Prognostic value of initial routine laboratory blood tests in patients with aneurysmal subarachnoid hemorrhage requiring mechanical ventilation: a retrospective cohort study.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) necessitating mechanical ventilation (MV) presents a serious challenge for intensivists. Laboratory blood tests reflect individual physiological and biochemical states, and provide a useful tool for identifying patients with critical condition and stratifying risk levels of death. This study aimed to determine the prognostic role of initial routine laboratory blood tests in these patients. Methods: This retrospective cohort study included 190 aSAH patients requiring MV in the neurosurgical intensive care unit from December 2019 to March 2022. Follow-up evaluation was performed in May 2022 via routine outpatient appointment or telephone interview. The primary outcomes were death occurring within 7 days after discharge (short-term mortality) or reported at time of follow-up (long-term mortality). Clinico-demographic and radiological characteristics, initial routine laboratory blood tests (e.g., metabolic panels and arterial blood gas analysis), and treatment were analyzed and compared in relation to mortality. Multivariable logistic and Cox regression analyses, with adjustment of other clinical predictors, were performed to determine independent laboratory test predictors for short- and long-term mortality, respectively. Results: The patients had a median age of 62 years, with a median World Federation of Neurosurgical Societies grade (WFNS) score of 5 and a median modified Fisher grade (mFisher) score of 4. The short- and long-term mortality of this cohort were 60.5% and 65.3%, respectively. Compared with survivors, non-survivors had more severe disease upon admission based on neurological status and imaging features and a shorter disease course, and were more likely to receive conservative treatment. Initial ionized calcium was found to be independently associate with both short-term [adjusted odds ratio (OR): 0.92; 95% confidence interval (CI): 0.86 to 0.99; P=0.020] and long-term mortality [adjusted hazard ratio (HR): 0.95; 95% CI: 0.92 to 0.99; P=0.010], after adjusting for potential confounders. Moreover, the admission glucose level was found to be associated only with short-term mortality (adjusted OR: 1.19; 95% CI: 1.06 to 1.34; P=0.004). Conclusions: Laboratory screening may provide a useful tool for the management of aSAH patients requiring MV in stratifying risk levels for mortality and for better clinical decision-making. Further study is needed to validate the effects of calcium supplementation and glucose-lowering therapy on the outcomes in this disease.

Ultrasound-guided acupotomy for trigger finger: a systematic review and meta-analysis.

BACKGROUND: Trigger finger is a common condition in the hand, and ultrasound-guided acupotomy for trigger finger has been widely used in recent years. PURPOSE: This study aims to investigate the efficacy and safety of ultrasound-guided acupotomy for trigger finger. METHODS: We searched for relevant studies in the Cochrane Library, China National Knowledge Infrastructure (CNKI), Embase, PubMed, Chinese Biomedical Literature Database (CBM), Wanfang Data, and other resources from their inception to January 2023. Randomized controlled trials of ultrasound-guided acupotomy for trigger finger were included. The meta-analysis was carried out using Review Manager 5.4 and Stata 15.1. RESULTS: Overall, 15 studies with 988 patients were included. The experimental group was treated with ultrasound-guided acupotomy, and the Control group received traditional acupotomy, traditional operation or injection of medication. Meta-analysis showed that the overall clinical effectiveness (OR = 4.83; 95% CI 2.49-9.37; I2 = 73.1%; P < 0.001) in the experimental group was significantly better than that of the control group. And the Visual Analogue Scale (VAS) score (WMD = - 1; 95% CI - 1.24, - 0.76; I2 = 99%; P < 0.001), the QuinneII classification (WMD = - 0.84; 95% CI - 1.28, - 0.39; I2 = 99.1%, P < 0.001), the incidence of complications (RR = 0.26; 95% CI 0.11, 0.63; I2 = 0%, P = 0.003), and the recurrence rate (RR = 0.14; 95% CI 0.03, 0.74; I2 = 0%; P = 0.021) were significantly lower in the experimental group. CONCLUSION: Our systematic review and meta-analysis can prove the effectiveness and safety of ultrasound-guided acupotomy in the treatment of trigger finger, but this still needs to be verified by a clinical standard large sample test.

[Hydrochemical Characteristics and Formation Causes of Ground Karst Water Systems in Gudui Spring Catchment].

As one of the famous karst springs in Shanxi Province, the Gudui spring is the only medium-low temperature hot spring, with a long history of development and a rich cultural accumulation. The karst groundwater in the Gudui spring catchment was taken as the research object. Through systematic sample collection and isotope analysis, hydrochemistry (Durov map, ion ratio, Gibbs map, and hydrogen and oxygen isotope) methods were comprehensively used to analyze groundwater hydrochemistry and groundwater system runoff characteristics. The87Sr/86Sr value of karst groundwater in the Gudui spring catchment was 0.709 to 0.717, and the Mg/(Mg+Ca) value was 0.27 to 0.74. By analyzing the Sr isotope composition and Mg/(Mg+Ca) and 1/Sr variation characteristics, it was concluded that the karst groundwater in the Gudui spring catchment was a mixture of deep hot water and shallow cold water. The karst water subsystem of Nanliang spring presented the characteristics of carbonate stratum runoff. The karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin exhibited the runoff characteristics of carbonate rock and igneous rock strata. The karst water subsystem of Taiershan Jiuyuanshan Gudui spring presented the runoff characteristics of carbonate rock and ancient silicoaluminate strata. The δ18O value in karst groundwater of Guodui spring area ranged from -11.46‰ to -7.81‰, and the average value was -10.08‰. The range of the δD value was -83.7‰ to -60.8‰, and the average value was -73.6‰. This showed that karst groundwater in the spring area was the result of mixing of various types of water. Through comparative analysis of hydrogen and oxygen isotopes of 2014 and 2021 sampling points at the same location, it was concluded that the change in water samples at the Guduiquan resulted from the gradual accumulation of water supplied by Sanquan Reservoir. The change in Sanquan Reservoir was due to the influence of Yellow River diversion. The karst groundwater in the spring area were characterized by large calcium ion, magnesium ion, and sodium ion values; a small potassium ion value; a large sulfate value; and a small chloride value. The hydrochemical types of karst groundwater in Gudui spring catchment could be divided into SO4-Na, SO4-Ca, HCO3-Na, HCO3-Mg, HCO3-Ca, and Cl-Na. The hydrochemical types of karst groundwater showed evident hydrochemical composition zoning from HCO3-Ca·Mg→HCO3·SO4-Ca·Mg→SO4·HCO3-Na·Ca→SO4·Cl-Na·Ca. According to the comprehensive analysis of hydrochemical isotope and hydrogeological conditions, the karst water subsystem of Nanliang spring was primarily recharged by rainfall infiltration in the exposed limestone area and river infiltration, and its karst groundwater was recharged by runoff from south to north to the karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin. The karst water subsystem of Taier Jiuyuan Mountain Gudui spring received rainfall infiltration supplement and upstream runoff supplement from the exposed limestone area. Its karst groundwater flowed from north to south and received the supply of Sanquan Reservoir from Yellow River water in the natural discharge area of Gudui spring.

Modulating endoplasmic reticulum stress in APP/PS1 mice by Gomisin B and Osthole in Bushen-Yizhi formula: Synergistic effects and therapeutic implications for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with no effective cure. Targeting endoplasmic reticulum (ER) stress pathway may offer a novel approach to ameliorate cognitive deficits in AD. Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine (TCM) prescription, has shown potential benefits for AD. To facilitate the development of new therapeutic agents for AD, it is important to identify the active components and the underlying mechanisms of BSYZ against AD. PURPOSE: The aim of this study was to systematically screen the active components of BSYZ that could improve learning and memory impairment in AD by modulating ER stress pathway. METHODS: A drug-target (D-T) network was constructed to analyze the herbal components of BSYZ. Network proximity method was used to identify the potential anti-AD components that targeted ER stress and evaluate their synergistic effects. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and the literature evidence were considered to select promising candidates for further validation. The selected components were tested in vitro using an AD cell model (APPswe-SH-SY5Y). In vivo anti-AD effects of the components were assessed in APP/PS1 double-transgenic mice. RESULTS: 58 potential anti-AD components targeting ER stress were detected by network proximity analysis, and 13 out of them were selected based on ADMET properties and literature evidence. In vitro experiments confirmed that 5 components, namely gomisin B, ß-Carotene, imperatorin, chrysophanol, and osthole (OST), exhibited anti-AD effects on the APPswe-SH-SY5Y model. Moreover, network proximity analysis suggested that OST and Gomisin B might have synergistic effects on modulating ER stress. In vivo experiments demonstrated that OST, Gomisin B, OST+Gomisin B, and BSYZ all improved learning and memory function in APP/PS1 mice. Gomisin B and OST also restored cellular morphology and tissue structure in APP/PS1 mice. Thioflavine-S (Th-S) staining revealed that they reduced amyloid plaque deposition in the brain tissue of AD model mice. The qPCR results indicated that BSYZ, OST, and Gomisin B differentially regulated IRE1α, PERK, EIF2α, DDIT3, and Caspase 12 expression levels, while the OST and Gomisin B co-administration group showed better efficacy. This trend was further confirmed by immunofluorescence experiments. CONCLUSION: This study identified the active components of BSYZ that could ameliorate learning and memory impairment in AD by targeting ER stress pathway. OST and Gomisin B exhibited synergistic effects on modulating ER stress and reducing amyloid plaque deposition in vivo. Overall, our study elucidated the molecular mechanisms of BSYZ and its active components in attenuating AD symptoms which suggested the therapeutic potential of TCM for AD.

Osthole/borneol thermosensitive gel via intranasal administration enhances intracerebral bioavailability to improve cognitive impairment in APP/PS1 transgenic mice.

Alzheimer's disease (AD) poses a significant threat to the global elderly population. Traditional Chinese medicine (TCM) has been widely utilized in the treatment of AD. Osthole, a bioactive ingredient classified as an "emperor" in many TCM formulas, has been demonstrated to effectively alleviate AD symptoms. However, its low bioavailability in the brain has limited its clinical application. This study aimed to increase the intracerebral bioavailability of osthole by using borneol as a "courier," based on the classical "Emperor-Minister-Assistant-Courier" model, and to investigate the enhanced pharmacological performance of osthole on AD. Results indicated that a suitable in situ thermosensitive gel matrix for intranasal administration mixed with osthole and borneol consists of P407 at 20%, P188 at 7%, and PEG300 at 6%. The concentration of osthole in the cerebrospinal fluid increased almost tenfold after intranasal administration of osthole/borneol compared to oral administration. Mechanisms showed that borneol as a "courier" opened up intercellular space and loosened the tight junctions of the nasal mucosa by suppressing ZO-1 and occludin expression, thereby expediting the nose-to-brain route and guiding osthole as "emperor" to its target in the brain. Osthole assisted by borneol demonstrated significantly improved efficiency in suppressing cleaved caspase-3 expression, increasing the Bcl-2/Bax ratio, improving T-SOD and catalase expression, reducing malondialdehyde levels, inhibiting neuron apoptosis, and decreasing Aß levels by inhibiting BACE1 expression to alleviate cognitive impairment in APP/PS1 mice compared to osthole alone. Overall, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol and provided a wider application of TCM for AD treatment with higher intracerebral bioavailability.

Development of a Completely New PFOS Alternative with Lower Surface Tension for Minimizing the Environmental Burden.

Improving the technical performance of related industrial products is an efficient strategy to reducing the application quantities and environmental burden for toxic chemicals. A novel polyfluoroalkyl surfactant potassium 1,1,2,2,3,3,4,4-octafluoro-4-(perfluorobutoxy)butane-1-sulfonate(F404) was synthesized by a commercializable route. It had a surface tension(γ) of 18.2 mN/m at the critical micelle concentration(CMC, 1.04 g/L), significantly lower than that of perfluorooctane sulfonate(PFOS, ca. 33.0 mN/m, 0.72 g/L), and exhibited remarkable suppression of chromium-fog at a dose half that of PFOS. The half maximal inhibitory concentration(IC50) values in HepG2 cells and the lethal concentration of 50%(LC50) in zebrafish embryos after 72 hpf indicated a lower toxicity for F404 in comparison to PFOS. In a UV/sulphite system, 89.3% of F404 were decomposed after 3 h, representing a defluorination efficiency of 43%. The cleavage of the ether C-O bond during the decomposition would be expected to form a short chain·C4F9 as the position of the ether C-O in the F404 fluorocarbon chains is C4-O5. The ether unit is introduced in the perfluoroalkyl chain to improve water solubility, biocompatibility and degradation, thereby minimizing the environmental burden. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s40242-023-3030-4.

[Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review].

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

Functional characterization, structural basis, and regio-selectivity control of a promiscuous flavonoid 7,4'-di-O-glycosyltransferase from Ziziphus jujuba var. spinosa.

A highly efficient and promiscuous 7,4'-di-O-glycosyltransferase ZjOGT3 was discovered from the medicinal plant Ziziphus jujuba var. spinosa. ZjOGT3 could sequentially catalyse 4'- and 7-O-glycosylation of flavones to produce 7,4'-di-O-glycosides with obvious regio-selectivity. For 7,4'-dihydroxyl flavanones and 3-O-glycosylated 7,4'-dihydroxyl flavones, ZjOGT3 selectively catalyses 7-O-glycosylation. The crystal structure of ZjOGT3 was solved. Structural analysis, DFT calculations, MD simulations, and site-directed mutagenesis reveal that the regio-selectivity is mainly controlled by the enzyme microenvironment for 7,4'-dihydroxyl flavones and 3-O-glycosylated 7,4'-dihydroxyl flavones. For 7,4'-dihydroxyl flavanones, the selectivity is mainly controlled by intrinsic reactivity. ZjOGT3 is the first plant flavonoid 7,4'-di-O-glycosyltransferase with a crystal structure. This work could help understand the catalytic mechanisms of multi-site glycosyltransferases and provides an efficient approach to synthesise O-glycosides with medicinal potential.

Molecular quantification for differentiation of fresh and dried Jinqian Baihua She.

Freshly-used crude drugs have unique functions and advantages in TCM practice of treating diseases. Jinlong Capsule is a patent traditional Chinese medicine product effective for treatment of hepatocarcinoma, and fresh Jinqian Baihua She (JBS, the body of juvenile Bungarus multicinctus) is one of its important ingredients. The emergence of counterfeit fresh JBS, often identified as dried JBS with almost identical appearance, poses a difficult problem in the quality control of the product. Herein we report a molecular quantification-based method for differentiation of fresh and dried JBS by determining the copy number of a specific DNA marker in the samples. Using species-specific primers and TaqMan probes, we established a real-time quantitative PCR system for amplification of a fragment in the 658-bp cytochrome oxidase subunit I (COI) region from JBS specimens. The amplicon copy number in the muscle tissues ranged from 1.14 × 107 to 4.83 × 107 copies/mg in fresh JBS samples, as compared with 1.13 × 105-8.91 × 106 copies/mg in dried JBS samples. Based upon Fisher discriminant analysis, we used 1.27 × 107 copies/mg as the cut-off value for differentiating fresh and dried JBS, which was validated in the single-blinded validation test of fresh and dried JBS samples. This qPCR system may provide an efficient means for accurate identification of fresh JBS to improve the quality control of the medicinal product.

Comparative Study on the Pharmacokinetics of Paeoniflorin, White Peony Root Water Extract, and Taohong Siwu Decoction After Oral Administration in Rats.

BACKGROUND AND OBJECTIVE: Taohong Siwu Decoction (TSD) is a classic traditional Chinese medicine (TCM) compound with pharmacological effects such as vasodilation and hypolipidemia. Paeoniflorin (PF) is one of the active ingredients of TSD. The aim of this study was to evaluate the pharmacokinetics of PF in herbal extracts and their purified forms in rats. METHOD: A sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) method for the determination of PF in rat plasma was developed. Rats were divided into three groups, and given PF solution, water extract of white peony root (WPR), or TSD by gavage. At different predetermined timepoints after gavage, blood was collected from the orbital vein. The pharmacokinetic parameters of PF in the plasma of rats in the three groups was determined. RESULTS: The pharmacokinetic studies showed that the time to reach maximum concentration (Tmax) of PF in the purified forms group was relatively high, while the half-lives (T½) of PF in the TSD and WPR groups were longer. Among the three groups, PF in the purified forms group had the maximum area under the concentration-time curve (AUC0-t = 732.997 µg/L·h) and the largest maximum concentration (Cmax = 313.460 µg/L), which showed a significant difference compared with the TSD group (P < 0.05). Compared with the purified group, the clearance (CLz/F = 86.004 L/h/kg) and the apparent volume of distribution (Vz/F = 254.787 L/kg) of PF in the TSD group increased significantly (P < 0.05). CONCLUSIONS: A highly specific, sensitive, and rapid HPLC-MS-MS method was developed and applied for the determination of PF in rat plasma. It was found that TSD and WPR can prolong the action time of paeoniflorin in the body.

C:N:P stoichiometric characteristics of mosses in Picea crassifolia forest in Helan Mountains, Ningxia, China.

To explore the stoichiometric characteristics of C, N and P and adaptive mechanism of mosses in mountain forest ecosystems, we set up 15 plots along the altitude gradient in Picea crassifolia forest in Helan Mountains, Ningxia. We analyzed the C:N:P stoichiometry of moss aboveground tissues and its relationship with environmental factors. The results showed the mean values of C, N and P concentration in moss aboveground tissues were 336.67, 20.31 and 0.66 mg·g-1, respectively. The mean value of aboveground tissue N:P was 33.4, indicating that the growth of mosses was limited by P. The C concentration in the aboveground tissues of mosses was positively correlated with soil total nitrogen concentration and negatively correlated with soil total phosphorus concentration. The N concentration in aboveground tissues of mosses was significantly negatively correlated with soil organic carbon and soil total nitrogen concentrations. Results of redundancy analysis showed that the interpretation rate of environmental factors on the stoichiometry was 48.5%, with canopy closure, soil total nitrogen and soil total phosphorus as the main factors. Canopy closure was the main environmental factor affecting the growth of mosses in P. crassifolia forest in Helan Mountains. High canopy closure facilitated the growth of mosses.

Network Pharmacology and Mechanism Studies of the Protective Effect of Ginseng against Alzheimer's Disease Based on Aß Pathogenesis.

Alzheimer's disease (AD) is a critical neurodegenerative disease that manifests as progressive intellectual decline and is pathologically characterized by a progressive loss of neurons in the brain. Despite extensive research on this topic, the pathogenesis of AD is not fully understood, while the beta-amyloid (Aß) hypothesis remains the dominant one and only a few symptomatic drugs are approved for the treatment of AD. Ginseng has been widely reported as an effective herbal medicine for the treatment of neurodegenerative diseases such as dementia. Therefore, we explore the protective effects of ginseng in AD by a network pharmacological approach based on the pathogenesis of Aß. Twenty-one major ginsenosides are screened based on ultraperformance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) data. Among them, MAPK8, MAPK9, BACE1, FLT1, CDK2, and CCR5 are the core targets. By molecular docking and validation with the in vitro cell model APPswe-SH-SY5Y, we find that ginsenosides Rg3 and Ro have good neuroprotective effects and can reduce the expression of Aß 1 - 42 in APPswe-SH-SY5Y. Finally, through RT-qPCR experiment, we find that ginsenoside Rg3 targeted MAPK8, FLT1, and CCR5, while ginsenoside Ro targeted MAPK8, MAPK9, FLT1, and CCR5 for its potential anti-AD efficacy.

PFAS-induced lipidomic dysregulations and their associations with developmental toxicity in zebrafish embryos.

Per- and polyfluoroalkyl substances (PFASs) are persistent environmental contaminants, posing developmental toxicity to fish and human. PFAS-induced lipid metabolism disorders were demonstrated using the zebrafish (Danio rerio) embryo model, but the detailed changes of lipid compositions and the influence of these changes on the biological development are still unclear. Herein, lipidomics analysis was performed to reveal the dysregulations of lipid metabolism in zebrafish embryos exposed to perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) through microinjection. Various abnormal phenotypes were observed, including heart bleeding, pericardium edema, spinal curvature and increased heart rate at 72 h after fertilization, especially in the PFOS exposure groups. Lipidomic profiling found downregulated phosphatidylethanolamines in the PFAS-exposed embryos, especially those containing a docosahexaenoyl (DHA) chain, indicating an excessive oxidative damage to the embryos. Glycerolipids were mainly upregulated in the PFOA groups but downregulated in the PFOS groups. These aberrations may reflect oxidative stress, energy metabolism malfunction and proinflammatory signals induced by PFASs. However, supplement of DHA may not be effective in recovering the lipidomic dysregulations and protecting from the developmental toxicity induced by PFASs, showing the complexity of the toxicological mechanisms. This work has revealed the associations between the abnormal phenotypes and dysregulations of lipid metabolism in zebrafish embryos induced by PFASs from the aspect of lipidomics, and discovered the underlying molecular mechanisms of the developmental toxicity of PFASs.

Porous organic framework as coating for stir bar sorptive extraction of carbamate pesticides from corn and potato samples.

Three porous organic frameworks (POFs) were synthesized by the reaction between phloroglucinol and 1,4-phthalaldehyde, 4,4'-biphenyldialdehyde or tris-(4-formylphenyl) amine; the products are named as POF-a, POF-b and POF-c, respectively. They were used to prepare POFs coated stir bars respectively for the extraction of four carbamate pesticides (CMPs). POF-c coated stir bar exhibited better adsorption performance than POF-a/b coated stir bar and commercial stir bars, probably due to the stronger conjugated structure and hydrophobicity of POF-c, and resultant hydrophobic, π-π and hydrogen bonding interactions between them. The adsorption mechanism for target CMPs was verified by characterization techniques and molecular dynamics simulation. A method of POF-c coated stir bar sorptive extraction-high performance liquid chromatography-variable wavelength ultraviolet detector was developed for the analysis of four CMPs in corn and potato samples. Under the optimal conditions, LODs of the method were between 0.017 and 0.048 µg/L, and the linear range for four CMPs was 0.1/0.2-200 µg/L.

Protective Effect of Shenfu Injection on Vascular Endothelial Damage in a Porcine Model of Hemorrhagic Shock.

OBJECTIVE: To investigate the effects of Shenfu Injection (, SFI) on endothelial damage in a porcine model of hemorrhagic shock (HS). METHODS: After being bled to a mean arterial pressure of 40±3 mm Hg and held for 60 min, 32 pigs were treated with a venous injection of either shed blood (transfusion group), shed blood and saline (saline group), shed blood and SFI (SFI group) or without resuscitation (sham group). Venous blood samples were collected and analyzed at baseline and 0, 1, 2, 4, and 6 h after HS. Tumor necrosis factor-α (TNF-α), serum interleuking (IL)-6, and IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM -1), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and Bcl-2, Bax, and caspase-3 proteins were determined by Western blot. RESULTS: The serum level of TNF-α in the SFI group was significantly lower than in the other groups at 0, 1, and 2 h after HS, while the level of IL-6 was lower at 4 and 6 h compared with the saline group (P<0.01 or P<0.05). The concentration of serum IL-10 was significantly higher in the SFI group than in the other groups at 0, 1, 4, and 6 h after HS (P<0.01). Western blot and immunohistochemistry of vascular tissue showed that the expression of caspase-3 was downregulated, and that of Bcl-2 and Bax was upregulated in the SFI group compared to other groups (P<0.05). CONCLUSION: SFI attenuated endothelial injury in the porcine model of HS by inhibiting cell apoptosis, suppressing the formation of proinflammatory cytokines, and reducing endothelial activation.

A spectrum-effect based method for screening antibacterial constituents in Niuhuang Shangqing Pill using comprehensive two-dimensional liquid chromatography.

To investigate and screen the active antibacterial constituents of Niuhuang Shangqing Pill (NSP), the current study developed a two-dimensional liquid chromatography (2DLC) method combining microcalorimetry technique. 60% ethanol extracts from 10 batches of different commercial NSP samples were analyzed and their chemical fingerprint were developed by the comprehensive 2DLC system of Shimadzu Nexera X2. Anti-streptococcus pneumoniae (SP) constituents were determined by microcalorimetry. Thermal kinetic parameters of the SP thermogram affected by 60% ethanol extracts from 10 NSP samples were analyzed by principal component analysis. Spectrum-effect correlation between comprehensive 2DLC fingerprint and the antibacterial activity were analyzed by orthogonal partial least squares (OPLS) and orthogonal partial least squares discriminant analysis (OPLS-DA). Findings showed that peak X1 (unknown), X9 (aloe-emodin), X10 (baicalein), X11 (unknown), X14 (wogonin), X15 (glycyrrhizic acid) and X17 (unknown) are the relevant components that are in positive correlation with inhibitory rate. Regarding inhibitory rate, X17 is the most powerful one, followed by X14, X15, X10, X11, X1 and X9, suggesting that compound X17, wogonin, glycyrrhizic acid and baicalein are the major active antibacterial components of NSP. The current method employing 2DLC with microcalorimetry technique proposes a new insight for screening and identifying antibacterial components in complex herbal formula.

Screening and verification of CYP3A4 inhibitors from Bushen-Yizhi formula to enhance the bioavailability of osthole in rat plasma.

ETHNOPHARMACOLOGICAL RELEVANCE: With the features of multiple-components and targets as well as multifunction, traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of various diseases for a long time. During the application of TCM, the researches about bioavailability enhancement of the bioactive constituents in formula are flourishing. Bushen-Yizhi formula (BSYZ), a TCM prescription with osthole (OST) as one of the main bioactive ingredients, have been widely used to treat kidney deficiency, mental retardation and Alzheimer's disease. However, the underlying biological mechanism and compound-enzyme interaction mediated bioavailability enhancement of OST are still not clearly illuminated. AIM OF THE STUDY: The aim of this study is to explore the material basis and molecular mechanism from BSYZ in the bioavailability enhancement of OST. Screening the potential CYP3A4 inhibitors using theoretical prediction and then verifying them in vitro, and pharmacokinetics study of OST in rat plasma under co-administrated of screened CYP3A4 inhibitors and BSYZ were also scarcely reported. MATERIALS AND METHODS: Screening of CYP3A4 inhibitors from BSYZ was performed with molecular docking simulation from systems pharmacology database. The screened compounds were verified by using P450-Glo Screening Systems. A multiple reaction monitoring (MRM) mass spectrometry method was established for OST quantification. Male Sprague-Dawley rats divided into four groups and six rats in each group were employed in the pharmacokinetics study of OST. The administrated conditions were group I, OST (20 mg/kg); group II, BSYZ (containing OST 1 mg/mL, at the dose of 20 mg/kg OST in BSYZ); group III, co-administration of ketoconazole (Ket, 75 mg/kg) and OST (20 mg/kg); group IV, co-administration of CYP3A4 inhibitor (10 mg/kg) and OST (20 mg/kg). They were determined by using HPLC-MS/MS (MRM) and statistical analysis was performed using student's t-test with p < 0.05 as the level of significance. RESULTS: 21 potential CYP3A4 inhibitors were screened from BSYZ compounds library. From the results of verification in vitro, we found 4 compounds with better CYP3A4 inhibition efficiency including Oleic acid, 1,2,3,4,6-O-Pentagalloylglucose, Rutin, and Schisantherin B. Under further verification, Schisantherin B exhibited the best inhibitory effect on CYP3A4 (IC50 = 0.339 µM), and even better than the clinically used drug (Ket) at the concentration of 5 µM. In the study of pharmacokinetics, the area under the curve (AUC, ng/L*h) of OST after oral administration of BSYZ, Ket and Schisantherin B (2196.23 ± 581.33, 462.90 ± 92.30 and 1053.03 ± 263.62, respectively) were significantly higher than that of pure OST treatment (227.89 ± 107.90, p < 0.01). CONCLUSIONS: Schisantherin B, a profoundly effective CYP3A4 inhibitor screened from BSYZ antagonized the metabolism of CYP3A4 on OST via activity inhibition, therefore significantly enhanced the bioavailability of OST in rat plasma. The results of this study will be helpful to explain the rationality of the compatibility in TCM formula, and also to develop new TCM formula with more reasonable drug compatibility.

Research on Classification of Fine-Grained Rock Images Based on Deep Learning.

Rock classification is a significant branch of geology which can help understand the formation and evolution of the planet, search for mineral resources, and so on. In traditional methods, rock classification is usually done based on the experience of a professional. However, this method has problems such as low efficiency and susceptibility to subjective factors. Therefore, it is of great significance to establish a simple, fast, and accurate rock classification model. This paper proposes a fine-grained image classification network combining image cutting method and SBV algorithm to improve the classification performance of a small number of fine-grained rock samples. The method uses image cutting to achieve data augmentation without adding additional datasets and uses image block voting scoring to obtain richer complementary information, thereby improving the accuracy of image classification. The classification accuracy of 32 images is 75%, 68.75%, and 75%. The results show that the method proposed in this paper has a significant improvement in the accuracy of image classification, which is 34.375%, 18.75%, and 43.75% higher than that of the original algorithm. It verifies the effectiveness of the algorithm in this paper and at the same time proves that deep learning has great application value in the field of geology.

Urinary metabonomics study of anti-depressive mechanisms of Millettia speciosa Champ on rats with chronic unpredictable mild stress-induced depression.

As a traditional Chinese medicine (TCM), Millettia speciosa Champ (MSC), exerts a wide range of pharmacological activities. Our research group previously found that MSC has antidepressant effects, but the specific antidepressant mechanisms remain unclear. Therefore, in this study, urine metabolomics based on ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) combined with pharmacodynamics was used to explore the pathogenesis of depression and the antidepressant effects of MSC. The results showed that MSC treatment could significantly improve chronic unpredictable mild stress (CUMS)-induced depression. Urine metabolic showed that the profiles of the CUMS model group were significantly separated from the control group, while the drug-treated groups were closer to the control group, especially the MSC group treated with a 14 g/kg dose of MSC. Furthermore, 9 metabolites, including glutaric acid, L-isoleucine, L-Dopa, sebacic acid, 3-methylhistidine, allantoin, caprylic acid, tryptophol, and 2-phenylethanol glucuronide, were identified as potential biomarkers of depression. Metabolic pathway analysis showed that these potential biomarkers were mainly involved in valine, leucine, and isoleucine biosynthesis, aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine degradation, tyrosine metabolism, histidine metabolism, fatty acid biosynthesis, and pentose and glucuronate interconversions. Through Receiver operating characteristic (ROC) analysis and Pearson correlation analysis, the combination of L-isoleucine, sebacic acid, and allantoin, were further screened out as potential pharmacodynamic biomarkers associated with the efficacy of MSC. This study suggests that the integration of metabolomics with pharmacodynamics helps to further understand the pathogenesis of depression and provides novel insight into the efficacy of TCM.

[ZHANG Ren's experiences in treatment of diabetic retinopathy with acupuncture].

ZHANG Ren, the chief physician, believes that diabetic retinopathy is located at eye and closely related to qi and yin. He proposes the treatment principle of this disease, i.e. combination of the primary and the secondary, in which, taking the eye as the treatment target and focusing on the symptoms. Acupuncture is provided for activating blood circulation and resolving stasis at the extra points, e.g. Xinming and Shangjianming, and also meridian points, e.g. Cuanzhu (BL 2) and Tongziliao (GB 1). The comprehensive application is emphasized with filiform needle, dermal needle and acupoint injection. Moreover, the mental and physical conditions are treated simultaneously to regulate emotions and the preventive idea is suggested on early treatment and persistent treatment.