Analysis of factors related to the development of ocular biometric parameters in Chinese children aged 6-10 years: a cross-sectional study.

OBJECTIVES: Emmetropia depends on the precise coordination of ocular biometry, including axial length (AL), corneal curvature, lens thickness and anterior chamber depth (ACD). Disruption of this coordination leads to refractive errors such as myopia. This article aimed to determine the factors affecting ocular biometry and myopia development in young children. DESIGN: A cross-sectional study. SETTING: This study was conducted in a primary school in the Yanqing district of Beijing, China. PARTICIPANTS: 792 students in grades 1-3 without hyperopia (>+2.00 D), strabismus, or amblyopia were selected. EXCLUSIONS: students had conditions affecting best corrected visual acuity and whose guardians refused to provide informed consent. Ocular biometric measurements and non-cycloplegia autorefraction were performed. The questionnaire addressed factors such as perinatal factors and environmental factors. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOMES: Ocular biometry and myopia. RESULTS: According to the multivariate logistic regression analysis, electronic screen use >2 hours/day (OR=2.175, p=0.013), paternal myopia (OR=1.761, p=0.002), maternal myopia (OR=1.718, p=0.005), taller height (OR=1.071, p<0.001), maternal education (OR=0.631, p=0.012) and maternal gestational hypertension (OR=0.330, p=0.042) were associated with myopia. AL was affected by female sex (OR=0.295, p<0.001), older age (OR=1.272, p=0.002) and taller height (OR=1.045, p<0.001). Female sex (OR=0.509, p<0.001), taller height (OR=1.046, p<0.001), use of electronic screens >2 hours each day (OR=3.596, p<0.001) and time spent outdoors >2 hours each day (OR=0.431, p=0.001) influenced ACD incidence. Central corneal thickness (CCT) was associated with older age (OR=1.113, p=0.008), paternal education (OR=1.474, p=0.007), premature birth (OR=0.494, p=0.031), history of blue light therapy in infancy (OR=0.636, p=0.041) and history of incubator therapy in infancy (OR=0.263, p=0.009). Only sex influenced corneal curvature. CONCLUSIONS: The factors associated with myopia were partly related to ACD and AL, and perinatal factors were associated with myopia and CCT. TRIAL REGISTRATION NUMBER: ChiCTR2200065398.

Traditional Pediatric Massage Enhanced Hippocampal GR, BDNF and IGF-1 Expressions and Exerted an Anti-depressant Effect in an Adolescent Rat Model of CUMS-induced Depression.

This study aimed to investigate the anti-depressant effect of traditional pediatric massage (TPM) in adolescent rats and its possible mechanism. The adolescent depression model in rats was established by using chronic unpredictable mild stress (CUMS). All rats were randomly divided into five groups (seven per group), including the groups of control (CON), CUMS, CUMS with TPM, CUMS with back stroking massage (BSM) and CUMS with fluoxetine (FLX). The tests of sucrose preference, Morris water maze and elevated plus maze were used to evaluate depression-related behaviors. Plasma corticosterone (CORT) level was measured by ELISA. The gene and protein expressions of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) were measured by RT-qPCR and IHC respectively. The results showed that CUMS induced depression-related behaviors in the adolescent rats, along with decreased weight gain and reduced hippocampal expressions of GR, IGF-1 and BDNF. TPM could effectively prevent depression-related behaviors in CUMS-exposed adolescent rats, manifested as increasing weight gain, sucrose consumption, ratio of open-arm entry, times of crossing the specific quadrant and shortening escape latency. TPM also decreased CORT level in plasma, together with enhancing expressions of GR, IGF-1 and BDNF in the hippocampus. These results may support the clinical application of TPM to prevent and treat adolescent depression.

China Medicinal Plants of the Ampelopsis grossedentata-A Review of Their Botanical Characteristics, Use, Phytochemistry, Active Pharmacological Components, and Toxicology.

Ampelopsis grossedentata (AG) is mainly distributed in Chinese provinces and areas south of the Yangtze River Basin. It is mostly concentrated or scattered in mountainous bushes or woods with high humidity. Approximately 57 chemical components of AG have been identified, including flavonoids, phenols, steroids and terpenoids, volatile components, and other chemical components. In vitro studies have shown that the flavone of AG has therapeutic properties such as anti-bacteria, anti-inflammation, anti-oxidation, enhancing immunity, regulating glucose and lipid metabolism, being hepatoprotective, and being anti-tumor with no toxicity. Through searching and combing the related literature, this paper comprehensively and systematically summarizes the research progress of AG, including morphology, traditional and modern uses, chemical composition and structure, and pharmacological and toxicological effects, with a view to providing references for AG-related research.

Study on the mechanism of electroacupuncture regulating macrophage polarization to improve ulcerative colitis in rats. / ç”µé’ˆè°ƒèŠ‚å·¨å™¬ç»†èƒžæžåŒ–æ”¹å–„å¤§é¼ æºƒç–¡æ€§ç»“è‚ ç‚Žçš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the effect of electroacupuncture(EA) at "Changbing Decoction" on alleviating ulcerative colitis (UC) and regulating the polarization of colonic macrophages in rats, so as to explore its mechanisms underlying improvement of UC. METHODS: Twenty-six male SD rats were randomly divided into 4 groups：normal group(6 rats), model group(8 rats), EA group(6 rats), and western medication group(6 rats). The rat model of UC was established by using 5% dextran sulfate sodium (DSS) solution drinking water for 7 days, followed by drinking 1% DSS solution during treatment period. After 7-day model establishment, EA treatment(10 Hz/50 Hz, 20 min) was applied to "Zhongwan"(CV12), bilateral "Tianshu"(ST25) and "Shangjuxu"(ST37) for 3 d, and rats in the western medication group were given mesalazine suspension(200 mg/kg) by gavage for 3 d. The body weight, spleen weight and colon length of rats were measured. The disease activity index (DAI) score was evaluated. The morphological changes and inflammatory cell infiltration of colon were detected after HE staining and pathological scores were eva-luated. The contents of tumor necrosis factor α(TNF-α), interleukin(IL)-1ß, IL-2 and IL-10 in serum were detected by ELISA. The protein expressions of M1 and M2 macrophage markers nitric oxide synthase (iNOS) and arginase 1(Arg1) were detected by fluorescence double staining and Western blot, respectively. Quantitative real-time PCR was used to detect iNOS and Arg1 mRNA expressions. RESULTS: Compared with the normal group, rats in the model group had increased pathological damage degree and inflammatory cell infiltration in the colon tissue, slowed-down body weight gain, decreased colon length, spleen weight, serum anti-inflammatory factors IL-2 and IL-10 contents, colonic Arg1/CD68 fluorescence positive expression, and Arg1 protein and mRNA expressions(P<0.01, P<0.05), as well as increased DAI scores, colon histopathological scores, contents of serum pro-inflammatory factors TNF-α and IL-1ß, colonic iNOS/CD68 fluorescence positive expression, iNOS protein and mRNA expressions(P<0.01). Compared with the model group, the above indicators were significantly improved in rats of the EA group and the western medication group(P<0.01, P<0.05). CONCLUSIONS: EA of "Changbing Decoction" can improve UC of rats by regulating the polarization of colonic macrophages, inhibiting the generation of M1 macrophages and promoting the generation of M2 macrophages.

Qualitative and quantitative analysis of the component variations of Raphani Semen during the stir-frying process and elucidation of transformation pathways of multiple components.

Raphani Semen (RS) encompasses two distinct application forms in Chinese clinical practice: raw RS (RRS) and stir-fried RS (SRS). They exhibit divergent drug properties and effects, as described in traditional Chinese medicine theory known as "Sheng shu yi zhi, sheng sheng shu jiang". The dissimilarity in RS's drug properties is intrinsically linked to alterations in its internal components during the stir-frying process. Previous studies have demonstrated that stir-frying renders myrosinase inactive, thereby preventing the enzymatic hydrolysis of glucosinolates in RS. However, the precise enzymatic hydrolysis pathway and products of glucosinolates remain unclear. Furthermore, it remains uncertain whether other components undergo changes influenced by endogenous enzymes. The objective of this study is to systematically analyze the chemical components disparities between RRS and SRS using high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-TOF-MS). Additionally, it seeks to elucidate the potential transformation pathways of multiple components from an enzymatic hydrolysis perspective. We have developed a sensitive and efficient high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QQQ-MS) method for quantifying the content of 5 characteristic components, including glucoraphenin, sinapine thiocyanate, sulforaphene, sinapic acid, and 3',6-disinapoylsucrose. Based on retention time and MS spectra, we have identified 19 characteristic components in both SRS and RRS, encompassing glucosinolates and sulfur-containing derivatives, oligosaccharide esters, and small-molecule phenolic acids. Notably, 18 of these components undergo changes during the enzymatic hydrolysis process, leading to the identification of 4 transformation pathways: glucoraphenin, 6-sinapoylglucoraphenin, 3',6-disinapoylsucrose and ß-D-(3,4-disinapoyl) furanofructosyl-α-D-(6-sinapisoyl) glucoside, along with 3'-O-sinapoyl-6-O-feruloylsucrose. Quantitative analysis reveals significant differences, including lower levels of glucoraphenin in RRS compared to SRS, higher sulforaphene and sinapic acid levels in RRS, while sinapine thiocyanate and 3',6-disinapoylsucrose remain unchanged before and after stir-frying. The results of this study highlight distinct chemical compositions between RRS and SRS. Additionally, the method of characterization and content determination constructed in this paper has strong practical value and provides a useful approach for comprehensively evaluating the chemical composition and quality of RS.

[Effect of electroacupuncture on colonic autophagy and AMPK/mTOR signaling pathway in rats with acute ulcerative colitis].

OBJECTIVE: To observe the effect of electroacupuncture （EA） at "Zhongwan" （CV12）, "Tianshu" （ST25） and "Shangjuxu" （ST37） （an acupoint prescription "Changbingfang" for treatment of intestinal disorders） on autophagy and expression of AMPK/mTOR signaling pathway in rats with ulcerative colitis （UC）, so as to explore its mechanism underlying improvement of UC. METHODS: Thirty-two male SD rats were randomly divided into control, model, medication and EA groups, with 8 rats in each group. The UC model was established by free drinking of 5% dextran sulfate sodium salt solution for 7 days. EA stimulation （10 Hz/50 Hz） was delivered to CV12, ST25 and ST37 for 20 min, once a day for 3 consecutive days. Rats of the medication group received gavage of mesalazine suspension （200 mg/kg） once a day, 3 times in total. The rats' general conditions were recorded for calculating the disease activity index （DAI） score （0-4 points）. Histomorphological changes of colon were observed via HE staining. The levels of serum interleukin 6 （IL-6）, tumor necrosis factor-α （TNF-α） and IL-10 were measured by ELISA. The mRNA expressions of LC3B and p62 were tested by fluorescence quantitative PCR. Western blot was used to detect the expression levels of LC3B, p62 and AMPK/mTOR pathway related proteins in colon tissues. RESULTS: Compared with the control group, the DAI score, contents of serum IL-6 and TNF-α, the expression levels of p62 protein and mRNA, ratio of p-mTOR/mTOR were significantly increased （P<0.01）； while the content of serum IL-10, the expression levels of LC3B mRNA, ratio of LC3BⅡ/LC3BⅠ and p-AMPK/AMPK were decreased （P<0.01, P<0.05） in the model group. Relevant to the model group, modeling-induced increases of DAI score, serum IL-6, TNF-α and IL-10 contents, expressions of p62 protein and mRNA, LC3B mRNA, ratio of p-mTOR/mTOR, LC3BⅡ/LC3BⅠ and p-AMPK/AMPK were reversed in both medication and EA groups （P<0.01, P<0.05）. The effect of EA was apparently superior to that of mesalazine in up-regulating ratio of LC3BⅡ/LC3BⅠ and p-AMPK/AMPK, p62 mRNA expression （P<0.01, P<0.05）, and in down-regulating ratio of p-mTOR/mTOR （P<0.05）. H.E. staining showed severe damage of the colonic mucosal barrier with infiltration of a large number of inflammatory cells in the model group, which was milder in medication and EA groups. CONCLUSION: EA of acupoint recipe "Changbingfang" can improve the symptoms in UC rats, which may be related to its functions in promoting colonic autophagy, increasing AMPK phosphorylation level, and decreasing mTOR phosphorylation level.

Acupuncture methods for insomnia disorder in the elderly: protocol for a systematic review and network meta-analysis.

BACKGROUND: Insomnia disorder remains one of the most common sleep disorders in the elderly, with high prevalence and substantial consequences for patients' general health. Despite that increasing clinical trials have indicated that acupuncture seems to be effective for insomnia disorder in the elderly, comparative efficacy and safety of different acupuncture methods for elderly individuals with insomnia disorder has been unclear. Therefore, this protocol outlined a plan to evaluate and rank the efficacy and safety of various acupuncture approaches for insomnia disorder in the elderly. METHODS: A systematic search of 8 bibliographic databases will be conducted from their inception to 18 June 2023, including Cochrane Library, MEDLINE (via PubMed), Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and Chinese Biomedical Literature Database (CBM). Randomized controlled trials investigating acupuncture methods for insomnia disorder in the elderly, published in English or Chinese will be included. The primary outcome is sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). Two reviewers will independently perform study selection, data extraction and risk assessment of bias. The quality of included literatures will be appraised using Cochrane risk-of-bias tool (ROB 2.0). ADDIS (Aggregate Data Drug Information System) V.1.16.8 will be used to conduct Bayesian network meta-analysis. The quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation System (GRADE). DISCUSSION: In this study, the results will provide credible evidence to assess the efficacy and safety of acupuncture therapies for elderly patients with insomnia disorder, assisting patients, physicians and clinical research investigators to select the most appropriate acupuncture method. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered at OSF ( https://osf.io/3kjpq/ ) with a registration number https://doi.org/10.17605/OSF.IO/3KJPQ .

Pulsatilla Decoction and its bioactive component ß-peltatin induce G2/M cell cycle arrest and apoptosis in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PAC), a malignancy that is fatal and commonly diagnosed at a late stage. Despite considerable advancements in cancer treatment, the survival rate of PAC remains largely consistent for the past 60 years. The traditional Chinese medicine formula Pulsatilla Decoction (PD) has been clinically used to treat inflammatory diseases for millennia and recently as a supplementary anti-cancer treatment in China. However, the bioactive ingredients and mechanisms underlying its anti-cancer effect remains unclear. METHODS: The composition and quality control of PD were verified through analysis by high performance liquid chromatography. Cell viability was determined using Cell Counting Kit-8 assay. The cell cycle distribution was analyzed through PI staining and flow cytometry analysis, while apoptotic cells were measured by double staining with Annexin V-FITC and PI. We used immunoblotting to examine protein expressions. The in vivo effects of ß-peltatin and podophyllotoxin were evaluated on a subcutaneously-xenografted BxPC-3 cell nude mice model. RESULTS: The current study demonstrated that PD markedly inhibited PAC cell proliferation and triggered their apoptosis. Four herbal PD formula was then disassembled into 15 combinations of herbal ingredients and a cytotoxicity assay showed that the Pulsatillae chinensis exerted the predominant anti-PAC effect. Further investigation indicated that ß-peltatin was potently cytotoxic with IC50 of ~ 2 nM. ß-peltatin initially arrested PAC cells at G2/M phase, followed by apoptosis induction. Animal study confirmed that ß-peltatin significantly suppressed the growth of subcutaneously-implanted BxPC-3 cell xenografts. Importantly, compared to podophyllotoxin that is the parental isomer of ß-peltatin but clinically obsoleted due to its severe toxicity, ß-peltatin exhibited stronger anti-PAC effect and lower toxicity in mice. CONCLUSIONS: Our results demonstrate that Pulsatillae chinensis and particularly its bioactive ingredient ß-peltatin suppress PAC by triggering cell cycle arrest at G2/M phase and apoptosis.

Manganese-enriched photonic/catalytic nanomedicine augments synergistic anti-TNBC photothermal/nanocatalytic/immuno-therapy via activating cGAS-STING pathway.

As the clinical efficacy of immunotherapy for triple-negative breast cancer (TNBC) remains limited, exploring new immunotherapy approaches is still indispensable. Mn2+ has been proven as a cGAS-STING agonist to remarkably enhance antitumor immunity. Here, we report a combined tumor-therapeutic strategy based on Prussian blue (PB)-mediated photothermal therapy with Mn2+-augmented immunotherapy by synergistically activating the cGAS-STING pathway. Mn-enriched photonic nanomedicine (MnPB-MnOx) were constructed by integrating MnOx onto the surface of Mn-doped PB nanoparticles. All components of MnPB-MnOx are biocompatible and biodegradable, wherein sufficient Mn are endowed through rational nanostructure design, conferring easier cGAS-STING activation. Additionally, tumor hyperthermia strengthened by MnPB under near-infrared light radiation, synergistic with the generation of reactive oxygen species catalyzed by MnOx, double hits cancer cells to release abundant tumor-associated antigens for further promoting immune response stimulation. The local anti-TNBC efficacy of photothermal/immuno-therapy has been proven effective in subcutaneous 4T1-bearing mice. Especially, it has been systematically demonstrated in bilateral orthotopic 4T1-bearing mice that the as-proposed treatment could successfully activate innate and adaptive immunity, and local therapy could engender systemic responses to suppress the distant tumors. Collectively, this work represents a proof-of-concept for a non-invasive Mn-based tumor-immunotherapeutic modality, providing a paradigm for the immunotherapy of metastatic-prone tumors.

Zhizhu decoction alleviates slow transit constipation by regulating aryl hydrocarbon receptor through gut microbiota.

CONTEXT: Slow transit constipation (STC), the most common type of constipation, seriously affects the life of patients. Zhizhu decoction (ZZD), a traditional Chinese medicine compound, has is effective against functional constipation, but the mechanism is still unclear. OBJECTIVE: This research explores the mechanism of ZZD on STC from the perspective of metabolomics and gut microbiota. MATERIALS AND METHODS: Fifty-four C57BL/6 mice were randomly divided into six groups (n = 9): control (control); STC (model); positive control (positive); low-dose (5 g/kg; L-ZZD), medium-dose (10 g/kg; M-ZZD), and high-dose (20 g/kg; H-ZZD) ZZD treatment. Following treatment of mice with ZZD for two weeks, the changes in intestinal motility, colon histology, intestinal neurotransmitters, and aryl hydrocarbon receptor (AHR) pathway determined the effects of ZZD on the pathophysiology of STC. LC-MS targeting serum metabolomics was used to analyze the regulation of ZZD on neurotransmitters, and 16S rRNA high-throughput sequencing was used to detect the regulation of the gut microbiome. RESULTS: ZZD had the highest content of naringin (6348.1 mg/L), and could significantly increase the 24 h defecations (1.10- to 1.42-fold), fecal moisture (1.14-fold) and intestinal transport rate (1.28-fold) of STC mice, increased the thickness of the mucosal and muscular tissue (1.18- to 2.16-fold) and regulated the neurotransmitters in the colon of STC mice. Moreover, ZZD significantly activated the AHR signaling pathway, and also affected the composition of gut microbiota in STC mice. DISCUSSION AND CONCLUSIONS: The beneficial effect and the possible mechanism of ZZD on STC could provide a theoretical basis for the broader clinical application of ZZD.

Prevalence of cervicovaginal human papillomavirus infection and genotype distribution in Shanghai, China.

BACKGROUND: The evaluation of human papillomavirus (HPV) prevalence rate dynamics and genotype distribution could support the adoption of more targeted prevention and treatment of cervical cancer. We aimed to assess the infection status and genotype characteristics of HPV among gynecological outpatients in Shanghai, China. METHODS: Clinical specimens were collected from patients attending gynaecological department of the Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and December 2019. The cervicovaginal infection of 17 high-risk genotypes and 10 low-risk genotypes were analyzed by Luminex-based multiple assays. RESULTS: The overall HPV infection rate was 18.81% (95% CI 18.31-19.30%) in Shanghai city, with high-risk, low-risk and mixed high- and low-risk HPV prevalence being 11.65% (95% CI 11.24-12.06%), 4.19% (95% CI 3.94-4.44%) and 2.96% (95% CI 2.74-3.17%), respectively. The five most prevalent high-risk genotypes were HPV-52 (2.95%), HPV-16 (2.34%), HPV-58 (2.07%), HPV-53 (1.67%) and HPV-39 (1.36%). The most common low-risk genotype was HPV-61 (1.52%), followed by HPV-6 (1.29%) and HPV-81 (1.19%). Moreover, the coverage of HPV genotype by nonavalent vaccine was 10.42%, and non-vaccine-covered high-risk genotype was 7.70%. The 15-24 years age group demonstrated the highest HPV prevalence (43.14%), and significant differences were observed among different age groups (P < 0.001). CONCLUSIONS: This study revealed the HPV prevalence and genotype distribution among women in Shanghai city, which could serve as guidance for HPV vaccination and preventative strategies against cervical cancer in this area.

Therapeutic effects of acupuncture in rheumatoid arthritis are associated with centromere protein F expression.

OBJECTIVE: The objective of this study is to study the critical role of CENPF in regulation of rheumatoid arthritis with acupuncture treatment. METHODS: PCA was used to analyze the different expression genes between AP treatment group and control group. Volcano plot and random forest model were used to analyze the decreased and increased expression genes. RT-qPCR and IF were used to measure the expression of CENPF in CIA model rat with or without AP treatment. The expression of MCP-1, TNF-α and IL-6 was measured by western blotting. The pathology character and arthritis index were used to analyze the severity of joint injury. RESULTS: PCA data showed that the expression of genes was different between AP treatment group and control group from GEO datasets. Volcano plot and random forest model analysis indicated that CENPF is the most significantly increased expression gene after AP treatment. RT-qPCR and IF assay showed that CENPF is reduced expression in CIA model rat, while CENPF is upregulated expression in CIA model rat with AP treatment. Furthermore, overexpression of CENPF reduced the increasing of MCP-1, TNF-α and IL-6 in CIA model rat. On the contrary, CENPF deficiency induced the expression of MCP-1, TNF-α and IL-6 in CIA model rat. Additionally, the expression of MCP-1, TNF-α and IL-6 in CIA model rat was suppressed, whereas knockdown of CENPF antagonized the decrease of MCP-1, TNF-α and IL-6 in CIA model rat with AP treatment. CONCLUSIONS: CENPF may be a key gene in regulation of the therapeutic effects of acupuncture in rheumatoid arthritis. Rheumatoid arthritis is a globally common autoimmune inflammatory disease found especially in China. Acupuncture (AP), a traditional Chinese medicine (TCM) treatment method, is commonly used for treating rheumatoid arthritis. Many studies have demonstrated that acupuncture alone or in combination with other treatments is beneficial to treat clinical situation of rheumatoid arthritis, thus improving function and quality of life. In this study, we found that centromere protein F (CENPF) is a key gene in rheumatoid arthritis with acupuncture treatment by using differentially expressed genes (DEGs) and random forest model analysis of GSE57983 and GSE77298. Acupuncture helps to up-regulate the expression of CENPF in tissues in rheumatoid arthritis. Functionally, overexpression of CENPF inhibits monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and Interleukin (IL)-6 expressions whereas deficiency of CENPF facilitates MCP-1, TNF-α, and IL-6 expressions in a collagen-induced arthritis (CIA) rat model. Furthermore, knocked down CENPF with acupuncture treatment antagonizes the inhibition of MCP-1, TNF-α, and IL-6 expressions in a CIA rat model. CENPF could be a crucial biomarker in regulating function of acupuncture in treating rheumatoid arthritis.

Dynamic network biomarker analysis and system pharmacology methods to explore the therapeutic effects and targets of Xiaoyaosan against liver cirrhosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan is a traditional Chinese herbal formula that has long been used to treat liver cirrhosis, liver failure, and hepatocarcinoma (HCC). However, little is known about its mechanism of action and targets in treating chronic liver disease. AIM OF THE STUDY: This study aimed to detect the critical transition of HCC progression and to explore the regulatory mechanism and targets of Xiaoyaosan treating liver cirrhosis (cirrhosis) using integrative medicinal research involving system biology and pharmacology. MATERIALS AND METHODS: We recruited chronic liver disease participants to obtain gene expression data and applied the dynamic network biomarker (DNB) method to identify molecular markers and the critical transition. We combined network pharmacology and DNB analysis to locate the potential DNBs (targets). Then we validated the DNBs in the liver cirrhosis rat models using Xiaoyaosan treatment. The expression of genes encoding the four DNBs, including Cebpa, Csf1, Egfr, and Il7r, were further validated in rat liver tissue using Western blot analysis. RESULTS: We found EGFR, CEBPA, Csf1, Ccnb1, Rrmm2, C3, Il7r, Ccna2, and Peg10 overlap in the DNB list and Xiaoyaosan-Target-Disease (XTD) network constructed using network pharmacology databases. We investigated the diagnostic ability of each member in the DNB cluster and found EGFR, CEBPA, CSF1, and IL7R had high diagnostic abilities with AUC >0.7 and P-value < 0.05. We validated these findings in rats and found that liver function improved significantly and fibrotic changes were relieved in the Xiaoyaosan treatment group. The expression levels of CSF1 and IL7R in the Xiaoyaosan group were significantly lower than those in the cirrhosis model group. In contrast, CEBPA expression in the Xiaoyaosan group was significantly higher than that in the cirrhosis model group. The expression of EGFR in the Xiaoyaosan group was slightly decreased than in the model group but not significantly. CONCLUSION: Using the DNB method and network pharmacology approach, this study revealed that CEBPA, IL7R, EGFR, and CSF1 expression was remarkably altered in chronic liver disease and thus, may play an important role in driving the progression of cirrhosis. Therefore, CEBPA, IL7R, EGFR, and CSF1 may be important targets of Xiaoyaosan in treating cirrhosis and can be considered for developing novel therapeutics.

Sex differences in the pharmacokinetics and tissue residues of Macleaya cordata extracts in rats.

Macleaya cordata extracts (MCE) are listed as feed additives in animal production by the European Food Authority. The core components of MCE are mainly sanguinarine (SA) and chelerythrine (CHE). This study aims to investigate sex differences in the pharmacokinetics and tissue residues of MCE in rats.Male and female rates were intragastrically administered MCE (1.25 mg·kg-1 body weight and 12.5 mg·kg-1 body weight dose for 28 days). SA and CHE concentrations were determined using high-performance liquid chromatography/tandem mass spectrometry.The peak plasma concentration (Cmax) and area under the curve (AUC) of both CHE and SA were higher in female than in male rats (12.5 mg·kg-1 body weight group), whereas their half-life (T1/2) and apparent volume of distribution (Vd) was lower (p < 0.05). Tissue rfesidue analysis indicated that SA and CHE were more distributed in male than in female rats and were highly distributed in the caecum and liver. SA and CHE were completely eliminated from the liver, kidney, lung, heart, spleen, leg muscle, and caecum after 120 h, indicating they did not accumulate in rats for a long time.Overall, we found that the pharmacokinetics and tissue residues of SA and CHE of male and female rats showed sex differences.

Traditional uses, phytochemistry, pharmacology and current uses of underutilized Xanthoceras sorbifolium bunge: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The Plant Xanthoceras sorbifolium Bunge (X. sorbifolia) has a long history of medicinal use as a traditional Chinese herbal medicine to deal with sterilizing, killing sperm, stabilizing capillary, hemostasis, lowering cholesterol, rheumatism, and pediatric enuresis. Additionally, X. sorbifolia is an oil crop for the production of edible oil due to the health-promotion effect. In recent years, X. sorbifolia has attracted worldwide attention as an important economic crop with low investment and high-income potential. AIM OF THE REVIEW: This review aims to provide a comprehensive appraisal of X. sorbifolia, including the traditional uses, nutrients, phytochemical data, biological activities, and current applications. The natural compounds of X. sorbifolia and potential utilization in pharmacology are highlighted. The aim of this review is to inspire the research enthusiasm to X. sorbifolia and promote the comprehensive utilization of X. sorbifolia. MATERIALS AND METHODS: The research information of X. sorbifolia was collected via Elsevier, American Chemical Society (ACS), PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu scholar, and Google scholar. Additionally, some information was collected from Ph.D. and Master's dissertations, as well as local books. RESULTS: The identification of approximately 195 major phytochemical compounds from different parts of X. sorbifolia is presented in this review, including triterpenoids, flavonoids, phenolic acids, coumarins, lignans, meroterpenoids, monoterpene, alkaloids, and sterol. Among them, triterpenoids, flavonoids, and phenolic acids are the major compounds. Extracts from X. sorbifolia exhibited a wide range of biological activities, such as antioxidant, antibacterial, anti-tumor, anti-neuroinflammatory, anti-adipogenesis, anti-obesity, anti-HIV, gastroprotective, immunoregulatory, and anti-inflammatory activities. CONCLUSIONS: Modern pharmacological studies have been well supported and clarified the traditional medicinal uses of X. sorbifolia, which brought a promising prospect for the pharmaceutical value of this plant. However, the related mechanisms between the structure and pharmacological effects were seldom reported. Also, at present, effective and in-depth research on X. sorbifolia is still relatively lacking. Moreover, there is little research on toxicological experiments. Further clinical trials should also be performed to accelerate the drug research and development.

Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis.

CONTEXT: Xiaoyaosan decoction (XYS), a classical Traditional Chinese Medicine (TCM) formula is used to treat liver fibrosis in clinics. OBJECTIVE: This study explores defined compound combinations from XYS decoction to treat liver fibrosis. MATERIALS AND METHODS: Network pharmacology combined with transcriptomics analysis was used to analyze the XYS decoction and liver depression and spleen deficiency syndrome liver fibrosis. From the constructed XYS-Syndrome-liver fibrosis network, the top 10 active formulas were developed by topological analysis according to network stability. The most active formula was determined by in vitro study. The anti-fibrosis effect was evaluated by in vitro and in vivo studies. RESULTS: According to the network XYS-Syndrome-liver fibrosis network, 8 key compounds and 255 combinations were predicted from in XYS. Luteolin, licochalcone A, aloe-emodin and acacetin formula (LLAAF) had a synergistic effect on the proliferation inhibition of hepatic stellate cells compared to individual compounds alone. The treatment of XYS and LLAAF showed a similar anti-liver fibrotic effect that reduced histopathological changes of liver fibrosis, Hyp content and levels of α-SMA and collagen I in CCl4-induced liver fibrosis in rats. Transcriptomics analysis revealed LLAAF regulated PI3K-Akt, AMPK, FoxO, Jak-STAT3, P53, cell cycle, focal adhesion, and PPAR signalling. Furthermore, LLAAF was confirmed to regulate Jak-STAT and PI3K-Akt-FoxO signalling in vitro and in vivo. CONCLUSIONS: This study developed a novel anti-liver formula LLAAF from XYS, and demonstrated its anti-liver fibrotic activity which may be involved in the regulation of Jak-STAT and PI3K-Akt-FoxO signalling.

Efficacy of combination of localized closure, ethacridine lactate dressing, and phototherapy in treatment of severe extravasation injuries: A case series.

BACKGROUND: The management of severe extravasation injuries is still controversial. Extravasation injuries can be treated in many ways. AIM: To present a series of patients with severe extravasation injuries due to infusion who were managed with ethacridine lactate dressing combined with localized closure and phototherapy. METHODS: In this study, we evaluated the data of eight patients, including six from the Department of Burn, one (with colorectal carcinoma) from the Veteran Cadre Department, and one (with leukemia) from the Hematology Department. Of these, three patients were male and five were female. Age of the patients ranged from 10 mo to 72 years, including two children (10 and 19 mo of age). In this study, the infusion was stopped immediately when the extravasation was identified. The extravasation event was managed routinely using a blocking solution. A ring-shaped localized closure was performed using the blocking agents. Moreover, ethacridine lactate dressing and phototherapy were applied for 3-5 d. RESULTS: In this study, the drugs contained in the infusates were iodixanol, norepinephrine, alprostadil, amino acids, fat emulsion, cefoselis, cefoxitin, and potassium chloride + concentrated sodium chloride. All of the patients achieved complete healing after treatment and no obvious adverse reactions were observed. CONCLUSION: The treatment of severe extravasation injuries using a combination of localized closure, ethacridine lactate dressing, and phototherapy resulted in satisfactory outcomes in patients.

A clinical study on plasma biomarkers for deciding the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia of premature infants.

Objective: The study was designed to investigate some plasma markers which help us to decide the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia (BPD) of premature infants. Methods: Thirty BPD infants were treated by dexamethasone. Among these cases, dexamethasone was significant effective in 10 cases, and no significant effective in 20 cases. These patients were divided into two groups as the significant effect (SE) group (n=10) and the non-significant effect (NE) group (n=20) according to the curative effect of dexamethasone. Fifteen non-BPD infants with gestational age and gender matching were selected as the control group. Plasma samples before and after dexamethasone treatment were collected from three infants chosen randomly from SEG for the data-independent acquisition (DIA) analysis. ELISA was further used to detect the levels of differential proteins LRP1 and S100A8 in all individuals, including SE, NE and control groups. Results: DIA analysis results showed that after dexamethasone treatment, there were a total of 52 plasma proteins that showed significant differences, of which 43 proteins were down-regulated and 9 proteins were up-regulated. LRP1 and S100A8 were two plasma proteins that were significantly changed after dexamethasone treatment. Compared with the control group, plasma LRP1 was significantly increased in BPD. Interestingly, the plasma concentration of LRP1 in the NE group was significantly higher than that in the SE group. S100A8, as an indicator of plasma inflammation, was significantly higher in BPD than the control group. Unlike LRP1, there was no significantly difference between the SE and NE group (P=0.279) before dexamethasone treatment. Conclusion: Elevated plasma LRP1 and S100A8 in BPD infants are two indicators that correlated with the efficacy of dexamethasone, and might be used as biomarkers for deciding the use of adjuvant corticosteroids therapy in the BPD.

Fucoxanthin extracted from Laminaria Japonica inhibits metastasis and enhances the sensitivity of lung cancer to Gefitinib.

ETHNOPHARMACOLOGICAL RELEVANCE: Laminaria japonica, a brown seaweed, has been used in Traditional Chinese Medicine (TCM) to treat a variety of diseases including lung cancer. AIM OF THE STUDY: To demonstrate the effects of Fucoxanthin (FX), a major active component extracted from Laminaria japonica on metastasis and Gefitinib (Gef) sensitivity in human lung cancer cells both in vitro and in vivo. MATERIALS AND METHODS: Invasion and migration of lung cancer cells were detected using the wound healing assay and transwell assay. Epithelial-to-mesenchymal transition (EMT) factors and PI3K/AKT/NF-κB pathways were analyzed by western blotting. RNA interference (RNAi) technology was used to silence TIMP-2 gene expression in A549 cells. The anti-metastatic effect of FX was evaluated in vivo in an experimental lung metastatic tumor model. On the other hand, cell counting kit-8 assay was used to study the cell viability of human lung cancer PC9 cells and Gef resistant PC9 cells (PC9/G) after Gef, FX or FX combined with Gef treatment. PC9 xenograft model was established to explore the anti-tumor effect of FX or combined with Gef. Immunohistochemistry staining assay and immunofluorescence staining assay were used to reveal the effects of FX on lung cancer cell proliferation and apoptosis. RESULTS: FX was able to significantly inhibit lung cancer cells migration and invasion in vitro. FX suppressed the expressions of Snail, Twist, Fibronectin, N-cadherin, MMP-2, PI3K, p-AKT and NF-κB, and increased the expression of TIMP-2. Furthermore, knockdown of TIMP-2 attenuated FX-mediated invasion inhibition. Additionally, we demonstrated that FX inhibited lung cancer cells metastasis in vivo. The anti-metastatic effects of FX on lung cancer cells might be attributed to inhibition of EMT and PI3K/AKT/NF-κB pathway. We further demonstrated that the anti-tumor activity of FX was not only limited to the drug sensitive cell lines, but also prominent on lung cancer cells with Gef resistant phenotype. Furthermore, in vivo xenograft assay confirmed that FX inhibited tumor growth and enhanced the sensitivity of lung cancer cells to Gef and this effect may be due to inhibition of tumor cell proliferation and activation of apoptosis. CONCLUSION: Collectively, our findings suggested that FX suppresses metastasis of lung cancer cells and overcomes EGFR TKIs resistance. Thus, FX is worthy of further investigation as a drug candidate for the treatment of lung cancer.

Xiaoyaosan decoction alleviated rat liver fibrosis via the TGFß/Smad and Akt/FoxO3 signaling pathways based on network pharmacology analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is an outcome of many chronic liver diseases and often results in cirrhosis, liver failure, and even hepatocarcinoma. Xiaoyaosan decoction (XYS) as a classical Traditional Chinese Medicine (TCM) formula is used to liver fibrosis in clinical practice while its mechanism is unclear. AIM OF THE STUDY: The aim of this study was to investigate the anti-fibrosis effect of XYS and to explore the molecular mechanisms by combining network pharmacology and transcriptomic technologies. MATERIALS AND METHODS: The carbon tetrachloride (CCl4)-induced liver fibrosis rat were treated with three doses of XYS. The liver fibrosis and function were evaluated by histopathological examination and serum biochemical detection. The fibrosis related protein a-SMA and collagen I were assessed by Western blot. Different expressed genes (DEGs) between XYS-treated group and model group were analyzed. The herb-component-target network was constructed combined the network pharmacology. The predict targets and pathways were validated by in vitro and in vivo experiments. RESULTS: With XYS treatment, the liver function was significantly improved, and fibrotic changes were alleviated. The a-SMA and collagen I expression levels in the liver were also decreased in XYS-treated rats compared with CCl4 model rats. 108 active components and 42 targets from 8 herbs constituted herb-compound-target network by transcriptomics and network pharmacology analysis. The KEGG pathway and GO enrichment analyses showed that the FoxO, TGFß, AMPK, MAPK, PPAR, and hepatitis B and C pathways were involved in the anti-fibrosis effects of XYS. In the liver tissues, p-FoxO3a and p-Akt expression levels were significantly increased in the CCl4 model group but decreased in the XYS-treated group. The TGFß1/Smad pathway and Akt/FoxO3 pathway were verified in LX2 cells by inhibiting phosphorylation of Smad3 and Akt activity, respectively. CONCLUSIONS: Our findings suggested that XYS markedly alleviated CCl4-induced liver fibrosis in histopathological and serum liver function analyses, and this effect may occur via the TGFß1/Smad and Akt/FoxO signaling pathways.