OBJECTIVE To identify tortoiseshell glue and antler glue in Qichong zuogui granules， and determine the contents of 12 chemical components. METHODS Identification and content determination were performed by using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. The identification was performed on Hypersil GOLD column with a mobile phase consisted of acetonitrile-0.1% formic acid solution （gradient elution）； the electrospray ion source was used to scan in the positive ion multi-reaction detection mode. The mass charge ratio （m/z） 631.3→546.4， 631.3→921.4 was the detection ion pair for tortoiseshell glue， and the m/z 765.4→554.0， 765.4→733.0 was the detection ion pair for antler glue. The determination method for 12 chemical components was as follows： Accucore C18 column， methanol-0.1% formic acid as mobile phase （gradient elution）； scanning range of positive and negative ions was m/z 100→1 000 with the electric spray ion source and single ion detection scanning mode. RESULTS Average retention times of the molecular ion peaks for characteristic peptide segments of tortoiseshell glue and antler glue were 6.28 and 6.77 min， respectively； the linear relationship of 12 chemical components was good within their respective concentration ranges， such as astragaloside Ⅳ， calycosin-7-O-β-D-glucoside， calycosin， chlorogenic acid， ferulic acid， betaine， amygdalin， rutin， hydroxysafflor yellow A， hyperoside， loganin， cyasterone （r＞0.999）； RSDs for precision， stability （24 h） and reproducibility tests were all less than 5%. The average sample recovery rates ranged from 98.04% to 101.08%. The average contents of 12 components were 1.83， 25.73， 13.76，56.71， 23.80， 49.82， 807.49， 15.01， 317.02， 60.21， 202.71 and 17.70 μg/g， respectively. CONCLUSIONS In this study， tortoiseshell glue and antler glue in Qixiong zuogui granules are identified， and the contents of 12 chemical components therein are determined. This provides a reference for the quality control of this granule.

ObjectiveBased on non-targeted metabolomics， to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus（T2DM） rats by Fuling Yunhua granules， and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats， half male and half female， were randomly divided into the control group， model group， and high， medium， low dose groups of Fuling Yunhua granules（20.70， 10.35， 5.18 g·kg^-1 in raw drug amount） and the positive drug group（pioglitazone hydrochloride tablets， 8.1 mg·kg^-1）. Except for the control group， other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ） to establish a T2DM rat model. After successful modeling， the treatment groups were administered the corresponding drugs by gavage， and the control group and model group were treated with an equal volume of saline by gavage， once/d， for 28 d. Fasting blood glucose（FBG） and glycosylated hemoglobin A1c（GHbA1c） levels were measured in all groups of rats during the administration period， and hematoxylin-eosin（HE） staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap MS）， and the data were processed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential metabolites were identified by the Human Metabolome Database（HMDB） and the Kyoto Encyclopedia of Genes and Genomes（KEGG）， and screened for differential metabolites with variable importance in the projection（VIP） value>1， P<0.05， and fold change（FC）<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0， then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic（ROC） curves. ResultCompared with the control group， the FBG level of rats in the model group increased significantly（P<0.01）， the GHbA1c content tended to increase， but the difference was not statistically significant， and the pancreatic tissue of rats was obviously damaged， the number of pancreatic islets decreased， and the pancreatic β-cells were obviously reduced， atrophied and enlarged. Compared with the model group， the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration（P<0.05， P<0.01）， the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced（P<0.05）， and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid， D-amino acid metabolism， steroid hormone biosynthesis， and glycerophospholipid metabolism in rats. Compared with the model group， the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted， and the pathway enrichment analysis found that D-amino acid metabolism， retinol metabolism， glycine， serine and threonine metabolism， tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol， D-piperidinic acid， D-serine， and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.

Stickler syndrome is a hereditary connective tissue disorder, characterized in ocular manifestations by high myopia and vitreous abnormalities. The progression of the disease can lead to giant retinal tear and rhegmatogenous retinal detachment, making it the most common cause of inherited pediatric retinal detachment. Surgical intervention is the primary treatment for retinal detachment associated with Stickler syndrome. However, there are currently no evidence-based management strategies. Patients typically require multiple surgeries, with low reattachment rates and high recurrence rates, emphasizing the importance of prophylactic treatment. Current prophylactic measures include scleral bucking, laser photocoagulation and retinal cryotherapy, but their absolute benefits remain insufficiently supported. This review summarizes recent advances in the prophylaxis and treatment of retinal detachment in Stickler syndrome, aiming to provide new insights and essential references for the prevention and treatment for such conditions.

BACKGROUND:Postmenopausal osteoporosis significantly increases the risk of fracture,which seriously affects the quality of life of patients.Exercise therapy is an important non-drug means and prevention and treatment strategy for patients with osteoporosis,in which strength training is the best mode,but its specific biological mechanism has not been determined. OBJECTIVE:To investigate the effects of strength training on bone morphology,materials and biomechanics in ovariectomized rats and to explore the mechanism of extracellular matrix remodeling. METHODS:Forty-eight female Sprague-Dawley rats were divided into sham operation group,sham operation exercise group,ovariectomized group and ovariectomized exercise group according to the random number table method.The menopausal animal model was established by bilateral ovariectomy in the ovariectomized group and ovariectomized exercise group,while sham operation was performed in the sham operation group and sham operation exercise group.Four weeks after operation,the sham operation exercise group and the ovariectomized exercise group underwent 12-week tail weight-bearing ladder training,and the sham operation group and the ovariectomized group were raised quietly in the cage.The bilateral femur and tibia were separated after training.The right tibia was used for dual-energy X-ray densitometry and biomechanical,biophysical and biochemical analyses,the left tibia was detected using micro-computed tomography for bone microstructural examination,the right femur was subjected to hematoxylin-eosin staining for histological observation,and the left femur was used for western blot and gelatin zymography detection of protein expression and enzyme activity of extracellular matrix metabolism-related factors,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximal load and stiffness decreased(P＜0.05),bone density,bone mineral density,bone inorganic matter content,bone calcium content decreased(P＜0.05),bone water content increased(P＜0.05),trabecular bone volume fraction,trabecular connectivity density,and trabecular number decreased(P＜0.05),trabecular separation,structural model index increased(P＜0.05),bone adipocyte number and cross-sectional area increased(P＜0.05),matrix metalloproteinase-2 activity decreased(P＜0.05),and protein expression of tissue inhibitor of metalloproteinase-1 and osteoprotegerin increased(P＜0.05)in the ovariectomized group.Compared with the ovariectomized group,the maximal load,stiffness,fracture load and resilience increased(P＜0.05),bone mineral density,bone mineral content,bone mineral density,bone inorganic matter content,and bone calcium content increased(P＜0.05),bone water content decreased(P＜0.05),trabecular separation and bone marrow area decreased(P＜0.05),trabecular bone thickness,cortical bone volume fraction,cortical bone area fraction,cortical bone thickness,and cortical bone porosity increased(P＜0.05),bone adipocyte number and cross-sectional area reduced(P＜0.05),matrix metalloproteinase-2 activity increased(P＜0.05),and protein expression of tissue inhibitor of metalloproteinase-1,Runt-related transcription factor 2 and osteoprotegerin decreased(P＜0.05)in the ovariectomized exercise group.To conclude,strength training can protect against bone injury caused by estrogen deficiency,which is characterized by improvement of bone biomechanical properties,bone tissue composition and bone microstructure,and its mechanism is related to the regulation of extracellular matrix remodeling.

Objective To investigate the effect of Euphorbia helioscopia on biological behaviors of non-small cell lung cancer(NSCLC)cells.Methods NSCLC cell lines PC-9 and A549 treated with different concentrations of Euphorbia helioscopia preparations were examined for changes in proliferation,apoptosis,invasion and migration using CCK-8 assay,colony formation assay,flow cytometry,wound healing assay and Transwell assay.Western blotting was performed to detect the changes in protein expressions of Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9 in the treated cells.PC-9 cells were injected subcutaneously into BALB/C nude mice to establish a nude mouse subcutaneous tumor model.According to the growth of subcutaneous tumors,mice were randomly divided into control group:gavaged daily with saline;Euphorbia helioscopia-treated group:gavaged daily with Euphorbia helioscopia 65 mg/mL,and Euphorbia helioscopia granules were dissolved in saline;cisplatin-treated group:injected intraperitoneally with cisplatin 4 mg/kg every 5 days,6 mice per group.The subcutaneous tumor volume and mass changes of mice were measured,and the toxic effects of Euphorbia helioscopia on heart,liver,spleen,lung and kidney as well as the therapeutic effects of Euphorbia helioscopia were observed in the mice bearing tumor.Results Euphorbia helioscopia granules concentration-dependently inhibited the proliferation and survival of PC-9 and A549 cells,significantly promoted cell apoptosis,suppressed invasion and migration abilities of the cells,up-regulated the expression levels of E-cadherin and Bax,and down-regulated the expressions of Bcl-2,vimentin,MMP2,and MMP9.In the tumor-bearing mice,treatment with Euphorbia helioscopia significantly inhibited tumor growth without producing obvious toxicity in the vital organs.Conclusion Euphorbia helioscopia can inhibit proliferation,invasion,and migration and induces apoptosis of NSCLC cells in vitro.

Objective To investigate the effect of Euphorbia helioscopia on biological behaviors of non-small cell lung cancer(NSCLC)cells.Methods NSCLC cell lines PC-9 and A549 treated with different concentrations of Euphorbia helioscopia preparations were examined for changes in proliferation,apoptosis,invasion and migration using CCK-8 assay,colony formation assay,flow cytometry,wound healing assay and Transwell assay.Western blotting was performed to detect the changes in protein expressions of Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9 in the treated cells.PC-9 cells were injected subcutaneously into BALB/C nude mice to establish a nude mouse subcutaneous tumor model.According to the growth of subcutaneous tumors,mice were randomly divided into control group:gavaged daily with saline;Euphorbia helioscopia-treated group:gavaged daily with Euphorbia helioscopia 65 mg/mL,and Euphorbia helioscopia granules were dissolved in saline;cisplatin-treated group:injected intraperitoneally with cisplatin 4 mg/kg every 5 days,6 mice per group.The subcutaneous tumor volume and mass changes of mice were measured,and the toxic effects of Euphorbia helioscopia on heart,liver,spleen,lung and kidney as well as the therapeutic effects of Euphorbia helioscopia were observed in the mice bearing tumor.Results Euphorbia helioscopia granules concentration-dependently inhibited the proliferation and survival of PC-9 and A549 cells,significantly promoted cell apoptosis,suppressed invasion and migration abilities of the cells,up-regulated the expression levels of E-cadherin and Bax,and down-regulated the expressions of Bcl-2,vimentin,MMP2,and MMP9.In the tumor-bearing mice,treatment with Euphorbia helioscopia significantly inhibited tumor growth without producing obvious toxicity in the vital organs.Conclusion Euphorbia helioscopia can inhibit proliferation,invasion,and migration and induces apoptosis of NSCLC cells in vitro.

Objective To explore the value of fractional order calculus(FROC)model diffusion weighted imaging(DWI)for evaluating pathological classification and differentiation degree of cervical cancer(CCA).Methods Totally 74 CCA patients were enrolled and divided into squamous cell carcinoma(SCC)group(n=54)and adenocarcinoma(ACA)group(n=20)based on pathological classification,also low differentiation group(n=33)and medium-high differentiation group(n=41)based on differentiation degree.Conventional MR examination and DWI with 12 b-values were performed,FROC model parameters(D,β,and p value)and the apparent diffusion coefficient(ADC)of mono-exponential model were obtained via software analysis.The parameters were compared between groups,and receiver operating characteristic curve of those being significantly different between groups were drawn,the area under the curves(AUC)were calculated to evaluate the diagnostic efficacy.Results Significant differences of ADC,D,and β values were found between SCC group and ACA group(all P＜0.05),and D value had the highest AUC(0.726)for distinguishing pathological classification CCA.Meanwhile,significant differences of D,β,p values and ADC were observed between low differentiation group and medium-high differentiation group(all P＜0.05),D value also had the highest AUC(0.865).AUC of the combined model constructed based on significant variables β and p values in logistic regression was 0.926,higher than that of each parameter alone(all P＜0.05).Conclusion FROC model DWI could be used to evaluate pathological classification and differentiation degree of CCA.

AIM:To investigate the impact of platycodin D(PD)on the viability,migration,invasion,apop-tosis and cell cycle of osteosarcoma cells in vitro,along with its underlying mechanisms.METHODS:Human osteosarco-ma cells MG63 and U2OS were divided into control group(0 μmol/L)and PD treatment group(6.25,12.5,25,50 and 100 μmol/L,respectively).Human osteosarcoma cells MG63 and U2OS were categorized into control groups(0 μmol/L PD)and PD treatment groups(6.25,12.5,25,50 and 100 μmol/L).The CCK-8 assay determined cell viability and identified effective treatment concentrations.MG63(15 μmol/L PD)and U2OS(25 μmol/L PD)were specifically ana-lyzed.Cell scratch and Transwell assays assessed migration and invasion.Hoechst 33342 staining examined nuclear mor-phological changes.Flow cytometry analyzed cell cycle distribution and apoptosis rate.Western blot measured protein ex-pression levels:cleaved caspase-3,cleaved PARP,c-Jun N-terminal kinase(JNK),p-JNK,B-cell lymphoma-2(Bcl-2),Bcl-2-ssociated X protein(BAX),matrix metalloproteinase 2(MMP-2),MMP-9,cyclin-dependent kinase 4(CDK4),cyclin D1,CDK1,cyclin B1,extracellular signal-regulated kinase(ERK)and p-ERK.Proteome sequencing of MG63 cells was performed.RESULTS:PD treatment significantly decreased cell survival,scratch healing rate,and invasive cell numbers,while increasing apoptosis rates(P<0.05).Morphological changes such as nuclear hyperchroma-tism and fragmentation were observed in PD-treated cells.PD induced G2/M phase arrest in MG63 and G0/G1 phase arrest in U2OS cells.PD treatment upregulated BAX,cleaved caspase-3,cleaved PARP,and p-JNK/JNK,while downregulat-ing Bcl-2,MMP-2,MMP-9,CDK4,cyclin D1,CDK1,cyclin B1,and p-ERK/ERK(P<0.05).Proteome sequencing re-vealed PD's involvement in cell division,cell cycle regulation,focal adhesion,apoptosis,and the MAPK signaling path-way.CONCLUSION:PD inhibits cell viability,migration,and invasion of osteosarcoma cells in vitro,while promoting apoptosis and inducing cell cycle arrest.These effects are likely mediated through modulation of the MAPK signaling path-way.

Objective To investigate the effect of intravenous ultrafine superparamagnetic iron oxide nanoparticles feraheme (generic name:ferumoxytol) on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion.Methods Thirty C57BL/6J mice were divided into sham operation group,saline control group,and feraheme group by the random number table (n =10 in each group).A permanent right middle cerebral artery occlusion model was induced by the modified suture method in the saline control group and the feraheme group,and no suture was inserted into the mice of the sham operation group.The intervention was performed by tail vein injection at 24 h after modeling.The sham operation group and the feraheme group were injected with 18 mg/kg feraheme,and the saline control group was injected with the same volume of normal saline.The neurobehavioral scores were conducted at 24 h (before the feraheme or saline injection) and 48 h (before the MRI exam) after modeling.MRI scans were performed at 48 h after modeling,and the cerebral infarction volume was calculated according to T2-weighted imaging.After the end of the scan,orbital blood was collected for the detection of serum tumor necrosis factor (TNF)-α,interleukin (IL)-1 β,and IL-6 levels.Then,the mice were sacrificed and the brain tissue was taken for HE staining and Ibal immunohistochemical staining.Results There were no significant differences in the infarct volume and neurological function score between the saline control group and the feraheme group.The serum levels of TNF-α,IL-1β,and IL-6 in the saline control group and the feraheme group were significantly higher than those in the sham operation group (P ＜0.05),but there was no significant difference between the saline control group and the feraheme group.Conclusion Intravenous injection of 18 mg/kg feraheme at 24 h after cerebral ischemia did not affect the infarct volume and inflammatory response,suggesting that this dose of feraheme can be used for molecular imaging studies of inflammatory response after cerebral ischemia.

Objective To explore methods to measure the management level of Chinese hospitals in natural conditions of Chinese hospitals, for improvement of their operation efficiency. Methods The methodology of World Management Survey( WMS) was introduced, and the questionnaire was localized using expert consultation method. Double-blind telephone interviews were conducted to investigate the management level of Chinese hospitals in the four dimensions of standardized operation, performance monitoring, target setting and talent management. Results The management level of hospitals in China varied greatly from places. Among them, the hospital management scoring was found to range from 2. 50 to 2. 75 in most cases, averaging 2. 55. These hospitals scored relatively poor at the four specific management practices of hospital layout(2.48), performance communication(2.27), talents retention, and clarity and comparability of objectives(2. 45). Management level of a hospital was correlated to such factors as its history, ownership form, human capital and hospital size. Conclusions This study uses WMS methodology to quantify Chinese hospital management. The overall management level of Chinese hospitals is expected to improve with much gaps to cover. At this stage, it is imperative to solve the unbalanced and inadequate development of hospital management levels, among regions, hospital grades and forms of ownership.