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 molecular mechanism of VRC01 resistance in HIV-1 subtype B′ strains isolated from a patient (DRVI01) with broadly neutralizing antibody (bNAb).Methods:Sequences of the HIV-1 subtype B′ strains isolated from patient DRVI01 were compared with those of HIV-1 subtype B′ strains that were isolated at the same time but sensitive to VRC01 antibody. Key amino acids that might affect the neutralization of VRC01 were selected according to literature reports. Effects of the selected amino acids on VRC01 neutralization were verified by site-directed mutation and sequence exchange of membrane proteins from different patients.Results:Single-point mutations of E279D and R282K in LoopD region and N460A and N463Q in V5 region reversed the viral sensitivity to VRC01 neutralization. Combined mutations in two or three above-mentioned sites significantly increased the viral sensitivity to VRC01 antibody compared with single-point mutations. Contrary to literature reports, the glycosylation site mutation of N276 had no influence on the viral sensitivity to VRC01.Conclusions:HIV-1 subtype B′ strains isolated from patient DRV01 with bNAb carried the mutations of D279 and K282 in LoopD region and N460 and N463 in V5 region, resulting in resistance to VRC01 antibody.

Objective:To evaluate the impact of runoff score on the patency of femoropopliteal artery (FPA) stent in patients with type 2 diabetes mellitus with ultrasonography.Methods:A retrospective review of a database of 127 patients with type 2 diabetes mellitus (127 limbs) undergoing femoropopliteal stents in Xuanwu Hospital from January 2016 to July 2018 was made. Demographic characteristics and possible related risk factors were recorded. The extent of FPA disease and the runoff lesions below the knee (anterior tibial artery, posterior tibial artery, and peroneal artery) were preoperative evaluated and regular followed-up by color Doppler ultrasonography (CDU). Femoropopliteal artery lesions were graded according to the Trans-Atlantic Inter-Society Consensus (TASCII), and the runoff lesions below the knee were scored according to the Society for Vascular Surgery (SVS). The patency and the predictors for in-stent restenosis were assessed using a Kaplan-Meier and Cox proportional hazards model.Results:Follow up period ranged from 1 month to 24 months.The total patency rates at the 3, 6, 12, 24 months were 91.5%, 70.9%, 45.7% and 31.7%, respectively. Post-procedural runoff score according to SVS criteria: 1-3 scores in 45 limbs, 3.5-5 scores in 37 limbs, 5.5-7 scores in 34 limbs, 7.5-10 scores in 11 limbs. The median runoff score was 4.Patients were stratified according to runoff scores (score ≤4 and >4 groups), and the difference of the patency rates between the two groups was statistically significant by Kaplan-Meier analysis and Log-rank test (χ 2=10.825, P=0.001). The runoff score affected patency significantly on COX analysis ( RR=1.155, P=0.006, 95% CI: 1.042-1.281). Conclusions:Compromised runoff negatively affects the patency of FPA stent. High post-procedural runoff score is a main risk factor related to loss of patency. CDU is a reliable method for monitoring patients with femoropopliteal stenting.

Objective:To investigate the distribution characteristics of atherosclerosis in patients with obstructive sleep apnea syndromes (OSAS) by ultrasonography and explore the differences of intracranial and extracranial atherosclerosis lesions.Methods:From July 2016 to July 2019, 139 patients with OSAS confirmed by the department of neurology and/or respiratory of Xuanwu Hospital, Capital Medical University were enrolled retrospectively. According to the results of polysomnography (PSG), patients were divided into 3 groups: mild degree (53 cases), moderate degree (35 cases) and severe degree (51 cases). Demographic parameters, distribution and the severity of atherosclerosis both in intracranial and extracranial arteries, and the incidence of ischemic stroke were compared among the three groups.Results:①Among 139 OSAS patients, there were more males (64.7%) than females (35.3%). Of all the risk factors for cerebrovascular diseases, the prevalence of hypertensin was the highest (50.4%), followed by hyperlipidemia (48.9%). The prevalences of hypertension and ischemic stroke, the body mass index (BMI) in severe OSAS group were higher than those in mild group (all P<0.017). ②The total detection rate of extracranial atherosclerosis (83.5%) was significantly higher than that of intracranial atherosclerosis (23.0%)( P<0.01). ③The extracranial atherosclerotic lesion with highest detection rate of was simple plaque formation (51.1%, 71/139 cases), and there was no significant difference in extracranial lesions among the three groups ( P=0.106). However, with the aggravation of OSAS degree, the stenosis degree of extracranial artery increased ( P=0.006), and there was a weak correlation between the severity of OSAS and the degree of extracranial artery stenosis ( r s=0.263, P=0.002). ④The incidence of middle cerebral artery stenosis accounted for 15.8%(22/139 cases) of intracranial arteries involved and there were no significant differences in the rate, degree and distribution of intracranial artery lesions among the three groups (all P>0.05). Conclusions:The detection rate of extracranial arterial lesions in OSAS patients is higher. With the aggravation of OSAS, the degree of atherosclerosis stenosis in extracranial arteries and the incidence of ischemic stroke trend to increase.

Objective To investigate the clinical value of 2 dimension late Gadolinium enhancement MRI (LGE-MRI) technique for the evaluation of atrial myocardial fibrosis in patients with atrial fibrillation. Methods Forty-nine cases of atrial fibrillation in our hospital from March 2015 to December 2016 were retrospectively collected. The LGE-MR was acquired by the Siemens 3.0 T MR machine before the catheter ablation.The findings of LGE-MR were evaluated by two experienced doctors. The left atrium(LA)were manually segmented into 8 regions in axial view.All patients were classified into 4 stages based on the extent of enhancement, stage 0: absence of enhancement, stage Ⅰ: enhancement appeared in minimal two consecutive slices in single region,stageⅡ:enhancement in two regions,stageⅢ:enhancement in three or more regions. All electroanatomic maps were obtained after electrical conversion during catheter ablation. The Kappa test was used to assess the consistency of LGE-MRI left atrial myocardial fibrosis and CARTO system of the left atrial endocardial voltage reconstruction. Results Forty-nine cases of atrial fibrillation with LGE-MRI and CARTO were included. There were 17 cases of atrial fibrosis stage 0,10 cases of stageⅠ,11 cases of stageⅡ,11 cases of stageⅢaccording to LGE-MRI findings;There were 17 cases of atrial fibrosis stage 0,19 cases of stageⅠ,12 cases of stageⅡ,11 cases of stage Ⅲ with reference to CARTO findings. The diagnostic accuracy of the LGE-MRI atrial fibrosis was 81.6%(40/49),of which the correlation was good(Kappa= 0.751,P<0.001). Conclusions LGE-MRI can accurately assess the degree of left atrial myocardial fibrosis in patients with atrial fibrillation,help to select the proper candidate and strategy in catheter ablation.

Objective To investigate the diagnostic value of PSV/PSVpop,a new parameter detected by color Doppler ultrasonography,for patients with severe s tenosis (70 ％-99 ％)in superficial femoral artery (SFA).Methods One hundred and eighty-five cases (234 limbs) with SFA stenosis detected by CDU and confirmed by DSA were included in this study.Peak systolic velocity of intra stenotic(PSV),proximal stenotic (PSVpro),and popliteal artery (PSVpop) were measured and recorded respectively.The ratio of PSV/PSVpro,PSV/PSVpop were calculated.Using DSA as the gold standard,the cut off values for the diagnosis of severe stenosis were determined with receiver operating characteristics (ROC) analysis.The efficacy of the above parameters were compared.Results The new parameter PSV/PSVpop≥4 had 96.3％ of sensitivity,91.6％ of specificity,94.4％ of accuracy,95.7％ of positive predictive value,and 91.4％ of negative predictive value and 0.978 of area under the ROC curve(AUC) could define 70％-99％ stenosis of SFA.The AUC of PSV/PSVpop was higher than those of the traditional parameters PSV(0.922) and PSV/ PSVpro(0.920),the difference was statistically significant (P ＜0.01).The AUC of combined parameter PSV/PSVpop + PSV surpassed conventional combined parameter PSV/PSVpro + PSV (0.978 ∶ 0.940,P ＜ 0.05),but had no statistically significant difference with single parameter of PSV/PSVpop (0.978 ∶ 0.978,P ＞ 0.05).Conclusions The diagnostic efficacy of PSV/PSVpop is superior to traditional hemodynamic parameters in the diagnosis of SFA severe stenosis.

Objective To evaluate the correlation between the types of vertebral artery occlusion and their compensatory hemodynamic changes and posterior circulation ischemia using color Doppler flow imaging combined with transcranial color-coded sonography.Methods From June 2015 to June 2016,A total of 108 patients with vertebral artery occlusion confirmed by vascular sonography,digital subtraction angiography (DSA) or CT angiography (CTA) were enrolled retrospectively.According to the magnetic resonance imaging (MRI)-diffusion weighted imaging (DWI) findings,they were divided into posterior circulation infarction (n=78 in infarction group) and non-posterior circulation infarction (n=30 in TIA group).Color Doppler flow imaging and transcranial color Doppler ultrasonography were used to examine the contralateral vertebral artery extracranial diameter, peak systolic velocity(PSV) and end diastolic velocity(EDV) of bilateral extracranial and intracranial vertebral arteries.The differences of the vertebral artery occlusion types,establishment of collateral circulation and hemodynamic changes of the contralateral vertebral artery were compared between the two groups.Results The patients with single vertebral artery occlusion in the infarction group and TIA group were 69 (88.5%) and 26 (86.7%) respectively;those with bilateral vertebral artery occlusion were 9 (11.5%) and 4 (13.3%) respectively.There was no significant difference in the number of vertebral artery occlusion between the two groups (χ2=0.000,P=1.000).The proportion of patients with vertebral artery occlusion in intracranial segment in the infarction group was higher than that in the TIA group (70.5% [55/78] vs.36.7% (11/30);χ2=10.444,P=0.001).The proportion of patients with the establishment of collateral circulation in the infarction group was lower than that in the TIA group (14.1% [11/78] vs.43.3% (13/30);χ2=10.711,P=0.001).The peak systolic velocity (PSV) and the end diastolic velocity (EDV) of contralateral extracranial vertebral artery in patients with single vertebral artery occlusion in the TIA group were higher than those in the infarction group (65±21 cm/s vs.57±15 cm/s,25±8 cm/s vs.20±7 cm/s,t=2.043 and 2.606 respectively,all P<0.05).Conclusion The establishment of collateral circulation and hemodynamic compensation of the contralateral vertebral artery after vertebral artery occlusion were closely associated with the occurrence of posterior circulation ischemia.

Objective To investigate the characteristics of epidemic and genotype/subtype distribution of hepatitis C virus (HCV) among entry travelers at Tengchong port,to provide references for HCV prophylaxis and treatment.Methods A total of 54 serum samples were collected from anti-HCV positive travelers at Tengchong port from June 2009 to June 2016.HCV NS5B gene was amplified using reverse transcription polyonerase chain reation (RT-PCR) and subsequently sequenced.Based on the obtained sequences and retrieved reference sequences,phylogenetic analysis was conducted to determine HCV genotype/subtype.Results HCV infection rate among entry travelers at Tengchong ports was 0.45 ％ (54/12 059).Forty five samples were successfully genotyped.Phylogenetically,HCV genotype 3b was revealed to be the predominant subtype (28.89 ％,13/45) in this population,followed by genotype 6n (20.0％,9/45),genotype 1b (17.78％,8/45),genotype 3a (13.33％,6/45),genotype 2a (11.11％,5/45),genotype 1a (2.22％,1/45) and genotype 6a (2.22％,1/45).The major genotype in Myanmar travelers was genotype 6,while in Chinese population,genotype 1 predominated.Genotype 6 in the population showed close phylogenetic relationship with strains prevalent in China and Southeast Asia.Genotype 3 was closely clustered with strains prevalent in China.Conclusions The distribution of HCV genotypes among entry travelers at Tengchong port is impacted by HCV epidemic strains both in Yunnan province and neighboring regions.This population serves as a transmitting media which may influence the epidemiological characteristics of HCV in Tengchong and neighboring areas.

Objective To investigate the evaluation value of anterior communicating artery patency for patients with severe carotid artery stenosis treated by carotid endarterectomy (CEA )with transcranial color Doppler ultrasonography. Methods From June 2014 to June 2015,89 consecutive inpatients with unilateral symptomatic severe carotid stenosis treated with CEA at the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University were enrolled retrospectively. They were divided into either a patent group (n=45)or a non-patent group (n=44)according to whether the anterior communicating artery was patent or not (DSA findings). Whether the anterior communicating artery was patent or not diagnosed by the transcranial color Doppler ultrasonography was compared with the consistency of the digital subtraction angiography (DSA)results. The differences of intraoperatively implemented temporary shunt rate and the differences of hemodynamic parameters including peak velocity (PSV),end-diastolic velocity (EDV),and pulsatility index (PI)of the preoperative and postoperative bilateral middle cerebral artery and anterior cerebral artery (ACA)of both groups were analyzed. Results Compared with the results of DSA, the sensitivity and specificity of transcranial color Doppler ultrasonography for preoperative evaluation of the patency of anterior communicating artery were 91. 1%(41/45)and 97. 7%(43/44)respectively,the total accordance rate was 94. 4%(84/89)(Kappa=0. 888,P<0. 01). The temporary shunt rate (2. 2%[1/45])of patients in CEA of the anterior communicating artery patent group was significantly lower than that of the non-patent group (20. 5%[9/44]). There was significant difference between the 2 groups (χ2 =5. 700,P =0. 017). PSV,EDV,and PI of the ipsilateral middle cerebral artery after procedure in both groups were higher than those before procedure. There were significant differences (the patent group:128 ± 41 cm/s vs. 77 ± 24 cm/s,55 ± 18 cm/s vs. 41 ± 13 cm/s,and 0. 92 ± 0. 14 vs. 0. 67 ± 0. 14;the non-patent group:139 ± 44 cm/s vs. 86 ± 31 cm/s,59 ± 22 cm/s vs. 44 ± 16 cm/s,and 0. 94 ± 0. 15 vs. 0.71 ± 0. 16;all P<0. 01). PSV and EDV of the contralateral ACA of the patent group were decreased after procedure. There were significant differences (125 ± 42 cm/s vs. 157 ± 57 cm/s,55 ± 24 cm/s vs. 72 ± 34 cm/s,all P<0. 01). There was no significant difference in PI of contralateral ACA before and after procedure (P >0.05). There were no significant differences in PSV,EDV and PI of the contralateral ACA in the non-patent group between after procedure and before procedure (all P>0. 05). Conclusions Transcranial color Doppler ultrasonography can accurately and objectively evaluate whether the anterior communicating artery is patent or not in patients with unilateral severe carotid stenosis. It has an important clinical significance for selective shunt in CEA and improving the success rate of CEA.

Objective To understand the development of healthcare-associated infection(HAI)management organ-izations in China in the past 30 years.Methods Development of HAI management organizations in 12 provinces (municipalities,autonomous regions)in China was surveyed.Results A total of 166 hospitals were surveyed,96 (57.83%)were tertiary hospitals.Among 164 hospitals which had a history of development of HAI management department,46(28.05%)before 1995,63(38.14%)in 1995-2005,and 55(33.54%)in 2005-2015 set up HAI management departments.HAI management professionals per 1 000 beds in 165 hospitals decreased from 4.80 in 1995 to 4.09 in 2015,occupational categories in HAI management departments in 1995 -2015 were significantly different (χ2 =26.22,P <0.01).The constituent ratios of education background and profession of HAI manage-ment professionals in each province in 1995-2015 were significantly different(χ2 =242.91,47.10,respectively,all P <0.01).In 1995 and 2005,70.81%,53.30% of professionals were with college degree or below;in 2015,the percentage of professionals with bachelor’s degree,doctoral degree,and master’s degree were 53.79%,2.45%, and 22.86% respectively.Most professionals were nursing staff,but the percentage decreased from 58.38% in 1995 to 45.96% in 2015.Conclusion Although HAI management organizations have developed for 30 years and made some achievements,there still remain some problems,the proportion of professionals needs to be enhanced,and personnel structure should be optimized.