OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Objective To assess functional abnormalities in frontoparietal attention network of patients with traumatic brain injury(TBI),and to analyze neural mechanism of its attention disorders based on independent component analysis(ICA).Methods Totally 84 TBI patients were prospectively enrolled and divided into mild(n=33),moderate(n=27)and severe TBI groups(n=24)according to symptoms,non-contrast enhanced MRI findings,Glasgow coma scale(GCS)and Mayo craniocerebral trauma grading criteria.ICA was used to extract and analyze the optimal independent components(IC)of the dorsal attention network(DAN)and ventral attention network(VAN).Multiple linear regression analyses were performed to explore the correlations of functional connectivity(FC)of brain regions being significantly different among groups within attention network and the scores of trail making test A/B(TMT-A/B).Results Compared with control group and mild TBI group,spatial distribution of DAN(especially bilateral frontal eye field[FEF])in moderate and severe TBI groups were significantly smaller,the clusters tended to be discrete,and the intensity were significantly weakened.The right temporal parietal junction(TPJ)and right ventral frontal cortex(VFC)of VAN in control group,mild and moderate TBI groups were significantly affected,and VFC connection strength was the highest in severe TBI group.FC intensity in right VFC of TBI patients was positively correlated with TMT-A score(r=0.654,P＜0.001),which in left FEF was negatively correlated with TMT-B score(r=—0.383,P＜0.001).Conclusion FC of frontoparietal attention network was abnormal in TBI patients,which might be neural mechanism for its attention behavior disorders.

Objective To observe the value of T1WI deep learning models for evaluating brain injury of neonatal hyperbilirubinemia(NHB).Methods Totally 106 NHB(defined as newborns with neonatal behavioral neurological assessment≤37,NHB group)and 119 non-NHB newborns(control group)in center A,as well as 34 NHB and 18 non-NHB newborns in center B were collected.ROI was delineated based on bilateral globus pallidus on T1WI.A total of 690 slices were obtained by preprocessing data of center A and then were divided into training set(n=552)and test set(n=138)at a ratio of 8∶2.ResNet18,DenseNet121 and EfficientNetB0 models was established,respectively.External validation was performed based on data of center B.Receiver operating characteristic curves were drawn,area under the curves(AUC)were calculated to evaluate the performance of models for assessing NHB brain injuries compared with traditional visual analysis.Results The AUC of ResNet18 model for evaluating NHB brain injury was 0.910-0.990,significantly higher than that of DenseNet121 model(0.710-0.820)and EfficientNetB0 model(0.640-0.740)(all P＜0.001).The accuracy,sensitivity and precision of ResNet18 model for evaluating NHB brain injury were all higher than those of visual analysis(all P＜0.05),while no significant difference of specificity was found between the above two(P＞0.05).Conclusion T1WI ResNet18 model showed excellent performance and generalization ability for evaluating NHB brain injury.

Objective To observe the value of T1WI deep learning models for evaluating brain injury of neonatal hyperbilirubinemia(NHB).Methods Totally 106 NHB(defined as newborns with neonatal behavioral neurological assessment≤37,NHB group)and 119 non-NHB newborns(control group)in center A,as well as 34 NHB and 18 non-NHB newborns in center B were collected.ROI was delineated based on bilateral globus pallidus on T1WI.A total of 690 slices were obtained by preprocessing data of center A and then were divided into training set(n=552)and test set(n=138)at a ratio of 8∶2.ResNet18,DenseNet121 and EfficientNetB0 models was established,respectively.External validation was performed based on data of center B.Receiver operating characteristic curves were drawn,area under the curves(AUC)were calculated to evaluate the performance of models for assessing NHB brain injuries compared with traditional visual analysis.Results The AUC of ResNet18 model for evaluating NHB brain injury was 0.910-0.990,significantly higher than that of DenseNet121 model(0.710-0.820)and EfficientNetB0 model(0.640-0.740)(all P＜0.001).The accuracy,sensitivity and precision of ResNet18 model for evaluating NHB brain injury were all higher than those of visual analysis(all P＜0.05),while no significant difference of specificity was found between the above two(P＞0.05).Conclusion T1WI ResNet18 model showed excellent performance and generalization ability for evaluating NHB brain injury.

Objective To assess functional abnormalities in frontoparietal attention network of patients with traumatic brain injury(TBI),and to analyze neural mechanism of its attention disorders based on independent component analysis(ICA).Methods Totally 84 TBI patients were prospectively enrolled and divided into mild(n=33),moderate(n=27)and severe TBI groups(n=24)according to symptoms,non-contrast enhanced MRI findings,Glasgow coma scale(GCS)and Mayo craniocerebral trauma grading criteria.ICA was used to extract and analyze the optimal independent components(IC)of the dorsal attention network(DAN)and ventral attention network(VAN).Multiple linear regression analyses were performed to explore the correlations of functional connectivity(FC)of brain regions being significantly different among groups within attention network and the scores of trail making test A/B(TMT-A/B).Results Compared with control group and mild TBI group,spatial distribution of DAN(especially bilateral frontal eye field[FEF])in moderate and severe TBI groups were significantly smaller,the clusters tended to be discrete,and the intensity were significantly weakened.The right temporal parietal junction(TPJ)and right ventral frontal cortex(VFC)of VAN in control group,mild and moderate TBI groups were significantly affected,and VFC connection strength was the highest in severe TBI group.FC intensity in right VFC of TBI patients was positively correlated with TMT-A score(r=0.654,P＜0.001),which in left FEF was negatively correlated with TMT-B score(r=—0.383,P＜0.001).Conclusion FC of frontoparietal attention network was abnormal in TBI patients,which might be neural mechanism for its attention behavior disorders.

OBJECTIVE To analyze the risk factors of substandard drug blood concentration of meropenem in patients with hospital acquired pneumonia （HAP）. METHODS Totally 130 HAP patients who were admitted to the intensive care unit of Suzhou Hospital Affiliated to Nanjing Medical University from January 2020 to June 2021 and received steady -state blood concentration test of meropenem were selected as the study subjects . The patient ’s age ，sex，body mass and other medical history were recorded . The steady-state blood trough concentration of meropenem was determined and its target was determined . Univariate and multivariate Logistic regression analysis were used to screen the risk factors for the substandard steady -state blood trough concentration of meropenem. The receiver operating characteristic （ROC）curve was drawn to screen the warning value of the risk factors and evaluate the predictive value of the risk factors . RESULTS The steady -state blood trough concentrations of 85 cases were ≥2 mg/L， and those of 45 cases were ＜2 mg/L. Multivariate Logistic regression analysis showed that age ，negative balance and brain injury were independent risk factors for the substandard steady-state blood trough concentration of meropenem （P＜ 0.05）.ROC curve showed that when the patient was 58 years old，the area under the ROC curve was the largest （0.744）， the sensitivity was 0.882，the specificity was 0.556，and the Youden index was 0.438；when the negative balance was 520.5 mL/24 h，the area under the ROC curve reached the maximum （0.827），the sensitivity was 0.722，the specificity was 0.905，and th e Youden index was 0.628. The creatinine clearance rate in the brain injury group was significantly higher than that in the non -brain injury group ，and the steady -state blood trough concentration of meropenem in the brain injury group was significantly lower than that in the non -brain injury group （P＜0.001）. CONCLUSIONS When the HAP patient ’s age is less than 58 years old ，the brain injury and the negative balance is more than 520.5 mL/24 h，the risk of substandard steady -state blood trough concentration of meropenem will increase .

Objective:To explore the risk factors of linezolid-induced thrombocytopenia (LIT) and evaluate their predictive value.Methods:Medical records of hospital acquired pneumonia (HAP) patients who admitted in Suzhou Municipal Hospital from July 2019 to October 2021 and received linezolid were collected and retrospectively analyzed. Clinical data including general information, comorbidities, linezolid application, laboratory test results, and trough concentration of linezolid was extracted. Patients were divided into LIT group and non-LIT group according to the occurrence of LIT. Clinical characteristics were compared between the 2 groups; risk factors of LIT in patients with HAP were analyzed using a binary logistic regression model, and the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated; the predictive value of the risk factors for LIT were evaluated using receiver operating characteristic (ROC) curve. Results:A total of 74 patients were included in the study, including 55 males and 19 females, aged 82 (73, 88) years. LIT occurred in 25 patients (33.8%). Compared with the non-LIT group, the age and trough concentration of linezolid in patients in the LIT group were higher [88 (81, 92) years vs. 79(70, 86) years, P=0.001; (19.6±10.3) mg/L vs. (9.8±6.4) mg/L, P<0.001], and the baseline platelet count and baseline creatinine clearance rate were lower [181(162, 212) ×10 9/L vs. 229 (169, 289) ×10 9/L, P=0.025; 31(19, 44) ml/(min·1.73 m 2) vs. 46 (27, 65) ml/(min·1.73 m 2), P=0.018]. Binary logistic regression analysis showed that the lower baseline creatinine clearance rate ( OR=0.974, 95 %CI: 0.951-0.998, P=0.035) and higher trough concentration of linezolid ( OR=1.156, 95 %CI: 1.059-1.261, P=0.001) were independent risk factors for LIT in HAP patients. ROC curve analysis showed that the threshold of the age, trough concentration of linezolid, baseline platelet count, and baseline creatinine clearance rate were 87 years (sensitivity 56.0%, specificity 83.7%), 15.4 mg/L (sensitivity 64.0%, specificity 87.8%), 189×10 9/L (sensitivity 67.3%, specificity 68.0%), and 45 ml/(min·1.73 m 2) (sensitivity 53.1%, specificity 80.0%), respectively. Patients were respectively divided into 2 groups according to the thresholds and the incidences of LIT were compared. The results showed that the incidences of LIT in patients with age and trough concentration of linezolid exceeding the thresholds and in patients with baseline plate count and baseline creatinine clearance rate lower than or equal to the thresholds were significantly higher than those in the other patients (all P<0.01). Conclusions:Baseline creatinine clearance rate, trough concentration of linezolid, age, and plate count are risk factors for LIT in HAP patients and their thresholds are 45 ml/(min·1.73 m 2), 15.4 mg/L, 87 years, and 189×10 9/L, respectively. These risk factors have good predictive value for the occurrence of LIT.

Objective:To explore the risk factors of linezolid-induced thrombocytopenia (LIT) and evaluate their predictive value.Methods:Medical records of hospital acquired pneumonia (HAP) patients who admitted in Suzhou Municipal Hospital from July 2019 to October 2021 and received linezolid were collected and retrospectively analyzed. Clinical data including general information, comorbidities, linezolid application, laboratory test results, and trough concentration of linezolid was extracted. Patients were divided into LIT group and non-LIT group according to the occurrence of LIT. Clinical characteristics were compared between the 2 groups; risk factors of LIT in patients with HAP were analyzed using a binary logistic regression model, and the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated; the predictive value of the risk factors for LIT were evaluated using receiver operating characteristic (ROC) curve. Results:A total of 74 patients were included in the study, including 55 males and 19 females, aged 82 (73, 88) years. LIT occurred in 25 patients (33.8%). Compared with the non-LIT group, the age and trough concentration of linezolid in patients in the LIT group were higher [88 (81, 92) years vs. 79(70, 86) years, P=0.001; (19.6±10.3) mg/L vs. (9.8±6.4) mg/L, P<0.001], and the baseline platelet count and baseline creatinine clearance rate were lower [181(162, 212) ×10 9/L vs. 229 (169, 289) ×10 9/L, P=0.025; 31(19, 44) ml/(min·1.73 m 2) vs. 46 (27, 65) ml/(min·1.73 m 2), P=0.018]. Binary logistic regression analysis showed that the lower baseline creatinine clearance rate ( OR=0.974, 95 %CI: 0.951-0.998, P=0.035) and higher trough concentration of linezolid ( OR=1.156, 95 %CI: 1.059-1.261, P=0.001) were independent risk factors for LIT in HAP patients. ROC curve analysis showed that the threshold of the age, trough concentration of linezolid, baseline platelet count, and baseline creatinine clearance rate were 87 years (sensitivity 56.0%, specificity 83.7%), 15.4 mg/L (sensitivity 64.0%, specificity 87.8%), 189×10 9/L (sensitivity 67.3%, specificity 68.0%), and 45 ml/(min·1.73 m 2) (sensitivity 53.1%, specificity 80.0%), respectively. Patients were respectively divided into 2 groups according to the thresholds and the incidences of LIT were compared. The results showed that the incidences of LIT in patients with age and trough concentration of linezolid exceeding the thresholds and in patients with baseline plate count and baseline creatinine clearance rate lower than or equal to the thresholds were significantly higher than those in the other patients (all P<0.01). Conclusions:Baseline creatinine clearance rate, trough concentration of linezolid, age, and plate count are risk factors for LIT in HAP patients and their thresholds are 45 ml/(min·1.73 m 2), 15.4 mg/L, 87 years, and 189×10 9/L, respectively. These risk factors have good predictive value for the occurrence of LIT.

Objective To optimize the extraction process of main iridoid glycosides in Damnacanthus officinarum Huang and evaluate the antioxidant activity of Damnacanthus officinarum Huang in vitro. Methods The classical heating-reflux extraction method was selected. The volume fraction of ethanol, the volume of solvent and extraction time were taken as the evaluation factors. The comprehensive score of extraction yield and the monotropein content were used as the evaluation indexes. An orthogonal test was designed to select the best extraction conditions. The total reducing capacity, DPPH clearance rate and hydroxyl radical scavenging rate were measured to determine its antioxidant activity in vitro. Results The optimal extraction process was the reflux with 6 times volume of 60% ethanol for 2 hours. Damnacanthus officinarum Huang has certain antioxidant capacity, and the activity of ethyl acetate part had the best effect. Conclusion The optimized extraction process is stable and feasible, which can be used for extraction of the iridoid glycosides from Damnacanthus officinarum Huang. This study has proved that Damnacanthus officinarum Huang has certain antioxidant activity.