In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Objective To investigate the clinical efficacy of Yiqi Huayu Decoction(mainly composed of Astragali Radix,Dioscoreae Rhizoma,Poria,fried Euryales Semen,Ecliptae Herba,Rosae Laevigatae Fructus,charred Crataegi Fructus,Ligustri Lucidi Fructus,Salviae Miltiorrhizae Radix et Rhizoma,and Leonuri Herba)combined with Calcium Dobesilate in the treatment of diabetic nephropathy(DN)with qi deficiency and blood stasis syndrome,and to observe the effect of the therapy on vascular endothelial growth factor(VEGF)and insulin-like growth factor 1(IGF-1).Methods Ninety patients with DN of qi deficiency and blood stasis type were randomly divided into an observation group and a control group,with 45 patients in each group.All patients received basic hypoglycemic therapy and treatment for controlling blood pressure and regulating lipid metabolism disorders.Moreover,the patients in the control group were given Calcium Dobesilate orally,and the patients in the observation group were given Yiqi Huayu Decoction combined with Calcium Dobesilate.The course of treatment lasted for 3 months.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function parameters and serum VEGF and IGF-1 levels in the two groups of patients were observed before and after the treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 3 months of treatment,the total effective rate of the observation group was 91.11%(41/45),and that of the control group was 75.56%(34/45).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P＜0.05).(2)After one month and 3 months of treatment,the TCM syndrome scores of both groups were significantly lower than those before treatment(P＜0.05),and the scores after 3 months of treatment in the two groups were significantly lower than those after one month of treatment(P＜0.05).The intergroup comparison showed that the reduction of TCM syndrome scores of the observation group was significantly superior to that of the control group after one month and 3 months of treatment(P＜0.01).(3)After treatment,the levels of renal function parameters such as serum creatinine(Scr),blood urea nitrogen(BUN),and glomerular filtration rate(GFR)in the two groups of patients were significantly improved compared with those before treatment(P＜0.05),and the observation group's effect on the improvement of all renal function parameters was significantly superior to that of the control group(P＜0.01).(4)After treatment,the serum VEGF and IGF-1 levels in the two groups of patients were significantly lower than those before treatment(P＜0.05),and the observation group's effect on the decrease of serum VEGF and IGF-1 levels was significantly superior to that of the control group(P＜0.01).(5)In the course of treatment,no significant adverse reactions occurred in the two groups of patients,with a high degree of safety.Conclusion Yiqi Huayu Decoction combined with Calcium Dobesilate exerts certain therapeutic effect in treating DN patients with qi deficiency and blood stasis syndrome.The combined therapy can effectively down-regulate the serum levels of VEGF and IGF-1,significantly improve the renal function,and alleviate the clinical symptoms of the patients,with a high degree of safety.

Since the convening of the 19th National Congress of the Communist Party of China, public health of the Chinese has significantly improved, but chronic diseases have hindered its further development. Proactive health is a positive approach to health management, with an emphasis on the prevention of diseases through a healthy lifestyle, which is of great significance to chronic disease prevention and control. Chronic diseases are becoming more prevalent among young age groups in China; thus, it is necessary to advance chronic disease prevention to adolescence. The implementation of proactive health has marked effects on chronic disease prevention and health promotion in adolescents. The integration of sports, health and education is an important way to promote the implementation of proactive health in adolescents and facilitate their healthy development. However, the integration is still insufficient, so synergistic development of the three fields is needed to improve relevant measures and optimize the effects of proactive health on adolescents.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.

AIM:To investigate the molecular mechanism of long noncoding RNA(lncRNA)SNHG1 in regu-lating ferroptosis to alleviate inflammation in CHME-5 human microglia induced by HIV-1 gp120 V3 loop.METHODS:CHME-5 human microglia were cultured in vitro,and were divided into 7 groups:blank group,random peptide group,gp120 V3 loop group(HIV-1 gp120 group),HIV-1 gp120+shCon group,HIV-1 gp120+SNHG1 sh2 group,HIV-1 gp120+SNHG1 sh2+ferrostatin-1(Fer-1;ferroptosis inhibitor)group,and HIV-1 gp120+SNHG1 sh2+EX527(Sirt1 in-hibitor)group.Normal CHME-5 cells were treated with random peptide or gp120 V3 loop for 24 h.After pretreatment of SNHG1 sh2 cells with inhibitors for 2 h,the cells were then treated with gp120 V3 loop for 24 h.The levels of inflammato-ry cytokines in the cell supernatants were detected by ELISA.Western blot was used to detect the protein expression levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),Sirt1 and p53.Microplate reader was used to detect the levels of intracellular ferrous ion(Fe2+)and malondialdehyde(MDA).RESULTS:(1)The results of ELISA showed that the expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β in HIV-1 gp120 group were significantly higher than those in blank group(P<0.05).Compared with HIV-1 gp120 group,the ex-pression levels of inflammatory cytokines in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.05).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of inflammatory factors in HIV-1 gp120+SNHG1 sh2+Fer-1 were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group were significant-ly increased(P<0.01).(2)The results of Western blot showed that compared with blank group,the expression levels of ferroptosis-related proteins SLC7A11 and GPX4 in HIV-1 gp120 group were significantly down-regulated(P<0.01).Com-pared with HIV-1 gp120 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2 group were sig-nificantly up-regulated(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly up-regulated(P<0.05),but the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+EX527 group were significantly down-regulated(P<0.01),and the expression level of p53 was significantly up-regulated(P<0.05).(3)Compared with blank group,the levels of Fe2+and MDA in HIV-1 gp120 group were significantly increased(P<0.05).Compared with HIV-1 gp120 group,the levels of Fe2+and MDA in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,Fe2+and MDA in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group was significantly increased(P<0.05).CONCLUSION:Knockdown of SNHG1 can attenuate the inflammation in microglia induced by HIV-1 gp120 V3 loop,which may be achieved by regulating ferrop-tosis-related signaling molecules through the Sirt1/p53 signaling pathway.

Objective:To clarify the effects of microwave radiation on anxiety-like behavior, the histomorphology of the secondary visual cortex, and calcium activity in neurons.Methods:36 C57BL/6N mice were selected and divided into control group and microwave radiation group according to the random number table method. In the simple behavioral testing, there were 8 mice in the control group and 7 mice in the radiation group. Combining fiber optic recording with behavioral experiments, there were 8 mice in the control group and 7 mice in the radiation group. Hematoxylin-eosin (HE) staining was conducted with 3 mice in each group. A high-power microwave simulated source in the X-band with a center frequency of 9.875 GHz and an average power density of 12 mW/cm 2 was used to irradiate the mice for 15 minutes, establishing a microwave radiation animal model. Then, anxiety-like behavior changes in the radiation group were identified using the open-field and elevated plus maze (EPM) tests. The effects of microwave radiation on the histomorphology of the secondary visual cortex were investigated using HE staining and optical microscopy. Based on the genetically encoded calcium imaging technique, as well as optical fiber recording combined with behavioral paradigms in the open field and the EPM, the changes of calcium activity in neurons in the V2M region of the secondary visual cortex were detected. Results:Compared to the control group, the radiation group showed a significant decrease in the frequency of exploring the central region of the open field and the open arm of the EPM ( t = 2.24, 3.10, P < 0.05). Furthermore, the radiation group exhibited the degeneration and apoptosis of some neurons in the secondary visual cortex, primarily manifested as pyknosis and deep staining, cell body shrinkage, and the slightly widening of perivascular space. Fiber optic recordings and behavioral experiments indicated that compared to the control group, mice in the radiation group exhibited significantly increased calcium activities in neurons of the secondary visual cortex when exploring the central region of the open field ( t = -2.75, P < 0.05) or the open arm of the EPM ( t = -2.77, -3.41, P < 0.05) compared to those before radiation after microwave exposure. Conclusions:Microwave radiation can induce anxiety-like behaviors and histopathological changes in the secondary visual cortex. Increased calcium activity in neurons of the secondary visual cortex is proved to be an important mechanism underlying the changes in anxiety-like behavior due to microwave radiation.

Objective:To compare proximal humerus internal locking system (PHILOS) and Multiloc intramedullary nail in the treatment of proximal humerus fracture-anterior dislocation.Methods:A retrospective study was performed to analyze the data of 33 patients with proximal humerus fracture-anterior dislocation who had been treated by open reduction and internal fixation from June 2015 to April 2021 at Department of Upper Limbs, Zhengzhou Orthopaedic Hospital. According to methods of internal fixation, the patients were divided into an extramedullary group and an intramedullary group. In the extramedullary group of 18 cases subjected to internal fixation with PHILOS, there were 8 males and 10 females with an age of (53.3 ± 10.6) years, and 1 2-part fracture, 15 3-part fractures and 2 4-part fractures by the Neer classification. In the intramedullary group of 15 cases subjected to internal fixation with Multiloc intramedullary nail, there were 8 males and 7 females with an age of (51.5 ± 11.2) years, and 14 3-part fractures and 1 4-part fracture by the Neer classification. The 2 groups were compared in terms of incision length, operation time, intraoperative blood loss, postoperative complications, and visual analog scale (VAS), range of shoulder motion, and Constant-Murley score at postoperative 12 months.Results:The 2 groups were comparable due to insignificant differences in their preoperative general data ( P>0.05). All patients were followed up for (20.8 ± 4.7) months. The incision length in the intramedullary group [(11.6 ± 1.7) cm] was significantly shorter than that in the extramedullary group [(17.6 ± 2.0) cm], and the intraoperative blood loss in the former [(106.7 ± 34.4) mL] was significantly lower than that in the latter [(151.7 ± 45.7) mL] ( P<0.05). The VAS scores at 1 week and 1 month after surgery [2.0 (2.0, 3.0) and 0.0 (0.0, 1.0) respectively] in the intramedullary group were significantly lower than those in the extramedullary group [3.0 (3.0, 3.3) and 1.0 (0.0, 1.3) respectively] ( P<0.05). The external rotation of the shoulder at the last follow-up in the intramedullary group (65.3° ± 15.5°) was significantly larger than that in the extramedullary group (50.6° ± 13.9°) ( P<0.05). There were no significant differences in operation time, incidence of postoperative complications, VAS score at 12 months after operation, Constant-Murley score or range of shoulder motion at the last follow-up between the 2 groups ( P>0.05). Conclusions:In the treatment of proximal humerus fracture-anterior dislocation, open reduction and internal fixation with both PHILOS and Multiloc intramedullary nail can result in a favorable prognosis when the fracture-dislocation is well reduced and fixated. However, the Multiloc intramedullary nail may lead to better early pain relief, less surgical invasion, and better functional recovery of the external rotation of the shoulder.

Objective To develop a nomogram based on pulmonary nodules preoperative CT signs and 3D quantitative parameters for predicting mediastinal lymph node metastases in patients with clinical stage ⅠA lung adenocarcinoma.Methods The imaging data of 164 patients who underwent preoperative CT scan and systematic lymph node dissection were analyzed retrospectively.Commercially available AI software was used to extract 3D quantitative parameters of pulmonary nodules automatically,and CT signs of pulmonary nodules were analyzed.Logistic regression was used to explore the role of these parameters in predicting pathological nodal involvement.A nomogram prediction model was established,then discrimination and calibration of the model were evaluated.Results Among 164 enrolled patients,19(11.6％)were tested positive for mediastinal lymph node metastases at pathology review.The nomogram incorporated spiculation,lobulation,the largest cross-sectional area,and carcinoembryonic antigen(CEA).The model showed great discrimination and calibration,with a C-index of 0.942[95％confidence interval(CI)0.923-0.961].The predicted value of the model fitted well with the actual observed value on the calibration curve.Conclusion The nomogram prediction model based on preoperative CT signs,3D quantitative parameters,and CEA can estimate the probability of mediastinal lymph node metastases in clinical stage ⅠA lung adenocarcinoma.This model may help with clinical decision-making and individualized evaluation.

Objective To investigate the dynamic changes of left ventricular longitudinal systolic function in patients with atrial septal defect(ASD)and pulmonary hypertension(PH)before and after interventional occlusion using echocardiography.Methods A total of 57 patients undergoing interventional occlusion in Zhongshan Hospital,Fudan University from September 2015 to January 2016 were enrolled.Patients were divided into PH group and non-PH group.Echocardiographic examinations were performed for all subjects one day before,one day after and 1-6 months after the interventional occlusion.Twenty healthy individuals were included as a control group.Global and regional longitudinal strain(LS)of the left ventricle were analyzed using TomTec software.Results There were 27 patients in the PH group and 30 patients in the non-PH group.At baseline,tricuspid annular plane systolic excursion(TAPSE)and tissue Doppler velocity of tricuspid annulus S'in both the PH and non-PH groups were higher than those in the control group(P＜0.05).Longitudinal systolic function of the right ventricle decreased significantly on the first day after occlusion(P＜0.05),and slightly increased 1-6 months after occlusion.Patients in the non-PH group showed a decreased LS in a small portion of the left ventricular segments 1 d and 1-6 months after occlusion(P＜0.05);patients in the PH group showed a decreased left ventricular global longitudinal strain(GLS)on the first day after occlusion(P＜0.05),primarily was in the basal and middle parts of the ventricle(P＜0.05),without significant change in the apical part,and the LS of the left ventricle tended to increase 1-6 months after occlusion.Conclusions With or without PH,longitudinal movement of the right ventricle in ASD patient is excessive before occlusion,and gradually improves after occlusion.Left ventricular GLS decreases in ASD patients with PH,with segmental differences 1 day after occlusion.

Objective:To study the therapeutic effect Tetrandrine (TET) on striatal injury caused by microwave radiation and underlying mechanism.Methods:C57BL/6N mice were randomly divided into blank control group (C), radiation control group (R), TET group (TET) and TET combined with radiation group (TET+ R). The mice of radiation group were exposed to 2.856 GHz 8 mW/cm2 microwave on whole-body for 15 min. TET (60 mg/kg) was injected intraperitoneally once a day for 3 consecutive days. The TET structure was verified by ultraviolet spectrophotometry. The open field experiment was used to detect the change of anxiety in mice. Histopathological and ultrastructural changes of the striatum were observed by light microscopy and transmission electron microscopy (TMT). Quantitative real-time PCR (qPCR) was used to detect gene expression changes of voltage-gated calcium channel (VGCC) subtype in the striatum.Results:The open field experiments showed that the time and distance of mice to explore the central region after microwave radiation were significantly lower than that before radiation ( t=4.60, 5.18, P<0.01), and the TET administration significantly improved these changes ( F=1.43, 4.37, P < 0.05). 7 d after microwave radiation, some neuronal nuclei in the striatum of mice contracted and could be stained deeply, which was more obvious in the globus pallidus area. The partial neuronal apoptosis, swelling and cavitation of glial cell mitochondria, blurring of synaptic gaps, and widening of perivascular gaps in the striatum were observed by TMT. The above lesions were significantly rescued after TET administration. But both microwave radiation and TET administration had no significant effect on the gene expressions of striatal VGCC ( P > 0.05). Conclusions:TET has a therapeutic effect on anxiety-like behavior and structural damage of striatum caused by microwave radiation, which is independent of the expression of striatal VGCC genes.