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Effect of Dahuang Zhechong Pills combined with TACE on VEGF, MMP-2, TGF-β1 and immune function of patients with primary liver cancer (blood stasis and collaterals blocking type)

Zhongguo Zhong Yao Za Zhi. 2021 Feb;46(3):722-729. doi: 10.19540/j.cnki.cjcmm.20200716.501.

ABSTRACT

To investigate the effects of Dahuang Zhechong Pills combined with hepatic arterial chemoembolization(TACE) on tumor index and immune function of patients with primary liver cancer(blood stasis and collaterals blocking type), observe its application values in treatment of such patients, and provide effective treatment means for this disease. From June 2019 to December 2019, 79 patients with confirmed primary liver cancer(blood stasis and collaterals blocking type) treated in Wenzhou Hospital of Traditional Chinese Medicine were included in this study, all of which were grouped with random number table method before inclusion in this study. 40 patients in the control group were treated with TACE, while 39 patients in the observation group were treated with Dahuang Zhechong Pills combined with TACE. The efficacy was compared between two groups after 4 weeks of treatment. The immune function indexes of serum CD4~+ cells, CD4~+/CD8~+, CD3~+ cells of the observation group were higher than those in control group after treatment(P<0.05), and tumor indexes such as serum alpha-fetoprotein(AFP), carbohydrate antigen 199(CA199) and glutamic-pyruvic transaminase(ALT), total bilirubin(TBiL) levels were lower than those in the control group, with statistically significant differences(P<0.05). Plasma vascular endothelial growth factor(VEGF), transforming growth factor-β1(TGF-β1), and matrix metalloprotei-nase-2(MMP-2) levels in the observation group were lower than those in the control group after treatment, with statistically significant differences(P<0.05). The total effective rate of the observation group was 87.18%, higher than 67.50% in the control group, and the benefit rate was 94.87% in the observation group, higher than 85.00% in the control group(P<0.05). The total incidence of adverse reactions such as bone marrow suppression, gastrointestinal reaction, fever, renal function injury and peripheral nerve injury in the observation group was 48.72%, lower than 82.50% in the control group, with statistically significant difference(P<0.05). In summary, the combination of Dahuang Zhechong Pills with TACE could improve immunity, protect liver function, and reduce the risk of metastasis and the incidence of adverse reactions from chemotherapy, so it is worth popularizing for patients with primary liver cancer(blood stasis and collaterals blocking type).

PMID:33645040 | DOI:10.19540/j.cnki.cjcmm.20200716.501

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Meta-analysis of efficacy and safety of sinomenine combined with methotrexate in treatment of rheumatoid arthritis

Zhongguo Zhong Yao Za Zhi. 2021 Jan;46(1):214-224. doi: 10.19540/j.cnki.cjcmm.20200322.501.

ABSTRACT

To systemically evaluate the efficacy and safety of sinomenine combined with methotrexate(SIN+MTX) in the treatment of rheumatoid arthritis(RA). Literature databases of Wanfang, CNKI, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were retrieved comprehensively for relevant clinical trials. The literature retrieval time was from database establishment to February 4, 2020. The quality of literatures was assessed by the Cochrane Evaluation Handbook 5.1.0, and qualified literature was reviewed and analyzed by using the RevMan 5.3 statistical software. Twenty randomized controlled trials met the inclusion criteria, and were enrolled in the Meta-analysis. The results showed that SIN+MTX remarkably reduced DAS28(MD=-0.85, 95%CI[-1.03,-0.67], P<0.000 01), and improved total efficiency(P<0.000 01). SIN+MTX could inhibit swollen joint count(MD=-1.19, 95%CI[-1.75,-0.63], P<0.000 1), tender joint count(MD=-1.58, 95%CI[-2.89,-0.28], P=0.02) and reduce morning stiffness time(MD=-8.44, 95%CI[-11.82,-5.07], P<0.000 01) compared with control group. The results showed that SIN+MTX was equal to control group in grip strength(SMD=0.20,95%CI[-1.11,1.51],P=0.77). SIN+MTX remarkably alleviated the erythrocyte sedimentation rate(MD=-9.87, 95%CI[-14.52,-5.22], P<0.000 1), C-reactive protein(SMD=-0.30, 95%CI[-0.51,-0.09], P=0.005), and rheumatoid factor(MD=-11.23,95%CI[-13.81,-8.65],P<0.000 01). The frequency of adverse reactions were reduced compared with that in the control group(P<0.000 01). Current clinical studies demonstrate that the efficacy and safety of SIN+MTX in the treatment of RA were superior to control group. However, due to the low quality and quantity of the included studies, high-quality randomized controlled trials are necessary to support the clinical evidences.

PMID:33645073 | DOI:10.19540/j.cnki.cjcmm.20200322.501

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Systematic evaluation and sequential Meta-analysis of modified Xuefu Zhuyu Decoction combined with Western medicine in treatment of leiomyoma

Zhongguo Zhong Yao Za Zhi. 2021 Jan;46(1):225-236. doi: 10.19540/j.cnki.cjcmm.20200401.501.

ABSTRACT

CNKI, PubMed and other databases were retrieved to extract eligible randomized controlled trial(RCT) about modified Xuefu Zhuyu Decoction(MXZD) combined with Western medicine(trial group) versus Western medicine alone(control group) in the treatment of leiomyoma. Therefore, a total of 25 RCTs were included, involving 2 328 patients. Bias risk evaluation tool in Cochrane Handbook 5.1.0 was used for evaluating the quality of these RCTs. Meta-analysis was performed for the reported indicators, including total efficiency, serum hormone level [progesterone(P), luteinizing hormone(LH), estradiol(E_2), follicle stimulating hormone(FSH)], uterine size, fibroids size and adverse reactions by using Stata 14.0 software. Meta-analysis showed that the total efficiency(RR=1.21,95%CI[1.17,1.25],P<0.05) of trial group was better than that of control group. Serum hormone level(WMD_P=-3.86,95%CI[-4.31,-3.41],P<0.05; WMD_(LH)=-3.64,95%CI[-4.47,-2.82],P<0.05; WMD_(E_2)=-39.99,95%CI[-53.45,-26.52],P<0.05; WMD_(FSH)=-3.79,95%CI[-4.86,-2.72],P<0.05), uterine size(WMD=-50.02,95%CI[-55.98,-44.06],P<0.05), fibroids size(WMD=-15.79,95%CI[-18.11,-13.46],P<0.05) and adverse reactions(RR=0.65,95%CI[0.48,0.88],P<0.05) of trial group were all lower than those of control group, with statistical significances. Trial sequential analysis(TSA) was performed by using TSA 0.9 software, and showed a reliable therapeutic effect of the experimental group. In short, our study indicated that modified Xuefu Zhuyu Decoction combined with Western medicine had a better therapeutic effect on leiomyoma than Western medicine alone, but more high-quality studies are needed to verify this conclusion in the future.

PMID:33645074 | DOI:10.19540/j.cnki.cjcmm.20200401.501

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Molecular and biological features of Culex quinquefasciatus homozygous larvae for two cqm1 alleles that confer resistance to Lysinibacillus sphaericus larvicides

Pest Manag Sci. 2021 Feb 28. doi: 10.1002/ps.6349. Online ahead of print.

ABSTRACT

BACKGROUND: Culex quinquefasciatus resistance to the binary toxin from Lysinibacillus sphaericus larvicides can occur because of mutations in the cqm1 gene that prevents the expression of the toxin receptor, Cqm1 α-glucosidase. In a resistant laboratory-selected colony maintained for more than 250 generations, cqm1REC and cqm1REC-2 resistance alleles were identified. The major allele initially found, cqm1REC, became minor and was replaced by cqm1REC-2. This study aimed to investigate the features associated with homozygous larvae for each allele to understand the reasons for the allele replacement and to generate knowledge on resistance to microbial larvicides.

RESULTS: Homozygous larvae for each allele were compared. Both larvae displayed the same level of resistance to the binary toxin (3500-fold); therefore, a change in phenotype was not the reason for the replacement observed. The lack of Cqm1 expression did not reduce the total specific α-glucosidase activity for homozygous cqm1REC and cqm1REC-2 larvae, which were statistically similar to the susceptible strain, using artificial or natural substrates. The expression of eight cqm1 paralog α-glucosidases was demonstrated in resistant and susceptible larvae. Bioassays in which cqm1REC or cqm1REC-2 homozygous larvae were reared under stressful conditions showed that most adults produced were cqm1REC-2 homozygous (69%). Comparatively, in the offspring of a heterozygous sub-colony reared under optimal conditions for twenty generations, the cqm1REC allele assumed a higher frequency (0.72).

CONCLUSION: Homozygous larvae for each allele exhibited a similar resistant phenotype. However, they presented specific advantages that might favor their selection and can be used in designing resistance management practices. This article is protected by copyright. All rights reserved.

PMID:33644981 | DOI:10.1002/ps.6349

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Association of metabolic score for insulin resistance and its 6-year change with incident type 2 diabetes mellitus

J Diabetes. 2021 Feb 28. doi: 10.1111/1753-0407.13161. Online ahead of print.

ABSTRACT

BACKGROUND: The evidence for the association between metabolic score for insulin resistance (METS-IR) and type 2 diabetes mellitus (T2DM) is limited. We aimed to explore the association of METS-IR and its 6-year change with risk of incident T2DM in a rural Chinese population.

METHODS: We analyzed data for 12 107 participants (mean age 50.48 years). A Cox proportional-hazard model was used to estimate the association of METS-IR with incident T2DM by using hazard ratios (HRs) and 95% confidence intervals (CIs); a logistic regression model was used to assess the association of 6-year METS-IR change with incident T2DM by using odds ratios (ORs) and 95% CIs. We used subgroup analyses of the association of METS-IR and its 6-year change with incident T2DM by sex, age, and baseline fasting plasma glucose (FPG) level as well as restricted cubic splines to describe the dose-response association.

RESULTS: The association of METS-IR and 6-year METS-IR change with incident T2DM was significant (per SD unit increase: HR = 1.80, 95% CI: 1.60-2.02 for METS-IR, OR = 1.42, 95% CI: 1.28-1.57 and OR = 1.59, 95% CI: 1.44-1.76 for relative and absolute METS-IR change). The significant association remained on subgroup analyses by sex, age, and baseline FPG level. Dose-response analysis demonstrated that the probability of incident T2DM was significantly increased with increasing METS-IR and 6-year METS-IR change.

CONCLUSIONS: Increased METS-IR and 6-year METS-IR change were positively associated with risk of incident T2DM in a rural Chinese population. METS-IR may be a vital indicator for identifying T2DM.

PMID:33644990 | DOI:10.1111/1753-0407.13161

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Effect of Valeriana jatamansi extract on fecal UPLC-MS/MS metabolomics in rats with diarrheal irritable bowel syndrome

Zhongguo Zhong Yao Za Zhi. 2021 Feb;46(3):678-684. doi: 10.19540/j.cnki.cjcmm.20201119.201.

ABSTRACT

The purpose of this study was to understand the pharmacodynamic effect of Valeriana jatamansi extract in diarrhea predominant irritable bowel syndrome(IBS-D) rat model induced by maternal separation combined with three kinds of stress, and observe the changes of endogenous metabolites in feces after intervention to find potential biomarkers and related metabolic pathways. The animal model of IBS-D was established by maternal separation combined with restraint, ice swimming and tail clamping. The therapeutic effect of each dose group of V. jatamansi extract was evaluated in terms of abdominal withdrawal reflex pressure threshold, fecal water content and immobility time of forced swimming test. In addition, rat feces were collected for detection of metabolic profiles of small molecular metabolites with UPLC-LTQ-Orbitrap MS platform, so as to find the biomarkers of differential metabolism with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogon partial least squares discrimination analysis(OPLS-DA). The results showed that as compared with the normal group, the threshold of abdominal withdrawal reflex pressure was decreased, the fecal water content was increased, and the immobility time of forced swimming test was prolonged in the model group. The results of fecal metabonomics showed that the levels of 39 metabolites were down-regulated and those of 37 metabolites were up-re-gulated. Further analysis showed that these metabolites were related to bile acid metabolism, unsaturated fatty acid metabolism, amino acid metabolism, ceramide metabolism and other metabolic pathways. This study proved that the extract of V. jatamansi had definite pharmacodynamic effect on IBS-D model rats, and the mechanism was discussed from the perspective of fecal metabonomics.

PMID:33645035 | DOI:10.19540/j.cnki.cjcmm.20201119.201

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Proton pump inhibitor use and the efficacy of chemotherapy in metastatic colorectal cancer: a post hoc analysis of a randomized phase 3 trial (AXEPT)

Oncologist. 2021 Feb 28. doi: 10.1002/onco.13735. Online ahead of print.

ABSTRACT

BACKGROUND: Concomitant use of proton pump inhibitors (PPIs) with capecitabine was suggested to be associated with poor outcomes in gastrointestinal cancers. We analyzed the differential impact of PPI use on capecitabine and fluorouracil using the dataset from the AXEPT trial, a phase III randomized trial that demonstrated the non-inferiority of modified XELIRI (mXELIRI; capecitabine plus irinotecan) with FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab in patients with metastatic colorectal cancer.

PATIENTS AND METHODS: Out of the per-protocol set (n=620), patients with information on concomitant medications (n=482) were included in this post-hoc analysis. PPI use was defined as concomitant exposure of capecitabine and the use of any PPI for 20% or more of the study period. The treatment-by-PPI-use interaction was examined after adjusting for stratification factors.

RESULTS: Of the 482 patients, 49 (10.1%) used PPI. Among the PPI users, the mXELIRI group tended to have poorer overall survival compared with the FOLFIRI group. In contrast, among the non-users, the overall survival of the mXELIRI group was significantly better than that of the FOLFIRI group. Similarly, a trend of worse progression-free survival with mXELIRI compared with FOLFIRI was observed in PPI users but not in non-users. Treatment-by-PPI-use interaction was significant for overall survival and progression-free survival.

CONCLUSION: The significant interaction between PPI use and the type of fluoropyrimidine in terms of overall and progression-free survival suggests that fluorouracil could be a more favourable option than capecitabine for patients with metastatic colorectal cancer using PPIs.

IMPLICATIONS FOR PRACTICE: This study showed a significant interaction between the use of proton pump inhibitors (PPIs) and the type of fluoropyrimidines. This interaction mainly comes from the positive impact of PPIs in the survival outcomes in the fluorouracil arm rather than a negative impact of PPIs in the capecitabine arm. The possible drug-drug interaction shown in this study suggests that fluorouracil, rather than capecitabine, could be a more appropriate choice of fluoropyrimidine for patients who are taking PPIs in the treatment of metastatic colorectal cancer.

PMID:33644953 | DOI:10.1002/onco.13735

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How to use statistics to claim antagonism and synergism from binary mixture experiments

Pest Manag Sci. 2021 Feb 28. doi: 10.1002/ps.6348. Online ahead of print.

ABSTRACT

We review statistical approaches applicable for the analysis of data from binary mixture experiments, which are commonly used in pesticide science for evaluating antagonistic or synergistic effects. Specifically, two different situations are reviewed, one where every pesticide is only available at a single dose level and a mixture simply combines these doses, and one where the pesticides and their mixture are used at increasing doses. The former corresponds to using factorial designs whereas the latter corresponds to fixed-ratio designs. We consider dose addition and independent action as references for lack of antagonistic and synergistic effects. Data from factorial designs should be analyzed using two-way analysis of variance models whereas data from fixed-ratio designs should be analyzed using nonlinear dose-response analysis. In most cases, independent action seems the more natural choice for factorial designs. In contrast, dose addition is more appropriate for fixed-ratio designs although dose addition is not equally compatible with all types of dose-response data. Fixed-ratio designs should be preferred as they allow validation of the assumed dose-response relationship and, consequently, provide much stronger claims about antagonistic and synergistic effects than factorial designs. Finally, it should be noted that, in any case, simple ways of summarizing pesticide mixture effects may come at the price of more or less restrictive modelling assumptions. This article is protected by copyright. All rights reserved.

PMID:33644956 | DOI:10.1002/ps.6348

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MRI Findings of Arachnoiditis, Revisited. Is Classification Possible?

J Magn Reson Imaging. 2021 Feb 28. doi: 10.1002/jmri.27583. Online ahead of print.

ABSTRACT

BACKGROUND: Prior imaging studies characterizing lumbar arachnoiditis have been based on small sample numbers and have reported inconsistent results.

PURPOSE: To review the different imaging patterns of lumbosacral arachnoiditis, their significance, and clinical implications.

STUDY TYPE: Retrospective.

POPULATION: A total of 96 patients (43 women; average age 61.3 years) with imaging findings of arachnoiditis (postsurgical: N = 49; degenerative: N = 29; vertebral fracture: N = 6; epidural and subdural hemorrhage: N = 3, infectious: N= 1; other: N = 8) from January 2009 to April 2018.

FIELD STRENGTH/SEQUENCE: Sagittal and axial T2-weighted Turbo Spin Echo at 1.5 T and 3 T.

ASSESSMENT: Chart review was performed to assess the cause of arachnoiditis, and imaging was reviewed by two musculoskeletal and three neurology radiologists, blinded to the clinical data and to each other’s imaging interpretation. Previous classification included a three-group system based on the appearance of the nerve roots on T2-weighted images. A fourth group was added in our review as “nonspecified” and was proposed for indeterminate imaging findings that did not fall into the classical groups. The presence/absence of synechiae/fibrous bands that distort the nerve roots and of spinal canal stenosis was also assessed.

STATISTICAL TESTS: The kappa score was used to assess agreement between readers for both classification type and presence/absence of synechiae.

RESULTS: Postsurgical (51%) and degenerative changes (30%) were the most common etiologies. About 7%-55% of arachnoiditis were classified as group 4. There was very poor classification agreement between readers (kappa score 0.051). There was also poor interreader agreement for determining the presence of synechiae (kappa 0.18) with, however, strong interreader agreement for the presence of synechia obtained between the most experienced readers (kappa 0.89).

DATA CONCLUSION: This study demonstrated the lack of consensus and clarity in the classification system of lumbar arachnoiditis. The presence of synechia has high interreader agreement only among most experienced readers and promises to be a useful tool in assessing arachnoiditis.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

PMID:33644967 | DOI:10.1002/jmri.27583

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Clinical implications of sperm DNA damage in IVF and ICSI: updated systematic review and meta-analysis

Biol Rev Camb Philos Soc. 2021 Mar 1. doi: 10.1111/brv.12700. Online ahead of print.

ABSTRACT

The clinical effect of sperm DNA damage in assisted reproduction has been a controversial topic during recent decades, leading to a variety of clinical practice recommendations. While the latest European Society of Human Reproduction and Embryology (ESHRE) position report concluded that DNA damage negatively affects assisted reproduction outcomes, the Practice Committee of the American Society for Reproductive Medicine (ASRM) does not recommend the routine testing of DNA damage for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Herein, our aim was to perform a systematic review and meta-analysis of studies investigating whether sperm DNA damage affects clinical outcomes in IVF and ICSI, in order to contribute objectively to a consistent clinical recommendation. A comprehensive systematic search was conducted according to PRISMA guidelines from the earliest available online indexing year until March 2020, using the MEDLINE-PubMed and EMBASE databases. We included studies analysing IVF and/or ICSI treatments performed in infertile couples in which sperm DNA damage was well defined and assessed. Studies also had to include information about pregnancy, implantation or live birth rates as primary outcomes. The NHLBI-NIH quality assessment tool was used to assess the quality of each study. Meta-analyses were conducted using the Mantel-Haenszel method with random-effects models to evaluate the Risk Ratio (RR) between high-DNA-damage and control groups, taking into account the 95% confidence intervals. Heterogeneity among studies was evaluated using the I2 statistic. We also conducted sensitivity analyses and post-hoc subgroup analyses according to different DNA fragmentation assessment techniques. We identified 78 articles that met our inclusion and quality criteria and were included in the qualitative analysis, representing a total of 25639 IVF/ICSI cycles. Of these, 32 articles had sufficient data to be included in the meta-analysis, comprising 12380 IVF/ICSI cycles. Meta-analysis revealed that, considering IVF and ICSI results together, implantation rate (RR = 0.74; 95% CI = 0.61-0.91; I2 = 69) and pregnancy rate (RR = 0.83; 0.73-0.94; I2 = 58) are negatively influenced by sperm DNA damage, although after adjustment for publication bias the relationship for pregnancy rate was no longer significant. The results showed a non-significant but detrimental tendency (RR = 0.78; 0.58-1.06; I2 = 72) on live birth rate. Meta-analysis also showed that IVF outcomes are negatively influenced by sperm DNA damage, with a statistically significant impact on implantation (RR = 0.68; 0.52-0.89; I2 = 50) and pregnancy rates (RR = 0.72; 0.55-0.95; I2 = 72), although the latter was no longer significant after correction for publication bias. While it did not quite meet our threshold for significance, a negative trend was also observed for live birth rate (RR = 0.48; 0.22-1.02; I2 = 79). In the case of ICSI, non-significant trends were observed for implantation (RR = 0.79; 0.60-1.04; I2 = 72) or pregnancy rates (RR = 0.89; 0.78-1.02; I2 = 44), and live birth rate (RR = 0.92; 0.67-1.27; I2 = 70). The current review provides the largest evidence to date supporting a negative association between sperm DNA damage and conventional IVF treatments, significantly reducing implantation and pregnancy rates. The routine use of sperm DNA testing is therefore justified, since it may help improve the outcomes of IVF treatments and/or allow a given couple to be advised on the most suitable treatment. Further well-designed controlled studies on a larger number of patients are required to allow us to reach more precise conclusions, especially in the case of ICSI treatments.

PMID:33644978 | DOI:10.1111/brv.12700