ObjectiveTo investigate the immunomodulatory effect of polysaccharides from Astragali Radix-Angelicae Sinensis Radix herb pair（Qi-gui polysaccharides） on lipopolysaccharide（LPS）-induced RAW264.7 macrophages and to characterize the structure of the active component Qi-gui homogeneous polysaccharide（AAPS-4a）， and evaluate its protective effect on ulcerative colitis（UC）. MethodsThe effects of six Qi-gui polysaccharides（0.01-100 mg·L^-1） on the proliferation of RAW264.7 cells were assessed by cell proliferation and activity assay（CCK-8）， and enzyme-linked immunosorbent assay（ELISA） was used to investigate the effects of the six polysaccharides（3， 10 mg·L^-1） on the secretion levels of tumor necrosis factor（TNF）-α， interferon（IFN）-β， and nitric oxide（NO） in LPS-induced RAW264.7 cells. After screening for active polysaccharides， high-performance size-exclusion chromatography（HPSEC） was used to determine its homogeneity and relative molecular weight， then its characteristic functional groups were identified by Fourier transform infrared spectroscopy（FT-IR）， monosaccharide composition was analyzed by high performance liquid chromatography（HPLC）， methylation analysis combined with gas chromatography-mass spectrometry（GC-MS） was performed to determine the types and linkage modes of sugar residues， and one- and two-dimensional nuclear magnetic resonance（NMR） were used to identify the sugar residue composition and configuration of the active polysaccharide. Finally， experimental animals were divided into the normal group， model group， AAPS-4a low-dose group（50 mg·kg^-1）， AAPS-4a high-dose group（100 mg·kg^-1）， and sulfasalazine（SASP） group （75 mg·kg^-1）. Except for the normal group， the acute UC mouse model was induced using 3.5% dextran sulfate sodium salt（DSS）. Each treatment group was administered the corresponding dose via oral gavage for 7 days， and changes in body weight were recorded. After treatment， the spleen index and disease activity index（DAI） score were calculated， TNF-α and interleukin-6（IL-6） levels in the serum were detected by ELISA， and histopathological changes in colon tissue were observed by hematoxylin-eosin（HE） staining. ResultsAt the cellular level， AAPS-4a exhibited a dose-dependent inhibition of LPS-induced increases in TNF-α， IFN-β， and NO levels（P<0.01）. Structural characterization of AAPS-4a revealed that it was a homogeneous polysaccharide with a relative molecular weight of 7.6×10³ Da， consisting of mannose（Man）， glucose（Glc）， and galactose（Gal） in a molar ratio of 1.3∶23.9∶1.0. It was primarily composed of five sugar residues of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp， and 1，2-α-D-Galp. In vivo experiments showed that compared with the normal group， the model group demonstrated markedly increased DAI score and spleen index， significantly reduced colon length， and significantly elevated levels of TNF-α and IL-6（P<0.01）. Compared with the model group， the AAPS-4a high-dose group significantly reduced the DAI score and spleen index， as well as TNF-α and IL-6 levels， and improved colonic atrophy（P<0.05， P<0.01）. Pathological observations showed that AAPS-4a significantly inhibited inflammatory cell infiltration in colon tissue and alleviated pathological damage. ConclusionAAPS-4a， a neutral homogeneous polysaccharide composed of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp and 1，2-α-D-Galp， is identified as a key bioactive component contributing to the anti-UC effect of the Qi-gui herb pair. Its immunoregulatory and anti-UC properties suggest its potential as a therapeutic agent for UC.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Trials within cohorts （TwiCs） are design methods derived from randomized controlled trials （RCTS）. They have been widely used in chronic disease areas such as tumors and cardiovascular diseases. The basis of the TwiCs design is a prospective cohort of specific diseases. When RCTS need to be implemented， some patients meeting the inclusion and exclusion criteria are randomly sampled from the cohort to receive "trial interventions"， while the remaining patients in the cohort who meet the inclusion and exclusion criteria continue to receive conventional treatment as control groups. By comparing the efficacy differences between the intervention measures of the trial group and the control group， the efficacy of intervention measures was evaluated. Within the cohort， the same process could be repeated to carry out multiple RCTS， so as to evaluate different intervention measures or compare the efficacy of different doses or timing of interventions. Compared with classical RCTS， TwiCs make it easier to recruit patients from the cohort and have higher external validity， providing a new research paradigm for improving the efficiency and applicability of RCTS in clinical practice. However， TwiCs may also face the challenge of poor compliance of patients in the cohort. Researchers need to take effective measures to control these patients in the design and operation of TwiCs. This article focused on the methodological key points during the implementation of TwiCs， including multi-stage informed consent （patients are informed of consent at three stages： entering the cohort， entering the trial group， and after the trial）， randomization procedures （only random sampling of patients from the cohort to receive "trial interventions"）， sample size calculation， and statistical analysis methods. The article also compared the differences between TwiCs and traditional RCTS and illustrated TwiCs research design and analysis with examples， so as to provide new research ideas and methods for clinical researchers.

Rhamnogalacturonan Ⅱ(RG-Ⅱ)is one of the structural domains of pectin whose structure is highly conserved among species.The main chain of RG-Ⅱ consists of approximately nine galacturonic acids linked by α-1,4 glycosidic bonds,with six well-defined side chains replacing them(A-F).The structures of the disaccharide side chains C and D and the monosaccharide side chains E and F in RG-Ⅱ from different sources remain essentially the same.In contrast,the oligosaccharide side chains A and B showed slight variability.Structural characterization of RG-Ⅱ can be achieved by molecular weight,monosaccharide composition,and mass spectrometry.The polysaccharides containing RG-Ⅱ structural domains in traditional Chinese medicines(TCMs)have high medicinal value.Isolation of RG-Ⅱ can be achieved using endo-polygalacturonase(Endo-PG)and Penicillium oxalicum.A substantial number of RG-Ⅱ standards can be rapidly prepared from red wine for the development of new quantitative methods to realize the quality control of active polysaccharides from traditional Chinese medicines and to promote the research process of polysaccharides from traditional Chinese medicines.

The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years， randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine （TCM）， but the quality of the implementation of blind methods is uneven， and the evaluation criteria have not yet been formed. In this paper， the data collection methods， calculation principles， advantages， and disadvantages of two quantitative quality evaluation methods of blind methods， namely James Blinding Index （JBI） and Bang Blinding Index （BBI）， were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time， a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally， the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Objective:To study the clinical efficacy of modified Shengyutang on patients with active stage psoriasis vulgaris due to Qi and blood deficiency. Method:The 134 cases were randomly divided into control group and observation group， with 67 cases in each group. The control group was given avic a capsule + Danggui Buxuewan， while the observation group was given avic a capsule + modified Shengyutang for 4 weeks， respectively. The psoriasis area and severity index （PASI）， dermatological life quality index （DLQI） and psoriasis vulgaris due to Qi and blood deficiency syndrome were observed before and after treatment. The serum growth factor ［endothelial cell specific molecule-1 （ESM-1）， transforming growth factor-β₁（TGF-β₁）， vascular endothelial cell growth factor （VEGF）］， hemorheological indicators ［high cut blood viscosity （HBV）， low cut blood viscosity （LBV）， erythrocyte sedimentation rate （ESR）］， CC cphenotype receptor（CCR）6， CC cphenotype ligand 20 （CCL20）， monocyte chemotactic protein-4 （MCP-4） in serum and tissue fluid of lesions were detected. Clinical efficacy and recurrence follow-up for 12 months were compared. The safety was evaluated between two groups. Result:Three cases in control group and one case in observation group fell off during the study period. The total effective rate was 96.97% （64/66） in observation group， which was higher than 81.25% （52/64） in control group （χ²=5.064， P<0.05）. During the 12-month follow-up， the recurrence rate was 20.31% （13/64） in observation group， which was lower than 51.92% （27/52） in control group （χ²=6.038， P<0.05）. Compared with control group after treatment， PASI， DLQI， TCM syndromes， ESM-1， TGF-β₁， VEGF， HBV， LBV， ESR， CCR6， CCL20 and MCP-4 in observation group were significantly reduced （P<0.05）. No obvious blood and urine routine， or heart， liver and renal dysfunction was observed in the two groups. The incidence of adverse reactions was 3.03% （2/66） in observation group， which was lower than 26.56% （17/64） in control group （χ²=5.764， P<0.05）. Conclusion:Modified Shengyutang can significantly improve the clinical symptoms of patients with active stage psoriasis vulgaris due to Qi and blood deficiency， with a low recurrence rate and the incidence of adverse reactions.

Objective:To explore the research hotspots in home care for the aged at home and abroad, so as to provide a reference for the research on the home care for the aged in China.Methods:Literature on home care for the aged at home and abroad was retrieved in China National Knowledge Infrastructure (CNKI) and Web of Science Core Collection from January 1, 2010 to July 8, 2020. SPSS, COOC and other softwares were used to visually analyze the retrieval results.Results:In the past ten years, the common research hotspots in home care for the aged at home and abroad focused on health education, family caregivers, quality of life, senile dementia, community care, and long-term care. Domestic and foreign scholars had different emphases on dementia and long-term care research. In the past ten years, the differences in the research hotspots of home care for the aged at home and abroad were reflected in the nursing model, family function, and physical and mental health management of the aged. Domestic scholars paid more attention to the management of elderly physical diseases, while foreign scholars paid more attention to the high-dimensional needs of elderly health management and dignity in the management of elderly diseases at home.Conclusions:In the past ten years, the differences in the research hotspots of home care for the aged at home and abroad are mainly concentrated on the nursing level. Domestic scholars paid more attention to disease care, while foreign scholars pay more attention to high-dimensional psychological needs and health level management. It prompts Chinese scholars to carry out research on the status of the high-dimensional needs of the aged, as well as related research on satisfaction strategies.

Objective To investigate the role of c-Jun NH2-terminal kinase (c-JNK) signaling pathway on voltage-gated potassium channel (Kv) remodeling in left ventricular myocytes of diabetic rats,and explore the intrinsic regulatory mechanism.Methods Forty-five SD rats were randomly divided into DM group (n=25,modeling with streptozotocin induction) and control group (n=20,fed with normal diet).Transient outward potassium current (Ito) of rats' ventricular myocytes in DM group and control group was recorded by whole-cell patch-clamp method.The c-Jun activity was detected using a non-radioactive JNK kinase assay kit (Cell Signaling Technology).JNK inhibitor SP600125 was used to incubate the cardiomyocytes of diabetes rats in vitro,and then the changes of I,o in cardiomyocytes were observed.Thioredoxin reductase (TrxR) inhibitor--auranofin (AF) was used to treat the rats' cardiomyocytes incubated with SP600125,and then the changes of Ito in cardiomyocytes were observed.The content of Kv4.2 was tested using anti-Kv4.2 antibody,and the results were analyzed using a UVP bioimaging system.Results The JNK activity in DM group rose more than 1 times compared with control group,while the density of Ito decreased significantly (Control:30.2 ± 3.3pA/pF,n=16;DM:15.3 ± 2.1pA/pF,n=17;P＜0.05).The ventricular myocytes of DM rats were treated with SP600125 (10μmol/Lol/L) for 4 hours,then the Ito density increased to control group level (DM+SP600125:32.3 ± 3.7pA/pF,n=18;Control:30.2 ± 3.3pA/pF,n=16;P＜0.05).There was no significant difference in the maximum Ito density between the treated with SP600125 (Control+SP600125:31.6 ± 3.4pA/pF,n=18) and untreated control groups.The Ito density in DM myocardial cells significantly increased after treatment with the membrane permeable protein inhibitor JNKI-1 (10μmol/L),and no changes were found in control group after the same treatment.The augmentation effect of SP600125 on Ito current in DM myocytes was significantly inhibited by TrxR inhibitor auranofin (lμmol/L) (DM+SP600125+AF:15.7 ± 3.3pA/pF,n=15),while AF did not change the Ito density in control group.The expression of Kv4.2 protein was significantly increased in DM rats after administration of SP600125,which was consistent with the changes of Ito current observed in the myocardium of DM rats,although not fully restored to the level of control group myocardium.JNK inhibitor did not markedly alter the expression of Kv4.2 protein in control group myocardium.Conclusions Kv channel remodeling in DM rat's myocardium is redox-regulated,and the Ito remodeling might be assisted with the persistent activation of c-JNK signaling pathway.It has showed that c-JNK activity is significantly increased in DM rat heart and the current density of Kv channels is reduced.The inhibition of JNK signaling pathway can markedly improve Kv channel reconstruction and the process may be regulated by thioredoxin system.

In the kidney, pericyte is the major source of myofibroblast (MyoF) in renal interstitium. It is reported that pericyte-myofibroblast transition（PMT）is one of the important pathomechanisms of renal interstitial fibrosis（RIF）. Among them, the main reasons for promoting RIF formation include pericyte recruitment, activation and isolation, as well as the lack of pericyte-derived erythropoietin. During the PMT startup process, pericyte activation and its separation from microvessels are controlled by multiple signal transduction pathways, such as transforming growth factor-β（TGF-β）pathway, vascular endothelial growth factor receptor (VEGFR) pathway and platelet derived growth factor receptor (PDGFR) pathway;Blocking of these signaling pathways can not only inhibit PMT, but also suppress renal capillaries reduction and further alleviate RIF. In clinic, many traditional Chinese medicine compound prescriptions, single traditional Chinese herbal medicine (CHM) and their extracts have the clear effects in alleviating RIF, and some of their intervention actions may be related to pericyte and its PMT. Therefore, the studies on PMT and its drug intervention will become the main development direction in the research field of anti-organ fibrosis by CHM.
Drugs, Chinese Herbal ; pharmacology ; Fibrosis ; Humans ; Kidney ; cytology ; drug effects ; pathology ; Myofibroblasts ; cytology ; Pericytes ; cytology ; Receptors, Platelet-Derived Growth Factor ; metabolism ; Signal Transduction ; Vascular Endothelial Growth Factor A ; metabolism