There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the K_D of which reached to 8.722×10^-10 g·mL^-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

Aim To evaluate the efficacy of the combination of leonurine(SCM),polygonatum polysaccharide(PSP)and deoxynojirimycin(DNJ)in hypoglycemic and antithrombotic aspects by establishing and using zebrafish type II diabetes combined with thrombosis model. Methods On the basis of the zebrafish type II diabetes model established by streptozotocin,phenylhydrazine(PH),arachidonic acid(AA)and ponatinib(PT)were used respectively to establish thrombosis models,which were divided into control group,model group,metformin+aspirin group,and the high,medium and low concentration groups of the combination drugs. After drug intervention in the experimental group,the thrombosis of tail vein was observed. Kit was used to determine the sugar content of juvenile fish tissues in each group. Quantitative analysis of cardiac erythrocytes by o-dianisidine staining method was used to calculate the inhibition rate of thrombus. Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the mRNA expressions of related genes in zebrafish. Results Compared with the model group,the combined drug could significantly increase the staining intensity of erythrocytes in zebrafish hearts,inhibit thrombosis,down-regulate the expression of thrombosis-related genes,and reduce tissue glucose content. Conclusions The combined use of the three drugs can effectively reduce the tissue sugar content and have antithrombotic effect,which show great potential in the development of drugs for the treatment of type II diabetes and thrombosis.

Hard capsules of traditional Chinese medicine(TCM) have different degrees of hygroscopicity, which affects the stability and efficacy of drugs. In this paper, 30 kinds of commercially available TCM capsules were used as the research object. The hygroscopicity curves of capsule contents, capsule shells, and capsules were tested respectively, and the first-order kinetic equation was used for fitting. The results show that during the 24 h hygroscopicity process, the capsule shell can reduce the weight gain caused by the hygroscopicity of the contents by 0.80%-53.0% and the hygroscopicity rate of the capsule contents by 1.74%-91.3%, indicating that the capsule shell has a strong delay effect on the hygroscopicity of the contents of the TCM capsules. Seven physical parameters of the contents of 30 kinds of TCM capsules were determined, and 14 prescription process-related parameters were sorted out. A partial least squares model for predicting the hygroscopicity rate of the contents of TCM capsules(with shell) for 24 h was established. It is found that the hygroscopicity rate of the capsule shell is positively correlated with the hygroscopicity of the contents of TCM capsules(with shell), suggesting that the capsule shell with a low hygroscopicity rate is helpful for moisture prevention. In addition, the pre-treatment process route of the preparation and the type of molding raw materials affect the hygroscopicity. A larger proportion of the extract in the capsule content and a smaller proportion of the fine powder of the decoction pieces indicate stronger hygroscopicity of the capsule content. The 24 h hygroscopicity rate of 15% was used as the classification node of hygroscopicity strength, and the hygroscopicity rate constant of 0.58 was used as the classification node of hygroscopicity speed. The classification system of hygroscopicity behaviors of TCM capsules was established: the varieties with strong and fast hygroscopicity accounted for about 6.67%, while those with strong and slow hygroscopicity accounted for about 33.3%; the varieties with weak and fast hygroscopicity accounted for about 26.7%, while those with weak and slow hygroscopicity accounted for about 33.3%. The classification system is helpful to quantify and compare the hygroscopicity behavior of different TCM capsules and provides a reference for the quality improvement, moisture prevention technologies, and material research of TCM capsules.
Medicine, Chinese Traditional ; Wettability ; Capsules ; Powders ; Technology ; Drugs, Chinese Herbal

OBJECTIVE: To investigate the biomechanical characteristics of different internal fixations for Pauwels type Ⅲ femoral neck fracture with defect, and provide reference for the treatment of femoral neck fracture. METHODS: Three-dimensional (3D) finite element models of femoral neck fractures were established based on CT images, including fracture and fracture with defects. Four internal fixations were simulated, namely, inverted cannulated screw(ICS), ICS combined with medial buttress plate, the femoral neck system (FNS) and FNS combined with medial buttress plate. The von Mises stress, model stiffness and fracture displacements of fracture models under 2 100 N axial loads were measured and compared. RESULTS: When femoral neck fracture was fixed by ICS and FNS, the peak stress was mainly concentrated on the surface of the screw near the fracture line, and the peak stress of FNS is higher than that of ICS;When the medial buttress plate was combined, the peak stress was increased and transferred to medial buttress plate, with more obvious of ICS fixation. For the same fracture model, the stiffness of FNS was higher than that of ICS. Compared with femoral neck fracture with defects, fracture model showed higher stiffness in the same internal fixation. The use of medial buttress plate increased model stiffness, but ICS increased more than FNS. The fracture displacement of ICS model exceeded that of FNS. CONCLUSION For Pauwels type Ⅲ femoral neck fracture with defects, FNS had better biomechanical properties than ICS. ICS combined with medial buttress plate can better enhance fixation stability and non-locking plate is recommended. FNS had the capability of shear resistance and needn't combine with medial buttress plate.
Humans ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Bone Screws ; Bone Plates ; Biomechanical Phenomena ; Finite Element Analysis

OBJECTIVE: To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM). METHODS: From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β₂-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed. RESULTS: Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy. CONCLUSION The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.
Humans ; Multiple Myeloma/drug therapy* ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Treatment Outcome ; Hematologic Diseases

Adolescent ; Adult ; Aged ; Exons ; Female ; Gastrointestinal Neoplasms ; genetics ; Gastrointestinal Stromal Tumors ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Proto-Oncogene Proteins c-kit ; genetics ; metabolism ; Young Adult

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

Objective To explore the influencing factors and correlation of positive surgical margin (PSM) and biochemical recurrence (BCR) in men after robot-assisted radical prostatectomy (RALP).Methods The clinical data of 190 patients with local or locally advanced prostate cancer who underwent RALP by single surgeon in the Department of Urology of Changhai Hospital from January 2016 to September 2017 were collected.Age was (67.5 ±6.9) years old;median body mass index (BMI),preoperative PSA,prostate weight were 24.2 kg/m2 (16.6-34.2 kg/m2),15.0 ng/ml (1.41-393.94 ng/ml) and 36.9 g (8.65-207.58 g) respectively.The group of surgical margin was divided into negative surgical margin,apex-only PSM,base-only PSM as well as apex and base PSM.Characteristics between patients stratified by surgical margin or BCR were compared using x2 test.The influencing factors of PSM were analyzed by logistic regression.Cox regression was used for the analysis of predictive factors of BCR.Log-rank test and Kaplan-Meier curves were used for comparing the BCR rate between the groups of surgical margin.Results Of all the 190 enrolled patients,total PSM rate was 24.7％ (47/190),apex-only PSM rate was 13.2 ％ (25/190),base-only PSM rate was 5.8％ (11/190),apex and base PSM rate was 5.8 ％ (11/190).Multivariate analysis showed the independent predictive factors influencing PSM were preoperative PSA (P =0.048) and pathological stage (P =0.004).The median follow-up period was 7.3 months (0.9-26.6months) and BCR happened in 19.5％ (37/190) patients.The rates of BCR were 15.4％ (22/143),16.0％ (4/25),27.3％ (3/11) and 72.7％ (8/11) in the patients with negative surgical margin,apexonly PSM,base-only PSM and both apex and base PSM respectively.Log-rank test revealed that the rate of BCR in patients with apex and base PSM was higher than that in patients with negative surgical margin (P ＜0.001) or patients with apex-only PSM(P =0.002).Cox analysis indicated that higher preoperative PSA (P =0.040),higher pathological stage (P =0.041) and higher pathological Gleason score (P =0.004) were the independent predictors of BCR.PSM was not a predictive factor of BCR (P =0.257).Conclusions Preoperative PSA and pathological stage are the influencing factors of PSM.Higher preoperative PSA,higher pathological stage and higher pathological Gleason Score are the predictive factors of BCR.PSM may not be a predictive factor of BCR.The relationship between PSM and BCR needs further study.

Chemical constituents in extract of Scrophulariae Radix and their metabolites in rat plasma after oral administration were identified by HPLC-LTQ-Orbitrap. Samples were separated by a Venusil MP C₁₈ column using a binary gradient elution. The information on the total ion chromatogram, the extraction chromatogram and the mass spectrogram in a negative mode were synthetically analyzed by comparing the retention time, MS and MS/MS spectra with literature data and some of reference standards to conduct a qualitative study on constituents of Radix Scrophulariae extract in vivo and in vitro. Totally 37 compounds from Scrophularia ningpoensis extract were detected including 12 iridoid glycosides, 20 phenylpropanoids and 5 unknown compounds. In vivo, harpagide, harpagoside and angoroside C were confirmed to enter into the blood in prototype forms. Besides, another 2 prototype compounds and 2 metabolites were detected in rat plasma after oral administration of S. ningpoensis extract. The results are beneficial for the determination of bioactive substances of S. ningpoensis and significant for further studies on S. ningpoensis.

Fingerprint technology is the key technology in modern Chinese medicine research, while spectrum-effect relationship research is the advanced stage of fingerprint research. Spectrum-effect relationship research can reveal the relationship between fingerprint and pharmacological effect through multiple statistical analyses, which can be used in Chinese medicine research. Spectrum-effect relationship has been used in many areas of Chinese medicine research, such as effective basis of single and compound Chinese medicine research, component compatibility research, processing mechanism research, pharmacological effect forecast research, technology optimization research, and so on. This paper systematically reviewed the application of spectrum-effect relationship in Chinese medicine research, and indicated some problems in spectrum-effect relationship research. At last, the authors give an outlook of the future of spectrum-effect relationship research.
Animals ; Biomedical Research ; China ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Spectrum Analysis