ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

Objective: To estimate the incidence and mortality of lung cancer in 2021 and their trends from 2014 to 2021 within cancer registration areas of Inner Mongolia Autonomous Region, so as to provide the basis for formulating localized strategies for lung cancer prevention and control. Methods: The data on lung cancer cases in cancer registration areas of Inner Mongolia Autonomous Region in 2021 were collected from the China Cancer Registration, encompassing data from 55 registries within the region. Crude incidence and crude mortality were calculated by genders, urban/rural rareas, and ages. The Chinese population-standardized rate was calculated using the age structure of the standard population from the Fifth National Population Census in 2000, while the world population-standardized rate was calculated using Segi's world standard population. To assess the trends in Chinese population-standardized incidence and mortality of lung cancer from 2014 to 2021, data from nine qualifying cancer registries were analyzed using the average annual percent change (AAPC). Results: In 2021, within Inner Mongolia Autonomous Region, the crude, Chinese population-standardized, and world population-standardized incidences of lung cancer were 58.96/100 000, 31.58/100 000, and 31.50/100 000, respectively. The crude, Chinese population-standardized, and world population-standardized mortalities were 46.48/100 000, 24.65/100 000, and 24.36/100 000 , respectively. The Chinese population-standardized incidence and mortality of lung cancer were 1.59-fold and 1.88-fold higher in males compared to females, and 1.08-fold and 1.10-fold higher in urban areas relative to rural areas. The crude incidence and mortality of lung cancer reached their peaks at age of 80-<85 years (379.91/100 000 and 474.31/100 000, respectively). From 2014 to 2021, the Chinese population-standardized incidence of lung cancer in Inner Mongolia Autonomous Region decreased from 43.28/100 000 to 31.41/100 000, showed a downward trend (AAPC=-3.312%, P<0.05), while the Chinese population-standardized mortality decreased from 31.55/100 000 to 24.11/100 000, showed no statistical significance (P>0.05). The Chinese population-standardized incidence of lung cancer in the group aged ≥75 years and the Chinese age-standardized mortality of lung cancer in the group aged 0-<45 years showed declining trends (AAPC=-4.307%, -7.355%, both P<0.05). Conclusions The disease burden of lung cancer in cancer registration areas of Inner Mongolia Autonomous Region has decreased, showing characteristics where the burden is higher in males than in females and slightly higher in urban areas than in rural areas. The elderly population represents a key group for lung cancer prevention and control.

ObjectiveTo investigate the value of platelet-albumin-bilirubin index （PALBI） combined with AIMS65 score in predicting rebleeding and death within 6 weeks after admission in patients with liver cirrhosis and acute upper gastrointestinal bleeding （AUGIB）. MethodsA retrospective study was conducted for 238 patients with liver cirrhosis and AUGIB who were hospitalized in The First Affiliated Hospital of Jinzhou Medical University from February 2021 to October 2022， and all patients were followed up for 6 weeks. According to the prognosis， they were divided into death group with 65 patients and survival group with 173 patients， and according to the presence or absence of rebleeding， they were divided into non-rebleeding group with 149 patients and rebleeding group with 89 patients. General data and laboratory markers （including blood routine， liver/renal function， and coagulation）， and PALBI， AIMS65 score， Child-Turcotte-Pugh （CTP） score， and Model for End-stage Liver Disease （MELD） score were calculated on admission. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. A multivariate logistic regression model analysis was used to investigate the risk factors for death or rebleeding within 6 weeks after admission in patients with liver cirrhosis and AUGIB. The receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to investigate the predictive efficacy of each scoring system， and the DeLong test was used for comparison of AUC. ResultsThere were significant differences between the death group and the survival group in hematemesis， past history of varices， albumin （Alb）， total bilirubin （TBil）， international normalized ratio （INR）， creatinine （Cr）， prothrombin time （PT）， systolic blood pressure， PALBI， AIMS65 score， CTP score， and MELD score （all P<0.05）. The multivariate logistic regression analysis showed that hematemesis （odds ratio ［OR］=4.34， 95% confidence interval ［CI］： 1.88‍ ‍—‍ ‍10.05， P<0.001）， past history of varices （OR=3.51， 95%CI： 1.37‍ ‍—‍ ‍8.98， P=0.009）， PALBI （OR=4.49， 95%CI： 1.48‍ ‍—‍ ‍13.64， P=0.008）， and AIMS65 score （OR=3.85， 95%CI： 2.35‍ ‍—‍ ‍6.30， P<0.001） were independent risk factors for death. The ROC curve analysis of each scoring system in predicting survival showed that CTP score， MELD score， PALBI， AIMS65 score， and PALBI combined with AIMS65 score had an AUC of 0.758， 0.798， 0.789， 0.870， and 0.888， respectively， suggesting that PALBI combined with AIMS65 score had a significantly larger AUC than the four scoring systems used alone （all P<0.05）. There were significant differences between the rebleeding group and the non-rebleeding group in hematemesis， history of diabetes， Alb， TBil， INR， Cr， PT， PALBI， AIMS65 score， CTP score， and MELD score （all P<0.05）. The multivariate logistic regression analysis showed that PALBI （OR=2.41， 95%CI： 1.17‍ ‍—‍ ‍4.95， P=0.017） and AIMS65 score （OR=1.58， 95%CI： 1.17‍ ‍—‍ ‍2.15， P=0.003） were independent risk factors for rebleeding. The ROC curve analysis of each scoring system in predicting rebleeding showed that CTP score， MELD score， PALBI， AIMS65 score， and PALBI combined with AIMS65 score had an AUC of 0.680， 0.719， 0.709， 0.711， and 0.741， respectively， suggesting that PALBI combined with AIMS65 score had the largest AUC （all P<0.05）， but with a relatively low specificity. ConclusionPALBI combined with AIMS65 score has a certain value in predicting death within 6 weeks after admission in patients with liver cirrhosis and AUGIB， with a better value than CTP score and MELD score alone. PALBI combined with AIMS65 score has a relatively low value in predicting rebleeding within 6 weeks， with an acceptable accuracy.

Renal interstitial fibrosis（RIF） is the main pathological manifestation of chronic kidney disease. Due to the complexity of the mechanism， there is no specific treatment for RIF in clinical practice. The abnormal activation of the phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt） signaling pathway and the activation of downstream target genes are key drivers of RIF induction and progression. Traditional Chinese medicine has the characteristics of precise efficacy and minimal toxic side effects， and the occurrence and development of RIF can be regulated by multiple targets and mutual coordination. This review focuses on the PI3K/Akt signaling pathway and summarizes the potential targets and regulatory mechanisms of traditional Chinese medicine in the treatment of RIF. It is found that various effective ingredients （such as sinomenine， mangiferin， coumarin derivates from Hydrangea paniculata， etc.） and formulas （such as Fushengong decoction， Qi-Bang-Yi-Shen formula， etc.） of traditional Chinese medicine can inhibit fibroblast proliferation， improve inflammation and oxidative stress， maintain mitochondrial stability， and slow down ferroptosis through this pathway， thereby delaying the occurrence and progression of RIF.

Qizhi Weitong granules composed of Bupleuri Radix， Paeoniae Radix Alba， Aurantii Fructus， Cyperi Rhizoma （processed）， Corydalis Rhizoma （processed）， and Glycyrrhizae Radix et Rhizoma have the effects of soothing the liver， regulating Qi movement， and harmonizing the stomach to relieve pain. This preparation is thus used for the treatment of liver depression， Qi stagnation， chest distension， and epigastric pain. It has become a first-line medication for the treatment of epigastric pain after years of clinical practice. At present， researchers have carried out extensive studies on Qizhi Weitong granules， including the optimization of the extraction and purification process， identification of chemical components， characterization of absorbed components， establishment of quality control methods， validation of pharmacological effect on digestive system diseases， exploration of the mechanism， and observation of clinical efficacy. The studies have achieved fruitful results. This article summarizes the research achievements related to Qizhi Weitong granules in recent years from pharmacological substances， quality control， pharmacological effect， mechanism of action， and clinical efficacy， aiming to provide ideas for in-depth research and modern development of Qizhi Weitong granules.

ObjectiveTo elucidate the pharmacodynamic substances responsible for the anti-inflammatory and analgesic effects of Cyperi Rhizoma by structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group， this study explored the in vivo efficacy of the flavonoids in Cyperi Rhizoma. The flavonoids in Cyperi Rhizoma and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， and available articles. The targets of the anti-inflammatory and analgesic effects were collected from DisGeNET and Online Mendelian Inheritance in Man （OMIM）. The common targets shared by flavonoids and the effects were selected as the direct targets of flavonoids endowing Cyperi Rhizoma with anti-inflammatory and analgesic effects， and protein-protein interaction （PPI） network of the core targets was constructed. The method of structure-activity omics was employed to correlate the structure and efficacy of one or more classes of chemical components in Cyperi Rhizoma with the targets as a bridge. The components were classified according to structure. Molecular docking of components to core targets was carried out via SYBYL-X 2.1.1， PyMol， and Discovery Studio 4.5 visualizer. Two targets with the highest binding affinity were selected to explore the relationship between compound structures and targets. ResultThe flavonoids in Cyperi Rhizoma exerted anti-inflammatory and analgesic effects on the mouse model of pain induced by formaldehyde. Eighteen components and 115 direct targets were screened out， and the core targets with high activities were protein kinase B1 （Akt1）， interleukin-1β （IL-1β）， cellular tumor antigen p53 （TP53）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and matrix metalloproteinase-9 （MMP-9）. According to the structures， the flavonoids in Cyperi Rhizoma were classified into bioflavonoids， flavonols， flavones， and flavanes. The molecular docking results showed that flavonoids of Cyperi Rhizoma had the highest binding affinity to TP53 and PTGS2. The results of structure-activity omics showed that bioflavonoids represented the best binding structure to the targets， while their polyhydroxyl etherification resulted in a significant decrease in the binding affinity to PTGS2. Glycosides had higher binding affinity to PTGS2. The introduction of the long-chain hydrocarbon group to the A ring of flavonols facilitated the binding to TP53， while the change of B ring substituents was not the main factor affecting the binding affinity. The 3，4-dihydroxyl flavane outperformed 3-hydroxyl flavane in the binding to TP53， while the two compounds showed similar binding affinity to PTGS2. ConclusionThe method of structure-activity omics was used to analyze the material basis for the anti-inflammatory and analgesic effects of flavonoids in Cyperi Rhizoma. Structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo reveal the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma by structure-activity omics. MethodOn the basis of the previous study about the screening of active components in vitro， this study explored the effects of flavonoids in Glycyrrhizae Radix et Rhizoma in vivo. The flavonoids in Glycyrrhizae Radix et Rhizoma and their direct targets for the anti-inflammatory and analgesic effects were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， DisGeNET， and Online Mendelian Inheritance in Man （OMIM）. STRING and Cytoscape 3.7.2 were employed to establish the protein-protein interaction （PPI） network of key targets. Molecular docking was performed to simulate the binding of five targets with high degrees to flavonoids in Glycyrrhizae Radix et Rhizoma， on the basis of which the key core targets were selected. The targets were used as a bridge to correlate the structures and effects of one or more classes of chemical components in Glycyrrhizae Radix et Rhizoma. According to the binding affinity between flavonoids with different structures in Glycyrrhizae Radix et Rhizoma and targets， the relationships between compound structures and core targets were discussed. ResultThe flavonoids in Glycyrrhizae Radix et Rhizoma reduced the content of prostaglandin E₂ （PGE₂） in the rat model of pain induced by formalin， demonstrating definite anti-inflammatory and analgesic effects. Sixty active compounds （flavonoids） with anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma were obtained. With the total score as the standard， prostaglandin-endoperoxide synthase 2 （PTGS2） and mitogen-activated protein kinase 3 （MAPK3） were selected as the key core targets of Glycyrrhizae Radix et Rhizoma for the anti-inflammatory and analgesic effects. Except that flavones showed selectivity of binding to MAPK3， the other flavonoids of Glycyrrhizae Radix et Rhizoma showed strong binding to PTGS2 and MAPK3， and the structures containing glycoside fragments showed stronger binding affinity to the targets. The introduction of chain olefins in the ring of chalcones facilitated the binding to the targets. The isopentenyl fragment in flavonols may cause the difference in binding affinity. The parallel combination of a ring into pyran ring in flavanes was not conducive to the binding to the target. The electric charge， liposolubility， and steric hindrance of the substituent group on the B ring of isoflavones directly affected the binding affinity. ConclusionThis study adopts structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma. Structure-activity omics provides new ideas and methods for predicting the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo elucidate the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba from structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group， a mouse model of foot swelling was induced by methyl aldehyde and used to study the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba in vivo. The core targets of the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. Molecular docking was conducted for the total glucosides of Paeoniae Radix Alba with the core targets， and the key core targets with high binding affinity were screened out according to the comprehensive score of each target and active structure. The structure-activity relationship was analyzed with targets as a bridge through the combination of compound structures and pharmacological effects. ResultThe total glucosides of Paeoniae Radix Alba had good anti-inflammatory and analgesic effects in vivo. The core targets of 23 active components of Paeoniae Radix Alba were epidermal growth factor receptor （EGFR）， signal transducer and activator of transcription 3 （STAT3）， vascular endothelial growth factor A （VEGFA）， cellular tumor antigen p53 （TP53）， and proto-oncogene transcription factor （JUN）. According to the structure of the parent nucleus， there were 16 pinane monoterpene glycosides， 4 pinene monoterpene glycosides， 2 monoterpene lactone glycosides， and 1 monoterpene ketone. The key core targets screened out by molecular docking were EGFR and STAT3. The structure-activity analysis of the active compound structures and the key core targets showed that the introduction of ketone group and benzene ring group on the parent nucleus affected the binding activity. ConclusionThis study analyzed the material basis for the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba from structure-activity omics， providing new ideas and methods for revealing the pharmacodynamic substances in traditional Chinese medicine.

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg^-1）， high-dose JTTP group （7.2 g·kg^-1）， and metformin group （0.2 g·kg^-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.