BACKGROUND:Metabonomics has been proved to analyze and observe the pathological process of rat myocardial infarction and the underlying mechanism. OBJECTIVE:To further analyze the metabolomic pathways of bioinformatics in rat models of myocardial infarction. METHODS:The experimental studies about rat myocardial infarction were retrieved from CNKI, WanFang, CqVip, PubMed and Embase databases. The metabolic products described in the literatures were col ected and summarized. Signaling pathways were analyzed using KEGG database molecular function annotation, the enzymes, translocators and their properties were analyzed by HMDB database. Metabolites pathway were visualized with MetPA. RESULTS AND CONSLUSION:A total of 26 metabolic products were identified in the included literatures and mainly participated in 29 metabolic pathways. Through topology analysis, 5 of the 10 metabolic pathways were selected and regarded as the metabolic pathways of myocardial infarction in rats, including aminoacyl-tRNA biosynthesis;glycine, serine and threonine metabolism;valine, leucine and isoleucine biosynthesis;biosynthesis of unsaturated fatty acids;phenylalanine, tyrosine and tryptophan biosynthesis. In conclusion, the bioinformatics analysis of metabolites in rats with myocardial infarction show that myocardial infarction is related to the metabolism and metabolic pathways of carbohydrates, proteins, fat and RNA.

This paper was aimed to study the effectiveness and safety of TanshinoneⅡA Sulfonate Sodium Injection in the treatment of unstable angina pectoris (UAP). Keywords such as coronary atherosclerotic heart disease, coronary heart disease, unstable angina, chest impediment, cardialgia, TanshinoneⅡA Sulfonate Sodium Injection, tanshinone injection, tanshinoneⅡA sulfonate, unstable, angina, randomized controlled trial (RCT), and clinical trials were searched in CNKI, VIP, Wanfang and Pubmed from the construction of database until October 31st, 2014. The inclusion criteria were RCT with clinical data integrity, similar literature research methods, and good balance between groups. The Jadad score method was used to carry out quality assessment. Meta-analysis was conducted by RevMan5.2 software. Count data was processed by odds ratio (OR). Measurement data was processed with the weighted mean differences (WMD). The 95% confidence interval (CI) was also calculated. The heterogeneity test result of included literatures was P > 0.05. The fixed effects model was used in the meta-analysis. On the other hand, random effect model was used. For the analysis results of more than 10 papers, the funnel plot was used in the analysis of publication bias. The results showed that a total of 34 studies were included. The results of meta-analysis suggested that the total efficiency of conventional treatment plus TanshinoneⅡA Sulfonate Sodium Injection for UAP was [OR = 3.83, 95%CI (3.11, 4.71),P < 0.000 01]. The electrocardiogram improvement rate was [OR = 3.34, 95%CI (2.61,4.28),P < 0.000 01]; plasma viscosity improvement was [WMD = -0.20, 95%CI (-0.38, -0.03),P = 0.03]; high shear viscosity of whole blood improvement was [WMD = -0.67, 95%CI (-0.85, -0.50),P < 0.000 01]; C-reactive protein improvement was [WMD = -2.66, 95%CI (-3.31, -2.00),P < 0.000 01]. It was concluded that the conventional treatment plus TanshinoneⅡA Sulfonate Sodium Injection for UAP had certain clinical effect with no obvious adverse reaction. However, due to the poor quality of the existing research literatures, the results should be further verified by large amount of high quality RCTs.

Objective: To evaluate the therapeutic efficacy of acupuncture plus Dang Gui Bu Xue Qu Feng Tang for benign essential blepharospasm (BEB). Methods: A prospective randomized controlled trial was performed. A total of 105 participants were randomized 1:1:1 into an acupuncture group, a herbal medicine group and an acupuncture plus herbal medicine group. Participants in the acupuncture group received manual acupuncture treatment, twice a week. Participants in the herbal medicine group received Dang Gui Bu Xue Qu Feng Tang, oral administration, once a day. Participants in the acupuncture plus herbal medicine group received both treatments. The therapeutic effects of the three groups were evaluated after four weeks of treatment. The primary outcome was the Jankovic rating scale (JRS) score, and the secondary outcome was the blepharospasm disability index (BSDI) score. Results: After four weeks of treatment, the JRS total scores significantly decreased in all three groups versus baseline (P<0.05). A greater reduction in the JRS total score was reported in participants in the acupuncture plus herbal medicine group (P<0.05), but there was no significant difference between the acupuncture group and the herbal medicine group (P>0.05). The acupuncture plus herbal medicine group had a greater decrease in the JRS severity score than the herbal medicine group (P<0.05). The reduction in the JRS frequency score was not significantly different among the three groups (P>0.05). The BSDI scores significantly decreased in all three groups versus baseline (P<0.05), but the reduction in the BSDI score was insignificantly different among the three groups (P>0.05). Conclusion: It is effective in the treatment of BEB either to use acupuncture and Dang Gui Bu Xue Qu Feng Tang alone or in combination. The combination therapy shows a more significant effect than either of the treatment alone.

Objective:To investigate the prevalence of uremic pruritus and related factors in patients undergoing hemodialysis.Methods:A total of 212 patients with uremia who undergo hemodialysis in the First Affiliated Hospital of Xiamen University in March 2021 were included in this cross-sectional study. Data including gender, age and blood biochemical indicators were collected. The 5D itch scale was used to evaluate skin itch in patients. The included patients were divided into pruritus and no pruritus groups according to evaluation results. Related indicators were compared between the two groups. Binary logistic regression analysis of skin itch related factors was performed.Results:According to 5D itch scale evaluation results, 129 patients (60.85%) of the 212 patients had no skin pruritus, and 83 patients (39.15%) had skin pruritus. In the pruritus group, age, hypersensitive C-reactive protein, alkaline phosphatase, brain natriuretic peptide, ferritin were 63.0 (51.0, 72.0) years, 1.66 (0.30, 7.85) mg/L, 93.0 (70.0, 118.0) U/L, 192.0 (84.9, 446.4) ng/L and 421.0 (291.6, 577.6) μg/L, respectively, which were significantly higher than 53.0 (42.0, 63.0) years, 0.40 (0.30, 1.88) mg/L, 79.0 (62.0, 99.0) U/L, 143.3 (65.8, 256.5) ng/L, 356.8 (203.3, 528.4) μg/L in the pruritus group ( Z = -3.14, -3.96, -3.05, -2.88, -2.11, all P < 0.05). Increased hypersensitive C-reactive protein, brain natriuretic peptide, ferritin levels ( Wald = 14.58, 4.17, 4.23, all P < 0.05) were independent risk factors for uremic pruritus. Conclusion:Uremic pruritus remains a serious problem in patients undergoing hemodialysis. Increased hypersensitive C-reactive protein, ferritin, brain natriuretic peptide levels are independent risk factors for uremic pruritus. In clinical work, physicians should focus on strengthening the early identification of patients, optimizing treatment measures, and improving the quality of life of patients.

Objective: To investigate the clinical efficacy of recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein combined with sodium hyaluronate in the treatment of rheumatoid arthritis (RA). Methods: Forty adult RA patients (12 males, 28 females) aged from 36 to 79 were selected in Department of Rheumatology of the Second People′s hospital of Datong from February 2016 to February 2018.The patients were randomly divided into the observation group and the control group according to the digital table, with 20 cases in each group.The observation group was treated by intra-articular injection of recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein and sodium hyaluronate, and the control group was only treated with recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein.The joint swelling, joint pain, joint mobility, morning stiffness, X-ray grade and total effective rate of the two groups were statistically analyzed before and after treatment. Results: Before treatment, there were no statistically significant differences in joint swelling, joint pain, joint mobility, morning stiffness, clinical score and X-ray grade between the two groups (all P>0.05). After treatment, the symptoms and signs of the two groups were obviously improved.The joint pain, joint pressure pain, joint activity, morning stiffness and clinical score in the observation group were (1.2±1.2)points, (0.8±0.7)points, (0.5±0.4)points, (0.7±0.7)points and (4.5±2.6)points, respetively, which were significantly better than those in the control group [(2.2±1.4)points, (1.5±0.9)points, (1.5±0.9)points, (1.5±0.6)points and (8.6±4.6)points, U=125, 111, 68, 89 and 97, all P<0.05]. The total effective rate of the observation group was 100% (20/20), while that of the control group was 75% (15/20), there was statistically significant difference between the two groups (χ²=14.10, P<0.01). Conclusion The injection of recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein combined with sodium hyaluronate in the treatment of RA can effectively improve the clinical symptoms of RA patients, and it is more effective than single use.It is worthy of popularizing in clinic.

Objective Based on the endoplasmic reticulum stress(ERS)inositol-requiring enzyme-1α(IRE1α)/apoptosis signal-regulated kinase 1(ASK1)/c-Jun N-terminal kinase(JNK)pathway to investigate the intervention effect of Ziziphi Spinosae Semen(ZSS)-Albiziae Flos(AF)on the depression model of rats,which were prepared by solitary rearing combined with chronic unpredictable mild stress(CUMS).Methods A total of 144 rats were randomly divided into normal group,model group,high-,medium-and low-dose groups of ZSS-AF,and Venlafaxine group.In addition to the normal group,the rats in other groups were isolated for 21 days combined with CUMS to prepare the depression model.The behavioral changes of rats were observed by open field test and Morris water maze test.The ultrastructural changes of hippocampal neurons were observed by transmission electron microscope.TUNEL staining was used to observe the apoptosis of nerve cells in hippocampus.The protein expression levels of IRE1α,phosphorylated(P)-IRE1α,ASK1,P-ASK1,JNK,P-JNK,B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax)and cysteme aspartate specific protease-3(Caspase-3)in hippocampus were detected by Western Blot.The mRNA expression levels of IRE1α,ASK1,JNK,Bax,Bcl-2 and Caspase-3 in hippocampus were detected by Real-Time PCR.Results Compared with the normal group,the scores of horizontal movement and vertical movement in the open field test of rats in the model group were decreased(P＜0.01).In the water maze test,the escape latency was increased and the number of crossing the original platform was decreased(P＜0.01).The number of hippocampal apoptosis was increased(P＜0.01).The protein expression levels of P-IRE1 α/IRE1 α,P-ASK1/ASK1,P-JNK/JNK,Bax,Caspase-3 and mRNA expressions of IRE1α,ASK1,JNK,Bax,Caspase-3 in hippocampus were increased,while the protein and mRNA expression levels of Bcl-2 were decreased(P＜0.01).Compared with model group,the scores of horizontal movement and vertical movement in the open field test of rats in each dose ZSS-AF groups and Venlafaxine group were increased(P＜0.01).In the water maze test,the escape latency was decreased and the times of crossing the original platform was increased(P＜0.01).The number of hippocampal apoptosis was decreased(P＜0.01).The mRNA expression levels of P-IRE1α/IRE1α,P-ASK1/ASK1,P-JNK/JNK,Bax,Caspase-3 protein and IRE1α,ASK1,JNK,Bax,Caspase-3 in hippocampus were decreased,while the protein and mRNA expression levels of Bcl-2 were increased(P＜0.05,P＜0.01).The effect of medium-dose ZSS-AF group was better than that of high-and low-dose groups.Conclusion ZSS-AF may play an antidepressant role by regulating IRE1α/ASK1/JNK pathway of endoplasmic reticulum stress.

ObjectiveTo study the effect of total flavone of Litchi Semen （TFL） on proliferation， apoptosis， migration， and invasion of hepatoma cells HepG2. MethodMethyl thiazolyl tetrazolium colorimetric （MTT） assay was used to detect the effect of different-dose TFL and cisplatin on the proliferation of HepG2 cells. TdT-mediated dUTP nick-end labeling （TUNEL） assay was used to detect the effects of low， medium， and high-dose （70， 140， 210 mg·L^-1） of TFL and cisplatin （60 mg·L^-1） on the apoptosis of HepG2 cells， thus selecting the optimal dose of TFL for the follow-up experiment. HepG2 cells were divided into a blank group， a TFL group （140 mg·L^-1）， a TFL+XL019 group （140 mg·L^-1 TFL+0.5 μmol·L^-1 XL019）， and a TFL+TPI-1 group （140 mg·L^-1 TFL+1 μmol·L^-1 TPI-1）. The effect of TFL on migration and invasion of HepG2 cells were examined by wound healing test and Transwell invasion assay， and the effect of TFL on the expression of epithelial-mesenchymal transition （EMT） marker in HepG2 cells were examined by cell immunofluorescence assay. Western blot was used to detect the expression of key proteins in Janus kinase 2（JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway after the intervention by TFL. ResultMTT assay showed that the proliferation of HepG2 cells was significantly inhibited by TFL and cisplatin at 24 and 48 h as compared with blank group （P<0.01）， and the half maximal inhibitory concentration （IC₅₀） of TFL on HepG2 cells was （136.7±2.40） mg·L^-1 at 24 h and （106.8±1.11） mg·L^-1 at 48 h. The IC₅₀ of cisplatin on HepG2 cells was （58.48±2.04） mg·L^-1 at 24 h and （5.15±0.56） mg·L^-1 at 48 h. The results of TUNEL assay showed that TFL induced apoptosis of HepG2 cells. The optimal dose of TFL was 140 mg·L^-1. The results of wound healing test showed that compared with the blank group， the TFL group， TFL+XL019 group， and the TFL+TPI-1 group significantly inhibited the migration of HepG2 cells （P<0.05， P<0.01）. As compared with the TFL group， the inhibitory effect of the TFL+XL019 Group was significantly increased （P<0.05）， while that of the TFL+TPI-1 group was significantly decreased （P<0.01）. The Transwell invasion assay showed that compared with the blank group， the TFL group， TFL+XL019 group， and the TFL+TPI-1 group significantly inhibited the invasion of HepG2 cells （P<0.01）. As compared with the TFL group， the inhibitory effect of the TFL+XL019 group was significantly increased （P<0.05）， while that of the TFL+TPI-1 group was significantly decreased （P<0.01）. The results of immunofluorescence showed the intervention of TFL up-regulated the expression of E-cadherin， and down-regulated the expression of Vimentin in HepG2 cells， which was stronger in the TFL+XL019 group and weaker in the TFL+TPI-1 group. The results of Western blot showed that compared with the blank group， the TFL group， TFL+XL019 group， and the TFL+TPI-1 group did not affect the expression of JAK2 or STAT3 protein， but significantly decreased the expression levels of phosphorylatied （p）-JAK2 and p-STAT3 （P<0.05， P<0.01）. As compared with the TFL group， the expression levels of p-JAK2 and p-STAT3 in the TFL+XL019 group were significantly decreased （P<0.01）， while those in the TFL+TPI-1 group were significantly increased （P<0.01）. Compared with the blank group， the TFL group significantly increased the expression level of Src-homology domain 2 containing protein tyrosine phosphatase-1（SHP-1） with sh2 domain （P<0.01）. ConclusionTFL has the effects of inhibiting the proliferation， promoting apoptosis of HepG2 cells， and reversing the EMT process of HepG2 cells to reduce the migration and invasion， which are presumably related to the activation of SHP-1 by TFL to block JAK/STAT3 signaling pathway.

Gastric cancer is a common malignant tumor of the gastrointestinal tract， with the pathogenesis remains to be fully elucidated. Although surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy have demonstrated obvious clinical efficacy in the treatment of gastric cancer， the patients suffer from complications and adverse effects. Basic experiments and clinical studies have proved that Chinese medicine can treat gastric cancer in a multi-component and multi-target manner， the mechanisms of which remain to be deciphered. Therefore， the mechanism of Chinese medicine against gastric cancer needs to be unveiled by network pharmacology and tools of molecular biology. According to Chinese medicine， the occurrence of gastric cancer is mainly attributed to liver Qi stagnation， phlegm stasis and Qi stagnation， body fluid deficiency and heat accumulation， deficiency of healthy Qi， and cancer toxin accumulation. According to the available literature， herbal compound formulas such as Sancao Tiaowei decoction， Xiaojianzhong decoction， and Yiqi Huayu Jiedu decoction focus on tonifying， clearing heat， and detoxifying， while herbal active components are mainly insecticidal， heat-clearing， blood-activating， stasis-removing， and Qi-regulating drugs. The therapeutic effects of these Chinese medicines are consistent with the etiology and pathogenesis of gastric cancer. It has been demonstrated that Chinese medicines play a role in promoting apoptosis and autophagy， blocking cell cycle， and reversing cellular drug resistance to treat gastric cancer by regulating phosphatidylinositol-3 kinase/protein kinase B （PI3K/Akt）， mitogen-activated protein kinase （MAPK）， nuclear factor-kappa B （NF-κB）， transforming growth factor-β （TGF-β）/Smad， Wnt/β-catenin， and Hedgehog signaling pathways， while there is a lack of systematic understanding. By systematically summarizing the signaling pathways related to the regulation of gastric cancer by Chinese medicine， this study aims to clarify the molecular mechanisms of Chinese medicine against the development， invasion， and metastasis of gastric cancer， with a view to providing new targets， perspectives， and ideas for the treatment of gastric cancer and promoting the modernization of traditional Chinese medicine.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.