Objective:To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing.Methods:Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results:Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) μm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) μm] ( t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] ( t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] ( t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests ( t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) ( t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) ( t=3.88, P=0.005; t=3.02, P=0.017). Conclusions:The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

With the acceleration of population aging and the continuous growth of the elderly population,frailty has become a global public health problem.At the same time,an increasing number of elderly people require surgical treatment,and people are paying more attention to the possible postoperative neurocognitive disorder.Frailty and neurocognitive disorder interact with each other,forming a vicious cycle.Improving one of them can improve the prognosis of the elderly.As one of the commonly used anesthetic drugs in clinical practice,dexmedeto-midine has neuroprotective effects.This article reviews the relationship between frailty and neurocognitive disorder,as well as the research progress of dexmedetomidine in improving perioperative neurocognitive disorder in frail elderly patients.

Objective:To investigate the effects of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy on complications and adverse outcomes of pregnancy.Methods:A retrospective analysis was conducted in 784 pregnant women including 111 cases of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy and 673 pregnant women with normal thyroid function as control group. All women were registered and delivered in the Department of Obstetrics of our hospital from April 2016 to April 2017. The complications and adverse outcomes of pregnancy in the two groups were analyzed.Results:Age, body weight before pregnancy, body mass index(BMI), 1 h plasma glucose and 2 h plasma glucose during oral glucose tolerance test in persistent isolated hypothyroxinemia group were higher than those in control group( P<0.05), with increased incidence of anemia during pregnancy( P<0.05). However, there were no significant differences in the incidences of gestational diabetes mellitus and gestational hypertension between the two groups( P>0.05). No significant statistical differences were found in macrosomia, stillbirth, neonatal malformation, postpartum hemorrhage, acute delivery, premature delivery, fetal intrauterine development delay, and small full-term infants between the two groups( P>0.05). Logistic regression analysis showed that age( OR=1.1, 95% CI 1.0-1.1, P=0.002) and pre-pregnancy body weight( OR=1.0, 95% CI 1.0-1.1, P=0.046) were risk factors for the occurrence of persistent isolated hypothyroxinemia in the first and second trimesters of pregnancy. Persistent isolated hypothyroxinemia in the first and second trimesters was associated with anemia during pregnancy( OR=1.9, 95% CI 1.1-3.2, P=0.024). Conclusions:Pregnant women who are older and heavier before pregnancy should pay more attention to their thyroid function. Pregnant women with persistent isolated hypothyroxinemia in the first and second trimesters should be concerned for anemia.

Objective:To investigate the current situation and needs of pharmaceutical training for general practice faculty.Methods:A self-designed questionnaire survey was conducted in April 2019. The participants were general practice faculty attending the national training course in Zhongshan Hospital and selected by convenience sampling method.Results:A total of 219 general practice teachers participated in the survey, 51.14% (112/219) of the participants thought that the current pharmaceutical knowledge did not meet the needs of pharmaceutical services in daily work, and 67.58% (148/219) attended pharmacy related training every year, and the frequency was mainly 1—2 times per year (56.62%, 124/219). The main reasons for attending the training were working needs (68.24%, 101/148) and willingness (55.41%, 82/148); 63.51% (94/148) of the participants thought that the training was moderate or less effective, mainly because of the weak strength of trainers (40.54%, 60/148), insufficient attention paid by trainers (37.16%, 55/148) and lack of depth (37.16%, 55/148). The survey showed that 76.26% (167/219) of general practice teachers had pharmaceutical training needs; and gender, working years and working experience in secondary and/or tertiary hospitals were influencing factors for pharmaceutical training needs. And female faculty, those working less than 10 years and with working experience in secondary hospitals had higher demand for pharmaceutical training. The expected pharmaceutical training focused primarily on the selection and optimization of medication schemes (72.60%, 159/219), interaction/incompatibility between medicines (62.10%, 136/219) and pharmaceutical care in medical treatment (57.08%, 125/219). The expected training methods were mainly interactive case analysis and discussion (69.41%, 152/219) through the internet or APP (such as WeChat) (54.34%, 119/219); the expected training frequency was no more than once in two months (36.07%, 79/219), better in working time (48.86%, 107/219) and each session was 30—45 minutes (38.36%, 84/219).Conclusion:General practice faculty has a high demand for pharmaceutical training. Targeted, individualized and systematic pharmaceutical training courses should be developed according to the pharmaceutical training needs of participants.

This paper discusses from two aspects of case writing and PBL implementation experience. PBL cases should be based on professional requirements and reflect professional characteristics. Health inspection and quarantine cases targeted at application-oriented talent cultivation can be integrated into relevant experimental skills items. At the same time, the forms of case writing are expanded according to the differences of theme forms, which are designed as parallel cases and serial cases, so as to be applicable to the curriculum integration in different areas. In the implementation of PBL teaching, students' learning status is the key to the efficiency of classroom discussion, which determines whether the implementation of PBL is completely autonomous learning or embedded instruction. Teachers should establish cooperative learning atmosphere to improve the efficiency of classroom discussion

Objective:To investigate the changes of dynamic functional connectivity between the default mode network (DMN) and executive control network (ECN) in the resting state in patients with alcohol use disorder (AUD).Methods:From September 2018 to June 2019, 23 cases of AUD group and 24 cases of healthy control (HC) group matched with age, gender, education level and handedness were collected at Renmin Hospital of Wuhan University. Mini-mental state examination (MMSE) and Michigan alcoholism screening test (MAST) were performed in all subjects for cognition and alcohol dependence score. All the subjects underwent T 1WI-3D structural imaging and resting state functional MRI (rs-fMRI) examination. Group spatial independent component analysis (ICA) was used to select the independent components of DMN and ECN. Then dynamic changes in the functional connectivity between the DMN and the DMN were obtained by sliding window approach and clustering method. Finally, the independent sample t test was used to compare the difference of general clinical data between the two groups, the linear correlation analysis was conducted in the parameter value and MMSE and MAST scores. Results:Compared with the HC group, the static functional connectivity analysis showed that the precuneus and posterior cingulate gyrus of the DMN were enhanced in the AUD group ( P=0.016, t=2.496). The DMN and ECN functional connectivity showed four different brain activity states, the proportion of state1 increased by 6.81% and state2 decreased by 6.83% in the AUD group, state3 and state4 were relatively stable. In state1, the internal functional connectivity of the DMN in the AUD group was enhanced, while the functional connectivity between DMN and ECN was mainly enhanced. In state2, the internal functional connectivity of the ECN was enhanced, and the connectivity between the DMN and ECN was mainly weakened. The mean dwell of state2 in the AUD group was negatively correlated with the MAST score ( r=-0.433, P=0.039). Conclusions:Dynamic functional connectivity patterns between DMN and ECN have been changed in patients with AUD. Dynamic functional connectivity can reveal transient changes in brain activity, which can provide certain imaging evidence for finding changes in AUD deep brain activity.

Objective:To investigate the correlation between radiation dose of the pelvic bone marrow of different anatomical bony sites and the incidence of neutrophil toxicity during the three-dimensional radiotherapy concurrent chemotherapy for cervical cancer.Methods:Clinical data of 117 cervical cancer patients who received three-dimensional radiotherapy concurrent chemotherapy from 2016 to 2018 were retrospectively analyzed. The dosimetric parameters included D mean, V 5Gy, V 10Gy, V 20Gy, V 30Gy, V 40Gy and V 50Gy. The correlation between the dosimetric parameters and the lowest neutrophil count was analyzed by linear regression analysis. Clinicopathological features and dosimetric parameters were included into the multivariate regression analysis model. Results:The incidence rates of neutrophil toxicity (grade 1-4) were 10.3%, 27.4%, 11.1% and 10.3%, respectively. The linear regression analysis showed that the D mean and V 50Gy of lumbosacral vertebrae (LS), the D mean, V 5Gy, V 10Gy, V 20Gy, V 30Gy, V 40Gy and V 50Gy of the ilium were significantly correlated with the grade 2-4 neutrophil toxicity ( P=0.035、<0.001、<0.001、=0.001、=0.003、=0.001、<0.001、<0.001、<0.001). Multivariate analysis demonstrated that the V 20Gy, V 30Gy and V 50Gy of the LS, the D mean, V 5Gy, V 10Gy, V 20Gy and V 30Gy of the ilium were significantly correlated with the grade 2-4 neutrophil toxicity ( P=0.046、0.038、0.049、0.041、0.039、0.029、0.036、0.029). Conclusion:During the process of three-dimensional radiotherapy concurrent chemotherapy for cervical cancer, the volume of medium-and high-dose of LS and the volume of low-and medium-dose of ilium are significantly correlated with the risk of neutrophil toxicity.

Objective:To evaluate the interobserver variation of pathologists in the morphological evaluation of non-invasive follicular thyroid neoplasm with papillary-like nuclear features(NIFTP).Methods:Nine pathologists from different regions in China were selected to evaluate the digital slides of 30 cases of NIFTP. Three score system was applied, including nuclear size and shape, membrane irregularity, and chromatin features. Individual histologic features were scored as either present(1)or absent(0). A total score of 0 or 1 was considered inadequate for the diagnosis of NIFTP and a total score of 2 or 3 was considered sufficient for the diagnosis of NIFTP.Results:Overall, 9 doctors had weak consistency in the interpretation of the 30 cases(Kappa value 0.081 4), in which the interpretation of the membrane irregularity had the best consistency(Kappa value 0.193 6)and the interpretation of nuclear size and shape revealed the worst consistency(Kappa value 0.102 2). The overall consistency of the evaluation from the 7 senior pathologists was better than that of all the pathologists(Kappa value 0.134 1), but it was still weak. The consistency of nuclear membrane irregularity(Kappa value 0.267 4)and nuclear chromatin features(Kappa value 0.257 3)was weak, but much better than that of nuclear size and shape(Kappa value 0.073 0). The interobserver consistency in our study was lower than that in Asian study generally. However, the judgement on membrane irregularity in our senior pathologists was better than that in Asian study.Conclusion:The interobserver variation on the evaluation of the nuclear features of NIFTP is probably due to the education level, working experience, personal understanding of the diagnostic criteria, the regional difference, and some uncertain reasons. There is overall a weak consistency in the interpretation of NIFTP by Chinese pathologists, and it is necessary to popularize the diagnostic criteria and specify the criteria in detail. It is important to exclude high-risk genetic mutation using immunohistochemical staining or molecular examination on those patients with morphology of NIFTP.

Objective To investigate the threshold values of insulin resistance ( IR) assessed by homeostasis model and the prevalence of IR in elderly people over 60 years old in Minhang district of Shanghai, and to evaluate the relationship between IR and metabolic syndrome ( MS) . Methods A total of 3003 elderly people aged 60 and over in the Jiangchuan community of Minhang District, Shanghai, were recruited, including 1286 males and 1717 females. Blood pressure, waist circumference, BMI, blood routine, serum creatinine, blood lipids, glucose, and fasting insulin were measured in all populations studied. Homeostasis model assessment ( HOMA) was used to estimate IR, and MS, and defined according to three diagnostic criteria including NCEP-ATPIII, IDF, and CDS. Results 75th percentile, 80th percentile and 90th percentile of HOMA values in 268 subjects with normotensive and normal BMI, glucose tolerance were considered as the thresholds of IR. The cut-off values were 2. 78, 3. 01 and 3. 56, respectively. And the prevalence of IR were 50. 0％, 42. 1％, and 27. 2％, respectively. IR level was significantly higher in people with MS. Based on the receiver operating characteristic ( ROC ) curve analysis, HOMA-IR and QUICKI index predicted MS well, and the optimal thresholds for diagnosing MS of HOMA-IR were 3. 17 for NCEP-ATPⅢ, 3. 02 for IDF and 3. 03 for CDS. BMI was the best factor for diagnosing IR among different MS components. Logistic regression analysis showed that gender, WC, BMI, SBP, HDL-C, TG, FBG and WBC were independent risk factors for IR. FBG≥5.84 mmol/L was the most dangerous factor of IR (OR=3.603,P<0.01), followed by WC≥85.4 cm(OR=2.152, P<0.01) and BMI≥24.6 kg/m2(OR=2.150,P<0.01). Conclusion The cut-off values of IR estimated by HOMA and the prevalence of IR were higher in elder subjects than other populations. IR was significantly positively correlated with MS. Excluding the conditions that insulin measurement were affected by external factors, HOMA-IR may predict the risk of MS. The components of MS were relative specific measurements of IR, FBG, BMI and WC were important risk predictors of IR in the elderly.

Argus Ⅱ retinal prosthesis system (Argus Ⅱ;Second Sight Medical products,Sylmar,CA) is the first prosthetic retinal device approved for humanitarian use by both FDA in America and CE in Europe.It is a potential treatment for patients with end-stage outer retinal diseases.The system contains several parts,the camera first captures image and transfers it into electrical stimulating parameters conveying spatial-temporal information.The microelectrode epiretinal array then stimulate underlying bipolar cells and retinal ganglion cells.Patients present significant increases on levels of discrimination,target localization,motion detection and navigation.Possible adverse events include conjunctival erosion,hypotony and culture-negative presumed endophthalmitis.Future developments of the Argus Ⅱ system will not only comprise upgrading of image processing software and hardware,but also further disclosing retinal and visual signal processing mechanism.