Modulating the Expression of Exercise-induced lncRNAs: Implications for Cardiovascular Disease Progression.

Recent research shows exercise is good for heart health, emphasizing the importance of physical activity. Sedentary behavior increases the risk of cardiovascular disease, while exercise can help prevent and treat it. Additionally, physical exercise can modulate the expression of lncRNAs, influencing cardiovascular disease progression. Therefore, understanding this relationship could help identify prospective biomarkers and therapeutic targets pertaining to cardiovascular ailments. This review has underscored recent advancements concerning the potential biomarkers of lncRNAs in cardiovascular diseases, while also summarizing existing knowledge regarding dysregulated lncRNAs and their plausible molecular mechanisms. Additionally, we have contributed novel perspectives on the underlying mechanisms of lncRNAs, which hold promise as potential biomarkers and therapeutic targets for cardiovascular conditions. The knowledge imparted in this review may prove valuable in guiding the design of future investigations and furthering the understanding of lncRNAs as diagnostic, prognostic, and therapeutic biomarkers for cardiovascular diseases.

The role of Ginkgo Folium on antitumor: Bioactive constituents and the potential mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. is a well-known and highly regarded resource in Chinese traditional medicine due to its effectiveness and safety. Ginkgo Folium, the leaf of Ginkgo biloba L., contains biologically active constituents with diverse pharmacological activities. Recent studies have shown promising antitumor effects of the bioactive constituents found in Ginkgo Folium against various types of cancer cells, highlighting its potential as a natural source of antitumor agents. Further research is needed to elucidate the underlying mechanisms and optimize its therapeutic potential. AIM OF THE REVIEW: To provide a detailed understanding of the pharmacological activities of Ginkgo Folium and its potential therapeutic benefits for cancer patients. MATERIALS AND METHODS: In this study, we conducted a thorough and systematic search of multiple online databases, including PubMed, Web of Science, Medline, using relevant keywords such as "Ginkgo Folium," "flavonoids," "terpenoids," "Ginkgo Folium extracts," and "antitumor" to cover a broad range of studies that could inform our review. Additionally, we followed a rigorous selection process to ensure that the studies included in our review met the predetermined inclusion criteria. RESULTS: The active constituents of Ginkgo Folium primarily consist of flavonoids and terpenoids, with quercetin, kaempferol, isorhamnetin, ginkgolides, and bilobalide being the major compounds. These active constituents exert their antitumor effects through crucial biological events such as apoptosis, cell cycle arrest, autophagy, and inhibition of invasion and metastasis via modulating diverse signaling pathways. During the process of apoptosis, active constituents primarily exert their effects by modulating the caspase-8 mediated death receptor pathway and caspase-9 mediated mitochondrial pathway via regulating specific signaling pathways. Furthermore, by modulating multiple signaling pathways, active constituents effectively induce G1, G0/G1, G2, and G2/M phase arrest. Among these, the pathways associated with G2/M phase arrest are particularly extensive, with the cyclin-dependent kinases (CDKs) being most involved. Moreover, active constituents primarily mediate autophagy by modulating certain inflammatory factors and stressors, facilitating the fusion stage between autophagosomes and lysosomes. Additionally, through the modulation of specific chemokines and matrix metalloproteinases, active constituents effectively inhibit the processes of epithelial-mesenchymal transition (EMT) and angiogenesis, exerting a significant impact on cellular invasion and migration. Synergistic effects are observed among the active constituents, particularly quercetin and kaempferol. CONCLUSION: Active components derived from Ginkgo Folium demonstrate a comprehensive antitumor effect across various levels and pathways, presenting compelling evidence for their potential in new drug development. However, in order to facilitate their broad and adaptable clinical application, further extensive experimental investigations are required to thoroughly explore their efficacy, safety, and underlying mechanisms of action.

ß-Elemene induced ferroptosis via TFEB-mediated GPX4 degradation in EGFR wide-type non-small cell lung cancer.

INTRODUCTION: ß-Elemene (ß-ELE), derived from Curcuma wenyujin, has anticancer effect on non-small cell lung cancer (NSCLC). However, the potential target and detail mechanism were still not clear. TFEB is the master regulator of lysosome biogenesis. Ferroptosis, a promising strategy for cancer therapy could be triggered via suppression on glutathione peroxidase 4 (GPX4). Weather TFEB-mediated lysosome degradation contributes to GPX4 decline and how ß-ELE modulates on this process are not clear. OBJECTIVES: To observe the action of ß-ELE on TFEB, and the role of TFEB-mediated GPX4 degradation in ß-ELE induced ferroptosis. METHODS: Surface plasmon resonance (SPR) and molecular docking were applied to observe the binding affinity of ß-ELE on TFEB. Activation of TFEB and lysosome were observed by immunofluorescence, western blot, flow cytometry and qPCR. Ferroptosis induced by ß-ELE was observed via lipid ROS, a labile iron pool (LIP) assay and western blot. A549TFEB KO cells were established via CRISPR/Cas9. The regulation of TFEB on GPX4 and ferroptosis was observed in ß-ELE treated A549WT and A549TFEB KO cells, which was further studied in orthotopic NOD/SCID mouse model. RESULTS: ß-ELE can bind to TFEB, notably activate TFEB, lysosome and transcriptional increase on downstream gene GLA, MCOLN1, SLC26A11 involved in lysosome activity in EGFR wild-type NSCLC cells. ß-ELE increased GPX4 ubiquitination and lysosomal localization, with the increase on lysosome degradation of GPX4. Furthermore, ß-ELE induced ferroptosis, which could be promoted by TFEB overexpression or compromised by TFEB knockout. Genetic knockout or inactivation of TFEB compromised ß-ELE induced lysosome degradation of GPX4, which was further demonstrated in orthotopic NSCLC NOD/SCID mice model. CONCLUSION: This study firstly demonstrated that TFEB promoted GPX4 lysosome degradation contributes to ß-ELE induced ferroptosis in EGFR wild-type NSCLC, which gives a clue that TFEB mediated GPX4 degradation would be a novel strategy for ferroptosis induction and NSCLC therapy.

High myopia control is comparable between multifocal rigid gas-permeable lenses and spectacles.

Purpose: Ocular pathology may be reduced by slowing myopia progression. The purpose of this study was to evaluate the potential of a novel custom-designed rigid gas permeable (RGP) contact lens to control high myopia by comparing the efficacy of multifocal RGP lenses and single-vision spectacles for high myopia control. Methods: The medical records of children fitted with spectacles or multifocal rigid gas-permeable lenses between January 2018 and May 2020 were retrospectively reviewed. Children (5-17 years) with non-cycloplegic spherical equivalent refraction of ≤ -6.00 D or spherical equivalent refraction > - 6.00 D with baseline axial length ≥ 26.5 mm, and astigmatism of ≥ -2.00 D were included. Axial length and refraction were measured at baseline, before fitting the participants with multifocal rigid gas-permeable lenses or spectacles, and at 1- and 2-year follow-up visits. Changes in axial length were compared between the groups. Results: Among the 77 children with 1-year follow-up data, the mean axial elongation was 0.20 ± 0.17 mm and 0.21 ± 0.14 mm in the multifocal rigid gas-permeable and control groups, respectively, without significant differences between groups (F = 0.004, p = 0.835). Among the 41 patients who completed 2 years of follow-up, the mean axial elongation values in the multifocal rigid gas-permeable and control groups were 0.21 ± 0.15 mm and 0.24 ± 0.13 mm, respectively, at the 1-year follow-up, and 0.37 ± 0.27 mm and 0.43 ± 0.23 mm, respectively, at the 2-year follow-up, without significant between-group differences at either time point (p = 0.224). Conclusion: Axial length increased at a similar rate in both the control (spectacles) and multifocal rigid gas-permeable lens groups, suggesting that multifocal rigid gas-permeable lenses have no significant impact on controlling high myopia progression compared with spectacles.

TFEB: a double-edged sword for tumor metastasis.

Transcription factor EB, a member of the microphthalmia-associated transcription factor (MiTF/TFE) family, is a master regulator of autophagy, lysosome biogenesis, and TAMs. Metastasis is one of the main reasons for the failure of tumor therapy. Studies on the relationship between TFEB and tumor metastasis are contradictory. On the positive side, TFEB mainly affects tumor cell metastasis via five aspects, including autophagy, epithelial-mesenchymal transition (EMT), lysosomal biogenesis, lipid metabolism, and oncogenic signaling pathways; on the negative side, TFEB mainly affects tumor cell metastasis in two aspects, including tumor-associated macrophages (TAMs) and EMT. In this review, we described the detailed mechanism of TFEB-mediated regulation of metastasis. In addition, we also described the activation and inactivation of TFEB in several aspects, including the mTORC1 and Rag GTPase systems, ERK2, and AKT. However, the exact process by which TFEB regulates tumor metastasis remains unclear in some pathways, which requires further studies.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) prevents the neuroinflammation induced dopaminergic neurodegeneration.

BACKGROUND: The excessive activation of the microglia leads to the release of inflammatory factors that contribute to neuronal cell loss and neurodegeneration in Parkinson's Disease (PD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) that belongs to a newly found neurotrophic factors (NTFs) family has been reported to promote neuronal survival in the PD models. However, the effects of the MANF on neuroinflammation in PD remain unclear. METHODS: AAV8-MANF virus was constructed to determine whether the high expression of MANF can protect the neuroinflammation-induced dopaminergic neurodegeneration in rats with 6-OHDA-induced PD. Rotarod performance test, immunofluorescent staining and western bolt were employed to evaluate the behavioral dysfunction, dopaminergic neurodegeneration, microglia activation, and signal activation. 6-OHDA treated SH-SY5Y cells and LPS treated BV-2 cells were used as the in vitro model for MANF neuroprotective and neuroinflammation mechanisms. Cell vitality and apoptosis were evaluated with MTT, CCK-8 and flow cytometric analysis. The AKT/GSK3ß-Nrf2 signaling and the TNF-α/IL6 expression were measured by Western Blot. RESULTS: Our findings indicated that the elevated MANF expression by the AAV8-MANF administration ameliorated the motor dysfunction and protected the dopaminergic neurons in the 6-OHDA treated rats. The upregulated CD11b in the rat SN caused by the 6-OHDA administration was significantly attenuated by the pretreatment of the AAV8-MANF. Furthermore, the levels of p-AKT, p-GSK3ß, BCL-2, and Nrf-2 were upregulated by the high expression of the MANF. Under the oxidative stress of the 6-OHDA, the MANF significantly reduced the apoptotic effect of the TNF-α on the SH-SY5Y cells. In the LPS treated BV-2 cells, the MANF reduced the production of the TNF-α and IL-6, via enhancing the Nrf-2, p-Akt, p-GSK3ß, and p-NF-κß level. CONCLUSIONS: These results suggested that the MANF prevented the dopaminergic neurodegeneration caused by the microglia activation in PD via activation of the AKT/GSK3ß-Nrf-2 signaling axis.

[Effects of urogenital mycoplasma and chlamydial infections on male fertility].

Objective： This study aimed to assess the impact of urogenital ureaplasma urealyticum (Uu), Mycoplasma hominis (Mh), and Chlamydia trachomatis (Ct) infections on semen quality in men.Methods： In this study, 1022 males were enrolled at the Department of Reproductive Medicine, Rizhao People's Hospital, Shandong Province from October 2014 to January 2023. The participants included 393 in the infertility group, 139 in the recurrent miscarriage group, and 490 in the control group. Based on age, 852 cases were < 36 years old, and 170 cases were ≥ 36 years old. All patients underwent routine semen analysis and tests for Uu, Mh, and Ct, with results statistically analyzed for their impact on semen quality and compared among different age groups. Results: Among the 1022 patients, 344 (33.6%) were Uu-positive, 49 (4.7%) were Mh-positive, and 31 (3.0%) were Ct positive. The sperm concentration, total sperm count, forward sperm motility rate (PR), sperm motility rate (PR+NP) and normal sperm morphology rate of Uu Mh and/or Ct-positive patients were significantly lower than those of the negative group, and the overall difference between the two groups was statistically significant (P<0.05). The positive rate of Uu infection was 41.7% in the infertility group, 30.2% in the recurrent miscarriage group and 28.2% in the control group, and the overall positive rate of the three groups was statistically significant(P<0.05). The positive rate of Mh infection was 6.9% in the infertility group, 8.6% in the recurrent miscarriage group and 2.0% in the control group, and the overall positive rate of the three groups was statistically significant (P<0.001). The positive rate of Ct infection was 6.1% in the infertility group, 2.9% in the recurrent miscarriage group and 0.6% in the control group, and the overall positive rate of the three groups was statistically significant (P<0.001). The positivity rate of Uu infection was 35.8% at the age of <36 years and 22.9% at the age ≥ 36 years, and there was a statistically significant difference in the positivity rate between the two groups (P<0.05). Conclusion: The prevalence of Uu infection in the male urogenital tract is significantly higher than that of Mh and Ct, which is the main pathogen of urogenital tract infection in men. Uu, Mh and Ct infections have adverse effects on sperm concentration, total sperm count, sperm forward motility rate (PR), sperm motility rate (PR+NP) and normal sperm morphology rate, which will lead to a decrease in semen quality and affect male fertility. Genital tract infections are closely related to age, and the prevalence of Uu infection is higher in the younger age group.

Defect-engineered surfaces to investigate the formation of self-assembled molecular networks.

Herein we report the impact of covalent modification (grafting), inducing lateral nanoconfinement conditions, on the self-assembly of a quinonoid zwitterion derivative into self-assembled molecular networks at the liquid/solid interface. At low concentrations where the compound does not show self-assembly behaviour on bare highly oriented pyrolytic graphite (HOPG), close-packed self-assembled structures are visualized by scanning tunneling microscopy on covalently modified HOPG. The size of the self-assembled domains decreases with increasing the density of grafted molecules, i.e. the molecules covalently bound to the surface. The dynamics of domains are captured with molecular resolution, revealing not only time-dependent growth and shrinkage processes but also the orientation conversion of assembled domains. Grafted pins play a key role in initiating the formation of on-surface molecular self-assembly and their stabilization, providing an elegant route to study various aspects of nucleation and growth processes of self-assembled molecular networks.

[Post-stroke shoulder-hand syndrome of phlegm-stasis obstruction treated with the combined therapy of eye acupuncture, Tengliao and rehabilitation training: a multi-central randomized controlled trial].

OBJECTIVE: To assess the efficacy on relieving pain and improving the range of motion of shoulder joint in post-stroke shoulder-hand syndrome of phlegm-stasis obstruction in treatment of the combined therapy of eye acupuncture, Tengliao (Chinese herbal warm dressing technique) and rehabilitation training (eye acupuncture + Tengliao + rehabilitation) as compared with the combined treatment of Tengliao and rehabilitation training (Tengliao + rehabilitation) and the simple rehabilitation training (rehabilitation). METHODS: A total of 356 patients with post-stroke shoulder-hand syndrome of phlegm-stasis obstruction were randomized into an eye acupuncture + Tengliao + rehabilitation group (group A, 122 cases, 2 cases dropped off), a Tengliao + rehabilitation group (group B, 120 cases, 3 cases dropped off) and a rehabilitation group (group C, 114 cases, 1 case dropped off). In the group C, the basic treatment was combined with routine rehabilitation training. In the group B, on the base of the treatment as the group C, Tengliao was exerted. A medical bag composed of over 20 Chinese herbal materials was heated and dressed at the affected area, 30 min each time, 5 times weekly. In the group A, besides the treatment as the group B, eye acupuncture was applied to heart region, kidney region, upper jiao region and lower jiao region, 30 min each time, 5 times weekly. The treatment lasted 28 days in all of three groups. Separately, before treatment, in 7, 14, 21 and 28 days of treatment, as well as in 14 days after treatment of follow-up, the score of visual analogue scale (VAS) for pain, the score of guides to evaluation of permanent impairment (GEPI) and the score of National Institutes of Health stroke scale (NIHSS) were observed in each group. RESULTS: The scores of VAS, GEPI and NIHSS were all improved with the treatment lasting in the three groups (P<0.000 1). In 7, 14, 21 and 28 days of treatment and in follow-up as well, VAS scores in the group A were all lower than the group C (P<0.05). After 14 days of treatment, GEPI score showed increasing trend, while NIHSS score showed decreasing trend in the group A compared with the group B. Before treatment, GEPI score was lower and NIHSS score was higher in the group A compared with the group C (P<0.05). It was suggested that the illness was slightly serious in the group A. After propensity score matching, in 14, 21 and 28 days as well as in follow-up, GEPI scores in the group A were higher than the group C respectively (P<0.05). Regarding NIHSS score at each time point, the difference had no statistical significance between the group A and the group C (P>0.05). CONCLUSION: The combined therapy of eye acupuncture, Tengliao and rehabilitation training obtains a better efficacy on post-stroke shoulder-hand syndrome of phlegm-stasis obstruction as compared with rehabilitation training.

The Up-regulation of TNF-α Maintains Trigeminal Neuralgia by Modulating MAPKs Phosphorylation and BKCa Channels in Trigeminal Nucleus Caudalis.

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous available medical interventions, the therapeutic effects are not ideal. To control the pain attacks, the need for more contemporary drugs continues to be a real challenge. Our previous study reported that Ca2+-activated K+ channels (BK Ca ) channels modulated by mitogen-activated protein kinases (MAPKs) in the trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some research studies demonstrated that inflammatory cytokine tumor necrosis factor alpha (TNF-α) could promote neuropathic pain. Meanwhile, the trigeminal nucleus caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is responsible for processing sensory and pain signals from the peripheral orofacial area. Thus, this study is aimed to further investigate whether TNF-α and MAPKs phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BK Ca channels. The results showed that TNF-α of the TNC region is upregulated significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) rats model, which displayed persistent facial mechanical allodynia. The normal rats with target injection of exogenous TNF-α to the fourth brain ventricle behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold decreased clearly. Meanwhile, the exogenous TNF-α increased the action potential frequency and reduced the BK Ca currents of TNC neurons significantly, which could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI model rats, respectively. Taken together, our work suggests that the upregulation of TNF-α in the TNC region would cause the increase of MAPKs phosphorylation and then the negative regulation of BK Ca channels, resulting in the TN.

Network Pharmacology-Based and Molecular Docking-Based Analysis of Suanzaoren Decoction for the Treatment of Parkinson's Disease with Sleep Disorder.

This study is aimed at exploring the possible mechanism of action of the Suanzaoren decoction (SZRD) in the treatment of Parkinson's disease with sleep disorder (PDSD) based on network pharmacology and molecular docking. Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the bioactive components and targets of SZRD, and their targets were standardized using the UniProt platform. The disease targets of "Parkinson's disease (PD)" and "Sleep disorder (SD)" were collected by OMIM, GeneCards, and DisGeNET databases. Thereafter, the protein-protein interaction (PPI) network was constructed using the STRING platform and visualized by Cytoscape (3.7.2) software. Then, the DAVID platform was used to analyze the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Cytoscape (3.7.2) software was also used to construct the network of the "herb-component-target-pathway." The core active ingredients and core action targets of the drug were verified by molecular docking using AutoDock software. A total of 135 Chinese herbal components and 41 corresponding targets were predicted for the treatment of PDSD using SZRD. Fifteen important signaling pathways were screened, such as the cancer pathway, TNF signaling pathway, PI3K-AKT signaling pathway, HIF-1 signaling pathway, and Toll-like receptor signaling pathway. The results of molecular docking showed that the main active compounds could bind to the representative targets and exhibit good affinity. This study revealed that SZRD has the characteristics and advantages of "multicomponent, multitarget, and multipathway" in the treatment of PDSD; among these, the combination of the main active components of quercetin and kaempferol with the key targets of AKT1, IL6, MAPK1, TP53, and VEGFA may be one of the important mechanisms. This study provides a theoretical basis for further study of the material basis and molecular mechanism of SZRD in the treatment of PDSD.

Novel compound heterozygous of PARKIN causes early-onset Parkinson's disease.

Genetics has an essential role in the development of early-onset Parkinson's disease (EOPD). Consequently, genetic screening is of great significance for the diagnosis and treatment of EOPD. In this study, we reported two EOPD with compound heterozygous in PARKIN detected by whole-exome sequencing (WES) and ligation-dependent probe amplification (MLPA). Two unrelated EOPD patients and their parents were enrolled in this study. Genetic analysis was performed through WES and verified by direct Sanger sequencing. In addition, MLPA was used to detect exon dosage. Detailed clinical manifestations and several scale assessments were collected for genotype and phenotype analysis. Compound heterozygous mutations in PARKIN were identified in both patients. c.735-1G > A and Ex2del were detected in Case A, while G284R (c.850 G > C) and Ex2del were found in Case B. These variants were confirmed to originate from their normal parents. The c.735-1G > A is a novel PARKIN variant, which was predicted to result from disappearing of the acceptor splice site by NetGene2. The G284R is a previously reported pathological mutation and the Ex2del is a hot variant of PARKIN found in the Asian population. The phenotypes of both patients are quite different, the main manifestation of case A is rigidity onset, while the case B starts with tremor and foot dystonia. In the present study, we reported a novel compound heterozygous form of PARKIN consisting of splice variant c. 735-1G > A and Ex2del. Moreover, we also found that tiny differences in genotypes of PARKIN may lead to obvious clinical phenotypic differences.

Effect of orthokeratology on axial length elongation in moderate myopic and fellow high myopic eyes of children.

CLINICAL RELEVANCE: The effects of orthokeratology (Ortho-K) on myopic eyes was examined, providing confidence to optometrists applying Ortho-K to high myopic and anisometropic children. BACKGROUND: Ortho-K slows the progression of low to moderate myopia. The effectiveness of Ortho-K in Chinese children with fellow moderate and high myopic eyes was determined. METHODS: This retrospective study included female (n = 35) and male (n = 30) children with moderate myopia in one eye (spherical equivalent refractive (SER) error ≤ -3.00 D, but > -6.00 D) and high myopia in the contralateral eye (SER error ≤ -6.00 D). Three age groups were included: 7-10-years (n = 18), 11-12-years (n = 21), and 13-15-years (n = 26). Baseline refraction and axial lengths were measured before fitting Ortho-K lenses worn nightly for at least eight-hours, and after one-year. RESULTS: Axial length increased 0.14 ± 0.13-mm (mean ± standard deviation) and 0.13 ± 0.16-mm in the moderate and high myopic groups respectively (p = 0.78). For females, axial elongation in the moderate and high myopic groups was 0.10 and 0.08-mm respectively. For males, it was 0.19-mm in both groups. Axial elongation in 7-10-year-old children with moderate and high myopic eyes was 0.24 ± 0.14 and 0.21 ± 0.15-mm respectively. In 11-12-year-old children, it was 0.12-mm in both myopic groups. In 13-15-year-old children, it was 0.09-mm in both groups. In moderate myopic eyes, axial elongation in the youngest group was greater than the other two age groups (p < 0.01). In high myopic eyes, there were no differences among the age groups (p = 0.06). CONCLUSIONS: Ortho-K was equally effective in reducing myopic progression in moderate and in contralateral high myopic eyes. Axial elongation was greater for males than females. For both sexes, it decreased at the same rate with increasing age, regardless of difference in myopia.

Antibody responses to SARS-CoV-2 in patients with COVID-19.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Acupuncture plus Chinese Herbal Medicine for Irritable Bowel Syndrome with Diarrhea: A Systematic Review and Meta-Analysis.

PURPOSE: To comprehensively evaluate the efficacy and safety of acupuncture combined with Chinese herbal medicine (CHM) in treating irritable bowel syndrome with diarrhea (IBS-D). METHODS: Relevant randomized controlled trials (RCTs) were systemically retrieved from electronic databases from inception to March 2018, including the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biological Medical Database (CBM, SinoMed), China Science and Technology Journal Database (VIP), and Wan Fang Data. Meanwhile, pooled estimates, including the 95% confidence interval (CI), were calculated for primary and secondary outcomes of IBS-D patients. Besides, quality of relevant articles was evaluated using the Cochrane Collaboration's risk of bias tool, and the Review Manager 5.3 and Stata12.0 softwares were employed for analyses. RESULTS: A total of 21 RCTs related to IBS-D were included into this meta-analysis. Specifically, the pooled results indicated that (1) acupuncture combined with CHM might result in more favorable improvements compared with the control group (relative risk [RR] 1.29; 95% CI 1.24-1.35; P =0.03); (2) the combined method could markedly enhance the clinical efficacy in the meantime of remarkably reducing the scores of abdominal pain (standardized mean difference [SMD] -0.45; 95% CI -0.72, -0.17; P = 0.002), abdominal distention/discomfort (SMD -0.36; 95% CI -0.71, -0.01; P = 0.04), diarrhea (SMD -0.97; 95% CI -1.18, -0.75; P < 0.00001), diet condition (SMD -0.73; 95% CI -0.93, -0.52; P<0.00001), physical strength (SMD -1.25; 95% CI -2.32, -0.19; P = 0.02), and sleep quality (SMD -1.02; 95% CI -1.26, -0.77; P < 0.00001) compared with those in the matched groups treated with western medicine, or western medicine combined with CHM. Additionally, a metaregression analysis was constructed according to the name of prescription, acupuncture type, treatment course and publication year, and subgroup analyses stratified based on the names of prescriptions and acupoints location were also carried out, so as to explore the potential heterogeneities; and (3) IBS-D patients treated with the combined method only developed inconspicuous adverse events; more importantly, the combined treatment had displayed promising long-term efficacy. CONCLUSIONS: Findings in this study indicate that acupuncture combined with CHM is suggestive of an effective and safe treatment approach for IBS-D patients, which may serve as a promising method to treat IBS-D in practical application. However, more large-scale, multicenter, long-term, and high-quality RCTs are required in the future, given the small size, low quality, and high risk of the studies identified in this meta-analysis.

[Effect of Shenqi Dihuang decoction on inflammatory factor, renal function and microcirculation in patients with early diabetic nephropathy].

To study the effect of Shenqi Dihuang decoction on inflammatory factor, renal function and microcirculation in patients with early diabetic nephropathy. A total of 205 cases of patient with early diabetic nephropathy treated in our hospital from March 2014 to April 2016 were selected and divided into two groups according to the admitted order, with 103 cases in clinical group and 102 in control group. Patients in control group were treated with melbine and captopril, which may be adjusted according to the clinical symptom. The clinical group was given Shenqi Dihuang decoction. Then the clinical efficady, inflammatory factors, renal function, endothelial function and hemorheology index were compared. Compared with 77.45% in the control group, the total effective rate of the clinical group was 92.23%. There was a significant increase (P<0.05). The comparison of the values of IL-6, IL-8, TNF-α and CRP between the two groups before and after treatment showed significant differences. The values of inflammatory factors in treatment group were lower than in control group (P<0.05). The comparison of the values of ß2-MG, Cys-C and urine m-ALB between the two groups before and after treatment showed significant differences. The values of renal function in treatment group were lower than those in control group (P<0.05). Compared with before treatment, ET-1 of the two groups after treatment decreased, while NO increased (P<0.05). Compared with the control group, the value of ET-1 in patients of the experimental group was lower after treatment, while NO was higher (P<0.05). The comparison of the values of whole blood viscosity, plasma viscosity, whole blood reduction viscosity, platelet aggregation rate and fibrinogen between the two groups before and after treatment showed significant differences. The value of hemorheology index in treatment group was lower than that in control group (P<0.05). Shenqi Dihuang decoction has a better effect on patients with early diabetic nephropathy. It can significantly intervene with inflammatory response, reduce proteinuria, protect the renal function of patients, and improve the patient's vascular endothelial function and blood rheology, so as to make microcirculation to recover to the normal level.

Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver.

Protein kinase B (PKB/Akt) plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that cytochrome P4502E1 (CYP2E1) plays causal roles in the pathogenesis of alcoholic fatty liver (AFL). We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver. Chronic ethanol exposure had no effects on the protein levels of phosphatidylinositol 3 kinase (PI3K) and phosphatase and tensin homologue deleted on chromosome ten (PTEN), and led to a slight decrease of phosphoinositide-dependent protein kinase 1 (PDK-1) protein level. Ethanol exposure resulted in increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ), an efficient CYP2E1 inhibitor. Interestingly, N-acetyl-L-cysteine (NAC) significantly attenuated chronic ethanol-induced hepatic fat accumulation and the decline of Akt phosphorylation at Thr308. In the in vitro studies, Akt phosphorylation was suppressed in CYP2E1-expressing HepG2 (CYP2E1-HepG2) cells compared with the negative control HepG2 (NC-HepG2) cells, and 4-HNE treatment led to significant decrease of Akt phosphorylation at Thr308 in wild type HepG2 cells. Lastly, pharmacological activation of Akt by insulin-like growth factor-1 (IGF-1) significantly alleviated chronic ethanol-induced fatty liver in mice. Collectively, these results indicate that CYP2E1-induced oxidative stress may be responsible for ethanol-induced suppression of Akt phosphorylation and pharmacological modulation of Akt in liver may be an effective strategy for the treatment of ethanol-induced fatty liver.

Efficacy of Modified Wuzhuyu Decoction Granule ( ) for Migraine Patients with Cold and Stasis Obstructing Meridian Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To study the efficacy of modified Wuzhuyu Decoction Granule (, MWDG) in the treatment of migraine patients with cold and stasis obstructing meridian syndrome. METHODS: This study was a randomized, double-blind, placebo-controlled trial. A total of 78 migraine patients with cold and stasis obstructing meridian syndrome were recruited and randomly assigned by a ratio of 2:1 into a treatment group (51 cases) and a placebo group (27 cases). Patients in the treatment group were treated with MWDG while placebo granules were applied in the control group. The treatment course lasted for 12 weeks with a follow-up of 4 weeks. The primary outcome measures included frequency and days of migraine attacks and the secondary outcome measures were analgesics consumption and visual analogue scale (VAS) scores. All outcome assessments were conducted respectively at baseline, the 4th, 8th and 12th week, and the end of follow-up. RESULTS: In the treatment group, significant decrease in frequency of migraine attacks were observed since the 4th week and that of analgesics consumption since the 8th week (both P<0.05). While, in the placebo group, significant decrease in frequency of migraine attacks were observed since the 8th week and that of analgesics consumption since the 12th week (both P<0.05). No significant decrease in days of migraine attacks and VAS scores of migraine pain were observed in both groups. Between the two groups, there were significant differences in VAS scores and intensity of pain appeared in the 8th week (P<0.05). However, no significant differences were found in days and frequency of migraine attacks and analgesics consumption (P>0.05). CONCLUSIONS: MWDG was probably effective in the treatment of migraine especially for alleviating pain intensity. Furthermore, MWDG could reduce the frequency of migraine attacks and analgesics consumption sooner than the placebo.

Endoplasmic reticulum stress plays an important role in methotrexate-related cognitive impairment in adult rats.

The patients receiving methotrexate (MTX) treatment are inclined to suffer from cognition impairment, since MTX can induce apoptosis of neurons, while the underlying molecular mechanisms remain unknown. Thus we hypothesized that MTX-induced apoptosis of hippocampal neurons via activating endoplasmic reticulum stress (ERS) pathway, which leads to cognitive impairment in adult rats. In order to confirm our hypothesis, twenty male Sprague-Dawley rats weighting 180-220 g were divided into two groups: the control group (physiological saline) and the MTX60 group (MTX 60 mg/kg). Spatial memory was assayed by the Morris water maze test (MWM). In the mean time, another twenty-four rats were divided into four groups: the control group (physiological saline), MTX60 (MTX, 60 mg/kg), MTX100 (MTX, 100 mg/kg) and MTX250 (MTX, 250 mg/kg). Then, we observed the pathological changes of the hippocampus by hematoxylin-eosin stained. The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were determined by Western blot and immunofluorescence. The apoptosis of neurons were assessed by TUNEL assay. The Morris water maze test showed that MTX induced spatial memory impairment in adult rats (P<0.05). The degenerated or apoptotic neurons were condensed and the number of neurons with nuclear pyknosis increased significantly in hippocampus CA1 area of rats in MTX groups. Additionally, both protein expressions of CHOP and caspase-12 and number of TUNEL positive cells were significantly increased in these MTX groups (P<0.05). The present results suggested that ERS mediated by apoptosis of hippocampal neurons might play an important role in the mechanism of MTX-induced cognitive impairment in adult rats.