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Herb pairs containing Curcumae Rhizoma (Ezhu): A review of bio-active constituents, compatibility effects and t-copula function analysis

J Ethnopharmacol. 2023 Oct 14:117199. doi: 10.1016/j.jep.2023.117199. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: An herbal pair is a classic form of clinical dispensing in Traditional Chinese Medicine (TCM), often used in prescriptions to enhance the effect or reduce potential side effects. It is the smallest component unit of Chinese medicine prescription and an essential bridge between Chinese medicine and prescription. Curcumae Rhizoma (called Ezhu in Chinese) is a representative TCM herb that promotes blood circulation and removes blood stasis. It has been used in Chinese medicine for thousands of years. Ezhu is generally used in clinical applications as a part of a “drug pair” to treat heartburn, stomach pain, tumour, amenorrhea and abdominal pain caused by blood stasis, qi stagnation and injury.

AIMS OF THE REVIEW: This review aims to summarize the latest and comprehensive situation of the biological activity and clinical application of drug pairs containing Ezhu, find the law of Ezhu compatibility application, and discuss the rationalization of Ezhu drug compatibility. For Ezhu, herb pairs to provide a theoretical basis for clinical research in TCM and serve as a research foundation for developing new drugs.

MATERIALS AND METHODS: Using a self-built prescription database and Apriori algorithm for association rule mining. A systematic search for studies on herb pairs containing Ezhu was carried out by using the internet databases of PubMed, CNKI, Baidu Scholar, Google Scholar and Web of Science, as well as other relevant textbooks, reviews and documents (e.g. Chinese Pharmacopoeia, 2020 edition, Chinese herbal classic books and PhD and MSc theses, etc.). Among them with keywords including “Curcumae Rhizoma”, “Ezhu”, “herb pairs”, “clinical application”, etc. and their combinations. Moreover, the t-copula function was used to analyse the dose-coupling effect of five drug pairs, including Ezhu.

RESULTS: The preliminary statistical analysis retrieved Ezhu prescriptions from self-built prescription database and internet databases. The results showed that the compatibility frequency of Ezhu with the other five Chinese medicines was high. Most of these selected herbal combinations are used to treat internal diseases. In this paper, the progress of the ethnopharmacology of Ezhu was reviewed, emphasizing the changes in bioactive components and compatibility of Chinese traditional medicine combinations such as Ezhu and Astragalus Curcuma (Sparganium stoloniferum Buch. -Ham; called Sanleng in Chinese), Ezhu and Astragali Radix (Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Astragalus membranaceus (Fisch.) Bge.; called Huangqi in Chinese). Some other varieties, such as Ezhu and Rhizoma Chuanxiong (Ligusticum chuanxiong Hort.; called Chuanxiong in Chinese), Trionycis Carapax (Trionyx sinensis Wiegmann; called Biejia in Chinese), and Coptidis Rhizoma (Coptis chinensis Franch., Coptis deltoidea C. Y. Cheng et Hsiao, Coptis teeta Wall.; called Huanglian in Chinese), are also recorded in ancient books but rarely researched. The dose of Ezhu is strongly correlated with the amount of Sanleng, Huangqi, Biejia, Chuanxiong and Huanglian, respectively. Furthermore, there was a positive correlation between them.

CONCLUSIONS: The bioactive components and compatibility effects of Ezhu herb pairs were studied in detail using data mining and t-copula function analysis. Ezhu and Astragalus Curcuma (Sanleng) mainly treat gynecological disorders by activating blood circulation and relieving congestion. Ezhu and Astragali Radix (Huangqi) drug pair and Ezhu and Trionycis Carapax (Biejia) drug pair are all commonly used in the clinical treatment of tumors, the former is mainly used clinically for the treatment of digestive tract-related inflammation and tumors, liver cancer and gynecological tumors, and the latter is commonly used for the treatment of malignant tumors, such as liver cancer and mammary cancer.

PMID:37844744 | DOI:10.1016/j.jep.2023.117199

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Anatomical variants of the retroaortic left renal vein

Ann Anat. 2023 Oct 14:152170. doi: 10.1016/j.aanat.2023.152170. Online ahead of print.

ABSTRACT

BACKGROUND: Anatomical variants of the left renal vein (LRV), such as the retroaortic (RLRV) and circumaortic (CLRV) course, are of surgical importance. Different morphological and topographical possibilities of the RLRV could occur. It was aimed at documenting the anatomical variables of the RLRV.

METHOD: A retrospective study on 375 computed tomography angiograms was performed. Five different anatomical types of LRV were documented: preaortic types 1 and 2 and retroaortic types 3 to 5.

RESULTS: In 344/375 cases, preaortic LRVs were found. In 31/375 cases, different types of RLRV were found: type 3a – single RLRV, 41.94%; type 3b – single RLRV with bifid caval end, 9.68%; type 3c – single RLRV with trifid caval end, 3.23%; type 4a – CLRV with extrahilar origin, 29.03%; type 4b – CLRV with renal sinus origin, 12.9%; type 5 – triple LRV (one preaortic LRV and two RLRVs), 3.23%. Reference vertebral levels were recorded for the prevertebral segment of the RLVR. The vertebral level of type 3a varied from the L1/L2 disc to the upper third of the L4 vertebra. Type 3b was found in 3/31 RLRV cases; in one of these, the hemiazygos vein was inserted by two roots into the LRV and its upper caval end trunk. There was a significant statistical association between type 3b and the vertebral level, all cases being centered on the middle third of the L4 vertebra.

CONCLUSIONS: New morphological possibilities of the LRV were distinguished, and a new anatomical classification system of the RLRV results. The RLRV variant should be documented case-by-case as it has its anatomical variables.

PMID:37844738 | DOI:10.1016/j.aanat.2023.152170

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Spectrum-effect relationship analysis based on HPLC-FT-ICR-MS and multivariate statistical analysis to reveal the pharmacodynamic substances of Ling-Gui-Zhu-Gan decoction on Alzheimer’s disease

J Pharm Biomed Anal. 2023 Oct 4;237:115765. doi: 10.1016/j.jpba.2023.115765. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) threatens elderly human health and still lacks effective treatment. Our previous work showed that LGZGD possessed a neuroprotective effect on the Aβ25-35-induced neurotoxicity in differentiated PC12 cells, indicating that LGZGD may be a potential drug for treatment of AD. However, its pharmacodynamic substances which show anti-inflammatory and anti-oxidant stress activities are still unrevealed. This research aims to reveal the pharmacodynamic substances of LGZGD on Aβ25-35-induced PC12 cell model of AD based on a spectrum-effect relationship study by using HPLC-FT-ICR-MS method and multivariate statistical analysis. Firstly, the chemical composition spectra of different combinations of LGZGD were recorded by HPLC-FT-ICR MS. Subsequently, Aβ25-35-induced PC12 cell model of AD was established and pharmacodynamic experiments were conducted to evaluate their anti-inflammatory and anti-oxidant activities, respectively. Finally, the potential pharmacodynamic substances were screened out through spectrum-effect relationship study accompanied by multivariate statistical analysis including bivariate correlation analysis (BCA), grey relational analysis (GRA), principal component analysis (PCA), partial least squares regression analysis (PLSR). As a result, a total of 96 chemical consistents in different combinations of LGZGD were discovered. Among them, 7 components such as isoglabrolide, licorice saponin E2, licorice saponin N2 and licoisoflavanone were directly linked with the anti-inflammatory effects, and 14 constituents such as tumulosic acid, polyporenic acid C, dehydrotumulosic acid, dehydropachymic acid, and pachymic acid were directly correlated with the anti-oxidative stress activities. In conclusion, we combined the HPLC-FT-ICR-MS spectra with pharmacodynamic indicators to develop the spectrum-effect relationships of LGZGD for the first time, and successfully revealed its potential pharmacodynamic substances in the treatment of AD from the anti-inflammatory and antioxidant pathways in the cell model.

PMID:37844366 | DOI:10.1016/j.jpba.2023.115765

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Statistical reliability of a relative standard deviation of chromatographic peak area estimated by a chemometric tool based on the FUMI theory

J Pharm Biomed Anal. 2023 Oct 10;237:115777. doi: 10.1016/j.jpba.2023.115777. Online ahead of print.

ABSTRACT

In pharmaceutical analysis using a high-performance liquid chromatography (HPLC) system, repeatability assessment is significant to obtain reliable and precise quantitative results. The purpose of the present study is to experimentally show the statistical reliability of a relative standard deviation (RSD) of peak area estimated by a chemometric tool based on probability theory, called the function of mutual information (FUMI) theory, which stochastically provided an RSD of peak area and SD of baseline areas with width k (s(k)) from noises and a signal on a single chromatogram. An ultra-high-performance liquid chromatography with ultraviolet detection (UHPLC-UV) for determining ergosterol was applied as an example of the repeatability assessment. In addition, the statistical reliability of an RSD of peak area in the UHPLC-UV system was certified according to a chi-square (χ2) distribution. The 712 values of s(k) were experimentally obtained from a data series of 1001 points in the noise regions of 712 chromatograms. The histogram of χ2 of s(k) was well-fitted to the χ2 distribution curve (freedom degree, ν = 50), indicating that the statistical reliability of an RSD of the peak area in the UHPLC-UV estimated by the FUMI theory (n = 1) was equivalent to that estimated by 50 runs of chromatographic measurements.

PMID:37844361 | DOI:10.1016/j.jpba.2023.115777

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Accuracy of an objective binocular automated phoropter for providing spectacle prescriptions

Clin Exp Optom. 2023 Oct 16:1-6. doi: 10.1080/08164622.2023.2266498. Online ahead of print.

ABSTRACT

CLINICAL RELEVANCE: Currently eye examinations are usually based on autorefraction followed by subjective refraction (SR) with a phoropter. An automated phoropter that can also perform autorefraction may facilitate the optometric workflow.

BACKGROUND: The efficiency and feasibility of an objective autorefraction and correction system are assessed by comparing objective refractive measurements with SR on the same subjects and evaluating the visual acuity (VA) values obtained after the objective refractive measurement and correction.

METHODS: Objective autorefraction and correction was performed on 41 subjects using an automated binocular phoropter system. The auto-phoropter performs autorefraction by wavefront measurement and corrects the spherical and cylindrical errors with tunable fluidic lenses while the patient looks at a visual display inside the instrument. The instrument outputs are optometric constants of spherical and cylindrical aberrations. After measurement and automated correction of the refractive errors, the VA values were assessed by having the subjects look at an integrated Snellen chart. The objective measurement results were statistically compared with their SR.

RESULTS: The correlations between SR and objective autorefraction and correction spherical equivalents (M) were 0.98 (0.97-0.99) and 0.96 (0.93-0.98), the vertical Jackson cross cylinder (J0) were 0.96 (0.92-0.98) and 0.95 (0.91-0.97), and the oblique Jackson cross cylinder (J45) were 0.73 (0.55-0.85) and 0.82 (0.69-0.90), for the right and left eyes, respectively, with the 95% confidence interval (CI) values in parentheses. 89.0% of the 82 eyes had at least 6/7.5 VA.

CONCLUSIONS: A significant agreement between the SR and objective autorefraction and correction was observed. An all-objective refractive assessment with instantaneous verification may improve the precision of eye prescriptions and possibly reduce the procedure time.

PMID:37844333 | DOI:10.1080/08164622.2023.2266498

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Regulatory Review Duration and Differences in Submission Times of Drugs in the United States and Europe, 2011 to 2020

Ann Intern Med. 2023 Oct;176(10):1413-1418. doi: 10.7326/M23-0623.

ABSTRACT

The speed of drug regulatory agencies in the United States and Europe is often a source of discussion. The objective of this research was to assess regulatory review duration of first and supplementary indications approved between 2011 and 2020 in the United States and Europe (European Union [EU] and Switzerland) and differences in submission times between the United States and Europe. Descriptive statistics were applied to review times between the jurisdictions and across the therapeutic areas. A regression analysis was done to estimate the association between approval agency and review times. The primary analysis cohort included 241 drugs approved in the United States, the EU, and Switzerland. Of these, 128 drugs had supplemental indications (331 in total) in the United States and 87 had supplemental indications (206 in total) in the EU. Overall median review duration from submission to approval subtracting the clock stop period was 39 weeks in the United States, 44 weeks in the EU, and 44 weeks in Switzerland. When review times within each drug were compared, the European Medicines Agency took a median of 3.7 weeks (IQR, -6.7 to 14.9 weeks) longer than the U.S. Food and Drug Administration and Swissmedic a median of 0.3 weeks (IQR, -10.6 to 15.3 weeks) longer. Median total review duration for supplemental indications was 26 weeks in the United States and 40 weeks in the EU. Applications were submitted a median of 1.3 and 17.9 weeks later in the EU and Switzerland, respectively, than in the United States. The regression analysis showed small differences in submission times between the United States and the EU (-2.1 weeks [95% CI, -11.7 to 7.6 weeks]) and larger differences between the United States and Switzerland (33.0 weeks [CI, 23.1 to 42.8 weeks]). It would be beneficial for patients if differences in submission times between the United States and Europe continue to be minimized.

PMID:37844306 | DOI:10.7326/M23-0623

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Normative Percentiles of Retinal Nerve Fiber Layer Thickness and Glaucomatous Visual Field Loss

Transl Vis Sci Technol. 2023 Oct 3;12(10):13. doi: 10.1167/tvst.12.10.13.

ABSTRACT

PURPOSE: Circumpapillary retinal nerve fiber layer thickness (RNFLT) measurement aids in the clinical diagnosis of glaucoma. Spectral domain optical coherence tomography (SD-OCT) machines measure RNFLT and provide normative color-coded plots. In this retrospective study, we investigate whether normative percentiles of RNFLT (pRNFLT) from Spectralis SD-OCT improve prediction of glaucomatous visual field loss over raw RNFLT.

METHODS: A longitudinal database containing OCT scans and visual fields from Massachusetts Eye & Ear glaucoma clinic patients was generated. Reliable OCT-visual field pairs were selected. Spectralis OCT normative distributions were extracted from machine printouts. Supervised machine learning models compared predictive performance between pRNFLT and raw RNFLT inputs. Regional structure-function associations were assessed with univariate regression to predict mean deviation (MD). Multivariable classification predicted MD, pattern standard deviation, MD change per year, and glaucoma hemifield test.

RESULTS: There were 3016 OCT-visual field pairs that met the reliability criteria. Spectralis norms were found to be independent of age, sex, and ocular magnification. Regional analysis showed significant decrease in R2 from pRNFLT models compared to raw RNFLT models in inferotemporal sectors, across multiple regressors. In multivariable classification, there were no significant improvements in area under the curve of receiver operating characteristic curve (ROC-AUC) score with pRNFLT models compared to raw RNFLT models.

CONCLUSIONS: Our results challenge the assumption that normative percentiles from OCT machines improve prediction of glaucomatous visual field loss. Raw RNFLT alone shows strong prediction, with no models presenting improvement by the manufacturer norms. This may result from insufficient patient stratification in tested norms.

TRANSLATIONAL RELEVANCE: Understanding correlation of normative databases to visual function may improve clinical interpretation of OCT data.

PMID:37844261 | DOI:10.1167/tvst.12.10.13

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Interdisiplinary and intraobserver reliability of the Greulich-Pyle method among Turkish children

J Pediatr Endocrinol Metab. 2023 Oct 18. doi: 10.1515/jpem-2023-0303. Online ahead of print.

ABSTRACT

OBJECTIVES: Greulich-Pyle (GP) is one of the most used method for bone age determination (BAD) in various orthopedic, pediatric, radiological, and forensic situations. We aimed to investigate the inter- and intra-observer reliability of the GP method between the most relevant disciplines and its applicability to the Turkish population.

METHODS: One-hundred and eighty (90 boys, 90 girls) patients with a chronological age younger than 18 (mean 9.33) were included. X-rays mixed by the blinded investigator were evaluated by two orthopedists, two radiologists, and two pediatric endocrinologists to determine skeletal age according to the GP atlas. A month later the process was repeated. As a statistical method, Paired t-test was used for comparison, an Intraclass Correlation Coefficients test was used for reliability and a 95 % confidence interval was determined. Results were classified according to Landis-Koch.

RESULTS: All results were consistent with chronological age (p<0.001), according to the investigators’ evaluations compared with chronological age. At the initial evaluation, the interobserver reliability of the method was 0.999 (excellent); at the second evaluation, the interobserver reliability was 0.997 (excellent). The intra-observer reliability of the method was ‘excellent’ in all observers. When results were separately evaluated by gender, excellent intraobserver correlation and excellent correlation with chronological age were found among all researchers (>0.9). When X-rays were divided into three groups based on age ranges and evaluated, ‘moderate’ and ‘good’ correlations with chronological age were obtained during the peripubertal period.

CONCLUSIONS: The GP method used in skeletal age determination has excellent inter- and intra-observer reliability. During the peripubertal period, potential discrepancies in bone age assessments should be kept in mind. This method can be used safely and reproducibly by the relevant specialists.

PMID:37844258 | DOI:10.1515/jpem-2023-0303

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Hierarchical temporal prediction captures motion processing along the visual pathway

Elife. 2023 Oct 16;12:e52599. doi: 10.7554/eLife.52599. Online ahead of print.

ABSTRACT

Visual neurons respond selectively to features that become increasingly complex from the eyes to the cortex. Retinal neurons prefer flashing spots of light, primary visual cortical (V1) neurons prefer moving bars, and those in higher cortical areas favor complex features like moving textures. Previously, we showed that V1 simple cell tuning can be accounted for by a basic model implementing temporal prediction – representing features that predict future sensory input from past input (Singer et al., 2018). Here we show that hierarchical application of temporal prediction can capture how tuning properties change across at least two levels of the visual system. This suggests that the brain does not efficiently represent all incoming information; instead, it selectively represents sensory inputs that help in predicting the future. When applied hierarchically, temporal prediction extracts time-varying features that depend on increasingly high-level statistics of the sensory input.

PMID:37844199 | DOI:10.7554/eLife.52599

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Effects of COVID-19 on Rate of Injury and Position-Specific Injury During the 2020 National Football League Season

J Strength Cond Res. 2023 Oct 16. doi: 10.1519/JSC.0000000000004602. Online ahead of print.

ABSTRACT

Costello II, JP, Wagner, JD, Dahl, VA, Cohen, JL, Reuter, AM, and Kaplan, LD. Effects of COVID-19 on rate of injury and position-specific injury during the 2020 National Football League season. J Strength Cond Res XX(X): 000-000, 2023-Because of the COVID-19 pandemic, the National Football League (NFL) made changes to its operations for the 2020 season. We hypothesize an increase in the rate of injuries during the 2020 season. Publicly available data were reviewed to identify NFL injuries from the 2015-2020 seasons. Player position, description of injury, date of injury, and injury setting were recorded. p ≤ 0.05 was considered statistically significant. For the 2020 season, compared with the 2015-2019 seasons, there was an increased risk of injury during the regular season overall relative risk (RR) = 1.308 (p < 0.05), week (W)1 RR = 7.33 (p < 0.05), W1-6 RR = 1.964 (p < 0.05), W7-12 RR = 1.8909 (p < 0.05), and during the postseason overall RR = 1.1444 (p < 0.05), calculated using analysis of variance. There was an overall increased risk of abdominal or core injuries RR = 1.248 (p < 0.05), groin or hip injuries RR = 2.534 (p < 0.05), and hamstring injuries RR = 3.644 (p < 0.05). There was an increased risk of hamstring injuries in cornerbacks RR = 3.219 (p < 0.05) and running backs RR = 1.1394 (p < 0.05), hip or groin injuries in guards RR = 1.105 (p < 0.05), Achilles tendon injuries in safeties RR = 1.6976 (p < 0.05), quadriceps injuries in running backs RR = 1.6191 (p < 0.05), and arm injuries in defensive tackles RR = 1.221 (p < 0.05). There was an increase in the overall rate of injuries in the 2020 NFL season, both in the regular season and postseason, compared with the 2015-2019 seasons. The overall rate of abdominal or core, groin or hip, and hamstring injuries increased. Specific player positions saw unique increases in rates of injuries. These findings may be due to numerous operational changes implemented, such as reduced in-person training and the elimination of the preseason, leading to suboptimal, sports-specific conditioning and increased risk of musculoskeletal injury.

PMID:37844189 | DOI:10.1519/JSC.0000000000004602