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 compare quality control (relative purity and specific activity) and process control [plasminogen (Pg) antigen recovery and potency recovery] indexes of samples before and after adding the Q chromatography step to the full chromatography process of human Pg, thereby determining whether the addition of this step could improve Pg recovery by affinity chromatography. Methods: A Q chromatography step was added before the Pg affinity chromatography in the original Pg chromatography process. The loading solution, flow through solution and eluate of Q chromatography and Pg affinity chromatography were collected. The potency of coagulation factor Ⅱ (FⅡ), Ⅶ (FⅦ), Ⅷ (FⅧ), Ⅸ (FⅨ), and Ⅹ(FⅩ) were detected by the coagulation method, the total protein content was detected by the BCA method, and the Pg potency was detected by the chromogenic substrate method. The content of specific plasma proteins was detected by immunoturbidimetry, the potency recovery of coagulation factors was calculated, and the flow direction of coagulation factors was analyzed. The recovery of different plasma protein antigens were calculated, and the distribution of impurity proteins was analyzed. The relative purity and specific activity of Pg, antigen content, and potency recovery in the target fractions were calculated and compared with the original process indicators, so as to determine the effect of adding Q chromatography on the original process. Furthermore, the reproducibility after process modification was assessed. Results: 100% of FⅡ, FⅩ, and FⅨ, 87.81% of FⅧ, and 40.44% of FⅦ in filtered plasma were removed by Q chromatography. The residual FⅦ (53.26%) and FⅧ (13.30%) in Q flow-through fraction were completely removed by Pg affinity chromatography. In both the original process (without Q-chromatography) and the modified process (with Q-chromatography), non-target plasma proteins mainly existed in the flow-through fraction of Pg affinity chromatography. The antigen recovery of IgM, ceruloplasmin (CER), and fibronectin (FNC) in Q-chromatography flow-through fraction were reduced. In contrast, antigen recovery of other plasma proteins [IgG, IgA, Pg, albumin (AlB), alpha-1-antitrypsin (AAT), and fibrinogen (Fg)] were all >90%, which were consistent with the protein composition and proportion in the original affinity chromatography loading solution. Compared with the recovery rate of Pg antigen in the original process (74.4%), the total recovery of Pg antigen in the modified process was significantly increased (89.97%). Compared with the recovery of IgG (97.48%) and Fg (95.32%) in the Pg affinity flows-through fraction of the original process, the modified process resulted in a slight reduction in the recovery of IgG (94.60%), while the recovery of Fg was not affected (95.05%). The potency recovery rate, specific activity, and relative purity of Pg after Q chromatography were 99.3%, 0.016 U/mg, and 0.15%. These values were the same as those of Pg affinity chromatography loading solution by the original process, indicating that introduction of Q chromatography did not affect subsequent Pg affinity chromatography. Compared with the recovery of Pg antigen in three batches of the original process (66.49±1.02)%, the recovery of Pg antigen in the affinity chromatography eluent of the modified process [five batches; (77.43±4.43)%] was significantly improved. Furthermore, the potency recovery was (86.80±4.28)%, the relative purity was (81.99±1.25)%, the specific activity was (8.679±1.073)U/mg, and the process was reproducible. Conclusion: The addition of Q chromatography could improve the recovery of Pg affinity chromatography in the full chromatography process.

【Objective】 To determine the ELISA kit for screening convalescence plasma with high potency of SARS-CoV-2 IgG by comparing and analyzing the plasma detection results of convalescent plasma collected in different periods via ELISA kits from two manufacturers and the results of mixed plasma with different potency via pseudovirus neutralization experiments. 【Methods】 Two ELISA kits from different manufacturers(named A, B) were used to detect the plasma of 269 convalescent patients collected from Feb.2020~Jan.2022. The correlation and concordance rate of the two results were analyzed to determine the kit preliminarily. According to the titers of diluted series of standard of the preliminary selected kit, 5 mixed plasma samples (G4-G128) with different potency were prepared. The correlation of ELISA IgG results of product A/B, as well as the pseudovirus neutralization test of the original strain, Omicron mutant BA.1 and BA.2 strains were analyzed. Combined with the outside-well dilution mode of the strongly positive samples, the kit for high potency of SARS-CoV-2 IgG screening was determined. 【Results】 When the internal control reference B2 was used as the standard, the detection sensitivity of product A and B was 1∶32 vs 1∶8; the detection sensitivity of product A was 4 times that of product B. The correlation Pearson r between the results given by two kits was 0.944 1(P<0.000 1). Product B with low sensitivity was primarily selected as an alternative kit. The ELISA IgG results of samples from mixed plasma showed that the order of correlation r between product A and B was 0.988. The correlation r between product A and neutralization antibody potency of the three viruses was original strain (0.978)>BA.2(0.970)>BA.1(0.799); the order of correlation r between ELISA IgG results of product B and neutralization antibody potency of the three viruses was original strain(0.994)>BA.2(0.968)>BA.1(0.804). If twice-diluted B2 was taken as the excellent standard, 55.4% of product B met the criterion, while 47.2% of product A met.For positive plasma with high IgG potency, the product B kit required a lower dilution of the sample, which was more convenient to operate. 【Conclusion】 Both of the ELISA IgG kit from product A and B can be used to screen IgG antibodies of SARS-CoV-2, while product B is more suitable for screening positive plasma with high IgG potency.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Objective:To observe the efficacy and safety of teriprizumab combined with bevacizumab in above the second line treatment of high-level microsatellite instability (MSI-H) type metastatic colorectal cancer (mCRC) patients.Methods:From February 2019 to September 2019, 56 patients with MSI-H mCRC admitted to the Third Affiliated Hospital of Guangdong Medical University were selected and divided into control group and test group by random number table method, with 28 cases in each group. The control group was treated with bevacizumab, and the test group was treated with teriprizumab combined with bevacizumab. The objective response rate (ORR), disease control rate (DCR), progression-free survival, overall survival and incidence of adverse reactions were compared between the two groups.Results:The ORR and DCR of the test group were 60.71% (17/28) and 75.00% (21/28) respectively, higher than 28.57% (8/28) and 46.63% (13/28) of the control group, with statistically significant differences ( χ2=5.85, P=0.016; χ2=4.79, P=0.029). The median progression-free survival of patients in the control group and the test group were 3.5 months and 5.8 months respectively, with a statistically significant difference ( χ2=9.83, P=0.003). The median overall survival of patients in the control group and the test group were 12.1 months and 16.2 months respectively, with a statistically significant difference ( χ2=6.13, P=0.007). There were no significant diffe-rences in the incidences of hematological reaction (17.86% vs. 14.29%, χ2=0.13, P=0.716), cardiovascular injury (10.71% vs. 14.29%, χ2=0.16, P=0.686), liver and kidney function injury (25.00% vs. 21.43%, χ2=0.10, P=0.752), gastrointestinal reaction (28.57% vs. 35.71%, χ2=0.33, P=0.567), skin and mucosal injury (7.14% vs. 10.71%, χ2=0.35, P=0.553), nervous system disease (3.57% vs. 14.29%, χ2=2.25, P=0.134), endocrine reaction (3.57% vs. 10.71%, χ2=1.29, P=0.256), alopecia (14.29% vs. 17.86%, χ2=0.13, P=0.716) and fatigue (25.00% vs. 28.57%, χ2=0.27, P=0.605) between the control group and the test group. Conclusion:The combination of teriprizumab and bevacizumab can improve the short-term and medium-long-term efficacy of patients with MSI-H mCRC, which is safe and reliable.

Objective To study the effect of enhancer of rudimentary homolog (ERH) gene on migration and invasion in human bladder cancer T24 and 5637 cells.Methods After knocking out the ERH gene of human bladder cancer T24 and 5637 cells,Wound healing assay,Transwell cell migration assay and Transwell cell invasion assay were used to verify the migration and invasion function.Cell migration related protein was detected by Western blot.Nude mouse tail vein transfer assay was used to study the metastasis ability of bladder cancer cells in vivo.Results (1) The Wound healing assay showed that there were significant differences in the migration cell counts of human bladder cancer 5637 and T24 (P ＜ 0.05).(2) There were significant differences in migration and invasion cell counts of Transwell assay (P ＜0.05).(3) Western blot showed that the expression of E-Cadherin in human bladder cancer 5637 cells and T24 cells was significantly increased (P ＜ 0.05) after knocking out ERH gene,while the expression of Fibronectin,Twist,Vimentin and Snail2 protein were significantly decreased (P ＜ 0.05).(4) Nude mouse tail vein transfer assay showed that lung metastases were significantly reduced in the ERH knockout group compared with the normal ERH group.Conclusions Both in vitro and in vivo experiments suggest that ERH knockout affects the migration and invasion of human bladder cancer T24 and 5637 cells.

Objective To study the effect and mechanism of Momordica anti-HIV protein of 30 ku (MAP30) on the migration of bladder cancer.Methods The IC50 of human bladder cancer 5637 and T24 cells was calculated by methyl thiazolyl tetrazolium (MTT) method.The migration ability of these two cells was evaluated by scratch migration test and Transwell cell migration test.The expression of migrating proteins such as matrix metalloproteinases (MMPs) and adhesion molecule N-cadherin were compared by Western blot.Results Scratch migration test:there were significant differences in migration rates of 5637 cells at 8 h and 22 h (P ＜ 0.05).There were significant differences in migration rates of T24 cells at 22 h (P ＜ 0.05),but no significant differences in migration rates at 8 h (P ＞ 0.05).The expression of Vimentin,Fibronectin,MMP-2,MMP-9 and N-Cadherin in 5637 cells and T24 cells of human bladder cancer decreased significantly after adding MAP30.The E-Cadherin expression in human bladder cancer 5637 cells were decreased,but no target band was detected in human bladder cancer T24 cells.Conclusions The ribosome-inactivating protein MAP30 can effectively inhibit the migration of human bladder cancer 5637 and T24 cells by inhibiting the EMT pathway and inhibiting the expression of MMPs.

Objective To investigate the effect of ERH gene knockdown on the proliferation and apoptosis of human bladder cancer T24 cells. Methods T24 cells infected by lentivirus with interference on ERH gene sequence were cloned to establish stable T24 cells clone in ERH gene suppression. The expression of ERH mRNA gene in bladder cancer was detected by using quantitative real time polymerase chain reaction (qPCR). The effects of ERH knockout on the cell proliferation and apoptosis were examined by using methylthiazolyl tetrazolium (MTT) assay, colony formation assay and flow cytometry. The effect of ERH knockout on the tumorigenic effect of T24 cells in vivo was verified by subcutaneous tumor formation in nude mice. Results After lentiviral transfection, qPCR results showed that the knockdown effect of ERH mRNA in ERH normal group (untreated T24 cells) was better than that in ERH gene knockdown group, and the difference was statistically significant [(1.006±0.126) vs. (0.079±0.007); t=12.72, P=0.0002]. After knocking out ERH gene, MTT assay showed that the proliferation ability of T24 cells in ERH gene knockdown group was weakened compared with ERH normal group, and the difference was statistically significant [A490 value: (0.13±0.00) vs. (0.66±0.01);t=104.61, P<0.0001]. Colony formation assay indicated that the ability of clone in ERH normal group was weakened compared with ERH gene knockdown group [(10.5 ±1.2) vs. (196.4 ±4.0); t= 73.63, P< 0.0001]. Flow cytometry showed that the cell apoptosis rate in ERH gene knockdown group was higher than that in ERH normal group [(11.0 ±0.5) ％ vs. (4.2 ±0.5) ％; t= 16.06, P<0.0001]. Imaging results of subcutaneous tumor formation in nude mice showed that the total fluorescence intensity of the tumor area in ERH gene knockdown group was (4.67 ±0.59) × 1010 μW/cm2, and the corresponding part in ERH normal group was (9.54±4.20) × 1010μW/cm2 (t=3.64, P=0.0051);tumor weight in ERH gene knockdown group was (0.80±0.62) g, and in ERH normal group was (1.79±0.71) g (t=3.33, P=0.0037). Conclusion ERH gene knockout can inhibit the proliferation of human bladder cancer T24 cells, and promote the cell apoptosis.

Objective To understand how social and cultural factors influence sexual perceptions, sexual practices, and HIV transmission among men who have sex with men at selected sites in China. Methods Qualitative methodology was used and face to face, semi-structured, in-depth interviews conducted from April 2013 to October 2015 in Sichuan, Jiangxi, Henan, Heilongjiang provinces and Chongqing municipality of China. Results A total of 184 men who have sex with men participated in the interviews. Forty-eight originated from Henan Province, and 12, 50, 47, and 27 from Jiangxi, Heilongjiang, Sichuan provinces and Chongqing municipality, respectively. A total of 122 participants (66.3%) were under 30 years of age, 111 were college graduates (61.3%), 140 were unmarried (76.5%), and 74 were HIV positive (40.2%). Among interviewees, 6% (11 MSM) were employed at nongovernmental organizations. The main findings revealed that:Owing to sociocultural influences and social norms, most homosexual men concealed their sexual orientation and married females so as to fulfill their family obligation;this may encourage HIV transmission from a high-risk population to the general population; the main features of male homosexual behaviors, as well as those of the associated community and subculture, included hedonism, less concern about health, drug abuse, encouraging of high risk behaviors among men who have sex with men, and negative attitudes regarding HIV prevention; subgroups among MSM were found to have differential HIV transmission risk behaviors, with young men more vulnerable to infection with HIV. Conclusion Sociocultural factors, including external socioenvironmental circumstances and internal MSM community subcultures, have adverse impacts on HIV transmission among men who have sex with men. Because there were varied behavior modes and HIV transmission risks among MSM subgroups, further study focusing on MSM subgroups is imperative, to provide a basis for more targeted and effective prevention strategies.

Objective To understand how social and cultural factors influence sexual perceptions, sexual practices, and HIV transmission among men who have sex with men at selected sites in China. Methods Qualitative methodology was used and face to face, semi-structured, in-depth interviews conducted from April 2013 to October 2015 in Sichuan, Jiangxi, Henan, Heilongjiang provinces and Chongqing municipality of China. Results A total of 184 men who have sex with men participated in the interviews. Forty-eight originated from Henan Province, and 12, 50, 47, and 27 from Jiangxi, Heilongjiang, Sichuan provinces and Chongqing municipality, respectively. A total of 122 participants (66.3%) were under 30 years of age, 111 were college graduates (61.3%), 140 were unmarried (76.5%), and 74 were HIV positive (40.2%). Among interviewees, 6% (11 MSM) were employed at nongovernmental organizations. The main findings revealed that:Owing to sociocultural influences and social norms, most homosexual men concealed their sexual orientation and married females so as to fulfill their family obligation;this may encourage HIV transmission from a high-risk population to the general population; the main features of male homosexual behaviors, as well as those of the associated community and subculture, included hedonism, less concern about health, drug abuse, encouraging of high risk behaviors among men who have sex with men, and negative attitudes regarding HIV prevention; subgroups among MSM were found to have differential HIV transmission risk behaviors, with young men more vulnerable to infection with HIV. Conclusion Sociocultural factors, including external socioenvironmental circumstances and internal MSM community subcultures, have adverse impacts on HIV transmission among men who have sex with men. Because there were varied behavior modes and HIV transmission risks among MSM subgroups, further study focusing on MSM subgroups is imperative, to provide a basis for more targeted and effective prevention strategies.