Toxicity Study on Crude Alkaloid Extracts of Houttuyniae herba Based on Zebrafish and Mice.

Houttuyniae herba has a long history of medicinal and edible homology in China. It has the functions of clearing heat and detoxifying, reducing swelling and purulent discharge, diuresis, and relieving gonorrhea. It is mainly distributed in the central, southeastern, and southwestern provinces of China. Houttuyniae herba has been designated by the National Ministry of Health of China as a dual-use plant for both food and medicine. Comprising volatile oils, flavonoids, and alkaloids as its primary constituents, Houttuyniae herba harbors aristolactams, a prominent subclass of alkaloids. Notably, the structural affinity of aristolactams to aristolochic acids is discernible, the latter known for its explicit toxicological effects. Additionally, the safety study on Houttuyniae herba mainly focused on the ethanol, methanol, or aqueous extract. In this study, both zebrafish and mice were used to evaluate the acute toxicity of the total alkaloids extracts from Houttuyniae herba (HHTAE). The zebrafish experiment showed that a high concentration (0.1 mg/mL) of HHTAE had a lethal effect on zebrafish embryos. Furthermore, the mice experiment results showed that, even at a higher dose of 2000 mg/kg, HHTAE was not toxic. In conclusion, HHTAE was of low safety risk.

Transcatheter arterial chemoembolisation combined with lenvatinib and cabozantinib in the treatment of advanced hepatocellular carcinoma.

OBJECTIVE: The objective of this study was to evaluate the effect and prognosis of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and cabozantinib in the treatment of advanced unresectable hepatocellular carcinoma (uHCC) and identify the predictors of prognosis related to cellular inflammation and body mass index (BMI). To the best of our knowledge, this is the first study to report the efficacy and prognosis of TACE combined with lenvatinib and cabozantinib in patients with uHCC and propose the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as predictors of response and survival outcomes in this context. METHODS: The clinicopathologic data of 217 patients with advanced uHCC who underwent TACE combined with systemic therapy (lenvatinib mesylate + cabozantinib) in the Department of Hepatobiliary Surgery, Dazhou Central Hospital between October 2017 and February 2020 were collected retrospectively, and the relevant parameters were analysed and compared. RESULTS: Univariate and multivariate logistic regression analyses showed that BMI, NLR, PLR and prothrombin time were independent factors for the objective response rate (ORR) of transformed therapy for uHCC (OR = 0.812 vs 1,290.68 vs 1.067 vs 0.626, 95 % CI: 0.719-0.897 vs 108.081-11,541.137 vs 1.037-1.099 vs 0.414-0.946, respectively, p < 0.05). The results showed that BMI, NLR and PLR had certain predictive values for the ORR in patients with liver cancer undergoing translational therapy (p < 0.05); the combined predictive effect of the three was the best, and the area under the curve (AUC) of BMI + NLR + PLR for predicting the ORR in patients with liver cancer undergoing translational therapy was 0.951 (95 % CI: 0.921, 0.964). A total of 181 patients experienced adverse reactions at different grades, including 104 cases at grade 1, 50 cases at grade 2, 22 cases at grade 3 and 5 cases at grade 4. There was a significant difference in overall survival (OS) between low- and high-NLR groups, low- and high-PLR groups and low- and high-BMI groups (χ2 = 9.644, 8.313 and 10.314, respectively, p < 0.05). There was a significant difference in progression-free survival (PFS) between the low- and high-NLR groups, the low- and high-PLR groups and the low- and high-BMI groups (χ2 = 8.965, 9.783 and 6.343, respectively, p < 0.05). CONCLUSION: Transcatheter arterial chemoembolisation combined with lenvatinib and cabozantinib is safe and effective in the treatment of advanced uHCC, with controllable adverse reactions. High NLR and PLR and low BMI values before treatment were independent risk factors for the ORR. Body mass index, NLR and PLR predicted responses to triple switch therapy and survival outcomes in uHCC. Patients with pretreatment NLR ≥ 2.96 and PLR ≥ 184.41 had worse OS and PFS rates. Patients with pretreatment BMI ≥ 23 kg/m2 had improved OS and a reduced risk of death.

New Transition Metal Coordination Polymers Derived from 2-(3,5-Dicarboxyphenyl)-6-carboxybenzimidazole as Photocatalysts for Dye and Antibiotic Decomposition.

Coordination polymers (CPs) are an assorted class of coordination complexes that are gaining attention for the safe and sustainable removal of organic dyes from wastewater discharge by either adsorption or photocatalytic degradation. Herein, three different coordination polymers with compositions [Ni(HL)(H2O)2·1.9H2O] (1), [Mn3(HL)(L)(µ3-OH)(H2O)(phen)2·2H2O] (2), and [Cd(HL)4(H2O)]·H2O (3) (H3L = 2-(3,5-dicarboxyphenyl)-6-carboxybenzimidazole; phen = 1,10-phenanthroline) have been synthesized and characterized spectroscopically and by single crystal X-ray diffraction. Single crystal X-ray diffraction results indicated that 1 forms a 2D layer-like framework, while 2 exhibits a 3-connected net with the Schläfli symbol of (44.6), and 3 displays a 3D supramolecular network in which two adjacent 2D layers are held by π···π interactions. All three compounds have been used as photocatalysts to catalyze the photodegradation of antibiotic dinitrozole (DTZ) and rhodamine B (RhB). The photocatalytic results suggested that the Mn-based CP 2 exhibited better photodecomposition of DTZ (91.1%) and RhB (95.0%) than the other two CPs in the time span of 45 min. The observed photocatalytic mechanisms have been addressed using Hirshfeld surface analyses.

[Driving Factors Analyze of Phytoplankton Community by Comparison of Population and Functional Groups and Water Quality Evaluation in Dongting Lake].

Phytoplankton is the most important component of water ecosystems, which could indicate the state of the water environment owing to its sensitivity to water environment variation. However, its response to the environment is influenced by classification methods. To understand the phytoplankton population(phyla and genera) and functional groups(FG) for driving response characteristics and applicability to the environment in Dongting Lake, a total of four samples were collected from the lake from March to December 2019, and the distribution characteristics of the phytoplankton population and functional groups and their responses to environmental factors were compared and analyzed. Meanwhile, the applicability of the TLI index, Shannon-Wiener index, and Q index was compared in Dongting Lake. The results showed that a total of 61 genera belonging to six phyla of phytoplankton were detected in Dongting Lake, which could be divided into 23 functional groups and nine dominant functional groups. The succession trend of functional groups was P/MP/D(March)→MP/P/J(June)→MP/H1(September)→Y/P/MP(December). The results of hierarchical segmentation showed that the population distribution and change in phytoplankton were driven by environmental factors more than the area in Dongting Lake. The main environmental factors affecting phytoplankton population and functional groups were water temperature(WT), permanganate index, dissolved oxygen(DO), conductivity(Cond), water level(WL), and total phosphorus(TP). RDA analysis showed that phytoplankton functional groups identified phytoplankton response to environmental factors better than phytoplankton population. It was shown that using the Q index to evaluate water quality had better applicability in Dongting Lake.

Resolvin D1 Induces mTOR-independent and ATG5-dependent Autophagy in BV-2 Microglial Cells.

OBJECTIVE: The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation. Autophagy is a catabolic process responsible for maintaining cellular homeostasis. In recent years, autophagy has been demonstrated to play an important role in neuroinflammation. Resolvin D1 (RvD1) is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities. However, whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation. The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways. METHODS: Mouse microglial cells (BV-2) were cultured, treated with RvD1, and examined by Western blotting, confocal immunofluorescence microscopy, transmission electron microscopy, and flow cytometry. RESULTS: RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes. Importantly, RvD1 had no significant effect on the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II (CaMK II) activation. Moreover, by downregulating ATG5, the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy. CONCLUSION: The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy, highlighting its therapeutic potential against neuroinflammation.

Secondary Mycobacterium abscessus Infection after Debridement in Child with Dog Bite: a Case Report.

BACKGROUND: In recent years, there have been increasing reports related to infection caused by Mycobacterium abscessus (MAB). As one of the most common mycobacterium iatrogenic infections, it is characterized by pulmonary infection. However, only a few reports of MAB-related skin and soft tissue infections are available. This study reported a 3-year-old child admitted to our hospital for a dog bite with MAB infection after debridement. METHODS: The diagnosis of MAB in this child was made after detecting the bacteria in the wound secretion based on secretion culture in clinical laboratory. RESULTS: The result of the first bacterial isolation and culture of wound secretion was negative. However, the results were positive two days later and was diagnosed as MAB infection for samples of the purulent secretions collected by puncture and aspiration during debridement from the red and swollen regions of the thigh. The drug sensitivity results suggested that the child was sensitive to cefoxitin. However, she was resistant to amikacin, linezolid, minocycline, imipenem, tobramycin, moxifloxacin, clarithromycin, and doxycycline. The combined treatment strategy was used for managing MAB infection with a good effect. CONCLUSIONS: The management of MAB soft tissue infection has limitations, like poor tolerance, toxicity, and mul¬ti-drug interaction. The combined treatment strategy is important for MAB infection, and monitoring adverse re-actions and toxicity is the key.

Combined chemo-endocrine therapy as a potential new option for HR+/HER2- advanced breast cancer: a prospective study of fulvestrant plus oral vinorelbine.

OBJECTIVE: Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro. This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) recurrent or metastatic breast cancer. METHODS: Patients were intramuscularly administered fulvestrant 500 mg (day 1 per cycle for 28 days) and oral vinorelbine (60 mg/m2 on days 1, 8, and 15 of each cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, objective response rate, disease control rate, duration of response, and safety. RESULTS: A total of 38 patients with HR+/HER2- advanced breast cancer included in the study were followed up for a median time of 25.1 months. The overall median PFS was 9.86 months [95% confidence interval (CI) 7.2-23.13], and the median PFS of the first-line and the second-line treatment population was 20.73 months (95% CI 9.82 to NR) and 4.27 months (95% CI 3.68 to NR), respectively. Most adverse events reported were of grade 1/2, and none were of grade 4/5. CONCLUSIONS: This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2- recurrent and metastatic breast cancer. The combination chemo-endocrine therapy was efficacious, safe, and promising for patients with HR+/HER2- advanced breast cancer.

ADAMTS4 Enhances Oligodendrocyte Differentiation and Remyelination by Cleaving NG2 Proteoglycan and Attenuating PDGFRα Signaling.

Although NG2 is known to be selectively expressed in oligodendrocyte precursor cells (OPCs) for many years, its expressional regulation and functional involvement in oligodendrocyte differentiation have remained elusive. Here, we report that the surface-bound NG2 proteoglycan can physically bind to PDGF-AA and enhances PDGF receptor alpha (PDGFRα) activation of downstream signaling. During differentiation stage, NG2 protein is cleaved by A disintegrin and metalloproteinase with thrombospondin motifs type 4 (Adamts4), which is highly upregulated in differentiating OPCs but gradually downregulated in mature myelinating oligodendrocytes. Genetic ablation of Adamts4 gene impedes NG2 proteolysis, leading to elevated PDGFRα signaling but impaired oligodendrocyte differentiation and axonal myelination in both sexes of mice. Moreover, Adamts4 deficiency also lessens myelin repair in adult brain tissue following Lysophosphatidylcholine-induced demyelination. Thus, Adamts4 could be a potential therapeutic target for enhancing oligodendrocyte differentiation and axonal remyelination in demyelinating diseases.SIGNIFICANCE STATEMENT NG2 is selectively expressed in OPCs and downregulated during differentiation stage. To date, the molecular mechanism underlying the progressive removal of NG2 surface proteoglycan in differentiating OPCs has been unknown. In this study, we demonstrate that ADAMTS4 released by differentiating OPCs cleaves surface NG2 proteoglycan, attenuates PDGFRα signaling, and accelerates oligodendrocyte differentiation. In addition, our study also suggests ADAMTS4 as a potential therapeutic target for promoting myelin recovery in demyelinating diseases.

Effect of Anterior Cervical Decompression Fusion and Partial Resection of Uncinate Vertebra Joint on Cervical Sagittal Sequence in Patients with Non-Single-Segment Radiculopathy and its Correlation with Curative Effect: A Retrospective Analysis.

OBJECTIVE: Analyze the effect of preservation or resection of the partial uncinate joint on the sagittal sequence of the cervical vertebrae in patients with non-single-segment radiculopathy and the correlation between the sagittal sequence of the cervical vertebrae and the long-term effect after surgery, we explored whether it is necessary to perform partial resection of the uncinate joint in patients with cervical spondylotic radiculopathy undergoing anterior cervical decompression and fusion (ACDF). METHODS: The study retrospectively analyzed 96 patients with cervical spondylotic radiculopathy with more than two segments from August 2016 to January 2021, who underwent ACDF (ACDF group, 45 patients) or ACDF combined with partial uncinate joint resection (ACDF + UT group, 51 patients). Partial resection of the uncinate joint indicated removal of part of the uncinate joint and osteophyte based on the compression of the nerve root during surgery, whereas the uncinate joints in the ACDF group were retained completely. The imaging data and functional scores of the two groups were recorded before surgery, 1 month after surgery, and at the last follow-up. A paired t-test or rank sum test was applied to analyze the data. In addition, the correlation between the imaging parameters and functional scores was validated using the Pearson's test. RESULTS: All 96 patients successfully completed the surgery and were followed up for at least 12 months, with an average follow-up time of 14 months. At the last follow-up, the pain visual analog scale (VAS), neck disability index (NDI), and neck pain and disability scale (NPAD) scores of the two groups were significantly lower than those before surgery, and the Japanese Orthopaedic Association (JOA) score was significantly higher than that before surgery. At the last follow-up, compared with the ACDF+UT group, the NDI and NPAD scores in the ACDF group decreased more significantly (p < 0.05), and C2-7SVA, △C2-7SVA (the difference between C2-7 SVA at last follow-up and before operation), and T1S values decreased significantly (p < 0.05). The C2-7 Cobb angle was positively correlated with the JOA score and T1S (p < 0.05) and negatively correlated with the VAS, NDI, and NPAD scores and CGH-C7SVA (p < 0.05). C2-7SVA was positively correlated with CGH-C7SVA and T1S (p < 0.05). CONCLUSION: Patients with non-single-segmental cervical spondylotic radiculopathy and ACDF with or without uncinate joint resection can have effective improvement in the clinical effect and sagittal balance; however, partial uncinate joint resection has a certain negative impact on the long-term reconstruction of sagittal balance and long-term effects in patients after surgery.

A Combination of In Silico ADMET Prediction, In Vivo Toxicity Evaluation, and Potential Mechanism Exploration of Brucine and Brucine N-oxide-A Comparative Study.

Brucine (BRU) and brucine N-oxide (BNO) are prominent, bioactive, and toxic alkaloids in crude and processed Semen Strychni. Studies have demonstrated that BRU and BNO possess comprehensive pharmacological activities, such as anti-inflammatory and analgesic. In this context, a comparative study of BRU and BNO was performed by combination analysis of in silico ADMET prediction, in vivo toxicity evaluation, and potential action mechanism exploration. ADMET prediction showed that BRU and BNO might induce liver injury, and BRU may have a stronger hepatoxic effect. The prediction was experimentally verified using the zebrafish model. The BRU-induced hepatotoxicity of zebrafish larvae had a dose-response relationship. The mechanism of BRU-induced hepatotoxicity might relate to phosphorylation, kinase activity, and signal transduction. By comparison, signal transduction and gap junctions might involve BNO-induced hepatotoxicity. Our results provided a better understanding of BRU- and BNO-induced hepatotoxicity. We also built a foundation to elucidate the material base of the hepatotoxicity of traditional Chinese medicine Semen Strychni.

Rapid Analysis of Aristolochic Acids and Aristolactams in Houttuyniae Herba by LC-MS/MS.

Houttuyniae herba, the Saururaceae plant Houttuynia cordata Thunb., has multiple therapeutic effects, including clearing heat, eliminating toxins, reducing swelling, discharging pus, and relieving stagnation. It has a long history as an edible and medicinal plant in China. Phytochemical studies show that the main constituents include volatile oil, flavonoids, and alkaloids. Aristolactam is a major alkaloid with a structure similar to toxic aristolochic acids. However, there has been no systematic study on aristolochic acids and alkaloids in Houttuyniae herba. Therefore, in this study, an LC-MS/MS method was developed to simultaneously detect seven alkaloids and five aristolochic acids in Houttuyniae herba from different origins. Six alkaloids (O-demethyl nornucifrine, N-nornucifrine, aristololactam AII, aristololactam FI, aristololactam BII, cepharadione B) were found and quantitatively determined in 75 batches of samples. Meanwhile, no aristolochic acids or aristololactams were found in Houttuyniae herba at a limit of detection (LOD) of ≤4 ng/mL. The method developed was fully validated in terms of LOD, limit of quantification (LOQ), linearity, precision, accuracy, and stability. These data clarify the content of the above safety-related components in Houttuyniae herba and provide a reference for further research into its safety.

Hidden blood loss of minimally invasive hybrid lumbar interbody fusion: an analysis of influencing factors.

BACKGROUND: Lumbar interbody fusion(LIF) is the leading way to treat Lumbar Degenerative Diseases(LDD). At present, there is a lack of research on the influencing factors of hidden blood loss in minimally invasive hybrid lumbar interbody fusion. This study comprehensively explores the definite factors affecting the hidden blood loss in minimally invasive hybrid lumbar interbody fusion. MATERIALS AND METHODS: One hundred patients with Lumbar degenerative diseases who underwent minimally invasive hybrid lumbar interbody fusion in our center were included. Demographics, laboratory data, surgical data, and radiographic data were collected. The Gross equation and Sehat equation were used to calculate the estimated value of hidden blood loss. Multi-factor linear regression analysis was used to determine the influencing factors of hidden blood loss. RESULT: We reviewed and collected 100 patients who underwent minimally invasive hybrid approach, mean age 65 ± 10 years, male: female 37:63; 17 patients of diabetes and 83 patients of non-diabetes; Total blood loss was 645.59 ± 376.37 ml, hidden blood loss was 421.39 ± 337.45 ml, the hidden blood loss percentage was 57 ± 26%. Results from the multi-factorial linear regression model: Diabetes (p < 0.05), hypertension (p < 0.05), psoas thickness (p < 0.05) and dorsal extensor group thickness (p < 0.05) were potential risk factors for postoperative hidden blood loss. CONCLUSION: Although minimally invasive hybrid approach is minimally invasive surgery, there is still a significant amount of hidden blood loss. There is a greater risk of blood loss in diabetes, hypertension and preoperative MRI assessment of thickness of the psoas, thickness of the dorsal extensor group.

Recent Advances of Silver-Based Coordination Polymers on Antibacterial Applications.

With the continuous evolution of bacteria and the constant use of traditional antibiotics, the emergence of drug-resistant bacteria and super viruses has attracted worldwide attention. Antimicrobial therapy has become the most popular and important research field at present. Coordination Polymer (CP) and/or metal-organic framework (MOF) platforms have the advantages of a high biocompatibility, biodegradability, and non-toxicity, have a great antibacterial potential and have been widely used in antibacterial treatment. This paper reviewed the mechanism and antibacterial effect of three typical MOFs (pure Ag-MOFs, hybrid Ag-MOFs, and Ag-containing-polymer @MOFs) in silver-based coordination polymers. At the same time, the existing shortcomings and future views are briefly discussed. The study on the antibacterial efficacy and mechanism of Ag-MOFs can provide a better basis for its clinical application and, meanwhile, open up a novel strategy for the preparation of more advanced Ag-contained materials with antibacterial characteristics.

[Spectral characteristics of sesquiterpene pyridine alkaloids from Tripterygium plants].

Sesquiterpene pyridine alkaloids are important components in Tripterygium plants, possessing a wide range of pharmacological activities, such as anti-inflammation immunosuppression, anti-tumor, anti-virus, and deinsectization, and are of great research value. They are composed of highly oxidized dihydro-ß-furansquiterpene and pyridine dicarboxylic acid through ester bonds. According to the structural characteristics of pyridine dicarboxylic acid fragments, they can be divided into various structural subtypes. Up to now, more than 110 sesquiterpene pyridine alkaloids have been isolated and identified from Tripterygium plants. This study reviewed the structural features and spectral(i.e., UV, IR, MS, and NMR) characteristics of sesquiterpene pyridine alkaloids and summarized the structural elucidation process in detail to provide references for their further research and development.

Discovery and molecular elucidation of the anti-influenza material basis of Banlangen granules based on biological activities and ultra-high performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has a wide range of applications, including human healthcare-associated treatments and bioactive compound discovery. However, complex chemical systems present a significant challenge for chemical-material-based research and quality control. For instance, Banlangen (BLG) granules is a well-acknowledged TCM preparation widely used in clinical treatment of virus infection. However, its chemical basis of anti-influenza efficacy remains unclear. AIM OF THE STUDY: In the present study, a systematic discovery strategy for identifying anti-influenza molecules based on biological activities and chemical analysis was established to contribute to the molecular elucidation of the anti-influenza material basis of Banlangen granules. MATERIALS AND METHODS: Hemagglutinase inhibition (HAI) and neuraminidase inhibition (NAI) assays were used to compare the anti-influenza activities of different fractions of BLG granules against H1N1, H5N1 and H7N9 viruses. A comparative qualitative analysis of the chemical constituents in BLG granules and their fractions was performed using ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS), in which a multiple mass spectrometry database platform and three compound identification strategies were used. The association between anti-influenza activities and chemical constituent characteristics was analyzed using multiple stoichiometries and data comparison strategies. RESULTS: The results showed that the chromatography fractions F3 and F4 of the BLG granules had the highest anti-influenza activity. A total of 88 compounds were identified in the BLG granules, including 31 alkaloids, 16 organic acids, 10 nucleosides, 8 phenylpropanoids, 6 sulfur-containing compounds, 5 amino acids, 4 aromatic compounds, 3 aldehydes and ketones, 2 flavonoids, 1 alcohol, 1 carbohydrate, and 1 aliphatic compound. Out of these, 31 characteristic compounds were identified in fractions F3-F4 as candidate compounds with anti-influenza activity. Additionally, 6-methoxyquinoline and 4-guanidinobutanal were identified in BLG granules and its raw material (Isatidis Radix) for the first time. CONCLUSION: In this study, we proposed a systematic discovery strategy to thoroughly investigate the anti-influenza activity, chemical identification, and constituents-activity relationship of BLG granules. These data not only provided a deeper understanding of the molecular mechanism of the activity of BLG granules, but also presented a basis for the discovery of potential novel drug candidates and quality evaluation and control of BLG granules.

Comprehensive Evaluation of the Quality of Tripterygium Glycosides Tablets Based on Multi-Component Quantification Combined with an In Vitro Biological Assay.

Tripterygium glycosides tablets (TGTs) are widely used in clinical practice to treat rheumatoid arthritis and other autoimmune diseases, with significant beneficial effects but also high toxicity, necessitating rigorous quality evaluation and control. In current study, a rapid resolution liquid chromatography tandem electrospray ionization triple quadrupole mass spectrometry (RRLC-ESI-MS/MS) method was developed and validated for the quantitative analysis of 14 components of ten batches of TGTs produced by different manufacturers, including four diterpenoids, three triterpenoids, and seven sesquiterpene alkaloids. Meanwhile, the NO inhibition effects of these TGTs were evaluated in LPS-induced RAW264.7 cells for their downstream anti-inflammatory activities, as well as their cytotoxicity. The results indicate that the TGTs from different manufacturers showed poor quality consistency, as evidenced by large variations in chemical profiles and biological effects, which may increase the risks associated with clinical use. To improve the quality status of TGTs, it is crucial to identify indicator components whose characterization can accurately reflect the efficacy and toxicity of TGTs from which they were derived. Our study reveals that triptolide, triptoquinone B, celastrol, and demethylzelaysteral considerably contributed to the anti-inflammatory activity and/or cytotoxicity of TGTs, implying that they should be further investigated as candidate indicator components for TGT quality control.

Desorption Electrospray Ionization Mass Spectrometry Imaging Illustrates the Quality Characters of Isatidis Radix.

For a long history, herbal medicines have made significant contributions to human health all around the world. However, the exploration of an effective approach to illustrate their inner quality remains a challenge. So, it is imperative to develop new methods and technologies to characterize and identify quality markers of herbal medicines. Taking Isatidis Radix, the dried root of Isatis indigotica as an example, desorption electrospray ionization (DESI), in combination with quadrupole-time-of-flight mass spectrometry (Q-TOF/MS), was applied in this work for the first time to reveal the comprehensive spatial distribution of metabolites and, further, to illustrate quality characters of this herbal medicine. After simple pretreatment, 102 metabolites including alkaloids, sulfur-containing compounds, phenylpropanoids, nucleosides, amino acids, organic acids, flavonoids, phenols, terpenes, saccharides, peptides, and sphingolipids were characterized, some of which were successfully localized and visualized in the transverse section of the root. Based on the ion images, samples with different quality characters were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 11 major influencing components exerting higher ion intensities in superior samples were identified as the potential quality markers of Isatidis Radix. Desorption electrospray ionization (DESI) mass spectrometry imaging (MSI), together with chemometric analysis could not only improve the understanding of the plant biology of herbal medicines but also be beneficial in the identification of quality markers, so as to carry out better quality control of herbal medicines.

Effect of tibial component overhang on survivorship in medial mobile-bearing unicompartmental knee arthroplasty.

BACKGROUND: Some studies have shown that the position of the tibial component in Oxford unicompartmental knee arthroplasty with a mobile bearing will affect the clinical outcome of patients. Hence, our study aimed to investigate the relationship between the overhang distance of the tibial component and the survival of the implant. METHODS: A retrospective analysis of patients who underwent unicompartmental knee arthroplasty at the same institution from 2014 to 2018 was presented. The study was divided into three groups: minor underhang group (underhang between -3 and 0 mm); minor overhang group (overhang 0-3 mm); and major overhang group (overhang ≥ 3 mm). Demographic and clinical profile characteristics of each group were compared, and survival curves of each group were also compared using Kaplan-Meier and modeled using multivariate Cox regression. RESULTS: A total of 351 knees were included in this study with a minimum follow up of three years and a mean follow up of 4.8 ± 1.5 years. The revision rates in each group were 3.6% (minor underhang group), 2.7% (minor overhang group), and 20.9% (major overhang group) (P < 0.001). From the three groups' cumulative survival rates, the major overhang group was significantly lower than the other two groups (log rank P < 0.001). Multivariate Cox regression showed an association between the major overhang group and implant survival rate (hazard ratio = 7.515, 95% confidence interval = 2.500-22.593, P < 0.001) CONCLUSION: The risk of revision will increase if the tibial component overhangs more than 3 mm medially. Moreover, the reasons for revision are generally bearing dislocation and aseptic loosening.

SECISBP2L-Mediated Selenoprotein Synthesis Is Essential for Autonomous Regulation of Oligodendrocyte Differentiation.

Thyroid hormone (TH) controls the timely differentiation of oligodendrocytes (OLs), and its deficiency can delay myelin development and cause mental retardation. Previous studies showed that the active TH T3 is converted from its prohormone T4 by the selenoprotein DIO2, whose mRNA is primarily expressed in astrocytes in the CNS. In the present study, we discovered that SECISBP2L is highly expressed in differentiating OLs and is required for DIO2 translation. Conditional knock-out (CKO) of Secisbp2l in OL lineage resulted in a decreased level of DIO2 and T3, accompanied by impaired OL differentiation, hypomyelination and motor deficits in both sexes of mice. Moreover, the defective differentiation of OLs in Secisbp2l mutants can be alleviated by T3 or its analog, but not the prohormone T4. The present study has provided strong evidence for the autonomous regulation of OL differentiation by its intrinsic T3 production mediated by the novel SECISBP2L-DIO2-T3 pathway during myelin development.SIGNIFICANCE STATEMENT Secisbp2l is specifically expressed in differentiating oligodendrocytes (OLs) and is essential for selenoprotein translation in OLs. Secisbp2l regulates Dio2 translation for active thyroid hormone (TH) T3 production in the CNS. Autonomous regulation of OLs differentiation via SECISBP2L-DIO2-T3 pathway.