11 years, and 12-17 years), 18-64, and ≥ 65 years. The ADEs about hepatobiliary disorders, thrombosis, skin and subcutaneous tissue disorders, infections, and so on were observed more differently in each age group. Meta-analysis results showed differences in the four system organ classes between adults and children with ITP: infections and infestations, general disorders and administration site conditions, skin and subcutaneous tissue disorders, and investigations. The adverse drug reactions in the latest version of instructions were searched in the databases to analyze their postmarketing safety signal strength. We observed signals of elevated alanine aminotransferase, aspartate aminotransferase, and blood bilirubin levels in all age groups. For children, urinary tract infection and back pain showed signals. Due to the inherent limitations of pharmacovigilance studies, more experiments are needed to assess the risks of eltrombopag in different ages.

Simultaneous online SPE-HPLC-MS/MS quantification of gefitinib, osimertinib and icotinib in dried plasma spots: Application to therapeutic drug monitoring in patients with non-small cell lung cancer.

Gefitinib, osimertinib and icotinib are the most commonly used tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) with EGFR mutation. Therapeutic drug monitoring (TDM) for these TKIs has become a standard and essential procedure. Dried plasma spots (DPS) was choosen for microsampling strategies for TDM, allowing easy and cost-effective logistics in many settings. This study developd and validated an assay for the simultaneous quantitative determination of gefitinib, osimertinib and icotinib in DPS by online solid-phase extraction-liquid chromatography-tandem mass spectrometry (online SPE-LC-MS) system. The TKIs were extracted from DPS with methanol and enriched on a Welch Polar-RP SPE column (30 × 4.6 mm, 5 µm), followed by separation on Waters X Bridge C18 analytical column(4.6 × 100 mm, 3.5 µm). The method achieved LLOQ of 2 ng mL-1 for gefitinib and osimertinib (4 ng mL-1 for icotinib), respectively (r2 > 0.99). Precision (within-run 1.54-7.41 % RSD; between-run 3.03-12.84 % RSD), accuracy (range from 81.47 % to 105.08 %; between-run bias 87.87-104.13 %). Osimertinib and icotinib were stable in DPS stored at - 40 °C for 30 days, 4 °C, 42 °C and 60 °C for 5 days and well-sealed 37 °C,75 % humidity (except gefitinib). Lastly, the assay was applied to TDM of TKIs in 46 patients and the results were compared to SALLE assisted LC-MS analysis, it could be confirmed that the developed method achieves similarly good results as the already established one and no bias could be detected. It implies that this method capable of supporting clinical follow-up TDM of TKIs in DPS from poor medical environment.

Quantitative Analysis of Camellia oleifera Seed Saponins and Aqueous Two-Phase Extraction and Separation.

At present, the technology used for the extraction and purification of Camellia oleifera saponins generally has the problems of high cost and low purity, and the quantitative detection of Camellia oleifera saponins also has the problems of low sensitivity and easy interference from impurities. To solve these problems, this paper aimed to use liquid chromatography for the quantitative detection of Camellia oleifera saponins, and to adjust and optimize the related conditions. In our study, the average recovery of Camellia oleifera saponins obtained was 100.42%. The RSD of precision test was 0.41%. The RSD of the repeatability test was 0.22%. The detection limit of the liquid chromatography was 0.06 mg/L, and the quantification limit was 0.2 mg/L. In order to improve the yield and purity, the Camellia oleifera saponins were extracted from Camellia oleifera Abel. seed meal by methanol extraction. Then, the extracted Camellia oleifera saponins were extracted with an ammonium sulfate/propanol aqueous two-phase system. We optimized the purification process of formaldehyde extraction and aqueous two-phase extraction. Under the optimal purification process, the purity of Camellia oleifera saponins extracted by methanol was 36.15%, and the yield was 25.24%. The purity of Camellia oleifera saponins obtained by aqueous two-phase extraction was 83.72%. Thus, this study can provide a reference standard for rapid and efficient detection and analysis of Camellia oleifera saponins for industrial extraction and purification.

Nitrogen Doped Porous Biochar/ß-CD-MOFs Heterostructures: Bi-Functional Material for Highly Sensitive Electrochemical Detection and Removal of Acetaminophen.

Acetaminophen (AC) is one of the most common over-the-counter drugs, and its pollutant in groundwater has attracted more attention due to its serious risk to human health. Currently, the research on AC is mainly focused on its detection, but few are concerned about its removal. In this work, for the first time, nitrogen-doped Soulangeana sepals derived biochar/ß-cyclodextrin-Metal-organic frameworks (N-SC/ß-CD-MOFs) composite was proposed for the simultaneous efficient removal and detection of AC. N-SC/ß-CD-MOFs combined the properties of host-guest recognition of ß-CD-MOFs and porous structure, high porosity, and large surface area of N-SC. Their synergies endowed N-SC/ß-CD-MOFs with a high adsorption capacity toward AC, which was up to 66.43 mg/g. The adsorption type of AC on the surface of N-SC/ß-CD-MOFs conformed to the Langmuir adsorption model, and the study of the adsorption mechanism showed that AC adsorption on N-SC was mainly achieved through hydrogen bonding. In addition, the high conductivity, large specific surface area and abundant active sites of N-SC/ß-CD-MOFs were of great significance to the high-performance detection of AC. Accordingly, the sensor prepared with N-SC/ß-CD-MOFs presented a wide linear range (1.0-30.0 µM) and a low limit of detection of 0.3 nM (S/N = 3). These excellent performances demonstrate that N-SC/ß-CD-MOFs could act as an efficient dual-functional material for the detection and removal of AC.

Novel Design of Citral-Thiourea Derivatives for Enhancing Antifungal Potential against Colletotrichum gloeosporioides.

Although much progress has been made in developing botanical fungicides to combat fungal diseases in crops, there remains a great need to improve the efficiency and long-term safety of these fungicides. This study proposes a novel strategy for designing citral-thiourea derivatives that feature such desirable properties. The motivation of the work herein was to enhance the antifungal activity of citral against C. gloeosprioides by exploiting the synergistic effect that arises from combining citral and thiourea compounds, thereby producing citral-thiourea derivatives that exhibit good long-term safety. The results revealed that the generated compounds e1, e3, e6, e18, and g showed remarkable antifungal activities against C. gloeosprioides, with corresponding EC50 values reaching 0.16, 1.66, 1.37, 4.76, and 4.60 mg/L, respectively, showing that the compounds significantly outperformed both the positive control kresoxim-methyl and the commercially available fungicide carbendazim. Furthermore, compound g showed stronger protective efficacy against C. gloeosprioides than carbendazim on mango fruit at 25 mg/L. Investigating the preliminary structure-activity relationship (SAR) of the compounds also revealed that the citral-thiourea derivatives exhibited higher antifungal activities against C. gloeosprioides compared to citral and thiourea compounds. This reinforcement of antifungal activity observed in the derivatives was found to be attributable to the two characteristics of low molecular size and the presence of a fluorine atom in the meta-position of the benzene ring. Beyond this, it was determined from QSAR that two molecular descriptors (the Kier-Hall index (order 3) and Tot dipole of the molecules) were negatively related to the antifungal activity of the citral-thiourea derivatives, while one other (the maximum resonance energy of a C-H bond) was positively related to their antifungal activity. More importantly, the citral-thiourea derivatives with high antifungal activities (i.e., compounds e1, e3, e6, e14, e15, e18, and g) exhibited negligible cytotoxicity to LO2 and HEK293T cell lines. The antifungal mechanism of the generated citral-thiourea derivatives was investigated by scanning electron microscopy (SEM) and relative conductivity. The derivatives were found to affect mycelial morphology and increase fungal cell membrane permeability, thereby resulting in the destruction of fungal cell membranes. These promising results provide novel insights into the study and potential application value of citral-thiourea derivatives as high-efficiency antifungal agents against C. gloeosprioides.

Bidirectional association between NAFLD and gallstone disease: a systematic review and meta-analysis of observational studies.

BACKGROUND: Growing evidence indicates an association between NAFLD and gallstone disease (GD), while some does not support this. The aim of this meta-analysis was to evaluate the bidirectional association between NAFLD and GD. RESEARCH DESIGN AND METHODS: Five electronic databases were searched from inception to May 2022. The association was analyzed based on the odds ratio (OR) and 95% confidence interval (CI) with Reviewer Manager 5.3. RESULTS: Ten studies involving 284,512 participants met the criteria for GD predicting the onset of NAFLD. GD patients had a higher incidence of NAFLD (OR:1.48, CI:1.32-1.65, p < 0.00001), especially the incidence of moderate-to-severe NAFLD (OR:1.63; CI:1.40-1.79), with females at a higher risk (OR: 1.84; CI: 1.48-2.29). The inverse association was explored in eight studies involving 326,922 participants. The GD incidence in NAFLD patients was higher (OR:1.71, CI:1.63-1.79, p < 0.00001) and may increase due to female sex (OR: 4.18; CI: 1.21-14.37) and high BMI (OR: 1.80; CI: 1.36-2.56), compared with the non-NAFLD group. Besides, this bidirectional association was also confirmed in the Chinese population. CONCLUSIONS: The findings supported positive concurrent and bidirectional relationships between NAFLD and GD. Therefore, clinicians may alert the possibility of NAFLD in patients with GD and vice versa.