OBJECTIVE To assess the correlation between the steady-state minimal concentration （cmin） and 24 h area under the drug concentration-time curve （AUC24）/minimal inhibitory concentration （MIC） ratio （AUC24/MIC） of vancomycin in pediatric patients， and analyze independent risk factors for treatment failure. METHODS Data of hospitalized children treated with vancomycin and receiving therapeutic drug monitoring in our hospital from January 2021 to July 2024 were retrospectively collected and divided into success group and failure group according to whether the treatment was successful or not. Spearman correlation analysis was used to analyze the correlation between cmin and AUC24/MIC of vancomycin， and one-way and multifactorial Logistic regression analyses were used to screen the independent risk factors for vancomycin treatment failure. RESULTS A total of 59 children were included， with 41 in the success group and 18 in the failure group. Compared with the failure group， AUC24/MIC of vancomycin was significantly higher in the success group （P＝0.038）， but there was no statistically significant difference in the cmin of the two groups （P＞0.05）； cmin of vancomycin was significantly positively correlated with AUC24/MIC （r＝0.499， P＜0.001）， but it has a certain efficacy in predicting the achievement of the AUC24/MIC standard （≥400） （area under the receiver operator characteristic curve＝0.696）， with an optimal cutoff value of 6.05 mg/L determined by the Youden index. The efficacy of AUC24/ MIC in predicting treatment failure was superior to cmin （areas under the receiver operator characteristic curve were 0.671 vs. 0.523， P were 0.038 vs. 0.684）， with higher sensitivity （83.3% vs. 66.7%）. Hypoproteinemia and AUC24/MIC≤369.1 were independent risk factors for vancomycin treatment failure （P＜0.05）. The incidence of nephrotoxicity was 3.4%. CONCLUSIONS There is a significant positive correlation between cmin and AUC24/MIC of vancomycin in pediatric patients； hypoproteinemia and AUC24/MIC≤369.1 are independent risk factors for vancomycin treatment failure in children.

Objective:To construct a predictive model based on preoperative heat shock protein 90 alpha (HSP90 alpha) and lymphocyte count/monocyte ratio (LMR), for prediction of the textbook outcome (TO) of intrahepatic cholangiocarcinoma after surgery, and evaluate the predictive value of the model.Methods:Retrospective analysis of data from 210 patients with intrahepatic cholangiocarcinoma admitted to Chengde Central Hospital from January 2022 to December 2023, including 122 males and 88 females, aged (61.3±5.5) years. The patients were randomly divided into a training set (147 cases) and a validation set (63 cases) according to a ratio of 7: 3. According to whether the patients achieved TO after surgery, the patients in the training set were divided into a TO group ( n=39) and a non-TO group ( n=108). The conditions of tumor length < 5 cm, lymph node metastasis, large vessel invasion, preoperative HSP90α decrease, and preoperative LMR increase were compared between the two groups. Based on the training set, univariate and multivariate logistic regression were used to analyze the influencing factors of postoperative TO in patients with intrahepatic cholangiocarcinoma. Based on multi-factor results, R 4.3.0 software was used to construct a prediction model for TO. The model was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DSA). Results:Multivariate logistic regression analysis showed that the tumor diameter < 5 cm ( OR=1.917, 95% CI: 1.104-4.024), no lymph node metastasis ( OR=2.489, 95% CI: 1.030-3.619), and no invasion of large vessels ( OR=2.565, 95% CI: 2.097-5.093), the decrease of HSP90α before surgery ( OR=3.161, 95% CI: 2.536-5.358), and the increase of LMR before surgery ( OR=2.088, 95% CI: 1.454-4.262) were the influencing factors for patients TO achieve postoperative TO (all P<0.05). A correlation nomogram model was built based on the above indicators. The area under the curve of the model predicting the postoperative TO of the patients in the training set and the test set were 0.875 (95% CI: 0.782-0.938) and 0.860 (95% CI: 0.767-0.912), respectively, indicating good predictive value of the model. The calibration curve was basically consistent with the standard curve, indicating that the model has good consistency and accuracy. DCA results showed that the models had good clinical net benefit in the threshold probability range of 0.1~0.8. Conclusion:The nomogram model based on perioperative HSP90α and LMR has good accuracy and clinical applicability in predicting the possibility of achieving TO after surgery for cholangiocarcinoma, which can provide a reference for clinical treatment.

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62⁺ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62⁺ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Objective To investigate the prevalence of skin diseases in pre-school children aged 0-7 years in cities of China.Methods From November 2014 to April 2015,12 cities were chosen as survey spots,and pre-school children aged 0-7 years served as respondents.A population-based study was conducted,and 40 vaccination clinics and 80 kindergartens were selected by stratified random sampling.A questionnaire survey and dermatological examination were performed by trained dermatologists.Results A total of 20 033 pre-school children received questionnaires,whose age was 2.41 ± 1.82 years (range,0.08-6.83 years).Among these respondents,7 823 children were found to have skin diseases,with the total prevalence of skin diseases being 39.05％ (7 823/20 033).Additionally,the prevalence of skin diseases reported in the 12 cities from high to low was as follows:66.96％ (612/914,Dalian),56.73％ (2 310/4 072,Shanghai),55.49％ (556/1 002,Wuhan),49.18％ (390/793,Taiyuan),47.16％ (316/670,Chengdu),41.93 ％ (566/1 350,Nanjing),41.03％ (318/775,Chongqing),35.98％ (240/667,Hefei),33.87％ (677/1999,Shenzhen),31.37％ (554/1 766,Changsha),23.52％ (1 107/4 706,Beijing),13.42％ (177/1 319,Shenyang).Totally,40 kinds of skin diseases were investigated,and the 10 most common skin diseases were eczema/infantile eczema/atopic dermatitis (18.71％,3 749/20 033),ichthyosis vulgaris(6.25％,1 253/20 033),lichen pilaris (5.73％,1 148/20 033),diaper dermatitis (5.29％,1 059/20 033),papular urticaria(5.25％,1 052/20 033),hemangioma/vascular malformation (3.86％,774/20 033),pityriasis alba (3.45％,691/20 033),infectious skin diseases (2.59％,519/20 033),urticaria(1.71％,344/20 033)and contact dermatitis (0.5％,100/20 033).Conclusion The total prevalence of skin diseases among pre-school children in cities of China is 39.05％,and eczema/atopic dermatitis is the most common skin disease.

Objective To select the largest non-toxic leaching solution concentration through the experimental observation of the cytotoxicity of the ostrich acellular corneal stromal leaching solution to the Chinese hamster lung fibroblasts cells(CHL) for the further chromosome distortion experiment.Methods The leaching solution made from the ostrich acellular corneal stromal material was diluted with concentrate of 1 ∶ 2,1 ∶ 4 and the original concentration were used to culture with the CHL cells,the negative and positive control were also set up at the same time,to evaluate the impact on cell growth after 24 hour by MTT colorimetric method.Results The leaching solution diluted with 1∶4 was non-toxic,and could promote the growth of the cells.Conclusion Combined with the results of classification and cell morphological features,this cytotoxicity test can be used to screen the best benchmark non-toxic concentrations for the chromosome aberration test of the CHL cells.

Objective To investigate the clinical effect of McDonald cervical cerclage and the affecting factors. Methods Between January 2002 to December 2013 in Peking University First Hospital we performed McDonald cervical cerclage for 116 single pregnant women. They were defined as the successful group who deliveried the live babies after 28 weeks after the cerclage and the failure group who deliveried in the second trimester. According to the surgical indications they were divided into preventive cerclage group and therapeutic cerclage group. Then we analyzed the curative effect and the affecting factors in the groups. Results (1) In the 116 cases, 12 cases (10.3%) failed, and 104 cases (89.7%) succeeded. In the successful group, 37 cases (35.6%,37/104) deliveried pretermly and 67 cases (64.4%) deliveried termly. And there were 56 cases of vaginal delivery (53.8%), and 48 cases (46.2%) of cesarean section. (2) Among the 116 cases, 48 cases (41.4%) were included in prophylactic cerclage group, the gestational age was (16.3± 2.2) weeks, 68 (58.6%) cases were included in therapeutic group, the gestational age was (24.0±2.2) weeks. The operation time was (22±9) minutes in preventive group and (24±13) minutes in therapeutic group,there was no statistical difference between the two groups (P>0.05). Live-birth rate between preventive cerclage group and therapeutic cerclage group was no statistically significant difference (P>0.05). The term birth rate (72.9%, 35/48) in preventive group was higher than that in therapeutic group (47.1%, 32/68), the difference was statistically significant (P<0.01). Neonatal hospitalization rate was lower in preventive group (14.6%, 7/48) than therapeutic group (36.8%, 25/68) , the difference was statistically significant (P< 0.01). (3) In the failure group placental pathology was examed in 7 cases. The placental tissue showed a large number of neutrophils infiltrating in 6 cases (6/7). In the successful group, 27 pregnant women deliveried between 28 to 33+6 weeks (26.0%,27/104), 10 pregnant women deliveried between 34 to 36+6 weeks 10 cases (9.6%, 10/104), 67 cases deliveried after 37 weeks (64.4%, 67/104). A lot of factors including maternal age, the previous cervix operation history, perioperative application of progesterone, operation time and preoperative invasive procedure were compared between the successful group and the failure group. Only maternal age and preoperative invasive proedcure were statistically significant (P<0.05) and the others had no statistical significance (P>0.05). (4) There were 68 cases in the therapeutic group, 7 cases failed, and 61 cases succeeded;the preoperative cervical os in failure group [ (21 ± 20) mm] was wider than that in successful group [(14±5) mm], the difference was statistically significant (P<0.05);and preoperative vaginal ultrasound measurement of cervical canal length were (18 ± 8) mm versus (19 ± 10) mm, there was no statistically significant difference (P>0.05). Conclusions The McDonald cervical cerclage for cervical incompetence is a simple, safe and high successful rate of intervention measures. The term labor rate of prophylactic cervical cerclage was higher than that of the therapeutic cerclage. Older maternal age and preoperative invasive procedure may be the risk factors for cerclage. The infection may play an important factor leading to the failure of McDonald cervical cerclage.

BACKGROUNDInsulin resistance (IR) plays an important pathophysiological role in the development of diabetes, dyslipidemia, hypertension, and cardiovascular disease. Moreover, IR can occur even in non-obese people without diabetes. However, direct detection of IR is complicated. In order to find a simple surrogate marker of IR early in non-obese people, we investigate the association of commonly-used biochemical markers (liver enzymes and lipid profiles) with IR in urban middle-aged and older non-obese Chinese without diabetes.

METHODSThis cross-sectional study included 1 987 subjects (1 473 women). Fasting blood samples were collected for measurement of glucose, insulin, liver enzymes, lipid profiles and creatinine. Subjects whose homeostasis model of assessment-IR (HOMA-IR) index values exceeded the 75th percentile (2.67 for women and 2.48 for men) of the population were considered to have IR. The area under the receiver operating characteristic curve (ROC) was used to compare the power of potential markers in identifying IR.

RESULTSTriglycerides (TG) and ratio of TG to high-density lipoprotein cholesterol (TG/HDL-C) discriminated IR better than other indexes for both sexes; areas under the receiver operating characteristic (ROC) curves (AUC) values were 0.770 (95% confidence interval 0.733-0.807) and 0.772 (0.736-0.809), respectively, for women and 0.754 (0.664-0.844) and 0.756 (0.672-0.840), respectively, for men. To identify IR, the optimal cut-offs for TG and TG/HDL-C ratio were 1.315 mmol/L (sensitivity 74.3%, specificity 71.0%) and 0.873 (sensitivity 70.1%, specificity 73.4%), respectively, for women, and 1.275 mmol/L (sensitivity 66.7%, specificity 74.4%) and 0.812 (sensitivity 75.8%, specificity 69.2%), respectively, for men.

CONCLUSIONTG and TG/HDL-C ratio could be used to identify IR in urban middle-aged and older non-obese Chinese without diabetes.

Aged ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Cholesterol, HDL ; blood ; Cross-Sectional Studies ; Diabetes Mellitus ; blood ; Female ; Humans ; Insulin Resistance ; physiology ; Liver ; enzymology ; Male ; Middle Aged ; Triglycerides ; blood

Background Ostrich acellular corneal stroma possesses a similar constitution to human corneal stroma,so it is expected to become one of ideal biological corneal carriers.Objective This study was to investigate the immunogenicity of acellular stroma carrier of ostrich cornea and offer the information for the development of industrialization and clinical use of acellular stroma carrier of ostrich cornea.Methods Twenty fresh ostrich eyeballs and 20 porcine eyeballs were collected.Acellular corneal stroma carriers of ostriches and pigs were prepared using low temperature freezing joint enzyme digestion method and desiccant dehydration method and sterilized by cobalt-60 irradiation.The corneal stroma carriers were preserved using drying and dehydration method.Forty-five male BALB/c mice were randomly divided into the sham operation group,ostrich acellular corneal stroma group and porcine acellular corneal stroma group.Acellular corneal stroma carriers of ostriches and pigs(wet weight after rewatering was 10 mg/piece) were subcutaneously implanted to the back of BALB/c mice,respectively.Wound healing and inflammatory response on the operative site were observed,and phenotype and activating rate of CD4+,CD8+ and CD25+in peripheral blood of mice were dynamically detected 7,14 and 28 days after ectopically implantation of heterogeneous corneal stroma by immunofluorescence labeling and flow cytometry analysis.Results No swelling and exudation were seen in the skin of operative site of the mice with a good healing of wound after surgery.There were no significant differences in the activating rates of CD4+,CD8+ and CD25+ cells in the peripheral blood of mice among the sham operation group,the porcine acellular corneal stroma group and ostrich acellular corneal stroma group in the three time points after surgery(CD4+:F=0.74,P=0.50;F=0.39,P=0.05;F=3.46,P=0.58.CD8+:F=1.75,P=0.21 ;F=1.14,P=0.35;F=0.78,P=0.48.CD25+:F=0.52,P=0.61 ;F=3.53,P=0.62;F=2.42,P=0.13).Conclusions The ostrich acellular heterogeneous corneal stroma carrier possesses low immunogenicity.It is inferred that ostrich acellular corneal stroma carrier can be used in heterogeneous corneal transplantation.

Objective To study the changes and mechanism of the function of islet βcells and insulin signal transduction molecules in rats after long-term period lipid infusion.Methods Thirty SpragueDawley (SD) rats were randomly divided into free fatty acid (FFA) and normal saline (NS) groups.Catheters were implanted under pentobarbital anesthesia in the right atrium via the jugular vein and the left carotid artery.A technique for a 72-h infusion in unrestrained rats was used for triglyceride and heparin or saline infusion.The infusion period was started on day 2 after surgery.After 72-h infusion,fasting serum insulin (Ins) and FFA in the blood were determined.The glucose infusion rat (GIR) was measured by hyperinsulinemia euglycemic clamp to evaluate the peripheral insulin resistance.The intravenous glucose tolerance test (ivgtt) and islet cell perifusion was conducted to evaluate the function of islet β-cell.The rats in two groups were sacrificed,and the pancreatic islets were isolated and collected.The levels of malondialdehyde (MDA) and reduced glutathione hormone (GSH) were detected in pancreatic tissues.The expressions of insulin receptor substrate-1 (IRS-1),insulin receptor substrate-2 (IRS-2),and glucose transporter-2 (Glut2)gene in islets were detected by real-time polymerase chain reaction (PCR).Results (1)The serum FFA concentration in the FFA group was higher than in NS group [(1.56 ± 0.21) mmol/L vs (0.65 ± 0.12)mmol/L,P ＜0.01].(2)The GIR was decreased significantly in FFA group compared with NS group(P ＜0.01).(3)The glucose that stimulated insulin secretion was decreased in the FFA group.(4)The levels of MDA were significantly higher in FFA group [(1.62 ± O.18) mmol/mg prot vs (0.76 ± 0.15) mmol/mg prot,P ＜0.01].The levels of GSH were lower in FFA group [(22.54 ±2.66) mg/g prot vs (36.58 ± 3.02) mg/g prot,P ＜ 0.01].(5) The gene cxprcssion of IRS-1 in islets was significantly decreased by [(36.8±1.8)％,P ＜0.01],and the expression of IRS-2 and Glut-2 was decreased by [(29.6±1.2) ％] and [(58.7 ± 2.1) ％] in FFA group,respectively(all P ＜0.01).Conclusions Lipid infusion in long time decreased the secretion of insulin and impaired the expression of insulin signal transduction molecules in islet βcells.

As an anchoring protein,receptor for activated C kinase 1 ( RACK1 ) can combine together with many kinds of intracellular signaling molecules and participate in many signal conduction in cells.Researchers have paid close attention to the role of RACK1 in signal transduction molecule network of tumor cells.Abundant studies reveal that RACK1 can regulate signal transduction by regulating tumorigenesis and immune escape in tumor cells,and then play important roles.