The impact of WeChat online education and care on the mental distress of caregivers and satisfaction of elderly postoperative colorectal cancer patients.

OBJECTIVE: WeChat-based nursing interventions alleviate mental distress. This study intended to investigate the effect of WeChat online education and care (WOEC) on the mental health of caregivers and the satisfaction of elderly postoperative colorectal cancer (CRC) patients. METHODS: In total, 92 elderly postoperative CRC patients and 92 caregivers were randomly separated into the WOEC group (46 patients and 46 caregivers) and the control care group (46 patients and 46 caregivers). Caregivers received corresponding intervention for 8 weeks. Beck depression inventory (BDI) and beck anxiety inventory (BAI) of caregivers, and self-report satisfaction (SRS) of patients were assessed. RESULTS: In caregivers, BDI scores at 8 weeks after enrollment (W8) (P = 0.024) and BAI score at W8 (P = 0.009), depression severity at W8 (P = 0.036), as well as anxiety severity at 4 weeks after enrollment (W4) (P = 0.028) and W8 (P = 0.047) were declined in the WOEC group versus the control care group. Regarding patients, SRS scores at W4 (P = 0.044) and W8 (P = 0.025), the satisfaction degree at W4 (P = 0.033) and W8 (P = 0.034), as well as the satisfied and very satisfied rates at W4 (P = 0.031) and W8 (P = 0.029) were elevated in the WOEC group versus the control care group. By subgroup analyses, WOEC exhibited favorable effects on reducing mental stress in caregivers of patients with eastern cooperative oncology group performance status at enrollment <3, and in caregivers with an education level of high school & university and above. CONCLUSION: WOEC effectively relieves mental stress in caregivers of elderly postoperative CRC patients, and also elevates satisfaction in these patients.

Virtual Reality-Based Exercise Rehabilitation in Cancer-Related Dysfunctions: Scoping Review.

BACKGROUND: Virtual reality-based exercise rehabilitation (VRER) is a promising intervention for patients with cancer-related dysfunctions (CRDs). However, studies focusing on VRER for CRDs are lacking, and the results are inconsistent. OBJECTIVE: We aimed to review the application of VRER in patients with CRDs. METHODS: This scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist framework. Publications were included from the time of database establishment to October 14, 2023. The databases were PubMed, Embase, Scopus, Cochrane, Web of Science, ProQuest, arXiv, IEEE Xplore, MedRxiv, CNKI, Wanfang Data, VIP, and SinoMed. The population included patients with cancer. A virtual reality (VR) system or device was required to be provided in exercise rehabilitation as an intervention. Eligible studies focused on VRER used for CRDs. Study selection and data extraction were performed by 2 reviewers independently. Extracted data included authors, year, country, study type, groups, sample size, participant age, cancer type, existing or potential CRDs, VR models and devices, intervention programs and durations, effectiveness, compliance, satisfaction, and safety. RESULTS: We identified 25 articles, and among these, 12 (48%) were randomized clinical trials, 11 (44%) were other experimental studies, and 2 (8%) were observational studies. The total sample size was 1174 (range 6-136). Among the 25 studies, 22 (88%), 2 (8%), and 1 (4%) included nonimmersive VR, immersive VR, and augmented reality, respectively, which are models of VRER. Commercial game programs (17/25, 68%) were the most popular interventions of VRER, and their duration ranged from 3 to 12 weeks. Using these models and devices, VRER was mostly applied in patients with breast cancer (14/25, 56%), leukemia (8/25, 32%), and lung cancer (3/25, 12%). Furthermore, 6 CRDs were intervened by VRER, and among these, postmastectomy syndromes were the most common (10/25, 40%). Overall, 74% (17/23) of studies reported positive results, including significant improvements in limb function, joint range of motion, edema rates, cognition, respiratory disturbance index, apnea, activities of daily living, and quality of life. The compliance rate ranged from 56% to 100%. Overall, 32% (8/25) of studies reported on patient satisfaction, and of these, 88% (7/8) reported satisfaction with VRER. Moreover, 13% (1/8) reported mild sickness as an adverse event. CONCLUSIONS: We found that around half of the studies reported using VRER in patients with breast cancer and postmastectomy dysfunctions through nonimmersive models and commercial game programs having durations of 3-12 weeks. In addition, most studies showed that VRER was effective owing to virtualization and interaction. Therefore, VRER may be an alternate intervention for patients with CRDs. However, as the conclusions were drawn from data with acknowledged inconsistencies and limited satisfaction reports, studies with larger sample sizes and more outcome indictors are required.

Association of Gene Polymorphisms in CXC Chemokine Receptor 5 with Rheumatoid Arthritis Susceptibility.

Rheumatoid arthritis (RA) is caused by complicated interactions between genes and the environment. CXC chemokine receptor 5 (CXCR5) is required for B and T follicular helper cell migration and humoral immunity generation. Therefore, this study aimed to assess whether polymorphisms of the CXCR5 gene are implicated in RA development and progression. This case-control study enrolled 285 RA patients and 291 healthy controls. The polymerase chain reaction-ligase detection reaction method was used to genotype rs630923, rs497916, rs3922, and rs676925 in the CXCR5 gene. Epidemiological, clinical, and laboratory data were collected retrospectively. The rs630923 A allele was associated with a higher risk of RA (AOR [adjusted odds ratio]=2.00, 95% confidence interval [CI] =1.14-3.53). However, in the RA group, the frequency of the rs497916 T allele was lower (AOR=0.69, 95% CI=0.51-0.93). Regarding rs3922, AG+GG genotype carriers were at a significantly lower risk for RA than AA genotype carriers (AOR=0.70, 95% CI=0.49-0.99). In the RA group, we found that the different genotypes were significantly associated with specific laboratory values, including rheumatoid factor, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, and alkaline phosphatase. This is the first report indicating that CXCR5 polymorphisms were associated with RA susceptibility. These findings lead to a rising possibility of identifying RA-susceptible individuals based on genetic markers.

Circulating IL-1ß, IL-17, and IP-10 as Potential Predictors of Hepatitis B Virus Infection Prognosis.

Circulating cytokines and chemokines play critical roles in hepatitis B virus (HBV) infection. Here, we explored the effects of proinflammatory and anti-inflammatory effector molecules on HBV progression, e antigen seroconversion, and liver function. Our results showed that circulating interleukin (IL)-17 may be helpful in HBV spontaneous clearance [odds ratio (OR) = 1.468, 95%confidence interval (CI) = 1.080-1.995, P = 0.014] and protective against HBV-related hepatoma development (OR = 0.933, 95%CI = 0.910-0.957, P < 0.001). IL-1ß negatively affected HBV clearance (OR = 0.052, 95%CI = 0.005-0.534, P = 0.013). In patients with chronic hepatitis B, interferon-γ-inducible protein-10 (IP-10) levels significantly increased in the group of abnormal liver function (P = 0.006). Furthermore, positive correlations of IP-10 with alanine aminotransferase and aspartate aminotransferase levels were observed (r s = 0.546 and 0.644, respectively; P < 0.001). In conclusion, inflammatory cytokines and chemokines may be a "double-edged sword" for HBV clearance and progression. Further exploration of the roles of IL-17, IL-1ß, and IP-10 in chronic HBV infection is needed.

Association of the MARCO polymorphism rs6761637 with hepatocellular carcinoma susceptibility and clinical characteristics.

Hepatocellular carcinoma (HCC) remains a significant health problem with a substantial genetic predisposition. The liver harbors the largest proportion of macrophages among all the solid organs. There is considerable controversy regarding the relationship between the macrophage receptor with collagenous structure (MARCO) and tumor development and progression. Accordingly, we performed this case-control study to determine whether associations exist between the MARCO single nucleotide polymorphism rs6761637 and HCC susceptibility and clinical characteristics. We successfully genotyped 586 HCC cases and 647 controls using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The overall genotype distribution of rs6761637 was similar in the HCC and control groups (P = 0.143). However, the CT + CC genotypes of rs6761637 were slightly more common in the HCC group among female (P = 0.021), overweight (body mass index ≥ 24 kg/m2, P = 0.003), and nonsmoking (P = 0.022) individuals. The minor C allele carriers had a 1.47-fold increased risk of developing large tumor nodules (P = 0.041). rs6761637 did not affect the recurrence-free or overall survival rate of patients with HCC (P = 0.247 and 0.304, respectively). In conclusion, this is the first report of the association between MARCO genetic variations and HCC risk. These results suggest that the MARCO rs6761637 polymorphism may play a regulatory role in HCC carcinogenesis, but it does not seem to predict prognosis.

NTCP polymorphisms were associated with fibrosis development in patients with chronic HBV infection.

INTRODUCTION: Sodium taurocholate cotransporting polypeptide has been identified as the hepatitis B virus (HBV) entry receptor. However, information regarding the role of sodium taurocholate cotransporting polypeptide variants in the development of HBV-related advanced cirrhosis and hepatocellular carcinoma is limited. METHODOLOGY: Overall, 581 patients with chronic HBV infection were divided into the liver fibrosis or cirrhosis group based on the Fibrosis-4 index. Further, 183 patients with hepatocellular carcinoma were distributed into early/intermediate and advanced/end stage groups based on Barcelona Clinic Liver Cancer Staging approach. Three single nucleotide polymorphisms were genotyped by high resolution melting curve method. Serum biomarkers of liver function were detected, and hepatocellular carcinoma properties were collected as well. RESULTS: Subjects with GA+AA genotypes at the rs4646287 polymorphism site were associated with a significantly higher rate of fibrosis development (rs4646287 GA+AA genotypes were 13.7% and 20.0% in the non-fibrosis and fibrosis group, respectively; p = 0.038). There were no significant differences between sodium taurocholate cotransporting polypeptide polymorphisms and hepatocellular carcinoma progression. The GA+AA genotype carriers of rs7154439 had relatively high albumin levels (p = 0.035). The rs2296651 GA genotype carriers tended to have solitary tumor nodule and without metastasis (p = 0.004 and 0.015, respectively). CONCLUSIONS: Rs4646287 was associated with HBV-related fibrosis development. Sodium taurocholate cotransporting polypeptide polymorphisms were correlated with serum albumin level as well as hepatocellular carcinoma multifocality and metastasis. Therefore, integrating sodium taurocholate cotransporting polypeptide polymorphisms to a risk stratification algorithm may help clinicians manage the chronic HBV infection patients better.

Genetic Polymorphisms in CD35 Gene Contribute to the Susceptibility and Prognosis of Hepatocellular Carcinoma.

CD35, an important molecule implicated in inflammation and immunity, is reportedly associated with several cancers. However, very few studies have investigated the relationship between CD35 polymorphisms and hepatocellular carcinoma (HCC). The current study was conducted to investigate the association between tag SNPs in CD35 and HCC susceptibility and postoperative recurrence, in an attempt to elucidate the gene-environment interactions in HCC. A total of 1233 Chinese Han people, including 647 healthy controls and 586 HCC cases, were sampled in this study. Six Tag SNPs (rs10494885, rs2296160, rs3737002, rs3849266, rs669117, and rs7525160) of CD35 were selected using the HaploView 4.2 program and genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Overall, the mutation genotypes CC/CG of CD35 rs7525160 significantly increased the risk of HCC. Stratification analysis indicated that CD35 rs7525160 CC/CG genotypes increased HCC risk in patients younger than 65 years and were closely related to the pathological type of poor prognosis of HCC. Cox proportional hazard ratio model analysis revealed that the rs7525160 CC/CG genotype remains a significant independent risk factor for postoperative recurrence of HCC. In conclusion, CD35 rs7525160 polymorphism may contribute to the susceptibility and prognosis of HCC in the Chinese Han population.

HBV upregulated triggering receptor expressed on myeloid cells-1 (TREM-1) expression on monocytes participated in disease progression through NF-Kb pathway.

The triggering receptor expressed on myeloid cells-1 (TREM-1) signal is related to the continuous amplification of inflammatory pathway. However, it is not clear whether and how HBV can regulated the expression of TREM-1 on monocyte participated in the progression of liver disease. Here, we showed that the expression of TREM-1 on monocyte subsets were increased significantly in HBV related liver cirrhosis group compared with chronic infected group and healthy control group. HBsAg and HBeAg could up-regulated TREM-1 on monocyte by NF-KB pathway, and at least last for 72 h. Increased TREM-1 on monocyte might associated with high level of inflammatory cytokine (TNF-a, IL-1ß and IL-6) and the activation of LX-2 cells. Bioinformatics analysis showed that the high expression of TREM-1 was related to the poor prognosis of hepatocellular carcinoma (HCC). The level of TREM-1 might help to predict the progression of HBV infected liver disease and treat target to prevent fibrosis progression.

Association of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 polymorphisms with systemic lupus erythematosus disease activity and biomarker levels: A case-control study in Chinese population.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with considerable genetic predisposition. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) is crucial for the innate immunity and implicated in SLE pathogenesis. Accordingly, we conducted a case-control study to find the association of NLRP3 variations with SLE susceptibility and disease activity.Three single nucleotide polymorphisms of NLRP3 (rs3806268, rs4612666, and rs10754558) were genotyped in 400 SLE patients and 400 healthy controls; the patients were further divided into mild-to-moderate or high disease activity subgroup. Serum cytokines, complements, and autoantibodies were also detected.We found that rs4612666 TT genotype conferred a higher risk of severe disease activity with adjusted odds ratio = 2.08, P = .02 and adjusted odds ratio  = 2.34, P = .01 in the codominant and recessive model, respectively. Nevertheless, there was no association between the 3 single nucleotide polymorphisms of NLRP3 gene and SLE susceptibility. In addition, C4 decreased significantly in rs3806268 GG (P < .001) and rs4612666 TT genotype carriers (P = .03). A higher trend of interleukin-1ß and interleukin-γ release were identified in rs3806268 AA and rs10754558 CC genotype carriers, respectively.NLRP3 polymorphisms are associated with SLE disease activity and hypocomplementemia. Interleukin-1ß and interleukin-γ levels in SLE patients are correlated with NLRP3 variants as well.

Structurally diverse sesquiterpenoids from the aerial parts of Artemisia annua (Qinghao) and their striking systemically anti-inflammatory activities.

Thirteen new sesquiterpenoids, arteannoides F-R (1-13), along with 13 known analogues (14-26), were isolated from the dried aerial parts of Artemisia annua L. Their structures, including absolute configurations, were unambiguously determined by a combination of physical data analyses (HRESIMS, 1D and 2D NMR, and ECD) as well as the crystal structures of 1, 5, 6, 15, 19, and 23. Among the isolated compounds, 1 features an unusual 11-oxatricyclo[6.2.1.04,9]undecan-2-ene ring system, 5 possesses an uncommon 4,11-ether bridged tricyclic framework, whereas 6 is a new eudesmane-type sesquiterpenoid formed via rearrangement of its carbon backbone. The systemically anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on PGE2, NO, TNF-α, and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Moreover, the structure activity relationships of some compounds are summarized, this study will provide new structural templates for discovering potential anti-inflammatory agents.

Highly sensitive and rapid determination of azathioprine metabolites in whole blood lysate by liquid chromatography-tandem mass spectrometry.

Individualized therapy involves genetic test of drug metabolism, which provides information about the initial dose and therapeutic drug monitoring for adjusting the subsequent dose. Consequently, toxic side effects are expected to be minimized and therapeutic effects to be maximized. In this study, an ultra-performance liquid chromatography tandem mass spectrometry method that was specific, accurate and sensitive was developed to simultaneously determine azathioprine two metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methyl-mercaptopurine riboside (6-MMPr) in the whole blood lysate. We precipitated the sample by trifluoroacetic acid under the protection of dithiothreitol, with 6-MMPr and 6-TGN being hydrolyzed to produce 6-methymercaptopurine and 6-thioguanine. In the chromatographic separation, Waters ACQUITY BEH C18 (2.1 × 100 mm, 1.7 µm) chromatographic column was applied and gradient elution was conducted with 0.02 mol/L ammonium acetate buffer (which contains 0.3% formic acid) and acetonitrile at a flow rate of 0.4 ml/min. Tandem mass spectrometry in multiple reaction monitoring mode was applied for detection via electrospray ionization source in positive ionization mode. The analyzing process lasted for no more than 2 min. The calibration curve for each metabolite fitted a least squares model (weighed 1/X) from 1.25 to 5000 ng/ml (r2 > 0.99). The ion pairs were detected as 6-MMP m/z 167.07 â†’ 152.15, 6-TG m/z 168.06 â†’ 134.13, and internal standard m/z 171.07 â†’ 137.14. Under the guidance of FDA guidelines for bioanalytical method validation, we carried out validation and obtained satisfactory results. The method was successfully utilized for monitoring the concentrations of each metabolite from 65 affected patients who had received azathioprine maintenance therapy and achieved optimal results.

Genetic association of E26 transformation specific sequence 1 polymorphisms with the susceptibility of primary biliary cholangitis in China.

Primary biliary cholangitis (PBC) is a chronic and cholestatic liver disease characterized by an autoimmune-mediated destruction of intrahepatic bile ducts. E26 transformation specific sequence 1 (ETS-1) is a transcription factor regulating the expression of various immune-related genes. The aim of our study was to identify the associations between the gene polymorphisms of ETS-1 with the susceptibility and clinical characteristics of PBC in Chinese Han population. Three single nucleotide polymorphisms (rs4937333, rs11221332 and rs73013527) of ETS-1 were selected based on relevant studies. Genotyping was executed with polymerase chain reaction-high resolution melting (PCR-HRM) assay. SNP rs4937333 of ETS-1 was prominent correlation with the susceptibility of PBC (P = 0.007, OR = 1.44, 95%CI = 1.10-1.88). For rs4937333, PBC patients carrying the allele T assumed high-level TP (P = 0.020), and homozygous genotype TT assumed low-level RDW (P = 0.033). For rs11221332, PBC patients carrying the allele T assumed high-level TP and HDLC (P = 0.004, P = 0.015, respectively). For rs73013527, PBC patients carrying the allele T assumed low-level PLT (P = 0.002), and homozygous genotype TT assumed high-level RDW (P = 0.021). In conclusion, Gene polymorphisms of ETS-1 present relevant with the susceptibility of PBC, and affect the expression of TP, HDLC, PLT and RDW concentrations in patients with PBC.

Increased Circulating Follicular Regulatory T-Like Cells May Play a Critical Role in Chronic Hepatitis B Virus Infection and Disease Progression.

Follicular helper T cells (TFH) and follicular regulatory T cells (TFR), subsets of T cells, co-regulate the reactions of germinal center (GC) B cells. TFH provide help to the GC response, while the TFR suppress those processes. Nevertheless, the role of circulating TFR (cTFR) and circulating TFH (cTFH) in chronic hepatitis B virus (HBV) infection remains limited. Twenty healthy controls (HCs), 24 patients with chronic hepatitis B (CHB), 23 with HBV-related liver cirrhosis (LC), and 18 with HBV-related hepatocellular carcinoma were enrolled in our study between October 2015 and September 2016. We detected the frequencies of cTFR-like cells and cTFH-like cells, the percentage of programmed cell death-1 (PD-1), inducible co-stimulator (ICOS), and interleukin-21 (IL-21) expressed on circulating CD4+CXCR5+ T cells by flow cytometry. Compared to the HC group, the percentage of cTFR-like cells and ratio of cTFR-like/cTFH-like were significantly increased in patients with HBV infection. A raised percentage of PD-1 on circulating CD4+CXCR5+ cells and decreased IL-21-producing circulating CD4+CXCR5+ cells were observed in CHB and LC. The production of IL-21 by circulating CD4+CXCR5+ cells was significantly higher in HBeAg negative group than the positive one. Patients with high levels of alanine aminotransferase and HBV-DNA accompanied increased CXCR5+PD-1+CD4+ T cells. In addition, the frequency of cTFR-like cells and the ratio of cTFR-like/cTFH-like were positively correlated with FIB-4 and APRI. Increased cTFR-like cells and impairment of circulating CD4+CXCR5+ T cells might participate in HBV chronic infection and HBV-related diseases.

Aspartate transaminase to platelet ratio index and gamma-glutamyl transpeptidase-to-platelet ratio outweigh fibrosis index based on four factors and red cell distribution width-platelet ratio in diagnosing liver fibrosis and inflammation in chronic hepatitis B.

BACKGROUND: The benefits of using serum markers to diagnose stages of liver disease in chronic hepatitis B (CHB) patients are controversial. We conducted a study to compare the clinical significance of four markers in evaluating liver inflammation and fibrosis in CHB patients. METHODS: A total of 323 treatment-naive CHB patients who received a liver biopsy and routine laboratory testing were enrolled in our study. We used the Scheuer scoring system as a pathological standard for diagnosing liver inflammation and fibrosis. The diagnostic performance of the fibrosis index based on four factors (FIB-4), the aspartate transaminase to platelet ratio index (APRI), the gamma-glutamyl transpeptidase-to-platelet ratio (GPR), and the red cell distribution width-platelet ratio (RPR) were analyzed with receiver-operating characteristic curves (ROC). RESULTS: No significant differences among the four indexes for diagnosing significant fibrosis (S ≥ 2) was found, while APRI and GPR were superior to FIB-4 and RPR in diagnosing moderate (G ≥ 2), severe (G ≥ 3) inflammation, and severe fibrosis (S ≥ 3). The AUROCs for diagnosing G ≥ 2 and G ≥ 3 were 0.732 and 0.861 for APRI, 0.726 and0.883 for GPR, 0.703 and0.705 for FIB-4, and 0.660 and 0.747 for RPR, respectively. The AUROCs for diagnosing S ≥ 2 and S ≥ 3 were0.724 and 0.799 for APRI, 0.714 and0.801 for GPR, 0.683 and0.730 for FIB-4, and 0.643 and 0.705 for RPR, respectively. CONCLUSION: APRI and GPR were more effective than FIB-4 and RPR at diagnosing liver inflammation and fibrosis.

Polymorphisms in sodium taurocholate cotransporting polypeptide are not associated with hepatitis B virus clearance in Chinese Tibetans and Uygurs.

An association between polymorphisms in the sodium taurocholate cotransporting polypeptide (NTCP) and the natural course of hepatitis B virus (HBV) infection in the Chinese Han population has been noted. However, it is not known whether these polymorphisms are associated with the risk of developing chronic HBV infection in other racial or ethnic populations. Accordingly, we conducted a candidate single nucleotide polymorphism (SNP) association study in Tibetan and Uygur HBV-infected patients. A total of 1302 subjects including 871 Tibetans and 431 Uygurs were recruited. According to their serological and clinical characteristics, each ethnic group was divided into two groups comprising spontaneous clearance individuals and persistently infected patients. Three SNPs were genotyped by a high resolution melting curve methodology. Among the SNPs, rs2296651 exhibited a minor allele frequency of <0.01. The frequency of allele A at rs4646287 was much higher in Tibetans (9.4% for Tibetans and 4.6% for Uygurs, p<0.001) than in Uygurs, but the frequency of allele A at rs7154439 was the opposite (15.7% for Tibetans and 20.5% for Uygurs, p=0.002). Irrespective of race, no significant differences in the frequency distributions of the three SNP alleles or genotypes were observed between the case and clearance groups. Moreover, none of the NTCP haplotypes were statistically different between the two groups. Data from the Tibetan patients could be grouped by HBeAg status, viral load and HBV genotype; however, no significant differences were found in the SNP genotype distribution for each characteristic. In conclusion, the NTCP polymorphisms we identified tended to be ethnicity-dependent. For Tibetans and Uygurs, no association of the three SNPs (rs7154439, rs4646287 and rs2296651) and their haplotypes with HBV chronicity was observed. Examination of SNPs in NTCP for their specific associations with the course of HBV infection in other ethnic minority groups is now required.

[Study on contribution of main components in Guizhi Fuling capsule based on molecular imprinting technique and activity screening].

To clarify the active components in Guizhi Fuling capsule in treatment of intrinsic dysmenorrhea, pelvic inflammation and hysteromyoma, main components were gradually knocked out from the capsules, the effects of knockout capsules on uterine contraction, TNF-α secretion, murine splenocytes (SPL) and hysteromyoma cells proliferation were evaluated, respectively. The inhibition of capsules on uterine contraction was weakened by gradient knockout of paeoniflorin, paeonol, and amygdalin. The suppression of capsulte on TNF-α secretion was reduced by gradient knockout of gallic acid, cinnamaldehyde, pentagalloylglucose, and pachyman. The promotion of SPL cells proliferation was reversed by gradient knockout of gallic acid, paeoniflorin, cinnamaldehyde, quercetin, and pachyman. The depression of capsules on hysteromyoma cells proliferation was attenuated by gradient knockout of paeoniflorin, paeonol, pentagalloylglucose, and albiflorin. In conclusion, the compounds mentioned-above could be the key active basis of Guizhi Fuling capsule in treatment of intrinsic dysmenorrhea, pelvic inflammation and hysteromyoma.

[Main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule].

Guizhi Fuling capsule is a traditional Chinese medicine composed of five kinds of medicinal plants, Cinnamomi Ramulus, Poria, Moutan Cortex, Persicae Semen, and Paeoniae Radix Alba. Pharmacology studies have shown that Guizhi Fuling capsule has many activities: anti-inflammatory, analgesic, anti-tumor, regulating smooth muscle, endocrine regulation and enhancing immunity. It achieved obvious effects in the treatment of uterine fibroids, pelvic inflammatory disease, dysmenorrheal, endometriosis, ovarian cysts, breast hyperplasia and other gynecological diseases. This paper reviewed the main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule in recent years.

Association of E26 Transformation Specific Sequence 1 Variants with Rheumatoid Arthritis in Chinese Han Population.

OBJECTIVE: E26 transformation specific sequence 1 (ETS-1) belongs to the ETS family of transcription factors that regulate the expression of various immune-related genes. Increasing evidence indicates that ETS-1 could contribute to the pathogenesis of autoimmune disease. Recent research has provided evidence that ETS-1 might correlate with rheumatoid arthritis (RA), but it's not clearly defined. In this study, we aimed to identify whether polymorphisms of ETS-1 play a role in Rheumatoid arthritis (RA) susceptibility and development in Chinese Han population. METHODS: Four single nucleotide polymorphisms (SNPs) within ETS-1 were selected based on HapMap data and previous associated studies. Whole blood and serum samples were obtained from 158 patients with RA and 192 healthy subjects. Genotyping was performed with polymerase chain reaction-high resolution melting (PCR-HRM) assay and the data was analyzed using SPSS17.0. RESULTS: A significantly positive correlation was observed between the SNP rs73013527 of ETS-1 and RA susceptibility, DAS28 and CRP (P<0.001, P = 0.001, and P = 0.028, respectively). Carriers of the haplotype CCT or TCT for rs4937333, rs11221332 and rs73013527 were associated with decreased risk of RA as compared to controls. No statistical significant difference was observed in the distribution of rs10893872, rs4937333 and rs11221332 genotypes between RA patients and controls. CONCLUSIONS: Our data further supports that ETS-1 has a relevant role in the pathogenesis and development of RA. Allele T of rs73013527 plays a protective role in occurrence of RA but a risk factor in the high disease activity. Rs10893872, rs11221332 and rs4937333 are not associated with RA susceptibility and clinical features.

[Monitor on influence of quality standard improvement upon Guizhi Fuling capsules efficacy].

In 2012, the preparation process and quality standard for Guizhi Fuling capsule were improved. To compare the effects and differences of capsules before (2011) and after(2012-2014) the improvement, evaluation models for intrinsic dysmenorrhea, pelvic inflammation and hysteromyoma were applied in rats. Models were induced by oxytocin, liqiud bacteria mixture and estrogen loading, respectively. The capsules (12 batchs/year, 48 bathcs in all), sampled randomly in 2011-2014, the effects were assessed using the three models. In anti-dysmenorrhea models, remarked reduction of writhing frequency, ET-1 and PGF2α content in uterus could be detected, as well as extension of writhing latency. In pelvic inflammation rats, depression of TNF-α and raise of IL-2 were induced by earh batch of capsules. In hysteromyoma model, uterine weight and smooth muscle proliferation, including E2 and P level in plasma, were lowered obviously by all batchs of capsules. Secondly, Guizhi Fuling capsules produced in 2012-2014 revealed better effectiveness than the ones manufactured in 2011. Moreover, pharmacodynamics indexes of the samples made in 2011 differed significantly between groups, which could not be observed in the ones ot 2012-2014. After tne preparation process and quality standard improvement, the effectiveness and homogeneity of Guizhi Fuling capsules were enhanced.

Insights into the inhibition and mechanism of compounds against LPS-induced PGE2 production: a pathway network-based approach and molecular dynamics simulations.

In comparison to the current target-based screening approach, it is increasingly evident that active lead compounds based on disease-related phenotypes are more likely to be translated to clinical trials during drug development. That is, because human diseases are in essence the outcome of the abnormal function of multiple genes, especially in complex diseases. Therefore, as a conventional technology in the early phase of active lead compound discovery, computational methods that can connect molecular interactions and disease-related phenotypes to evaluate the efficacy of compounds are in urgently required. In this work, a computational approach that integrates molecular docking and pathway network analysis (network efficiency and network flux) was developed to evaluate the efficacy of a compound against LPS-induced Prostaglandin E2(PGE2) production. The predicted results were then validated in vitro, and a correlation with the experimental results was analyzed using linear regression. In addition, molecular dynamics (MD) simulations were performed to explore the molecular mechanism of the most potent compounds. There were 12 hits out of 28 predicted ingredients separated from Reduning injection (RDN). The predicted results have a good agreement with the experimental inhibitory potency (IC50) (correlation coefficient = 0.80). The most potent compounds could target several proteins to regulate the pathway network. This might partly interpret the molecular mechanism of RDN on fever. Meanwhile, the good correlation of the computational model with the wet experimental results might bridge the gap between molecule-target interactions and phenotypic response, especially for multi-target compounds. Therefore, it would be helpful for active lead compound discovery, the understanding of the multiple targets and synergic essence of traditional Chinese medicine (TCM).