ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine （SCOP） and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups： control （0.9% NaCl， n=10）， model （SCOP 1 mg·kg^-1·d^-1， n=10）， low-， medium-， and high-dose Dihuang Yinzi （SCOP 1 mg·kg^-1·d^-1 + Dihuang Yinzi 5.5， 11.0， and 22.0 g·kg^-1·d^-1， n=10）， and donepezil （SCOP 1 mg·kg^-1·d^-1 + donepezil 0.84 mg·kg^-1·d^-1， n=10）. Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week， and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week， 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 （SIRT2）， α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid （AMPA） receptor 1 （GluA1）， protein kinase A （PKA）， cAMP response element-binding protein （CREB）， phosphorylated-CREB （p-CREB）， postsynaptic density protein 95 （PSD95）， growth-associated protein-43 （GAP-43）， and synaptophysin （SYN） in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin （DCX） in the hippocampal dentate gyrus （DG） region. ResultsCompared with the control group， the model group showed impaired learning and memory （P<0.01）， obvious neuronal damage in the hippocampal CA1 region， a reduction in neuron survival （P<0.01）， a decrease in DCX expression in the hippocampal DG region （P<0.01）， down-regulated proteins levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 in the hippocampal tissue （P<0.05， P<0.01）， and an up-regulated protein level of SIRT2 （P<0.01）. Compared with the model group， the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory （P<0.05， P<0.01）， while the low-， medium-， and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival （P<0.05， P<0.01）. The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression （P<0.05， P<0.01）. The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 （P<0.05， P<0.01） and down-regulation in the protein level of SIRT2 （P<0.01）. ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2， activating the PKA/CREB signaling pathway， improving synaptic plasticity， and reducing hippocampal neuronal damage.

Objective:To analyze pathogenic characteristics of viral diarrhea in children aged <5 years in Hebei Province and provide reference for the prevention and control of viral diarrhea in children.Methods:Stool samples were collected from in-patients with diarrhea under five years old from sentinel hospitals in Lulong County of Hebei between 2010 and 2020. ELISA detected rotavirus antigen, and then positive samples were genotyped by semi nested reverse transcription PCR of two rounds. Calicivirus, genotyping astrovirus, and adenovirus were detected by real-time fluorescence quantification PCR. The data were analyzed by using software SPSS 20.0.Results:In 2 925 detected stool samples, 1 919 (65.61%) were positive. The positive rates of rotavirus, calicivirus, adenovirus, and astrovirus were 42.80% (1 252/2 925), 22.12% (647/2 925), 6.19% (181/2 925), 3.56% (104/2 925). Viral diarrhea was mainly caused by rotavirus infection, accounting for 59.30% (1 017/1 715) between 2010 and 2017, and by calicivirus infection accounting for 53.43% (109/204) between 2018 and 2020. The peak positive rate of rotavirus occurred in winter, with the highest rate in infants aged 12 to 17 months (52.96%,483/912). In the rotavirus positive samples, G9P[8] was mainly detected strains (58.31%,730/1 252), followed by G3P[8] (8.15%,102/1 252). The calicivirus-positive samples were mainly infected with norovirus GⅡ. Sequence analysis indicated that the main type was GⅡ.4 [P31] between 2011 and 2016 and GⅡ.3 [P12] in 2018.Conclusions:Rotavirus and calicivirus were the main pathogens causing infant diarrhea in children under five years old in Hebei from 2010 to 2020. Winter was the main epidemic season.

Gallstone is a common and frequent disease and frequent incidence, secondary infection and cancer seriously affect the health of patients. Academic organizations in different regions have issued multiple guidelines and consensus to promote the normative diagnosis and treatment of gallstones. However, in clinical practice, most symptomatic gallstones are treated, while the formation and prevention process of gallstones are ignored, making the concept of treating without a disease has not been strengthened.This article reviews the risk factors and mechanisms of gallstone formation, and points out the importance of effective prevention during stone formation. In the stage of gallstone formation, the high risk factors of stone formation can be analyzed through two aspects of injury factors and protective factors, and the high risk groups of stone formation can be screened out. According to the pathophysiological progression of gallstones, personalized prevention and follow-up strategies can be developed for the stone formation stage of gallstones.

Objective:To explore the lag effect and correlation between daily average temperature and the incidence of other infectious diarrhea in Hebei Province.Methods:The data of meteorological factors (including temperature and average daily temperature) and the daily incidence of other infectious diarrhea in Zhangjiakou City, Chengde City, Tangshan City, Qinhuangdao City, Baoding City, Langfang City, Cangzhou City, Shijiazhuang City, Hengshui City, Xingtai City, and Handan City in Hebei Province from 2017 to 2020 were collected. Eleven prefecture-level cities were divided into four regions, including east, north, middle and south regions. Distributed lag non-linear model was applied to examine the non-linear associations and the lag effect of daily mean temperature on daily incidence of other infectious diarrhea. Meanwhile, the cold and hot effects were used to estinuate the lag-response relationship on the incidence of other infectious diarrhea.Results:A total of 231 008 cases of other infectious diarrhea were reported in Hebei Province. The seasonal distribution was obvious, showing a bimodal distribution of large peaks in summer and small peaks in winter. An inverse S-shaped association between average daily temperature and cumulative risk ratio ( RR) of other infectious diarrhea was observed in Hebei Province. Both high temperature (higher than 27.50 ℃) and low temperature (less than 13.67 ℃) could increase the risk of other infectious diarrhea. When the temperature was lower than 13.00 ℃, the lag time and RR had a U-shaped association (lag four to seven days, 23 to 30 days). Meanwhile, when it was higher than 13.00 ℃, it had an inverted U-shaped association (lag 5 to 21 days). A comparison of four regions of Hebei Province showed that the lag time from south to north was extended from six days to 30 days at low temperature effects with temperature P5=-7.24 ℃. When the temperature getting hot ( P95=28.25 ℃), the risk occurred at lag 0 days, and the lag time gradually got short from north to south. Thus, the high temperature effect reached maximum quickly with a relative short duration. Conclusions:The inverse S-shaped non-linear association between daily average temperature and the incidence of other infectious diarrhea in Hebei Province is observed. Both low temperature and high temperature are associated with increased risk of other infectious diarrhea. But the impact of low temperature is more notable, which has a relative long duration.

Objective:To understand the influence and lag effect of meteorological factors on the incidence of hand, foot and mouth disease (HFMD) in Shijiazhuang.Methods:The daily incidence data of HFMD in Shijiazhuang during 2017-2019 were collected from Chinese Information System for Disease Control and Prevention. The hourly meteorological data were collected form meteorological stations of Shijiazhuang of Chinese meteorological data network. The distributed lag nonlinear model was built for statistical analysis by software R 3.6.2.Results:When the daily average temperature was 15-26 ℃, the risk of incidence of HFMD increased at lag 3-6 days. However, the risk was highest when the temperature was 25 ℃ at lag 3 days ( RR=1.03,95% CI:1.00-1.06). When the daily average relative humidity was more than 80%, the risk of incidence of HFMD increased at lag 5-18 days. However, the risk was highest at lag 9 days ( RR=1.04, 95% CI: 1.02-1.06).When the daily average air pressure ranged from 999 hPa to 1 007 hPa, the risk of incidence of HFMD increased at lag 5-8 days. However, the risk was highest at lag 6 days ( RR=1.01, 95% CI: 1.00-1.02).When the daily average precipitation ranged from 15 to 32 mm, the risk of incidence of HFMD increased at lag 3-18 days. However, the risk was highest at lag 6 days ( RR=1.11, 95% CI: 1.02-1.19). Conclusions:Meteorological factors increased the risk of incidence of HFMD such as higher daily average temperature (15-26 ℃), higher daily average humidity (>80%), lower daily average air pressure (999-1 007 hPa) and higher daily average precipitation (15-32 mm) in Shijiazhuang during 2017-2019. They were all correlated with the incidence of HFMD with certain lag days. It is suggested to use these meteorological indicators for the early warning of HFMD.

Objective:To understand the epidemiological characteristics of cases with severe and fatal hand, foot, and mouth disease (HFMD) caused by other enterovirus in Hebei province, 2013-2017. Genetic characteristics of the main pathogen cosackie virus A6 (CoxA6) were also analyzed to further clarifying the characteristics and rules of genetic evolution on this virus.Methods:Descriptive epidemiological methods were used to analyze the distribution of severe and fatal cases with HFMD caused by other enterovirus in Hebei, 2013-2017. The VP1 sequences of CoxA6 were phylogenetically analyzed, using the Mega 5.2 software package.Results:A total of 86 severe and fatal cases with HFMD caused by other enterovirus were reported, accounting for 1.12%, comparing to all the HFMD caused by other enterovirus. Cases began to rise in April, and peaked in May-July. 65.12% of the cases occurred in children between 1 and 5 years old. The sex ratio between male and female was 1.39∶1. A total of 93.02% of the cases were children outside the child care settings. A total of 39 positive strains were identified, with positive isolation rate as 45.35%. Phylogenetic analysis on the VP1 sequences of CoxA6 strains in this study revealed that CoxA6 strains belonged to sub-genotypes D3a and D3b.Conclusions:Severe and fatal HFMD cases that caused by other enterovirus in Hebei province was with seasonal feature, consistent with the overall trend of this disease, 2013-2017. No new evolutionary branch appeared in the CoxA6 strain.

Current therapies for hereditary neuropathy are often difficult to control or have low patient tolerance,so it is imperative to explore new therapies??Gene therapy has been shown that in many studies it may be applied to nervous system diseases and may become an effective treatment for hereditary nervous system ion channel diseases in the future??At the same time,the continuous progress of photogenetics, chemical genetics and gene editing technology also provides a good basis for the development of gene therapy for hereditary neuropathy??We will review the methods, mechanisms, transduction vectors, promoters and administration routes of gene therapy for hereditary neurological ion channel disease??

Objective: To analyze the epidemiological characteristics of severe and deceased cases of hand, foot and mouth disease (HFMD) in Hebei province, so as to provide reference for prevention and control of the disease. Methods: Severe and deceased HFMD cases reported from the National Disease Surveillance Information Management System and the laboratory testing result in Hebei province from 2010 to 2016 were analyzed. Descriptive epidemiological method involving the distribution of population, area, time and pathogeny were used for the analysis. Results: From 2010 to 2016, 3 803 severe HFMD cases and 162 deceased cases were reported in Hebei province, and the ratio of severe cases among all HFMD patients was 0.75%. A chi-square test showed that the incidence of severe HFMD between males and females was significantly different (χ²=239.37, P<0.001), and scattered children were the main patient. Infants less than six months of age had the highest ratio of severe HFMD cases, the group of one-year-old and younger children had the highest proportion of severe HFMD cases. The severe ratio and severe incidence of Xingtai, Langfang and Hengshui were the top three prefectures having the highest proportions of severe cases. The number of severe cases fluctuated over the past 7years, but showed a downward trend. The constituent ratios of EV-A71 in severe cases and deaths were 79.25% and 92.66%, respectively. Conclusions Severe HFMD epidemics showed a declining trend in Hebei province. EV-A71 is still the main pathogen of both severe and fatal cases. It is necessary to strengthen the prophylactic and therapeutic measures for the young children (< 2 years).

Objective: To understand epidemiological characteristics of the pathogens and evolution of the genotype associated with infectious diarrhea epidemic caused by norovirus in Hebei Province. Methods: A total of 8 infectious diarrhea outbreaks caused by norovirus were reported from Jan 2015 to Dec 2016, of which epidemic treatment materials and specimens were collected at the same time. Norovirus nucleic acid was detected by using real-time PCR, and the partial ORF2 of the all positive specimens were amplified by RT-PCR and sequenced. Phylogenetic tree was constructed by using Mega5.2 based on partial ORF2 sequences of norovirus to perform phylogenetic analysis. Results: A total of 8 norovirus outbreaks, involving 265 cases who were mainly for residential inhabitents, children and students, were reported during this period, and the overall attack rate ranged from 0.70% to 8.13%. The overall positive detection rate of norovirus was 66.25%. The PCR products were sequenced, and sequencing result were obtained for 28 samples, which included GⅠ.3, GⅡ.2, GⅡ.4, GⅡ.13 and GⅡ.17. Conclusions Multiple genotypes of infectious diarrhea outbreaks caused by norovirus were found in Hebei province.

Objective To investigate the expression of IFN-γ, IL-5, IL-17 and TGF-βby Th cells and Th17 cells in rats with allergic rhinitis upon the intervention of IL-10.Methods SD rats were ran-domly divided into three groups including allergic rhinitis ( AR ) group, IL-10 treated group and control group (n=10).Rats in AR group and IL-10 treated group were sensitized by injection of ovalbumin (OVA) and aluminum hydroxide on the 1st, the 7th and the 14th days.The rats treated with equal volume of saline were set up as the control.The corresponding interventions ( OVA, OVA and IL-10, saline) were respec-tively given to rats in each group on the 21th day for 7 consecutive days.The clinical manifestations in rats were observed within 30 minutes after each administration.Serum samples were collected at 48 hours after the last challenge for the detection of IgE and OVA-sIgE.ELISA and Western blot assay were performed to detect IFN-γ, IL-5, IL-17 and TGF-βin nasal mucosa samples.Results Some characteristic symptoms of AR were observed in rats from AR group and IL-10 treated group.Compared with IL-10 treated rats, rats in AR group showed severe clinical symptoms such as constant rubbing and tearing of the eyes (P<0.05).The levels of IgE and OVA-sIgE in serum samples and the levels of IFN-γ, IL-5, IL-17 and TGF-βin nasal tis-sues were significantly increased in rats with RA (P<0.05), but were reduced with IL-10 intervention (P<0.05).Conclusion Exogenous IL-10 could be used to treat AR by reducing the expression of IFN-γ, IL-5, IL-17 and TGF-βin nasal tissues.