[Toxic effect and mechanism of Tripterygium glycosides on ovarian germline stem cells of mice in vitro by Notch signaling pathway].

The ovarian germline stem cells(OGSCs) cultured in the optimized culture system were used as the research object to observe the effect of Tripterygium glycosides(TG) on OGSCs and explore the mechanism of reproductive toxicity by the Notch signaling pathway. Cell counting kit-8(CCK-8) was used to observe the viability level of OGSCs in mice cultured in vitro by TG of 3.75, 7.5, and 15 µg·mL~(-1). Immunofluorescence technology and reverse transcription-polymerase chain reaction(RT-PCR) were used to detect the protein and gene expression level of OGSCs marker mouse vasa homologue(MVH) and octamer-binding transcription factor 4(Oct4) by TG of 3.75 µg·mL~(-1). RT-PCR detected the gene expression of neurogenic locus Notch homolog protein 1(Notch1), Hes family BHLH transcription factor 1(Hes1), and jagged canonical Notch ligand 1(Jagged1). The RNA was extracted for transcriptome analysis to analyze the mechanism of action of TG intervention on OGSCs. 3.75 µg·mL~(-1) of TG was combined with 40 ng·mL~(-1) Notch signaling pathway γ-secretagocin agonist jagged canonical notch ligand(Jagged) for administration. CCK-8 was used to detect the viability level of OGSCs. Double immunofluorescence technology was used to detect the protein co-expression of MVH with Hes1, Notch1, and Jagged1. The results showed that compared with the blank group, the TG administration group significantly inhibited the activity of OGSCs(P<0.01 or P<0.001). It could reduce the protein and gene expression of OGSC markers, namely MVH and Oct4(P<0.05, P<0.01, or P<0.001). It could significantly inhibit the gene expression of Notch1, Hes1, and Jagged1(P<0.001). Transcriptomic analysis showed that TG affected the growth and proliferation of OGSCs by intervening Jagged1, a ligand associated with the Notch signaling pathway. The experimental results showed that the combination of Notch signaling pathway γ-secretagorein agonist Jagged could significantly alleviate the decrease in OGSC viability induced by TG(P<0.001) and significantly increased the OGSC viability compared with the TG group(P<0.001). It also could significantly increase the co-expression of MVH/Jagged1, MVH/Hes1, and MVH/Notch1 proteins(P<0.01 or P<0.001). It suggested that TG play the role of γ-secretagorease inhibitors by downregulating the OGSC markers including MVH and Oct4 and Notch signaling pathway molecules such as Notch1, Hes1, and Jagged1, participate in the OGSC pathway, and mediate reproductive toxicity caused by the Notch signaling pathway.

Effect of electroacupuncture of Governor Vessel on mitochondrial fusion and proliferation and differentiation of neural stem cells in spinal cord injury rats. / ç”µé’ˆç£è„‰å¯¹è„Šé«“æŸä¼¤å¤§é¼ è„Šé«“ç»„ç»‡çº¿ç²’ä½“èžåˆåŠç¥žç»å¹²ç»†èƒžå¢žæ®–åˆ†åŒ–çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Dazhui" (GV14) and "Jizhong"(GV6) of the Governor Vessel (GV) on mitochondrial fusion and neural stem cell (NSC) proliferation and differentiation in the spinal cord of rats with spinal cord injury (SCI), so as to investigate its mechanisms underlying improvement of SCI. METHODS: SD rats were randomly divided into sham operation, model and EA groups, with 15 rats in each group. The SCI model was established by using a precision impactor. EA (20 Hz/100 Hz, 1-2 mA) was applied to GV14 and GV6 for 30 min, once daily for 14 days. The rats' hindlimb locomotor function in each group was assessed using the Basso-Beattie-Bresnahan (BBB) locomotor scale. Histopathological changes of the injured spinal cord tissue and the number of neurons were evaluated after H.E. staining and Nissl staining. The expressions of Nestin, mitochondrial fusion-related protein optic atrophy-1 (OPA1) and NSC markers sex-determining region Y-box 2 (SOX2) in the injured spinal cord tissue were detected by immunofluorescence staining. The protein and mRNA expression levels of Nestin in the spinal cord tissue were detected by quantitative real-time PCR and Western blot, separately. RESULTS: Compared with the sham operation group, the BBB scores after modeling, and the number of neurons were significantly decreased (P<0.001), while the mean fluorescence intensity values of Nestin, SOX2 and OPA1, and the expressions of Nestin mRNA and protein considerably increased (P<0.001, P<0.01, P<0.05) in the model group. After EA intervention and in comparison with the model group, the BBB scores at the 7th and 14th day, the number of neurons, the mean fluorescence intensity values of Nestin, SOX2 and OPA1, and the expressions of Nestin mRNA and protein were strikingly increased (P<0.05, P<0.01, P<0.001) in the EA group. H.E. staining showed swollen, ruptured and necrotic neurons of the spinal cord, with a large number of vacuoles and severe inflammatory cell infiltration after modeling, which was relatively milder in the EA group. CONCLUSIONS: EA stimulation of GV14 and GV6 can promote the recovery of motor function in rats with SCI, which may be related to its effects in promoting mitochondrial fusion and enhancing the proliferation and differentiation of NSCs.

Design, synthesis and biological evaluation of bakuchiol derivatives as multi-target agents for the treatment of Alzheimer's disease.

The concept of multi-target-directed ligands offers fresh perspectives for the creation of brand-new Alzheimer's disease medications. To explore their potential as multi-targeted anti-Alzheimer's drugs, eighteen new bakuchiol derivatives were designed, synthesized, and evaluated. The structures of the new compounds were elucidated by IR, NMR, and HRMS. Eighteen compounds were assayed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in vitro using Ellman's method. It was shown that most of the compounds inhibited AChE and BuChE to varying degrees, but the inhibitory effect on AChE was relatively strong, with fourteen compounds showing inhibition of >50% at the concentration of 200 µM. Among them, compound 3g (IC50 = 32.07 ± 2.00 µM) and compound 3n (IC50 = 34.78 ± 0.34 µM) showed potent AChE inhibitory activities. Molecular docking studies and molecular dynamics simulation showed that compound 3g interacts with key amino acids at the catalytically active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and binds stably to acetylcholinesterase. On the other hand, compounds 3n and 3q significantly reduced the pro-inflammatory cytokines TNF-α and IL-6 released from LPS-induced RAW 264.7 macrophages. Compound 3n possessed both anti-acetylcholinesterase activity and anti-inflammatory properties. Therefore, an in-depth study of compound 3n is expected to be a multi-targeted anti-AD drug.

Butyrate Prevents the Pathogenic Anemia-Inflammation Circuit by Facilitating Macrophage Iron Export.

Most patients with inflammatory bowel disease (IBD) develop anemia, which is attributed to the dysregulation of iron metabolism. Reciprocally, impaired iron homeostasis also aggravates inflammation. How this iron-mediated, pathogenic anemia-inflammation crosstalk is regulated in the gut remains elusive. Herein, it is for the first time revealed that anemic IBD patients exhibit impaired production of short-chain fatty acids (SCFAs), particularly butyrate. Butyrate supplementation restores iron metabolism in multiple anemia models. Mechanistically, butyrate upregulates ferroportin (FPN) expression in macrophages by reducing the enrichment of histone deacetylase (HDAC) at the Slc40a1 promoter, thereby facilitating iron export. By preventing iron sequestration, butyrate not only mitigates colitis-induced anemia but also reduces TNF-α production in macrophages. Consistently, macrophage-conditional FPN knockout mice exhibit more severe anemia and inflammation. Finally, it is revealed that macrophage iron overload impairs the therapeutic effectiveness of anti-TNF-α antibodies in colitis, which can be reversed by butyrate supplementation. Hence, this study uncovers the pivotal role of butyrate in preventing the pathogenic circuit between anemia and inflammation.

Acupuncture Pretreatment Reduces Skeletal Muscle Inflammatory Response in EIMD Rats by Activating cGAS-STING-NF-κB Signaling Pathway.

Acupuncture pretreatment (AP) has a good skeletal muscle protective effect. The present study investigated whether acupuncture pretreatment could improve ultrastructural changes and skeletal muscle inflammation in exercising skeletal muscle injury. Eighty-eight male SD rats were randomly divided into a blank group (C), an exercise group (E), and an acupuncture pretreatment group (AP). Among them, the E and AP groups were divided into five subgroups of 0h, 12h, 24h, 48h, and 72h according to the extraction time after exercise, with 11 groups and eight rats in each group. The study involved simulating skeletal muscle injury caused by intermittent downhill running centrifugal exercise. The researchers used various methods to observe changes in mitochondrial structure and cGAS-STING-NF-κB p65 protein content of classical inflammatory response signaling pathway. These methods included transmission electron microscopy to observe skeletal muscle, Western Blot to detect changes in protein content, and reverse transcription polymerase chain reaction (RT-qPCR method) to detect cytoplasmic mtDNA gene fragment ND1, D-LOOP and cGAS-STING- NF-κB p65 protein RNA. The aim was to investigate the changes in NF-κB p65 protein RNA. Changes in NF-κB p65 protein RNA content and mtDNA gene fragment ND1 and D-LOOP content; changes in serum IL-8 and IFN-ß content were detected by enzyme-linked immunosorbent assay (ELISA); WB, RT-qPCR, ELISA assays aimed to study the skeletal muscle injury and mitochondrial structural damage in group E relationship skeletal muscle tissue level, cytoplasmic mtDNA fragment gene ND1, and D-LOOP content in skeletal muscle tissue of group E. In comparison to group C, the levels of cGAS-STING-NF-κB p65 protein expression and mRNA, and the serum levels of IL-8 and IFN-ß were significantly higher in group E . However, the acupuncture pretreatment group (AP) reduced the extent of damage to skeletal muscle mitochondria and the levels of cytoplasmic mtDNA fragment genes ND1 and D-LOOP. Also, the high expression of cGAS-STING-NF-κB p65 protein, mRNA, and the levels of IL-8 and IFN-ß were inhibited in the AP group. The results indicated that AP ameliorated exercise-induced skeletal muscle injury and reduced skeletal muscle inflammation produced after centrifugal exercise. This was achieved by inhibiting the overexpression of the cGAS-STING-NF-κB signaling pathway.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature.

Objective: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. Methods: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. Results: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. Conclusion: These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

[Clinical symptoms and distribution characteristics traditional Chinese medicine syndromes of pulmonary nodules].

A cross-sectional study method combined with two types of traditional Chinese medicine(TCM) syndrome differentiation methods was adopted to investigate the clinical symptoms and distribution characteristics of TCM syndromes in patients with pulmonary nodules from the perspectives of number, size, nature, and stability of pulmonary nodules by using the χ~2 test, systematic clustering and Apriori algorithm correlation analysis. The common clinical symptoms of pulmonary nodules were fatigue(77.35%) and irritability(75.40%), and 40 symptoms were clustered into 3 groups(digestive system symptoms, respiratory system symptoms, and emotional and systemic symptoms) and 8 major symptom categories. The proportion of cold and heat in complexity syndrome(63.43%) was higher based on cold-heat syndrome differentiation. The top two syndromes were Qi deficiency syndrome(88.03%) and Qi depression syndrome(83.17%) based on disease syndrome differentiation. Yang deficiency syndrome(60.52%) was more than Yin deficiency syndrome(50.16%). There were higher proportions of phlegm syndrome(78.67%) and Yang deficiency syndrome(69.33%) of so-litary pulmonary nodules in terms of the number of pulmonary nodules. In terms of size, the proportion of phlegm syndrome decreased as the mean diameter of pulmonary nodules increased, while the proportions of Yang deficiency syndrome and blood stasis syndrome increased. The distribution of Qi depression syndrome was more in those with mean diameter<10 mm(85.02%, P=0.044) and cold syndrome was more in those with mean diameter ≥10 mm(16.67%, P=0.024). In terms of the nature of pulmonary nodules, the proportions of Qi depression syndrome and heat syndrome decreased with the increase in solid components of pulmonary nodules, while the proportions of Yin deficiency syndrome and cold and heat in complexity syndrome increased. The blood stasis syndrome accounted for a higher proportion of pulmonary nodules with solid components. In terms of the stability of pulmonary nodules, dampness syndrome(72.97%), blood stasis syndrome(37.84%), and cold and heat in complexity syndrome(70.27%) accounted for higher proportions. In addition, patients with new nodules presented higher proportions in Qi inversion syndrome(52.00%, P=0.007) and cold and heat in complexity syndrome(66.00%, P=0.008). Meanwhile, 11 syndromes were associated and 4 common compound syndromes were obtained(Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome). Qi deficiency syndrome and Qi depression syndrome could be associated with other syndromes. The results show that the main clinical symptoms of pulmonary nodules are fatigue and irritability. The main TCM syndromes of pulmonary nodules are Qi deficiency syndrome, Qi depression syndrome, Yang deficiency syndrome, and cold and heat in complexity syndrome. The distribution of TCM syndromes is significantly correlated with the size of pulmonary nodules and the presence or absence of new nodules. The common compound syndromes are Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome.

Rapid identification of chemical components in Xuelian granule by UHPLC-Q-orbitrap-HRMS based on enzyme activity in vitro.

BACKGROUND: Xuelian granule (XL), a traditional Chinese medicine (TCM) formula, has been used for the treatment of diabetic nephropathy for a long time as a hospital preparation. Because the active ingredients in the XL that can help to treat diabetic nephropathy are still unclear, which limits the interpretation for its pharmacological mechanism, further development and subsequent study on the material basis of its efficacy. METHODS: In this study, a screening method based on inhibition activity against aldose reductase (AR) was employed for activity-directed chemical analysis of XL using ultra-high performance liquid chromatography combined with quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-orbitrap-HRMS) technique. RESULTS: A total of 178 compounds, including 46 terpenes, 47 organic acids, 25 flavonoids, 29 phenylethanoid glycosides, and 31 other types, were tentatively identified from XL which might responsible for its AR inhibition activity. CONCLUSION: This is the first study for a systematic, rapid, and accurate qualitative analysis of XL. This research provides a scientific and experimental basis for further researches on pharmacodynamics material basis and quality control of XL.

[Traditional application and modern research progress on new foreign medicinal resources].

Chinese medicinal resources are the material basis for the survival and development of traditional Chinese medicine(TCM)and the sustainable development of Chinese medicinal resources is also an important project for the modernization of TCM in China. With the increasing demand for Chinese medicinal resources in China, over-exploitation has destroyed Chinese medicinal resources, resulting in a shortage of many natural medicinal resources in China and making the sustainable development of TCM in trouble. The introduced new foreign medicinal resources have become effective supplement and replacement for Chinese medicinal resources to some extent. However, the development and utilization of new foreign medicinal resources in China are different. To fully understand the development of new foreign medicinal resources in China, this paper, taking 43 new foreign medicinal resources such as Acacia nilotica as objects, sorted out the introduction forms and policies of new foreign medicinal resources, overviewed its current development status in China, summarized the application experience of new foreign medicinal resources in the place of origin, as well as the research progress and problems of new foreign medicinal resources in China and abroad, and analyzed the research situation, which can enrich Chinese medicinal resources and other uses, promote the sustainable development of Chinese medicinal resources, and provide ideas for further development and research of new foreign medicinal resources.

Screening of anti-thrombin active components from Ligusticum chuanxiong by affinity-ultrafiltration coupled with HPLC-Q-Orbitrap-MSn.

INTRODUCTION: Ligusticum chuanxiong ('chuanxiong') is a traditional Chinese medicine for promoting blood circulation and removing blood stasis, which is often used to treat thrombotic diseases. However, its potential anticoagulant active ingredients have been unexplored. OBJECTIVES: The study aims to establish an affinity ultrafiltration mass spectrometry (AUF-MS) method for rapid screening of anti-thrombin active components of chuanxiong and to verify it in vitro. METHOD: In this study, the chemical constituents of different parts of chuanxiong were determined. A method for rapid screening of anticoagulant active ingredients by AUF-MS was established using thrombin as an affinity receptor target. Subsequently, the anticoagulant effect of such ligands was verified by in vitro anticoagulation experiments such as chromogenic substrate method and in vitro coagulation assay. Then the possible interaction mechanism between these ligands and thrombin was further studied by molecular docking. RESULTS: Twenty-one components were detected from different parts of chuanxiong. And three potential anti-thrombin active components were screened: ferulic acid, chlorogenic acid, isochlorogenic acid A by AUF coupled with high-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (HPLC-Q-Orbitrap-MSn ). The in vitro activity experiments and molecular docking revealed that these potential ligands exhibited strong binding ability and inhibitory activities on thrombin. CONCLUSION: The present study revealed that chuanxiong is a traditional Chinese medicine with excellent anticoagulation effects. Meanwhile, the integrated strategy based on AUF-MS, in vitro experiments and molecular docking also provided a powerful tool for further exploration of active ingredients responsible for the anticoagulant activity in chuanxiong.

[Effect of acupuncture at Weizhong (BL 40) on bladder urination function based on ultrasound].

OBJECTIVE: To observe the effect of acupuncture at Weizhong (BL 40) with deqi on bladder urination function. METHODS: A total of 60 healthy subjects were randomized into an observation group and a control group, 30 subjects in each group. Under the guidance of ultrasound, acupuncture was applied Weizhong (BL 40) on both sides. In the observation group, the needling depth was reached to the tibial nerve, and lifting-thrusting twirling method was used to induce deqi. In the control group, the needling depth was reached to the superficial fascia, and no manipulation was operated to induce deqi. The needles were retained for 10 min and acupuncture was given once in both groups. The bilateral ureteral ejection frequency and volume of the bladder were observed by ultrasound before and after acupuncture, and the score of clinical evaluation scale of deqi sensation was observed in both groups. RESULTS: After acupuncture, the frequency of bilateral ureteral ejection in the observation group and the bladder volume in the two groups were increased compared before acupuncture (P<0.05), and the frequency of bilateral ureteral ejection, bladder volume and score of clinical evaluation scale of deqi sensation in the observation group were higher than those in the control group (P<0.05, P<0.01). CONCLUSION: Acupuncture at Weizhong (BL 40) with deqi improves the bladder urination function. Ultrasound visualization improves the standardization and safety of acupuncture, intuitively evaluates the acupuncture effect, and provides an objective basis for the correlation between meridian points specificity and zang-fu organs.

Cytochalasans from the Endophytic Fungus Aspergillus sp. LE2: Their Structures, Antibacterial and NO Production Inhibitory Activities.

Six new cytochalasans-namely, aspergicytochalasins A-F (1-6)-together with five known analogs were isolated and characterized from the endophytic fungus Aspergillus sp. from the medicinal plant Lonicera japonica. The structures of the new compounds were established by NMR and MS methods as well as single crystal X-ray diffractions. Compounds 3 and 4 showed weak antibacterial activities to Staphylococcus aureus, with MIC values of 128 and 64 µg/mL, respectively. Compounds 1, 3, 5 and 6 showed inhibitory activities on NO production, with IC50 values less than 40 µM.

Effects of resveratrol supplementation on cardiac remodeling in hypertensive patients: a randomized controlled clinical trial.

Resveratrol (RES) has been demonstrated to be protective in the cardiovascular system in animal studies, but the evidence is limited in humans. The purpose of the study was to evaluate the effect of RES supplementation on cardiac remodeling in patients with hypertension. Eighty Subjects were randomly divided into RES group (plus RES 400 mg/d in addition to conventional therapy, n = 43) and control group (conventional therapy, n = 37). The main outcomes of the study were changes within cardiac-remodeling parameters. Secondary outcomes were changes in anthropometric parameters, arterial stiffness parameters and mechanism indices. There was no statistically significant difference between the RES group and control group in terms of baseline characteristics. After 6 months, the RES group had smaller left atrial, lower E/e', higher left ventricular global longitudinal strain and lower biomarkers indicating cardiac fibrosis (expressed by decreases in procollagen type I C-peptide and galectin-3) compared to the control group. However, there was no significant difference in left ventricular structure between the two groups. Although the RES group showed a significant decrease in brachial-ankle pulse wave velocity compared to the pre-intervention value, the difference between the RES and the control groups was not obvious. What's more, compared with the control group, the serum levels of sirtuin3, superoxide dismutase and klotho were significantly increased in the RES group. In conclusion, RES supplementation can alleviate left atrial remodeling, improve left ventricular diastolic function and may alleviate cardiac fibrosis in hypertensive patients, and could be used as an adjunct to conventional therapies of hypertensive heart disease.

[Chemical constituents in different parts of Ixeris sonchifolia based on UPLC-LTQ-Orbitrap-MS~n].

The chemical constituents in stem leaf, root, and flower of Ixeris sonchifolia were identified by the ultra performance li-quid chromatography coupled with linear ion trap quadrupole-orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS~n). The separation was performed on an Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) with a mobile phase of water(containing 0.1% formic acid, A)-acetonitrile(B) with gradient elution. With electrospray ionization source, the data of 70% methanol extract from stem leaf, root and flower of I. sonchifolia were collected by high-resolution full-scan Fourier transform spectroscopy, data dependent acquisition, precursor ion scan, and selected ion monitoring in the negative and positive ion modes. The compounds were identified based on accurate molecular weight, retention time, fragment ions, comparison with reference standard, Clog P and references. A total of 131 compounds were identified from the 70% methanol extract of I. sonchifolia, including nucleosides, flavonoids, organic acids, terpenoids, and phenylpropanoids, and 119, 110, and 126 compounds were identified from the stem leaf, root and flower of I. sonchifolia, respectively. In addition, isorhamnetin, isorhamnetin-7-O-sambubioside and caffeylshikimic acid were discovered from I. sonchifolia for the first time. This study comprehensively analyzed and compared the chemical constituents in different parts of I. sonchifolia, which facilitated the discovery of effective substances and the development and application of medicinal material resources of I. sonchifolia.

Network pharmacology and in vivo studies reveal the pharmacological effects and molecular mechanisms of Celastrol against acute hepatic injury induced by LPS.

Sepsis is currently the main factor of death in the ICU, and the liver, as an important organ of immunity and stable metabolism, can be acutely damaged during sepsis, and the mortality rate of patients with sepsis complicated by acute liver injury is greatly increased. Celastrol (CEL) is derived from the root bark of Tripterygium wilfordii Hook.f.. As a traditional Chinese medicine, CEL has anti-inflammatory, anti-cancer, anti-oxidant, and other biological activities. Obtain CEL and AHI intersection targets via database and construct protein-protein interaction (PPI) network by STRING. GO functional enrichment and KEGG pathway analyses were performed by R studio. Targets were finally selected to perform molecular docking simulations with CEL. In vivo experiments based on the model of AHI were established by intraperitoneal injection of Lipopolysaccharide (LPS) 4 h, and pre-treated with CEL (0.5 mg/kg, 1 mg/kg, 1.5 mg/kg). The results are as follows: 273 genes with the intersection of CEL and AHI were obtained, and GO and KEGG enrichment analysis were used to design the mechanism of inflammation, apoptosis, and oxidative stress-related injury. By constructing the PPI network selected top 10 targets are: STAT3, RELA, MAPK1, MAPK3, TP53, AKT1, HSP90AA1, JUN, TNF, MAPK14, predicted CEL protection AHI design related pathways of MAPK and PI3K/AKT-related signal pathways. In vivo experiments, CEL inhibited the activation of MAPK and PI3K/AKT related pathways, reduced inflammatory response, apoptosis, and oxidative stress, and significantly improved LPS-induced AHI. In summary, this study predicted the mechanisms involved in the protective effect of CEL on AHI through network pharmacology. In vivo, CEL inhibited MAPK and PI3K/AKT-related signaling pathways, and reduced inflammatory response, apoptosis, and oxidative stress to protect LPS-induced AHI.

[Kaiqiao Jieyin acupuncture combined with repetitive transcranial magnetic stimulation for post-stroke aphasia: a randomized controlled trial].

OBJECTIVE: To observe the effect of Kaiqiao Jieyin acupuncture (acupuncture for opening orifices and relieving aphasia) combined with repetitive transcranial magnetic stimulation (rTMS) on language ability and daily life communication ability in patients with post-stroke aphasia (PSA). METHODS: Fifty-six patients with PSA were randomly divided into an observation group and a control group, 28 cases in each group. Both groups received routine symptomatic treatment. The control group was treated with speech rehabilitation training and rTMS. On the basis of the treatment in the control group, the observation group was treated with Kaiqiao Jieyin acupuncture at the speech area Ⅰ, Fengchi (GB 20), Tongli (HT 5), Lianquan (CV 23), Panglianquan (Extra), etc. Panglianquan (Extra) on both sides were connected to electroacupuncture, with intermittent wave, 2 Hz in frequency. The above treatment was performed once a day for 5 consecutive days, followed by 2 days of rest for 2 weeks. The scores of western aphasia battery (WAB, including scores of spontaneous speech, auditory comprehension, repetition, naming and score of aphasia quotient [AQ]) and communication abilities in daily living (CADL) in the two groups were compared before and after treatment. RESULTS: After treatment, the spontaneous speech, auditory comprehension, repetition, naming scores and AQ scores in both groups were higher than those before treatment (P<0.05), and the increase in the observation group was greater than the control group (P<0.05). The CADL scores of the two groups were higher than those before treatment (P<0.05). CONCLUSION: Kaiqiao Jieyin acupuncture combined with rTMS can improve the language ability and daily life communication ability of PSA patients.

Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for mild-to-moderate depression: An assessor-blinded, randomized, non-inferiority trial.

AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.

Quantification of Local Vessel Wall and Plaque Volume Change for Assessment of Effects of Therapies on Carotid Atherosclerosis Based on 3-D Ultrasound Imaging.

We developed a new method to measure the voxel-based vessel-wall-plus-plaque volume (VWV). In addition to quantifying local thickness change as in the previously introduced vessel-wall-plus-plaque thickness (VWT) metric, voxel-based VWV further considers the circumferential change associated with vascular remodeling. Three-dimensional ultrasound images were acquired at baseline and 1 y afterward. The vessel wall region was divided into small voxels with the voxel-based VWV change (ΔVVol%) computed by taking the percentage volume difference between corresponding voxels in the baseline and follow-up images. A 3-D carotid atlas was developed to allow visualization of the local thickness and circumferential change patterns in the pomegranate versus the placebo groups. A new patient-based biomarker was obtained by computing the mean ΔVVol% over the entire 3-D map for each patient (ΔVVol%¯). ΔVVol%¯ detected a significant difference between patients randomized to pomegranate juice/extract and placebo groups (p = 0.0002). The number of patients required by ΔVVol%¯ to establish statistical significance was approximately a third of that required by the local VWT biomarker. The increased sensitivity afforded by the proposed biomarker improves the cost-effectiveness of clinical studies evaluating new anti-atherosclerotic treatments.

Effect of acupuncture pretreatment on inflammatory response of exercise-induced skeletal muscle damage in rats based on TLR9/MyD88/NF-κB signaling pathway. / 基于TLR9/MyD88/NF­κBä¿¡å·é€šè·¯æŽ¢è®¨é’ˆåˆºé¢„å¤„ç†å¯¹è¿åŠ¨æ€§éª¨éª¼è‚ŒæŸä¼¤å¤§é¼ ç‚Žæ€§ååº”çš„å½±å“.

OBJECTIVES: To observe the effects of acupuncture pretreatment on toll-like receptor 9/myeloid differentiation factor 88/nuclear factor-κB (TLR9/MyD88/NF-κB) signaling pathway and inflammatory response in the rats with exercise-induced skeletal muscle damage (EIMD) and explore the underlying mechanism of this pretreatment for EIMD. METHODS: A total of 88 male SD rats were randomly divided into a blank group (8 rats), a model group (40 rats) and an acupuncture pretreatment group (40 rats). In the model group and the acupuncture pretreatment group, 5 subgroups were randomized according to the sampling time of 0, 12, 24, 48 and 72 h of modeling, with 8 rats in each one, respectively. Before modeling, in the acupuncture pretreatment group, acupuncture was delivered at bilateral "Zusanli" (ST 36) and "Guanyuan" (CV 4) for 20 min, once daily for consecutive 7 days. By one-time intermittent downhill centrifugal exercise on animal experimental treadmill, EIMD model was established in the model group and the acupuncture pretreatment group. The ultrastructure of gastrocnemius muscle was observed under transmission electron microscope. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum were detected by ELISA. The protein and mRNA expression of TLR9, MyD88 and NF-κB p65 in the gastrocnemius tissue of rats was detected by the Western blot and real-time PCR, respectively. RESULTS: Compared with the blank group, the gastrocnemius ultrastructure in the model group showed the damage of different degrees, with myofilaments disarranged and twisted, mitochondria obviously swollen and mitochondrial crista partially defected. Compared with the model group, the injury was mild, most of muscle fibers were arranged neatly and the number of mitochondria increased remarkably in the acupuncture pretreatment group. Compared with the blank group, in the model group, the serum IL-6 levels increased at 0, 12, 24 and 48 h after modeling in the rats (P<0.01), and TNF-α levels were elevated at each time point after modeling (P<0.05, P<0.01). In the acupuncture pretreatment group, the serum IL-6 levels were reduced at 12, 24 and 48 h after modeling (P<0.01, P<0.05), and the TNF-α levels decreased at 24, 48 and 72 h after modeling (P<0.01) when compared with those in the model group at the same time points separately. The serum IL-6 and TNF-α levels ascended and then tended to decline in the model group and the acupuncture pretreatment group. Compared with the blank group, the protein and mRNA expression of TLR9 and NF-κB p65 in the gastrocnemius tissue increased at 12, 24, 48 and 72 h after modeling (P<0.01, P<0.05), and the protein and mRNA expression levels of MyD88 in the gastrocnemius tissue at each time point after modeling were elevated (P<0.05, P<0.01) in the model group. When compared with the model group at the same time points, in the acupuncture pretreatment group, the protein expression of TLR9 in the gastrocnemius tissue decreased at 12, 24, 48 and 72 h after modeling (P<0.05, P<0.01), and the mRNA expression of TLR9 was declined at 24, 48 and 72 h after modeling (P<0.01, P<0.05); the protein and mRNA expression of MyD88 in the gastrocnemius decreased at 24, 48 and 72 h after modeling (P<0.01, P<0.05), and that of NF-κB p65 was reduced at 24 h and 48 h after modeling (P<0.01). The protein and mRNA expression of TLR9, MyD88 and NF-κB p65 in the gastrocnemius tissue showed a trend of decrease after increase in the model group and the acupuncture pretreatment group. CONCLUSIONS: Acupuncture pretreatment can alleviate exercise-induced skeletal muscle damage, which may be related to modulating the expression of TLR9/MyD88/NF-κB signaling pathway to inhibit the inflammatory response.

Kaiqiao Jieyin acupuncture combined with repetitive transcranial magnetic stimulation for post-stroke aphasia: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Kaiqiao Jieyin acupuncture (acupuncture for opening orifices and relieving aphasia) combined with repetitive transcranial magnetic stimulation (rTMS) on language ability and daily life communication ability in patients with post-stroke aphasia (PSA).@*METHODS@#Fifty-six patients with PSA were randomly divided into an observation group and a control group, 28 cases in each group. Both groups received routine symptomatic treatment. The control group was treated with speech rehabilitation training and rTMS. On the basis of the treatment in the control group, the observation group was treated with Kaiqiao Jieyin acupuncture at the speech area Ⅰ, Fengchi (GB 20), Tongli (HT 5), Lianquan (CV 23), Panglianquan (Extra), etc. Panglianquan (Extra) on both sides were connected to electroacupuncture, with intermittent wave, 2 Hz in frequency. The above treatment was performed once a day for 5 consecutive days, followed by 2 days of rest for 2 weeks. The scores of western aphasia battery (WAB, including scores of spontaneous speech, auditory comprehension, repetition, naming and score of aphasia quotient [AQ]) and communication abilities in daily living (CADL) in the two groups were compared before and after treatment.@*RESULTS@#After treatment, the spontaneous speech, auditory comprehension, repetition, naming scores and AQ scores in both groups were higher than those before treatment (P<0.05), and the increase in the observation group was greater than the control group (P<0.05). The CADL scores of the two groups were higher than those before treatment (P<0.05).@*CONCLUSION@#Kaiqiao Jieyin acupuncture combined with rTMS can improve the language ability and daily life communication ability of PSA patients.