Network pharmacology analysis combined with experimental validation to explore the therapeutic mechanism of salidroside on intestine ischemia reperfusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Salidroside (SAL), a phenolic natural product present in Rhodiola rosea, are commonly used in the treatment of various ischemic-hypoxic diseases, including intestinal ischemia-reperfusion (IR) injury. However, their efficacy and potential mechanisms in the treatment of intestinal IR injury have not been investigated. OBJECTIVE: The objective of the present study is to investigate the pharmacological mechanism of action of SAL on intestinal IR injury using a network pharmacology approach combined with experimental validation. METHODS: In the present study, we used the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and analysis platform and Comparative Toxicogenomics Database (CTD) to predict possible target genes of SAL, collected relevant target genes of intestinal IR injury from GeneCards and DisGenet websites, and collected summary data to screen common target genes. Then, the protein-protein interaction (PPI) target network was constructed and analyzed by STRING database and Cytoscape 3.8.2 with the above intersecting genes. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed and the component-target-pathway network was constructed, followed by the use of molecular docking and molecular dynamic simulation to verify the possible binding conformation between SAL and candidate targets to further explore the potential targets of SAL in the treatment of intestinal IR injury. Finally, an in vivo model of mouse superior mesenteric artery ligation was established to assess the anti-intestinal IR injury effect of SAL by assessing histopathological changes in mouse small intestine by HE staining, detecting inflammatory factor expression by ELISA kit, and detecting the expression of key protein targets by Western blotting. RESULTS: A total of 166 SAL target genes and 1740 disease-related targets were retrieved, and 88 overlapping proteins were obtained as potential therapeutic targets. The pathway enrichment analysis revealed that the pharmacological effects of SAL on intestinal IR injury were anti-hypoxic, anti-inflammatory and metabolic pathway related, and the molecular docking and molecular dynamic simulation results showed that the core bioactive components had good binding affinity for TXNIP and AMPK, and the immunoblotting results indicated that the expression levels of TXNIP and AMPK in the small intestinal tissues of mice in the drug-treated group compared with the model group were significantly changed. CONCLUSION: SAL may target AMPK and TXNIP domains to act as a therapeutic agent for intestinal IR. These findings comprehensively reveal the potential therapeutic targets for SAL against intestinal IR and provide theoretical basis for the clinical application of SAL in the treatment of intestinal IR.

[Therapeutic observation on Fu's acupuncture for cervical spondylosis of vertebral artery type based on Tongtuo method].

OBJECTIVE: To verify the superiority of Fu's acupuncture for cervical spondylosis of vertebral artery type (CSA) based on Cheng's Tongtuo method. METHODS: A total of 150 patients with CSA were randomly divided into a Tongtuo Fu's acupuncture group, a Tongtuo acupuncture group and a conventional Fu's acupuncture group, 50 cases in each group. Under the guidance of the theory of Tongtuo method, the Tongtuo Fu's acupuncture group was treated with Fu's acupuncture, the distal Tong method was performed at the distal myofascial trigger point (MTrP) of the dorsal forearm, and then the Tuo method was performed at the proximal MTrP of the cervical muscle group. In the Tongtuo acupuncture group, acupuncture was given at distal acupoints (Neiguan [PC 6], Quchi [LI 11], Taichong [LR 3], Xingjian [LR 2], etc.), and then at proximal acupoints (Fengchi [GB 20] and Baihui [GV 20]). In the conventional Fu's acupuncture group, Fu's acupuncture was only performed at the MTrP of cervical muscle group. Each group was treated once a day, 3 days were taken as one course, and 2 courses were given. The score of cervical vertigo symptoms and function evaluation scale, peak systolic velocity (PSV) and resistance index (RI) of vertebral artery were observed before and after treatment in the 3 groups. RESULTS: After treatment, the scores of cervical vertigo symptoms and function evaluation scale and PSV in each group were higher than those before treatment (P<0.01), and the RI was lower than that before treatment (P<0.01). The score of cervical vertigo symptoms and function evaluation scale and PSV in Tongtuo Fu's acupuncture group were higher than those in the other two groups (P<0.01), and the RI was lower than that in the other two groups (P<0.01). CONCLUSION: Fu's acupuncture based on Tongtuo method could improve the symptoms of cervical vertigo and the blood flow state of vertebral artery in patients with CSA, and the curative effect is better than Tongtuo acupuncture and conventional Fu's acupuncture.

[Clinical observation of the therapeutic effect on posterior circulation ischemic vertigo treated with "xiao xingnao kaiqiao" acupuncture].

OBJECTIVE: To observe the short-term and long-term clinical effect on posterior circulation ischemic vertigo treated with "xiao xingnao kaiqiao" acupuncture (minor regaining consciousness and opening orifice) and explore its effect mechanism. METHODS: Ninety patients with posterior circulation ischemic vertigo were randomly divided into a treatment group and a control group, 45 cases in each group. The patients of the two groups were all treated on the base of neurological medicine. In the control group, Flunarizine Hydrochloride was prescribed for oral administration (5 mg, once daily, for 21 days totally). In the treatment group, acupuncture of "xiao xingnao kaiqiao" was provided at Yintang (EX-HN3), bilateral Neiguan (PC6), bilateral Sanyinjiao (SP6), Baihui (GV20), bilateral Fengchi (GB20), bilateral Wangu (GB12) and bilateral Tianzhu (BL10). The needles were retained for 30 min, once daily for 21 days totally. The changes in vertigo score of traditional Chinese medicine (TCM) were observed, and the changes in the mean blood velocity (Vm) of the left vertebral artery (LVA), the right vertebral artery (RVA) and the basilar artery (BA) as well as the vascular pulsatility index (PI) were monitored and determined by transcranial Doppler (TCD). Additionally, the recurrence rate was followed up after 3 months to evaluate the long-term clinical effects. RESULTS: After treatment, the total effective rate of the treatment group was 91.11% (41/45) and 75.56% (34/45) in the control group. The total effective rate in the treatment group was higher than that in the control group (P<0.05). Compared with their own pre-treatment, the vertigo scores of TCM were reduced in either the treatment group or the control group after treatment (P<0.05) and the score in the treatment group was lower than that in the control group (P<0.05). Compared with their own pre-treatment, Vm and PI were all improved after treatment in either group (P < 0.05). After treatment, the improvements in Vm and PI of LVA、RVA and BA in the treatment group were better than those in the control group (P<0.05). In the follow-up after 3 months, the recurrence rate was 19.51% (8/41) in the treatment group and was 50.00% (17/34) in the control group. The recurrence rate in the treatment group was lower than that in the control group (P<0.05). CONCLUSION: "Xiao xingnao kaiqiao" acupuncture obviously relieves the clinical symptoms of posterior circulation ischemic vertigo. The mechanism of acupuncture is potentially related with its effects in improving Vm and PI of LVA,RVA and BA, as well as improving blood supply of brain tissue.

[Application of functional magnetic resonance imaging in acupoint functional significance of encephalic region].

Literatures of study on acupoint functional effect of encephalic region with functional magnetic resonance imaging (fMRI) are collected from the database of China National Knowledge Information (CNKI) and Wan fang database. Analysis and comments are made respectively from the status quo of studies on combination of single acupoint, two acupoints and multiple acupoints under both physiological and pathological conditions. The results show that the corresponding encephalic regions can be specifically activated by acupuncture. And different regions can be activated by different acupoints. However, studies on single acupoint, two acupoints and three acupoints are the major researches carried out at present. It is still lack of observation on effect of commonly-used combinations in clinic. Moreover, the reliability of the research results are also affected by disunity of operations protocol, reinforcing or reducing manipulations, intensity or depth of stimulation and duration of needling retention. Therefore, it is necessary to establish a unified and standard operation protocol to strictly control the bias factors which may affect the result of research in the future, and take patients as the study target as much as possible, so as to further explore the central effect mechanism.

Clinical research into Qufeng Zhidong Recipe used to treat 31 children with tic disorder.

OBJECTIVE: To assess the therapeutic effect and adverse reaction of Qufeng Zhidong Recipe (a recipe for dispelling wind to stop abnormal movement) used to treat children with tic disorder (TD). METHODS: The enrolled patients were randomized into a TCM group (31 cases) treated with Qufeng Zhidong Recipe and a Western medicine group (30 cases) treated with haloperidol and trihexyphenidyl. Two courses of treatment were observed with 12 weeks as one course. The therapeutic effect and adverse reaction were assessed with Yale Global Tic Severity Scale (YGTSS), Tic Symptom Score Scale (TSSS), TCM Syndrome Score Scale (TCMSSS), Treatment Emergent Symptom Scale (TESS) and laboratory examinations. RESULTS: The total effective rate was 100% in the TCM group and 60% in the Western medicine group with statistical significance in difference (P < 0.05). All the scores in the TCM group were better than those in the Western medicine group (P < 0.05). CONCLUSION: Qufeng Zhidong Recipe can obviously relieve the symptoms and signs of TD children without toxic side-effects.

Multicenter clinical study on the treatment of children's tic disorder with Qufeng Zhidong Recipe.

OBJECTIVE: To assess the effect and adverse reaction of Qufeng Zhidong Recipe (QZR) in treating children's tic disorder (TD). METHODS: With multicenter randomized parallel open-controlled method adopted, the patients enrolled were assigned to two groups, 41 cases in the Chinese medicine (CM) group and 40 in the Western medicine (WM) group. They were treated by QZR and haloperidol plus trihexyphenidyl respectively for 12 weeks as one course. In total, two courses of treatment were given. The curative effect and adverse reactions were evaluated by scoring with Yale Global Tic Severity Scale (YGTSS), Traditional Chinese Medicine Syndrome Scale (TCMSS), and Treatment Emergent Symptom Scale (TESS), as well as results of laboratory examinations. RESULTS: After one course of treatment, the markedly effective rate in the CM and the WM group was 14.6% and 17.5%, respectively, and the total effective rate 43.9% and 47.5%, respectively, which showed insignificant difference between groups (P>0.05). However, after two courses of treatment, markedly effective rate in them was 73.2% and 7.5%, and the total effective rate was 100.0% and 57.5%, both showing significant differences between groups (P<0.05). Besides, the adverse reactions occurred in the CM group was less than that in the WM group obviously. CONCLUSION: QZR has definite curative effect with no apparent adverse reaction in treating TD, and it can obviously improve the symptoms and signs and upgrade the quality of life and learning capacities in such patients.

[Clinical observation of XELOX (Capecitabine puls Oxaliplatin): an adjuvant chemotherapy regimen used in stage III colorectal cancer].

OBJECTIVE: To evaluate the efficacy and safety of an adjuvant chemotherapy regimen: XELOX (Capecitabine puls Oxaliplatin) used after curative resection for stage III colorectal cancer. METHODS: From Jan. 1998 to Jan. 2004, 256 cases with stage III colorectal cancer randomized received de Gramont, modified FOLFOX4 (mFOLFOX4) and XELOX regimens. The 3-year disease-free survival (DFS) and overall survival (OS) were compared within the three groups and relative prognosis factors within mFOLFOX4 and XELOX groups. Therapeutic adverse events were recorded and analyzed with Kaplan-Meier test. RESULTS: 98, 87 and 71 cases were respectively enrolled in the de Gramont, mFOLFOX4 and XELOX groups, mFOLFOX4 and XELOX had superior efficacy compared with de Gramont regimen. The two former could significantly improve 3-year DFS (79.7% vs. 66.2%, P = 0.015; 81.5% vs. 66.2%, P = 0.004) and medium survival time (40.2 mon vs. 37.8 mon, P = 0.024; 41.4 mon vs. 37.8 mon, P = 0.014). Meanwhile they could respectively decrease the ratio of recurrence risk by 18.0% (P = 0.024) and 21.0% (P = 0.003). The relative benefit of mFOLFOX4 versus XELOX didn't differ for 3-year DFS [hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.79-1.12, P = 0.13] and OS (HR: 0.87, 95% CI: 0.84-1.06, P = 0.54). In the analysis of DFS in relative prognosis factors, XELOX had a better trend of survival advantage. mFOLFOX4 had higher adverse events within these regimens, especially in grade 3 or 4 neutropenia and peripheral neurologic adverse events. CONCLUSION: XELOX maintains its efficacy and safety ratio in advanced colorectal cancer. Patients have good tolerance and compliance. The regiment is deserves to be applied in clinical treatment. Oxaliplatin;

[Effect of carbamazepine and valproate on bone metabolism in children with epilepsy].

OBJECTIVE: To assess bone health in epileptic children who have been treated with carbamazepine (CBZ) or valproate (VPA) by using quantitative ultrasound (QUS) and determining the biochemical indices of bone metabolism, and to provide a proposal to improve quality of life of epileptic children. METHODS: Ninety-two epileptic children who had been treated with CBZ or VPA for more than two years were evaluated for bone mineral density (BMD) at the mid-shaft tibia and the distal third of the radius. Biochemical indices of bone metabolism including urine deoxypyridinoline (DPD) and serum osteocalcin (OC), and daily calcium intake were also evaluated. Thirty-five age-matched healthy children were used as controls. Reduced BMD was defined as speed of sound (SOS) Z scores of the mid-shaft tibia and (or) the distal third of the radius less than -0.7. RESULTS: BMD was reduced in epileptic children significantly when compared to the controls (P < 0.05). In addition, a negative correlation was found between the duration of anti-epileptic drugs (AEDs) use and BMD (r(s) = -0.21 - -0.31, P < 0.05), the lowest BMD was observed in those who had been treated for the longest time. The serum values of OC in epileptic children were significantly reduced relative to the controls (P < 0.01), children who took VPA had the lowest value of OC. However, the urine values of DPD showed no significant difference between epileptic and healthy children (P > 0.05); children who took CBZ had the highest value of DPD. Thirty-two epileptic children (35%) and five (14%) sex- and age-matched healthy children had reduced BMD, significant difference was found between them (P < 0.05). Moreover, epileptic children with reduced BMD seemed to have higher body mass index (BMI) (P < 0.05), take less daily calcium intake (P < 0.01), and had longer duration of AEDs (P < 0.01). The two risk factors of having reduced BMD in epileptic children were those who had been treated with AEDs for more than five years and higher BMI, while the protective factor was daily calcium intake. CONCLUSIONS: Long-term use of CBZ or VPA is associated with bone metabolism abnormalities, which include reduced BMD and decreased bone turnover (mainly decreased bone formation). Long-term anti-epileptic therapy is an important factor for impaired bone health in epileptic children, and that low calcium intake and high BMI could be two aggravating factors. QUS is a useful method to evaluate BMD of epileptic children who are on long-term anti-epileptic therapy, and to recognize the status of bone health, in helping to promote bone health and improve quality of life in epileptic children by the use of calcium and vitamin D supplementation.