Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

Objective:To analyze the influencing factors for depression in primary school children aged 9-10 years in Jiangsu Province, and to construct a risk prediction model.Methods:A retrospective study.A total of 1 162 primary school children aged 9-10 years from 3 primary schools in 3 regions of Jiangsu Province were recruited.Their demographic data were collected, and they were surveyed by the Depression Anxiety Stress Scales-21 (DASS-21), the Strengths and Difficulties Questionnaire (SDQ), and the Family Environment Scale (FES). Children were divided into control group (1 059 cases) and depression group (103 cases) based on the depression scores obtained from the DASS-21 scale.Multivariate Logistic regression analysis was used to analyze the influencing factors for depression in primary school students aged 9-10 and construct a risk prediction model. Results:There were significant differences in the economic development region, physical activities, academic performance, student cadres, parents′ education level, frequency of parental quarrels, SDQ and FES dimension scores between control group and depression group (all P<0.05). Among them, economic development areas (Northern Jiangsu and Southern Jiangsu), student cadres, father′s education level (elementary school and below) and intimacy of the FES scale were protective factors for depression in elementary school children; while emotional symptoms, peer problems and the total difficulty score in the SDQ scale, and the conflict in the FES scale were the risk factors for depression in elementary school children.The prediction model was created based on the influencing factors: Logit ( P)=-1.390×economic development area (Northern Jiangsu) -1.508×economic development area (Southern Jiangsu) -1.248×student cadres -2.206×father′s education level (primary school and below) -1.145×father′s education level (junior high school)+ 3.316×emotional symptoms in the SDQ+ 0.979×peer problems in the SDQ+ 2.520×total difficulty score in the SDQ -1.697×cohesion in the FES + 0.760×conflict in the FES -0.678.The area under the curve of receiver operating characteristic was 0.931, with the sensitivity and specificity of 85.42% and 91.83%, respectively. Conclusions:The regional level of economic development, class or school cadres, father′s education level, peer problems, total difficulty score, cohesion and conflict in the family are influencing factors for depression among primary school children aged 9-10 years in Jiangsu Province.The created prediction model can effectively assess the depressive risk factors in this population, which is conductive to achieve the early recognition and intervention of depression in them.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Objective:To analyze the risk of missed diagnosis in patients with PI-RADS score>3 and negative prostate initial biopsy and to explore its risk factors.Methods:The clinical data of 268 patients with negative prostate biopsy in Northern Jiangsu People's Hospital from May 2013 to December 2018 were retrospectively analyzed. The patients were divided into observation group (PI-RADS score>3) and control group (PI-RADS score≤ 3) according to different PI-RADS scores. There were insignificant differences in age [(67.4(60.0, 74.0)years and 65.6(66.5, 72.0)years], prostate volume of initial biopsy [62.4(40.0, 72.0)ml and 60.8(38.0, 77.0)ml], biopsy cores [ 20.6(18.0, 22.0)cores and 20.4(18.0, 22.0)cores] between the observation group (n=124) and the control group(n=144)(all P>0.05). But there were significant differences in PSA [17.5(6.5, 23.0)ng/ml and 11.5(6.3, 12.0)ng/ml], PSAD[0.316(0.128, 0.363)ng/ml 2 and 0.211(0.106, 0.256)ng/ml 2], prostate inflammation of the initial biopsy [70 (56.5%) and 32 (22.2%)] between the observation group and the control group(all P<0.05). According to the follow-up results after the initial biopsy, the two groups of repeated biopsy were compared.Furthermore, Logistic regression was used to conduct univariate and multivariate analysis to explore the risk factors of patients with PI-RADS>3 for positive repeated biopsy. At the same time, the receiver operating characteristic curve (ROC curve) was used to analyze the accuracy of the risk factors. Results:There were significant differences in repeated biopsy rate [ 27.4%(34/124)and 14.6%(21/144)], CsPCa detection rate[ 41.4%(14/34) and 4.8%(1/21)]between the observation group and the control group(all P<0.05). The positive rate of repeated biopsy in the observation group (41.1%) was higher than that in the control group (23.8%), but there was no statistical difference ( P=0.248). The risk of positive repeated biopsies in the observation group was 2.24 times than that in the control group. Univariate analysis found repeated biopsy PSA ( P =0.02, OR=1.438, 95% CI 1.161-1.896), PSA ratio (repeated biopsy PSA/initial biopsy PSA) ( P=0.011, OR=10.087, 95% CI 1.714-59.36) were risk factors for positive of repeated biopsy in patients with PI-RADS score >3. Multivariate analysis also found that repeated biopsy PSA ( P=0.017, OR=1.15, 95% CI 1.076-2.123), PSA ratio ( P=0.032, OR=10.2, 95% CI 0.883-116.168) were risk factors for positive repeated biopsy. ROC curve analysis, the accuracy of repeated biopsy PSA (AUC=0.971, P<0.001, 95% CI 0.926-1.000), PSA ratio (AUC=0.839, P=0.001, 95% CI0.707-0.971) to predict positive of repeated biopsy were high. The cut-off values were 21.3 ng/ml and 1.4, respectively. The accuracy was higher when combines repeated biopsy PSA with PSA ratio (AUC=0.993, P<0.001, 95% CI 0.974-1.000). Conclusions:Patients with negative PI-RADS score > 3 have a higher risk of missed diagnosis of CsPCa than those with PI-RADS score≤3. When PSA>21.3 ng/ml and PSA ratio>1.4 during follow-up, the possibility of missed diagnosis in the initial biopsy is high.

Objective: To investigate the clinical value of modified transperineal template-guided prostate biopsy (mTTPB) in the detection of prostate cancer. Methods: A total of 217 patients were enrolled in this study. All the patients were randomly divided into 2 groups. The control group (n=112) underwent transperineal template-guided prostate biopsy (TTPB) which was traditional transperineal template-guided 11-region biopsy. On the basis of the control group, the apex of prostate was divided into four areas for biopsy in the observation group (mTTPB). The positive rate of apex and the incidence of complications were analyzed. The prostatic specimens from the radical prostatectomy underwent whole mount sections examination. The prostate biopsy results were compared with the postoperative pathological results. Results: The average age of the control group and the observation group were (68.5±7.9) years and (67.3±8.5) years, PSA were (31.2±18.9) ng/ml and (29.7±19.5) ng/ml, prostate volume were (44.6±15.2) ml and (41.3±17.3) ml, respectively. In the control group, the positive rates of prostate cancer in 1-10 region were 24.1% (27/112), 27.7%(31/112), 23.2% (26/112), 28.6% (32/112), 26.8% (30/112), 25.0% (28/112), 26.8% (30/112), 19.6% (22/112), 25.9% (29/112), 25.0% (28/112), respectively, with an average of 25.3%. In the observation group, the positive rates in 1-10 region were 27.6% (29/105), 28.6% (30/105), 22.9% (24/105), 26.7% (28/105), 25.7% (27/105), 24.8% (26/105), 27.6% (29/105), 21.9% (23/105), 27.6% (29/105), 26.7% (28/105), respectively, with an average of 26.0%. There was no statistical difference between the two groups (P=0.904). The positive rate of apical prostate cancer in the control group and observation group was 37.5% (42/112) and 44.8% (47/105), respectively, and there was no statistical difference between the two groups (P=0.277). Patients were grouped according to PSA>20 ng/ml and PSA≤20 ng/ml. When PSA>20 ng/ml, the positive rate of apex was 58.6% (34/58) and 56.6% (30/53) respectively in the control group and the observation group, and there was no statistical difference between the two groups (P=0.830). When PSA≤20 ng/ml, the positive rate of apex was 14.8% (8/54) in the control group and 32.7% (17/52) in the observation group, with statistically significant differences (P=0.030). Before radical prostatectomy, 12 cases (57.1%) in the control group and 19 cases (73.1%) in the observation group showed apical invasion by biopsy. Results of whole mount sections examination in the control group showed that there were 19 cases (90.5%) with apical invasion, which was statistically different from that before surgery (P=0.035). The results of whole mount sections examination in the observation group showed that there were 23 cases (88.5%) with apex invasion, which had no statistical difference compared with that before surgery (P=0.291). There were no significant differences in the incidence of hematuria, fever, urinary retention and perineal discomfort between the observation group and the control group (all P>0.05). Conclusions mTTPB can significantly improve the detection rate of apical prostate cancer without increasing the incidence of complications, especially for patients with PSA≤20 ng/ml. Hence is safe and efficacious.

Objective Create patient-derived xenograft (PDX) model of bone and soft tissue sarcoma,and analyze the success rate of PDX model,observe the effects of chemotherapy on PDX models and its coincidence,and provide a theoretical basis for screening sensitive second and third line drugs.Methods Collected 31 cases of bone and soft tissue sarcoma from January 2015 to May 2016,which included 12 male and 19 female,with an average age of (28.5±19.9) y.The tumor tissue was obtained the day of operation,and it was cut into 2 mm3 pieces and injected into the flank of BAL B/C nude mice or SCID mice.Tumor was passaged when the diameter reached 1-2 cm and the P0 tissue was froze.If there was no obvious tumor mass grows out for 3 months,the model creation will be stopped.We inoculated the mice with patients sample with or without chemotherapy,observed the effect of chemotherapy on the success rate of PDX modeling and the success rate of modeling of different pathological types,and also observed the relationship between the success rate of PDX modeling and the prognosis of patients.For the drug sensitivity test,3 mice was used in each group,and chemotherapy was given,T/C was used to evaluate the inhibition ratio after drug treatment.Results 31 PDX models were inoculated.The total success rate is 45.2％.Pathology of the PDX models and their success rates:24 osteosarcoma models,success rate is 37％;2 leiomyosarcoma models,success rate is 100％;2 chondrosarcoma models,success rate is 50％;1 Ewing sarcoma model successed;1 fibrosarcoma model and 1 synovial sarcoma model,were not successed.Post chemotherapy model success rate is 33％ (4/12),compared with 53％(10/19) of model success rate that without chemotherapy.And there is relationship between success rate of PDX model creation and patient outcome.The faster the PDX model creation,the worse the outcome.The drug sensitivity of PDX model coincides the clinical situation.Conclusion The success rate of creating PDX model of bone and soft tissue sarcoma is around 30％-40％,and it is related to the pathology and whether got chemotherapy or not,PDX models coincide sarcomas clinical situation,and it is hopefully to use PDX model in selecting personalized drugs.

Objective To provide a practical device and protocol to hold conscious rats for subsequent operations which can overcome the disadvantages of existing methods .Users can complete the experiment more efficiently , with or without prior experience .Methods Using transparent plastic film , plastic sealing machine and sponge to make a simple device for holding rats , by taking advantage of their escaping nature .To compare the performance of the new method and existing methods for holding and injecting rats .Results Compared with existing methods , the new device and method can reduce the time-consuming to hold rats by 44.7%, from 18.13 seconds to 10.03 seconds.For holding and injecting , the new method can reduce the time-consuming by 55.3%, from 139.33 seconds to 52.26 seconds .Conclusions The new device and method is good for holding and injecting rats or drawing blood from the caudal veins .It can shorten the time of operation and reduce the stress reaction in the animals .It’ s especially helpful for inexperienced experimenters such as students in teaching and research tasks .