ObjectiveBased on the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway， this study aimed to observe the effect of the Huazhuo Jiedu prescription on renal fibrosis in 5/6 nephrectomy rats and explore its underlying mechanism. MethodsA total of 67 SPF-grade male SD rats were used， of which 11 were randomly selected as the normal group. A chronic renal failure （CRF） model was established using 5/6 nephrectomy. The successfully modeled rats were randomly assigned to the model group， losartan potassium group （4.5 mg·kg^-1）， and low- （1.175 g·kg^-1）， medium- （2.35 g·kg^-1） and high-dose （4.7 g·kg^-1） Huazhuo Jiedu prescription groups， with 9 rats per group. Each group received an equivalent volume of saline or the corresponding concentration of Huazhuo Jiedu prescription by gavage once daily for 8 weeks. Hematoxylin-eosin （HE） and Masson staining were used to observe renal tissue pathological changes. Transmission electron microscopy examined renal ultrastructure. Immunohistochemistry （IHC） detected expressions of α-smooth muscle actin （α-SMA） and transforming growth factor-β₁ （TGF-β₁）. Western blot analyzed expression levels of microtubule-associated protein Ⅰ light chain 3Ⅱ （LC3Ⅱ）， Beclin1， p62， AMPK， phosphorylated AMPK （p-AMPK）， mTOR， and phosphorylated mTOR （p-mTOR）. ResultsCompared with the normal group， the model group exhibited glomerular shrinkage， mesangial and interstitial thickening， and tubular vacuolar degeneration， with no evident autophagosomes or autophagolysosome structures. Expression levels of α-SMA and TGF-β₁ were significantly increased （P0.01）， while p-AMPK/AMPK， Beclin1， and LC3Ⅱ were significantly decreased （P0.01）， and p-mTOR/mTOR and p62 were significantly increased （P0.01）. Compared with the model group， the medium- and high-dose Huazhuo Jiedu prescription groups and the losartan potassium group showed varying degrees of pathological improvement. Autophagosomes with double- or multiple-layer membranes and autophagolysosomes with monolayer membranes containing undegraded organelles were observed. Renal α-SMA and TGF-β₁ protein expression levels were markedly reduced （P0.05， P0.01）， p-mTOR/mTOR and p62 were significantly decreased （P0.05， P0.01）， and p-AMPK/AMPK， Beclin1， and LC3Ⅱ expression levels were significantly increased （P0.05， P0.01）. ConclusionHuazhuo Jiedu prescription may improve renal fibrosis in 5/6 nephrectomy rats by regulating the AMPK/mTOR signaling pathway and enhancing autophagy.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

Objective:To explore the relationship between executive function and gait in cases of mild amnestic cognitive impairment (aMCI).Methods:Twenty aMCI hospital patients formed an observation group, while 20 healthy counterparts were the control group. Both groups underwent the Tinetti test, followed by the " normal walking" single-task test and the " normal walking + Go/No-go" dual-task test. The pace, step width, stride length, Go/No-go task response time and accuracy rate were recorded.Results:In the single-task test, there was no significant difference in pace or stride width between the two groups, but the average stride length of the observation group (1.11±0.04)cm was significantly shorter than that of the control group. However, in the dual-task test, the average pace time (0.96±0.08)sec and stride length (1.02±0.06)cm of the observation group were significantly smaller than the control group′s averages, while their step width (0.11±0.02)cm was significantly wider. There was no significant difference between the two groups in the response time in a single (Go/No-go) task, but in the dual-task test, the observation group′s average time was significantly longer than the control group′s and the accuracy was significantly poorer. Both the error rate and the non-response rate were significantly higher than among the control group.Conclusions:Mild amnestic cognitive impairment reduces stride length and pace when walking and impairs executive function.

To investigate the application value of slanted gel pads in carotid ultrasonography by comparing the parameters obtained by slanted gel pads with different angles. Methods The right common carotid artery was examined by ultrasonography in 50 adult patients with negative carotid artery ultrasonography. The peak systolic velocity （PSV，cm /s） and Doppler Angle of the common carotid artery were measured without and with the use of slanted gel pads of 18°，25° and 32°. Results The PSV of common carotid artery was 90.10±8.12 cm/s，84.42 ±7.91 cm/s，78.30 ±7.88 cm/s，（72.25 ±7.62）cm/s without and with the use of slanted gel pads of 18°，25° and 32°，the differences were statistically significant（P<0.01）；The Doppler angle correction were（59.78±0.51）°，（54.92±1.51）°，（50.78± 2.48）° and （46.22±2.82）°，respectively. The differences were statistically significant（P<0.01），and the CV were 0.008，0.027，0.049 and 0.061，respectively.Conclusion Increasing the angle of slanted gel pads can significantly reduce the carotid artery PSV and Doppler angle，potentially improve the accuracy of ultrasonic evaluation of carotid artery flow velocity，and has no obvious effect on the coefficient of variation of PSV.

Objective:To analyze the effect of role standardized progressive nursing model on delivery fear and delivery outcome of primiparas.Methods:Using the convenient sampling method, a total of 200 primiparas who were admitted to Ruian Maternal and Child Health Hospital of Zhejiang Province from January to December 2020 were selected as the research objects. According to the random number table method, they were divided into the control group and the observation group, with 100 cases in each group. Patients in the control group were given routine nursing intervention, while patients in the observation group were given role standardization progressive nursing mode on the basis of the control group. Childbirth Attitude Questionnaire (CAQ) and Childbirth Self-Efficacy Inventory-32 (CBSEI-32) were used to investigate, and the outcomes of delivery in the two groups were counted.Results:Before intervention, there was no statistically significant difference in CAQ and CBSEI-32 scores between two groups ( P>0.05) . After intervention, the scores and total scores of all dimensions of CAQ in the observation group were lower than those in the control group, and the outcome expectation, delivery self-efficacy expectation score in CBSEI-32 were higher than those in the control group, and the differences were all statistically significant ( P<0.05) . There was no statistically significant difference in the incidence of postpartum hemorrhage, lateral perineal resection and premature rupture of membranes in the observation group ( P>0.05) . The cesarean section rate in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The role standardized progressive nursing model can alleviate the fear of delivery, improve the sense of self-efficacy during delivery and improve the outcome of delivery, which is worthy of clinical application.

Objective:To investigate the clinical phenotypes, therapy and genetic features of aldehyde dehydrogenase 7 family member A1 (ALDH7A1) gene mutations in five cases of pyridoxine dependent epilepsy (PDE) with diagnosis confirmed by next generation sequencing.Methods:Retrospective analysis was carried out on clinical data of five cases of PDE children with early epilepsy onset who were treated in the Department of Neurology of Children′s Hospital Affiliated to Zhengzhou University from February 2018 to November 2019. Next generation sequencing approach was used for genetic sequencing of proband ALDH7A1 gene and the first generation Sanger was used for validation of family members. And the characteristics of gene mutations were analyzed.Results:Among the five children diagnosed with PDE, the male to female ratio was 4 ∶ 1 and ages at clinic visit ranged from two months to 10 months old. In clinical phenotypes, all five cases experienced onset in neonatal period, with repeated seizures, manifested as myoclonus, spasms or focal paroxysm. The administration of antiepileptic drugs performed poorly in seizure control while long term oral intake of large dose pyridoxine showed better efficacy. All the five cases of children came from compound heterozygous mutations of father and mother, i.e. slicing homozygous mutation c.247-2(IVS2)A>T, missense mutation c.584A>G (p.N195S) and nonsense mutation c.1003C>T(p.R335 *), missense mutation c.1553G>C(p.R518T) and c.1547A>G(p.Y516C), missense mutation c.1547A>G(p.Y516C) and frameshift mutation c.1566_1568delTAC, missense mutation c.1061A>G(p.Y354C) and nonsense mutation c.841C>T(p.Q281X, 259), among which c.247-2(IVS2)A>T was novel splicing site mutation not reported before. Conclusions:PDE is induced by ALDH7A gene mutation. Early clinical manifestations are mostly onset of refractory epilepsy in neonatal period. Antiepileptic drugs perform poorly in terms of efficacy while pyridoxine can control seizure effectively. Gene analysis should be conducted on such patients for confirmed diagnosis.

Objective To study the relationship between serum betatrophin and early growth of macrosomia.Method Full-term macrosomia born in the Maternity and Children's Branch of Ruian People's Hospital of Zhejiang Province from January to June 2018 followed up to 6 months and their mother were enrolled in the prospective case-control study as the fetal macrosomia group.The full-term infants appropriate for gestational age,who met all the above requirements were randomly enrolled in the AGA group in a 1∶1 ratio.Enzyme linked immunosorbent assay (ELISA) was used to detect the level of blood betatrophin at birth and 6 months respectively,and the relationship between serum betatrophin level and the growth and development of infants was analyzed.Result A total of 4 823 live births were delivered during the study period,308 of them were full-term macrosomia,the incidence was 6.4％.30 cases were included in the macrosomia group and the AGA group,respectively.The level of blood betatrophin at birth and 6 months in the macrosomia group were higher than that in the AGA Group [(1 088.3 ± 67.8) ng/L vs.(929.5 ± 81.0) ng/L,(1 057.1 ± 114.2) ng/L vs.(976.4 ±76.6) ng/L],and the differences were statistically significant (P ＜ 0.01).The incidence of overweight was 26.7％ (8/30) in the macrosomia group and 6.7％ (2/30) in AGA group at 6 months of age,the difference was statistically significant (P ＜ 0.05).The level of blood betatrophin in overweight infants was statistically significantly higher than that in non-overweight infants (P ＜ 0.001).There was a positive correlation (P ＜ 0.001) between the level of blood betatrophin at the age of 6 months and the weight,body length,Z-score of weight/body length,triglyceride level at birth and the age of 6 months,and the level of umbilical blood betatrophin.But it was not correlated to gender,feeding pattern,other components of blood lipid,blood glucose and insulin in the cord blood and mother's blood,and the level of blood betatrophin in mother's blood (P ＞ 0.05).Conclusion The betatrophin is involved in the regulation of infant growth and development,which is associated with the occurrence of overweight.

Objective:To explore the temporal and spatial characteristics of pneumoconiosis in Hebei Province from 2009 to 2018, and to provide evidence for the policy development of pneumoconiosis prevention and control.Methods:In February 2019, a database of pneumoconiosis incidence from 2009 to 2018 in Hebei Province was built. The spatial-temporal distribution of pneumoconiosis in Hebei Province was displayed based on barycenter migration technology and spatial autocorrelation analysis.Results:A total of 6099 cases of pneumoconiosis were reported in Hebei Province from 2009 to 2018, the top 5 pneumoconiosis were silicosis(4399, 72.13%) , coal worker pneumoconiosis (1298 , 21.28%) , ceramics pneumoconiosis (224, 3.67%) , welding worker's pneumoconiosis(76, 1.25%) , and casting worker's pneumoconiosis(48, 0.79%). The focus of pneumoconiosis from 2009 to 2014 moved from Tangshan in the northeast to Zhangjiakou in the northwest, and moved to Chengde in the north from 2015 to 2017, and moved back to Tangshan in 2018. The incidence of pneumoconiosis was globally autocorrelation ( P <0.05) from 2009 to 2011 and 2014 to 2018. The high-high gathering areas were located in Zhangjiakou, Chengde and other areas. Conclusion:The barycenter of pneumo- coniosis in hebei province from 2009 to 2018 is relatively stable, mainly locates in the northern part of Hebei Province over the years. There is an obvious regional aggregation, and the aggregation type is mainly high-high aggregation, which indicates that relevant departments should focus on strengthening the prevention and treat- ment of aggregation areas on the basis of overall planning.

Objective:To explore the temporal and spatial characteristics of pneumoconiosis in Hebei Province from 2009 to 2018, and to provide evidence for the policy development of pneumoconiosis prevention and control.Methods:In February 2019, a database of pneumoconiosis incidence from 2009 to 2018 in Hebei Province was built. The spatial-temporal distribution of pneumoconiosis in Hebei Province was displayed based on barycenter migration technology and spatial autocorrelation analysis.Results:A total of 6099 cases of pneumoconiosis were reported in Hebei Province from 2009 to 2018, the top 5 pneumoconiosis were silicosis(4399, 72.13%) , coal worker pneumoconiosis (1298 , 21.28%) , ceramics pneumoconiosis (224, 3.67%) , welding worker's pneumoconiosis(76, 1.25%) , and casting worker's pneumoconiosis(48, 0.79%). The focus of pneumoconiosis from 2009 to 2014 moved from Tangshan in the northeast to Zhangjiakou in the northwest, and moved to Chengde in the north from 2015 to 2017, and moved back to Tangshan in 2018. The incidence of pneumoconiosis was globally autocorrelation ( P <0.05) from 2009 to 2011 and 2014 to 2018. The high-high gathering areas were located in Zhangjiakou, Chengde and other areas. Conclusion:The barycenter of pneumo- coniosis in hebei province from 2009 to 2018 is relatively stable, mainly locates in the northern part of Hebei Province over the years. There is an obvious regional aggregation, and the aggregation type is mainly high-high aggregation, which indicates that relevant departments should focus on strengthening the prevention and treat- ment of aggregation areas on the basis of overall planning.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.