Objective:To investigate the value of serum free light chain(sFLC)and serum calcium ion in the diagnosis and prognosis of multiple myeloma(MM).Methods:Forty patients with MM treated in Henan Provincial People's Hospital from January 2018 to January 2022 were selected as the observation group,and 40 healthy volunteers were selected as the control group.The differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc between the two groups were compared.Meanwhile,the differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc in different international staging systems(ISS),chemotherapy efficacy and prognosis patients were analyzed.Results:The levels of sFLC-κ[(98.39±21.19)vs(12.01±4.45)mg/L],sFLC-λ[(210.20±45.54)vs(14.10±5.11)mg/L]and proportions of hypocalcemia(65％vs 0)in the observation group were significantly higher than those in the control group(P＜0.05),while sFLC-κ/λ ratio[(0.44±0.10)vs(0.87±0.12)]and serum calcium ions[(1.98±0.46)vs(2.42±0.40)mmol/L]were significantly lower than those in the control group(P＜0.05).The sFLC-κ,sFLC-λ,the proportion of hypocalcemia and the course of hypocalcemia in ISS stage Ⅲ patients in the observation group were significantly higher than those in stage Ⅰ and Ⅱ patients(P＜0.05),while sFLC-κ/λ ratio,and serum calcium ions were significantly lower than those in stage Ⅰ and Ⅱ patients(P＜0.05).The levels of sFLC-κ[(107.76±21.22)vs(94.67 ±20.11)mg/L],sFLC-λ[(245.54±41.12)vs(205.54±50.22)mg/L]of patients with hypocalcemia in the observation group was significantly higher than those without hypocalcemia(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those without hypocalcemia[(0.42±0.04)vs(0.47±0.06);P＜0.05].The levels of sFLC-κ[(107.29±20.14)vs(91.11±18.92)mg/L],sFLC-λ[(247.98±42.26)vs(179.29±39.32)mg/L]in patients with ineffective chemotherapy were significantly higher than those in patients with effective chemotherapy(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those in patients with effective chemotherapy[(0.43± 0.10)vs(0.50±0.09);P＜0.05)].The area under the ROC curve for sFLC-κ,sFLC-λ,sFLC-κ/λ predicting ineffective chemotherapy was 0.803,0.793 and 0.699 respectively,P＜0.05.There was no significant difference in sFLC-κ,sFLC-λ,sFLC-κ/λ ratio,serum calcium ion,hypocalcemia ratio and hypocalcemia course between survival and death patients(P＞0.05).Conclusion:sFLC and serum calcium are related to 1SS stage of MM patients.sFLC level has a certain value to predict the curative effect of chemotherapy in MM patients.However,the prognostic values of sFLC and serum calcium are not yet confirmed for MM patients.

Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.
Humans ; Medicine, Chinese Traditional ; China ; Reference Standards ; Technology ; Drugs, Chinese Herbal/therapeutic use*

Collecting and summarizing human use experience(HUE) data, forming high-quality data and evidences that can be used for evaluation are the key links of HUE research on traditional Chinese medicine(TCM). The collection, collation and summary of human experience data were discussed in this paper. It is pointed out that the collection of HUE should be focus on the source of prescription of new traditional Chinese medicines, and be summarized based on dialectical thinking, experience in medication, characte-ristics of prescription and clinical application. The collected contents include prescription, process, clinical location and applicable population, efficacy data and safety data, etc. The methods include interview, clinical data summary and data mining. When the data formed based on HUE information is used as drug registration information, it is necessary to ensure that the data source is legal and compliant, and the ownership of intellectual property is clear.Data sources should meet the requirements of medical ethics. To avoid conflict of interest, data analysis should be conducted by an independent third party. It is necessary to develop the quality control measures of HUE data to ensure the data traceability, integrity, consistency and accuracy, and avoid data bias.The data of HUE should include the key data such as accurate clinical location and applicable population, recognized clinical efficacy and safety.After the formation of HUE, the statistical analysis plan of empirical data of human use should be formulated. Through strict data processing, statistical analysis and clinical interpretation, HUE can be produced for evaluation.
Data Collection ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Prescriptions ; Quality Control

This article proposes that the research and development of new Chinese medicines should be based on the clinical values of traditional Chinese medicine(TCM), and expounds the multiple clinical values of new Chinese medicines such as therapeutic effects, adjuvant treatment effects, improvement of disease symptoms, improvement of quality of life, prevention of diseases, etc., so as to broaden the clinical indications of new Chinese medicines. It is pointed out that the clinical value of TCM determines the clinical efficacy evaluation method of new Chinese medicines, so as to construct a clinical evaluation system of new Chinese medicines with the characteristics of TCM. It is proposed that the clinical value of new Chinese medicines should be found under the guidance of TCM theo-ry and clinical practice, and the theoretical innovation of TCM should be emphasized. There is no difference in the clinical value of drugs, and the key is to meet the clinical needs of patients. The research and development of new Chinese medicines ignores the theoretical guidance of Chinese medicine, and relying solely on animal experiment data may lead to failure of clinical trials. Different from the individualized treatment of TCM clinical syndrome differentiation, summarizing the core pathogenesis of TCM is the basis for the development of new Chinese medicines. It is necessary to summarize the pathogenesis of the disease under the guidance of TCM theory and encourage the application of modern medical methods to clarify the diagnosis of the disease. In view of the characteristics of new Chinese medicine research and development, it is proposed that the supporting role of human experience should be emphasized, and the technical points of clinical trials of new syndrome-type Chinese medicines should be explained.The use of objective indicators for syndrome evaluation, the selection of appropriate scales, and the formulation of reasonable treatment courses are advocated. During the research and development of new Chinese medicines, it is not only necessary to pay attention to modern medical safety indicators, but also to observe the evolution of TCM syndromes and specific TCM symptoms.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Quality of Life ; Research ; Syndrome

ObjectiveThe methods based on bladder cancer markers which could be applied to early diagnosis and postoperative recurrence monitoring of bladder cancer were current research hotspots. This study aims to screen aptamers that specifically recognize human bladder cancer cell lines (EJ, T24, BIU87) through cell-based systematic evolution of ligand by exponential enrichment (CELL-SELEX).MethodsFor CELL-SELEX screening, bladder cancer cell lines EJ, T24, and BIU87 were used as positive control cells. HCV 29 (human normal urothelial cell line), 293T (human embryonic kidney cell line), huh7 (human hepatocellular carcinoma cell line) were used as negative control cells. PCR upstream primers were labeled with FITC, downstream primer was labeled with Biotin. ssDNA fragments collected from each round were amplified by PCR, and the amplified product was then purified using a DNA purification Kit. The biotin-streptavidin magnetic separation methods were used to isolate the PCR product to obtain secondary FITC-ssDNA for the next CELL-SELEX round. The screening process was monitored by flow cytometry. ssDNA pool with the highest binding rates to bladder cancer cell lines(EJ, T24, and BIU87) was selected to PCR amplification, product purification, molecular cloning, and sequencing. According to the sequencing results, the secondary structure of the aptamer was pre-simulated by Dnaman software. Aptamer labeled with FITC was synthesized in vitro, flow cytometry was used to detect the binding rate of the aptamer to bladder cancer cell lins (EJ, T24 and BIU87).ResultsWith the advance of the CELL-SELEX process, the binding rate of FITC-ssDNA to bladder cancer cell lins (EJ, T24, and BIU87) increased gradually. By the 15th round, the binding rate of FITC-ssDNA to EJ cells reached the highest level. The apt1 had the highest enrichment among the 15th round ssDNA pool. By the 18th round, the binding rate of FITC-ssDNA to T24 or BIU87 cells reached the highest level. The apt2 and apt3 had the highest enrichment among the 18th round ssDNA pool. DNA structure prediction showed that the secondary structure of apt1, apt2, and apt3 was mainly stem-loop structure. Flow cytometry showed that the highest binding rate was FITC-apt1 to EJ cells, FITC-apt2 to T24 cells, and FITC-apt3 to BIU87 cells, respectively. There is no significant combination between these aptamers with the negative cells.ConclusionIn this study, three kinds of aptamers with high specificity for bladder cancer cell lines were successfully screened by CELL-SELEX. The apt1 can specifically recognize EJ cells, apt2 can specifically recognize T24 cells and apt3 can specifically recognize BIU87 cells, all of which provide experimental evidence for early diagnosis and targeted therapy technology research of bladder cancer.

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
Child ; Factor VIII/therapeutic use* ; Hemarthrosis ; Hemophilia A/drug therapy* ; Hemorrhage ; Humans ; Retrospective Studies

Background:Traditional tissue engineering methods to fabricate urinary tract patch have some drawbacks such as compromised cell viability and uneven cell distribution within scaffold.In this study,we combined three-dimensional (3D) bioprinting and tissue engineering method to form a tissue-engineered urinary tract patch,which could be employed for the application on Beagles urinary tract defect mode to verify its effectiveness on urinary tract reconstruction.Methods:Human adipose-derived stem cells (hADSCs) were dropped into smooth muscle differentiation medium to generate induced microtissues (ID-MTs),flow cytometry was utilized to detect the positive percentage for CD44,CD105,CD45,and CD34 of hADSCs.Expression of vascular endothelial growth factor A (VEGFA) and tumor necrosis factor-stimulated gene-6 (TSG-6) in hADSCs and MTs were identified by Western blotting.Then the ID-MTs were employed for 3D bioprinting.The bioprinted structure was encapsulated by transplantation into the subcutaneous tissue of nude mice for 1 week.After retrieval of the encapsulated structure,hematoxylin and eosin and Masson's trichrome staining were performed to demonstrate the morphology and reveal collagen and smooth muscle fibers,integral optical density (IOD) and area of interest were calculated for further semiquantitative analysis.Immunofluorescent double staining of CD31 and a-smooth muscle actin (α-SMA) were used to reveal vascularization of the encapsulated structure.Immunohistochemistry was performed to evaluate the expression of interleukin-2 (IL-2),α-SMA,and smoothelin of the MTs in the implanted structure.Afterward,the encapsulated structure was seeded with human urothelial cells.Immunofluorescent staining of cytokeradns AE1/AE3 was applied to inspect the morphology of seeded encapsulated structure.Results:The semi-quantitative assay showed that the relative protein expression of VEGFA was 0.355 ± 0.038 in the hADSCs vs.0.649 ± 0.150 in the MTs (t--3.291,P =0.030),while TSG-6 expression was 0.492 ± 0.092 in the hADSCs vs.1.256 ± 0.401 in the MTs (t =3.216,P =0.032).The semi-quantitative analysis showed that the mean IOD of IL-2 in the MT group was 7.67 ± 1.26,while 12.6 ± 4.79 in the hADSCs group,but semi-quantitative analysis showed that there was no statistical significance in the difference between the two groups (t =1.724,P =0.16).The semi-quantitative analysis showed that IOD was 71.7 ± 14.2 in noninduced MTs (NI-MTs) vs.35.7 ± 11.4 in ID-MTs for collagen fibers (t =3.428,P =0.027) and 12.8 ± 1.9 in NI-MTs vs.30.6 ± 8.9 in ID-MTs for smooth muscle fibers (t=3.369,P=0.028);furthermore,the mean IOD was 0.0613 ±0.0172 in ID-MTs vs.0.0017 ± 0.0009 in NI-MTs for α-SMA (t =5.994,P =0.027),while 0.0355 ± 0.0128 in ID-MTs vs.0.0035 ± 0.0022 in NI-MTs for smoothelin (t=4.268,P =0.013),which indicate that 3D bioprinted structure containing ID-MTs could mimic the smooth muscle layer of native urinary tract.After encapsulation of the urinary tract patch for additional cell adhesion,urothelial cells were seeded onto the encapsulated structures,and a monolayer urothelial cell was observed.Conclusion:Through 3D bioprinting and tissue engineering methods,we provided a promising way to fabricate tissue-engineered urinary tract patch for further investigation.

OBJECTIVE: A strain of Aspergillus niger (A. niger), capable of releasing bound phenolic acids from wheat bran, was isolated. This strain was identified by gene sequence identification. The antioxidant and anti-inflammatory capacity of ferulic acid released from wheat bran by this A. niger strain (FA-WB) were evaluated. METHODS: Molecular identification techniques based on PCR analysis of specific genomic sequences were conducted; antioxidant ability was examined using oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA) assays, and erythrocyte hemolysis assays. RAW264.7 cells were used as a model to detect anti-inflammatory activity. RESULTS: The filamentous fungal isolate was identified to be A. niger. ORAC and CAA assay showed that FA-WB had better antioxidant activity than that of the ferulic acid standard. The erythrocyte hemolysis assay results suggested that FA-WB could attenuate AAPH-induced oxidative stress through inhibition of reactive oxy gen species (ROS) generation. FA-WB could significantly restore the AAPH-induced increase in intracellular antioxidant enzyme activities to normal levels as well as inhibit the intracellular malondialdehyde formation. TNF-a, IL-6, and NO levels indicated that FA-WB can inhibit the inflammation induced by lipopolysaccharide (LPS). CONCLUSION Ferulic acid released from wheat bran by a new strain of A. niger had good anti-inflammatory activity and better antioxidant ability than standard ferulic acid.
Animals ; Anti-Inflammatory Agents ; metabolism ; pharmacology ; Antioxidants ; metabolism ; pharmacology ; Aspergillus niger ; genetics ; isolation & purification ; metabolism ; Coumaric Acids ; metabolism ; pharmacology ; DNA, Fungal ; analysis ; Dietary Fiber ; microbiology ; Erythrocytes ; drug effects ; metabolism ; Fermentation ; Hep G2 Cells ; Humans ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; pharmacology ; Mice ; RAW 264.7 Cells ; Sheep ; Tumor Necrosis Factor-alpha ; metabolism

PURPOSE: The purpose of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in patients with follicular lymphoma (FL) at baseline and mid-treatment with ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans. MATERIALS AND METHODS: The study analyzed data from 48 patients with FL who were treated in Jiangsu Province Hospital and reviewed their baseline PET-CT scans. TMTV and TLG were computed by using the absolute value of 2.0, 2.5, and 3.0 thresholding method, respectively. RESULTS: Median age was 53 years, 75.0% of patients had stage III to IV disease, 43.8% had a Follicular Lymphoma International Prognostic Index 1 (FLIPI1) score of 3 to 5 and 20.8% had a FLIPI2 score of 3 to 5. Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off values for TMTV3.0 and TLG3.0 were 476.4 (sensitivity, 85.7%; specificity, 78.0%; area under the curve [AUC], 0.760; p=0.003) and 2,676.9 (sensitivity, 71.4%; specificity, 78.0%; AUC, 0.760; p=0.003). On multivariable analysis, TMTV3.0 and TLG3.0 were independent predictors of both progression-free survival (PFS) (hazard ratio [HR], 5.406; 95% confidence interval [CI], 1.326 to 22.040; p=0.019 and HR, 6.502; 95% CI, 1.079 to 39.182; p=0.042) and overall survival (OS) (HR, 4.111; 95% CI, 1.125 to 15.027; p=0.033 and HR, 5.885; 95% CI, 1.014 to 34.148; p=0.049). ROC curve analysis showed the optimal cut-off values for ΔTMTV3.0 and ΔTLG3.0 were 66.3% (sensitivity, 85.7%; specificity, 63.4%; AUC, 0.774; p < 0.001) and 64.5% (sensitivity, 85.7%; specificity, 65.9%; AUC, 0.777; p < 0.001). CONCLUSION: Baseline TMTV and TLG are strong predictors of PFS and OS in FL. Furthermore, interim TMTV (ΔTMTV > 66.3%) and TLG (ΔTLG > 64.5%) reduction are valuable tools for early treatment response assessment in FL patients.
Area Under Curve ; Disease-Free Survival ; Electrons ; Glycolysis ; Humans ; Lymphoma, Follicular ; Methods ; Prognosis ; ROC Curve ; Sensitivity and Specificity ; Tumor Burden

Antineoplastic Agents ; Dasatinib ; Humans ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Protein Kinase Inhibitors ; Pyrimidines/therapeutic use*