Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

OBJECTIVE To evaluate the consistency between the quetiapine LC-MS/MS kit and the laboratory-built method(reference method) in the detection results of quetiapine therapeutic drug monitoring. METHODS A total of 120 remaining plasma samples were collected from patients receiving quetiapine therapeutic drug monitoring from March to October in 2021. The plasma concentration of quetiapine was detected by kit and reference method respectively. The analysis of correlations and consistency was performed by outlier analysis, linear regression and Bland-Altman method. RESULTS No outliers were detected. The linear regression equation was Y=1.018X+4.400(r=0.998), indicating a good correlation. The Bland-Altman plot analysis showed good agreement between the two measurements. CONCLUSION The detection results of quetiapine LC-MS/MS kit and reference method are in good agreement. The kit can be used for clinical quetiapine treatment drug monitoring.

【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P<0.05). The unqualified rate of HBsAg, anti HCV, anti HIV and anti TP was (0.15±0.09)%, (0.05±0.04)%, (0.06±0.03)% and (0.20±0.05)% respectively. The average unqualified rate, average hemolysis rate, average insufficient volume rate and the abnormal hematocrit rate of samples in 17 blood bank laboratories was 0.21‰, 0.08‰, 0.01‰ and 0.02‰ respectively. There were differences in the retest concordance rates of four HBsAg, anti HCV and anti HIV reagents, and three anti TP reagents among 17 blood bank laboratories (P<0.05). The usage rate of ELISA reagents was (114.56±3.30)%, the outage rate of ELISA was (10.23±7.05) ‰, and the out of range rate of ELISA was (0.90±1.17) ‰. There was no correlation between the out of range rate, outrage rate and usage rate (all P>0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.

In light of the liver injury risk associated with the oral administration of Xianlin Gubao oral preparation, this study compared the differences in liver injury induced by two different extraction processes in rats and explored the correlation between hepatotoxicity and extraction process from the perspective of the differences in the content of the relevant components. Thirty male Sprague-Dawley(SD) rats were randomly divided into a normal group, tablet extract groups of different doses, and capsule extract groups of different doses, with 6 rats in each group. Each group received continuous oral administration for 4 weeks. The assessment of liver injury caused by different extracts was conducted by examining rat body weight, liver function blood biochemical indicators, liver coefficient, and liver pathological changes. In addition, a high-performance liquid chromatography(HPLC) method was established to simultaneously determine the content of icariin, baohuoside I, and bakuchiol in the extracts to compare the differences in the content of these three components under the two extraction processes. The results showed that both extracts caused liver injury in rats. Compared with the normal group, the tablet extract groups, at the studied dose, led to slow growth in body weight, a significant increase in triglyceride levels(P<0.05), a significant decrease in liver-to-brain ratio(P<0.05), and the appearance of hepatic steatosis. The capsule extract groups, at the studied dose, resulted in slow growth in body weight, a significant increase in aspartate aminotransferase levels(P<0.05), a significant decrease in body weight, liver weight, and liver-to-brain ratio(P<0.05), and the presence of hepatic steatosis and inflammatory cell infiltration. In comparison, the capsule extraction process had a higher risk of liver injury. Furthermore, based on the completion of the liquid chromatography method, the content of icariin and baohuoside Ⅰ in the capsule extract groups was 0.83 and 0.81 times that in the tablet extract groups, respectively, while the bakuchiol content in the capsule extract group was 29.80 times that in the tablet extract groups, suggesting that the higher risk of liver injury associated with the capsule extraction process may be due to its higher bakuchiol content. In summary, the differences in rat liver injury caused by the two extracts are closely related to the extraction process. This should be taken into consideration in the formulation production and clinical application.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/pathology* ; Fatty Liver ; Tablets ; Body Weight ; Plant Extracts ; Phenols

Endoplasmic reticulum is one of the most important organelles in maintaining cellular homeo⁃ stasis, mainly involved in intracellular lipid synthesis, protein folding and calcium ion homeostasis. Trau⁃ ma, ischemia and hypoxia and other pathological changes can cause protein folding dysfunction in the en⁃ doplasmic reticulum, triggering endoplasmic reticulum stress (ERS). Spinal cord injury (SCI) is a com⁃ mon traumatic disease with anextremely high disability rate, which seriously affects the quality of life. There is no safe and effective clinical methods so far. Investigations have shown that ERS is one of the important pathological changes leading to cell death and neuronal dysfunction after SCI, and is closely as⁃ sociated with signaling pathways such as apoptosis, autophagy, and inflammation in neurons after SCI; however, the molecular mechanisms between ERS and SCI have not yet been thoroughly investigated. A deeper understanding and exploration of the potential molecular mechanisms associated with ERS and SCI may be the future SCI therapeutics. In this paper, we first summarized the relationship between the chan⁃ ges of ERS⁃related genes and the pathological process of SCI, Then the interrelationships between ERS and the apoptosis, inflammation, and autophagy signaling pathways after SCI were analyzed, starting from the three main modes of regulation, including unfolded protein response (UPR), endoplasmic reticulum⁃ associated degradation (ERAD), and endoplasmic reticulophagy (ER⁃phagy),Finally, we summarize the relevant drugs and application prospects of targeting ERS for SCI in recent years, which may provide a theoretical basis for targeting the ERS pathway for SCI and provide some ideas and insights for the de⁃ velopment of future therapeutic strategies after SCI.

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Objective:To investigate the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM).Methods:A diagnostic test. In this prospective study, patients with T2DM who underwent both IVIM-DWI and renal biopsy at the First Medical Center of Chinese PLA General Hospital between October 2017 and September 2021 were consecutively enrolled. IVIM-DWI parameters including perfusion fraction (f), pure diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured in the renal cortex, medulla, and parenchyma. Patients were divided into the DN group and NDRD group based on the renal biopsy results. IVIM-DWI parameters, clinical information, and diabetes-related biochemical indicators between the two groups were compared using Student′s t-test or Mann-Whitney U test. The correlation of IVIM-DWI parameters with diabetic nephropathy histological scores were analyzed using Spearman′s correlation analyzes. The diagnostic efficiency of IVIM-DWI parameters for distinguishing between DN and NDRD were assessed using the receiver operating characteristic (ROC) curves. Results:A total of 27 DN patients and 23 NDRD patients were included in this study. The DN group comprised 19 male and 8 female patients, with an average age of 52±9 years. The NDRD group comprised 16 male and 7 female patients, with an average age of 49±10 years. The DN group had a higher D* value in the renal cortex and a lower f value in the renal medulla than the NDRD group (9.84×10 -3 mm 2/s vs. 7.35×10 -3 mm 2/s, Z=-3.65; 41.01% vs. 46.74%, Z=-2.29; all P<0.05). The renal medulla D* value was negatively correlated with DN grades, interstitial lesion score, and interstitial fibrosis and tubular atrophy (IFTA) score ( r=-0.571, -0.409, -0.409; all P<0.05) while the renal cortex f value was positively correlated with vascular sclerosis score ( r=0.413, P=0.032). The renal cortex D* value had the highest area under the curve (AUC) for discriminating between the DN and NDRD groups (AUC=0.802, sensitivity 91.3%, specificity 55.6%). Conclusion:IVIM-derived renal cortex D* value can be used non-invasively to differentiate DN from NDRD in patients with T2DM that can potentially facilitate individualized treatment planning for diabetic patients.

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies