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

This study explored how the human cortical folding pattern composed of convex gyri and concave sulci affected single-subject morphological brain networks, which are becoming an important method for studying the human brain connectome. We found that gyri-gyri networks exhibited higher morphological similarity, lower small-world parameters, and lower long-term test-retest reliability than sulci-sulci networks for cortical thickness- and gyrification index-based networks, while opposite patterns were observed for fractal dimension-based networks. Further behavioral association analysis revealed that gyri-gyri networks and connections between gyral and sulcal regions significantly explained inter-individual variance in Cognition and Motor domains for fractal dimension- and sulcal depth-based networks. Finally, the clinical application showed that only sulci-sulci networks exhibited morphological similarity reductions in major depressive disorder for cortical thickness-, fractal dimension-, and gyrification index-based networks. Taken together, these findings provide novel insights into the constraint of the cortical folding pattern to the network organization of the human brain.
Humans ; Cerebral Cortex/anatomy & histology* ; Male ; Female ; Magnetic Resonance Imaging ; Adult ; Connectome/methods* ; Young Adult ; Nerve Net/anatomy & histology* ; Neural Pathways ; Depressive Disorder, Major/diagnostic imaging*

Calcific aortic valve disease(CAVD)is the most common disease affecting the heart valves,character-ized by thickening,fibrosis,and mineralization of the aortic valve leaflets.Currently,there is no effective pharmacologi-cal treatment.Aortic valve calcification is a complex and multifactorial process involving valve inflammation,fibrosis,calcification,valve thickening and outflow tract obstruction.The exact pathophysiological mechanisms of CAVD are not fully understood,but many studies have suggested that innate immune cells play a key role in the development of aortic valve calcification.This review focuses on the current role of innate immune cells in the development of CAVD.

Objective To analyze the effects of GATA binding protein 3(GATA3)mediated mini RNA-21(miR-21)/phosphatase and tensin homologue(PTEN)axis missing from human chromosome Chromosome 10 on the proliferation and invasion of endometrial cancer cells.Methods HEC-1-A cells were transfected and divided into control group,GATA3 empty plasmid group,GATA3 overexpression plasmid group,GATA3 siRNA negative control group,and GATA3 siRNA group.Detect the expression levels of GATA3,miR-21,PTEN,proliferation,apoptosis rate,migration,and invasion in each group of cells.Results Compared with the hEEC group,the expression levels of GATA3 and miR-21 in cells of the HEC-1-A group,HEC-1-B group,and Ishikawa group increased,while the expression levels of PTEN decreased(P<0.05).Compared with the GATA3 empty plasmid group,the GATA3 overexpression plasmid group showed an increase in GATA3,miR-21 mRNA expression,pro-liferation rate,migration distance,number of invading cells,and Vimentin levels,while the PTEN mRNA expression,apoptosis rate,Caspase-9,Bax,and E-cadherin levels decreased(P<0.05);Compared with the GATA3 siRNA negative control group,the GATA3,miR-21 mRNA expression,proliferation rate,migration distance,number of invading cells,and Vimentin level decreased,while the PTEN mRNA expression,apoptosis rate,Caspase-9,Bax,and E-cadherin levels increased(P<0.05).Conclusion Downregulation of GATA3 expression can regulate the miR-21/PTEN axis,slow down the proliferation of HEC-1-A cells,and promote apoptosis of HEC-1-A cells.

Objective:To investigate the expression, methylation and prognosis of DKK2 in non-small cell lung cancer, and also its effect and correlation with the sensitivity of hypofractionated radiotherapy sensitivity in non-small cell lung cancer.Methods:qPCR, online database and Kaplan-Meier survival curve were used to detect the expression, methylation and prognosis of DKK2 in NSCLC samples. A549 cells was set as the research objects, and cloning formation experiment and Western blot were used to evaluated the effects of DKK2 on hypofractionated radiotherapy in NSCLC.Results:Compared with the normal tissues, the expression of DKK2 mRNA in NSCLC samples was down-regulaged [ (0.00042±0.0001) vs (0.00065±0.0002), P<0.001]. Data taken from an online methylation database showed that compared with normal tissue, DKK2 hypermethylated in NSCLC, and its methylation was significantly negatively correlated with the mRNA expression. Downregulated DKK2 expression was inversely correlated with its methylation status ( P=0.034). The hypofractionated radiotherapy sensitivity of NSCLC patients was 53.3%. Compared with radiosensitivity group, DKK2 mRNA expression was significantly down-regulated in radioresistance group[ (0.00064±0.0002) vs (0.00043±0.0002), P<0.001]. The progression free survival of radiotherapy sensitive group was better than that of radiotherapy resistant group (median PFS: 21.4 months vs 4.6 months). Ectopic expression of DKK2 in A549 lines inhibited colony formation after irradiation with 4 Gy X-ray radiotherapy. Western blot further showed that restoration of DKK2 expression resulted in upregulation of DNA damage markers γ-H2AX[ (1.00±0.24) vs (3.22±0.41), P<0.001], and the difference was statistically significant. Conclusion:DKK2 expression is downregulated in NSCLC due to methylation, which may be acted as an important target to predict the hypofractionated radiotherapy sensitivity of NSCLC.

Objective:To investigate the clinical characteristics and surgical effects of acute calculous cholecystitis (ACC) in high altitude area of Tibet.Methods:The retrospective cohort study was conducted. The clinicopathological data of 182 ACC patients who underwent surgery in the 954th Hospital of Army from January 2016 to December 2020 were collected. There were 56 males and 126 females, aged (41±13)years. Of the 182 patients, 61 cases undergoing open cholecystec-tomy were divided into the open group, and 121 cases undergoing laparoscopic cholecystectomy (LC) were divided into the laparoscopic group. Observation indicators: (1) clinical characteristics of ACC in high altitude area; (2) surgical situations; (3) postoperative complications; (4) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect postopera-tive complications of patients up to October 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measure-ment data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Results:(1) Clinical characteristics of ACC in high altitude area. Of the 182 patients, cases with symptom duration as <3 days, 3 days to 1 month, >1 month and ≤12 months, >12 months were 37, 43, 57, 45, respectively. Seventy-seven of the 182 patients were combined with other diseases before surgery. (2) Surgical situations. Two cases in the open group were found common bile duct stones during the operation, and underwent choledochotomy and T-tube drainage. Nine cases in the laparoscopic group were converted to laparotomy, including 3 cases with severe abdominal adhesion and ineffective hemostasis, 6 cases with anatomical variation of Calot triangle. The conversion to laparotomy rate was 7.438%(9/121). The other patients in the open group and the laparoscopic group completed surgery successfully. The operation time, volume of intraoperative blood loss, time to postoperative first out-of-bed activities, time to postoperative first flatus, cases with indwelling drainage tube, cases with acute simple cholecystitis, acute suppurative cholecystitis, acute gangrene cholecystitis, gallbladder perforation of disease pathological type, postoperative white cell count, postoperative neutrophil percentage, duration of postoperative hospital stay were (109±42)minutes, 50(45,100)mL, (16.1±1.5)hours, (31.4±11.9)hours, 33, 25, 27, 6, 3, (6.8±1.9)×10 9/L, 72.7%±7.4%, (7.3±1.7)days for the open group. The above indicators were (98±43)minutes, 20(20,50)mL, (12.9±1.4)hours, (26.7±12.1)hours, 51, 56, 51, 9, 5, (7.1±2.4)×10 9/L, 70.5%±8.7%, (6.4±1.7)days for the laparoscopic group. There were significant differences in the volume of intraopera-tive blood loss, time to postoperative first out-of-bed activities, time to postoperative first flatus, duration of postoperative hospital stay between the two groups ( Z=?6.75, t=14.41, 2.46, 3.45, P<0.05). There was no significant difference in the operation time, cases with indwelling drainage tube, diseases pathological type, postoperative white cell count, postoperative neutrophil percentage between the two groups ( t=1.66, χ2=2.33, 0.84, t=?0.71, 1.66, P>0.05). (3) Postoperative complica-tions. Postoperative complications occurred in 7 of the 61 patients in the open group and 5 of the 121 patients in the laparoscopic group. There was no significant difference in the postoperative complications between the two groups ( χ2=2.46, P>0.05). (4) Follow-up. Of the 182 patients, 115 cases including 35 cases in the open group and 80 cases in the laparoscopic group were followed up for 12(range, 3?24)months. During the follow-up, 1 case of the 35 patients in the open group had abdominal pain and jaundice, which was diagnosed as choledocholithiasis. The patient was improved after stone removal with endoscopic retrograde cholangiopancreatography. Two cases of the 35 patients in the open group had upper abdominal pain with fever and were improved after anti-infection treatment. Of the 80 patients in the laparoscopic group, 1 case had upper abdominal pain and 1 case had dyspepsia and anorexia, respectively. The two cases were improved after symptomatic treatment. Conclusions:Patients with ACC in the high altitude area of Tibet have high ratio of preoperative complications, long diseases history and high incidence rates of pyogenic perforation of the gallbladder. Patients with ACC in the high altitude area undergoing LC is safe and effective. Compared with open cholecystectomy, LC have less volume of intraoperative blood loss, faster postoperative recovery and shorter duration of postoperative hospital stay.

Objective:To evaluate the reporting quality of clinical guidelines on skin diseases published in journals in China.Methods:The CNKI, VIP, Wanfang and SinoMed databases were searched from January 2009 to October 2019 for clinical guidelines on skin diseases published in journals in China. Two reviewers independently screened the literature, and extracted and cross-checked data. The reporting quality of these clinical guidelines was evaluated by using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) , and statistical analysis was carried out with Excel 2017 software.Results:A total of 17 clinical guidelines on skin diseases were included, including 13 Western medicine guidelines and 4 Chinese medicine guidelines. Among the 13 Western medicine guidelines, the number of guidelines reporting the following areas in the RIGHT statement, namely basic information, background, evidence, recommendations, review and quality assurance, funding and declaration and management of interests, and other information, was 9, 6, 0, 4, 0, 1 and 1 respectively; among the 4 Chinese medicine guidelines, the number of guidelines reporting the above 7 areas in the RIGHT statement was 4, 3, 3, 3, 3, 2 and 2 respectively.Conclusion:There is still considerable room for improvement in the overall reporting quality of clinical guidelines on skin diseases published in journals in China during the past 10 years, and the RIGHT statement is recommended for improving the reporting quality in guideline development.

Objective:To explore the treatment of levator complex in conjoint fascial sheath suspension correction on severe ptosis, and to seek a reliable and less complications operation.Methods:From October 2016 to February 2020, 40 eyes of 24 patients with severe ptosis (6 males and 18 females, aged from 10 to 73 years, with an average of 34.4 years) were divided into study group and control group. 20 eyes in study group were treated with combined fascia sheath suspension and levator palpebrae muscle complex tension-free shortening correction, while 20 eyes in control group were treated with combined fascia sheath suspension and levator palpebrae muscle complex tension-free shortening correction The effects and complications of the two groups were compared.Results:Follow-up studies were conducted at 1 week, 3 month and 6 months after operation. There was no significant difference between the two methods at different time points after operation, and the incidence of complications in the study group was less than that in the control group at 1 week after operation.Conclusions:Combined with fascial sheath suspension and levator palpebrae muscle complex tension-free shortening in the treatment of severe blepharoptosis has less complications and reliable curative effect in the early postoperative period, but it still needs to be improved to obtain more lasting curative effect.

ObjectiveTo compare the effect of two analgesia methods in silver needle therapy among patients with myofascitis.Methods Totally 181 eligible patients with myofascitis were collected from January 2015 to March 2016 and were divided into observation group and control group by random number table. Patients in the control group (n=90) were given partial external lidocaine ointment and diclofenac sodium lidocaine hydrochloride intramuscular injection an hour before the treatment. Patients in the observation group (n=91) first received partial external lidocaine ointment an hour before the treatment,then received flurbiprofen axetil intravenous infusion and intravenous drip 15 minutes before the treatment. Visual analogue scale (VAS) was applied to evaluate the pain that before treatment,at the moment of acupuncture,during the treatment,at the moment of pulling out the needles,and a day after the treatment. Moreover,the clinical effect of two groups was also evaluated after a course of treatment.Results The VAS scores at the moment of acupuncture and during the treatment of the observation group were (7.71±0.80) and (6.71±1.17),while the data in the control group were (4.14±1.06) and (3.58±0.84) (P<0.05). There were no significant differences in the VAS scores before treatment,after pulling out the needles,and a day after treatment,and the clinical effect between two groups (P>0.05).Conclusions Flurbiprofen axetil injection can effectively reduce the pain in silver needle therapy among patients with myofascitis and can also improve patients′ compliance.

Objective To research the change rule of peripheral serum Th1/Th2/Th17 balance and relevant cytokines in atopic dermatitis(AD) and to further study its immunologic mechanism .Methods The levels of peripheral serum IFN‐γ,IL‐4 ,IL‐17 ,IL‐21 and IL‐23 in the patients with AD were detected by the flow immunofluorescence technology and the detection results were performed the statistical analysis ,thus the change rule of Th1/Th2/Th17 balance in AD was analyzed .Results The IL‐4 level in peripheral serum of the patients with AD was increased compared with the healthy control group (P<0 .05);the IFN‐γ/IL‐4 and IFN‐γ/IL‐17 in the AD group were significantly decreased compared with the control group (P<0 .01);IL‐17 was positively corre‐lation with SCORAD scores of AD severity (P<0 .05) .Conclusion Th1/Th2 and Th1/Th17 are decreased in the AD course .Th1/Th2/Th17 balance drift may be the important mechanism of AD pathogenesis .