Objective · To establish a replicative senescence model of human gingival fibroblasts (hGFs), investigate changes in aging related biological characteristics, and provide an efficient cell model for further study on the aging in periodontal diseases. Methods · hGFs were isolated from healthy gingival tissues and cultured with tissue block method in vitro. The tissue source was verified with immunofluorescence. hGFs were continuously cultured and cumulative population doublings (CPD) were calculated and used to draw the curves. Changes in the proliferative capacity of hGFs with CPDs of 10.82, 20.65, 29.52, 42.22, 60.79, and 70.03 were examined with CCK-8. Real-time PCR was used to evaluate changes in the mRNA expression of senescence-related genes p16INK4a and p21Cip1. Results · CPD curves showed that after continuous culture, the CPD value increased gradually and became stable after achieving 70.03. hGFs became flatter and more cell rocessesappeared with the increase of CPD value. The cell proliferative capacity declined and mRNA levels of p16INK4a and p21Cip1 significantly increased (P=0.000). Conclusion · A replicative senescence model of hGFs is established throughcontinuous culture. CPD curves can reflect the aging of hGFs.

BACKGROUND: Cerebrovascular disease often causes dysfunction of the brain nerve, and nerve cel apoptosis is the important factor of cerebral nerve dysfunction. The excessive expression of c-fos can block the transduction of intracelular signal so that producing some apoptosis-promoting factors, which involve in nerve cel apoptosis process after ischemia injury of brain. Bcl-2 is an inhibited factor. It might to be the key to treat ischemic cerebrovascular disease by inhibiting or reducing the apoptosis of nerve cels after ischemia injury. OBJECTIVE: To investigate the therapeutic effect and mechanism of the Total Flavone of Hawthorn Leaf on chronic cerebral ischemia rats. METHODS: A total of 72 healthy male Sprague-Dawley rats were randomly divided into sham surgery group, model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model in the model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Total Flavone of Hawthorn Leaf group and ginkgo leaf group respectively received 140 mg/kg Total Flavone of Hawthorn Leaf and 12.3 mg/kg ginkgo leaf intragastricaly for 36 days from 36 days after model induction. Model group and sham surgery group received 3.5 mL/kg physiological saline intragastricaly. RESULTS AND CONCLUSION: Compared with the model group, the expression of c-fos protein significantly deceased in the Total Flavone of Hawthorn Leaf group (P < 0.01), Bcl-2 expression levels significantly increased (P < 0.01), and Ca2+ content decreased (P < 0.05). Moreover, no significant difference in above indexes was detected between Total Flavone of Hawthorn Leaf group and ginkgo leaf group (P> 0.05). These data indicated that the protective effect of Total Flavone of Hawthorn Leaf on chronic cerebral ischemia was associated with its inhibition of neuronal apoptosis. Its mechanism of anti-apoptosis might be associated with up-regulating expression of Bcl-2, down-regulating expression of c-fos and decreasing Ca2+ content in brain.

Objective To assess the reliability and validity of the Chinese version of the neuropsychiatric inventory (CNPI). Methods The CNPI was administered to 219 caregivers of patients with Alzheimer's disease (AD). Each caregiver was retested 4 weeks after initial testing. Results The Cronbach a coefficient of the total symptom scale was 0.69. The Cronbach α coefficient of the total caregiver distress subscale was 0.72. The Cronbach α coefficient of the entire inventory was 0. 82. The test-retest coefficients ranged from 0.66 to 0.98 (P < 0.01). Principal axis factoring analysis of the symptom subscale yielded a five-factor solution which contributed to 67.0% of the cumulative variance. Factor 1, which included aberrant motor behavior, hallucinations, delusion and irritability had the most significant contribution to the cumulative variance. Principal axis factoring analysis of the caregiver distress subscale also yielded a five-factor solution which contributed to 70.2% of the cumulative variance. Factor 1, which included depression, delusion, sleep/night behavior, aberrant motor behavior, and irritability had the most significant contribution to the cumulative variance. Conclusion This Chinese version of NPI is a reliable and valid tool for measuring neuropsychiatric disturbances in patients with AD.

Early diagnosis of pulmonary diseases is of great significance for their prevention and treatment. Serum Krebs von den Lungen-6 (KL-6) assay can reflect the damage degree of alveolar epithelium and stromal tissue, and is simple, non-invasive and low-cost. Pervious study showed that the serum KL-6 level was higher in patients with various interstitial lung diseases (e.g. idiopathic pulmonary fibrosis and connective tissue disease, primary Sjögren's syndrome, rheumatoid arthritis, idiopathic inflammatory myopathy and systemic sclerosis combined with interstitial lung disease), non-small cell lung cancer, various pneumonias and chronic obstructive pulmonary disease compared to healthy controls. Therefore, serum KL-6 has good sensitivity and specificity for the early diagnosis of these diseases. Occupational pneumoconiosis is an interstitial lung disease with a well-established etiology. Pervious study has shown that serum KL-6 level was higher in patients with occupational silicosis, occupational asbestosis, and dust-exposed workers compared to healthy controls. However, due to the limited sample size and the inconsistent findings on different studies, further research is needed to study the role of serum KL-6 in the early diagnosis of pneumoconiosis. Future studies should increase the sample size, improve the detection methods for serum KL-6, explore its feasibility as an early diagnostic biomarker for occupational pulmonary diseases, and investigate the efficacy andvalue of its combined application with other biomarkers in the early diagnosis of various pulmonary diseases, including occupational lung diseases, to fully exploit its predictive role in pulmonary diseases.

Objective To investigate the value of CT calcification type of hepatic alveolar echinococcosis(HAE)for predicting its lymph node metastasis.Methods Totally 100 patients with HAE confirmed by surgical pathology were retrospectively collected,among them 50 with lymph node metastases were divided into metastasis group,while the other 50 with lymph node reactive hyperplasia into non-metastasis group.Patients'general data,as well as preoperative CT findings,including the number,location,the maximum diameter and calcification type of lesions were compared between groups.Multivariate logistic regression analysis was performed for clinical and CT features being significant different between groups to screen the independent predictors of HAE lymph node metastasis.Receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the predictive efficacy of CT calcification type alone and combining with other independent predictors for predicting node metastasis of HAE.Results A total of 62 groups of lymph node metastases were detected in 50 patients in metastasis group,including 39 cases with single group lymph node metastasis,10 cases with 2 groups lymph node metastasis and 1 case with 3 groups lymph node metastasis.There were significant differences of location,the maximum diameter and CT calcification type of HAE lesions within liver between groups(all P＜0.05),which were all independent predictors of HAE lymph node metastasis(all P＜0.05).The AUC of CT calcification type alone and combining with other independent predictors for predicting node metastasis of HAE was 0.757 and 0.859,respectively,which were significant different(P=0.002).Conclusion CT calcification type of HAE could effectively predict lymph node metastasis,and the predictive efficacy might be improved by combining location and maximum diameter of HAE lesions.

Objective:To determine the correlation between the diabetes mellitus control and periodontitis.Methods:This study was a cross-sectional survey using stratified system sampling model design. The target population was the patients with diabetes investigated from May to July 2018 in Huangpu District of Shanghai. In the present study, severe periodontitis was defined as at least at two sites in different quadrants with probing depth (PD)≥6 mm and clinical attachment loss (CAL)≥ 5 mm. Edentulous induced by periodontitis were also classified as severe periodontitis and the others were classified as non-severe periodontitis subjects. Diabetes control levels were divided into the following three groups: poorly controlled group [glycated hemoglobin (HbA1c)>7.5% and fasting blood glucose (FPG)>7.0 mmol/L], well controlled group (6.5%≤HbA1c≤7.5％ or 6.1 mmol/L≤FPG≤7.0 mmol/L) and ideally controlled group (HbA1c<6.5% and FPG<6.1 mmol/L). SPSS 25.0 was used for statistical analysis. Chi square test was used for demographic data and frequency distribution, α=0.05, two-sided test. Ordinal regression model was used for PD and diabetes control status to balance confounding factors (including age, gender, education and smoking status). After matching the propensity scores between severe periodontitis group and non-severe periodontitis group, logistic regression analysis was used to analyze the level of diabetes control and periodontitis.Results:A total of 5 220 adults over the age of 18 with a medical history of diabetes participated in the survey, of which 3 064 subjects with diabetes mellitus type 2 (T2DM) who were given both oral and laboratory examinations and were included in this study. Statistics showed that the prevalence of moderate and severe periodontitis was 10.57% (324/3 064). In the severe periodontitis group, 79.01% (256/324) of the subjects were over 65 years old, 55.56% (180/324) were male, 58.33% (189/324) had lower education level than high school level, and 21.91% (71/324) were smokers, which were significantly higher than those in the non-severe periodontitis group ( P<0.01). In different T2DM status groups, the percentage of severe periodontitis increased with the aggravation of T2DM status. In severe periodontitis group, the proportion of patients with poor glycemic control was higher. T2DM patients with poor glycemic control accounted for 68.52% (222/324) in severe periodontitis group, which was significantly higher than the proportion of non-severe periodontitis group of 60.99% (1 671/2 740) ( P<0.05). The regression coefficient of PD was 0.191, and PD had a significant negative effect on the level of blood glucose ( P<0.01). There was a significant positive correlation between diabetes glycemic control and severe periodontitis ( OR=2.800, P<0.05). Conclusions:In Huangpu District of Shanghai, among T2DM patients, the age of severe periodontitis group was higher than that of non-severe periodontitis group, most of them were male, with lower education level and higher proportion of smoking. The severity of diabetes was related to periodontitis and the proportion of severe periodontitis was higher in patients with poor glycemic control.

Objective:To evaluate the association between periodontitis and mild cognitive impairment (MCI), and explore the potential local oral risk factors for MCI.Methods:The study included 70 middle-aged and elderly subjects (44 females and 26 males) with periodontal disease who were first diagnosed by the Department of Periodontology or referred by the Department of Geriatrics in Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from January 2021 to January 2022. In this study, the control group consisted of periodontal disease patients without cognitive impairment, and the case group (MCI group) consisted of those diagnosed with MCI referred by the geriatrics specialists. Full-mouth periodontal examinations of all subjects were performed and periodontal indicators were recorded by periodontists, while digital panoramic radiographs were taken. The severity of periodontitis was defined according to the 1999 classification, and the staging and grading of periodontitis were defined according to the 2018 American Academy of Periodontology and European Federation of Periodontology classification. The mini-mental state examination scale was chosen by geriatricians to evaluate the cognitive function of the included subjects. The cubital venous blood was drawn to detect the expression levels of inflammatory factors such as hypersensitive C-reactive protein (hs-CRP), interleukin (IL)-1β, IL-6 and tumor necrosis factor-α(TNF-α) in serum. Independent-samples t test and chi-square test were used to analyze the differences in population factors, periodontal-related indexes and serum inflammatory factors between the two groups (α=0.05). Odds ratios ( OR) for MCI according to the severity of periodontitis and main periodontal clinical indexes were calculated by binary Logistic analysis. Results:Thirty-nine subjects were included in the control group and thirty-one in the MCI group. The age of the study population was (58.3±6.2) years (range: 45-70 years). The comparison between two groups showed that the control group was with higher educational background (χ2=9.45, P=0.024) and 2.6 years younger than the MCI group [(57.1±6.0) years vs. (59.7±6.3) years, t=-1.24, P=0.082]. The number and proportion of moderate to severe periodontitis in control group were significantly lower compared to those in MCI group (17 cases with 43.6% vs. 23 cases with 74.2%, χ2=6.61, P=0.010), and the OR of moderate to severe periodontitis adjusted by age and educational background was 3.00 (95 %CI: 1.01-8.86, P=0.048). Compared with the grading (χ2=5.56, P=0.062) of periodontitis, staging had a greater impact on MCI (χ2=7.69, P=0.041), moreover the proportion of MCI in stage Ⅰ grade A periodontitis was significantly lower than any other type of periodontitis (χ2=13.86, P=0.036). In addition, less presence of deep periodontal pockets [probing depth (PD)≥6 mm] (17.9% vs. 41.9%, χ2=4.87, P=0.027), fewer number of PD≥4 mm (6.48±6.70 vs. 11.03±8.91, t=-2.44, P=0.017), lower plaque index (1.42±0.56 vs. 1.68±0.57, t=-1.91, P=0.059) and gingival index (1.68±0.29 vs. 1.96±0.30, t=-3.93, P<0.001) were in the control group than in the MCI group. However, there were no significant differences between the two groups in the levels of serum inflammatory factors, such as hs-CRP, IL-1β, IL-6 and TNF-α ( P>0.05). Conclusions:It appears a strong correlation between moderate to severe periodontitis and the incidence of MCI in middle-aged and elderly people. Moreover, deep and increased number of periodontal pockets, poor oral hygiene, and severe gingival inflammation can be potentially associated risk factors for MCI.

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism* ; Bipolar Disorder/metabolism* ; Depressive Disorder, Major/diagnosis* ; Early Diagnosis ; Humans ; Oxidative Stress