There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

AIM: To explore the mechanism of Ginkgo biloba in the treatment of steroid-induced osteonecrosis of the femoral head based on network pharmacology. METHODS: The active ingredients and targets of Ginkgo biloba were predicted by the TCMSP, ADME, and PharmMapper databases. The disease targets related to steroid-induced osteonecrosis of the femoral head were searched by the GeneCards and OMIM databases. Cytoscape 3.6.1 was used to construct a protein-protein interaction network. The core target analysis, modular analysis, GO enrichment analysis, and KEGG pathway analysis of the targets of Ginkgo biloba in the intervention of steroid-induced osteonecrosis of the femoral head were performed by the STRING database. RESULTS: In this study, a total of 16 active ingredients of Ginkgo biloba and 547 targets were screened, of which 133 targets were related to steroid-induced femoral head necrosis. By PPI network topology analysis, TP53, AKT1, IL6, VEGFA, MAPK1, JUN, MAPK8, EGFR, EGF, and MYC were identified as the core targets. GO modularization analysis showed that these core targets were mainly related to apoptosis and angiogenesis. GO enrichment analysis was used to analyze the biological processes, cellular localization, and molecular functions of the core targets. KEGG enrichment analysis showed that the targets were mainly involved in molecular signaling pathways, among which the PI3K/AKT signaling pathway was the most relevant. CONCLUSION: Ginkgo biloba can inhibit steroid-induced osteonecrosis of the femoral head through multiple components, targets, and pathways, which provides the theoretical basis and reference for subsequent cell and animal experiments.

OBJECTIVE: To review the research progress in the construction strategy and application of bone/cartilage immunomodulating hydrogels. METHODS: The literature related to bone/cartilage immunomodulating hydrogels at home and abroad in recent years was reviewed and summarized from the immune response mechanism of different immune cells, the construction strategy of immunomodulating hydrogels, and their practical applications. RESULTS: According to the immune response mechanism of different immune cells, the biological materials with immunoregulatory effect is designed, which can regulate the immune response of the body and thus promote the regeneration of bone/cartilage tissue. Immunomodulating hydrogels have good biocompatibility, adjustability, and multifunctionality. By regulating the physical and chemical properties of hydrogel and loading factors or cells, the immune system of the body can be purposively regulated, thus forming an immune microenvironment conducive to osteochondral regeneration. CONCLUSION Immunomodulating hydrogels can promote osteochondral repair by affecting the immunomodulation process of host organs or cells. It has shown a wide application prospect in the repair of osteochondral defects. However, more data support from basic and clinical experiments is needed for this material to further advance its clinical translation process.
Hydrogels ; Cartilage ; Bone and Bones ; Tissue Engineering/methods*

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Objective:To investigate the feasibility and safety of laparoscopic radical resection of hilar cholangiocarcinoma at multiple centers in China.Methods:Between December 2015 and August 2019, the clinical data of 143 patients who underwent LRHC in Affiliated Hospital of North Sichuan Medical College, Second Hospital of Hebei Medical University, Affiliated Hospital of Xuzhou Medical University, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Hunan Provincial People′s Hospital, the First Hospital Affiliated to Army Medical University, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, West China Hospital of Sichuan University, Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Chongqing Medical University were collected prospectively. There were 92 males and 51 females with age of (64±11) years (range: 53 to 72 years). Bismuth type: type I, 38 cases (26.6%), type Ⅱ, 19 cases (13.3%), type Ⅲa, 15 cases (10.5%), type Ⅲb, 28 cases (19.6%) and type Ⅳ, 43 cases (30.0%). The patients within the first 10 operation cases in each operation time (the first 10 patients in each operation team) were divided into group A (77 cases), and the patients after 10 cases in each operation time were classified as group B (66 cases); the cases with more than 10 cases in the center were further divided into group A 1 (116 cases), and the center with less than 10 cases was set as group A 2 (27 cases). T test or Wilcoxon test was used to compare the measurement data between groups, and the chi square test or Fisher exact probability method was used to compare the counting data between groups. Kaplan Meier curve was used for survival analysis. Results:All patients successfully completed laparoscopic procedure. The mean operation time was (421.3±153.4) minutes (range: 159 to 770 minutes), and the intraoperative blood loss was 100 to 1 500 ml (median was 300 ml) .Recent post-operative complications contained bile leakage, abdominal bleeding, abdominal infection, gastrointestinal bleeding, and delay gastric emptying, pulmonary infection, liver failure, et al.The post-operative hospital stay was (15.9±9.2) days. The operation time in group B was relatively reduced ( (429.5±190.7)minutes vs. (492.3±173.1)minutes, t=2.063, P=0.041) and the blood loss (465 ml vs. 200 ml) was also reduced ( Z=2.021, P=0.043) than that in group B. The incidence of postoperative biliary fistula and lung infection in patients in group A was significantly higher than that in group B (χ 2=4.341, 0.007; P=0.037, 0.047) .Compared with group A 2, the operation time in group A 1 was relatively reduced( (416.3±176.5)minutes vs. (498.1±190.4)minutes, t=2.136, P=0.034) , the incidence of bile leakage and abdominal cavity infection in group A 1 was lower than that in group A 2 (χ 2=7.537, 3.162; P=0.006, 0.046) . Kaplan Meier survival curve showed that the difference of short-term survival time between group A and group B was statistically significant ( P<0.05) . Conclusions:The completion of laparoscopic hilar cholangiocarcinoma radical surgery is based on improved surgical skills, and proficiency in standardized operation procedures.It is feasible for laparoscopic radical resection of hilar cholangiocarcinoma to well experienced surgeon with cases be strictly screened, but it is not recommended for widespread promotion at this exploratory stage.

Objective:To investigate the feasibility and safety of laparoscopic radical resection of hilar cholangiocarcinoma at multiple centers in China.Methods:Between December 2015 and August 2019, the clinical data of 143 patients who underwent LRHC in Affiliated Hospital of North Sichuan Medical College, Second Hospital of Hebei Medical University, Affiliated Hospital of Xuzhou Medical University, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Hunan Provincial People′s Hospital, the First Hospital Affiliated to Army Medical University, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, West China Hospital of Sichuan University, Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Chongqing Medical University were collected prospectively. There were 92 males and 51 females with age of (64±11) years (range: 53 to 72 years). Bismuth type: type I, 38 cases (26.6%), type Ⅱ, 19 cases (13.3%), type Ⅲa, 15 cases (10.5%), type Ⅲb, 28 cases (19.6%) and type Ⅳ, 43 cases (30.0%). The patients within the first 10 operation cases in each operation time (the first 10 patients in each operation team) were divided into group A (77 cases), and the patients after 10 cases in each operation time were classified as group B (66 cases); the cases with more than 10 cases in the center were further divided into group A 1 (116 cases), and the center with less than 10 cases was set as group A 2 (27 cases). T test or Wilcoxon test was used to compare the measurement data between groups, and the chi square test or Fisher exact probability method was used to compare the counting data between groups. Kaplan Meier curve was used for survival analysis. Results:All patients successfully completed laparoscopic procedure. The mean operation time was (421.3±153.4) minutes (range: 159 to 770 minutes), and the intraoperative blood loss was 100 to 1 500 ml (median was 300 ml) .Recent post-operative complications contained bile leakage, abdominal bleeding, abdominal infection, gastrointestinal bleeding, and delay gastric emptying, pulmonary infection, liver failure, et al.The post-operative hospital stay was (15.9±9.2) days. The operation time in group B was relatively reduced ( (429.5±190.7)minutes vs. (492.3±173.1)minutes, t=2.063, P=0.041) and the blood loss (465 ml vs. 200 ml) was also reduced ( Z=2.021, P=0.043) than that in group B. The incidence of postoperative biliary fistula and lung infection in patients in group A was significantly higher than that in group B (χ 2=4.341, 0.007; P=0.037, 0.047) .Compared with group A 2, the operation time in group A 1 was relatively reduced( (416.3±176.5)minutes vs. (498.1±190.4)minutes, t=2.136, P=0.034) , the incidence of bile leakage and abdominal cavity infection in group A 1 was lower than that in group A 2 (χ 2=7.537, 3.162; P=0.006, 0.046) . Kaplan Meier survival curve showed that the difference of short-term survival time between group A and group B was statistically significant ( P<0.05) . Conclusions:The completion of laparoscopic hilar cholangiocarcinoma radical surgery is based on improved surgical skills, and proficiency in standardized operation procedures.It is feasible for laparoscopic radical resection of hilar cholangiocarcinoma to well experienced surgeon with cases be strictly screened, but it is not recommended for widespread promotion at this exploratory stage.

Objective: To explore experience of wound treatment of extremely severe mass burn patients involved in August 2nd Kunshan factory aluminum dust explosion accident. Methods: On August 2nd, 2014, 98 extremely severe burn mass patients involved in August 2nd Kunshan factory aluminum dust explosion accident were admitted to 20 hospitals in China. The patients with complete medical record were enrolled in the study and divided into microskin graft group with 56 patients and Meek skin graft group with 42 patients. Split-thickness skin in area of residual skin were resected to repair wounds of patients in microskin graft group and Meek skin graft group by microskin grafting and Meek miniature skin grafting, respectively. The residual wound size on 28 days post injury and wound infection after skin grafting of patients in the two groups, and position of donor site of all patients were retrospectively analyzed. Data were processed with t test and chi-square test. Results: The size of residual wound of patients in Meek skin graft group on 28 days post injury was (59±13)% total body surface area (TBSA), which was obviously smaller than that in microskin graft group [(70±14)%TBSA, t=4.379, P<0.05]. Twenty-nine patients in microskin graft group and 11 patients in Meek skin graft group suffered from obvious wound infection after skin grafting. Wounds of patients in two groups were repaired with residual skin around wound in head, trunk, groin, armpit, and uncommon donor sites of scrotum (4 patients), vola (10 patients), and toe or finger web (8 patients). Conclusions Meek skin graft is the first choice for wound repair of extremely severe burn mass patients, with faster wound healing, less wound infection. Uncommon donor sites of scrotum, vola, and toe or finger web can also be used for wound repair in case of lack of skin.

Objective To explore the effect of expressive writing intervention on social support,resilience and school maladjustment in university freshman.Methods Selecting the freshmen volunteer of 600 university freshmen of Shandong,through the scale before the test recovery and comprehensive scoring chosen the part of low grade college students as the intervention object and were divided into writing expression(n=60) person and control group(n=60).The intervention group received a positive subject writing expression and the control group in the normal writing.Before and after the intervention tested the social support rating scale,the resilience scale for Chinese adolescents and the the student adaptation to college questionnaire were tested to evaluate the effect of active writing expression intervention.Results (1)After intervention,the intervention group and the control group had significant differences among the scales,objective support (t =-2.36,P＜0.05),learning adaptation(t=-1.98,P＜0.05) and subjective support (t=-2.56,P＜0.05),target focus(t=-2.66,P＜0.01),emotional control(t=-2.81,P＜0.01),family support (t=-3.46,P＜0.01),adaptation (t=-2.73,P＜0.01),support utilization (t=-5.91,P＜0.01) and social support score (t =-4.04,P＜ 0.01),positive cognition (t=-2.73,P＜0.01),interpersonal assistance (t=-3.13,P＜0.01),resilience score (t=-7.40,P＜0.01),life adaptation (t=-3.83,P＜ 0.01),emotional state (t =-3.39,P＜ 0.01),and school adaptation score (t=-3.46,P＜0.01).(2)There was no significant difference in objective support between the control group before intervention and after intervention.In addition,the remaining dimensions such as subjective support (20.72±2.46,22.96±2.81,t=4.54,P＜0.01),support utilization (7.49± 1.40,9.86± 1.90,t =7.56,P＜0.01) and social support score (36.79±4.24,41.89±5.18,t=5.76,P＜0.01) were significantly increased.The intervention group had significant difference among target focus (15.98±2.86,17.89±3.35,t=3.28,P＜0.01),emotional control (14.98±2.77,15.70±2.71,t=3.35,P＜0.01),positive cognition (14.61 ± 2.04,16.26±3.09,t=3.36,P＜0.01),interpersonal assistance (15.30±2.44,17.49±2.73,t=4.52,P＜0.01),resilience score(77.65±6.01,88.25±5.74,t=9.63,P＜0.01) and family support(16.77±2.28,19.58± 2.44,t =6.35,P＜ 0.01).In the intervention group of school adaptation scale,life adaptation (40.44± 6.36,45.12± 7.21,t=3.68,P＜0.01),emotional state (34.04±6.99,38.84±5.95,t=3.95,P＜0.01) and school adaptation score (145.21 ±22.86,160.51±21.78,t=3.66,P＜0.01),interpersonal assistance (32.30±5.34,35.23±5.18,t=2.98,P＜0.01),learning adaptation (38.44±7.06,41.32± 5.92,t=2.36,P＜0.05) were significantly increased.Conclusion Written expression intervention has a positive effect on improving the low level of social support,the poor resilience and freshman's adaptation to college.