Osteoarthritis （OA） is characterized by articular cartilage degeneration， synovial hyperplasia， hyperosteogeny， and narrowing of joint space， which can be caused by trauma， inflammation， and other factors. With the increasing global population aging， the incidence of OA is rising year by year， making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex， including oxidative stress， autophagy， and apoptosis. Recent studies have found that ferroptosis， a new type of cell death， is also an important pathogenic factor in OA， characterized by a series of complex changes such as iron ion accumulation， glutathione （GSH） depletion， and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation， delay extracellular matrix （ECM） degradation， and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement， but there are limitations. Traditional Chinese medicine （TCM） has been widely used in the treatment of various diseases because of its low cost， low drug resistance， and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets， multiple levels， and aspects， but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism， lipid peroxidation， cysteine/glutamate transporter system Xc^- （system Xc^-）/GSH/glutathione peroxidase 4 （GPX4） pathway， nicotinamide adenine dinucleotide phosphate（NADPH）/ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀） pathway， tumor protein p53 in OA， and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs.

Objective:To investigate interleukin-37 (IL-37) expression in patients with diabetic kidney disease (DKD), and to assess the regulation of exogenous IL-37 on CD8 + T cell function in DKD patients. Methods:A cross-section study was carried out. Twenty healthy controls, thirty-six patients with diabetes mellitus type 2 (T2DM), and forty-seven DKD patients were enrolled in the study. Peripheral blood was collected. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble IL-1 receptor 8 (IL-1R8) levels in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-18 receptor α chain (IL-18Rα), IL-1R8 and immune checkpoint molecules levels in CD8 + T cells were measured by flow cytometry. CD8 + T cells were purified, and were stimulated with recombinant IL-37. CD8 + T cells were co-cultured with HEK293 cells in either direct contact or indirect contact manner. Levels of perforin, granzyme B, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The proportion of target cell death was assessed by measuring lactate dehydrogenase level. Results:Plasma IL-37 levels in DKD patients [(63.42±23.30) ng/L] were significant lower than those in healthy controls [(143.02±50.67) ng/L] and T2DM patients [(87.88±40.62) ng/L] ( t=8.848, P<0.001; t=3.456, P<0.001). Plasma IL-37 level had good predictive values for T2DM in health individuals and for DKD in T2DM patients [the area under the curve was 0.797 (95% CI 0.676-0.917, P<0.001) and 0.691 (95% CI 0.576-0.807, P=0.003), respectively]. Plasma IL-37 level was negatively correlated with urea nitrogen ( r=-0.313, P=0.032) and creatinine ( r=-0.477, P<0.001), and positively correlated with estimated glomerular filtration rate (eGFR) ( r s=0.478, P<0.001) in DKD patients. IL-1R8 + CD8 + cell proportion in DKD patients (33.60%±9.47%) was significantly higher compared to healthy controls (16.29%±5.97%) and T2DM patients (17.13%±4.85%) ( t=7.545, 9.516, both P<0.001), but did not correlate with fast blood glucose, urea nitrogen, creatinine, or eGFR (all P>0.05). There were no statistical differences of IL-18Rα + CD8 + cell proportion, soluble IL-1R8 level, or immune checkpoint molecule proportion in CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). Perforin and granzyme B secretions by CD8 + T cells were significantly elevated in DKD patients compared with healthy controls [(108.78±12.42) ng/L vs. (94.60±10.07) ng/L, t=3.096, P=0.005; (261.34±48.79) ng/L vs. (166.28±30.80) ng/L, t=3.387, P=0.002] and T2DM patients [(108.78±12.42) ng/L vs. (92.58±14.71) ng/L, t=3.263, P=0.003; (261.34±48.79) ng/L vs. (170.66±39.24) ng/L, t=2.627, P=0.014]. There were no significant differences of either IFN-γ or TNF-α secretions by CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). In direct contact co-culture manner, CD8 + T cell-induced HEK293 cell death was down- regulated (13.03%±4.97% vs. 17.88%±5.19%, t=2.235, P=0.037). The levels of perforin [(222.02±25.79) ng/L vs. (294.30±25.58) ng/L, t=6.603, P<0.001], granzyme B [(416.27±90.24) ng/L vs. (524.71±115.53) ng/L, t=2.454, P=0.023], IFN-γ [(23.66±4.20) ng/L vs. (35.18±8.51) ng/L, t=4.026, P<0.001] and TNF-α [(1.62±0.29) μg/L vs. (2.09±0.57) μg/L, t=2.302, P=0.034] were also reduced as well. In indirect contact co-culture manner, there were no significant differences of CD8 + T cell-induced HEK293 cell death, perforin, or granzyme B levels between no stimulation and IL-37 stimulation (all P>0.05). IFN-γ and TNF-α levels in the supernatants were reduced in response to IL-37 stimulation [(23.56±6.24) ng/L vs. (32.56±9.90) ng/L, t=2.550, P=0.019; (1.41±0.31) μg/L vs. (2.10±0.44) μg/L, t=4.011, P<0.001]. Conclusion:IL-37 level is reduced in DKD patients.Exogenous IL-37 suppresses the cytotoxicity of CD8 + T cells in DKD patients.

Skeletal muscle wasting refers to a loss of skeletal muscle mass and function.Mitochondrial quality control(MQC)is the basis by which normal physiological mitochondrial function is maintained and mainly involves the regulation of mitochondrial biogenesis,mitochondrial dynamics(fission/fusion),and mitophagy.MQC maintains muscle homeostasis by regulating the relative stability of mitochondrial shape,quantity,and quality.As an economical and effective treatment for muscular atrophy,exercise interventions are widely used,but the relationship between exercise intervention and MQC is not clear.This paper discusses the role of mitochondrial biogenesis,mitochondrial dynamics,and mitophagy in skeletal muscle atrophy and related molecular targets.We thoroughly analyze the mechanisms by which MQC-mediated exercise can improve the skeletal muscle atrophy caused by aging,disuse,and cancer cachexia in order to provide theoretical guidance for intervention.

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder. Its phenotype is highly variable with incomplete penetrance. 22q11.2DS is a rare disease, and the research progress is relatively slow, which has restricted its treatment and intervention. In recent years, much progress has been made in the pathogenic mechanism and genome-wide association study of 22q11.2DS. In this review, the pathogenesis of 22q11.2DS was summarized. Thereafter, the molecular and pathological mechanisms of TBX1 and DGCR8 genes were clarified. Finally, factors affecting the penetrance of cardiac and immune system phenotypes were reviewed. This review may enhance the understanding of 22q11.2DS and has important clinical implications on the prenatal diagnosis, genetic counseling, treatment and intervention of this disease.

Objective To observe the inhibitory effect of Tirofiban on different shear-induced platelet aggregation, and to provide medication suggestions for the treatment of thrombosis in different hemodynamic environment. Methods Polydimethylsiloxane ( PDMS)-glass microchannel chips were fabricated by soft lithography. The whole blood of healthy volunteers anticoagulated with sodium citrate was collected and incubated with different concentrations of Tirofiban in vitro. The blood flowed through the straight microchannel or channel with 80% narrow for 150 seconds at the speed of 11 μL/ min and 52 μL/ min, respectively. The wall shear stress rates in straight channel at 11 μL/ min and 52 μL/ min were 300 s-1 and 1 500 s-1, respectively. The maximum wall shear rates in the channel with 80% occlusion at 11 μL/ min and 52 μL/ min were 1 600 s-1 and 7 500 s-1, respectively. The adhesion and aggregation images of fluorescent labeled platelets on glass surface were photographed with the microscope, and the fluorescent images were analyzed with Image J. The platelet surface coverage ratio was used as a quantitative index of platelet aggregation behavior, and the IC50 of Tirofiban for platelet inhibition was calculated under different shear rates. Flow cytometry was used to detect the platelet activation index (CD62P, PAC-1) in the whole blood at 52 μL/ min in channel with 80% occlusion. Results Tirofiban inhibited platelet aggregation in a dose-dependent manner, and the inhibitory effect was related to the shear rate. Under the shear rates of 11 μL/ min and 52 μL/ min, the aggregation was almost completely inhibited when the concentration in straight channel reached 100 nmol / L. When the concentration in channels with 80% occlusion reached 1 μmol / L, the aggregation was almost completely inhibited. IC50 values at 11 μL/ min and 52 μL/ min in straight channel were 2. 3 nmol / L and 0. 5 nmol / L, respectively. IC50 values at 11 μL/ min and 52 μL/ min in channels with 80% occlusion were 20. 73 nmol / L and 4. 5 nmol / L. Pathologically high shearforce induced an increase in platelet activation, which could be inhibited by Tirofiban. Conclusions Tirofiban can effectively inhibit shear-induced platelet aggregation, and different concentrations of Tirofiban should be given according to the thrombus formed in different shear force environment in clinic practice

Objective:To explore the effects of micro class combined with modular teaching on experimental teaching of internal medicine and basic nursing.Methods:Four classes of nursing students of Batch 2016 were selected as the research objects by drawing lots, and 148 nursing undergraduates were randomly divided into two groups. The combined teaching group adopted micro class combined with modular teaching, and the modular teaching group adopted modular teaching method. The examination scores, SDLRS (self-directed learning readiness scale for nursing education) scores, medical education environment and teaching satisfaction of the two groups were compared. SPSS 22.0 was conducted for chi-square test and t test. Results:The scores of internal medicine nursing, basic nursing and operation skills in the combined teaching group were significantly higher than those in the traditional teaching group ( P<0.05); at the end of the semester, the scores of self-management, love of learning, self-control and SDLRS total score of the combined teaching group were higher than those of the modular teaching group ( P<0.05); the scores of learning perception, teacher perception, environment perception and total score of the combined teaching group were higher than those of the modular teaching group ( P<0.05); the teaching satisfactions with improving learning interest, learning efficiency, learning initiative and mastering key contents better in the combined teaching group were higher than those in the modular teaching group ( P<0.05). Conclusion:The combination of micro class and modular teaching can improve the examination results and self-directed learning readiness of nursing students, improve the internal environment of medical education, and students' teaching satisfaction is high.

This paper reviews the clinical research literature of traditional Chinese medicine (TCM) on treating chronic obstructive pulmonary disease (COPD) in recent years. It is believed that TCM has curative effect in the treatment of acute exacerbation or remission of COPD. The treatment principle for acute stage of COPD includes phlegm, heat and dampness, and the chronic stage lung, spleen and kidney. TCM can improve the clinical symptoms and quality of life, with various treatments and less adverse reactions. However, there are some limitations such as small sample size, lack of in-depth discussion on the mechanism of trwatment, lack of standardized syndrome differentiation and outcomes evaluation standards.

To review the literatures on the treatment of COPD combined with anxiety and depression treated by TCM in recent years, which conclude that to treat this kind of disease is usually by taking drugs, as well as non-drug therapy such as traditional Chinese exercises, acupuncture and massage, and music, etc, which could improve patients unhealthy emotions and quality of life. The recent clinical researches on TCM treatment has been increased, but the overall number of the research of this kind is limited, with problems such as small sample size, singular observing indicator, and requiring multi-center research. There still lacks related basic research and needs more attention.

OBJECTIVE： To establish the quality standard for Kazakhstan medicine Peganum harmala. METHODS： Ten batches of P. harmala collected in Xinjiang Kazakh region were selected as research objects to investigate their characteristics. Qualitative identification of harmaline and harmine was conducted by TLC. The contents of water， total ash， acid-insoluble ash and ethanol extract were tested according to Chinese Pharmacopoeia（2015 edition）. The contents of harmaline and harmine were determined by HPLC. The determination was performed on X-bridge C18 column（250 mm×4.6 mm，5 μm） with mobile phase consisted of acetonitrile-ammonium acetate buffer （adjusted to 6 with glacial acetic acid， gradient elution） at the flow rate of 1 mL/min. The detection wavelength was set at 267 nm， and column temperature was 25 ℃. The sample size was 5 μL. RESULTS： TLC identification results showed that 10 batches of medicinal material showed clear spots at the same position as harmaline and harmine reference substances. Water， total ash， acid-insoluble ash should not be more than 12％，22％，2％， respectively； ethanol extract must not be less than 16％. HPLC results showed that the linear ranges of harmaline and harmine were 15.22-301.40，15.09-301.80 μg/mL； RSDs of precision， reproducibility and stability tests were all lower than 4％； average recoveries were 100.22％ and 100.94％（all RSD＜2％）. The determination results showed that the content of total alkaloids （harmaline and harmine） should not be less than 6.5 mg/g. CONCLUSIONS： Based on the original standard， test items are added in this study. TLC method is established to identify harmaline and harmine. HPLC method is established to determine their contents. Established quality standard can be used for comprehensive quality control of P. harmala from Xinjiang Kazakh region.

Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on the expression of caveolin-1 (Cav-1) with lipopolysaccharide (LPS)-induced lung injury (LI) in rats.Methods Thirty SPF healthy male Sprague-Dawley rats,weighing 170-190 g,were divided into 3 groups (n =10each) using a random number table method:control group (group C),LPS-induced LI group (group LI)and PHCD group.LI was produced by injecting LPS 0.2 ml (5 mg/kg) via the trachea in anesthetized rats.PHCD 0.5 ml (2 mg/kg) was intraperitoneally injected at 1 h before establishing the model in group PHCD.Arterial blood samples were collected at 24 h after establishing the model for blood gas analysis and for determination of serum tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) concentrations by enzyme-linked immunosorbent assay.Rats were then sacrificed,and the lungs were removed.The main bronchus was lavaged,and the broncho-alveolar lavage fluid (BALF) was collected for calculation of the percentage of polymorphonuclear neutrophils (PMNs).Lung tissues were obtained for examination of pathological changes and for determination of myeloperoxidase (MPO) activity (by colorimetric assay),wet/dry weight ratio (W/D ratio),and expression of Cav-1 and nuclear factor kappa B (NF-sB) in nucleoprotein (by Western blot).Results Compared with group C,pH value and PaO2 were significantly decreased,the PaCO2,percentage of PMNs in BALF,W/D ratio and MPO activity were increased,the Car-1 expression was down-regulated,the expression of NF-κB in nucleoprotein was up-regulated,and the serum TNF-α and IL-1β concentrations were increased in group LI (P＜0.05).Compared with group LI,pH value and PaO2 were significantly increased,the PaCO2,percentage of PMNs in BALF,W/D ratio and MPO activity were decreased,the Cav-1 expression was up-regulated,the expression of NF-κB in nucleoprotein was down-regulated,and the serum TNF-α and IL-1β concentrations were decreased (P＜0.05),and the path ological changes of lung tissues were significantly attenuated in group PHCD (P＞0.05).Conclusion The mechanism by which PHC reduces LPS-induced LI may be related to up-regulating the expression of Cav-1 and mitigating inflammatory responses in lung tissues of rats.