Role of lymphotoxin alpha as a new molecular biomarker in revolutionizing tear diagnostic testing for dry eye disease.

Dry eye disease (DED), primarily classified as multifactorial ocular surface disorder, afflicts tens of millions of individuals worldwide, adversely impacting their quality of life. Extensive research has been conducted on tear film analysis over the past decades, offering a range of tests to evaluate its volume, health, and integrity. Yet, early diagnosis and effective treatment for DED continue to pose significant challenges in clinical settings. Nevertheless, by recognizing key phenomena in DED such as ocular surface inflammation, hyperosmolarity, and tear film instability, this article provides a comprehensive overview of both traditional and recently developed methods for diagnosing and monitoring DED. The information serves as a valuable resource not only for clinical diagnosis but also for further research into DED.

Time-Series-Dependent Global Data Filtering Strategy for Mining and Profiling of Xenobiotic Metabolites in a Dynamic Complex Matrix: Application to Biotransformation of Flavonoids in the Extract of Ginkgo biloba by Gut Microbiota.

Efficient characterization of xenobiotic metabolites and their dynamics in a changing complex matrix remains difficult. Herein, we proposed a time-series-dependent global data filtering strategy for the rapid and comprehensive characterization of xenobiotic metabolites and their dynamic variation based on metabolome data. A set of data preprocessing methods was used to screen potential xenobiotic metabolites, considering the differences between the treated and control groups and the fluctuations over time. To further identify metabolites of the target, an in-house accurate mass database was constructed by potential metabolic pathways and applied. Taking the extract of Ginkgo biloba (EGB) co-incubated with gut microbiota as an example, 107 compounds were identified as flavonoid-derived metabolites (including 67 original from EGB and 40 new) from 7468 ions. Their temporal metabolic profiles and regularities were also investigated. This study provided a systematic and feasible method to elucidate and profile xenobiotic metabolism.

[Mechanism of acupuncture and moxibustion in treatment of chronic fatigue syndrome from perspective of intestinal flora].

Intestinal flora dysbiosis may play an important role in the occurrence and development of chronic fatigue syndrome (CFS), which may induce the inflammatory response and metabolic disturbance of patients with CFS. Acupuncture and moxibustion may achieve anti-fatigue effect by affecting the diversity and quantity of intestinal flora, improving intestinal barrier function, and regulating brain-gut peptides.

Inhibition of Connexin 36 attenuates HMGB1-mediated depressive-like behaviors induced by chronic unpredictable mild stress.

BACKGROUND: High mobility group box 1 (HMGB1) released by neurons and microglia was demonstrated to be an important mediator in depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which could lead to the imbalance of two different metabolic approaches in kynurenine pathway (KP), thus enhancing glutamate transmission and exacerbating depressive-like behaviors. Evidence showed that HMGB1 signaling might be regulated by Connexin (Cx) 36 in inflammatory diseases of central nervous system (CNS). Our study aimed to further explore the role of Cx36 in depressive-like behaviors and its relationship with HMGB1. METHODS: After 4-week chronic stress, behavioral tests were conducted to evaluate depressive-like behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Western blot analysis and immunofluorescence staining were used to observe the expression and location of Cx36. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the concentrations of inflammatory cytokines. And the excitability and inward currents of hippocampal neurons were recorded by whole-cell patch clamping. RESULTS: The expression of Cx36 was significantly increased in hippocampal neurons of mice exposed to CUMS, while treatment with glycyrrhizinic acid (GZA) or quinine could both down-regulate Cx36 and alleviate depressive-like behaviors. The proinflammatory cytokines like HMGB1, tumor necrosis factor alpha (TNF-α), and interleukin-1ß (IL-1ß) were all elevated by CUMS, and application of GZA and quinine could decrease them. In addition, the enhanced excitability and inward currents of hippocampal neurons induced by lipopolysaccharide (LPS) could be reduced by either GZA or quinine. CONCLUSIONS: Inhibition of Cx36 in hippocampal neurons might attenuates HMGB1-mediated depressive-like behaviors induced by CUMS through down-regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload.

[Phytochemistry of Cannabis sativa and its variation in different types].

Cannabis sativa, also known as marijuana or hemp, is an annual herb which belongs to Cannabinaceae family. It is often dioecious, originally produced in Central Asia and now is widely distributed in the world, wild or cultivated, with many varieties. As an ancient plant, C.sativa has been used for thousands of years, and its fiber has been used in many aspects, but it is also widely disputed because it contains tetrahydrocannabinol(THC), a psychoactive ingredient. It has been listed as one of the three major drugs by "United Nations Drug Convention", along with heroin and cocaine. Nowadays, with the deepening and comprehensive understanding of C.sativa, it has been widely studied because of its great economic value in the fields of textile, chemicals for daily use, medicine and so on. In this paper, the literature about the chemical compositios and species variation of C.sativa at home and abroad was reviewed in order to provide some reference for its researches.

Comprehensive chemical profiling of Jia-Wei-Qi-Fu-Yin and its network pharmacology-based analysis on Alzheimer's disease.

Jia-Wei-Qi-Fu-Yin (JWQFY) is a newly developed anti-Alzheimer's disease (AD) prescription modified from a classical traditional Chinese medicine formula, Qi-Fu-Yin (QFY). However, a systematic understanding of its chemical constituents and molecular mechanisms is still elusive. To address this problem, comprehensive chemical profiling followed by network pharmacology-based analysis of JWQFY was performed. Firstly, a total of 136 compounds were characterized by high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF MS), 17 of them were specifically identified in JWQFY comparing with QFY. Seventy compounds were further quantified via a validated HPLC coupled with triple quadrupole tandem mass spectrometry (QQQ MS) method. Then the protein targets of the seventy compounds were gathered from public databases for network construction. As a result, fifty-seven compounds were filtered, which interacted with 655 targets. Thirty-four of them were mapped into the KEGG pathway of AD, indicating JWQFY might exert anti-AD effects by anti-inflammation, neuronal apoptosis intervening, Aß production inhibition and phosphorylating tau protein moderating. Furthermore, in the compound-target-AD network, a list of hub compounds and hub targets was identified based on their topological features, including the degree, node betweenness and closeness. Four of the hub compounds were specifically originated from JWQFY, supporting the modification rationality of this formula. This study provided a scientific basis for understanding the bioactive compounds and the multi-target mechanism of JWQFY.

Association between uveitis and psoriatic disease: a systematic review and Meta-analysis based on the evidence from cohort studies.

AIM: To conduct a systematic review and Meta-analysis to examine the association between uveitis and psoriatic disease, and to evaluate whether one condition predisposes individuals to the other. METHODS: We performed a comprehensive search of PubMed and EMBASE to identify cohort studies examining the association between uveitis and psoriatic disease [psoriasis and/or psoriatic arthritis (PsA)]. We used a random-effects model to calculate the pooled relative risks (RRs) adjusted for confounders, along with the 95% confidence intervals (CIs). RESULTS: This Meta-analysis included a total of 6 studies and a maximum of 80 178 648 participants. Compared with non-psoriatic controls, uveitis risk was significantly elevated in patients with psoriasis (RR=1.49; 95%CI: 1.08-2.07), and PsA (RR=3.16; 95%CI: 2.16-4.63). Furthermore, pre-existing uveitis was associated with a significantly increased risk of psoriasis (RR=1.62; 95%CI: 1.44-1.83), and PsA (RR=4.44; 95%CI: 3.52-5.60). CONCLUSION: The results of this systematic review and Meta-analysis suggest an overall positive bidirectional association between uveitis and psoriatic disease (psoriasis and PsA), warranting increased awareness among clinicians involved in the management of these two conditions. Therefore, there remains a need for more detailed studies of the possible common pathogenesis of psoriatic disease and uveitis.

A modified data filtering strategy for targeted characterization of polymers in complex matrixes using drift tube ion mobility-mass spectrometry: Application to analysis of procyanidins in the grape seed extracts.

BACKGROUNDS: Polymers, widely existing in food or dietary materials, have been attracting researchers, facing challenges, and needing effective strategies on targeted characterization in complex matrixes. METHODS: A modified data filtering strategy (including locating with drift time and m/z ranges, multiple mass defect filtering, validating MS information, and evaluating MS/MS spectra) was developed and applied for procyanidins in the grape seed extracts (GSE) using drift tube ion mobility-mass spectrometry. The procyanidin ions' trendlines were predicted by multi-model regression. Their collision cross-sections (CCSs) were calculated using single-field methods. RESULTS AND DISCUSSION: Totally, 769 CCSs belonging to 686 procyanidins with polymer degrees at 1-15 were characterized. The exponent regression was the most reasonable model (r2 ≥ 0.9379) to reveal the trendlines. The change tendency of CCSs with their polymer degrees, charge states, and linkage types were investigated. CONCLUSION: This study provided an innovative strategy for targeted characterization of polymers in complex matrixes.

Manual annotation combined with untargeted metabolomics for chemical characterization and discrimination of two major crataegus species based on liquid chromatography quadrupole time-of-flight mass spectrometry.

Hawthorn is a popular functional food. In China, Crataegus pinnatifida Bunge. and C. pinnatifida Bge. var. major N. E. Brown are two major species that are used for the preparation of hawthorn products. Accordingly, it is crucial to explore the chemical differences between these two species for the market standardization of hawthorn products. In this study, we integrated manual annotation with untargeted metabolomics based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry for compound characterization and discrimination of the two hawthorn species. We characterized 78 compounds in the two species including saccharides, glycosides, organic acids, phenols, flavonoids and triterpenoids. Moreover, 47 differential compounds and 17 false positive ions were recognized and fully reviewed. The 47 identified compounds were then used to build a partial least squares discriminant analysis model that successfully discriminated C. pinnatifida Bge. and C. pinnatifida Bge. var. major N.E.Br.

A strategy for screening bioactive components from natural products based on two-dimensional cell membrane chromatography and component-knockout approach.

Cell membrane chromatography (CMC) is a bioaffinity chromatographic method used to screen active compounds from natural products. However, since the receptor capacity of CMC column is limited, high content/affinity compounds may cause column overloading and thus lead to ignorance of other positive candidates. For avoiding this effect and comprehensively discovering bioactive components, a strategy based on two-dimensional CMC and component-knockout approach was proposed. As an illustrative case study, red yeast rice (RYR), a rice product with good myocardial protective effect in clinical studies, was selected as the model experimental sample. For discovering its potential cardioprotective compounds, a CMC model with H9c2 rat cardiac myoblasts (H9c2/CMC) with good selectivity, stability and reproducibility was established. By using two-dimensional H9c2/CMC-HPLC coupled with QTOF MS system, three components were firstly screened out. After knocking out high content/affinity compound, another four bioactive compounds were then found. By this two-round screening, column overloading caused by high concentration or infinity compounds was avoided, and trace compounds were enriched. As a result, one pigment and six monacolins from RYR were fished out. The results indicate the proposed strategy might be used to discover active compounds from complex matrix.

Rapid characterization of chemical markers for discrimination of Moutan Cortex and its processed products by direct injection-based mass spectrometry profiling and metabolomic method.

BACKGROUND: Processing of herbal medicines is a characteristic pharmaceutical technique in Traditional Chinese Medicine, which can reduce toxicity and side effect, improve the flavor and efficacy, and even change the pharmacological action entirely. It is significant and crucial to perform a method to find chemical markers for differentiating herbal medicines in different processed degrees. PURPOSE: The aim of this study was to perform a rapid and reasonable method to discriminate Moutan Cortex and its processed products, and to reveal the characteristics of chemical components depend on chemical markers. METHODS: Thirty batches of Moutan Cortex and its processed products, including 11 batches of Raw Moutan Cortex (RMC), 9 batches of Moutan Cortex Tostus (MCT) and 10 batches of Moutan Cortex Carbonisatus (MCC), were directly injected in electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF MS) for rapid analysis in positive and negative mode. Without chromatographic separation, each run was completed within 3 min. The raw MS data were automatically extracted by background deduction and molecular feature (MF) extraction algorithm. In negative mode, a total of 452 MFs were obtained and then pretreated by data filtration and differential analysis. After that, the filtered 85 MFs were treated by principal component analysis (PCA) to reduce the dimensions. Subsequently, a partial least squares discrimination analysis (PLS-DA) model was constructed for differentiation and chemical markers detection of Moutan Cortex in different processed degrees. The positive mode data were treated as same as those in negative mode. RESULTS: RMC, MCT and MCC were successfully classified. Moreover, 14 and 3 chemical markers from negative and positive mode respectively, were screened by the combination of their relative peak areas and the parameter variable importance in the projection (VIP) values in PLS-DA model. The content changes of these chemical markers were employed in order to illustrate chemical changes of Moutan Cortex after processed. CONCLUSION: These results showed that the proposed method which combined non-targeted metabolomics analysis with multivariate statistics analysis is reasonable and effective. It could not only be applied to discriminate herbal medicines and their processing products, but also to reveal the characteristics of chemical components during processing.

An UPLC-MS/MS method for simultaneous determination of multiple constituents in Guizhi Fuling capsule with ultrafast positive/negative ionization switching.

Guizhi Fuling capsule (GFC), a traditional Chinese medicine (TCM) with effects of promoting blood circulation and dissipating blood stasis, has been widely used in the clinic. Because of the complex matrix and various chemical structure types, quality control of GFC remains great challenge. In the present study, an ultra performance liquid chromatography hybrid triple-quadrupole mass spectrometry (UPLC-QQQ MS) method with ultrafast positive/negative ionization switching was developed for simultaneous determination of 18 bioactive components in GFC, including methyl gallate, ethyl gallate, oxypaeoniflorin, benzoic acid, albiflorin, paeonolide, paeoniflorin, 1, 2, 3, 4, 6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, pachymic acid, amygdalin, cinnamaldehyde, paeonol, cinnamic acid, 4-hydroxybenzoic acid, and gallic acid. Separation was performed on an Agilent Zorbax Extend-C18 column (2.1 mm × 50 mm, 1.8 µm), using a gradient elution with acetonitrile and water containing 0.1% formic acid. Cholic acid was selected as the internal standard. This newly developed method was fully validated for linearity, precision, accuracy, and stability, and then applied to quality assessment of GFC. Finally, the batch-to-batch reproducibility of GFC samples was evaluated by the cosine ration and Euclidean distance method, which showed high quality consistency. The results demonstrated that the developed method pro vided a reasonable and powerful manner for quality control of GFC.

Highly sensitive strategy for identification of trace chemicals in complex matrix: Application to analysis of monacolin analogues in monascus-fermented rice product.

Trace analysis of chemical analogues was always a hot topic and attracted the researchers' attentions. In this study, a database/multi-step filtering strategy was developed by using HPLC-Chip-MS system for comprehensive characterization of monacolin analogues in monascus-fermented rice product (MFRP). This strategy mainly included three steps, including chemical profile of MFRP by HPLC-Chip-MS, establishment of monacolin analogue database, multi-step filtering of monacolins based on modified mass defect filtering. All target compounds showed the symmetrical peak shapes and high MS response by using nanoflow HPLC-Chip-MS. According to the previous literature and experimental MS data, a database including 720 monacolin analogues was established. The original 522 ions in MFRP were automatically extracted by molecular feature extraction function. And then, through rectangular mass defect filtering and analogues distribution area filtering, 298 ions were further excluded. Finally, a total of 84 monacolins including 16 new compounds were unambiguously identified or tentatively characterized based on MS/MS information. In comparison with conventional mass defect filtering method, the proposed method was accurately able to exclude false positive results. The 438 false positive results were excluded in our study, while only 250 ones would be filtered out by using conventional method. This study provided a sensitive and powerful method for rapidly characterization of trace chemicals in complex matrix.

Advancing and Lengthening Genioplasty in Contouring of the Receding and Short Chin.

BACKGROUND: In East Asia, receding and short chin are common complaints of patients who do not have satisfied lower face. In most former studies, receding and short chin are considered and treated separately. But during the clinical work, the authors found that, in many patients, neither vertical elongation nor horizontal advancement of the chin is sufficient to achieve a harmonious result. In regards of this problem, the authors performed an advancing and lengthening genioplasty and the results were aesthetically satisfactory. STUDY DESIGN: Twenty-six patients with receding and short chin were involved in this study. After presurgical computed tomography (CT) scan, advancing and lengthening genioplasty with/without other osteotomy operations were performed on all the patients. All patients underwent postoperative CT scan and had at least 3-month follow-up. RESULT: All patients were satisfied with the final results. According to the postoperative CT images and 3-month follow-up, no severe complications occurred. CONCLUSION: For patients with receding and short chin, advancing and lengthening genioplasty is a reliable therapy to obtain harmonious East Asian lower face.

Multivariable optimization of the micellar system for the ionic liquid-modified MEKC separation of phenolic acids.

An ionic liquid (IL)-modified micellar electrokinetic chromatography (MEKC) method was proposed for the separation and determination of eight phenolic acids. In order to increase separation efficiency and selectivity, the micelle system consisting of aqueous mixtures of ILs, Tween 20 and borate was optimized using a D-optimal design. A 16-run experimental plan was carried out. The results indicated that the addition of ILs in background electrolyte could significantly alter the electrophoretic behavior and improve the resolution of target analytes. By evaluating the electropherograms obtained, a satisfactory separation condition for all analytes was achieved in 10min with optimized buffer composed of 0.70% (w/w) 1-butyl-3-methylimidazolium tetrafluoroborate, 8.1% (w/w) polyoxyethylene sorbitan monolaurate (Tween 20) and 10mM sodium borate at pH 9.2. Under these conditions, all calibration curves showed good linearity (r(2)>0.9969), and accuracy (recoveries ranging from 94.71 to 106.85%). Finally, the proposed method was successfully applied to determine the phenolic acids in a Chinese medicine compound, compound danshen dripping pills.

Moxibustion for the treatment of pressure ulcers: study protocol for a pilot, multicentre, randomised controlled trial.

INTRODUCTION: Pressure ulcers are common in the elderly and immobile. Currently, there are few proven effective treatments for pressure ulcers. This trial aims to evaluate the feasibility, efficacy and safety of moxibustion for pressure ulcers. METHODS/ANALYSIS: This is a multicentre, two-armed, parallel-design randomised controlled trial (RCT). 30 eligible patients with pressure ulcers will be randomised in a ratio of 1:1 to the treatment group and control group. The participants in the treatment group will undergo indirect moxibustion for 30 min before application of a dressing, one session daily, five sessions weekly for 4 weeks. The patients in the control group will only receive a dressing, applied in the same way as in the treatment group. Both groups will be followed up for 3 months. The primary outcome measures will be wound surface area (WSA) and proportion of ulcers healed within trial period (PUHTP). The secondary outcomes will be the Pressure Ulcer Scale for Healing (PUSH Tool), visual analogue scale (VAS) and adverse events. All outcomes will be evaluated at the beginning of the study, at the end of the second week, at 4 weeks after randomisation and at 1 and 3 months after treatment cessation. ETHICS/DISSEMINATION: This trial has undergone ethical scrutiny and been approved by the ethics review boards of First Affiliated Hospital of Heilongjiang University of Chinese Medicine and Second Affiliated Hospital of Heilongjiang University of Chinese Medicine (Permission number: HZYEYLP2014). The results of this study will provide clinical evidence for the feasibility, efficacy and safety of moxibustion for pressure ulcers. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-13003959.