Chinese Medicine Prevention and Treatment of Tumor Based on Ferroptosis： A Review / 中国实验方剂学杂志

Ferroptosis is a new type of cell death caused by abnormal accumulation of iron-dependent reactive oxygen species （ROS） and imbalance of redox with the participation of iron ions. In recent years， studies have found that ferroptosis is associated with various diseases and can especially regulate the development of tumors. Chinese medicine has unique advantages in tumor prevention and treatment. How to use ferroptosis theory to guide the prevention and treatment of cancer and other tumor diseases by Chinese medicine is a new research hotspot. This paper summarizes the proposal， action mechanism， and signaling pathway of ferroptosis， its application in tumor therapy， and the research on the activity of Chinese medicine based on ferroptosis. Results found that the occurrence of ferroptosis is related to iron metabolism， lipid ROS metabolism， and other signaling pathways and gene expressions. Ferroptosis can regulate tumor initiation and development， treatment， and tumor immunity， which provides strategies for tumor treatment and anti-tumor drug development. By analyzing the biological activity of Chinese medicine against ferroptosis， we found that Chinese medicines （Scutellariae Radix， Puerariae Lobatae Radix， Astragali Radix， Ginkgo， Epimedii Folium， Artemisiae Annuae Herba， and Salviae Miltiorrhizae Radix et Rhizoma）， Chinese herbal compounds （ Naotaifang， Si Junzitang， and Shenmai injection）， and Chinese medicine effective components （baicalein， dihydroartemisinin， puerarin， piperlongumine， luteolin， and quercetin） can exert antitumor and other biological activities by regulating ferroptosis. Therefore， Chinese medicine has great potential in preventing and controlling tumors and other diseases by regulating ferroptosis. This paper provides theoretical basis and research ideas for the in-depth study of ferroptosis theory and guides the prevention and treatment of tumor diseases by Chinese medicine.

Associations between normal serum levels of uric acid and knee symptoms, joint structures in patients with knee osteoarthritis / 中华疾病控制杂志

Objective To investigate the associations between normal serum uric acid (UA) levels and knee symptoms and structural changes in patients with knee osteoarthritis (OA).Methods A total of 205 patients with knee OA were enrolled. According to the inclusion and exclusion criteria, 122 patients with OA were included in the study. The general condition of patients were investingated. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess severity of the knee joint symptoms. The Kellgren-Lawrence (K-L) grading system was used to assess radiological severity of the knee joint. Osirix software was used to assess changes of knee structure in magnetic resonance imaging (MRI). Peroxidase method was used to measure the serum levels of uric acid. Patients with normal range of uric acid were included in the study.Results The patients with lower levels of UA (split at the median level, 263 μmol/L) had a higher proportion of women, lower height, weight and lower proportions of K-L grade≥2. After adjustment for sex, age and body mass index, serum UA was negatively associated with total WOMAC scores (β=-16.15, P=0.018), WOMAC pain (β=-3.15, P=0.037), and WOMAC stiffness (β=-1.65, P=0.025). However, there were no significant associations between serum UA levels and knee joint structure changes.Conclusions In OA patients with normal serum UA, serum UA is negatively associated with the severity of joint symptoms, suggesting that UA within normal range may play a protective role in OA symptoms.

Effect of Combination Therapy of Tetramethylpyrazine with Methotrexate on Inflammatory Reac- tions and Hemorheology in Collagen-induced Arthritis Rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of combination therapy of tetramethylpyrazine (TMP) with methotrexate (MTX) on collagen induced arthritis (CIA) rats.</p><p><b>METHODS</b>Totally 55 male SD rats were stratified by body weight. Nine of them were randomly recruited as the normal control group. The rest 46 were immunized with type II bovine collagen (C II) for establishing rheumatoid arthritis (RA) model. Forty successfully modeled rats were randomly divided into 4 groups according to swollen toe degree, i.e., the CIA group, the TMP group, the MTX group, and the TMP plus MTX group, 10 in each group. Rats in the MTX group were administered with MTX (1. 2 mg/kg) , once per week for 4 continuous weeks. Those in the TMP group were administered with 40 mg/kg TMP, once per day for 10 continuous days, and then discontinued for 7 successive days, and continued for another 10 successive days. Rats in the TMP plus MTX group were administered with a mixture of equal dose MTX and TMP, and when MTX was discontinue, TMP was administered according to the way in the TMP group. Equal volume of saline solution was given to rats in the normal control group and the CIA group. Clinical parameters including ankle width (mediolateral diameter) and hindpaw swelling were measured at day 0, 4, 11, 18, and 26 after treatment. Rats were sacrificed 28 days after treatment, their knee joints and ankle joints were collected for pathological analyses. Serum levels of IL-1β, IL-6, and IL-17A were detected by ELISA. Changes of fibrinogen (FIB) and platelet aggregation rate (PAg) were detected.</p><p><b>RESULTS</b>Compared with the normal control group, the ankle width and hindpaw swelling increased significantly (P < 0.01), contents of FIB and PAg increased obviously (P < 0.05, P < 0.01), serum levels of IL-1β, IL-6, and IL-17 increased remarkably (P <0. 01) in the CIA group. Obvious cell proliferation, inflammatory cell infiltration, hyperemia and edema of synovial tissues could be seen. Pannus formed and immerged in cartilages, resulting in necrosis. Compared with the model group, changes of ankle width and hindpaw swelling were all alleviated in each medicated group (P <0. 05, P <0. 01). Of them, the effect was superior in the MTX group to that of the TMP group and the MTX plus TMP group (P < 0.05, P < 0.01). Contents of FIB, serum levels of IL-1β and IL-6 decreased significantly in the MTX group (P < 0.05). Contents of FIB, serum levels of IL-1β and IL-6 decreased significantly in the TMP group and the MTX plus TMP group (P < 0.05). Besides, serum levels of FIB and IL-6 were obviously lower in the MTX plus TMP group than in the TMP group and the MTX group (P < 0.01). Levels of PAg and IL-17A were more significantly lowered in the TMP group than in the MTX plus TMP group and the MTX group. Pathological changes could be alleviated in each medicated group, with the optimal effect obtained in the MTX plus TMP group.</p><p><b>CONCLUSION</b>Combination of TMP with MTX could significantly ameliorate inflammatory reactions and FIB contents of CIA rats.</p>

Xiayuxue Decoction (symbols; see text) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of ancient Chinese medical formula Xiayuxue Decoction ([symbols; see text], XYXD) on activation of hepatic stellate cells (HSCs) and defenestration of sinusoidal endothelial cells (SECs) in CCl4-induced fibrotic liver of mice.</p><p><b>METHODS</b>High performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCl4 exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 (CD31). Whole liver lysates were detected of α-smooth muscle actin (α-SMA) and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA, F-actin, DNA fragmentation through confocal microscopy, Western blot, terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan, respectively.</p><p><b>RESULTS</b>Amygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% (P<0.01), as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% (P<0.05) respectively. In vitro, XYXD (12.5 μg/mL, 50 μg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent, demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% (P<0.05). Besides, XYXD induced the apoptosis of HSC-T6 cells by 20.0% (P<0.05) and 49.5% (P<0.01), evidenced by enhanced TUNEL positivity. Moreover, ultrastructural observation suggested XYXD inhibited defenestration of SECs, which was confirmed by 31.1% reduction of protein level of CD31 (P<0.05).</p><p><b>CONCLUSIONS</b>XYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases.</p>

Flavonoids from the seeds of Alpinia galanga Willd / 药学学报

Ten flavonoids were isolated from the 95% ethanol extract of the seeds of Alpinia galanga Willd. with a combination of various chromatographic techniques, including silica gel, Sephadex LH-20 and preparative HPLC. On the basis of spectroscopic data analysis, they were elucidated as (2R, 3S)-pinobaksin-3-cinnamate (1), (2R, 3R)-pinobaksin-3-cinnamate (2), pinocembrin (3), pinobaksin (4), 3-O-acetylpinobaksin (5), galangin (6), galangin-3-methylether (7), kumatakenin (8), 3-methylkaempferol (9) and (2R, 3R)-3, 5-dihydroxy-7-methoxyflavanone (10). Among them, compound 1 is a new compound, compounds 2, 5 and 10 were isolated from the genus Alpinia for the first time, and others were isolated from this plant for the first time.

Effects of whole lung lavage on pulmonary function and exercise capacity in patients with pneumoconiosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of whole lung lavage (WLL) on the pulmonary function and exercise capacity in patients with pneumoconiosis.</p><p><b>METHODS</b>Forty-one patients with pneumoconiosis who quit dust-exposed work not more than 6 months before underwent WLL. Clinical symptom assessment, pulmonary function test, and cardiopulmonary exercise test were performed before and one week after WLL, and the results were compared.</p><p><b>RESULTS</b>The patients with pneumoconiosis showed no significant changes in clinical symptoms after WLL. At one week after WLL, the patients with pneumoconiosis showed nonsignificant increases in forced vital capacity, forced expiratory volume in one second (FEV1.0), and percent predicted FEV1 (P > 0.05); peak oxygen uptake (peak VO₂) increased from 2140.6 ± 353.2 ml/min before WLL to 2374.6 ± 362.4 ml/min after WLL, percent predicted peak VO₂ increased from 82.2 ± 13.7% before WLL to 91.0 ± 14.0% after WLL, peak VO₂/kg increased from 30.6 ± 3.5 ml/min×kg before WLL to 34.2 ± 3.7 ml/min×kg after WLL, and ventilatory equivalent for carbon dioxide decreased from 30.6 ± 3.1 before WLL to 26.1 ± 2.7 after WLL (P < 0.05).</p><p><b>CONCLUSION</b>WLL can remarkably improve the oxygen uptake and ventilatory efficiency in patients with pneumoconiosis during exercise, so it can improve the exercise capacity of these patients.</p>

Correlation analysis between cytokines levels in serum and bronchoalveolar lavage fluid, blood T cell subsets and pneumoconiosis severity / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To analyze the correlation between the pneumoconiosis severity and the cytokines levels in serum and bronchoalveolar lavage fluid (BALF) or blood T cell subsets.</p><p><b>METHODS</b>The subjects were divided into five groups: control group (6 cases), group exposed to dusts (6 cases) and 3 pneumoconiosis groups (36 in stage I, 12 in stage II and 10 in stage III). ELISA was used to detect IL-6, sIL-2R and TNF-α levels in serum and BALF. The subsets of blood T cells were classified by flow cytometer.</p><p><b>RESULTS</b>As compared with control group and group exposed to dusts, the levels of serum IL-6 and sIL-2R in patients with II or III stages significantly increased, which were positively correlated with pneumoconiosis stages (r(1) = 0.74, r(2) = 0.81, P < 0.05). The level of serum TNF-α significantly decreased in patients with III stages, as compared with control group and group exposed to dusts. There was a negative correlation between serum TNF-α level and pneumoconiosis severity (r = -0.58, P < 0.05). There was a positive correlation between the levels of IL-6, sIL-2R and TNF-α in BALF and the levels of IL-6, sIL-2R and TNF-α in serum (r(1) = 0.77, r(2) = 0.96 and r(3) = 0.88, P < 0.05). The proportion of CD(4)(+)T cells and the ratio of CD(4)(+)/CD(8)(+) decreased dramatically in patients with II and III stages. But there was no correlation between these values and disease severity.</p><p><b>CONCLUSION</b>The immune function in Th cell was inhibited. The levels of IL-6, sIL-2R and TNF-α in serum and BALF were associated with the severity of pneumoconiosis.</p>

Application of transbronchial lung biopsy in pneumoconiosis diagnosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the role of transbronchial lung biopsy (TBLB) pathology in pneumoconiosis diagnosis.</p><p><b>METHODS</b>During Jan 2003 to Jun 2010 in our hospital. 418 patients exposed to dusts were examined with TBLB. The chest radiographs of all subjects showed the pneumoconiosis-like opacities. Because the dust property or accumulated doses didn't match with abnormality on chest radiographs or there were no a series of chest radiographs, it was required for subjects to perform the TBLB for diagnosis. Three hundred seventy nine cases with satisfying samples served as the study subjects. The dust deposition, fibrosis and birefringent particles were found in TBLB pathological examinations. From May 2005, the Prussian blue iron reaction test was conducted on the TBLB samples. A panel made pneumoconiosis diagnosis according to GBZ 70-2002 and GBZ 70-2009 Pneumoconiosis Diagnostic Criteria, consulting subjects' accounts and pathologic results.</p><p><b>RESULTS</b>Among 379 subjects, 376 cases (99.2%) showed the lung interstitial fibrosis, 228 cases (60.2%) demonstrated the dust deposition, 111 cases (29.3%) expressed the birefringent particles by polarized light microscopy. Birefringent particles positive rate was 37.8% (62/164) in 164 patients exposed to either silica or potter dusts or cement dusts or coal-silica dusts or foundry dusts, which was much higher than that (22.7%, 49/215) in patients exposed to other dusts (welding fume or asbestos or aluminum dusts) (P < 0.05). The positive rate of Prussian blue iron reaction in 177 patients exposed to welding fume or burnishing dusts was 53.1% (94/177), which was significantly higher than that (23.2%, 13/56) in patients exposed to other dusts (cement dusts, casting dusts or silica) (P < 0.001). There were no significantly differences in rates of lung fibrosis, dust deposition and birefringent particles between pneumoconiosis and none-pneumoconiosis subjects. The rate of lung fibrosis in pneumoconiosis cases was significantly higher than that in non- pneumoconiosis cases (P < 0.05).</p><p><b>CONCLUSION</b>TBLB could provide the evidence of exposure to dusts and pathological changes, which may be useful to the pneumoconiosis diagnosis.</p>

Pathologic analysis of transbronchial lung biopsy in workers exposed to dusts / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the role of transbronchial lung biopsy (TBLB) in pathologic diagnosis of pneumoconiosis.</p><p><b>METHODS</b>In our hospital during May 2011 and Sep 2011, the TBLB samples from 35 cases occupationally exposed to dusts were compared with the video-assisted thoracoscopic surgery or lobectomy samples from 27 cases not exposed to dusts for pathological indexes, including fibrotic proliferation, nodule or nodule-like, dust deposition and needle-shaped birefringent particles.</p><p><b>RESULTS</b>In group exposed to dusts, there were 6 cases (17.1%) with the moderate dust deposition and 28 cases (80.0%) with fibrotic proliferation. But in group not exposed to dusts, there were 0 case with the moderate dust deposition and 11 cases (40.0%) with fibrotic proliferation. There were significant differences between two groups (P < 0.05). In group exposed to dusts, there were 6 cases (17.1%) with Nodules-like and needle-shaped birefringent particles, but in group not exposed to dusts, there was 0 case with Nodules-like and needle-shaped birefringent particles.</p><p><b>CONCLUSION</b>TBLB could provide the evidence of pathological changes in lung tissue induced by dusts, and TBLB play an important role in pneumoconiosis diagnosis.</p>

The reliance and significance of stability as a new way to reveal the essence of syndrome in Chinese medicine / 中国中西医结合杂志

Stability is the important feature of the control system. Stability exists extensively in the biological systems such as different cell types during the process of individual development, new biological properties formed under the environment and/or diet factors, drug addition, long-term memory formation, and so on. The underlying mechanisms generally include epigenetically modification, the emergence of certain substance with long half life, the formation of positive feedback loop, and the activation of stem cells. Introduction of stability into researches of Chinese medicine syndrome is essentially to explore the mechanisms of quantitative changes into the qualitative alternation. It is also helpful for us to choose an appropriate time window of animal models for Chinese syndrome and to consider what are the core effects of Chinese materia medica in improving syndrome. The stability not only meets the features of Chinese medicine theories, but also agrees with the progress of modern systems theory and biology. We hope it could promote studies on Chinese medicine syndrome.

Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro / 中西医结合学报

To investigate the effects of icariin, an effective extract from traditional Chinese medicine Epimedium pubescens with the function of tonifying kidney, in promoting osteogenesis of mesenchymal stem cell line C3H10T1/2, and to explore the underlying mechanism.

Study of optimization of whole lung lavage applied to pneumoconiosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe and evaluate the performances of intermittent positive pressure ventilation, beta-2 adrenergic receptor agonist, and pressure lavage in promoting residual fluid absorption and improving blood oxygen saturation during massive whole lung lavage (WLL).</p><p><b>METHODS</b>A total of 155 patients were randomly divided into pressure ventilation (PV) group (n = 28), adrenaline (Ad) group (n = 31), PV plus Ad group (n = 29), pressure infusion bag (PIB) group (n = 30), and control group (n = 32). The patients underwent staged MWLL of bilateral lungs. The blood oxygen saturation (SpO2) of arterial blood of finger, chest X-ray findings, clinical symptoms, and lung functions were observed before and after MWLL.</p><p><b>RESULTS</b>There were no significant differences in change in clinical symptoms among the five groups after MWLL (P > 0.05). The Ad group showed 6.3% increase in forced vital capacity (FVC) and 10.9% increase in forced expiratory flow at 25% of vital capacity (FEF(25%)) after MWLL (P < 0.05). The control group showed 5.7% decrease in FVC, 10.9% increase in forced expiratory volume in one second (FEV(1.0)), and 12.0% increase in FEF(25%) after MWLL (P < 0.05). No significant difference was found in other groups (P > 0.05). During and after MWLL, the incidence rates of hypoxemia in PV group, PV plus Ad group, and control group were 0, 0, and 12.5% (8/64), respectively (P < 0.01). There were no significant differences in total amount of lavage fluid and amount of residual fluid in the lung among all groups (P > 0.05). The smallest difference between the optical densities of the two lung fields on chest x-ray at 3 h after WLL was 0.152 ± 0.053 in the PV plus Ad group, compared to 0.194 ± 0.074 in the PV group, 0.197 ± 0.054 in the PIB group, 0.214 ± 0.054 in the Ad group, and 0.241 ± 0.109 in the control group, with significant differences between the saline group and other groups except Ad group (P < 0.05).</p><p><b>CONCLUSION</b>Pressure ventilation, adrenaline, and pressure lavage can promote the transportation and absorption of residual fluid in the lung and decrease the incidence of hypoxemia during WLL.</p>

A logical framework derived from philosophy of language for analysis of the terms of traditional Chinese medicine and an example for analysis of "kidney essence" / 中西医结合学报

The true meanings of the terms of traditional Chinese medicine (TCM) need to be analyzed on a logical basis. It is not suitable to use a new term to interpret an old term of TCM, or arbitrarily specify the special term of TCM corresponding to some substances of modern medicine. In philosophy of language, language has a logical structure, which reflects the structure of the world, that is to say, language is the picture of the world in a logical sense. Using this idea, the authors collected the ancient literature on "kidney essence", and extracted each necessary condition for "kidney essence". All necessary conditions formed a sufficient condition to define the term "kidney essence". It is expected that this example can show the effectiveness of philosophy of language in analysis of the terms of TCM.

Effects of active ingredients in three kidney-tonifying Chinese herbal drugs on gene expression profile of bone marrow stromal cells from a rat model of corticosterone-induced osteoporosis / 中西医结合学报

To observe the effects of icariin, psoralen and oleanolic acid, the three active ingredients of Yinyanghuo (Herba Epimedii Brevicornus), Buguzhi (Fructus Psoraleae) and Nuzhenzi (Fructus Ligustri Lucidi), respectively, on gene expression profile of bone marrow stromal cells (BMSCs) from rats with corticosterone-induced osteoporosis.

Effects of centrifugating pressure on the function of preosteoblast OCT-1 / 医用生物力学

Objective To investigate the feasibility of simulating gravity pressure and observe its effect on preosteoblast OCT 1 by centrifugation. Method OCT-1 cells were cultured in 1% agarose gel with a final concentration of 2×107 cells per millilitre. The experiment was divided into two groups according to the duration: one day (1 d) and five days (5 d). Each group was further divided into three subgroups: 0 r/min (control), 200 r/min, and 500 r/min. The 200 r/min group and 500 r/min group were centrifuged for three hours once a day for one day or five days respectively. The control group was kept in the same environment without centrifugation. Results The ColⅠpositive staining was slightly strengthened in the 1d 200 r/min group while it was even more strengthened in the 1d 500 r/min group. Conversely, the positive staining was stronger in the 5d 200 r/min group than that in the 5d 500 r/min group. The markers related to osteoblast differentiation such as Alkaline phosphatise (ALP), Type I collagen α2 (Col1α2), Osteocalcin (OC) and runt-related transcription factor-2 (Runx2) mRNA expression were all up regulated after centrifugation. ConclusionsCentrifugation is a practical method for cell pressure and plays a significant role in promoting the differentiation of preosteoblast OCT-1, which can be used as a new method to simulate the gravity.

Effects of Qishe Pill on vertebral hyperostosis induced by upright posture in rats / 中西医结合学报

To observe the effects of Qishe Pill, a compound traditional Chinese herbal medicine, on lumbar vertebral bone formation induced by long-time upright posture in rats and to investigate the potential mechanism.

Preventive and therapeutic effects of Yiqi Huayu Recipe on degeneration of articular cartilage in rats with osteoarthritis / 中西医结合学报

To study the efficacy and possible mechanism of Yiqi Huayu Recipe (YQHYR), a compound traditional Chinese herbal medicine, in preventing and treating degeneration of the articular cartilage in rats with osteoarthritis (OA).

Mechanism of Yiqi Huayu Bushen recipe in treating cervical syndrome in rats with qi deficiency, blood stasis and kidney deficiency / 中西医结合学报

To explore the mechanism of Yiqi Huayu Bushen Recipe (YHBR), a compound traditional Chinese herbal medicine, in treating cervical syndrome (CS) with qi deficiency, blood stasis and kidney deficiency in rats.

Mechanism of Yiqi Huayu Bushen Recipe in treating cervical syndrome with kidney deficiency in rats / 中西医结合学报

To research the action mechanism of Yiqi Huayu Bushen Recipe (YHBR), a compound of traditional Chinese herbal medicine, in treating cervical syndrome (CS) with kidney deficiency in rats.

Establishment of a rat model of cervical syndrome with qi deficiency, blood stasis and kidney deficiency / 中西医结合学报

To establish a rat model of cervical syndrome with qi deficiency, blood stasis and kidney deficiency.