Type 2 diabetes macrovascular disease is the main cause of death in type 2 diabetes mellitus. In recent years, the modern medical research and treatment of type 2 diabetes macrovascular disease has made some progress, but the international clinical trials suggest that the current treatment can not effectively reduce the incidence of this disease. Many clinical practices show that the effect of traditional Chinese medicine on this disease is exact, so that the clinical workers on the treatment of type 2 diabetes mellitus macrovascular disease of the status quo, now from the etiology and pathogenesis,clinical research, experimental research on the literature published in recent years, to provide reference for clinical treatment.

Objective:To explore the correlation between fluoride intake and serum alkaline phosphatase (ALP) in pregnant women of different gestational periods in endemic fluorosis area.Methods:Pregnant women in Rencheng District, Jinxiang County, Jiaxiang County of Jining City and Yuncheng County of Heze City were selected in April 2020. According to the gestational weeks, pregnant women were divided into early pregnancy group (0 - 12 weeks), middle pregnancy group (13 - 27 weeks) and late pregnancy group (> 27 weeks). The levels of urinary fluoride, ALP, osteocalcin (BGP), C-terminal peptide of β-Ⅰ collagen (β-CTX) and N-terminal propeptide of type Ⅰ collagen (PINP) of pregnant women in each group were measured, and the correlation between urinary fluoride and ALP, BGP, β-CTX, and PINP in pregnant women of different gestational periods was analyzed.Results:A total of 372 pregnant women were selected, including 97 cases in early pregnancy group, 169 cases in middle pregnancy group and 106 cases in late pregnancy group. There was no significant difference in urinary fluoride level between the three groups [(1.20 ± 0.25), (1.23 ± 0.19), (1.24 ± 0.30) mg/L, P > 0.05]. There was significant difference in serum ALP among the three groups ( P < 0.05), among them, the ALP level in early pregnancy was significantly lower than those of middle pregnancy group and late pregnancy group ( P < 0.05), and the ALP level in middle pregnancy was significantly lower than that of late pregnancy group ( P < 0.05). There was no significant differences in serum β-CTX among the three groups ( P > 0.05). There were significant differences in serum BGP and PINP levels among the three groups ( P < 0.05). The serum BGP and PINP levels in late pregnancy group were significantly higher than those of early pregnancy group and middle pregnancy group ( P < 0.05), and there were no significant differences in serum BGP and PINP levels between early pregnancy group and middle pregnancy group ( P < 0.05). There was a significant positive correlation between urinary fluoride and ALP in early pregnancy group ( r = 0.364, P < 0.05), but no significant correlation between urinary fluoride and BGP, β-CTX and PINP ( r = 0.164, 0.117, 0.136, P > 0.05). There was a significant positive correlation between urinary fluoride level and ALP in middle pregnancy group ( r = 0.417, P < 0.05), but no significant correlation between urinary fluoride level and BGP, β-CTX and PINP ( r = 0.127, 0.108, 0.129, P > 0.05). There was no significant correlation between urinary fluoride level and ALP, BGP, β-CTX and PINP in late pregnancy group ( r = 0.179, 0.158, 0.184, 0.149, P > 0.05). Conclusions:The urinary fluoride level of pregnant women in endemic fluorosis area is relatively stable in gestational period. The urinary fluoride level affects the ALP secretion of pregnant women in early and middle pregnancy. It is still necessary to strengthen the measures of improving water quality and defluoridation to reduce the impact of excessive fluoride intake on pregnancy complications in endemic fluorosis area.

Objective To establish a culture method for primary human nail matrix cells in serumfree media.Methods Nail matrix tissues were collected from 9 patients,who received nail or toe amputation and nail bed repair in Peking University Shenzhen Hospital between January 2016 and December 2016,and cultured in the serum-free DEME/F-12 media at a 37℃ incubator with an atmosphere of 5％ CO2 in air for 2-3 days.Then,primary human nail matrix cells were cultured in keratinocyte serumfree media (CnT-07),and the morphology of human nail matrix cells was observed by microscopy during the culture process.Immunofluorescence cytochemistry with anti-keratin 5 (K5) and K10 was performed to identify the acquired cells,and flow cytometry to analyze the cell purity.Results After 2 or 3 days of the culture,some cells began to crawl out from the tissue.On day 10,large cell masses were formed,some cells were morphologically similar to epithelioid cells arranged in a paving stone-like pattern,and some were flat giving a spindle-shaped or star-shaped appearance.Immunofluorescence cytochemistry showed that some cells could express both K5 and K10,which proved the existence of nail matrix cells,and 37.6％ of the cells expressed K10.Conclusion Human primary nail matrix cells could be successfully cultured by using the tissue culture method with serum-free culture media,and the nail matrix cells cultured in vitro can express both K5 and K10.

Objective To reveal the mechanism of action of AS-Ⅳ on HepG2 cells based on molecular dynamics simulation and experimental evaluation. Methods We constructed a "drug-disease" network pharmacological map, analyzed the core genes of astragaloside Ⅳ (AS-Ⅳ) in HCC, screened key signaling pathways, and established a "drug-target" molecular dynamics model. In vitro assay was used to detect migration, proliferation and invasion abilities. Flow cytometry and qRT-PCR were used to detect the effect of AS-Ⅳ on the cell cycle and apoptosis, and the expression of core gene of HepG2. Results The core target of AS-Ⅳ acting on HCC was VEGFA. Compared with the control group, the high concentration of AS-Ⅳ significantly inhibited the migration, invasion and proliferation of HepG2 cells, blocked the metastasis of HepG2 cells from G₁ to G₂ phase, promoted their apoptosis, down-regulated VEGFA expression and up-regulated TGF-β1 expression. Conclusion AS-Ⅳ may inhibit the proliferation of hepatocellular carcinoma cells through multi-target and multi-pathway.

Enhancement of health management capability and resource utilization efficiency of hospitals has become an imperative need to deepen the healthcare reform. The high-value consumables are subject to point-to-point accurate tracking based on code scan, relying on the hospital′s WeChat official account for WeChat-based management. The WeChat platform enables the system to automatically push the preset procurement plan to the mobile terminal of the managers via the low-inventory alarm at the departments. On the other hand, vendors can use their own mobile terminals to receive in time the plans, query product inventory, and last month invoicing information. These measures facilitate the hospital management on high-value consumables.

BACKGROUNDVon Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene. Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China. This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China, and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.

METHODSAn epidemiological investigation of family members was done to collect the general information. A retrospective study of clinical VHL cases was launched to collect the relative clinical data. Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family. The VHL gene screening was performed by directly analyzing DNA sequence output. At last, we summarized the VHL gene mutation in China by the literature review.

RESULTSA five-generation North-western Chinese family afflicted with VHL disease was traced in this research. The family consisted of 38 living family members, of whom nine were affected. The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas (8), central nervous system hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3), renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the same chromosome region as VHL. Sequence analysis resulted in the identification of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3 of the 167 th codon of VHL. All affected individuals shared this mutation, whereas the unaffected family members and an additional 100 unrelated healthy individuals did not. To date, 49 mutations have been associated with this disease in Chinese populations. The most frequent VHL mutations in China are p.S65 W, p.N78 S, p.R161Q and p.R167 W.

CONCLUSIONSThe results supported the notion that the genomic sequence that corresponds to the 167 th residue of VHL is a mutational hotspot. Further research is needed to clarify the molecular role of VHL in the development of organ-specific tumors.

Adolescent ; Adult ; Asian Continental Ancestry Group ; China ; Female ; Haplotypes ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Retrospective Studies ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; Young Adult ; von Hippel-Lindau Disease ; diagnosis ; genetics

Objectives To determine the short term relationship between the number of old allergic rhinitis(AR) patients and the air quality index(AQI) data in autumn and winter in Beijing.Methods Between October 2015 and December 2015,the AQI index data and the number of old outpatients with AR in Beijing Hospital were collected and the relation between them was evaluated by Pearson correlation analysis.Results The AR patients aged over 60 were 1 892 cases (36.72％ of the total number of outpatients).The males were 953 (50.4％),The females were 939 (49.6％).The number of old outpatients with AT changed from 4/d to 39/d.When the AQI rised,the total number of old outpatients was increased;however,when the AQI rised to a certain extent,especially to the serious pollution value (＞300),the number of old outpatients was declined.Pearson correlation analysis showed that there was a negative correlation between the amount of old AR patients and the AQI in the high incidence of air pollution seasons in Beijing (r=0.311,P＜0.01).Conclusions Air pollution is one of the most important reasons for the increased rate of AR patients in the elderly.

Objective To evaluate the application of fractional exhaled nitric oxide (FeNO) in the reducing treatment of bronchial asthma.Methods From October 2015 to September 2016,60 asthmatic patients with FeNO＞25 ppb were randomized into FeNO group and control group with 30 cases in each group.Patients in both groups were treated with combined inhaled corticosteroids and long-acting beta 2 agonist (ICS/LABA) starting with low doses;the dosage was adjusted according to the symptom control alone in control group,while in FeNO group the dosage was adjusted according to the symptom control and FeNO level.After 1 year-follow up,the Asthma Control Test (ACT) scores,Asthma Life Questionnaire (mini AQLQ)scores,pulmonary function,FeNO levels,blood eosinophil counts,total IgE,hierarchical control level,cumulative corticosteroid use and cumulative months of leukotriene receptor antagonists (LTRA) use were compared before and after treatment within group,and between two groups.Stratified analysis was carried out in the patients complicated with allergic rhinitis.Results After treatment,ACT scores,mini AQLQ scores and FEV1/pred (％) were significantly higher than those before treatmentin both groups (t=10.755,10.189,8.632 and 13.311,8.102,12.456,respectively,all P＜0.05),while the FeNO,EOS and total IgE levels were significantly lower than those before treatment (t=8.005,3.313,3.924 and 8.967,3.885,3.270,respectively,all P＜0.05),and the numbers of patients with good control were significantly increased (Z=-5.035 and-4.976 respectively,P＜0.05).Compared with control group,FeNO level was lower,mini AQLQ scores of symptom scores and emotional scores were higher and the average numbers of asthma attacks per patient per year were less after treatment in FeNO group (t=2.912,4.214,4.589,U=2.154,all P＜0.05).However,there was no significant difference in cumulative corticosteroid use and cumulative months of LTRA use between two groups (U=564.000 t=1.921 and 0.165,respectively,P＞0.05).For patients complicated with allergic rhinitis,the numbers of acute asthma attack were increased and the cumulative dosage of systemic corticosteroid use was higher in control group than those in FeNO group (both P＜0.05).Conclusion The reducing treatment strategy based on FeNO level and symptom control is of clinical value for patients with bronchial asthma,especially for those complicated with allergic rhinitis.

Objective To evaluate the diagnostic value of virtual touch imaging quantification (VTIQ) technique in the differential diagnosis between benign and malignant breast lesions.Methods From September to December 2015, the imaging data of 115 breast lesions in 100 patients confirmed by pathology on conventional ultrasound (2DUS) and VTIQ were retrospectively analyzed. The breast nodules were examined by 2DUS firstly and then the lesions were classified by breast imaging reporting and data system (BI-RADS). The maximum, minimum and average of shear wave velocity (SWV) values were obtained from multiple SWV measurement under the VTIQ speed mode. According to the pathology results, receiver operating characteristic (ROC) curve were plotted to determine the most accurate SWV value and the cut-off value for differential diagnosis. And the diagnosis efficiency was compared between 2DUS and VTIQ.Results There were 38 malignant nodules and 77 benign nodules in 115 breast nodules. BI-RADS grading≥4b level was set as the malignant nodules and grading≤ 4a level as the benign nodules. The SWVmax, SWVmin, and SWVmean on VTIQ of benign and malignant breast nodules were (5.11±1.61) m/s, (2.90±0.86) m/s, (3.73±1.02) m/s, and (7.22±0.94) m/s, (4.33±1.31) m/s, (5.73±1.11) m/s. There were significant differences between malignant and benign breast nodules in SWVmax, SWVmin, and SWVmean on VTIQ (t=-7.442,-7.047,-9.356, allP<0.001). Based on the area under curve of ROC, the SWVmean value in the nodule was the best value in comparison with other SWV values. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of diagnose malignant lesion conducted by 2DUS were 89.5％, 85.7％, 87.0％, 0.63 and 0.84, respectively. The cut-off value of VTIQ mean was 4.34 m/s. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value for the diagnosis of malignant lesion conducted by VTIQ were 89.5％, 85.7％, 87.0％, 0.76 and 0.95, respectively. The diagnosis efficiency of VTIQ was better than 2DUS.Conclusion The study proved that the VTIQ SWVmean is the best parameter for differential diagnosis and VTIQ plays an important role in differential diagnosis of breast nodules.

Objective:To study the iodine nutritional status of pregnant women in the third trimester in the Southwest of Shandong Province, analyze its impact on their cardiac electrical activity, and provide a basis for scientific supplementation of iodine during pregnancy.Methods:From January 2021 to June 2022, a cross-sectional survey was conducted using cluster random sampling method. According to the inclusion and exclusion criteria, 200 pregnant women in the third trimester were selected from 3 tertiary hospitals in three cities in the Southwest of Shandong Province, and were divided into the third trimester group ( n = 600), and 100 non-pregnant women were selected as the control group ( n = 300). The urinary iodine content was detected by arsenic-cerium catalytic spectrophotometry, and the pregnant women in the third trimester group were subdivided into iodine deficiency subgroup [G1 subgroup, median urinary iodine (MUIC) < 150 μg/L] based on the MUIC, iodine excess subgroup (G2 subgroup, MUIC≥500 μg/L) and moderate iodine subgroup (G3 subgroup, 150 μg/L≤MUIC < 500 μg/L). Chemiluminescence immunoassay was used to measure the serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT 4) and free triiodothyronine (FT 3). The cardiac electrical indexes were detected by a 12-lead surface electrocardiogram (ECG) machine. Results:There was no statistically significant difference in urinary iodine levels between pregnant women in the third trimester group and non-pregnant women in the control group among the 3 tertiary hospitals in the Southwest of Shandong Province ( H = 3.63, 3.27, P > 0.05). In the third trimester group, the proportion of pregnant women in the G1, G2 and G3 subgroups was 27.67% (166/600), 6.83% (41/600) and 65.50% (393/600), respectively. There was a statistically significant difference in urinary iodine levels between the subgroups and the control group ( H = 11.56, P < 0.001). The serum FT 3 and FT 4 levels in the G2 subgroup were lower than those in the G1 and G3 subgroups ( P < 0.001), but there was no statistically significant difference in serum TSH levels among the three subgroups ( P > 0.05). The normal rates of ECG in the G1, G2, G3 subgroups, and the control group were 38.55% (64/166), 41.46% (17/41), 92.37% (363/393), and 95.33% (286/300), respectively. The difference between the groups were statistically significant (χ 2 = 461.25, P < 0.001), the normal rate of ECG in the G1 and G2 subgroups was lower than that in the control group ( P < 0.001). Short P-R intervals and ST-T changes were the most common abnormal ECG in the third trimester group. Conclusions:The incidence of iodine deficiency, iodine excess, and other abnormal iodine nutritional status in pregnant women in the third trimester of the Southwest of Shandong Province is relatively high. Short P-R intervals, ST-T changes, and other arrhythmia caused by this are more common. It is necessary to strengthen monitoring of iodine nutritional status and ECG during pregnancy, and adjust intervention strategies such as iodine supplementation in a timely manner.