AIM: To investigate the effects of three extracts of Fufang Dihuang decoction on the relaxation of mesentery artery in streptozotocin(STZ)-induced diabetic rats. METHODS: Diabetic rat model was induced by i.p injection STZ at a dosage of 60 mg?kg~ -1 . 30 d later, 95% ethanol, 70% ethanol or water extract of Radix Rehmanniae was p.o administrated for 30 d at the dosage of 107.8 , 154.7 and 56.8 mg?kg~ -1 , respectively. On the 60th day, the responses of mesentery artery were determined in the absence or presence of L-argine (L-Arg), N-Nitro-L-argine (NLA) and Indomethacin (Ind). RESULTS: The relaxation of mesentery artery of diabetic rat was diminished compared with the normal control. The basal release of NO and the L-argine-induced release of NO decreased 64.6 %, 77.6 % respectively in diabetic group compared with the normal control, with the decreased proportion of NO in the endothelium dependent relaxation. 95% and 70% ethanol extract of Fufang Dihuang decoction ameliorated the impaired release of NO in rat's mesentery artery. CONCLUSION: Abnormal relaxation of mesentery artery in diabetic rat may be due to the decreased releasing of NO. The extracts of Fufang Dihuang decoction can protect the endothelium cells and improve the relaxation of mesentery artery, among them 70% ethanol extract exert the best potency, followed by 95% ethanol extract. And the water extract has a poor effect.

BACKGROUND: Children and adolescents are in the growth and development stage, so the use of the same reconstruction methods as adults is easy to induce complications including limb length differences, high graft failure rate and re-surgical intervention. Simultaneously, the occurrence of osteoarthritis will also be advanced. OBJECTIVE: To explore the anatomical characteristics of the anterior cruciate ligament between children, adolescents and adults on MRI, and to provide an anatomical basis for the reconstruction of the anterior cruciate ligament in children and adolescents. METHODS: A retrospective analysis of patients undergoing knee MRI examination in Qingdao Municipal Hospital from October 2016 to October 2018 was conducted. These patients were divided into child and adolescent group and adult group (n=48 per group). The angle between the anterior cruciate ligament and the tibia and femur on the sagittal plane and the position of the anterior cruciate ligament tibial insertion, the angle between the anterior cruciate ligament and the tibia on the coronal plane, the tibial insertion of the anterior cruciate ligament and femur, and the position of the femur stop point on the axial position were measured in both groups. The data obtained from the measurement of the anterior cruciate ligament of children and adolescents were processed. The growth curves of the shape and position of the anterior cruciate ligament of children and adolescents were drawn, and the law of its growth changes was analyzed. RESULTS AND CONCLUSION: (1) The angle between the sagittal plane of the anterior cruciate ligament and the femur (t=﹣2.906, P<0.05), the angle between the sagittal plane of the anterior cruciate ligament and the tibia (t=﹣10.280, P < 0.05), the anterior cruciate ligament angle between the coronal plane and the tibia (t=﹣5.714, P<0.05) were smaller in the child and adolescent group than those of the adult group, and the difference was significant. (2) The ratio of the tibia coronal plane of the anterior cruciate ligament (t=﹣7.263, P < 0.05) and the ratio of the anterior cruciate ligament and femur axial plane (t=﹣7.378, P < 0.05) were lower in the child and adolescent group than those of the adult group, and the difference was significant. (3) There was no significant difference in the anterior cruciate ligament and tibia sagittal plane ratio (t=﹣1.588, P>0.05) and anterior cruciate ligament and femoral coronal surface ratio (t=﹣1.647, P>0.05) between the child and adolescent group and the adult group. (4) The growth curve results showed that during the growth and development, the angle between the anterior cruciate ligament and the femur and tibia on the sagittal plane and the angle with the tibia on the coronal plane changed from small to large (P<0.05). The relative position of the tibial insertion in the coronal position changed from small to large, which indicates that during the growth and development, the tibial insertion moved from inside to outside relative to the inside of the tibial plateau on the coronal plane (P < 0.05). (5) The relative position of femoral insertion in the axial position changed from small to large, suggesting that during the growth and development, the femoral insertion moved from the outside to the inside relative to the lateral femoral condyle (P<0.05). (6) There was no significant difference in the tibial insertion and the femoral insertion between the child and adolescent group and adult group (P>0.05).

Objective By summarizing experimental data of animal models of type 2 diabetes mellitus(T2DM)and its microvascular complications in rats and mice as animal models,the biochemical indexes were analyzed in order to provide theoretical reference for future experiments.Methods The main topics of"type 2 diabetes""diabetic nephropathy""diabetic foot"and"diabetic retinopathy"were searched on China National Knowledge Infrastructure and PubMed databases to screen out the journal literatures related to T2DM and microvascular complications in clinical and animal experiments published from October 31,2019 to October 31,2022.The subjects,disease types,detection indicators and other contents recorded in the literature were sorted out and summarized,and a database was established for statistical analysis.Results A total of 510 literatures were selected,among which fasting blood glucose was the most frequently used biochemical index in T2DM experiment,urine protein level was the most frequently used biochemical index in diabetic nephropathy experiment,and serum inflammatory factors were the most frequently used biochemical index in diabetic foot and diabetic retinopathy experiment.Conclusions By analyzing the application frequency of biochemical indicators in T2DM and its microvascular complications,this study can provide an important reference for clinical diagnosis and treatment of the disease and the development of animal experiments.

Objective:To investigate the efficacy of continuous irrigation and drainage combined with lesion debridement surgery in the treatment of purulent bone and joint infections in children.Methods:A case-control study was conducted to retrospectively analyze the clinical data of 76 children with purulent bone and joint infections who received treatment at Hangzhou Children's Hospital from January 2021 to October 2022. Based on different treatment methods, these children were divided into a control group and an observation group, with 38 cases in each group. The control group received lesion debridement surgery, while the observation group underwent continuous irrigation and drainage combined with lesion debridement surgery. The clinical outcomes of the two groups were compared.Results:The total response rate in the observation group was 97.37% (37/38), which was significantly higher than that in the control group [76.32% (29/38), χ2 = 7.36, P < 0.05]. After treatment, the white blood cell count, erythrocyte sedimentation rate, and percentage of neutrophils in the observation group were (4.32 ± 0.95) × 10 9/L, (14.20 ± 2.50) mm/h, and (52.12 ± 8.45)%, respectively, all of which were significantly lower than those in the control group [(5.68 ± 1.02) × 10 9/L, (22.35 ± 3.35) mm/h, and (66.65 ± 6.20)%, t = 6.01, 12.01, 8.54, all P < 0.05]. The levels of interleukin-6, C-reactive protein, procalcitonin, and tumor necrosis factor-α in the observation group were (5.20 ± 1.02) ng/L, (8.20 ± 1.11) mg/L, (0.80 ± 0.12) μg/L, and (3.20 ± 1.02) ng/L, respectively, which were significantly lower than those in the control group [(8.12 ± 1.10) ng/L, (14.34 ± 2.20) mg/L, (1.12 ± 0.20) μg/L, and (7.50 ± 1.12) ng/L, t = 11.99, 15.36, 8.45, 17.49, all P < 0.05). At 1 week, 1 month, and 3 months after treatment, the Visual Analog Scale scores in the observation group were significantly lower than those in the control group ( t = 3.14, 2.33, 11.36, all P < 0.05). The recurrence rate in the observation group was significantly lower than that in the control group [2.63% (1/38) vs. 21.05% (8/38), χ2= 4.53, P < 0.05). Conclusion:Continuous irrigation and drainage combined with lesion debridement surgery is more effective for treating purulent bone and joint infections in children than lesion debridement surgery alone. This combined therapy can more effectively reduce inflammatory responses, alleviate pain, and lead to a lower recurrence rate.

Autoantibodies ; China ; Cohort Studies ; Follow-Up Studies ; Humans ; Idiopathic Pulmonary Fibrosis

Objective:To evaluate the impact of metastatic site on the prognosis in patients with metastatic renal cell carcinoma (mRCC), and it′s value for modifying the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria.Methods:The data of 218 patients pathologically diagnosed with mRCC were analyzed retrospectively in West China Hospital from Jan. 2009 to Dec. 2019. Among all patients, 71.6%(156/218) were male, and 89.0% (194/218) underwent nephrectomy. Most of the patients were pathologically diagnosed with renal clear cell carcinoma (176 patients, 80.7%). Lung (137/218, 62.8%) was the most observed metastatic site, following by bone (47/218, 26.1%), lymph node (37/218, 17.0%) and liver (23/218, 10.6%). All patients were classified into favorable (26 patients, 11.9%), intermediate (126 patients, 57.8%) or poor (37 patients, 17.0%) risk group according to IMDC criteria. Endpoints of this study were progression-free survival (PFS), overall survival (OS) and tumor response. The impact of metastatic sites on patients’ prognosis was analyzed, and those that had significant relationship with prognosis were then added into IMDC criteria and a modifying IMDC model was established. Predictive value of this model was further evaluated by calculating concordance index (C-index).Results:In the whole cohort, median PFS and OS were 13.0 and 33.0 months. Survival analysis suggested that patients with bone ( P=0.004), brain ( P=0.042) and liver ( P=0.046) had significantly shorter OS. Thus, patients were divided into two groups: patients with bone/brain/liver metastasis (82 patients, 37.6%) and patients with other metastatic sites (136 patients, 62.4%). Compared with patients with other metastatic sites, those who with bone/brain/liver metastasis had inferior tumor response by TKIs treatment (disease control rate: 51.2% vs. 73.5%, P=0.004). Multivariate analysis suggested that bone/brain/liver metastasis had negative impact on OS (25.0 vs. 47.0 mo, P=0.039). Furthermore, bone/brain/liver metastasis also showed significant relationship with shorter OS in IMDC low (30.0 vs. 62.0 months, P=0.036), intermediate (31.0 vs. 48.0 months, P=0.048) or high (7.0 vs. 18.0 months, P=0.037) risk group, indicating that metastatic site had predictive value for prognosis of mRCC patients. Based on that, bone/brain/liver metastasis were added into the IMDC criteria, and weighting each parameter was weighted according to its coefficient to patients’ OS. Finally, a modified IMDC scoring system were established. C-index of this modified model was 0.669 (0.599 for current IMDC criteria). Conclusions:Bone/brain/liver metastasis in mRCC patients indicated a shorter OS duration. When adding bone/brain/liver metastasis as a predictive parameter for prognosis of mRCC patients into IMDC criteria, the modified IMDC criteria could offer more accurate prediction for patients’ survival.

Objective To systematically review the correlation between fluoride exposure through drinking water and dental fluorosis of school-age children,and to provide a theoretical basis for further development of prevention strategies against dental fluorosis.Methods Such databases as China National Knowledge Infrastructure (CNKI),WanFang Data,VIP Database and China Biology Medicine Disc (CBM) were searched through computer to find out the relationship between fluoride exposure through dringking water and occurrence of dental fluorosis.The retrieval time was from January 1,2000 to January 1,2018.Meta-analysis was performed using RevMan 5.3.Funnel plot and fail-safe method were used to evaluate publication bias,and these data were analyzed sensitivity with random and fixed effect models.Results Totally 20 literatures entered into this study,79 814 people in fluoride exposure group,and 181 876 people in control group.The meta-analysis showed that,20 literatures were inhomogeneous through the heterogeneity test,which was analyzed in the random effect model,the pooled odds ratio (OR) value and 95％ confidence interval (95％CI) was 4.25 (3.66-4.94),which suggested that the risk of dental fluorosis in the fluoride exposure group was 4.25 times higher than that in control group.Funnel plot was asymmetrical,the fail-safe number was 47 791.56,which was 2 389.6 (47 792/20) times higher than included literatures.Literatures publication bias was small,sensitivity analysis revealed that the results were basically reliable.Conclusion Excessive fluoride exposure through dringking water could be one of the main risk factors leading to dental fluorosis.

The aim of the study was to develop a simple, rapid and accurate LC-MS/MS method for the determination of digoxin.Digoxin-d3 was taken as the internal standard (IS), and sample preparation was achieved by liquid-liquid extraction.Chromatographic separation was performed on a Kinetex C18 column (2.1 mm × 50 mm, 2.6 μm; Phenomenex) using an isocratic elution with merely 2 min for each sample.The mobile phase consisted of water and acetonitrile solutions, both containing 1 mmol/L ammonium acetate and 1 mmol/L formic acid (55∶45).The detection was conducted on a TripleQuadTM 4500MD mass spectrometer coupled with electrospray ionization interface under positive-ion multiple reaction monitoring mode.The transitions were m/z 798.5 → 651.3 and m/z 801.6 → 654.4 for digoxin and digoxin-d3, respectively.Results showed that the method was linear over the range of 0.100-20.0 ng/mL.The selectivity, accuracy and precision, recovery and stability of the method were all within the acceptable limits with no matrix effect.This method was successfully applied to a girl treated with digoxin with substantial improvement of therapeutic effect and elimination of toxic reaction, so it can provide valuable fuidance and reference for individualized medication in clinical practice.

Objective:To identify the pathogenic gene of a pedigree with symphalangism and to prove the pathogenicity of this locus in vitro.Methods:The clinical data of patients’families were collected at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, peripheral blood was collected and genomic DNA was extracted and NOG, FGF9, GDF5 exon regions were amplified by PCR, and the exon gene mutations were detected by first-generation sequencing technique. The structure of noggin-GDF5 protein complex was simulated in silicon. COS-7 cells were transfected with 5 μg empty plasmid, wild type plasmid and V202G mutant plasmid in vitro. Each group of plasmids was transfected into 3 well cells. The experiment was repeated for 3 times, and the expression of noggin protein was detected by Western blotting. C2C12 cells were also transfected with the above plasmids in vitro for osteogenic differentiation. By applying alkaline phosphatase staining and quantitative assay. Relative expression level of osteoblast-related genes Col1α1, ALP and Runx2 were detected by qRT-PCR. Each group of plasmids was transfected into 3 well cells, and the experiment was repeated for 3 times. All statistical analysis were performed by Prism 6 software. The result were shown as mean±standard deviation, and the comparison between groups was done by unpaired t-test. Data were considered statistically significant when P value is less than 0.05. Results:Both the proband and his mother suffered from symphalangism. The result of Sanger sequencing showed that there was a heterozygous missense mutation of NOG gene (p.V202G) in all patients in this pedigree. No disease-related mutations were detected in FGF9 and GDF5. Computer three-dimensional mechanism simulation showed that the site was located at the α helix. The result of Western blotting showed that the expression of mutant protein was significantly lower than that of wild type. Osteogenic differentiation in vitro showed that the inhibitory effect of V202G mutant protein on osteogenic differentiation decreased. The quantitative result of alkaline phosphatase staining showed that the alkaline phosphatase activity in the vector group was (12.3±0.8) U/L, and the alkaline phosphatase activity in the wild type plasmid group was (2.6±0.3) U/L, which was significantly lower than that in the vector group ( t=11.550, P<0.001). The alkaline phosphatase activity in the mutant plasmid group was (10.8±0.3) U/L. There was no significant difference between the mutant group and the vector group ( t=1.830, P=0.141). The mRNA expression level of osteogenesis-related genes was consistent with the above result . Compared with vector group, the expression of osteogenesis-related genes in wild-type noggin group decreased significantly ALP、 Col1α1 and Runx2 ( t=5.987, 4.498, 4.170; P=0.004, 0.011, 0.014). There was no significant difference between mutant plasmid group and blank vector group in ALP、 Col1α1 and Runx2 ( t=0.433, 0.177, 1.159; P=0.688, 0.868, 0.311). Conclusions:NOG gene c. 605T < G p. V202G is a novel mutation in symphalangism, which is located in the α helix of noggin protein, leading to the decrease of the expression of noggin protein and the manifestation of ankylosis.