Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

The fingerprint of Boenninghausenia albiflora var. albiflora was established by ultra performance liquid chromatography(UPLC), and the content of 12 active components including chlorogenic acid was determined. Multivariate statistical analysis was used to explore the indicator components of B. albiflora var. albiflora and a comprehensive evaluation system was created for the quality of B. albiflora var. albiflora. In this study, 33 batches of B. albiflora var. albiflora with different sources were collected and studied, and the UPLC fingerprint of B. albiflora var. albiflora was developed. There were 37 common peaks, of which 12 components were identified, and the content of these 12 components was measured. In combination of the common peaks and the content of chemical components, multivariate statistical analysis was performed, and the results showed that 6 components [daphnoretin, isoimperatorin, astragalin, imperatorin, neochlorogenic acid, and isoquercitrin(weight coefficient>0.1)] were selected as chemical markers for the quality of B. albiflora var. albiflora. Technique for order of preference by similarity to ideal solution(TOPSIS) analysis and chemometrics revealed that the quality of S32, S28 and S29 were superior, while that of S12, S7 and S16 were inferior. The quality evaluation method of B. albiflora var. albiflora constructed in this study was accurate and reliable, with simpleness and easiness to operate. It is suggested that the 6 above-mentioned active components could be used as indicator components for quality control of B. albiflora var. al-biflora. The samples were harvested during the flowering and fruiting period, which is from the beginning of July to the end of August.
Chromatography, High Pressure Liquid/methods* ; Chromatography, Liquid ; Drugs, Chinese Herbal/chemistry* ; Multivariate Analysis ; Quality Control

Patrinia villosa, regarding its functions in clearing heat and detoxification and eliminating carbuncles and pus, is widely used as a traditional medicinal herb that contains rich nutrition and substances such as various amino acids, vitamins, and soluble su-gar, and it is also an edible wild herb in Chinese folk tradition for 2 000 years. In 1973, Japanese scholars firstly separated three iridoids from Japanese P. villosa, and by 2021, chemical components such as flavonoids, iridoids, organic acids, triterpenoids, phenylpropanoids, and steroids have been found, which have multiple pharmacological effects, including antioxidant, antitumor, anti-diarrhea, antibacterial, sedative, and liver protection capabilities. Studies indicate that flavonoids, saponins, phenylpropanoids, and triterpenoids in P. villosa are vital substances for its pharmacological activities. However, the quality of this medicinal material cannot be controlled due to the unclear records in ancient books in the past dynasties and different drug use habits in different places, and thus its circulation is chaotic. At present, researchers have used flavonoids, organic acids, phenylpropanoids, triterpenoid saponins, and other compounds to conduct studies in this regard. Therefore, on the basis of the existing literature resources, we comprehensively summarize the chemical constituents, pharmacological activities, and quality control of P. villosa to further provide a reference for the safety and effectiveness of clinical drug use and lay a foundation for the follow-up experimental research.
Patrinia/chemistry* ; Flavonoids/pharmacology* ; Saponins ; Triterpenes/pharmacology* ; Iridoids ; Quality Control

Naoxintong capsule has beneficial effects for activating blood circulation, dispersing blood stasis and dredging collateral. It is widely used in the treatment of coronary heart disease, angina pectoris, stroke and cardiovascular disease. However, the pharmacodynamic basis and possible mechanism of its preventive effects are not clear. In this study, 10 male and 10 female C57BL/6 mice were used, and were randomly divided into the control group (saline) and Naoxintong group. Adaptively fed for 7 days in common conditions, mice were given Naoxintong capsule or saline for 3 days via intragastric administration. Serum was collected from 6 mice in each group 1 h after the last administration. Serum proteins were prepared to do two-dimensional gel electrophoresis. Then image analysis and mass spectrometry detection were carried out to screen and identify the differentially expressed proteins and make bioinformatics analysis. It was found that 24 differentially expressed proteins between Naoxintong group and control group. Compared with the control group, 12 proteins were increased, and 12 were decreased. The proteins were involved in apoptosis signal pathway and vascular endothelial growth factor signal transduction pathway, in which vasohibin-1 is a negative feedback regulation factor in angiogenesis. Western blot showed that the expression of vasohibin-1 in Naoxintong group was reduced, which is consistent with the result in two-dimensional electrophoresis. Serum proteins expression is different between Naoxintong and control groups. The targets of these differentially expressed proteins include endothelial cells, inflammatory cells and platelets. The changes on proteins showed that Naoxintong capsule may ameliorate coronary heart disease and ischemic cerebrovascular disease, and provide potential biological markers to prevent ischemic disease.

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy

Alzheimer′s disease ( AD ) is a common neurodegenerative disorder that causes progressive memory and cognitive impairment and ul-timately leads to death of patients.Aggregation of amyloid β-peptide ( Aβ) is a central event in AD pathogenesis, which is based onβ-sheet formation of Aβpeptides.β-Sheet breaker peptides are oligopeptides that can prevent and/or reverse β-sheet formation and thus represent a promising class of candidates for treatment of AD. This review is to summarize the progress of β-Sheet breaker peptides made in the past few decades.

Objective To investigate the effects of Saussurea involucrata extract pretreatment on the expression of the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) in focal cerebral ischemia/reperfusion in mice and its possible neuroprotective mechanism.Methods Seventy-two Kunming mice were randomly divided into four groups:sham operation,saline,Saussurea involucrata extract,and edaravone groups (n =18 in each group).Saussurea involucrata extract 0.8 g/kg was given intraperitoneally in the Saussurea involucrata extract group; edaravone 3 mg/kg was given in the edaravone group; and the same volume of saline was given in the saline group.A model of middle cerebral artery occlusion (MCAO) was induced after 7 days of continuous injection.Cerebral infarct volume was determined by 2,3,5-triphenyltetrazolium staining.Immunohistochemical staining was used to detect TLR4-positive cells in ischemic brain tissue.Reverse transcriptase polymerase chain reaction was used to detect the expression of TLR4/NF-κB mRNA.Results The cerebral infarct volume in mice in the saline,Saussurea involucrata extract and edaravone groups was 131.55± 28.25 mm3,84.10 ±13.92 mm3 and 65.10 ± 6.78 mm3,respectively.There were significant difference (F =10.158,P =0.012).The infarct volume in the Saussurea involucrata extract group (P =0.020) and edaravone group (P0.005) was significantly less than that in the saline group,and there was no significantly difference between the 2 groups.The numbers of cortex and TLR4 positive cells in hippocampus area at the ischemic sides in the saline group were significantly more than those in the sham operation group (all P ＜0.001).The numbers of positive cells of cortex and TLR4 in the Saussurea involucrata extract group and the edaravone group were significantly decreased compared to the saline group (all P ＜ 0.05),and there was no significant differences between the Saussurea involucrata extract group and the edaravone group.The expressions of TLR4,p50,and p65 mRNA in the saline group were significantly up-regulated compared to the sham operation group (all P =0.000).Saussurea involucrata extract could significantly down-regulate the expressions of TLR4,p50,and p65 mRNA at 24 hours after ischemia/reperfusion (all P =0.000).Edaravone could significantly down-regulate the expressions of TLR4 and p65 mRNA (all P =0.000) and it had a down-regulated trend for the expression of p50 mRNA (P =0.053); while there was no significant difference in the expressions of TLR4 and p65 mRNA between the Saussurea involucrata extract group and the edaravone group.Conclusions Saussurea involucrata extract pretreatment may significantly reduce the cerebral infarct volume,down-regulate the expressions of TLR4 and NF-κB subunit,and play a neuroprotective effect by inhibiting inflammatory response after ischemia.

Objective The purpose of the present study is to compare the pharmacokinetic and biodistribution properties of 99Tcm N-mercaptopyridine-N-oxide (99 Tcm N-MPO) with 99 Tcm-sestamibi (99 Tcm-MIBI) in normal dogs, and to investigate the potential of 99TcmN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Methods Twelve healthy mongrel dogs were injected intravenously with 99TcmN-MPO (n = 6) or 99Tcm-MIBI (n = 6). Tracer kinetics in body fluids were determined by collecting blood of 1 ml via a femoral vein catheter at 30 s, 1,2,3,4,5, 10, 20, 30, 40, 60and 90 min post-injection (p. i.). The collected blood samples were weighed and counted for radioactivity in a γ-counter. Anterior and posterior planar γ-camera images were collected at 10, 20, 30, 60, 90, and 120 min after injection, with organ uptake quantified by region-of-interest (ROIs) analysis. For comparison, 99Tcm-MIBI was also evaluated in the same twelve dogs. Canine infarct models were set up by micro-invasive interventional embolization. SPECT images in the canine infarct model were collected 24 hours after myocardial infarction at 30 min and 60 min after the administration of 99Tcm N-MPO (n = 5) or 99Tcm-MIBI (n = 5). Results Both of 99Tcm N-MPO and 99Tcm-M1BI had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min [99TcmN-MPO: (35. 77 ± 6. 31)% ID/mg ,99Tcm-MIBI (34. 46 ± 6. 83) % ID/mg] and less than 5% at 30 min p. i. [99Tcm N-MPO(3. 11 ± 1.44) % ID/mg,99Tcm-MIBI (2.93 ±0. 39)% ID/mg] . After injection, 99TcmN-MPO showed significant accumulation in the myocardium and prolonged retention. This rapid liver clearance of 99TcmN-MPO led to favorable heart-to-liver ratios, reaching values of 0. 54 ±0. 06 at 10 min, 1.02 ±0. 06 at 30 min, and 1.38 ±0. 06 at 60 min p. i.In contrast, the heart/liver ratio of 99Tcm-MIBI remained low at all time points (0. 46 ± 0. 03 at 10 min,0. 63 ±0. 03 at 30 min, and 0. 62 ± 0. 12 at 60 min p. i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of 99TcmN-MPO, but not 99Tcm-MIBI. Conclusion The combination of high heart uptake and rapid liver clearance makes 99TcmN-MPO a promising new radiotracer for myocardial perfusion imaging.

OBJECTIVE: To explore the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and erythropoietin in the hippocampus of aging rats, and to investigate the role of HIF-1alpha and erythropoietin in the aging of nervous system. METHODS: The expression of Nissl body, HIF-1alpha, and erythropoietin in the CA1 region of the hippocampus in different months was observed by Nissl staining and immunohistochemical technique. RESULTS: Nerve cells became bigger and appeared sparse, and the Nissl bodies decreased with age. HIF-1alpha positive cells increased significantly with age in the CA1 region of the hippocampus (P<0.05). The expression of erythropoietin presented a parabola with aging in the CA1 region of the hippocampus. The increase from 3 to 18 months and the reduction from 18 to 30 months of erythropoietin positive cells had statistical significance (both P<0.05). CONCLUSION HIF-1alpha and erythropoietin are parallelly incremental before middle age, and are separated after middle age, suggesting decreased activity of HIF-1alpha and recession of protein synthesis function may be the main reasons for decreased expression of erythropoietin in the brain during aging. Strengthened endogenous HIF-1alpha activity and supply of exogenous erythropoietin may delay the aging of the nervous system.
Aging ; metabolism ; Animals ; Erythropoietin ; metabolism ; Hippocampus ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUNDThe hematopoietic microenvironment (HM) plays a critical role in malignant cell growth, patient survival, and response to chemotherapy in hematologic malignancies. However, mechanisms associated with this environmental influence remain unclear. In this study, we investigated the role of bone marrow derived mesenchymal stem cells (MSCs) in U937 cell line, to find out the relations between leukemia drug resistance and the MSCs.

METHODSU937 cells were cultured in suspension or grew adherently with MSCs. The cell growth curve was drawn and the cell cycle was measured by flow cytometry. Apoptosis and sensitivity of U937 to daunoblastina (DNR) were quantified by DNA ladder detection and trypan blue exclusion assays, respectively. The gene expression profile chip technology was used to determine and analyze the changes in apoptosis-related gene expression after adherent culture and the expression of MDR1 mRNA was assessed by reverse transcriptional polymerase chain reaction (RT-PCR) at the same time.

RESULTSIn the adherent culture, the proliferation of the U937 cells was inhibited, the G0/G1 phase cells increased (F = 64.9726, P < 0.0001), G2/M phase cells were decreased (F = 98.1361, P < 0.0001) and the natural apoptosis rate was decreased (F = 24.0866, P < 0.0001) compared with those in the suspended culture. U937 cell viability was enhanced and cell apoptosis was blocked during DNR treatment in adherent culture with MSCs. Thirty-nine differently expressed genes were screened from the 487 apoptosis related genes in the adherent culture U937 cells. Among the 37 upregulated genes, Bcl-XL was upregulated most significantly. Two genes were downregulated. Adherent culture did not induce MDR1 mRNA expression in U937 cells.

CONCLUSIONSMSCs play a role in modulating the proliferation of U937 cells and response of U937 cells to DNR, and Bcl-XL apoptosis-inhibiting gene may be most important in determining the sensitivity of leukemic cells to treatment, which is not related to MDR1.

Apoptosis ; drug effects ; Bone Marrow Cells ; physiology ; Cell Proliferation ; Daunorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Genes, MDR ; Humans ; Immunophenotyping ; Mesenchymal Stromal Cells ; physiology ; U937 Cells ; drug effects