Objective:To discuss the protective effect of velvet antler peptide(VAP)in the osteoporosis(OP)model rats,and to clarify the possible mechanism.Methods:Sixty 12-week-old SD rats were randomly divided into control group,model group,positive drug group(treated with 1 mg·kg-1·d-1 of alendronate sodium by gavage),low dose of VAP group(treated with 100 mg·kg-1·d-1 VAP),medium dose of VAP group(treated with 200 mg·kg-1·d-1 VAP),and high dose of VAP group(treated with 300 mg·kg-1·d-1 VAP),and there were ten rats in each group.Except for control group,the rats in the other groups were injected with dexamethasone(2 mg·kg-1)to replicate the OP rat model,while the rats in control group were injected with the equivalent volume of saline twice a week for 11 consecutive weeks.Dual-energy X-ray absorptiometry was used to detect the bone mineral density(BMD)of femur tissue of the rats in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of serum calcium(Ca2+),phosphate(P),osteoprotegerin(OPG),alkaline phosphatase(ALP),and osteocalcin(OCN)in serum of the rats in various groups;biochemical method was used to detect the malondialdehyde(MDA)level and superoxide dismutase(SOD)activity in serum of the rats in various groups;HE staining was used to observe the pathomorphology of bone tissue of the rats in various groups;Western blotting method was used to detect the expression levels of silent information regulator 1(SIRT1),catalase(CAT),Runt-related transcription factor 2(RUNX2),and forkhead box protein O1(FOXO1)proteins in bone tissue of the rats in various groups.Results:Compared with control group,the BMD of femoral tissue of the rats in model group was decreased(P<0.05);compared with model group,the BMD of femur tissue of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were increased(P<0.05 or P<0.01).Compared with control group,the levels of Ca2+,P,OPG,and SOD activities in serum of the rats in model group were decreased(P<0.05),and the levels of ALP,OCN,and MDA were increased(P<0.05);compared with model group,the level of OPG in serum of the rats in low dose of VAP group was significantly increased(P<0.05),the levels of Ca2+,P,OPG,and activities of SOD in serum of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were significantly increased(P<0.05 or P<0.01),and the levels of ALP,OCN,and MDA in serum of the rats in positive drug group and different doses of VAP groups were decreased(P<0.05 or P<0.01).The HE staining results showed that compared with control group,the rats in model group had fewer bone cells and disordered arrangements in the bone tissue,thinner bone trabeculae with large fractures,and an expanded marrow cavity;compared with model group,the rats in positive drug group,medium dose of VAP group,and high dose of VAP group had thicker bone trabeculae arranged more tightly.The Western blotting results showed that compared with control group,the expression levels of SIRT1,CAT,RUNX2,and FOXO1 proteins in bone tissue of the rats in model group were decreased(P<0.05);compared with model group,the expression levels of SIRT1,CAT,RUNX2,and FOXO1 proteins in bone tissue of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were significantly increased(P<0.05 or P<0.01).Conclusion:VAP has the protective effect against OP in the rats,and its mechanism may be related to mediating the antioxidant stress action through the SIRT1/FOXO1 signaling pathway.

BACKGROUND:To investigate the prognostic value of the peripheral perfusion index(PPI)in patients with septic shock. METHODS:This prospective cohort study,conducted at the emergency intensive care unit of Peking University People's Hospital,recruited 200 patients with septic shock between January 2023 and August 2023.These patients were divided into survival(n=84)and death(n=116)groups based on 28-day outcomes.Clinical evaluations included laboratory tests and clinical scores,with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission.Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses.Receiver operator characteristic(ROC)curve was used to assess predictive performance.Mortality rates were compared,and Kaplan-Meier survival plots were created. RESULTS:Compared to the survival group,patients in the death group were older and had more severe liver damage and coagulation dysfunction,necessitating higher norepinephrine doses and increased fluid replacement.Higher lactate levels and lower PPI levels at 0 h,6 h,and 12 h were observed in the death group.Multivariate Cox regression identified prolonged prothrombin time(PT),decreased 6-h PPI and 12-h PPI as independent risk factors for death.The area under the curves for 6-h PPI and 12-h PPI were 0.802(95%CI 0.742-0.863,P<0.001)and 0.945(95%CI 0.915-0.974,P<0.001),respectively,which were superior to Glasgow Coma Scale(GCS),Sequential Organ Failure Assessment(SOFA)scores(0.864 and 0.928).Cumulative mortality in the low PPI groups at 6 h and 12 h was significantly higher than in the high PPI groups(6-h PPI:77.52%vs.22.54%;12-h PPI:92.04%vs.13.79%,P<0.001). CONCLUSION:PPI may have value in predicting 28-day mortality in patients with septic shock.

Nuclear factor E2-related factor 2 (Nrf2) is a major regulator of redox homeostasis in cells, and Nrf2 signaling pathway has anti-inflammatory, anti-oxidative stress, and anti-fibrosis effects while plays an important role in wound healing and pathological scar formation and progression. This article reviewed the related research regarding the effect of oxidative stress and Nrf2 signaling pathway on pathological scars, furthermore, it investigated the relationship between Nrf2 signaling pathway, oxidative stress and pathological scars, providing a new perspective for the study of mechanism and clinical prevention and treatments of pathological scars.

Nuclear factor E2-related factor 2 (Nrf2) is a major regulator of redox homeostasis in cells, and Nrf2 signaling pathway has anti-inflammatory, anti-oxidative stress, and anti-fibrosis effects while plays an important role in wound healing and pathological scar formation and progression. This article reviewed the related research regarding the effect of oxidative stress and Nrf2 signaling pathway on pathological scars, furthermore, it investigated the relationship between Nrf2 signaling pathway, oxidative stress and pathological scars, providing a new perspective for the study of mechanism and clinical prevention and treatments of pathological scars.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of Asp,Guad,Adeno,Arg,Ade,Cyti,Phe,Leu,Ile,Glu,Ser,Gln,Gly,Ala,Hyp,Thr,Pro and Lys in Asini Corii Colla.METHODS The analysis was performed on a 45℃ thermostatic Waters BEH C18column(2.1 mm×50 mm,1.7 μm),with the mobile phase comprising of acetonitrile(containing 0.1% formic acid)-water flowing at 0.35 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive ion scanning with multiple reaction monitoring mode.Subsequently,chemical pattern recognition was performed by hierarchical clustering analysis,principal component analysis and orthogonal partial least squares-discriminant analysis.RESULTS Eighteen nucleosides and free amino acids showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 98.0%-104.9% with the RSDs of 1.6%-4.9% .Seventeen batches of samples were clustered into two categories,two principal components demonstrated the accumulative variance contribution rate of 60.75%,Leu,Phe,Ade and Guad were potential index constituents.CONCLUSION This stable and reliable method can be used for the quality control of Asini Corii Colla.

Abstract: Objective　The study aims to investigate the diagnosis quality and accuracy of syphilis cases reported by medical facilities in Inner Mongolia, understand possible problems and influencing factors in reporting and diagnosis, providing evidence for the better formulation of syphilis control and prevention. Methods　Cross-sectional survey was conducted with 2 counties sampled randomly from 12 municipals of Inner Mongolia, different medical facilities were covered. Syphilis cases reported from July 2019 to June 2020 in medical institutions of different categories were sampled and checked. The quality and accuracy of syphilis case reporting were evaluated according to the identifiers in "Syphilis Diagnosis (WS 273-2018)" and "National STD Case Reporting Quality Management Scheme (2018)". In addition, the basic information of medical institutions and the implementation of syphilis detection in laboratories were investigated, and the physicians who reported the case first were interviewed to understand their mastery of syphilis diagnosis and reporting, thus analyzing the major factors influencing the accuracy of reports. Results　The reporting rate of syphilis in medical institutions in Inner Mongolia was 99.04% (311/314), the missing-report rate was 0.96% (3/314), the timely reporting rate was 98.05% (1 659/1 692), the completeness rate was 99.64% (1 686/1 692), the correct rate was 99.35% (1 681/1 692), the accuracy rate of internet-based input was 84.63% (1 432/1 692). There were statistical differences in the quality (&chi;2=13.95, P<0.05; &chi;2=11.40, P<0.05) and accuracy （&chi;2=30.06, P<0.05; &chi;2=44.93, P<0.05) of reports among different municipals and different types of medical facilities. The accuracy rate of syphilis reporting by medical institutions was 86.17% (1 458/1 692), the correct rate for classifying diagnosis was 87.06% (1 473/1 692), and the accuracy rate of staging was 90.25% (1 527/1 692). Multivariate logistic regression results showed that whether the first-clinic physician attended training in the past three years [OR=6.26, 95%CI: (2.12-18.46)] and whether they grasped the key points of syphilis classification standard [OR=2.79, 95%CI: (1.21-6.46)] influenced report accuracy. Conclusions　The quality of reports in Inner Mongolia medical institutions is generally high, but the accuracy rate of reporting and correctness of network input have not yet reached the target requirement of 95%. There is still room for improvement in reporting and diagnostic capabilities. It is suggested to further strengthen the training frequency and coverage for physicians on syphilis diagnosis standard.

Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-β-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.
Rats ; Humans ; Animals ; Tandem Mass Spectrometry/methods* ; Chromatography, Liquid/methods* ; Rats, Sprague-Dawley ; Liquid Chromatography-Mass Spectrometry ; Protein Binding ; Renal Dialysis ; Drugs, Chinese Herbal ; Blood Proteins ; Chromatography, High Pressure Liquid/methods*

A gas chromatography-triple quadrupole mass spectrometry(GC-MS) method was established for the simultaneous determination of eleven volatile components in Cinnamomi Oleum and the chemical pattern recognition was utilized to evaluate the quality of essential oil obtained from Cinnamomi Fructus medicinal materials in various habitats. The Cinnamomi Fructus medicinal materials were treated by water distillation, analyzed using GC-MS, and detected by selective ion monitoring(SIM), and the internal standards were used for quantification. The content results of Cinnamomi Oleum from various batches were analyzed by hierarchical clustering analysis(HCA), principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) for the statistic analysis. Eleven components showed good linear relationships within their respective concentration ranges(R~2>0.999 7), with average recoveries of 92.41%-102.1% and RSD of 1.2%-3.2%(n=6). The samples were classified into three categories by HCA and PCA, and 2-nonanone was screened as a marker of variability between batches in combination with OPLS-DA. This method is specific, sensitive, simple, and accurate, and the screened components can be utilized as a basis for the quality control of Cinnamomi Oleum.
Gas Chromatography-Mass Spectrometry ; Plant Oils ; Oils, Volatile ; Drugs, Chinese Herbal/analysis* ; Cluster Analysis

Objective:To understand the iron content and transferrin receptor 1 (TfR1) expression levels in keloid and normal skin tissues, an in vitro model of keloid fibroblasts (KFB) ferroptosis induced by Erastin was constructed, and the effects of Erastin and Ferrostatin-1(Fer-1) on cell viability, ferrous ion (Fe 2+) content and lipid peroxidation, ferroptosis and fibrosis-related regulatory factors were examined. Methods:Six keloid tissues and six normal skin tissues were collected from the First Affiliated Hospital of Xinjiang Medical University from March to June 2022, and the tissue iron content kit was used to determine the iron content in the dermis of the two tissues, and TfR1 protein expression was detected in the two tissues by Western blot. Primary KFB and normal skin fibroblasts (NFB) were obtained by tissue block culture method, and the effect of different concentrations of Erastin and Fer-1 on cell activity was detected by using Erastin-induced KFB ferroptosis model and CCK-8 method to screen the appropriate drug concentration. The follow-up experiments were divided into five groups: NFB group, control group, Erastin (0.6 μmol/L) group, Fer-1 (1 μmol/L) group, and Erastin (0.6 μmol/L) +Fer-1 (1 μmol/L) group, while KFB was used as the experimental object in the last 4 groups. Cell migration ability was detected by scratch assay, and malondialdehyde (MDA), reactive oxygen species (ROS) and Fe 2+ content in each group of cells were detected by fluorescent probe method and kits; the protein expression of TfR1, glutathione peroxidase 4 (GPx4), solute carrier family 7 member 11 (SLC7A11), α-smooth muscle actin (α-SMA) and type I collagen (COL-1) in each group of cells were detected by Western blot, and the protein expression and localization of TfR1, Gpx4 in KFB were detected by immunofluorescence. GraphPad Prism 9.0 statistical software was used, and the measurement data were expressed as Mean±SD. Independent sample t-test was used for comparison between 2 groups, and one-way ANOVA was used for comparison between multiple groups, then LSD-t test was used for pairwise comparison between groups. P< 0.05 indicated that the differences were statistically significant. Results:The iron content and TfR1 protein expression were significantly higher in keloid compared with normal skin tissue ( P<0.01). The proliferation rate of KFB with different Erastin concentrations decreased gradually, the IC 50 was 0.61 μmol/L, and Fer-1 had no obvious toxicity to KFB in the range of 0.1~20 μmol/L. Scratch test showed that the migration rate of control group was significantly higher than that of NFB group ( P< 0.01) ; compared with the control group, KFB migration rate decreased significantly after Erastin intervention ( P<0.01) ; compared with the Erastin group, KFB migration was significantly accelerated in the Erastin+Fer-1 group ( P<0.01). Compared with the NFB group, ROS, MDA levels were significantly increased in the control group ( P< 0.01) ; compared with the control group, ROS, MDA levels and Fe 2+ content were significantly higher in the Erastin group ( P<0.01), while ROS, MDA levels and Fe 2+ content were significantly lower in the Fer-1 group ( P<0.01) ; compared with the Erastin group, MDA, ROS levels and Fe 2+content in the Erastin+ Fer-1 group were significantly decreased ( P<0.01). Western Blot showed that, compared with the NFB group, iron death indexes of SLC7A11 and GPx4 protein expression were significantly reduced ( P<0.01 or P<0.05), TfR1 protein expression was increased ( P<0.01), and fibrosis indexes of α-SMA and COL-1 protein expression were significantly increased ( P<0.01) in the control group; compared with the control group, SLC7A11 expression was reduced ( P<0.01) and TfR1, COL-1 expression increased ( P<0.01), while SLC7A11, GPx4 expression increased ( P< 0.01) and TfR1, α-SMA, COL-1 expression significantly decreased ( P<0.01) in the Fer-1 group; compared with the Erastin group, the GPx4, SLC7A11 expression was increased ( P< 0.01) and TfR1, α-SMA, COL-1 expression was significantly decreased ( P< 0.01) in the Erastin+Fer-1 group, suggesting that Fer-1 was able to reverse Erastin-induced ferroptosis and pro-fibrotic effects in KFB. Immunofluorescence showed that GPx4 was expressed in both nucleus and cytoplasm. Compared with control group, Fer-1 increased the fluorescence intensity of GPx4 in KFB ( P<0.01). Compared with Erastin group, the fluorescence intensity of GPx4 in Erastin+ Fer-1 group was significantly increased ( P<0.01). TfR1 was mainly expressed in cytoplasm. Compared with control group, Erastin increased the fluorescence intensity of TfR1 in KFB ( P< 0.05), while Fer-1 group significantly decreased it ( P < 0.01). Compared with Erastin group, the fluorescence intensity of TfR1 in Erastin+Fer-1 group was significantly reduced ( P<0.01). Conclusions:Iron overload and free iron increase in keloids. Erastin induces ferroptosis in KFB and aggravates keloid fibrosis. Fer-1 reverses the oxidative damage and iron accumulation induced by Erastin and effectively inhibits ferroptosis and keloid fibrosis in KFB.