Objective To investigate and analysis the actuality and demands of scientific researchers in state clinical research facility of TCM, in order to provide evidences for policy making. Methods All the trainees taken part in the meeting for the training of clinical research method were assigned to answer the self-designed questionnaire. Results Of all these people, 47.58 percent people had senior professional title, 84.14 percent people had doctorate or master degree, 57.24 percent people had participated in project research at provincial or ministerial level as key personnel, 35.17 percent people had participated in a key disease research as directors, 65.52 percent people had taken methodology training of clinical research,30.34% of who trained by evidence-based medicine. The majority of these people had clear understanding in methodology of clinical research, who believed that evidence-based medicine and system evaluation are the most difficult subjects to understand and practice, hoping to learn more about the knowledge on statistics. Conclusion Clinical researchers of state clinical research facility of TCM had sound basis for scientific research, but relatively lacking of key disease research and systematic knowledge of scientific methodology, which needed to be enhanced.

Objective: To investigate the mutual prediction relationship between peer relationship and internalizing problem. Methods: One-year follow up survey was conducted with a sample of 220 preschool children from 4 kindergartens in Shandong province. The quality of peer relationship and degree of internalizing problem were evaluated with the Peer Relationship Scale and the Child Behavior Checklist Cross-lagged panel analysis was used for mutual prediction among variables. Results: The quality of preschool children’s peer relationship showed an increasing trend with grade(F=6.40, 4.81, P<0.01), while the degree of internalizing problem showed a downward trend(F=7.65, 5.46, P<0.01). The predictive effect of pre-test peer relationship and internalizing problem on post-test corresponding behaviors were all statistically significant (β=0.56, 0.49, P<0.01). The predictive effect of pre-test peer relationship on post-test internalizing problem was statistically significant(β=-0.19, P<0.05). Conclusion Both peer relationship and internalizing problem has a certain stability across time, and early peer relationship and internalizing problem could predict later corresponding behaviors. Early peer relationship can predict later internalizing problem, while early internalizing problem cannot predict later peer relationship.

Objective To examine the short-term prognostic value of procalcitonin ( PCT ) combined with coagulation factors for cirrhotic patients complicated with spontaneous bacterial peritonitis (SBP).Methods Clinical data of 128 cirrhotic patients complicated with SBP admitted in Jinhua Central Hospital from June 2014 to October 2017 were retrospectively analyzed .In 3 months after admission , 83 patients survived ( survival group ) and 45 patients died ( fatal group ) .The factors related to prognosis were analyzed with Logistic regression and the prediction model was constructed with the weights derived from regression coefficients.The ROC curve and the area under the curve (AUC) of combination of PCT with coagulation factors were used to predict the survival of patients .Results Univariate analysis indicated that the level of PCT , total bilirubin ( TBil ) , serum creatinine ( Scr ) , prothrombin time ( PT ) , prothrombin activity ( PTA ) , blood coagulation factor Ⅱ, Ⅴ, Ⅶ, Ⅸ, Ⅹ, Ⅺ and Ⅻ were factors affecting the prognosis of cirrhotic patients complicated with SBP (P<0.01).Multivariate analysis showed that PCT , blood coagulation factors Ⅴ and Ⅸ were independent factors of short-term prognosis of cirrhotic patients complicated with SBP.The constructed predictive model was Logit (P) =1.200+0.099 ×PCT-0.026 × clotting factor Ⅴ-0.038 ×clotting factor Ⅸ.The sensitivity and specificity of the model were 0.822 and 0.675, respectively, and the AUC was 0.829.Compared with the classic MELD score , the difference was not statistically significant (P>0.05).Conclusions The predictive model based on PCT and coagulation factors Ⅴand Ⅸcan effectively predict the short-term survival of cirrhotic patients complicated with SBP . The overall prognostic ability is not different from MELD score , but the model is more simple and easier to apply.

Objective: To observe the cellular damage of low-dose combined exposure to Hg, Pb and Cd on hippocampal neurons in rat. Methods: SH-SY5Y cells were randomly divided into 8 groups by 2×2×2 factorial design: control group, Pb exposure group, Hg exposure group, Pb+Hg exposure group, Pb+Cd exposure group, Hg+Cd exposure group and Pb+Cd+Hg exposure group. And the cell viabilities were measured. On this basis, an animal model was established. Twenty eight-week-old SD pregnant rats were randomly divided into four groups by random number table, and five in each group: the control group(distilled water), 1-fold metal mixture exposure group (1×MM, poisoning solution containing mercury chloride 0.15 mg/L, lead acetate trihydrate 25 mg/L, cadmium chloride 7.5 mg/L), 5-fold metal mixture exposure group (5×MM, poisoning solution containing mercury chloride 0.75 mg/L, lead acetate trihydrate 125.00 mg/L, cadmium chloride 37.50 mg/L), 10-fold metal mixture exposure group (10×MM, poisoning solution containing mercury chloride 1.50 mg/L, lead acetate trihydrate 250.00 mg/L, cadmium chloride 75.00 mg/L). Pregnant rats drank water until delivery. Twenty male pups were selected and exposed to these metals through breast milk until weaned. The heavy metals dose of poisoning water was adjusted, and then the weaned rats were exposed to heavy metals via drinking poisoning water until adulthood (postnatal day 83). The blood samples and brain hippocampus samples were collected to observe the ultrastructural changes of hippocampus, and to determine the levels of Hg, Pb and Cd in blood. In addition, apoptosis rate and fluorescence intensity of reactive oxygen species and intracellular free calcium concentration ([Ca²⁺]_i) in hippocampal neurons were measured. Results: Cellular factorial design analysis showed that Hg+Pb+Cd (at no observed adverse effect level, 1.0, 0.5 and 0.1 μmol/L, respectively)had a interaction on cell viability after 48 or 72 hours of combined exposure (P<0.05). The results of ultrastructure showed that mitochondria decreased, ridges and matrixes gradually dissolved in rat hippocampal neurons of 5×MM group; nuclear chromatin aggregated, more ridges and matrixes dissolved and the mitochondria also decreased in rat hippocampal neurons of 10×MM group. The concentration of Hg, Pb and Cd in the blood of 1×MM group, 5×MM group and 10×MM group were higher than those in the control group, and the differences were statistically significant (P<0.001). There was no significant difference in apoptosis rate between the 1×MM group and the control group. The apoptosis rate of 5×MM group and 10×MM group was higher than that in the control group, and the differences were statistically significant (P<0.001). There was no statistically significant difference in the fluorescence intensity of reactive oxygen species in hippocampal neurons of the 1×MM group and the control group. The fluorescence intensity of reactive oxygen species in the 5×MM group and the 10×MM group was higher than that in the control group, the difference was statistically significant (P<0.05). There was no significant difference in the fluorescence intensity of [Ca²⁺]_i between the 1×MM group and the control group. The fluorescence intensity values of [Ca²⁺]_i in the 5×MM group and the 10×MM group were higher than the control group, the differences were statistically significant (P<0.001). Conclusion Low-level combined exposure to Hg, Pb, and Cd caused synergistic neurotoxic damage, and the process may be related to the changes of neuronal apoptosis, reactive oxide species, and [Ca²⁺]_i levels.

Objective: To investigate the clinical effect of concentrated growth factor (CGF) applied in guided bone regeneration (GBR) for severe bone deficiency in the anterior maxilla. Methods : Forty patients with bone defects in the anterior maxilla were chosen to be treated with GBR, 20 patients were treated with CGF applied in GBR as the observation group, and the other 20 patients were treated only with GBR as the control group. The evaluation of wound healing was performed after the operation, and bone augmentation was evaluated half a year after the operation. Results: The first-stage healing rate of soft tissue wounds in the observation group was 100% and 75% in the control group, and the primary healing rate in the observation group was better than that in the control group (P=0.017). The changes in bone width of the observation group were （3.70 ± 0.28） mm, and those of the control group were （2.96 ± 0.16） mm. The bone augmentation in the observation group was higher than that in the control group (P=0.000). Conclusion CGF applied in GBR has a good effect on bone augmentation for severe bone deficiency in the anterior maxilla.

Objective:To investigate the clinical value of muscle index changing value during neoadjuvant chemotherapy in predicting the prognosis of gastric cancer after radical gastrec-tomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 362 gastric cancer patients undergoing neoadjuvant chemotherapy combined with radical gastrectomy in 3 medical centers, including 163 cases in Fujian Medical University Union Hospital, 141 cases in the Affiliated Hospital of Qinghai University and 58 cases in St. Mary′s Hospital, from January 2010 to December 2017 were collected. There were 270 males and 92 females, aged from 26 to 79 years, with a median age of 61 years. Of 362 patients, 304 cases in Fujian Medical University Union Hospital and the Affiliated Hospital of Qinghai University were allocated into modeling group and 58 cases in St. Mary′s Hospital were allocated into validation group. Observation indicators: (1) changes of indicators including body composition parameters, tumor markers and stress status indicators in patients in modeling group during neoadjuvant chemotherapy; (2) follow-up and survival of patients; (3) analysis of risk factor affecting prognosis of patients in modeling group; (4) construc-tion and comparison of prognostic prediction models; (5) evaluation of prognostic prediction models. Follow-up was conducted using outpatient examination, telephone interview and mail communication to detect postoperative survival of patients up to April 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Univariate and multivariate analysis were performed using the COX proportional hazard model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Changes of indicators including body composition parameters, tumor markers and stress status indicators in patients in modeling group during neoadjuvant chemotherapy: the subcutaneous adipose index, visceral adipose index, muscle index, carcinoem-bryonic antigen, CA19-9, body mass index, prognostic nutritional index and modified systemic inflammation score of 304 gastric cancer patients in the modeling group before neoadjuvant chemotherapy were 31.2 cm 2/m 2(range, 0.6?96.0 cm 2/m 2), 25.1 cm 2/m 2(range, 0.1?86.3 cm 2/m 2), 47.1 cm 2/m 2(range, 27.6?76.6 cm 2/m 2), 43.2 μg/L(range, 0.2?1 000.0 μg/L), 108.7(range, 0.6? 1 000.0)U/mL, 21.9 kg/m 2(range, 15.6?29.7 kg/m 2), 46.8(range, 28.6?69.0), 1.0±0.8, respectively. The above indicators of 304 gastric cancer patients in the modeling group before radical gastrec-tomy were 32.5 cm 2/m 2(range, 5.1?112.0 cm 2/m 2), 25.4 cm 2/m 2(range, 0.2?89.0 cm 2/m 2), 47.0 cm 2/m 2(range, 16.8?67.0 cm 2/m 2), 17.0 μg/L(range, 0.2?1 000.0 μg/L), 43.9 U/mL(range, 0.6?1 000.0 U/mL), 21.6 kg/m 2(range, 31.1?29.0 kg/m 2), 47.7(range, 30.0?84.0), 1.0±0.8, respectively. The changing value of above indicators of 304 gastric cancer patients in the modeling group during neoadjuvant chemotherapy were 1.4 cm 2/m 2(range, ?31.0?35.1 cm 2/m 2), 0.2 cm 2/m 2(range, ?23.5?32.6 cm 2/m 2), ?0.1 cm 2/m 2(range, ?18.2?15.9 cm 2/m 2), ?26.2 μg/L(range, ?933.5?89.9 μg/L), ?64.9 U/mL(range, ?992.1?178.6 U/mL), ?0.3 kg/m 2(range, ?9.7?7.1 kg/m 2), 0.9(range, ?27.1?38.2), 0.0±0.8, respec-tively. (2) Follow-up and survival of patients: 284 of 304 patients in the modeling group were followed up for 3 to 130 months, with a median follow-up time of 36 months. During follow-up, 130 cases died of tumor recurrence and metastasis and 9 cases died of non-tumor causes. The 5-year overall survival rate was 54.6%. Fifty-two of 58 patients in the validation group were followed up for 2 to 91 months, with a median follow-up time of 29 months. During follow-up, 21 cases died with the 5-year overall survival rate of 63.8%. (3) Analysis of risk factor affecting prognosis of patients in modeling group: results of univariate analysis showed that the postoperative pathological type and postoperative pathological staging were related factors affecting 5-year overall survival rate [ hazard ratio=1.685, 2.619, 95% confidence interval(CI): 1.139?2.493, 1.941?3.533, P<0.05] and 5-year progression free rate survival of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio=1.468, 2.577, 95% CI: 1.000?2.154, 1.919?3.461, P<0.05). Results of multivariate analysis showed that the postoperative pathological type and postoperative pathological staging were independent influencing factors for 5-year overall survival rate of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio=1.508, 2.287, 95% CI: 1.013?2.245, 1.691?3.093, P<0.05) and the postoperative patholo-gical staging was an independent influencing factor for 5-year progression free survival rate of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio= 2.317,95% CI: 1.719?3.123, P<0.05). (4) Construction and comparison of prognostic prediction models: the area under curve (AUC) of prognostic prediction model of subcutaneous adipose index changing value, visceral adipose index changing value, carcinoembryonic antigen changing value, CA19-9 changing value, body mass index changing value, prognostic nutritional index changing value, modified systemic inflammation score changing value for 304 gastric cancer patients in the modeling group were 0.549(95% CI: 0.504?0.593), 0.501(95% CI: 0.456?0.546), 0.566(95% CI: 0.521?0.610), 0.519(95% CI: 0.474?0.563), 0.588(95% CI: 0.545?0.632), 0.553(95% CI: 0.509?0.597), 0.539(95% CI: 0.495?0.584). The AUC of prognostic prediction model of muscle index changing value was 0.661(95% CI: 0.623?0.705) with significant differences to the AUC of prognostic predic-tion model of subcutaneous adipose index changing value, visceral adipose index changing value, carcinoembryonic antigen changing value, CA19-9 changing value, body mass index changing value, prognostic nutritional index changing value, modified systemic inflammation score changing value, respectively ( Z=3.960, 5.326, 3.353, 4.786, 2.455, 3.448, 3.987, P<0.05). The optimum cut-off value was 0.7 cm 2/m 2 for prognostic prediction model of muscle index changing. Kaplan-Meier survival curve showed there were significant differences of overall survival and progression free survival for gastric cancer patients with subcutaneous adipose index changing value <0.7 cm 2/m 2 and ≥0.7 cm 2/m 2 in the modeling group ( χ2 =27.510, 21.830, P<0.05). The nomogram prognostic prediction model was cons-tructed based on 3 prognostic indicators including muscle index change value combined with postoperative pathological type and postoperative pathological staging and the AUC of nomogram prognostic prediction model were 0.762(95% CI: 0.708?0.815) and 0.788(95% CI: 0.661?0.885) for the modeling group and the validation group, respectively. The AUC of postoperative pathological staging prognostic prediction model were 0.706(95% CI: 0.648?0.765) and 0.727(95% CI: 0.594?0.835)for the modeling group and the validation group, respectively. There were significant differences of the AUC between the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging and the postoperative pathological staging prognostic prediction model in the modeling group and the validation group, respectively ( Z=3.522, 1.830, P<0.05). (5) Evaluation of prognostic prediction models: the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging showed that patients with score of 0-6 were classified in the low risk group, patients with score of >6 and ≤10 were classified in the moderate-low risk group, patients with score of >10 and ≤13 were classified in the moderate-high risk group and patients with score of >13 were classified in the high risk group. Kaplan-Meier survival curve showed there were significant differences of the overall survival between the low risk group, moderate-low risk group, moderate-high risk group and high risk group patients in the modeling group and the validation group, respectively ( χ2 =75.276, 14.989, P<0.05). Results of decision making curve showed the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging had better clinical utility than the postoperative pathological staging prognostic prediction model in the modeling group and the validation group. Conclusions:The muscle index changing value of gastric cancer patient during neoadjuvant chemotherapy can be used as a prognostic indicator for gastric cancer patient prognosis after radical gastrectomy. The risk score of the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging can be used to evaluate the survival and prognosis of gastric cancer patients after radical gastrectomy.

OBJECTIVE：To systematically evaluate the effects of CYP1A2 gene polymorphisms on blood concentrations of antipsychotic drugs （haloperidol，clozapine，olanzapine），and to provide evidence-based reference for the clinical drug use . METHODS：Retrieved from Cochrane Library ，PubMed，Embase，CBM，CNKI and Wanfang data ，during the inception to Nov. 2019，cross-sectional study was conducted to investigate the effects of CYP1A2 gene polymorphisms on blood concentrations of antipsychotic drugs （haloperidol，clozapine，olanzapine）were collected. After screening the literature ，extracting the data and quality evaluation with Q-Genie tool ，Meta-analysis was performed by using Rev Man 5.3 software. RESULTS ：A total of 11 cross-sectional studies were included ，with a total of 914 patients. Of these ，haloperidol was used in 2 studies，clozapine was used in 5 studies，and olanzapine was used in 4 studies. Meta-analysis showed that there was no statistically significant difference in the blood concentration of haloperidol between CYP1A2（－2964G＞A）G/G type and G/A+A/A type [SMD ＝－0.22，95％CI（－0.66， 0.23），P＝0.35]. The blood concentration of clozapine in CYP1A2（－163C＞A）A/C type was significantly lower than C/C type [SMD ＝0.31，95％CI（0.01，0.62），P＝0.04]；there was no statistical significance in blood concentration of clozapine between A/A type and C/C type [SMD ＝0.09，95％CI（－0.21，0.40），P＝0.56]，between A/A type and A/C type [SMD ＝－0.22，95％CI（－0.55， 0.10），P＝0.18]，between CYP1A2（－2467delT）delT/delT type and T/T type [SMD ＝－0.11，95％CI（－0.75，0.52），P＝0.72]， between delT/T type and T/T type [SMD ＝0.01，95％CI（－0.33，0.34），P＝0.97]，between delT/delT type and delT/T type [SMD ＝ －0.15，95％CI（－0.80，0.05），P＝0.66]. The blood concentration of olanzapine in CYP1A2（－163C＞A）A/A type was signifi- cantly lower than A/C type [SMD ＝－0.31，95％CI（－0.55， － 0.08），P＝0.009]；there was no statistically significant difference in the blood concentration of olanzapine between A/A liukefeng-num.1@163.com type and C/C type [SMD ＝－0.20，95％CI（－0.61，0.21），P＝ 0.34]，between A/C type and C/C type [SMD ＝0.06，95％CI E-mail：hnmuzj@163.com （－0.35，0.47），P＝0.77]，between CYP1A2（－2467delT）delT/T type and T/T type [SMD ＝0.28，95％CI（－0.15，0.71），P＝0.20]. CONCLUSIONS：CYP1A2（－163C＞A）A/C type is related to the reduction of clozapine blood concentration ，and A/A type is related to the reduction of olanzapine blood concentration. CYP1A2 （－163C＞A）gene polymorphism is significance for guiding individualized medication of schizophrenia patients.

Objective:To investigate the association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in China.Methods:A total of 2 393 participants aged 65 years and older were recruited in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study, during 2017 to 2018. Information on demographics characteristic, life style and health status were collected by questionnaire and physical examination, and venous blood was collected to detect the levels of blood oxidative stress and hypertriglyceridemia. The linear or non-linear association between oxidative stress and hypertriglyceridemia was described by restrictive cubic splines (RCS) fitting multiple linear regression model. The generalized linear mixed effect model was conducted to assess the association between oxidative stress and hypertriglyceridemia.Results:A total of 2 393 participants, mean age was 84.6 years, the youngest was 65 and the oldest was 112, the male was 47.9%(1 145/2 393), the triglyceride level was (1.4±0.8) mmol/L. The hypertriglyceridemia detection rate was 9.99%(239/2 393). The results of multiple linear regression model with restrictive cubic spline fitting showed that MDA level was linear association with triglyceride level; SOD level was nonlinear association with triglyceride level. MDA level had significantly association with hypertriglyceridemia, and the corresponding OR value was 1.063 (95% CI: 1.046,1.081) with 1 nmol/ml increment of blood MDA; SOD level had significantly association with hypertriglyceridemia, and the corresponding OR value was 0.986(95% CI: 0.983,0.989) with 1 U/ml increment of blood SOD. Conclusion:Among the elderly aged 65 and older in 9 longevity areas in China, MDA and SOD levels were associated with the risk of hypertriglyceridemia.

Objective:To investigate the association between blood lead concentrations and cognition impairment among Chinese older adults aged 65 or over.Method:Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. This study included 1 684 elderly aged 65 years and older. Information about demographic characteristics, socioeconomic factors, health status and cognitive function score of respondents were collected by questionnaire survey and physical examination. Venous blood of the subjects was collected to detect the blood lead concentration. Subjects were stratified into four groups ( Q 1- Q 4) by quartile of blood lead concentration. Multivariate logistic regression model was used to analyze the association between blood lead concentration and cognitive impairment. The linear or non-linear association between blood lead concentration and cognitive impairment were described by restrictive cubic splines (RCS). Results:Among the 1 684 respondents, 843 (50.1%) were female and 191 (11.3%) suffered from cognition impairment. After adjusting for confounding factors, the OR value and 95% CI of cognition impairment was 1.05 (1.01-1.10) for every 10 μg/L increase in blood lead concentration in elderly; Compared with the elderly in Q 1, the elderly with higher blood lead concentration had an increased risk of cognitive impairment. The OR value and 95% CIof Q2, Q3 and Q4 groups were 1.19 (0.69-2.05), 1.45 (0.84-2.51) and 1.92 (1.13-3.27), respectively. Conclusion:Higher blood lead concentration is associated with cognitive impairment among the elderly aged 65 years and older in 9 longevity areas in China.