Traditional Chinese medicine(TCM) injections boast a definite efficacy and have been widely used in clinic. However, the problems in medication safety have been attracted increasing attention. Pharmacokinetics is of significance to guiding TCM injection administration regimen design and improving safety and effectiveness in clinical use. In recent years, with the improvement of ideas, technology and methods of TCM studies, the pharmacokinetic studies of TCM injections have been broadly performed, with a notable progress. This paper reviewed the advance in pharmacokinetics studies of TCM injections in recent ten years, which mainly focused on pre-clinical concentration-time course, distribution, metabolism and excretion in vivo based on analysis techniques, pharmacokinetic interactions of constitutes, impact of pathological state, pharmacokinetic interactions between TCM injection and chemical drugs, and clinical pharmacokinetics studies of TCM injections, in the expectation of providing reference for studies on quality control, product development and rational clinical use of TCM injections.
Drugs, Chinese Herbal ; Injections ; Medicine, Chinese Traditional ; Quality Control

OBJECTIVE: To investigate the effect of autophagy gene Beclin1 silencing on enhancing the drug sensitivity of imatinib-resistant human myeloid leukemia cell line K562/IMA. METHODS: Imatinib-resistant human myeloid leukemia cell line K562/IMA was constructed by the combination of the first dose of high-dose shock therapy and gradual increase of dose. Imatinib interfered with K562 and K562/IMA cell lines. Cell viability was detected by CCK-8. Apoptosis rate was detected by flow cytometry. Western-blot assay was used to determine the drug resistance level. The expression of Beclin1 in drug resistant strains was detected. Small interfering RNA (siRNA) transfected Beclin1 siRNA-Beclin1 was used to silence the Beclin1 gene of K562/IMA. Control group (control), siRNA negative control group (siRNA-NC) and Beclin1 siRNA group (siRNA-Beclin1) were set up. RT-QPCR and Western-blot were used to identify the expression level of Beclin1 protein and mRNA in each group after silencing. CCK-8 method was used to detect the sensitivity of each group of cells to imatinib, and the half inhibitory concentration IC50 was calculated. The apoptosis rate of each group was detected by flow cytometry. The expression levels of Beclin 1, Bcl-2, Bax, cleaved-caspase 3, caspase-3 and cytochrome C(cyto-C) were detected by Western-blot assay, and the metastatic and invasive ability of cells was detected by Transwell chamber. RESULTS: K562 / IMA cell lines were resistant to imatinib at 10 μmol•L-1, and the expression of Beclin1 was higher than that of K562 cell lines. The cell viability of K562/IMA was significantly higher than that of K562 cell lines in the gradient concentration range, while the apoptosis rate was lower than that of K562 cell lines. After siRNA silencing Beclin-1, the cell viability and apoptosis rate of siRNA-Beclin 1 group were significantly lower than those of control group, and the IC50 value of half inhibitory concentration was significantly lower than that of control group. The levels of Bax, cleaved-caspase 3, caspase-3 and cyto-C in the cells were significantly higher than those in the control group, while the levels of Bcl-2 were significantly lower than those in the control group. CONCLUSION: Beclin1 plays an important role in imatinib resistance in human myeloid leukemia, and autophagy may be involved in the drug resistance process. After silencing Beclin1, cell resistance level can be reduced and drug sensitivity improved.

Objective: To study the mechanism of interleukin (IL)-17 in mice with non-alcoholic fatty liver disease for promoting M1-type macrophage polarization to exacerbate liver inflammation, and to provide references for the mechanism of NAFLD occurrence and development. Methods: A mouse model of NAFLD was constructed by high-fat diet. Mice were divided into control group, model group, IL-17 group, and anti IL-17 group. Histopathological changes of the liver were observed by HE staining. The serum levels of ALT and AST in peripheral blood of mice was detected by chemical colorimetry. Macrophages labeled with F4/80-PE, CD11C-FITC was designated as M1-type macrophages, those labeled with F4/80-PE, and CD206-APC was designated as M2-type macrophages. The proportion of M1 and M2 macrophages infiltrated into the liver tissues of mice were measured by flow cytometry. CD168 expression level of liver tissues was detected using immunohistochemistry. Protein and mRNA levels of the marker molecules (iNOS, TNF-alpha and IL-6) of M1 macrophages were detected using ELISA and RT-Q PCR. Western blot was used to detect the protein expression of JAK-STAT signal pathway and the expression level of MCP-1. Data were analyzed using one-way ANOVA and t-test. Results: High-fat diet NAFLD mice model was successfully constructed. IL-17 had increased the proportion of M1 macrophages in mice liver tissues and decreased the proportion of M2 macrophages (P < 0.05). The proportion of M1 and M2 macrophages in the liver tissues of normal mice was 7.9% ± 1.1% and 19.2% ± 1.8%. The proportion of M1 and M2 macrophages in the model group was 17.3% ± 2.5% and 15.0% ± 2.1. The proportion of M1 macrophages (33.8% ± 4.2%) in IL-17 group was higher than model group, while the proportion of M2 macrophages (7.8% + 1.0%) in IL-17 group was lower than model group. Protein and mRNA marker levels of M1 macrophage (iNOS, IL-12, TNFα and IL-6) in liver tissues were significantly higher than model group, control group, and anti-IL-17 group (P < 0.05). The expression levels of JAK1, STAT1, MCP-1, and CD168 in mice liver tissues of IL-17 group had increased (P < 0.05). The levels of aspartate and alanine aminotransferases in peripheral blood of mice in IL-17 group were significantly higher than other three groups (P < 0.05). Conclusion IL-17 can promote M1-type macrophage polarization, and exacerbates the liver inflammatory response to accelerate the progression of NAFLD in mice.

OBJECTIVETo explore the cytotoxic responses of spleen T lymphocytes (CTL) in BALB/c mice induced by recombinant HSP110-HER2/neu ICD complex.

METHODSTumor-bearing mouse model was immunized by HSP110-HER2/neu ICD complex. The IFN-γ level secreted by activated spleen T lymphocytes was detected by enzyme linked immunospot assay (ELISPOT). The corresponding CTL activity was measured by granzyme release assay.

RESULTSThe BALB/c mouse model of human mammary tumor highly expressing HER2/neu was established. HSP110-HER2/neu ICD complex immunization led to a significantly higher level of INF-γ than that in HSP110-P(789-797) immunized and HER2/neu ICD immunized mice. HSP110-HER2/neu ICD complex immunized animals also show significant CTL activity. The results of immunohistochemical staining showed that the number of blue spots in the PBS group was 4.57 ± 1.33, HSP110 group 6.83 ± 2.08, HER2/neu ICD group 16.17 ± 2.86, HSP110-P(789-797) group 43.67 ± 4.78, and SP110-HER2/neu ICD group 76.51 ± 8.17. The number of IFN-γ-secreting spleen lymphocytes in the HSP110-HER2/neu ICD group was significantly higher than that in the HSP110-P(789-797) group, and that of HSP110-P(789-797) group was significantly higher than that of HER2/neu ICD group (P < 0.01). The target cell-killing rate of the PBS group was (8.15 ± 1.27)%, HSP110 group (9.51 ± 1.51)%, HER2/neu ICD group (14.03 ± 2.45)%, HSP110-P(789-797) group (25.99 ± 3.04)% and HSP110-HER2/neu ICD group (38.15 ± 3.95)% (all P < 0.01).

CONCLUSIONSHSP110-HER2/neu ICD complex can promote the proliferation and maturation of T lymphocytes into CTLs, and might be used as anti-tumor vaccine to induce potent cytotoxic T lymophocyte immunoresponse against specific tumor cells.

Animals ; Breast Neoplasms ; metabolism ; pathology ; Cancer Vaccines ; immunology ; Cell Line, Tumor ; Cell Proliferation ; Female ; HSP110 Heat-Shock Proteins ; immunology ; Humans ; Interferon-gamma ; metabolism ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Random Allocation ; Receptor, ErbB-2 ; immunology ; metabolism ; Recombinant Proteins ; immunology ; Spleen ; cytology ; immunology ; T-Lymphocytes ; cytology ; immunology ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; Vaccines, Synthetic ; immunology

Anterior Cruciate Ligament Injuries ; Biomechanical Phenomena ; Humans ; Knee Joint/surgery* ; Posterior Cruciate Ligament/surgery* ; Posterior Cruciate Ligament Reconstruction ; Reconstructive Surgical Procedures ; Robotics

OBJECTIVE: To compare the femoral and tibial tunnel positions of anterior cruciate ligament reconstruction using the modified transtibial (MTT) technique and anteromedial (AM) portal technique. METHODS: Between January 2017 and September 2020, 78 patients with anterior cruciate ligament rupture underwent single-bundle reconstruction with the modified transtibial technique in 39 cases (group MTT) and through anteromedial approach in 39 cases (group AM). There were 25 males and 14 females in group MTT, with an average age of (37.0±2.3) years old; 27 males and 12 females in group AM, with an average age of (37.5±2.2) years old. CT scan of the affected knee was conducted one week after the surgery to measure and compare the femoral tunnels positioning (Fx, Fy), tibial tunnels positioning in the frontal plane(Tx1), tibial tunnels positioning in the sagittal plane (Ty1), and tibial tunnels positioning in the axial plane (Tx2, Ty2) in patients undergoing anterior cruciate ligament reconstruction through Mimics software. RESULTS: Three-dimensional CT reconstruction after the surgery showed that the average Fx and Fy were(25.2±2.1)% and (34.9±3.0)% respectively and the Tx1 and Ty1 were (45.5±3.3)% and (44.7± 3.0)% respectively, while the Tx2 and Ty2 were (47.0±3.0)% and (39.9±4.2)% respectively in group MTT. In group AM, the average Fx and Fy were (26.0±2.0)% and (36.1±3.9)% respectively and the Tx1 and Ty1 were (46.5±3.1)% and (45.6± 3.1)% respectively, while the Tx2 and Ty2 were (47.4±2.5)% and (39.6±3.9)% respectively. There were no statistically significant differences in the femoral and tibial tunnels between the two groups ( CONCLUSION Both the MTT and AM technique can achieve good anatomical positioning of the femoral and tibial tunnels, without significant differences in the positioning of the bone tunnels.
Adult ; Anterior Cruciate Ligament/surgery* ; Anterior Cruciate Ligament Injuries/surgery* ; Anterior Cruciate Ligament Reconstruction ; Female ; Femur/surgery* ; Humans ; Knee Joint/surgery* ; Male ; Software ; Tibia/surgery* ; Tomography, X-Ray Computed

Objective To explore the causes of pulmonary infection of stroke patient during recovery period. Methods 122 stroke patients combined with pulmonary infection in neural rehabilitation department from January 2008 to July 2011 were analyzed for the relative causes according to clinical nursing. Results Repeated pulmonary infection was correlated with dysphagia and tracheotomy of acute stage (P<0.05); Bilateral pulmonary infection was correlated with dysphagia, tracheotomy of acute stage and age (P<0.05). Conclusion Pulmonary infection is correlated with dysphagia, tracheotomy of acute stage and age in sequence.

OBJECTIVE: To compare and analyze the biomechanical differences between different transosseous techniques in arthroscopic repairment of rotator cuff injuries by finite element analysis. METHODS: Finite element models of traditional arthroscopic transosseous(ATO) technique, giant needle technique, and ArthroTunneler(AT) technique were established based on the shoulder CT data of a healthy adult. Then, loads of 10 N and 20 N were applied to the sutures on the different technical models, respectively. Compare and analyze the stress changes of the bone tunnels and sutures of the three models were compared and analyzed. RESULTS: Under the same condition of loading, the stress on the lateral bone tunnels and sutures of the traditional ATO technology model was the largest, followed by the giant needle technology model. The stress on the mid-section bone tunnels and sutures of the AT technology model was the largest, followed by the giant needle technology model. Under the different conditions of loading, the high-stress areas of the three models were mainly concentrated on the contact area between the sutures and the bone tunnels. Besides, compared with the traditional ATO technology model, the stress distribution of the lateral bone tunnels and sutures of the giant needle technology and AT technology model were more dispersed, but there was obvious stress concentration phenomena in the stress distribution in the mid-section bone tunnels and sutures in the AT technology model. CONCLUSION Compared with the traditional ATO technique, both the giant needle technique and the AT technique can reduce the risk of cutout between the bone tunnel and suture, and may be better treatments for rotator cuff tear. However, compared with the giant needle technique, the application of AT technique in patients with osteoporosis may be limited.
Adult ; Humans ; Rotator Cuff Injuries/surgery* ; Rotator Cuff/surgery* ; Finite Element Analysis ; Arthroscopy/methods* ; Suture Techniques

The creative viewpoint of -, the master of Zhejiang school of Chinese medicine is introduced regarding the theories of acupuncture-moxibustion and acupoints. It is stated by master that the five-tissue needling methods are applicable not only for physical disorders, but also for disorders. Of these methods, the nearby bone needling method presents an instructive significance in treatment of pain disorder. The "reinforcing in the upper and reducing in the lower" needling method supplements the reinforcing and reducing theory of acupuncture. Master has put forward the theory of flexible selection of acupoint, the phenomenon of acupoint groups and the application of transverse acupoint composition, as well as the measures for intensifying needling induction, promoting regulation of acupuncture and improving clinical effect. Besides, the seven Chinese characters are used to summarize acupoint composition, meaning "main point, supplementary point, nearby point, corresponding point, back- point, front- point and extra point" separately. This creative viewpoint provides a clearer and more feasible mode in treatment with acupuncture-moxibustion and is instructive proactively in clinical practice.

Short-term intermittent fasting (IF) is beneficial to weight control in patients with nonalcoholic fatty liver disease, but the impact of long-term IF is not clear. In this study, healthy C57BL/6N mice with 4-month alternate day fasting (ADF) were used to study the effects of long-term IF on systemic and liver lipid metabolism. The results showed that, compared with the Ad Libitum group, the weight and food conversion rate of mice in the ADF group were markedly decreased and increased respectively, and the liver index and the liver content of triglyceride were significantly increased by pathological examination. qRT-PCR analysis revealed that the mRNA expression of the lipogenesis gene Pparγ and lipolysis gene Atgl was up-regulated in the ADF group (P < 0.05). Western blot analysis showed that the ratio of microtubule associated protein LC3-II/LC3-I was increased, while the abundance of autophagy adaptor protein p62 was decreased in the ADF group. In addition, autophagy signal positive regulation key factor AMPK phosphorylation was increased (P < 0.05), and negative regulation factor mTOR phosphorylation was decreased (P < 0.05) in the ADF group, indicating that hepatocyte autophagy activity was elevated. Taken together, ADF for 4 months results in an excessive liver triglyceride accumulation, accompanied by a marked decrease in liver mTOR phosphorylation and a significant increase in hepatic autophagy.
Mice ; Animals ; Intermittent Fasting ; Mice, Inbred C57BL ; Liver/pathology* ; TOR Serine-Threonine Kinases ; Lipid Metabolism ; Autophagy ; Triglycerides