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 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 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 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.

OBJECTIV E To establish the method for evaluating the quality o f Plantago asi atica and fried P. asiatica . METHODS The fingerprints of 15 batches of P. asiatica and 15 batches of fried P. asiatica were established by HPLC. The common peaks were identified with the Similarity Evaluation System for Chromatographic Fingerprinting of TCM （2012 edition）， and similarity evaluation was performed. Analysis of chemical pattern recognition was performed by using SPSS 25.0 and SIMCA-P 14.1 software（cluster analysis ，principal component analysis and orthogonal partial least squares regression analysis ）. The markers which affected the difference in the quality between P. asiatica and fried P. asiatica were screened with variable importance projection（VIP）value greater than 1. RESULTS There were 18 common peaks in the fingerprints of 15 batches of P. asiatica and 13 common peaks in the fingerprints of 15 batches of fried P. asiatica . A total of 8 common peaks were found in both of them. Their similarities were greater than 0.920. Two common peaks were identified as geniposidic acid ，acteoside. The results of cluster analysis showed that when the spacing was 10，the 30 batches of samples could be clustered into three categories ，with S 1-S5 as one，S16-S20 as one ，S6-S15 and S 21-S30 as one . The results of the pri ncipal component analysis showed that the cumulative variance contribution rate of the first two principal components was 82.575％ . The results of the orthogonal partial least squares regression analysis showed that the VIP values of the three common peaks were greater than 1，namely peak E（acteoside）， peak D （geniposidic acid ） and peak G. CONCLUSIONS Established fingerprints are stable ，simple sina.com and rapid. It can be used for the quality evaluation of P. asiatica and fried P. asiatica ，by combining with analysis of chemical pattern recognition. Acteoside ，geniposidic acid and the component represented by peak G may be the markers affecting the difference in quality of P. asiatica and fried P. asiatica .

ObjectiveTo explore the effects of anxiety and depression on Internet gaming disorder in medical students， and to evaluate the moderating effect of gender， so as to provide references for the prevention and intervention of Internet gaming disorder in medical students. MethodsIn November 2021， a total of 11 771 medical students from a medical college in Sichuan province participated in an online survey through Wenjuanxing platform. Participants completed the Self-rating Anxiety Scale （SAS）， Self-rating Depression Scale （SDS） and the nine-item Internet Gaming Disorder Scale-Short Form （IGDS9-SF）. Then a hierarchical multiple regression analysis was conducted to discuss the moderating role of gender in the relationships between anxiety， depression and Internet gaming disorder in medical students. Results①Males scored lower on SDS （t=-8.302， P<0.01）， and higher on IGDS9-SF than females （t=33.384， P<0.01）. ②SAS score of medical students was positively correlated with SDS score （r=0.735， P<0.01）， SAS and SDS scores were positively correlated with IGDS9-SF score in medical students （r=0.288， 0.238， P<0.01）. ③Anxiety and depression could positively predict Internet gaming disorder （β=0.245， 0.058， t=18.864， 4.444， P<0.01）. ④Gender played a moderating effect between anxiety and Internet gaming disorder （β=-0.194， t=-4.518， P<0.01）. ConclusionAnxiety and depression have a positive predictive effect on Internet gaming disorder in medical students. Furthermore， the effects of anxiety on Internet gaming disorder are moderated by gender， and the anxiety of male students exhibits a markedly stronger impact on Internet gaming disorder than that of female students.