A systematic review and network meta-analysis comparing various non-pharmacological treatments for older people with mild cognitive impairment.

BACKGROUND AND OBJECTIVE: Non-pharmacological therapy appeared to alleviate Mild Cognitive Impairment (MCI) symptoms and signs, according to systematic studies. This network meta-analysis aimed to assess the impact of non-pharmacological therapies on improving cognition in individuals with MCI and identified the most effective intervention. METHODS: We reviewed six databases in search of potentially relevant studies of non-pharmacological therapies such as Physical exercise (PE), Multidisciplinary intervention (MI), Musical therapy (MT), Cognitive training (CT), Cognitive stimulation (CS), Cognitive rehabilitation (CR)，Art therapy (AT), general psychotherapy or interpersonal therapy (IPT), and Traditional Chinese Medicine (TCM) (such as acupuncture therapy, massage, auricular-plaster and other related systems) and others. Excluded the literature such as missing full text, missing search results, or no reporting specific values and combined with the inclusion criteria and exclusion criteria in this article, the literature ultimately included in the analysis addressed the following seven non-drug therapies PE, MI, MT, CT, CS, CR, AT. Mini-mental state evaluation paired meta-analyses were undertaken by taking weighted average mean differences with confidence intervals (CI) of 95%. The network meta-analysis was conducted to compare various therapies. RESULTS: A total of 39 randomized controlled trials, including two three-arm studies, with 3157 participants were included. PE was most likely to be the most effective intervention to slow down the cognitive ability of patients (SMD = 1.34, 95%CI: 0.80, 1.89). CS and CR had no significant effect on cognitive ability. CONCLUSIONS: The non-pharmacological therapy had the potential to greatly promote the cognitive ability of the adult population with MCI. PE had the best chance of being the best non-pharmacological therapy. Due to the limited sample size, substantial variability among different study designs, and the potential for bias, the results should be regarded with caution. Our findings should be confirmed by future multi-center randomized controlled, high-quality large-scale studies.

The Daily Intake Levels of Copper, Selenium, and Zinc Are Associated with Osteoarthritis but Not with Rheumatoid Arthritis in a Cross-sectional Study.

The present study examined potential association between the daily intake and serum levels of copper (Cu), selenium (Se), and zinc (Zn) and the risk of osteoarthritis (OA) and rheumatoid arthritis (RA) using data from the National Health and Nutrition Examination Survey (NHANES). Daily intake and serum concentrations of Cu, Zn, and Se in 4200 adults from the 2011-2016 NHANES were examined and divided into normal, OA patients, and RA patients. The level of serum Cu was higher in OA and RA than in non-arthritis, while the levels of serum Se and Zn were no different in the three groups. Serum Se and Zn, but not Cu, concentrations were highly correlated with daily intake. Cu, Se, and Zn intake was independently associated with increased risk of OA, but not with RA. And there was a trend for higher odds of OA among participants in the higher Cu, Se, and Zn intake. Future large longitudinal studies are warranted to confirm these findings.

Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study.

STUDY QUESTION: What are the roles of maternal 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C combination polymorphisms on the embryological and clinical outcomes of IVF/ICSI? SUMMARY ANSWER: Our study reveals for the first time that the oocyte maturation potential gradually decreases with a reduction of maternal MTHFR activity determined by combined C677T/A1298C polymorphisms, while embryo quality was worse in women with intermediate MTHFR activity. WHAT IS KNOWN ALREADY: Although many previous studies have explored the association between MTHFR polymorphisms and IVF/ICSI outcomes, the results remain contradictory due to inadequate samples, no adjustment for potential confounders and/or the study of C677T and A1298C separately. Few studies have systematically investigated the exact role of MTHFR activity determined by combined C677T/A1298C polymorphisms on the embryological and clinical outcomes of IVF/ICSI. STUDY DESIGN SIZE DURATION: This is a retrospective cohort study investigating 1160 women who were referred for MTHFR genotyping and IVF/ICSI treatment at Peking University Third Hospital from May 2017 to May 2020. PARTICIPANTS/MATERIALS SETTING METHODS: Women who were referred for MTHFR genotyping and their first IVF/ICSI treatment at our hospital were included and those undergoing preimplantation genetic testing cycles were excluded. The included women were divided into different cohorts according to their C677T, A1298C and combined C677T/A1298C genotypes. The embryological outcomes, including oocytes retrieved, metaphase II oocytes, oocyte maturation rate, normal fertilization rate and transplantable embryo rate, were evaluated by generalized linear regression models. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate and live birth rate, were evaluated by log-binomial regression models. All outcomes were adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Women with the combined 677TT/1298AA genotype (hereafter abbreviated as TT/AA, as with other combined genotypes), whose enzyme activity was the lowest, had a lower oocyte maturation rate compared with those with the wild-type genotype (P = 0.007). Moreover, the oocyte maturation rate decreased linearly with the decline in MTHFR enzyme activity determined by combined C677T/A1298C genotypes (P-trend = 0.001). The combined CC/AC, CC/CC&CT/AA and CT/AC genotypes with intermediate enzyme activity were associated with a lower transplantable embryo rate (P = 0.013, 0.030 and 0.039, respectively). The differences in clinical outcomes between women with wild-type genotype and combined C677T/A1298C variant genotypes were not significant. LIMITATIONS REASONS FOR CAUTION: Our study population had comparable embryological outcomes but worse clinical outcomes than other women undergoing IVF/ICSI treatment at our hospital. Therefore, the results related to the clinical outcomes should be generalized with caution. In addition, we did not detect the folate concentration of each patient during pregnancy. However, this might not have much influence on our results because almost all of our study participants took sufficient folic acid around pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: We provide a holistic view of the effect of MTHFR C677T and A1298C polymorphisms on the IVF/ICSI outcomes, which can contribute to providing reasonable folic acid supplementation suggestions for women with different MTHFR genotypes, especially for those with a low oocyte maturation rate and/or low embryo quality. STUDY FUNDING/COMPETING INTERESTS: This work was funded by the National Natural Science Foundation of China (31871447, and 82101677), the National Key Research and Development Program (2019YFA0801400) and the Natural Science Foundation of Beijing Municipality (7202226). The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

[Effect and mechanism of Poria cocos polysaccharides on myocardial cell apoptosis in rats with myocardial ischemia-reperfusion injury by regulating Rho-ROCK signaling pathway].

This study aimed to investigate the effect and underlying mechanism of Poria cocos polysaccharides(PCP) on myocardial cell apoptosis in the rat model of myocardial ischemia-reperfusion injury(MI/RI). Male SPF-grade SD rats were randomly divided into a sham group(saline), a model group(saline), low-and high-dose PCP groups(100 and 200 mg·kg~(-1)), and a fasudil group(10 mg·kg~(-1)), with 16 rats in each group. Except for the sham group, the other four groups underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion for 2 h to establish the MI/RI model. The myocardial infarct area was assessed by TTC staining. Histological changes were observed through HE staining. Myocardial cell apoptosis was evaluated using TUNEL staining. Serum lactate dehydrogenase(LDH), creatine kinase MB(CK-MB), interleukin-1ß(IL-1ß) and IL-18 levels, myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were detected by ELISA. Protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved caspase-3, Ras homolog gene A(RhoA), myosin phosphatase target subunit 1(MYPT-1), phosphorylated MYPT-1(p-MYPT-1), and Rho-associated coiled-coil forming kinase 1(ROCK 1) were measured by Western blot. Pathological staining of myocardial tissue revealed that in the model group, there was focal necrosis of myocardial tissue, myocardial cell swelling, unclear boundaries, and neutrophil infiltration. These pathological changes were alleviated in the low-and high-dose PCP groups and the fasudil group. Compared with the model group, the low-and high-dose PCP groups and the fasudil group showed significantly reduced myocardial infarct area and myocardial cell apoptosis rate. Compared with the sham group, the model group exhibited elevated serum LDH, CK-MB, IL-1ß and IL-18 levels, increased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and decreased myocardial SOD levels and Bcl-2 protein expression. Compared with the model group, the PCP groups and the fasudil group showed lowered serum LDH, CK-MB, IL-1ß and IL-18 levels, decreased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and increased myocardial SOD levels and Bcl-2 protein expression. PCP exhibited a certain preventive effect on myocardial tissue pathological damage and myocardial cell apoptosis in MI/RI rats, possibly related to the inhibition of the Rho-ROCK signaling pathway activation, thereby reducing oxidative stress and inflammatory responses.

[Mechanism of Qingwei Powder in treatment of periodontitis based on UPLC-Q-TOF-MS, GC-MS, network pharmacology and molecular docking].

The present study explored the mechanism of Qingwei Powder(QP) in the treatment of periodontitis based on chromatography-mass spectrometry and network pharmacology-molecular docking techniques. UPLC-Q-TOF-MS and GC-MS were used to identify the chemical constituents of QP. The active components and targets were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and their targets were predicted using SwissTargetPrediction. Targets related to periodontitis were obtained from GeneCards, OMIM, and DisGeNET. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. Cytoscape 3.7.2 was used to construct the "chemical component-target-disease" network. The targets were analyzed for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by clusterProfiler R, and the "chemical component-target-pathway" network was constructed. The binding activity of the active components to the target proteins was verified by molecular docking. A total of 189 chemical components were obtained by UPLC-Q-TOF-MS and GC-MS, including 39 active components with 180 potential targets related to periodontitis. Target enrichment analysis of the active components yielded 92 KEGG pathways. Twenty KEGG pathways, 34 active components, and 99 targets were involved in the "chemical component-target-pathway" network. Molecular docking verified a good binding ability of the key targets to the key compounds. This study preliminarily indicates that QP is effective in treating periodontitis through multiple components, multiple targets, and multiple pathways, which reflects the complex system of Chinese medicine. This study provides the theoretical foundation for the subsequent research on the material basis and key quality attributes of QP.

Meta-analysis of efficacy and safety of sustained release oxycodone hydrochloride rectal administration for moderate to severe pain.

OBJECTIVE: This study aims to evaluate the efficacy and safety of oxycodone hydrochloride (OxyContin) rectal administration in cancer pain patients. This is geared towards providing the research evidence for a novel route of OxyContin administration. METHODS: Relevant randomized controlled trials (RCTs) were searched in electronic databases, including PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). Moreover, unpublished academic data were obtained by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of transrectal Oxycodone administration of sustained-release tablets for moderate and severe pain patients were searched in the databases from inception to December 2020. RESULTS: According to the inclusion criteria, a total of 8 RCTs were included, with a total of 648 patients. Meta analysis results showed that there was no statistically significant difference in the efficacy of moderate to severe pain control between the rectal administration group and the oral administration group (RR = 1.04, 95%CI: 0.99-1.10, p = 0.13>0.05). At the same time, the incidence of adverse reactions in the rectal administration group was low. In terms of constipation, the rectal administration group was less than the oral administration group, with a statistically significant difference (RR = 0.43, 95%CI: 0.31-0.58, p< 0.00001). In terms of nausea and vomiting, the rectal administration group was less than the oral administration group, and the difference was statistically significant(RR = 0.30, 95%CI: 0.21-0.42, p<0.00001). In terms of sleepiness, there was no significant difference between the two groups(RR = 0.54, 95%CI: 0.26-1.15, p = 0.11>0.05). In terms of dizziness, there was no statistically significant difference between the two groups (RR = 0.43, 95%CI:0.27-0.68, p = 0.31>0.05). In terms of dyuria, there was no statistically significant difference between the two groups (RR = 0.37, 95%CI: 0.02-7.02, p = 0.51>0.05). In terms of KPS scores there was no significant difference was noted between the rectal and oral administration groups (RR = 1.04, 95%CI: 0.89-1.21, p = 0.63>0.05). CONCLUSION: In summary, we found no significant differences in efficacy between rectal administration of OxyContin and oral administration. Thus, rectal administration should be considered in managing cancer pain among patients with difficulty in oral OxyContin administration. PROSPERO REGISTRATION NUMBER: CRD42021209660.

Efficacy of paeoniflorin on models of depression: A systematic review and meta-analysis of rodent studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin, a bioactive compound extracted from the traditional Chinese herb, Paeonia lactiflora Pall, has been demonstrated to possess efficient antidepressant activity in previous studies. AIM OF THE STUDY: Our systematic review and meta-analysis aimed to assess the effectiveness of paeoniflorin in relieving depressive-like behaviors in animal models. MATERIALS AND METHODS: We searched for in vivo studies on the antidepressant effects of paeoniflorin in rodents using electronic databases from their inception to April 2021. The measurements of animal behavioral tests, including the sucrose consumption, forced swimming, tail suspension, and open field tests, were regarded as the outcomes. RESULTS: Fourteen studies involving 416 animals met the inclusion criteria and were included in the meta-analysis. Statistical analysis revealed remarkable differences between the paeoniflorin and control groups. Furthermore, the paeoniflorin group showed great efficiency in improving depressive-like symptoms of animals in the sucrose consumption, forced swimming, tail suspension, and open field tests. CONCLUSIONS: Our meta-analysis demonstrates that paeoniflorin can significantly improve depressive-like symptoms in animals and suggests that it can be a potential therapy for patients with depression in the future.

Inhibitory effect of main phenolic acid components of Jacobaea cannabifolia (Less.) on inflammation caused by PM2.5.

PM2.5 is an important environmental problem threatening human health at present, which poses serious harm to human body after inhalation. J. cannabifolia is a traditional Chinese medicine which exhibits anti-inflammatory effect. This study aimed to investigate the inhibitory effect of main phenolic acid components of J. cannabifolia on inflammation caused by PM2.5. Effect of PM2.5 on cell activity and apoptosis were determined by MTT, flow cytometry and calcein AM/PI staining. PHBA, PHPAA, and mixture of PHBA and PHPAA of different concentrations were given to RAW264.7 cells pretreated with PM2.5. The effect of drugs on cellular inflammatory factors was detected by ELISA. The expressions of TLRs related signal pathway at protein and gene levels were detected by western blot and qRT-PCR. The results showed that PM2.5 had no effect on cell activity and apoptosis within the determined concentration range. PHBA and PHPAA could markly inhibit the level of IL-1ß, IL-6, and TNF-α in RAW264.7 cells. Furthermore, the expressions of TLR2, TLR4, MyD88, IRAK1, TRAF6, TAK1, IKKß, and NF-κB induced by PM2.5 were markedly inhibited by PHBA and PHPAA at protein and gene levels. This study demonstrated that PHBA and PHPAA could attenuated inflammation caused by PM2.5 through suppressing TLRs related signal pathway.

A research on the mechanism of NSAID-related gastric ulcer treated by jia wei wu qi san based on the p38mapk signal pathway.

This study aims to explore the mechanism of NSAID-related gastric ulcer treated by JIA WEI WU QI SAN. Clean-grade SD rats were randomly divided into four groups. Group A was assigned as the control group. Groups B, C and D were intragastrically administered with 2.5mg/kg of indomethacin solution QD after 48 hours. After 15 days of treatment, group B was administered with 0.9% sodium chloride, group C was given rabeprazole (2mg/kg), and group D was administered with JIA WEI WU QI SAN (2g/kg). Abdominal aorta sampling was performed, and gastric tissues were isolated on the 29th day. The protein expression of p-P38MAPK and COX-2 were detected by western blot, while the concentration of PGE2 and IL-1 were determined by ELISA. (1) The expression of IL-1ingroup B dramatically declined in group D (P<0.01). (2)The expression of PGE-2dramatically increased in group D(P<0.01). (3) The expression of COX-2 increased in group D (P<0.05). (4) The expression of p-P38MAPK decreased in group D (P<0.05). JIA WEI WU QI SAN has multiple functions, including the activation of the p-P38MAPK signaling pathway, which promote the activation of COX-2, induce the arachidonic acid to increase the level of PG, and decrease the concentration of IL-1, thereby inducing an inflammatory reaction, and promote gastric mucosa repair.

Effects of Three Needling Manipulations of Zusanli (ST 36) on Deqi Sensations and Surface Myoelectricity in Healthy Participants.

OBJECTIVE: To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations. METHODS: Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed. RESULT: Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P<0.05, OR>1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01). CONCLUSIONS: The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

Folic Acid Supplementation and the Association between Maternal Airborne Particulate Matter Exposure and Preterm Delivery: A National Birth Cohort Study in China.

BACKGROUND: Potential modification of the association between maternal particulate matter (PM) exposure and preterm delivery (PTD) by folic acid (FA) supplementation has not been studied. OBJECTIVE: We examined whether FA supplementation could reduce the risk of PTD associated with maternal exposure to PM in ambient air during pregnancy. METHOD: In a cohort study covering 30 of the 31 provinces of mainland China in 2014, 1,229,556 primiparas of Han ethnicity were followed until labor. We collected information on their FA supplementation and pregnancy outcomes and estimated each participant's exposure to PM with diameters of ≤10µm (PM10), 2.5µm (PM2.5), and 1µm (PM1) using satellite remote-sensing based models. Cox proportional hazard regression models were used to examine interactions between FA supplementation and PM exposures, after controlling for individual characteristics. RESULTS: Participants who initiated FA ≥3 months prior to pregnancy (38.1%) had a 23% [hazard ratio (HR)=0.77 (95% CI: 0.76, 0.78)] lower risk of PTD than women who did not use preconception FA. Participants with PM concentrations in the highest quartile had a higher risk of PTD [HR=1.29 (95% CI: 1.26, 1.32) for PM1, 1.52 (95% CI: 1.46, 1.58) for PM2.5, and 1.22 (95% CI: 1.17, 1.27) for PM10] than those with exposures in the lowest PM quartiles. Estimated associations with a 10-µg/m3 increase in PM1 and PM2.5 were significantly lower among women who initiated FA ≥3 months prior to pregnancy [HR=1.09 (95% CI: 1.08, 1.10) for both exposures] than among women who did not use preconception FA [HR=1.12 (95% CI: 1.11, 1.13) for both exposures; pinteraction<0.001]. The corresponding association was also significantly lower for a 10-µg/m3 increase in PM10 [HR=1.03 (95% CI: 1.02, 1.03) for FA ≥3 months before pregnancy vs. 1.04 (95% CI: 1.03, 1.04) for no preconception FA; pinteraction<0.001]. CONCLUSION: Our findings require confirmation in other populations, but they suggest that initiating FA supplementation ≥3 months prior to pregnancy may lessen the risk of PTD associated with PM exposure during pregnancy among primiparas of Han ethnicity. https://doi.org/10.1289/EHP6386.

SWL-1 Reverses Fluconazole Resistance in Candida albicans by Regulating the Glycolytic Pathway.

Candida albicans is a ubiquitous clinical fungal pathogen. Prolonged use of the first-line antifungal agent fluconazole (FLC) has intensified fungal resistance and limited its effectiveness for the treatment of fungal infections. The combined administration of drugs has been extensively studied and applied. SWL-1 is a lignin compound derived from the Traditional Chinese Medicine Schisandra chinensis. In this study, we show that SWL-1 reverses resistance to fluconazole in C. albicans when delivered in combination, with a sharp decrease in the IC50 of fluconazole from >200 to 3.74 ± 0.25 µg/ml, and also reverses the fluconazole resistance of C. albicans in vitro, with IC50 from >200 to 5.3 ± 0.3 µg/ml. Moreover, killing kinetics curves confirmed the synergistic effects of fluconazole and SWL-1. Intriguingly, when SWL-1 was administered in combination with fluconazole in a mouse model of systemic infection, the mortality of mice was markedly decreased and fungal colonization of the kidney and lung was reduced. Further mechanistic studies showed that SWL-1 significantly decreased intracellular adenosine 5'-triphosphate (ATP) levels and inhibited the function of the efflux pump responsible for fluconazole resistance of C. albicans. Proteomic analysis of the effects of SWL-1 on C. albicans showed that several enzymes were downregulated in the glycolytic pathway. We speculate that SWL-1 significantly decreased intracellular ATP levels by hindering the glycolysis, and the function of the efflux pump responsible for fluconazole resistance of C. albicans was inhibited, resulting in restoration of fluconazole sensitivity in FLC-resistant C. albicans. This study clarified the effects and mechanism of SWL-1 on C. albicans in vitro and in vivo, providing a novel approach to overcoming fungal resistance.

Study on association between shear wave elastography parameters and clinicopathological characteristics in breast cancer: A protocol for systematic review.

BACKGROUND: This study aims to explore the association between shear wave elastography parameters (SWEPs) and clinicopathological characteristics (CPCs) in breast cancer (BC). METHODS: The electronic databases of Cochrane Library, MEDLINE, EMBASE, Allied and Complementary Medicine Database, WANGFANG, VIP, and China National Knowledge Infrastructure will be used to search for studies dated from database inception to the present. No limitations of language and publication status will be applied in this study. Only case-controlled study and randomized controlled trials investigating the association between SWEP and CPC in BC will be included. Cochrane risk of bias will be used to assess study quality for each included study. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will provide accurate data to appraise the association between SWEP and CPC in BC. CONCLUSION: This study will summarize the most recent evidence to improve our understanding of the association between SWEP and CPC in BC. OSF REGISTRATION NUMBER:: osf.io/vmkwu.

[Mechanism of Hematopoietic Reconstruction in Mice Treated with Danggui Buxue Decoction combined with Muscle-Derived Stem Cell Transplantation].

OBJECTIVE: To investigate the mechanism of hematopoietic reconstruction in mice treated with Danggui Buxue Decoction (DBD) combined with the muscle-derived stem cell transplantation (MDSCT). METHODS: Female Kunming mice were randomly divided into the 6 groups: irradiation model, the bone marrow transplantation, the MDSC transplantation, the DBD 1 (4.5 g/kg), 2 (13.5 g/kg), and 3 (22.5 g/kg) + MDSC transplantation. After a week of oral administration of normal saline or different doses of DBD, The mice were exposied to 8 Gy 137Cs γ ray and were followed by bone marrow or MDSC transplantation. The expression levels of Notch1, Jagged1 and Hes1 in bone marrow, thymus and spleen were measured at 3 and 8 weeks after irradiation and transplantation. RESULTS: In the bone marrow, 3 weeks after above-mentioned treatment, the expression of Notch1 mRNA increased obviously and the expression of Jagged1, Hes1 mRNA decreased obviously in each intervention group, compared with the irradiation model group. 8th week after treatment, the expression of Notch1 mRNA decreased obviously in each intervention group, the Jagged1 mRNA expression decreased obviously except the bone marrow group, and Hes1 mRNA expression increased (P＜0.05) in each intervention group. 3 weeks after treatment, compared with the irradiation model group, the expression of Notch1 mRNA in the thymocytes increased only in DBD1+MDSC group, Jagged1, Hes1 mRNA was increased in the MDSC transplantation group and the DBD1、2+MDSC group. 8th week after treatment, the expression of Notch1, Jagged1 mRNA expression decreased in each intervention group, the expression of Hes1 mRNA increased obviously in the MDSC transplantation group and the DBD1、2+MDSC group (P＜0.05). In the spleen, 3 weeks after treatment, the expression of Notch1, Jagged1 mRNA in the spleen of each intervention group decreased obviously, compared with the irradiation model group. The expression of Jagged1, Hes1 mRNA in each intervention group were increased obviously 8th week after treatment (P＜0.05). CONCLUSION: MDSC transplantation after pretreatment of DBD can improve the hematopoietic reconstitution in mice with lethal dose radiation damage. Notch1、Jagged1 and Hes1 play different roles in this process, but the concrete mechanism needs to be further studied.

[Inner-heating acupuncture of lumbar degenerative lesions based on ß-catenin signaling pathway].

OBJECTIVE: By observing the effect of inner-heating acupuncture on the expression of Wnt1, Axin and ß-catenin in the intervertebral disc of rats with lumbar degenerative disease and to explore the regulatory mechanism of inner-heating acupuncture on the apoptosis of annulus fibrosus cells in rats with lumbar degenerative disease. METHODS: Forty SD rats were randomly divided into normal group, model group, inner heating acupuncture group and acupuncture group with 10 rats in each group. Except for normal group, all rats were modeled. Bilateral Da Chang Shu were selected for inner-heating acupuncture and acupuncture treatment. Western-bolt assay was used to detect the expression of Wnt1, Axin and ß-catenin in rat intervertebral discs. RESULTS: Compared with the model group, Wnt1 and ß-catenin expression in annulus fibrosus cells of rats in the inner heating acupuncture group and the acupuncture group were significantly decreased(P<0.05);the expression of Axin in annulus fibrosus of rats in the inner heating acupuncture group was significantly increased(P<0.05). There was no significant difference in the expression of Axin in annulus fibrosus of rats between acupuncture group and model group(P>0.05). CONCLUSION: Inner heating acupuncture can down regulate the expression of Wnt1 and ß-catenin and up regulate the expression of Axin in annulus fibrosus of rats with lumbar degenerative desease. It is suggested that the mechanism may be to regulate the expression of related factors in the ß-catenin signaling pathway, so as to achieve the goal of treating lumbar degenerative diseases.

Shegan-Mahuang Decoction ameliorates asthmatic airway hyperresponsiveness by downregulating Th2/Th17 cells but upregulating CD4+FoxP3+ Tregs.

ETHNOPHARMACOLOGICAL RELEVANCE: Shegan-Mahuang Decoction (SMD), also named Yakammaoto or Shegan-Mahuang Tang, is a classic formula of traditional Chinese medicine with nine herbs, including Asarum sieboldii Miq., Aster tataricus L.f., Ephedra sinica Stapf, Belamcanda chinensis (L.) Redouté, Pinellia ternata (Thunb.) Breit., Schisandra chinensis (Turcz.) Baill., Tussilago farfara L., Zingiber officinale Roscoe, and Ziziphus jujuba Mill. SMD was originally discovered by Zhang Zhongjing in Eastern Han dynasty. It has been widely used as traditional medicine to treat flu-like symptoms in China and Japan for around twenty centuries. It was also utilized for the treatment of the early stage of acute asthma. However, the immune mechanisms underlying its therapeutic effects remain unknown. AIM OF THE STUDY: This study was set to investigate the effects of SMD on asthmatic airway hyperresponsiveness and its impacts on adaptive immunity in a mouse model of asthma. MATERIALS AND METHODS: The HPLC fingerprint profile of the water extract of SMD recorded 22 peaks, including those equivalent to guanosine, chlorogenic acid, tectoridin, 6-gingerol and wuweizisu B, as described previously (Yen et al., 2014). Airway hyperresponsiveness was assessed by measuring the airway resistance. Cellular infiltration was measured via H&E staining and immunochemistry while gene expression was analyzed using real-time RT-PCR. Treg frequency was determined through flow analysis whereas cytokine production in the supernatant was evaluated using ELISA. Finally, mTOR and NF-kB signalings were analyzed via Western blotting. RESULTS: We found that SMD largely corrected the imbalance of Th cell subsets in asthmatic mice with a significant inhibition of Th2 and Th17 cytokine production, thereby reducing asthmatic airway hyperresponsiveness. Moreover, lung function tests showed that SMD reduced airway hyperresponsiveness while immunohistochemical analyses demonstrated that SMD attenuated pulmonary infiltration of CD3+ and CD4+ T cells. Further, we observed a significant increase in the proportion of CD4+Foxp3+ Tregs in SMD-treated asthmatic mice. We also found that SMD downregulated gene expression of GATA3 and ROR-γt in murine lung tissue. In addition, both mTOR- and NF-kB-related protein expressions were reduced in the lung tissue of SMD-treated mice. SMD inhibited Th2/Th17 cytokine production by CD4+ T cells and also their mTOR activity in vitro. CONCLUSIONS: Our findings demonstrate that SMD attenuates asthmatic airway hyperresponsiveness by hindering Th2/Th17 differentiation, promoting CD4+FoxP3+ Treg generation and suppressing mTOR and NF-kB activities.

[Clinical experience of professor LIU Xiao-ying's external treatment of supporting the middle for pediatric diseases].

It is well believed that children's spleen is often insufficient, as the structure and qi of spleen-stomach are incomplete. The deficiency of spleen-stomach plays an important role in the occurrence, development and pathogenesis of pediatric diseases. Professor LIU Xiao-ying has inherited the academic thought of NI Zhu-ying, a famous physician of TCM, and proposed the external treatment method of "supporting the middle". This method emphasizes the constant care of the spleen-stomach of children in the aspect of acupoint selection, and adoptes the external treatment of children's tuina, supporting-yang cupping therapy (including warming tuina, warming moxibustion and warm scrapping), acupuncture (including abdominal acupuncture, intradermal needling) to treat children's diseases of spleen, lung, kidney and others, which has achieved satisfactory therapeutic effects.

Lineariifolianoids M-O, three rare sesquiterpene lactone dimers inhibiting NO production from Inula lineariifolia.

Three rare squiterpene lactone dimers lineariifolianoids M-O (1-3) were isolated from Inula lineariifolia for the first time. Their structures and absolute configuration were established on the basis of by NMR and MS spectroscopic data and X-ray crystallography. Furthermore, those three compounds exhibited significant inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages with IC50 values of 1.421, 1.087 and 1.243 µM, respectively.

Mindfulness-Based Interventions for Insomnia: A Meta-Analysis of Randomized Controlled Trials.

Objective: Mindfulness-based interventions (MBIs) are clinically effective for insomnia, but the research findings have been mixed. This meta-analysis of randomized controlled trials (RCTs) examined the effect of MBIs on insomnia. Method: Both English (PubMed, PsycINFO, Embase, and Cochrane Library databases) and Chinese (WanFang and CNKI) databases were systematically and independently searched. Standardized mean differences (SMDs) and risk ratio (RR) with their 95% confidence intervals (CIs) were calculated using the random effects model. Results: Five RCTs (n = 520) comparing MBIs (n = 279) and control (n = 241) groups were identified and analyzed. Compared to the control group, participants in the MBIs group showed significant improvement in insomnia as measured by the Pittsburgh Sleep Quality Index (n = 247; SMD: -1.01, 95% CI: -1.28 to -0.75, I2 = 0%, p < 0.00001) at post-MBIs assessment. Conclusion: In this comprehensive meta-analysis, MBIs appear to be effective in the treatment of insomnia. Further studies to examine the long-term effects of MBIs for insomnia are needed.

[Treatment of knee osteoarthritis with six-step manipulation combined with extracorporeal shock wave].

OBJECTIVE: To observe the clinical effect of six-step manipulation combined with extracorporeal shock wave in the treatment of knee osteoarthritis. METHODS: Seventy-six patients with KOA from December 2016 to June 2018 were divided into control group and treatment group, 38 in each group. The patients in the control group were treated with oral medicine combined with extracorporeal shock wave therapy, while the patients in the treatment group were treated with six-step manipulation combined with shock wave therapy. The VAS score, WOMAC score and clinical efficacy of the two groups were compared before treatment, 1 day, 1 month and 6 months after treatment. RESULTS: There was no significant difference in VAS score and WOMAC score between the two groups before treatment(P>0.05). VAS score and WOMAC score in treatment group were significantly lower than those in control group at 1 day, 1 month and 6 months after treatment, and the difference was statistically significant(P<0.05). CONCLUSIONS: Six-step manipulation combined with extracorporeal shock wave therapy can significantly alleviate pain and improve knee function in patients with knee osteoarthritis, and the clinical effect is obvious.