ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

In this study, we designed a core competency-oriented formative assessment system for standardized residency training. A formative assessment information platform was established according to this formative assessment system. We described the business process design in detail and how to use information technology for assessment data application. The corresponding data were fed back to residents, instructors, rotation departments, specialty bases, and residency training management departments to promote continuous quality improvement. Meanwhile, we demonstrated the difficulties, deficiencies, and future direction of the construction of formative assessment information platform.

The chemical constituents of Rehmanniae Radix Preparatawere prepared according to the traditional method of "jiu zheng jiu shai" and investigated using multiple chromatographic methods. Six alkaloids were isolated and their structures were elucidated from spectral data and physicochemical properties, as follows: rehmanniae alkaloid A (4-{[(5-O-á-D-galactopyranosyloxy)methyl]-1H-pyrrole-2-carbaldehyde-1-yl}butyric acidmethyl ester) (1), baimantuoluoamide B (2), capparisine C (3), harman-3-carboxylic acid (4), (2S)-1-[2-(furan-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carboxylate (5), and 1-[2-(furan-2-yl)-2-oxoethyl]pyrrolidin-2-one (6). Among them, compound 1 is a new alkaloid. Compounds 2-6 were newly isolated from Rehmannia glutinosa Libosch.The effect of compounds 1-6 on NRK-52e cell injury induced by LPS was investigated. The results show that compounds 1-3 exhibit protective effects against LPS-induced damage to NRK-52e cells.

AIM:To analyze the imageological changes of acute and chronic central serous chorioretinopathy (CSC) by 2 types of optical coherence tomography (OCT). METHODS:A retrospective analysis was performed, inclu-ding data of 60 eyes from 56 patients with CSC diagnosed by conventional eye examination, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA), which were divided into acute group (28 eyes of 28 patients) and chronic group (32 eyes of 28 patients) according to imageological examinations and duration (6 months). Optical coher-ence tomography angiography (OCTA) and spectral domain optical coherence tomography ( SD-OCT) were performed to study the vessel density of the chorioretinal leyers and the integrity of the outer retinal structure. RESULTS:In the pa-tients with chronic CSC, OCTA in 4 eyes ( 12.50% ) revealed the presence of a distinct choroidal neovascularization (CNV), while no evidence of CNV in ICGA was observed. However, no sign of CNV in acute CSC group both on OCTA and ICGA was found. The occurrence of 'dark areas' in chronic CSC was much higher than that in acute CSC ( P <0.01). In addition, the integrity of the outer retinal structure (defined as tissue between external limiting membrane and retinal pigment epithelium) in acute group was significantly better than that in chronic group ( P <0.01). CONCLU-SION:Our study demonstrates the existing secondary CNV that is not demonstrated by ICGA in the chronic CSC patients, and the different characteristics of retinochoroid structures between acute and chronic CSC in OCTA and SD-OCT are ob- served. Chronic CSC has more severe structural changes.

Objective:To study the acute toxicity in mice and cytotoxicity of the impuritiy(3-amino-2-piperidinone hydrochloride) in ornithine. Methods:The mice were given the impurity by intravenous injection.The acute toxicity was observed and LD50in mice was calculated by Bliss method. According to the result of LD50,the mice were given the impurity respectively at high,medium and low dose. The changes of general condition and body weight were recorded,and the blood biochemical indices and histomorphology of organs and tissues were observed after 14 days. The cytotoxicity was measured on fibroblasts(L929) cells. Results:The LD50and 95% con-fidence limit of the impurity (intragastric administration) was 758.49-848.08 mg·kg-1.All the detected indices of the three groups (660,330 and 170 mg·kg-1) including general condition,weight change,biochemical indices,organ morphological and histological change were all within the normal ranges. The impurity significantly decreased the viability of L929 cells. The NOAEL value was 660 mg·kg-1in mice. Conclusion:The impurity has certain toxicity to mice and cells. The data can provide experimental basis for the quality standard establishment for ornithine and the safety improvement in clinic use.

Innovative self-efficacy is the degree of self-confidence in the individual's ability to per-form innovative activities. Although the theory of innovation self-efficacy is shorter, but as an important indicator of innovation ability measurement, it has been accepted by scholars in various countries, and innovative self-efficacy provides a new perspective for the cultivation of innovative talents. The research of innovation self-efficacy is still the initial stage. Chinese and foreign scholars have made some progress in measuring tools, antecedents, aftereffect and development, but there are still obvious differences and defi-ciencies,and the research results are not abundant.The future research will focus on the measurement tools, influencing factors and research direction of three aspects of systematic research to improve the theory of innovation self-efficacy.

OBJECTIVES: To explore the relationship between the change rules of volatile organic compounds （VOCs） in rat muscle and postmortem interval （PMI）. METHODS: A total of 120 healthy rats were divided randomly into 12 groups （10 for each group）. After the rats were sacrificed by cervical dislocation, the bodies were kept at （25±1） ℃. Rat muscle samples were separately obtained at 12 PMI points, including 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 d. The VOCs in rat muscles were collected, detected and analyzed by headspace solid-phase microextraction （HS-SPME） coupled to gas chromatography-mass spectrometer （GC-MS）. RESULTS: In total, 15 species of VOCs were identified, including 9 aromatic compounds, 3 sulfur compounds, 2 aliphatic acids and 1 heterocyclic compound. The species of VOCs increased with PMI： no species were detected within 1 day, 3 species were detected on day 2, 9 on day 3, 11 on day 4, 14 from day 5 to 7, and 15 from day 8 to 10. Total peak area of 15 species of VOCs was significantly correlated to PMI （adjusted R²=0.15-0.96）： the regression function was y=-17.05 x²+ 164.36 x-246.36 （adjusted R²=0.96） from day 2 to 5, and y=2.24 x+101.13 （adjusted R²=0.97） from day 6 to 10. CONCLUSIONS The change rules of VOCs in rat muscle are helpful for PMI estimation.
Animals ; Autopsy ; Gas Chromatography-Mass Spectrometry/methods* ; Muscles/pathology* ; Rats ; Solid Phase Microextraction ; Volatile Organic Compounds/chemistry*

The composition and potency of the high temperature (40℃) stress induced size variants of a recombinant humanized monoclonal antibody (rhumAb1) were characterized by means of SEC-HPLC, nonreduced CE-SDS, liquid chromatography coupled with mass spectrometry (LC-MS) and antibody dependent cell-mediated cytotoxicity (ADCC) assay. The molecular masses of the four size variants (SEC-1-SEC-4) separated by SEC-HPLC and seven size variants (NR-1-NR-7) detected by non-reduced CE-SDS were all characterized by LC-MS. The major low molecular weight variants were generated due to the hinge region fragmentation of heavy chain. The hinge region cleavage was found mainly in the Ser221-Cys-Asp-Lys-Thr-His-Thr-Cys228 sequence, in which C222-D223 and H226-T227 were the major cleavage sites. The size variants of rhumAb1, namely dimer and fragments, have significantly reduced ADCC activity in comparison with the intact rhumAb1 drug product. This study provided insights into the stability profiling for rhumAb1 drug product. The study protocols presented here may be applicable to the analytical characterization of other monoclonal antibody-based therapeutic products.

Objective To investigate the safety of thalidomide in the treatment of immune-related bowel diseases for providing clinical reference.Methods Thirty-five patients with immune-related bowel diseases (31 Crohn's disease,2 ulcerative colitis and 2 Behcet's disease) treated with thalidomide were enrolled in this study.The incidence,type,severity,duration of thalidomide related adverse drug reaction (ADR) and the dose-effect relationship of neurotoxicity were analyzed.Results All the patients were treated with a mean dose of thalidomide (109.29 ± 30.37) mg/d for (18.8 ± 12.4) months,and 33 occurred ADR.The three most frequent ADR were numbness [51.4％ (18/35)],somnolence [48.6％ (17/35)] and dermatitis [37.1％ (13/35)].The median time to development of these three ADR were 6.50,0.25,and 1.00 months,respectively.Severe ADR leading to withdrawal accounted for 20.0％ (7/35),including reasons of peripheral neuritis (3/7),dermatitis (2/7) and myelosuppression (2/7).The incidence of peripheral neuritis was not significantly related to the maximal and initial dose of thalidomide (P ＞ 0.05).Conclusions Although the incidence of ADR was relatively high during the treatment of thalidomide,most of them were mild and well tolerated.Thalidomide can be safely used in patients with immune-related bowel diseases under close monitoring.

BACKGROUNDMultidrug resistance (MDR) is a main reason for paclitaxel (TAX) treatment failure. Indirubin-3'-monoxime (IRO) and Matrine are traditional Chinese medicines, which may reverse the resistance of tumor cells to some chemotherapy drugs, but the relationship between paclitaxel resistance and Matrine is still unclear. The aim of this study was to explore the potential molecular mechanism of IRO and Matrine in reversal of TAX resistance.

METHODSIn this study, MTT assay was used to measure the non-cytotoxic dosage of IRO and Matrine on NCI-H520/TAX25 cells and determine the reversal extent of TAX resistance under non-toxic doses. In addition, RT-PCR and Western blotting were used to evaluate the mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 cells using semi-quantitative methods.

RESULTSThere was no obvious inhibition on sensitive cell strains and drug-resistant strains, when the final concentration was at lest 4 µmol/L for IRO and 100 µmol/L for Matrine. So 4 µmol/L of IRO and 100 µmol/L of Matrine were considered as the reversal dosage. When 4 µmol/L of IRO or 100 µmol/L of Matrine were used together with TAX, the sensitivity to TAX increased evidently in NCI-H520/TAX2 cells; the reversal rate of IRO and Matrine was about 1.92 (43.56/22.6 nmol/L) and 1.74 (43.56/25.0 nmol/L), respectively. The mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 decreased significantly (P < 0.05) after addition of IRO or Matrine in TAX treatment, compared to that of TAX treatment alone.

CONCLUSIONThe decrease in both mRNA expression and protein level of survivin, Oct-4, and Sox-2 might be the molecular mechanism, by which IRO and Matrine mediate the reversal of TAX resistance.

Alkaloids ; pharmacology ; Blotting, Western ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Humans ; Indoles ; pharmacology ; Inhibitor of Apoptosis Proteins ; genetics ; metabolism ; Octamer Transcription Factor-3 ; genetics ; metabolism ; Oximes ; pharmacology ; Paclitaxel ; pharmacology ; Quinolizines ; pharmacology ; SOXB1 Transcription Factors ; genetics ; metabolism