Evaluation of A Liver Yin Deficiency Mouse Model Based on Untargeted Metabolomics / 中国实验方剂学杂志

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS）， to evaluate the establishment of a mouse model of liver Yin deficiency by thyroid tablet suspension combined with 10% carbon tetrachloride（CCl4） from the perspective of non-targeted metabolomics， in order to lay the foundation for the establishment of a traditional Chinese medicine（TCM） syndrome model. MethodA total of 24 mice were randomly divided into blank group and model group. The model group was given thyroid tablet suspension（0.003 2 g·kg-1） by gavage for 14 consecutive days， and 10% CCl4（5 mL·kg-1） was intraperitoneally injected once a week to establish a liver Yin deficiency model， while the blank group was injected with an equal amount of olive oil intraperitoneally and gavaged with an equal amount of distilled water， and was fed with normal feed. After the modeling was completed， 6 mice in each group were randomly selected， the levels of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， cyclic adenosine monophosphate（cAMP）， cyclic guanosine monophosphate（cGMP）， interleukin（IL）-6， IL-10， tumor necrosis factor-α（TNF-α）were measured in the mice serum， and malondialdehyde（MDA）， superoxide dismutase（SOD）， total protein（TP）， hydroxyproline（HYP） and other indicators were measured in the mice liver. Liver tissue sections were taken for hematoxylin-eosin（HE） staining and observing pathological changes. The remaining 6 mice in each group were subjected to UPLC-Q-TOF-MS combined with principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen differential metabolites in the liver Yin deficiency mouse model， Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used to analyze the corresponding metabolic pathways of differential metabolites. ResultCompared with the blank group， mice in the model group showed liver Yin deficiency manifestations such as reduced body weight， fatigue and sleepiness， disheveled and lusterless hair， irritability. The levels of ALT， cAMP/cGMP， IL-6， AST， MDA， cAMP， TNF-α significantly increased（P<0.05， P<0.01）， while the levels of SOD， IL-10 and cGMP significantly decreased（P<0.05， P<0.01）， and the changes of HYP and TP were not statistically significant. Hepatic steatosis and distortion of the radial arrangement of the liver plate cells were seen in the section images of the model group， endogenous substances were clearly separated， and 252 differential metabolites were identified in the serum samples， which were mainly involved in the metabolic pathways of purine metabolism， steroid hormone biosynthesis and pyrimidine metabolism. A total of 229 differential metabolites were identified in the liver samples， mainly involving nucleotide metabolism， purine metabolism， steroid hormone biosynthesis， pyrimidine metabolism， antifolate resistance， insulin resistance， primary bile acid biosynthesis， prostate cancer， sulfur relay system， arachidonic acid metabolism and other metabolic pathways. ConclusionThe successful establishment of liver Yin deficiency model in mice by CCl4 combined with thyroid hormone is evaluated through the investigation of serum and liver metabolomics， combined with biochemical indicators， which provides a biological basis and experimental foundation for the Yin deficiency syndrome model of TCM.

Meta-analysis of Distribution Frequency of Traditional Chinese Medicine Syndrome in Primary Osteoporosis / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the distribution of traditional Chinese medicine（TCM） syndromes of primary osteoporosis（POP） in China by using evidence-based medicine methods， and to understand the distribution law of the syndromes. MethodChina National Knowledge Infrastructure（CNKI）， VIP Chinese Science and Technology Journal Database（VIP）， WanFang Data Knowledge Service Platform（WanFang） and China Biology Medicine（CBM） were searched to obtain representative literature， and each database was searched from the 1994 World Health Organization defined diagnostic criteria for osteoporosis until May 1， 2023. Two researchers independently screened literature according to the criteria， extracted data， and cross-checked them. Meta analysis was conducted using R4.1.3， and subgroup analysis was performed. ResultA total of 56 Chinese papers were included， involving 14 415 patients. After standardized classification of syndromes， 11 articles were excluded， and Meta analysis results of the ultimately included 45 Chinese articles showed that the distribution frequencies of liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome in 12 723 patients were 27%［95% confidence interval（CI） 0.24-0.31］， 32%（95% CI 0.29-0.36）， 36%（95% CI 0.30-0.42）. Subgroup analysis showed that there was a statistically significant difference in the distribution of the three TCM syndromes in the north and south（P<0.05）. In addition， the incidence of TCM syndrome fractures in different types of POP was 15%（95% CI 0.09-0.24） for liver-kidney Yin deficiency syndrome， 20%（95% CI 0.12-0.30） for spleen-kidney Yang deficiency syndrome， and 31%（95% CI 0.25-0.39） for kidney deficiency and blood stasis syndrome. ConclusionThe distribution of syndromes in POP patients is mainly kidney deficiency， accompanied by liver and spleen dysfunction. Liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome are all the main syndromes of POP and osteoporotic fractures， and kidney deficiency and blood stasis syndrome is most closely related to the development of osteoporotic fractures. The reference standards for syndrome determination among the included studies are inconsistent， and in the future， it is necessary to focus on their determination standards to obtain consensus research results， at the same time， conduct large-scale syndrome research to obtain representative research results， providing a basis for clinical practice and research.

Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor drugs for the treatment of wet age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical efficacy of Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor(VEGF)in the treatment of wet age-related macular degeneration(wARMD).METHODS: A total of 58 patients(58 eyes)with wARMD who were treated in Ningbo Eye Hospital from September 2020 to November 2022 were collected. They were divided into two groups according to randomized digital table: 29 patients(29 eyes)for the combination group and the other 29 patients(29 eyes)for the injection group. The injection group was only given intravitreal injection of conbercept; the combination group was orally administrated with Yishen Yanggan Mingmu formula combined with intravitreal injection of conbercept. The best corrected visual acuity(BCVA), central macular thickness(CMT)and the improvement of traditional Chinese medicine(TCM)syndromes after 3mo of treatment were observed and the clinical efficacy was evaluated.RESULTS: After 3mo of treatment, the total improved effective rate of the combination group(76%)was higher than the rate of the injection group(66%). After the treatment, the BCVA of the two groups was both higher than that before treatment(P&#x003C;0.05), the CMT in both groups was lower than that before the treatment(P&#x003C;0.05), and the improvement of CMT of the combination group was better than the injection group(-155.93±143.79μm vs. -95.36±56.81μm, P&#x003C;0.05). After 3mo of treatment, each kinds of TCM syndrome in the combination group were significantly improved compared with those syndromes before the treatment(P&#x003C;0.001). In the injection group, only blurred vision was improved(P&#x003C;0.05). After the treatment, the scores of dizziness and insomnia, soreness and weakness of waist and knees, paleness and cold limbs, dry eyes and fatigue in the combination group were significantly lower than the injection group(P&#x003C;0.001).CONCLUSIONS: The Yishen Yanggan Mingmu formula combined with intravitreal anti-VEGF drug injection is effective in the treatment of wARMD.

Prediction Model of Treatment Effect of Anlotinib on Extensive-stage Small Cell Lung Cancer Based on Combination of Disease and Syndrome Information / 肿瘤防治研究

Objective To construct a nomogram prediction model for the treatment effect of anlotinib with the participation of traditional Chinese medicine syndrome elements on the patients with extensive-stage small cell lung cancer (ES-SCLC) who previously received multiple lines of chemotherapy. Methods The clinical data of 127 patients with ES-SCLC who received at least two cycles of anlotinib treatment were retrospectively studied. Kaplan-Meier method was used to analyze the relationship between each factor and the overall survival time. Cox regression analysis was applied to screen the independent influencing factors of the prognosis of patients with ES-SCLC. R language was employed to build a nomogram prediction model, C-index was used to evaluate the model, and calibration curve was adopted to verify the accuracy of the model. Results Age, PS score, brain metastases, qi deficiency syndrome, yin deficiency syndrome, and blood stasis syndrome were related risk factors for ES-SCLC treated with anlotinib. PS score, brain metastasis, and blood stasis syndrome were independent prognostic factors. On the basis of these three independent influencing factors, a nomogram model was established to predict the prognosis of patients with ES-SCLC treated with anlotinib. The predicted risk was close to the actual risk, showing a high degree of coincidence. Conclusion The nomogram model established with PS score, blood stasis syndrome elements, and brain metastasis as independent factors can predict the prognosis of patients with ES-SCLC receiving second- and third-line treatment of anlotinib.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine / 中国结合医学杂志

OBJECTIVE@#To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine.@*METHODS@#Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.@*RESULTS@#Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD.@*CONCLUSIONS@#Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Medication Rules of Pinelliae Rhizoma Processed Products in Syndrome Differentiation and Treatment of Insomnia Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo analyze and summarize the medication rules of different Pinelliae Rhizoma processed products in the syndrome differentiation and treatment of insomnia using data mining. MethodThe literature on the treatment of insomnia with Pinelliae Rhizoma was retrieved from the China National Knowledge Infrastructure （CNKI）， VIP， and PubMed databases over the past 10 years. An Excel database was constructed to record the prescriptions of different Pinelliae Rhizoma processed products in the treatment of insomnia. SPSS 26.0 software was used for frequency analysis of traditional Chinese medicine （TCM） syndromes related to insomnia， compatibility of drugs， drug effects， and properties. SPSS 26.0 was also used for cluster analysis， factor analysis， and IBM Modeler 18.0 plugin for association rule analysis of the core compatibility of different Pinelliae Rhizoma processed products and combinations. ResultAfter applying inclusion and exclusion criteria， 125 relevant articles were finally included. The commonly used processed products of Pinelliae Rhizoma in the treatment of insomnia were Pinelliae Rhizoma Praeparatum， Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， and Pinelliae Rhizoma Praeparatum cum Alumine. Among them， Pinelliae Rhizoma Praeparatum was the most frequently used. All three processed products of Pinelliae Rhizoma were often used for insomnia with such TCM syndromes as phlegm-heat disturbing the heart， phlegm-dampness obstructing the interior， and liver Qi stagnation. The compatible drugs were sweet， bitter， and pungent in flavor， cold in nature， and acted on the lung， spleen， heart， and liver meridians， with functions of nourishing deficiency， clearing heat， and calming the mind. The common prescriptions used were Wendantang， Chaihu Longgu Mulitang， Banxia Xiexintang， and Xiaochaihutang， with doses ranging from 6 to 30 g. The core drug combinations were Pinelliae Rhizoma Praeparatum-Poria-Ziziphi Spinosae Semen， Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine-Jujubae Fructus-Codonopsis Radix， and Pinelliae Rhizoma Praeparatum Cum Alumine-Scutellariae Radix-Bupleuri Radix. ConclusionThis study， for the first time， analyzed and summarized the compatibility and prescription application rules of commonly used processed products of Pinelliae Rhizoma in the treatment of insomnia from the perspective of TCM syndrome differentiation， which provides a theoretical basis for the rational， safe， and effective use of Pinelliae Rhizoma in the treatment of insomnia in TCM.

Clinical Efficacy of Danzhi Jiangtang Capsules on Patients with Type 2 Diabetes Mellitus Complicated with Lower-extremity Macroangiopathy and Serum Levels of Hcy and Cys C / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Danzhi Jiangtang capsules with the functions of replenishing Qi， nourishing Yin， and dredging collaterals on patients with type 2 diabetes mellitus （T2DM） combined with lower-extremity macroangiopathy and serum levels of homocysteine （Hcy） and cystatin C （Cys C）. MethodA total of 80 eligible patients who were treated in the department of endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2017 to December 2019 were randomized into the treatment group （40 cases） and control group （40 cases）. Both groups received the basic therapies for diabetes and Danzhi Jiangtang capsules （oral） was added to the treatment group. The levels of glycosylated hemoglobin A1c （HbA1c）， fasting plasma glucose （FPG）， 2-hour postprandial glucose （2 hPG）， fasting C-peptide （C-P）， and 2-hour postprandial C-peptide （2 hC-P）， triglycerides （TG）， total cholesterol （TC）， high density lipoprotein cholesterol （HDL-C）， and low density lipoprotein cholesterol （LDL-C） and serum levels of Hcy and Cys C were measured and the traditional Chinese medicine（TCM） syndrome scores were calculated before and after treatment in the two groups. ResultAfter 12 weeks of treatment， levels of HbA1c， FPG， and 2 hPG were lower than those before treatment in the two groups （P<0.05）. Levels of C-P （P<0.05） and 2 hC-P were higher than those before treatment in the two groups. After treatment， levels of HbA1c， FPG， and 2 hPG in the treatment group were lower than those in the control group （P<0.05）， while levels of C-P and 2 hC-P showed no significant difference between two groups. After treatment， the levels of TG， TC， and LDL-C were lower than those before treatment （P<0.05） and HDL-C level was higher than that before treatment （P<0.05） in both groups. After treatment， levels of TG and LDL-C in the treatment group were lower than those in the control group （P<0.05）， and levels of TC and HDL-C demonstrated no significant difference between two groups. After the treatment， the TCM syndrome score was lower than that before the treatment in both groups （P<0.05） and lower in the treatment group than in the control group （P<0.05）. The overall effective rate of the treatment group was higher than that of the control group （χ２=7.585， P<0.05）. The levels of Cys C and Hcy were lower than those before treatment in the two groups （P<0.05） and lower in the treatment group than in the control group （P<0.05）. Doppler echocardiography of the lower limbs showed no obvious improvement in the control group after treatment. However， for the treatment group， slight decrease in intima-media thickness of the lower limb arteries and a slight reduction in the plaque area were observed， but the difference was not statistically significant. ConclusionDanzhi Jiangtang capsules has definite therapeutic effect on T2DM combined with lower-extremity macroangiopathy， which can improve glucolipid metabolism and reduce serum levels of Hcy and Cys C. This study can serve a reference for the prevention and treatment of T2DM combined with macroangiopathy.

Syndrome Differentiation-based Treatment of Diarrhea-predominant Irritable Bowel Syndrome with Chinese Medicine via 5-HT Signaling Pathway： A Review / 中国实验方剂学杂志

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a chronic functional bowel disorder characterized by abdominal pain and diarrhea， with visceral hypersensitivity and abnormal gastrointestinal dynamics as the pathophysiological basis. The brain-gut interaction plays a role in pain-related functional gastrointestinal disorders， especially IBS-D. 5-Hydroxytryptamine （5-HT）， as an important brain-gut peptide regulating gastrointestinal function， affects brain activity， gastrointestinal motility， pain perception， mucosal inflammation， and immune response through brain-gut interaction and is associated with the occurrence and development of IBS-D. In recent years， traditional Chinese medicine （TCM） has shown great potential to mitigate gastrointestinal symptoms and improve the quality of life with its holistic view and treatment based on syndrome differentiation. Studies have shown that TCM treats IBS-D by regulating the 5-HT signaling pathway. With a focus on syndrome differentiation in TCM， this paper systematically describes the efficacy and mechanism of TCM in treating different TCM syndromes of IBS-D via the 5-HT signaling pathway， aiming to provide a scientific basis for TCM treatment of this disease.

Construction and Validation of A Predictive Model Including TCM Pathogenic Syndrome for Short-term Efficacy of PD-1 Inhibitors in Advanced Non-small Cell Lung Cancer / 肿瘤防治研究

Objective To evaluate predictive factors affecting the short-term efficacy of PD-1 inhibitors in non-small cell lung cancer (NSCLC) and to construct a prediction model. Methods From October 2019 to November 2021, 221 patients with advanced NSCLC who met the inclusion criteria and were treated with PD-1 inhibitors were prospectively enrolled. Patients who were enrolled before May 1st, 2021 were included inthe modeling group (n=149), whereas those who enrolled thereafter were included in the validation group (n=72). The general clinical data of patients, information of the four TCM diagnoses were collected, and TCM syndrome elements were identified. R software version 4.0.4 was used in constructing a nomogram clinical prediction model of objective response rate. The predictive ability and discrimination of the model were evaluated and externally validated by using a validation group. Results After two to four cycles of PD-1 inhibitor therapy in 221 patients, the overall objective response rate was 44.80%. Multivariate logistic regression analysis of the modeling group showed that the TPS score (OR=0.261, P=0.001), number of treatment lines (OR=3.749, P=0.002), treatment mode (OR=2.796, P=0.019), qi deficiency disease syndrome elements (OR=2.296, P=0.043), and syndrome elements of yin deficiency disease (OR=3.228, P=0.005) were the independent predictors of the short-term efficacy of PD-1 inhibitors. Based on the above five independent predictors, a nomogram prediction model for the short-term efficacy of PD-1 inhibitors was constructed. The AUC values of the modeling and validation groups were 0.8317 and 0.7535, respectively. The calibration curves of the two groups showed good agreement between the predicted and true values. The mean absolute errors were 0.053 and 0.039, indicating that the model has good predictive performance. Conclusion The nomogram model constructed on the basis of the syndrome elements of Qi-deficiency disease and Yin-deficiency syndrome of TCM, as well as TPS score, number of treatment lines and treatment mode, is a stable and effective tool for predicting the short-term efficacy of PD-1 inhibitors in advanced non-small cell lung cancer.

Analysis of traditional Chinese medicine syndromes in patients with coronavirus disease 2019 in plateau areas / 中华危重病急救医学

Objective:To analyze the distribution characteristics of traditional Chinese medicine (TCM) syndromes in patients with coronavirus disease 2019 (COVID-19) in plateau areas, and to provide theoretical basis for further clinical treatment of patients with COVID-19.Methods:From August 9 to August 24, 2022, patients with COVID-19 admitted to the Third People's Hospital of Tibet Autonomous Region (designated hospital for COVID-19) were included, and their baseline characteristics (age, gender, source), clinical classification and distribution of TCM syndrome types were collected and analyzed. Data analysis was performed using SPSS 26.0 statistical software.Results:A total of 161 COVID-19 patients were enrolled with ethnic distribution: 124 (77.02%) Tibetans, 35 (21.74%) Han, and 2 (1.24%) Hui, 68 males and 93 females. The male-to-female ratio was 0.73∶1. Aged 1 to 94 years, the average age was (39.06±23.64) years old, of which 4 patients were under 1 year old (excluded because the information was missing). A total of 157 patients were enrolled, and 124 patients (78.9%) were under 60 years old, including 120 cases of common type, 4 cases of severe type, 0 cases of critical type, 7 cases over 80 years old, 1 case over 90 years old, and 32 cases under 18 years old. The clinical manifestations of the patient are mainly cough, expectoration, fever, aversion to cold, dry throat, headache, fatigue, running nose, dry mouth, bitter mouth, etc. Most of the tongue is pale, red, and white greasy moss or thin white coating. In TCM, the most common syndrome was cold-dampness blocking lung syndrome (99 cases, 63.06%), followed by cold-dampness stagnant lung syndrome (22 cases, 14.01%), damp-heat accumulating lung syndrome (22 cases, 14.01%), and humidity stagnant lung syndrome (11 cases, 7.01%). Syndromes of epidemic (2 cases, 1.27%), epidemic toxins blocking the lung pattern (1 cases, 0.64%), toxins with dryness intense heat in both qi and ying phases pattern (0 cases) accounted for less than 2%, and the distribution of various syndrome types in COVID-19 patients was uneven ( χ2 = 0.48, P < 0.05). Conclusion:The most common TCM syndromes of COVID-19 patients in Lhasa are cold-dampness blocking lung syndrome, followed by cold-dampness stagnant lung syndrome, damp-heat accumulating lung syndrome, and humidity stagnant lung syndrome.

New Proposals for Application of Terahertz Imaging Technique in Chinese Medicine / 中国结合医学杂志

The rapid development of terahertz technology promotes the realization of various terahertz imaging systems. Terahertz technology features terahertz waves as good non-invasive illumination sources due to their high spectral resolution, penetration and safety. The terahertz imaging technique (TIT) has gradually been extended from the biomedical field to the field of Chinese medicine (CM), and it has become a powerful tool for seeking scientific evidence for CM theories with the use of modern science and technology. This paper reviews the current application of TITs in the field of CM research, and most importantly offers novel proposals for the application of TITs in CM research from the perspective of CM syndrome objectification and acupuncture research and cites existing reports as reference to the feasibility of these new proposals.

DNA Methylation and Transcription of HLA-F and Serum Cytokines Relate to Chinese Medicine Syndrome Classification in Patients with Chronic Hepatitis B / 中国结合医学杂志

OBJECTIVE@#To explore the molecular bases of Chinese medicine (CM) syndrome classification in chronic hepatitis B (CHB) patients in terms of DNA methylation, transcription and cytokines.@*METHODS@#Genome-wide DNA methylation and 48 serum cytokines were detected in CHB patients (DNA methylation: 15 cases; serum cytokines: 62 cases) with different CM syndromes, including dampness and heat of Gan (Liver) and gallbladder (CHB1, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan stagnation and Pi (Spleen) deficiency (CHB2, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan and Shen (Kidney) yin deficiency (CHB3, DNA methylation: 5 cases, serum cytokines: 16 cases), CHB with hidden symptoms (HS, serum cytokines:16 cases) and healthy controls (DNA methylation: 6 cases). DNA methylation of a critical gene was further validated and its mRNA expression was detected on enlarged samples. Genome-wide DNA methylation was detected using Human Methylation 450K Assay and furthered verified using pyrosequencing. Cytokines and mRNA expression of gene were evaluated using multiplex biometric enzyme-linked immunosorbent assay (ELISA)-based immunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively.@*RESULTS@#Totally 28,667 loci, covering 18,403 genes were differently methylated among CHB1, CHB2 and CHB3 (P<0.05 and |Δβ value| > 0.17). Further validation showed that compared with HS, the hg19 CHR6: 29691140 and its closely surrounded 2 CpG loci were demethylated and its mRNA expressions were significantly up-regulated in CHB1 (P<0.05). However, they remained unaltered in CHB2 (P>0.05). Levels of Interleukin (IL)-12 were higher in CHB3 and HS than that in CHB1 and CHB2 groups (P<0.05). Levels of macrophage inflammatory protein (MIP)-1α and MIP-1β were higher in CHB3 than other groups and leukemia inhibitory factor level was higher in CHB1 and HS than CHB2 and CHB3 groups (P<0.05). IL-12, MIP-1α and MIP-1β concentrations were positively correlated with human leukocyte antigen F (HLA-F) mRNA expression (R2=0.238, P<0.05; R2=0.224, P<0.05; R=0.447, P<0.01; respectively). Furthermore, combination of HLA-F mRNA and differential cytokines greatly improved the differentiating accuracy among CHB1, CHB2 and HS.@*CONCLUSIONS@#Demethylation of CpG loci in 5' UTR of HLA-F may up-regulate its mRNA expression and HLA-F expression was associated with IL-12, MIP-1α and MIP-1β levels, indicating that HLA-F and the differential cytokines might jointly involve in the classification of CM syndromes in CHB.@*REGISTRATION NO@#ChiCTR-RCS-13004001.

Evaluation of Qi-deficiency Model Based on Urine Non-targeted Metabonomics / 中国实验方剂学杂志

ObjectiveTo evaluate the success of Qi-deficiency model of Balb/C-nu mice established by swimming exhaustion test from the view of biomarkers and metabolic pathways by metabonomics. MethodBalb/C-nu mice were randomly divided into the normal group and Qi-deficiency group， Qi-deficiency model was established by swimming with 5% body weight metal fixed at the tail for 15 consecutive days until exhaustion （nose tip immersion time>5 s）. The urine metabonomics was analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS）， and the mobile phase was acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-1 min， 5%-8%A； 1-4 min， 8%-8.5%A； 4-5 min， 8.5%-12%A； 5-10 min， 12%-40%A； 10-12 min， 40%-100%A； 12-15 min， 100%A）， the flow rate was 0.3 mL·min-1， the injection volume was 10 μL， electrospray ionization （ESI） in positive and negative ion modes was used in MS analysis， the MS data were acquired in full-scan mode from m/z 50-1 000. Principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， human metabolome database （HMDB）， high collision energy ion fragments collected by MSE and tandem MS （MS/MS） ion information were used to identify potential biomarkers. Kyoto Encyclopedia of Genes and Genomes （KEGG） database and MetaboAnalyst 5.0 were used to analyze the corresponding metabolic pathways and pathway enrichment of biomarkers. ResultEndogenous substances in urine of mice in normal group and Qi-deficiency group were obviously separated， and there were 24 biomarkers with significant difference. The metabolic pathways involved in these biomarkers were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism， steroid hormone biosynthesis and tryptophan metabolism. Among them， the metabolic pathways related to energy were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism and steroid hormone biosynthesis. ConclusionThrough the investigation of urine metabonomics， combined with the physical signs， the Qi-deficiency model established by swimming exhaustion test in Balb/C-nu mice is successfully evaluated， and it is also verified that there is a close correlation between Qi-deficiency and energy metabolism.

Evaluation of Qi-deficiency Model Based on Urine Non-targeted Metabonomics / 中国实验方剂学杂志

ObjectiveTo evaluate the success of Qi-deficiency model of Balb/C-nu mice established by swimming exhaustion test from the view of biomarkers and metabolic pathways by metabonomics. MethodBalb/C-nu mice were randomly divided into the normal group and Qi-deficiency group， Qi-deficiency model was established by swimming with 5% body weight metal fixed at the tail for 15 consecutive days until exhaustion （nose tip immersion time>5 s）. The urine metabonomics was analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS）， and the mobile phase was acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-1 min， 5%-8%A； 1-4 min， 8%-8.5%A； 4-5 min， 8.5%-12%A； 5-10 min， 12%-40%A； 10-12 min， 40%-100%A； 12-15 min， 100%A）， the flow rate was 0.3 mL·min-1， the injection volume was 10 μL， electrospray ionization （ESI） in positive and negative ion modes was used in MS analysis， the MS data were acquired in full-scan mode from m/z 50-1 000. Principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， human metabolome database （HMDB）， high collision energy ion fragments collected by MSE and tandem MS （MS/MS） ion information were used to identify potential biomarkers. Kyoto Encyclopedia of Genes and Genomes （KEGG） database and MetaboAnalyst 5.0 were used to analyze the corresponding metabolic pathways and pathway enrichment of biomarkers. ResultEndogenous substances in urine of mice in normal group and Qi-deficiency group were obviously separated， and there were 24 biomarkers with significant difference. The metabolic pathways involved in these biomarkers were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism， steroid hormone biosynthesis and tryptophan metabolism. Among them， the metabolic pathways related to energy were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism and steroid hormone biosynthesis. ConclusionThrough the investigation of urine metabonomics， combined with the physical signs， the Qi-deficiency model established by swimming exhaustion test in Balb/C-nu mice is successfully evaluated， and it is also verified that there is a close correlation between Qi-deficiency and energy metabolism.

Application of metabonomics in study of traditional Chinese medicine syndrome:a review / 中国中药杂志

Syndrome is a nonlinear "internal-excess external-deficiency", "dynamic spatial-temporal" and "multi-dimensional" complex system and thus only by using a versatile method can the connotation be expounded. Metabonomics, which is dynamic, holistic, and systematic, is consistent with the overall mode of traditional Chinese medicine(TCM)(holistic view and syndrome differentiation and treatment). Therefore, metabonomics is very important for the research on the differentiation, material basis, and metabolic pathways of syndromes, and efficacy on syndromes. This study reviewed the application of metabonomics in the study of TCM syndromes in recent years, which is expected to objectify the research on TCM syndromes.

Biological connotation of four traditional Chinese medicine syndromes of rheumatoid arthritis based on "disease-syndrome-symptom" association network / 中国中药杂志

The present study explored the biological connotation of traditional Chinese medicine(TCM) syndromes of rheumatoid arthritis(RA) from the "disease-syndrome-symptom" association network. RA patients with four TCM syndromes(dampness-heat obstruction, phlegm-stasis obstruction, Qi-blood deficiency, and liver and kidney deficiency), three for each type, were assigned as the RA TCM syndrome group, and three healthy volunteers as the normal control group. The differential gene sets of four syndromes were screened out through transcriptome expression profiling and bioinformatics mining. The relevant gene sets of syndrome-related clinical symptoms were collected from TCMIP v2.0(http://www.tcmip.cn/). The "disease-syndrome-symptom" association networks of four RA syndromes were established by using the intersection genes of syndrome-related differential genes and symptom-related genes, and the key network target genes of each syndrome were screened out and the corresponding biological functions were mined through topological feature calculation and enrichment analysis. The genes associated with clinical symptoms such as vasculitis, joint pain, and fever in the damp-heat obstruction syndrome ranked the top, and the key network target genes of this syndrome were most significantly enriched in the pathways related to material and energy metabolism and thermal reaction biological processes. The clinical symptom-related genes of the phlegm-stasis obstruction syndrome were most significantly enriched in the pathways related to "immunity-inflammation", nervous system regulation, and sensory response. The clinical symptoms such as hypoglycemia, hypotension, weight loss, palpitation, and arrhythmia in Qi-blood deficiency syndrome were predominant, and its key network target genes were most significantly enriched in the pathways related to the nervous system and "immunity-inflammation" response. The abnormal symptoms in the liver and kidney in the liver and kidney deficiency syndrome were commonly seen, and its key network target genes were most significantly enriched in the "immunity-inflammation" regulatory pathways, and liver and kidney development and metabolic response. In conclusion, the differences and connections of the biological basis between different TCM syndromes of RA are in line with the theoretical interpretation of TCM on the etiology and pathogenesis of RA. This study summarized the objective essence of syndromes to a certain extent from the "disease-syndrome-symptom" association network and is expected to provide a theoretical basis for the discovery of serum biomarkers of RA syndromes.

Influence of syndrome differentiation and diet on traditional Chinese medicine syndrome score of patients with liver cirrhosis and ascites based on "Gu Ben Kai Qu" theory / 中国实用护理杂志

Objective:To explore the effect of dialectical diet on traditional Chinese medicine (TCM) syndrome score of cirrhotic ascites patients based on "Gu Ben Kai Qu" theory.Methods:From March 2019 to January 2020, 84 patients with liver cirrhosis and ascites admitted to Shuguang Hospital Affiliated to Shanghai University of TCM were randomly divided into two groups according to the different dialectical types of the subjects, 14 cases in each group. Three non-syndrome differentiation diet groups were given routine nursing care of liver cirrhosis ascites. On the basis of routine nursing, the corresponding medicinal diet was selected according to syndrome differentiation based on "Gu Ben Kai Qu" theory. Patients with spleen and kidney yang deficiency syndrome selected Shenqi lean meat decoction. Patients with Yin deficiency of liver and kidney selected Wolfberry and ophiopogon spareribs decoction. Patients with qi stagnation and blood stasis syndrome selected Danggui Sanqi spareribs decoction. The TCM syndrome score scale for liver disease and the curative effect evaluation of cirrhosis ascites were used to evaluate the effect.Results:Eighty effective cases were included. On the first day of admission, the 14th day and the second week after discharge, the TCM syndrome scores of liver disease were as follows: the group (a1b1) with the spleen and kidney yang deficiency syndrome was 46.38±8.56, 34.20±8.42, 31.40±4.22, respectively. The group (a1b2) with the liver kidney yin deficiency syndrome was 41.50±8.71, 31.35±8.63, 31.12±4.94. The group(a1b3) with the qi stagnation and blood stasis syndrome was 45.92±7.86, 35.17±7.57, 30.83±7.32, respectively. The non-syndrome differentiation diet group (a2b1) with the spleen and kidney yang deficiency syndrome was 46.29±8.38, 39.79±7.65, 36.64±6.83, respectively. The non-syndrome differentiation diet group (a2b2) with the liver and kidney yin deficiency syndrome was 40.50±8.12, 38.10±8.93, 35.38±8.24, respectively. The non-syndrome differentiation diet group (a2b3) with the qi stagnation and blood stasis syndrome was 45.62±7.99, 41.83±7.31, 38.83±7.96, respectively. The comparison of TCM syndrome scores of liver disease at three time points was statistically significant ( χ2 value was 63.998, P<0.05), and the comparison between groups was statistically significant ( χ2 value was 20.993, P<0.05). On the 14th day and the second week after discharge, there were significant differences between the groups with the syndrome differentiation diet and another three groups with non-syndrome differentiation diet ( F values were 3.244, 3.489, all P<0.05). Conclusions:Based on the theory of "strengthening the foundation and opening channels", the syndrome differentiation group can effectively reduce the TCM syndrome score of patients with cirrhosis ascites, improve the symptoms and enhance the curative effect. With the development of time, the score of TCM syndrome in patients with liver disease become lower. On the 14th day of admission, patients with Yin deficiency of liver and kidney given medicated diets had significant effect; patients with spleen kidney yang deficiency syndrome or qi stagnation and blood stasis had significant effect in 2 weeks after discharge; which can effectively improve the clinical symptoms of patients with cirrhosis ascites to worthy of clinical application.

Effect of Xintongtai Regulating p38 MAPK/AP-1 on Traditional Chinese Medicine Syndrome Score and Collagen Fibers in VSMCs of Rabbits with Atherosclerosis： An Exploration Based on Theory of Heart Receiving Qi From Spleen / 中国实验方剂学杂志

Objective:To explore the effects of Xintongtai （XTT） on traditional Chinese medicine （TCM） syndrome score and collagen fibers in vascular smooth muscle cells（VSMCs） of rabbits with atherosclerosis in the regulation of p38 mitogen-activated protein kinase （p38 MAPK）/activator protien-1 （AP-1）signaling pathway. Method:A total of 120 rabbits of SPF grade were randomly divided into the sham operation group， combined phlegm and blood stasis model group， rosuvastatin group， and low-， middle-， and high-dose XTT groups. The rabbit model of atherosclerosis due to combined phlegm and blood stasis was established by exposing them to high-fat diet and balloon injury. Following modeling， the corresponding drugs were administered by gavage for eight weeks （2.3， 4.6， 9.2 g·kg^-1 for low-， middle-， and high-dose XTT groups and 0.55 mg·kg^-1for rosuvastatin group）. At the end of medication， the abdominal aorta was isolated and stained with htoxylin-eosin （HE） for observing the vulnerable plaque. Matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） were detected by immunohistochemistry （IHC）. The collagen fiber decomposition in VSMCs was observed after Masson staining. The protein expression levels of p38 MAPK and AP-1 in aorta was assayed by Western blotting. The combined phlegm and blood stasis syndrome was scored based on TCM syndrome scoring scale. Result:Compared with the model group， XTT at each dose and rosuvastatin significantly decreased MMP-9 content， increased TIMP-1， down-regulated p38 MAPK protein expression， and weakened the nuclear translocation of AP-1 （<italic>P</italic><0.01）. Compared with the low-dose XTT group， the middle- and high-dose XTT groups and rosuvastatin group exhibited obviously lowered MMP-9，elevated TIMP-1， down-regulated p38 MAPK protein expression， and diminished AP-1 nuclear translocation （<italic>P</italic><0.05，<italic>P</italic><0.01）. The TCM syndrome scores of the middle- and high-dose XTT groups and rosuvastatin group were significantly improved as compared with that in the model group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The comparison with the low-dose XTT group revealed a remarkable improvement in TCM syndrome score of the middle- and high-dose XTT groups and rosuvastatin group （<italic>P</italic><0.01）. As demonstrated by Masson staining， the smooth muscle fibers in the model group were arranged in disorder， accompanied by enhanced collagen decomposition， thinned fibrous cap， and increased plaque vulnerability. Compared with the model group， the VSMCs in each XTT group and rosuvastatin group were orderly arranged， manifested as decreased collagen fiber decomposition and increased plaque stability. Conclusion:XTT down-regulates the expression of p38 MAPK and MMP-9， increases the level of TIMP-1， reduces the nuclear translocation of AP-1， diminishes the decomposition of collagen fibers in VSMCs， and improves the score of combined phlegm and blood stasis syndrome. XTT alleviates arteriosclerosis due to combined phlegm and blood stasis by regulating p38 MAPK/AP-1 signaling pathway and downstream cytokines and stabilizing vulnerable plaques.

Effect Evaluation of Strychnos nux-vomica L. with Integrative Methods for Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma Patients: A Self-Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To explore the clinical effect and adverse reactions of Strychnos nux-vomica in bortezomib-induced peripheral neuropathy (BIPN) of patients with multiple myeloma (MM).@*METHODS@#A total of 19 MM patients with BIPN were enrolled and Nux Vomica Capsule (NVC, 0.4 g, thrice daily) were orally administrated for 30 days. Comparative analysis on parameters between pre- and post-therapy, including peripheral neuropathy (PN) grade, neurotoxicity score, Chinese medicine (CM) syndrome score, total neuropathy score (TNS), coagulation function, and serum nerve growth factor (NGF) levels were conducted. The adverse events were monitored.@*RESULTS@#In BIPN of MM patients who received NVC, PN grade was lowered, neurotoxicity score was obviously decreased (P⩽0.01), and both CM syndrome score and TNS were remarkably decreased (P0.05). No evident adverse reactions were observed during the course of treatment.@*CONCLUSION@#Strychnos nux-vomica L. has significantly effect with a good safety in treatment of BIPN in MM patients.

Research progress of change of platelet in blood stasis syndrome and effect of traditional Chinese medicine / 中国中药杂志

The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.