Astragalus polysaccharide improves diabetic ulcers by promoting M2-polarization of macrophages to reduce excessive inflammation via the ß-catenin/ NF-κB axis at the late phase of wound-healing.

Ethnopharmacological relevance: Astragalus polysaccharide (APS), the most biologically active ingredient of Astragali Radix, is used to treat diabetes mellitus (DM)-related chronic wounds in traditional Chinese medicine for several decades. This herb possesses an anti-inflammatory effect. Our study proved that APS can reduce excessive inflammation at the late phase of wound-healing in diabetic ulcers. Aim of the study: To clarify the molecular mechanism of APS in promoting wound-healing via reducing excessive inflammation in diabetic ulcers during the late stages of wound-healing. Methods and materials: The rat model of the diabetic ulcers was established via intraperitoneal injection of streptozocin (60 mg/kg). We detected the regulation of APS on diabetic ulcers by measuring wound-healing rates. Bioinformatics was used to predict the target genes of APS, and autodocking was used to predict the combination of APS and target genes. Immunohistochemistry, Enzyme-linked immunosorbent assay, Western blot, immunofluorescence staining, flow cytometry, and flow cytometric sorting were investigated. Results: The results demonstrated that APS promoted wound-healing and inhibited excessive inflammation at the late phase of wound-healing in diabetic rats. Mechanistic findings showed that APS promoted the expression of ß-catenin and Rspo3 while inhibiting the expression of NF-KB and GSK-3ß, which leads to the transformation of M1-type macrophages into M2-type macrophages and thus reducing excessive inflammation at the late phase of wound-healing in diabetic ulcers. Conclusion: We found an interesting finding that APS promoted the polarization of macrophages towards M2-type through the ß-catenin/NF-κB axis to reduce excessive inflammation at the late phase of wound-healing. Therefore, APS may be a promising drug for treating diabetic ulcers in clinic.

Corrigendum to "Acupuncture regulates the Th17/Treg balance and improves cognitive deficits in a rat model of vascular dementia" [Heliyon 9 (2) (February 2023) Article e13346].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e13346.].

Acupuncture regulates the Th17/Treg balance and improves cognitive deficits in a rat model of vascular dementia.

Objective: The present study was developed to explore the impact of acupuncture on the Th17/Treg balance in the brain and the periphery and associated changes in cognitive deficits in a rat model of vascular dementia (VD). Methods: Male Wistar rats (8 weeks old) were randomly assigned to sham-operated (Gs, n = 10), and operation (n = 30) groups. A VD model was established for all rats in the operation group via the permanent bilateral occlusion of the common carotid artery. Behavioral screening of these rats was conducted via a hidden platform trial at 2 months post-operation. These operation group rats were then further subdivided into impaired (Gi) and acupuncture (Ga) groups (n = 10/group). Acupuncture was performed over a 21-day period for rats in the Ga group. A Morris water maze (MWM) test was used to assess cognitive function for rats in all groups. Flow cytometry and fluorescent staining were used to detect Th17 and Treg cells in samples from these animals based on IL-17/FoxP3 or CD4+FoxP3+/CD4+RORγt+ staining profiles. Results: Relative to the Gs group, escape latency values for rats in the Gi group were significantly increased. Following treatment, rats in the Ga group exhibited significant reductions in escape latency values as compared to rats in the Gi group (P < 0.05). The relative Treg proportion in the peripheral blood and spleen additionally trended upwards in these Ga rats as compared to those in the Gi group (P > 0.05), whereas the frequency of Th17 cells in the peripheral blood and spleen of Ga group rats trended downward relative to the Gi group (P > 0.05). Significantly fewer CD4+RORγt+ and RORγt+ cells were detected in the Ga group relative to the Gi group, whereas CD4+FoxP3+ and FoxP3+ cell counts were increased (P < 0.01). Conclusion: In summary, VD model rats exhibited dysregulated Th17/Treg homeostasis. Acupuncture treatment was sufficient to reduce the frequency and numbers of Th17 cells in these animals while increasing Treg cell levels, thereby alleviating cognitive deficits with respect to both spatial learning and memory impairment. Consequently, the therapeutic benefits of such acupuncture treatment may be attributable to the regulation of the Th17/Treg balance and associated improvements in cognitive function.

Perioperative management and operative treatment of malignant tumor of anal canal merging severe abdominal protuberance / 中华胃肠外科杂志

Objective: To report the perioperative management and robot-assisted minimally invasive surgery results of one case with malignant tumor of anal canal combined with severe abdominal distention. Methods: A 66-year-old male suffer from adenocarcinoma of anal canal (T3N0M0) with megacolon, megabladder and scoliosis. The extreme distention of the colon and bladder result in severe abdominal distention. The left diaphragm moved up markedly and the heart was moved to the right side of the thoracic cavity. Moreover, there was also anal stenosis with incomplete intestinal obstruction. Preoperative preparation: fluid diet, intravenous nutrition and repeated enema to void feces and gas in the large intestine 1 week before operation. Foley catheter was placed three days before surgery and irrigated with saline. After relief of abdominal distention, robotic-assisted abdominoperineal resection+ subtotal colectomy+colostomy was performed. Results: Water intake within 6 hours post-operatively; ambulance on Day 1; anal passage of gas on Day 2; semi-fluid diet on Day 3; safely discharged on Day 6. Conclusion: Robotic-assisted minimally invasive surgery is safe and feasible for patients with malignant tumor of anal canal combined with severe abdominal distention after appropriate and effective preoperative preparation to relieve abdominal distention.

Clinical study of modified Shishi Niubangzi Decoction combined with strengthening tendons-waist exercise on lumbar disc herniation / 国际中医中药杂志

Objective:To observe the clinical effect of modified Shishi Niubangzi Decoction combined with strengthening muscle-waist exercise on lumbar disc herniation (LDH).Methods:Randomized controlled trial. A total of 60 patients with LDH admitted to the Pinggu Hospital, Beijing Traditional Chinese Medicine Hospital, were enrolled as the research objects between September 2020 and September 2021. According to the random number table, they were randomly divided into the treatment group and control group, 30 in each group. Both groups were given routine basic treatments (strengthening tendons-waist exercise and three-position six-step manipulation). On this basis, the treatment group was treated with modified Shishi Niubangzi Decoction, while the control group was treated with non-steroidal anti-inflammatory drugs (ibuprofen codeine sustained-release tablets). Both groups were treated for 4 weeks. The responsive rates, back pain intensity, leg pain and numbness by Visual Analogue Scale (VAS) and lumbar function by Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) were compared between the two groups.Results:The response rate of treatment group was significantly higher than that of control group (93.3% vs. 73.3%; χ2=4.32, P=0.038). After treatment, scores of JOA (subjective symptoms, signs, activities of daily living) in the treatment group were significantly higher than those in the control group ( t=3.86, 2.71, 2.21, P<0.05). After treatment, scores of back pain (2.12±0.21 vs. 3.02±0.32, t=12.88), leg pain (2.04±0.64 vs. 2.64±0.66, t=3.58), lower limb numbness (1.75±0.24 vs. 2.41±0.70, t=4.89) in the treatment group were significantly lower than those in the control group ( P<0.01). At 1 week and 1 month after treatment, ODI scores in treatment group were significantly lower than those in control group ( t=10.22, 5.59; P<0.05). Conclusion:The modified Shishi Niubangzi Decoction combined with strengthening tendons-waist exercise can improve responsive rates, improve lumbar pain and function in LDH patients.

Metabolomics-based comparative analysis of the effects of host and environment on Viscum coloratum metabolites and antioxidative activities / 药物分析学报

Viscum coloratum(Komn.)Nakai is a well-known medicinal hemiparasite widely distributed in Asia.The synthesis and accumulation of its metabolites are affected by both environmental factors and the host plants,while the latter of which is usually overlooked.The purpose of this study was to comprehensively evaluate the effects of host and habitat on the metabolites in V.coloratum through multiple chemical and biological approaches.The metabolite profile of V.coloratum harvested from three different host plants in two habitats were determined by multiple chemical methods including high-performance liquid chromatography-ultraviolet(HPLC-UV),gas chromatography-flame ionization detector(GC-FID)and ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-QTOF/MS).The differences in antioxidant efficacy of V.coloratum were determined based on multiple in vitro models.The multivariate statistical analysis and data fusion strategy were applied to analyze the dif-ferences in metabolite profile and antioxidant activity of V.coloratum.Results indicated that the metabolite profile obtained by various chemical approaches was simultaneously affected by host and environment factors,and the environment plays a key role.Meanwhile,three main differential metab-olites between two environment groups were identified.The results of antioxidant assay indicated that the environment has greater effects on the biological activity of V.coloratum than the host.Therefore,we conclude that the integration of various chemical and biological approaches combined with multivariate statistical and data fusion analysis,which can determine the influences of host plant and habitat on the metabolites,is a powerful strategy to control the quality of semi-parasitic herbal medicine.

Effect of Gupi Xiaoji Decoction on Pyroptosis of HepG2.2.15 Cells Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo screen the active antitumor components of Gupi Xiaoji decoction by network pharmacology and molecular docking based on the pyroptosis mediated by cysteinyl aspartate-specific protease 1 （Caspase-1） and explore its molecular mechanism in intervening in the pyroptosis of HepG2.2.15 cells through in vitro experiments. MethodThe compounds and targets of Gupi Xiaoji decoction were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） to obtain the corresponding gene symbols. The targets of Caspase-1 were collected from GeneCards，online mendelian inheritance in man（OMIM），PharmGKB，and TTD，and the compound-gene target regulatory network was constructed by Cytoscape. The protein-protein interaction（PPI） network was established and analyzed by STRING. The mechanism of the effective components of Gupi Xiaoji decoction on Caspase-1 was predicted by gene ontology（GO） functional enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The molecular docking was verified with AutoDock Vina. The plasma medicated with Gupi Xiaoji Decoction was prepared and HepG2.2.15 cells were cultured in vitro. HepG2.2.15 cells were divided into a blank plasma group，a VX-765 group，a VX-765+medicated plasma group， and a medicated plasma group. After 48 hours of intervention with 15% medicated plasma， the expression and distribution of gasdermin D-N （GSDMD-N） on the surface of the cell membrane were detected by immunofluorescence staining. The release of lactic dehydrogenase （LDH）， interleukin（IL）-1β，and IL-18 in the cell supernatant was measured by enzyme-linked immunosorbent assay（ELISA） kits. The expression of Caspase-1 and GSDMD-N was measured by Western blot. ResultThe mitogen-activated protein kinase 14 （MAPK14），MAPK1，protein kinase B1 （Akt1）， MAPK8， V-Jun sarcoma virus oncogene homolog （JUN）， and TP53 screened by network pharmacology were the main targets. The compounds 7-hydroxy-5，8-dimethoxy-2-phenyl-chromone，wogonin，rhamnazin，moslosooflavone，isorhamnetin，7-O-methylisomucronulatol，formononetin，calycosin，luteolin，quercetin，kaempferol，β-sitosterol，and baicalein screened by network pharmacology were the main active components of Gupi Xiaoji decoction. Go enrichment analysis showed that multiple biological processes were involved， including responses to oxidative stress and metal ions，ubiquitin-like protein ligase binding，and phosphatase binding. KEGG pathway enrichment analysis showed MAPK pathway，nuclear factor（NF）-κB pathway，p53 pathway， and hypoxia-inducible factor-1（HIF-1） pathway were involved. Molecular docking showed that the targets had good binding with the components. In vitro experiments displayed that compared with the blank plasma group，the VX-765 group showed weakened GSDMD-N fluorescence signal，reduced release of LDH，IL-1β，and IL-18，and declining expression of Caspase-1 and GSDMD-N（P<0.01）， and the medicated plasma group showed increased GSDMD-N fluorescence signal， increased release of LDH，IL-1β，and IL-18，and up-regulated expression of Caspase-1 and GSDMD-N（P<0.01）. ConclusionGupi Xiaoji Decoction can induce the pyroptosis of HepG2.2.15 cells by regulating Caspase-1 through multiple targets and multiple pathways.

Data Mining and Systems Pharmacology to Elucidate Effectiveness and Mechanisms of Chinese Medicine in Treating Primary Liver Cancer / 中国结合医学杂志

OBJECTIVE@#To identify specific Chinese medicines (CM) that may benefit patients with primary liver cancer (PLC), and to explore the mechanism of action of these medicines.@*METHODS@#In this retrospective, singlecenter study, prescription information from PLC patients was used in combination with Traditional Chinese Medicine Inheritance Supports System to identify the specific core drugs. A system pharmacology approach was employed to explore the mechanism of action of these medicines.@*RESULTS@#Taking CM more than 6 months was significantly associated with improved survival outcomes. In total, 77 putative targets and 116 bioactive ingredients of the core drugs were identified and included in the analysis (P<0.05). A total of 1,036 gene ontology terms were found to be enriched in PLC. A total of 75 pathways identified from Kyoto Encyclopedia of Genes and Genomes were also enriched in this disease, including fluid shear stress, interleukin-17 signaling, signaling between advanced glycan end products and their receptors, cellular senescence, tumor necrosis factor signaling, p53 signaling, cell cycle signaling, steroid hormone biosynthesis, T-helper 17 cell differentiation, and metabolism of xenobiotics by cytochrome. Docking studies suggested that the ingredients in the core drugs exert therapeutic effects in PLC by modulating c-Jun and interleukin-6.@*CONCLUSIONS@#Receiving CM for 6 months or more improves survival for the patients with PLC. The core drugs that really benefit for PLC patients likely regulates the tumor microenvironment and tumor itself.

An Integrated Gut Microbiota and Network Pharmacology Study on Fuzi-Lizhong Pill for Treating Diarrhea-Predominant Irritable Bowel Syndrome.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the most common chronic functional gastrointestinal diseases with limited treatments. Gut microbiota play an important role in chronic gastrointestinal diseases. In traditional Chinese medicine (TCM), Spleen-Yang deficiency (SYD) is one of the root causes of IBS-D. Fuzi-Lizhong pill (FLZP) is well known for its powerful capacity for treating SYD and has a good clinical effect on IBS-D. However, the mechanism of FLZP on the gut microbiota of IBS-D has not been fully clarified. Our present study aimed to reveal the mechanism of FLZP regulating gut microbiota of IBS-D. The body mass, CCK, MTL, and Bristol fecal character score were used to verify the establishment of the IBS-D model. IL-6, TNF, IL-1ß, and IFN-γ were crucial targets screened by network pharmacology and preliminarily verified by ELISA. Eighteen gut microbiota were important for the treatment of IBS-D with FLZP. Bacteroidetes, Blautia, Turicibacter, and Ruminococcus_torques_group were the crucial gut microbiota that FLZP inhibits persistent systemic inflammation in the IBS-D model. Lactobacillus is the crucial gut microbiota that FLZP renovates intestinal immune barrier in the IBS-D model. In summary, FLZP can affect bacterial diversity and community structures in the host and regulate inflammation and immune system to treat IBS-D.

The relationship between red blood cell distribution width and metabolic syndrome in patients with impaired glucose tolerance / 中国医师杂志

Objective:To evaluate the relationship between red blood cell distribution width (RDW) and metabolic syndrome (MS) in patients with impaired glucose tolerance (IGT).Methods:A total of 415 patients with abnormal glucose tolerance were screened by oral glucose tolerance test in Changsha Traditional Chinese Medicine Hospital (Changsha Eighth Hospital) from October 2015 to September 2019. General data were collected and blood routine and biochemical indexes were detected. There were 193 cases in the observation group and 222 cases in the control group. The RDW and other clinical indicators were compared between the two groups, the correlation between RDW and other indicators was analyzed, and the risk factors of metabolic syndrome were analyzed.Results:⑴ The RDW, systolic blood pressure (SBP), diastolic blood pressure (DBP), height (Ht), weight (Wt), waist circumferenc (Wc), triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), creatinine (Cr), uric acid (UA), alanine aminotransferase (ALT), high sensitive C-reactive protein (hs-CRP), body mass index (BMI) of the observation group were significantly higher than those of the control group, while the high density lipoprotein (HDL) was significantly lower than that of the control group, with statistically significant difference ( P<0.05); ⑵ correlation analysis showed that RDW was positively correlated with SBP, DBP, Ht, Wt, Wc, TG, CHOL, Cr, UA, ALT, hs-CRP, BMI, and negatively correlated with HDL ( P<0.05); ⑶ binary logistic regression analysis showed that RDW, Wt, Wc, CHOL, HDL, LDL and hs-CRP were independent risk factors for MS in patients with impaired glucose tolerance. Conclusions:The increase of RDW is a predictor of metabolic syndrome in people with abnormal glucose tolerance, which may provide some reference value for the prevention and treatment of metabolic syndrome.

[Advances in studies on steroidal alkaloids and their pharmacological activities in genus Veratrum].

Genus Veratrum plants contain a diversity of steroidal alkaloids, so far at least 184 steroidal alkaloids attributed to cevanine type(A-1～A-69), veratramine type(B-1～B-21), jervanine type(C-1～C-31), solanidine type(D-1～D-10) and verazine type(E-1～E-53), respectively, have been isolated and identified in the genus Veratrum. Their pharmacological activities mainly focused on decreasing blood pressure, anti-platelet aggregation and anti-thrombosis, anti-inflammatory and analgesic, and antitumor effect. This paper classified and summarized the 184 kind of steroidal alkaloids from the Veratrum plants and their major pharmalogical activities in order to provide the scientific basis for the further development and utilization of active alkaloids.

Discovery of LY3325656: A GPR142 agonist suitable for clinical testing in human.

The discovery and optimization of a novel series of GPR142 agonists are described. These led to the identification of compound 21 (LY3325656), which demonstrated anti-diabetic benefits in pre-clinical studies and ADME/PK properties suitable for human dosing. Compound 21 is the first GPR142 agonist molecule advancing to phase 1 clinic trials for the treatment of Type 2 diabetes.

Effects of electroacupuncture of different frequencies on electromyography, NOS and ICC of colon in rats with slow transit constipation / 针灸推拿医学（英文版）

Objective: To observe the effects of electroacupuncture (EA) of different frequencies on transmission function, electromyography, nitric oxide synthase (NOS) content and interstitial cells of Cajal (ICC) expression of colon in rat models with slow transit constipation (STC). Methods: Of the 50 healthy male Wistar rats, 10 were randomly selected as a normal group and fed with ordinary diet, and the remaining 40 rats were fed with the diet added with the compound diphenoxylate at a dose of 8 mg/(kg·bw) each day for continuous 120 d. The 40 successfully established STC rat models were randomly divided into a model group, a low-frequency EA group (2 Hz), a high-frequency EA group (100 Hz), and a variable-frequency EA group (2 Hz/100 Hz), with 10 rats in each group. Rats in the normal and the model groups were not given any treatment; the low-frequency EA and the high-frequency EA groups were given EA at Tianshu (ST 25), Zusanli (ST 36) and Zhigou (TE 6) with continuous wave at the designated frequency, and the variable-frequency EA group received sparse-dense wave (2 Hz/100 Hz) EA at the same acupoints, once a day for a total of 15 d. After treatment, the colonic transmission function, electromyography, NOS content and ICC expression (calculated by the difference in the area of the C-kit positive cells) of the rats in each group were measured. Results: For the colonic transmission function, compared with the normal group, the first black stool excretion durations of rats in the other groups were significantly prolonged (all P<0.05); compared with the model group, the first black stool excretion durations of rats in the three EA groups were significantly shortened (all P<0.05), which was significantly shorter in the variable-frequency EA group than in the low-frequency EA and high-frequency EA groups (both P<0.05). For the colonic electromyography, compared with the normal group, the amplitude was significantly increased and the frequency was accelerated in rats of the other groups (all P<0.05); compared with the model group, the amplitude was significantly reduced and the frequency was slowed down in the three EA groups (both P<0.05); compared with the low-frequency EA and the high-frequency EA groups, the amplitude was reduced and the frequency was significantly reduced in rats of the variable-frequency EA group (both P<0.05). Compared with the normal group, the colonic NOS contents were significantly increased in the other groups (all P<0.05); compared with the model group, the NOS contents were significantly reduced in the three EA groups (all P<0.05); compared with the low-frequency EA and the high-frequency EA groups, the content was significantly reduced in the variable-frequency EA group (all P<0.05). For the area of rat colonic C-kit-positive cells, compared with the normal group, the areas were significantly reduced in rats of other groups (all P<0.05); compared with the model group, the areas were increased significantly in the three EA groups (all P<0.05); compared with the low-frequency EA group, the area was increased significantly in the variable-frequency EA group (P<0.05). Conclusion: EA, especially EA at the 2 Hz/100 Hz variable-frequency, has a positive treatment effect on the STC model rats. It may improve rats' colonic function by regulating the electromyography, NOS content and ICC expression of colon.

Effect of Bushen Zhuangdu Recipe on Mitochondrial Apoptotic Pathway in Degenerative Intervertebral Disc Cells in Rats / 中国实验方剂学杂志

Objective:To explore the mechanism of mitochondrial apoptotic pathway in rat degenerative intervertebral disc cells in improving intervertebral disc degeneration under the action of Bushen Zhuangdu recipe. Method:The 100 SD male rats were randomly divided into blank group, model group, low, medium and high dose Bushen Zhuangdu recipe group (0.38,0.77,1.53 g·kg-1).Histopathological changes of rat intervertebral discs were observed by hematoxylin-eosin(HE) staining after 4 weeks of continuous administration of Chinese medicine. The apoptotic rate of nucleus pulposus cells in degenerative intervertebral discs was detected by TUNEL(terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling), and the levels of active Cysteinyl aspartate-specific proteinase-3(active Caspase-3), B cell leukemia-2(Bcl-2), cytochrome C (cytC) and Bcl-2-associated X protein(Bax) protein in intervertebral discs were detected by Western blot. Result:Compared with blank group, the histopathological score of intervertebral disc in the model group was significantly increased, the apoptosis rate of nucleus pulposus was significantly increased (PPPPPPConclusion:Bushen Zhuangdu recipe may improve the degeneration of intervertebral disc by reducing the expression of active Caspase-3, cytC and Bax, increasing the expression of Bcl-2 and inhibiting the apoptotic pathway of mitochondria in a dose-dependent manner.

Effect of Modified Guipitang Combined with Xingnao Kaiqiao Acupuncture in Treatment of Heart and Spleen Insufficiency Syndrome of Non-dementia Vascular Cognitive Impairment / 中国实验方剂学杂志

Objective: To explore the curative effect and partial mechanism of modified Guipitang combined with Xingnao Kaiqiao acupuncture in the treatment of non-dementia vascular cognitive impairment (VCIND). Method: Totally 122 patients with VCIND admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (TCM) from May 2017 to October 2018 were randomly divided into modified decoction group (39 cases), acupuncture group (42 cases) and combination group (41 cases). All of the three groups were orally given routine anticoagulants and lipid-lowering drugs. The decoction group was orally given modified Guipitang 150 mL/times, 2 times/day, in addition to the routine treatment, the acupuncture group was treated with Xingnao Kaiqiao acupuncture method in addition to the routine treatment, involving Shuigou, Neiguan (bilateral), Sanyinjiao (bilateral), Sishencong, Xuanzhong (bilateral) and Taixi (bilateral) acupoints, 2 times/day, for six days a week, the combined group was treated with Xingnao Kaiqiao acupuncture in addition to modified Guipitang. All of the three groups were treated for 8 weeks. The Montreal cognitive assessment scale (MoCA scale, Beijing version) and activity of daily life (ADL) scale, TCM symptoms and clinical efficacy were scored before treatment, 4 weeks after treatment and 8 weeks after treatment in three groups. Serum levels of calcitonin gene-related peptide (CGRP) and cone-like protein-1 (VILIP-1) were measured by enzyme-linked immunosorbent assay at different time points. Result: Compared with decoction group and acupuncture group, MoCA score, ADL score and TCM syndrome score of the combined group were decreased, the total effective rate was increased significantly after 4 and 8 weeks of treatment, the serum CGRP content was increased, and the VILIP-1 content was decreased. Conclusion: Modified Guipitang combined with Xingnao Kaiqiao acupuncture has a definite curative effect on VCIND with heart and spleen insufficiency syndrome. Its mechanism may be related to the expansion of blood vessels, the alleviation of blood supply of brain and the reduction of neuron injury.

Effect of Qufu Shengji ointment(QFSJO) on promoting the healing of infectious wounds / 中国骨伤

OBJECTIVE@#To explore the clinical effect of Qufu Shengji ointment(QFSJO) in promoting the wound healing after trauma.@*METHODS@#From January 2014 to June 2018, 60 patients with soft tissue injury, skin defect and wound infection caused by violent trauma were admitted, including 32 males and 28 females, aged from 18 to 65 years, with an average age of 41.3 years. Among them, 30 patients were treated with QFSJO (QFSJO group) and 30 patients were treated with normal saline iodophor (control group). The reduction rate of wound area, the days of decayed flesh, the time of new epithelium and the recovery rate of 28 days after dressing change were compared between the two groups.@*RESULTS@#In the QFSJO group, after using large dose of QFSJO, the pus of the wound increased, the granulation grew, and the new epithelium appeared on the edge of the wound, showing a rapid healing phenomenon. The wound healing rate of QFSJO group was higher than that of the control group at all time points, and the time of decaying flesh and new epithelium appeared in QFSJO group was earlier than that of the control group. The recovery rate of QFSJO group was significantly higher than that of the control group(<0.05). All the patients were followed up, and the duration ranged form 6 to 12 months, with an average of 9.4 months. The exposed areas of bone and teadon were covered well. The vital signs of the two groups were stable and no adverse reactions occurred.@*CONCLUSIONS@#QFSJO can promote the growth of granulation tissue, promote the production of new skin, and accelerate the healing of infectious wound after trauma.

Effects of electroacupuncture of different frequencies on SP and VIP expression levels in colon of rats with slow transit constipation / 针灸推拿医学（英文版）

Objective:To observe the effects of electroacupuncture (EA) of different frequencies on the expression levels of substance P (SP) and vasoactive intestinal peptide (VIP) in the colon of rats with slow transit constipation (STC).Methods:One hundred healthy male Sprague-Dawley (SD) rats were randomly divided into a normal group,a model group,a low-frequency EA group,a high-frequency EA group and a variable-frequency EA group,with 20 rats in each group.The rats in the normal group were fed with normal diet.The rats in the other groups were fed with phenethylpiperidine in the diet at a dose of 8 mg/(kg·bw) per day,for 120 d,to establish the STC model.Rats in the normal group and the model group did not receive any treatment;rats in the low-frequency EA group were treated with 2 Hz continuous wave EA,rats in the high-frequency EA group were treated with 100 Hz continuous wave EA,and rats in the variable-frequency EA group were treated with 2 Hz/100 Hz sparse-dense EA.The current intensity of the EA was determined by the slight vibration of the rat limbs without painful screaming.The intervention was performed once a day,15 min/time for continuous 15 d.After treatment,the intestinal transit function and the expression levels of SP and VIP in the colon of the rats in each group were determined.Results:After treatment,the defecation duration of the first dark stool in the model group was significantly longer than that in the normal group (P＜0.05);the defecation durations of the first dark stool in the low-frequency EA group,high-frequency EA group and variable-frequency EA group were significantly shorter than the duration in the model group (all P＜0.05);compared with the low-frequency EA group,the first dark stool defecation duration of rats in the variable-frequency EA group was significantly shorter (P＜0.05);compared with the normal group,the SP and VIP expression levels in the colon of the model group were significantly decreased (both P＜0.01);the SP and VIP expression levels in the colon of the low-frequency EA group,the high-frequency EA group and the variable-frequency EA group were significantly higher than those in the model group (all P＜0.05);compared with the high-frequency EA group,the SP expression levels in the colon in the low-frequency EA group and the variable-frequency EA group were significantly increased (both P＜0.05);compared with the low-frequency EA group,the VIP expression levels in the colon in the high-frequency EA group and the variable-frequency EA group were significantly increased (both P＜0.05).Conclusion:EA improves the intestinal function of STC model rats by regulating the expression levels of SP and VIP in rat colon.The EA stimulation with 100 Hz continuous wave,2 Hz/100 Hz sparse-dense wave shows a better improvement in the colonic transit function in STC rats,followed by 2 Hz continuous wave.

Hypolipidemic effect of SIPI-7623, a derivative of an extract from oriental wormwood, through farnesoid X receptor antagonism / 中国天然药物

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.

Hypolipidemic effect of SIPI-7623, a derivative of an extract from oriental wormwood, through farnesoid X receptor antagonism / 中国天然药物

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.

Effects of electroacupuncture of different frequencies on free radicals in hippocampus of mice with vascular dementia / 针灸推拿医学（英文版）

Objective:To observe the effects of electroacupuncture (EA) of three different frequencies (2 Hz,80 Hz and 2 Hz/80 Hz) on the free radicals in hippocampus of vascular dementia (VD) model mice.Methods:A total of 100 Kunming mice were randomly divided into a sham operation group,a model group,a 2 Hz EA group,an 80 Hz EA group and a 2 Hz/80 Hz EA group,with 20 mice in each group.The ischemia-reperfusion VD model was established by repeated blockade of bilateral common carotid arteries.Mice in EA groups began EA treatment on the 4th day after the operation.Baihui (GV 20),Dazhui (GV 14),Geshu (BL 17) and Zusanli (ST 36) were punctured and then connected to EA instrument,with different waves of 2 Hz,80 Hz or 2 Hz/80 Hz (10 min/time) applied accordingly,once a day.During the jumping stand experiment,the learning performance,memory performance and hippocampal calcitonin gene-related peptide (CGRP),nitric oxide synthase (NOS),malondialdehyde (MDA),changes in superoxide dismutase (SOD) and true choline esterase (TChE) were observed.In hippocampus,the CGRP level was determined by radioimmunoassay;the MDA level was determined by thiobarbituric acid colorimetric method;the activities of NOS and TChE were determined by spectrophotometry;the activity of SOD was determined by xanthine oxidase method.Results:Compared with the sham operation group,the performances of learning and memory decreased significantly in the model group (P＜0.01);in hippocampus,the CGRP level decreased,the MDA level increased,the activities of NOS and TChE increased,and the activity of SOD decreased in the model group.Compared with the model group,the learning and memory performances of the EA groups were significantly improved (P＜0.05 or P＜0.01);in hippocampus,the CGRP level increased,the MDA level decreased,the NOS and TChE activities decreased,and the SOD activity increased (P＜0.05 or P＜0.01).Among EA groups,the 2 Hz/80 Hz EA group was superior to the 2 Hz EA group and the 80 Hz EA group (P＜0.05 or P＜0.01).Conclusion:EA can improve the cognitive impairment of mice with ischemia-reperfusion VD.The mechanism may be related to the improvement of cerebral blood circulation,regulation of the central neurotransmitters,fighting lipid peroxidation and promoting nerve cell repair.The therapeutic effects of EA with different frequencies were different,and the intervention effect by EA at 2 Hz/80Hz is the most significant.