[Quality control of Tianwang Buxin Pills based on UPLC fingerprint and multi-component quantification].

Tianwang Buxin Pills have demonstrated therapeutic effects in clinical practice, whereas there is a serious lack of comprehensive quality control to ensure the safety and effectiveness of clinical medication. In this study, ultra-performance liquid chromatography(UPLC) was employed to establish the fingerprint and the method for simultaneously determining the content of seven components of Tianwang Buxin Pills. Furthermore, chemometrics was employed to identify the key factors for the stable quality, which provided a reference for the comprehensive quality control and evaluation of this preparation. There were 25 common peaks in the UPLC fingerprints of 15 batches of Tianwang Buxin Pills, from which thirteen compounds were identified. A quantitation method was established for seven pharmacological components(α-linolenic acid, salvianolic acid B, glycyrrhetinic acid, schisandrin A, ß-asarone, 3,6'-disinapoylsucrose, and ligustilide). The principal component analysis(PCA) and partial least square discriminate analysis(PLS-DA) were performed to determine the key pharmacological components for controlling the quality stability of Tianwang Buxin Pills, which included 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone. The established fingerprint and multi-component content determination method have strong specificity, stability, and reliability. In addition, 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone are the key pharmacological components that ensure the quality stability between batches and can be used to comprehensively control the quality of Tianwang Buxin Pills. The findings provide a scientific basis for the quality evaluation and standard establishment of Tianwang Buxin Pills.

Impact of intravitreal triamcinolone injection following epiretinal membrane peeling on ectopic inner foveal layer classification.

PURPOSE: This study aimed to evaluate the impact of intravitreal triamcinolone acetonide (TA) administration after peeling of idiopathic epiretinal membranes (iERM) on both anatomical and visual outcomes, utilizing the ectopic inner foveal layer (EIFL) staging scheme. METHODS: In this retrospective case-control study, we analyzed 43 eyes from 43 patients diagnosed with iERM between June 2019 and December 2021. All participants were categorized into the TA or control groups based on administering intravitreal TA injection following ERM peeling. We thoroughly reviewed the clinical data, including the preoperative and postoperative best-corrected visual acuity (BCVA), central foveal thickness (CFT), and macular cube volume (VOL), with ERM stages classified according to the EIFL staging scheme. RESULTS: The study enrolled 22 eyes in the TA and 21 in the control groups. Following a mean follow-up period of 11.07 ± 2.02 months, noteworthy improvements in EIFL stages were observed in both cohorts (p < 0.01), but without significant distinctions between groups. In the TA group, 63.64% of eyes demonstrated improvements in EIFL stages, while the control group exhibited 76.19% (p = 0.37). At the final visit, both groups experienced a noteworthy reduction in the postoperative CFT and VOL (p < 0.05), coupled with significant improvement in BCVA (p < 0.01). No substantial differences appeared between the two groups concerning BCVA, CFT, and VOL (all p > 0.05). CONCLUSIONS: Our study suggested that concurrent intravitreal TA injection following ERM removal did not provide additional benefits regarding anatomical and visual improvement in iERM cases classified as Stages 2 and 3.

TikTok video as a health education source of information on heart failure in China: a content analysis.

Background: Heart failure (HF) is a complex and life-threatening syndrome associated with significant morbidity and mortality. While TikTok has gained popularity as a social media platform for sharing HF-related information, the quality of such content on TikTok remains unexplored. Methods: A cross-sectional analysis was conducted on TikTok videos related to HF in China. The sources of the videos were identified and analyzed. The content comprehensiveness of the videos was evaluated using six questions that covered definition, signs and symptoms, risk factors, evaluation, management, and outcomes. The reliability and quality of the videos were assessed using three standardized evaluation instruments: DISCERN, JAMA benchmarks, and the Global Quality Scale. Additionally, the correlation between video quality and video characteristics was further investigated. Results: Among the video sources, 92.2% were attributed to health professionals, while news agencies and non-profit organizations accounted for 5.7% and 2.1%, respectively. The content comprehensiveness score for the videos was 3.36 (SD 3.56), with news agencies receiving the highest scores of 4.06 (SD 3.31). The median DISCERN, JAMA, and GQS scores for all 141 videos were 26.50 (IQR 25.00-28.750), 2.00 (IQR 2.00-2.00), and 2.00 (IQR 2.00-2.00), respectively. Videos from health professionals had significantly higher JAMA scores compared to those from non-profit organizations (P < 0.01). Correlation analysis between video quality and video characteristics showed positive correlations between content comprehensiveness scores and video duration (r = 0.420, P < 0.001), number of comments (r = 0.195, P < 0.05), and number of shares (r = 0.174, P < 0.05). GQS scores were negatively or positively correlated with the number of days since upload (r = -0.212, P < 0.05) and video duration (r = 0.442, P < 0.001). Conclusion: The overall quality of the videos was found to be unsatisfactory, with variations in quality scores observed across different video sources. Content comprehensiveness was inadequate, the reliability and quality of the information presented in the videos was questionable. As TikTok continues to grow as a platform for health information, it is essential to prioritize accuracy and reliability to enhance patients' self-care abilities and promote public health.

Use of Tofacitinib for infant-onset STING-associated vasculopathy: A case report from China.

BACKGROUND: Stimulator of interferon gene (STING)-associated vasculopathy with onset in infancy (SAVI), caused by gain-of-function mutations in human transmembrane protein 173 (TMEM173), is characterized by widespread chronic inflammation primarily affecting the skin and lungs. Although SAVI is an inflammatory disease, typical anti-inflammatory agents have limited or no effect. METHODS AND RESULTS: A 1-year-old boy presented with recurrent facial rashes since he was 8 months. Moreover, he suffered from recurrent oral ulcers, chronic cough, and failure to thrive. Laboratory parameters showed elevated erythrocyte sedimentation rate (ESR) and immunoglobulin levels. Chest high-resolution computed tomography (HRCT) showed interstitial lung disease (ILD). Whole-exome sequencing revealed a heterozygous mutation in the TMEM173 gene (c.463G > A, p.V155M). Ultimately, the patient was diagnosed with SAVI. Tofacitinib was initiated at the age of 19 months, resulting in the alleviation of facial rashes and improvement of ILD within 3 months. CONCLUSION: SAVI is a difficult-to-treat type I interferonopathy. We hope that JAKi treatment will prove valuable for SAVI patients.

Relationship between the Degree of Illness in Elderly Patients with Rheumatoid Arthritis and Parameters of Musculoskeletal Ultrasound and Oswestry Dysfunction Index and Clinical Value Analysis.

Objective: The aim of the study is to explore the relationship between the degree of illness in elderly patients with rheumatoid arthritis (RA) and parameters of musculoskeletal ultrasound (MSUS) and Oswestry Dysfunction Index (ODI) and its clinical value. Methods: The clinical data of 100 elderly patients with RA admitted to our hospital from May 2016 to May 2022 were retrospectively analyzed. The patients were divided into four groups, including the remission group (DAS28 ≤ 2.6, n = 25), low activity group (2.6 ≤ DAS28 ≤ 3.2, n = 25), middle activity group (3.2 ≤ DAS28 ≤ 5.1, n = 25), and high activity group (DAS > 5.1, n = 25) according to the disease activity score-28 (DAS28). All patients underwent ultrasonic detection to compare the relationship between the degree of illness in elderly patients with RA and parameters of MSUS and ODI. Results: The total semiquantitative score of MSUS and ODI score in the remission group were obviously lower than those in the other three groups (P < 0.001). The degree of illness in elderly patients with RA was positively correlated with parameters of MSUS (r = 0.886, P < 0.001). The degree of illness in elderly patients with RA was positively correlated with ODI (r = 0.907, P < 0.001). Conclusion: The degree of illness in elderly patients with RA is closely related to parameters of MSUS and ODI, and the parameters of MSUS have a higher evaluation value for the degree of illness in elderly patients with RA, which are correlated with ODI.

Effects of Etco2 on the Minimum Alveolar Concentration of Sevoflurane that Blunts the Adrenergic Response to Surgical Incision: A Prospective, Randomized, Double-Blinded Trial.

BACKGROUND: CO2 has anesthetic potency and effectively influences the circulatory system. We investigated the effects of Etco2 on the minimum alveolar concentration of sevoflurane that blunts the adrenergic response to surgical incision (MAC-BAR) in patients undergoing radical surgery for gastric carcinoma. METHODS: Ninety patients undergoing radical gastric-carcinoma surgery under general anesthesia were enrolled and randomly assigned into 3 groups. After intubation, the Etco2 in group L (n = 30), group N (n = 30), and group H (n = 30) was adjusted to 25 mm Hg ≤ Etco2 <30 mm Hg, 30 mm Hg ≤ Etco2 < 40 mm Hg, and 40 mm Hg ≤ Etco2 < 45 mm Hg, respectively, by changes in controlled ventilation. Hemodynamics and depth of anesthesia were observed before and after skin incision. The MAC-BAR of sevoflurane for each group was determined using an up-and-down sequential-allocation technique. RESULTS: To obtain 7 crossovers, 25, 26, and 26 patients were used in group L, group N, and group H, respectively. The MAC-BAR of sevoflurane using the up-and-down method for group H was significantly lower than that for group L (2.3% [95% confidence interval {CI}, 2.2-2.4] vs 2.9% [95% CI, 2.7-3.0]; difference, -0.6% [95% CI, -0.7 to -0.4], P < .001) and group N (2.3% [95% CI, 2.2-2.4] vs 2.8% [95% CI, 2.8-2.9]; difference, -0.5% [95% CI, -0.7 to -0.4], P < .001), while no significant difference was found between group L and group N (P = 1.000). CONCLUSIONS: Higher Etco2 levels (Etco2 values equal to 40 mm Hg or higher) can effectively decrease the MAC-BAR of sevoflurane in patients undergoing radical surgery for gastric carcinoma.

Basic Fibroblast Growth Factor Attenuates Injury in Myocardial Infarction by Enhancing Hypoxia-Inducible Factor-1 Alpha Accumulation.

BACKGROUND: The combination of antiapoptotic and angiogenic actions may represent a pharmacotherapeutic strategy for the treatment of myocardial infarction. Fibroblast growth factor (FGF) is expressed in various cell types including endothelial and muscle cells and promotes their survival, migration, and proliferation. METHODS AND RESULTS: Myocardial microvascular endothelial cells were divided into four treatment groups, the sham, hypoxia, basic FGF (bFGF), and bFGF plus 2-methoxyestradiol groups, and subjected to in vitro apoptotic analysis and Matrigel assays. An in vivo model of myocardial infarction was established by ligaturing the left coronary artery of mice in the four treatment groups. Cardiac performance, myocardial injury, endothelial cell angiogenesis, and myocardial apoptosis were assessed. bFGF administration after myocardial infarction improved cardiac function and cell viability, attenuated myocardial injury and apoptosis, and enhanced angiogenesis. Western blotting of HIF-1α, p-AKT, VEGF, p53, BAX, and Bcl-2 showed that bFGF increased HIF-1α, p-AKT, VEGF, and Bcl-2 and decreased BAX protein levels. CONCLUSION: The results of the present study indicated that bFGF attenuates myocardial injury by inhibiting apoptosis and promoting angiogenesis via a novel HIF-1α-mediated mechanism and a potential utility of bFGF in protecting against myocardial infarction.

Sulodexide attenuates endoplasmic reticulum stress induced by myocardial ischaemia/reperfusion by activating the PI3K/Akt pathway.

Acute myocardial ischaemia/reperfusion (MI/R) injury causes severe arrhythmias with a high rate of lethality. Extensive research focus on endoplasmic reticulum (ER) stress and its dysfunction which leads to cardiac injury in MI/R Our study evaluated the effects of sulodexide (SDX) on MI/R by establishing MI/R mice models and in vitro oxidative stress models in H9C2 cells. We found that SDX decreases cardiac injury during ischaemia reperfusion and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase and reduced malondialdehyde in mice plasm, increased Bcl-2 expression, decreased BAX expression in a mouse model of MI/R. In vitro, SDX exerted a protective effect by the suppression of the ER stress which induced by tert-butyl hydroperoxide (TBHP) treatment. Both of the in vivo and in vitro effects were involved in the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway. Inhibition of PI3K/Akt pathway by specific inhibitor, LY294002, partially reduced the protective effect of SDX. In short, our results suggested that the cardioprotective role of SDX was related to the suppression of ER stress in mice MI/R models and TBHP-induced H9C2 cell injury which was through the PI3K/Akt signalling pathway.

A long noncoding RNA NR_045363 controls cardiomyocyte proliferation and cardiac repair.

Long noncoding RNAs (lncRNAs) play important roles in the regulation of genes involved in cell proliferation. We have previously sought to more globally understand the differences of lncRNA expression between human fetal heart and adult heart to identify some functional lncRNAs which involve in the process of heart repair. We found that a highly conserved long noncoding RNA NR_045363 was mainly expressed in cardiomyocytes and rarely in non-cardiomyocytes. NR_045363 overexpression in 7-day-old mice heart could improve cardiac function and stimulate cardiomyocyte proliferation after myocardial infarction. Furthermore, NR_045363 knockdown inhibited proliferation of primary embryonic cardiomyocytes, while NR_045363 overexpression enhanced DNA synthesis and cytokinesis in neonatal cardiomyocytes in vitro. Mechanistic analysis revealed that NR_045363 promoted cardiomyocyte proliferation through interaction with miR-216a, which regulated the JAK2-STAT3 pathway. Our results showed that NR_045363 is a potent lncRNA modulator essential for cardiomyocyte proliferation.

miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease.

BACKGROUND/AIMS: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. METHODS: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-ß-related genes. RESULTS: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-ß via targeting Smad7 in HUVECs. CONCLUSION: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-ß pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment.

miR­186, a serum microRNA, induces endothelial cell apoptosis by targeting SMAD6 in Kawasaki disease.

Kawasaki disease (KD) is an acute, self­limited vasculitis that predominantly affects medium­sized arteries, particularly the coronary arteries. Recent studies have indicated that microRNAs are involved in many diseases, including KD. However, the detailed mechanism remains unclear. The aim of the present study was to explore the role of miR­186 in KD and potentially discover a new target for KD treatment. The results demonstrated that miR­186 was upregulated in serum from patients with KD and KD serum could increase miR­186 transcript levels in endothelial cells (HUVECs). Overexpression of miR­186 mimic induced HUVEC apoptosis through mitogen­activated protein kinase (MAPK) activation by targeting and inhibiting SMAD family member 6 (SMAD6). Furthermore, KD serum induced HUVEC apoptosis through miR­186. In conclusion, the present results suggested that KD serum­associated miR­186 has an essential role in endothelial cell apoptosis by activating the MAPK pathway through targeting the SMAD6 gene.

Characterization of the Principal Constituents of Danning Tablets, a Chinese Formula Consisting of Seven Herbs, by an UPLC-DAD-MS/MS Approach.

Danning Tablets are a traditional Chinese formula showing broad clinical applications in hepatobiliary diseases and containing a diversity of bioactive chemicals. However, the chemical profiling of the formula, which serves as the material foundation of its efficacy, is really a big challenge as Danning Tablets consist of seven herbs from different origins. An ultra-performance liquid chromatography coupled to diode array detection and electrospray ionization mass spectrometry (UPLC-DAD-ESI-MS/MS) approach was developed to characterize the principal polyphenol constituents in the formula. As a result, a total of 32 constituents, including 14 anthraquinones and their glucosides, four anthrones, two naphthalene glycosides, two stilbenes and 10 flavonoids were identified based on their retention time, UV absorption and MS/MS fragmentation patterns. The sources of these compounds were also illustrated. Most of the bioactive anthraquinone derivatives were found in Rhei Radix et Rhizoma or Polygoni Cuspidati Rhizoma et Radix, which are the Emperor drugs in the formula for its clinic usage. These findings indicate the merit of using this integrated UPLC-DAD-ESI-MS/MS approach to rapidly illustrate the chemical foundation of complex formulas. The present study will facilitate the quality control of Danning Tablet formulas as well as the individual herbs.

A rare gastric neuroendocrine carcinoma coexisting with Brunner's gland adenoma: A case report.

Gastric neuroendocrine carcinoma (G-NEC) is a rare neoplasm known for its aggressive behavior and poor prognosis. Brunner's gland adenoma (BGA) is a rare benign proliferative lesion that develops most commonly in the duodenum. To the best of our knowledge, no cases of G-NEC coexisting with BGA have previously been reported. The present study therefore reports the first case of G-NEC combined with BGA. A 67-year-old female presented with upper abdominal discomfort. No distant metastases were detected upon pre-operative abdominal computed tomography imaging. The patient underwent a radical distal gastrectomy, D2 lymphadenectomy and Billroth I gastroenterostomy. The resected masses were histologically confirmed to be G-NEC and BGA, respectively. The patient did not receive neoadjuvant or adjuvant chemotherapy or radiotherapy, and remains alive with no evidence of metastasis or recurrence at four years post-surgery.

Fibroblast growth factor receptor 4 protein expression and clinicopathological features in gastric cancer.

AIM: To investigate fibroblast growth factor receptor 4 (FGFR4) protein expression in Chinese patients with resectable gastric cancer (GC) and the association with clinicopathological characteristics and survival. METHODS: One hundred and seventy-five GC patients who underwent curative surgical procedures were enrolled in this study. The protein expression of FGFR4 in formalin-fixed, paraffin-embedded (FFPE) GC tissues was determined by immunohistochemical (IHC) analysis. Patient clinicopathological data and survival information were also collected and χ(2) statistical analysis was performed to analyze FGFR4 protein expression in the subgroups with differing clinicopathological characteristics including; gender, age, tumor location, differentiation, tumor-node-metastasis stage, macroscopic type, depth of invasion, lymph node metastases, distant metastasis, neural invasion and vascular invasion. Furthermore, some common molecular markers of GC in our cancer center, including p53, p27, topoisomerase IIα (Topo IIα) were also determined by IHC and their association with FGFR4 protein expression evaluated. The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using the log rank test. RESULTS: Seventy seven cases (44%) were found to have high expression of FGFR4 protein. Significantly different FGFR4 expression was observed between gastric cancers with differing expression of Topo IIα (log rank χ(2) = 9.4760, P = 0.0236). No significant differences were observed between subgroups defined by any of the other clinicopathological characteristics. The median survival time of the FGFR4 high expression (77 cases) and low expression groups (98 cases) was 27 mo and 39 mo, respectively. The five-year survival rates and median survival times of gastric cancers with high FGFR4 expression were worse than those with low expression (30.8% vs 39.2%, 27 mo vs 39 mo), respectively, however, no significant difference was observed in survival time (log rank χ(2) = 1.0477, P = 0.3060). Survival analysis revealed that high expression of FGFR4 was a predictor of poor outcome in GC patients if the tumor was small (less than or equal to 3 cm in size) (log rank χ(2) = 5.5033, P = 0.0190), well differentiated (log rank χ(2) = 7.9757, P = 0.0047), and of T1 or T2 stage invasion depth (log rank χ(2) = 4.8827, P = 0.0271). CONCLUSION: Our results suggest that high tumor expression of FGFR4 protein is not an independent risk factor for GC cancer initiation, but is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or in the early stages of invasion.

Assessment and prognostic analysis of EGFR, HER2, and HER3 protein expression in surgically resected gastric adenocarcinomas.

AIM: To investigate the significance of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, and HER3 expression on survival outcomes in Chinese gastric cancer patients. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded specimens from 121 patients who underwent gastrectomy at Shanghai Renji Hospital from 2007-2010 were retrospectively examined. Fluorescence in situ hybridization and immunohistochemistry techniques were used to identify gene amplification and protein overexpression. Correlations between the expression or amplification of HER family genes and clinicopathological parameters were then determined using statistical analysis. RESULTS: EGFR protein overexpression, an increase in HER2 copy number and gene amplification, and HER3 protein overexpression were identified in 33.1%, 17.4%, and 62.0% of samples, respectively. Statistical analysis showed a significant association between EGFR expression and tumor invasion depth or tumor stage. HER2 was also shown to be significantly associated with the tumor grade. In addition, EGFR protein overexpression was found to be significantly associated with worse overall survival (P=0.03). CONCLUSION: The HER family members showed a high expression in gastric cancer. EGFR protein expression was associated with overall survival.

Fibroblast growth factor receptor 4 Gly388Arg polymorphism in Chinese gastric cancer patients.

AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival. METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 age- and sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ(2) test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ(2) test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC. RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ(2) = 3.589, P = 0.166) and alleles (χ(2) = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ(2) = 5.449, P = 0.020), well differentiated (log rank χ(2) = 12.798, P = 0.000), T1 or T2 stage (log rank χ(2) = 4.745, P = 0.029), without lymph node involvement (log rank χ(2) = 6.647, P= 0.010), and at an early clinical stage (log rank χ(2) = 4.615, P = 0.032). CONCLUSION: Our results suggest that the FGFR4 Gly388Arg polymorphism is not a risk factor for GC cancer initiation but that it is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or at an early clinical stage.

Investigation of the absorbed and metabolized components of Danshen from Fuzheng Huayu recipe and study on the anti-hepatic fibrosis effects of these components.

ETHNOPHARMACOLOGY: Fuzheng Huayu recipe (FZHY) was formulated on the basis of Chinese medicine theory in treating liver fibrosis. It has a significant efficacy against liver fibrosis caused by chronic hepatitis B, with the action mechanisms of inhibition of hepatic stellate cell activation, protection of hepatocyte oxidative injury and regulations of hepatic matrix remodeling etc. AIM OF THE STUDY: To identify the absorbed components and metabolites of Danshen in FZHY in rat serum, and find their active components for anti-liver fibrosis. MATERIAL AND METHODS: A valid high performance liquid chromatography-electrospray ionization ion trap mass spectrometry (HPLC-ESI/MS(n)) method was established to investigate the absorbed and metabolized compounds of Danshen in FZHY in rat serum after oral administration. Mass spectra were acquired in both negative and positive modes. Otherwise, to evaluate the anti-hepatic fibrosis efficacies of absorbed and metabolized compounds, the LX-2 cell line of hepatic stellate cell (HSC), which was crucial cellular basis of fibrogenesis, was cultured and incubated with absorbed compounds, the cytotoxicity was determined with the cellomics Multiparameter Cytotoxicity Kit 1 by High Content Screening (HCS), the cell proliferation was assayed with EdU-DNA incorporation, and the cell activation was analyzed through α-smooth muscle actin (α-SMA) expression with high content screening technology. RESULTS: More than 11 compounds and 2 metabolites from Danshen were identified in the serum after oral administration of FZHY by comparing their mass spectra and retention behavior with reference compounds or literature data. Among these compounds, there were no obvious changes in nuclear morphology, membrane permeability with blow 96 µM of six polar compounds treatment in comparison with control cells, respectively. And the salvianolic acid B (6 µM, 48 µM), caffeic acid (6 µM, 48 µM) and rosmarinic acid (48 µM) could obviously inhibit LX-2 cells proliferation, down-regulate α-SMA expression. CONCLUSION: The results proved that the established method could be applied to analyze the absorbed into blood compounds of Danshen after oral administration FZHY. These absorbed compounds included 11 compounds and 2 metabolites of Danshen. Among them, the salvianolic acid B, caffeic acid and rosmarinic acid were the effective components of FZHY to anti-hepatic fibrosis effects.

Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer.

AIM: To investigate human epidermal growth factor receptor 2 (HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival. METHODS: One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study. HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) analysis on formalin-fixed paraffin-embedded gastric cancer samples from all patients. For scoring, Hofmann's HER2 gastric cancer scoring system was adopted. All cases showing IHC3+ or FISH positivity were defined as HER2 positive. Patient clinicopathological data and survival information were collected. Finally, χ² statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including; gender, age, tumor location, Lauren classification, differentiation, TNM staging, depth of invasion, lymph node metastases and distant metastasis. The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection. RESULTS: According to Hofmann's HER2 gastric cancer scoring criteria, 31 cases (15.74%) were identified as HER2 gene amplified and 19 cases (9.64%) were scored as strongly positive for HER2 membrane staining (3+), 25 cases (12.69%) were moderately positive (2+) and 153 cases (77.66%) were HER2 negative (0/1+). The concordance rate between IHC and FISH analyses was 88.83% (175/197). Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression, with 24 of these cases being eligible for Herceptin treatment according to United States recommendations, and 29 of these cases eligible according to EU recommendations. Highly consistent results were detected between IHC3+, IHC0/1 and FISH (73.68% and 95.42%), but low consistency was observed between IHC2+ and FISH (40.00%). The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively (28.57% vs 13.43%, P = 0.0103; 37.25% vs 11.64%, P < 0.0001), but were not correlated with gender, age, tumor location or TNM stage, depth of invasion, lymph node metastases and distant metastasis. In poorly-differentiated gastric cancer patients, those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis (26.47% vs 7.14%, P = 0.0021). This association was not present in those patients with well-differentiated gastric cancer (28.57% vs 43.33%, P = 0.2832). Within our patient cohort, 26 cases were lost to follow-up. The median survival time for the remaining 171 patients was 18 mo. The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively. Overall survival was not significantly different between HER2-positive and negative groups (χ(2) = 0.9157, P = 0.3386), but in patients presenting well-differentiated tumors, the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group (P = 0.0123). In contrast, patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2. Furthermore, the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender, age, tumor location, TNM classification, lymph node metastases and distant metastasis. CONCLUSION: Patients with intestinal type gastric cancer (GC), well-differentiated GC and poorly-differentiated GC without lymph node metastasis, may all represent suitable candidates for targeted therapy using Herceptin.

FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547.

PURPOSE: FGFR gene aberrations are associated with tumor growth and survival. We explored the role of FGFR2 amplification in gastric cancer and the therapeutic potential of AZD4547, a potent and selective ATP-competitive receptor tyrosine kinase inhibitor of fibroblast growth factor receptor (FGFR)1-3, in patients with FGFR2-amplified gastric cancer. EXPERIMENTAL DESIGN: Array-comparative genomic hybridization and FISH were used to identify FGFR2 amplification in gastric cancer patient tumor samples. The effects of FGFR2 modulation were investigated in gastric cancer cells with FGFR2 amplification and in patient-derived gastric cancer xenograft (PDGCX) models using two approaches: inhibition with AZD4547 and short hairpin RNA (shRNA) knockdown of FGFR2. RESULTS: Amplification of the FGFR2 gene was identified in a subset of Chinese and Caucasian patients with gastric cancer. Gastric cancer cell lines SNU-16 and KATOIII, carrying the amplified FGFR2 gene, were extremely sensitive to AZD4547 in vitro with GI50 values of 3 and 5 nmol/L, respectively. AZD4547 effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules and induced apoptosis in SNU-16 cells. Furthermore, inhibition of FGFR2 signaling by AZD4547 resulted in significant dose-dependent tumor growth inhibition in FGFR2-amplified xenograft (SNU-16) and PDGCX models (SGC083) but not in nonamplified models. shRNA knockdown of FGFR2 similarly inhibited tumor growth in vitro and in vivo. Finally, compared with monotherapy, we showed enhancement of in vivo antitumor efficacy using AZD4547 in combination with chemotherapeutic agents. CONCLUSION: FGFR2 pathway activation is required for driving growth and survival of gastric cancer carrying FGFR2 gene amplification both in vitro and in vivo. Our data support therapeutic intervention with FGFR inhibitors, such as AZD4547, in patients with gastric cancer carrying FGFR2 gene amplification.

Immunophenotype classification and therapeutic outcomes of Chinese primary gastrointestinal diffuse large B-cell lymphoma.

BACKGROUND: Recent studies showed that diffuse large B-cell lymphoma (DLBCL) could be classified into germinal centre B cell-like (GCB) and non-germinal centre B cell-like (non-GCB) phenotypes according to CD10,Bcl-6 and MUM1 expression. But primary gastrointestinal DLBCL has rarely been studied. This study was aimed to investigate the relationship between immunophenotypic classification, therapeutic outcomes and the prognosis of patients with primary gastrointestinal DLBCL. METHODS: Between 1998 and 2010, there were 151 patients studied at Shanghai Renji Hospital with a histopathological diagnosis of primary gastrointestinal DLBCL. Immunohistochemistry was performed using EnVision methods for CD10, BCL-6 and MUM1. The clinicopathologic features and follow-up data were analyzed by the Kaplan-Meier method, log-rank test and χ2 test. RESULTS: According to the expression of CD10, BCL-6 and MUM1, 31.8 % (48/151) of the cases belonged to the GCB subtype and 68.2 % (103/151) belonged to the non-GCB subtype. There was a significant difference of local lymph node metastasis between the GCB and non-GCB groups (P < 0.05). Patients in the GCB group had a better survival rate than those in the non-GCB group (5-year survival rate, 65.2 % vs 36.4 %, P < 0.05). In the GCB group, there was no significant difference in survival rates in patients receiving R-CHOP and CHOP therapy (P > 0.05). In the non-GCB group, the survival rate in patients treated with R-CHOP therapy was significantly longer than those treated with CHOP therapy (5-year survival rate, 62.8 % vs 30.8 %, P < 0.05). CONCLUSIONS: The immunophenotype classification of gastrointestinal DLBCL, which is closely related to local lymph node metastasis, is found to have prognostic significance. Immunophenotype classification is also useful in selecting the chemotherapy protocol.