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

The article summarizes the clinical experience of Professor JIA Chunsheng in treating cubital tunnel syndrome with various traditional Chinese medicine therapies,including superficial point-toward-point auricular acupuncture,ordinary acupuncture,fire-needle therapy,and oral Chinese medication,to inherit his academic characteristics,such as meridian-identified and stage-identified treatments,stressing the patient's body constitution and state,and emphasizing the holistic treatment,and to provide references for the popular science education and clinical treatment of cubital tunnel syndrome.

Objective:To determine the predictive value of preoperative monocyte-to-lymphocyte ratio(MLR) for prognosis in elderly patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy(RNU).Methods:A retrospective study was performed on 168 elderly patients who underwent RNU in Beijing Hospital between March 2004 to February 2019.Males accounted for 44.6% (75 patients) and females 55.4%(93 patients) of the patients. Median age at the time of surgery was 73(69-78) years, and 110 (65.5%) patients suffered from hydronephrosis. There were 147 cases(87.5%)with single tumor, and 21 cases(12.5%)with multiple tumors, including 75(46.6%) cases in renal pelvis or pelvi-ureteric junction, and 93(53.4%)cases in ureter. Open RNU was performed in 106(63.1%) patients, and laparoscopic method in 62(32.9%) patients. The optimal cutoff value of MLR was set as 0.22 by using the median.χ 2 test, which was used to detect the association between MLR(≤0.22 vs.>0.22) and clinicopathological variables. Survival analyses were performed using the Kaplan-Meier method and were compared using the log-rank test. Additional subgroup analyses(low grade vs. high grade) were performed according to pathological grade. Univariate and multivariate analysis by Cox’s proportional hazards model was used to determine the significance of MLR in respect to OS and PFS. Results:The follow-up period ranged from 19.2 to 86.9 months (median 51.9 months). Next, the cohort was divided into 2 groups , including 77 patients with low MLR(≤0.22) and 91 patients with high MLR(>0.22). High MLR was significantly more frequent in male patients(31.2% vs.56.0%), as well as those undergoing laparoscopic surgery (54.5% vs.70.3%)(All P<0.05). Based on a Cox univariate proportional hazards analysis, male gender( HR=1.793, 95% CI 1.003-3.205, P=0.049), presence of lymph node metastasis( HR=6.809, 95% CI 2.124-17.454, P=0.001) and high MLR( HR=2.287, 95% CI 1.259-4.154, P=0.007)were associated with poor OS. Male gender( HR=1.758, 95% CI 1.066-2.902, P=0.027), presence of lymph node metastasis( HR=6.524, 95% CI 2.542-16.748, P<0.001), lymphovascular invasion(LVI) ( HR=2.348, 95% CI 1.139-4.838, P=0.021), high MLR( HR=2.801, 95% CI 1.657-4.735, P<0.001)and PLR( HR=1.663, 95% CI 1.003-2.757, P=0.049) were significantly associated with subsequent PFS. By multivariate analysis, tumor site( HR=2.050, 95% CI 1.079-3.892, P=0.028), lymph node metastasis ( HR=6.641, 95% CI 1.852-23.811, P=0.004) and MLR( HR=2.089, 95% CI 1.062-4.113, P=0.033) were the independent risk factors for OS in elderly patients with UTUC. Tumor side( HR=2.024, 95% CI 1.033-3.965, P=0.040), multifocality ( HR=2.992, 95% CI 1.161-7.713, P=0.023), lymph node metastasis ( HR=6.454, 95% CI 2.026-20.564, P=0.002) and MLR( HR=2.866, 95% CI 1.554-5.284, P=0.001) were associated with PFS.The multivariate analysis of the significant risk factors established a postoperative risk stratification model for OS and PFS. The results showed significant differences among the 3 subgroups of patients with low(0 risk factor), intermediate(1 risk factor), or high risk(2-3 risk factors)(All P<0.05). Conclusion:MLR was an independent risk factor for OS and PFS in elderly patients with UTUC and patients with elevated MLR have worsen prognosis.

Objective:To investigate the effect of maximal androgen blockade(MAB)therapy on serum calcium, phosphorus and other metabolic indices in elderly patients with prostate cancer.Methods:Clinicopathological data of prostate cancer patients treated with MAB in our department from January 2010 to December 2018 were retrospectively analyzed.All patients underwent prostate biopsy for definitive diagnosis.Detailed data on patient's age, body mass index(BMI), previous medical history, treatment plan and peripheral blood indicators before and after endocrine treatment, such as blood calcium, phosphorus, hemoglobin, fasting blood glucose, triglycerides and cholesterol, were collected.Results:Patients had a mean age of(75.5±5.8)years and a mean BMI of(24.6±3.2)kg/m 2.Blood calcium levels exhibited a downward trend after MAB treatment compared pre-treatment[(2.12±0.44)mmol/L vs.(2.17±0.31)mmol/L, t=0.82, P=0.42], but had no significant difference.Serum phosphorus concentrations were higher and the calcium-phosphorus ratio was lower after MAB treatment than before treatment[(1.02±0.26)mmol/L vs.(1.17±0.34)mmol/L, 2.10±0.28 vs.1.88±0.60, t=-4.12 and 3.56, P<0.01]. After MAB treatment, blood fasting glucose[(6.50±1.55)mmol/L vs.(5.34±1.04)mmol/L, t=-7.82, P<0.01], triglycerides[(1.66±1.32)mmol/L vs.(1.22±0.59)mmol/L, t=-3.38, P<0.01]and cholesterol[(4.70±1.08)mmol/L vs.(4.16±0.90)mmol/L, t=-4.72, P<0.01]were elevated, while hemoglobin concentrations[(122.11±20.43)g/L vs.(130.78±23.98)g/L, t=3.98, P<0.01]were decreased compared with pre-treatment levels. Conclusions:MAB therapy can cause varying degrees of metabolic abnormalities in calcium and phosphorus metabolism, hemoglobin concentrations, blood glucose and lipid levels in elderly prostate cancer patients.The above indicators should be closely monitored during treatment, and treatment-related complications should be proactively prevented.

OBJECTIVE To analyze trimethylation of genome-wide histone H3 lysine 4(H3K4met3) induced by silicon dioxide(SiO2)through chromatin immunoprecipitation linked to microarrays(ChIP-chip)in lung fibroblast(LF)of rats. METHODS A primary co-culture model of rat alveolar macrophages (AM)and LF in vitro. AM were exposed to 100 mg · L-1 free SiO2 for 24 h,before LF were collected and the phenotype of LF was determined after transdifferentiation by immunohistochemistry. ChIP-chip was used to profile the variations of trimethylation in H3K4 of lung fibroblasts in CpG island regions. ChIP-qPCR was used to validate the microarray results. The mRNA expression of nfib and kpna3 was analyzed by qRT-PCR. RESULTS Totally 1815 (518 increased and 1297 decreased) genes of H3K4met3 displayed significant differences in SiO2 100 mg·L-1 group compared with control group(Cy3/Cy5 value>2.0 or <0.5,NimbleScan V2.5 software). The results of ChIP-qPCR were quite consistent with those of microarray. CONCLUSION There are significant differences in methylation of genome-wide H3K4 between SiO2 100 mg·L-1 group and control group. These novel candidate genes may become potential biomarkers or new interfered targets.

OBJECTIVETo evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).

METHODSPatients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.

RESULTSA total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).

CONCLUSIONAnagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.

Humans ; Hydroxyurea ; administration & dosage ; therapeutic use ; Platelet Aggregation Inhibitors ; administration & dosage ; therapeutic use ; Platelet Count ; Quinazolines ; administration & dosage ; therapeutic use ; Thrombocythemia, Essential ; drug therapy ; Treatment Outcome

Objective To compare the efficacy and side effects between systemic chemotherapy and hepatic arterial infusion by combination of oxaliplatin and 5-fluorouracil (FOLFOX-6) with 5-fluorouracil in the patients who have developed hepatic metastasis after colorectal cancer operation. The factors that would affect the prognosis without operational treatment were also analyzed. Methods 46patients who had signed the informed consents were allocated into two groups: the group with general chemotherapy (Trial Group includes 26 cases) and the one with hepatic arterial infusion chemotherapy (Control Group includes 20 cases). The total effective rate, the prognosis, the cytoxicitic side effects,quality of life, the total survival rate and the responses were the main parameters determined. Kaplan-Meier was used to analyze Mono-factor to the prognostic responses and the Cox mode was used to analyze poly-factor to the prognostic responses. Results The overall survival rate was significantly higher by using systemic treatment versus HAI(median, 15. 0 v 11.2 months;P＜0.05). The difference in overall responsive rate (CR+PR) between the two groups was statistically significant (50% v 10%;P=0. 011). No significant difference was found in PS scale during the treatment. (P=0. 126). Except for myelosuppression and abdominal pain, no significant difference was found in the other side effects. Univariate analysis revealed that the invasive lesions to serosa, the distribution of liver metastases, the size and number of liver metastases, primary carcinoma involving lymph nodes and the treatment were correlated with prognoses. Cox regression analysis showed that the larger diameter of liver metastases, the number of liver lesions, primary carcinomas involved in serosal layer and the treatment modules were independent prognostic factors. Conclusions The oxaliplatin-based FOLFOX-6 chemotherapy regiment has a better responsive rate and survival rate than the traditional infusion with 5-fluorouracil to the main hepatic artery for interventional therapy. The diameter of the hepatic metastasis larger than 5em, multiple hepatic metastasis and the primary lesions penetrating serosal layer suggest the poor prognosis. The oxaliplatin-based systematic chemotherapy has a better prognosis. Therefore,it is worth carrying on further study on modification of traditional hepatic arterial infusion and on evaluation of therapy by combination of the hepatic arterial infusion with the systematic chemotherapy.

BACKGROUND: The uterine arterial embolization which is a major method to treat hysteromyoma has bean widely used in clinic and achieved a satisfactory therapeutic efficacy. The study addressing the effect of trisacryl gelatin microspheres on uterine arterial embolization in a hysteromyoma guinea pig model has less bean reported yet. OBJECTIVE: To vedfy the feesibility of trisacryl gelatin microspheres to uterine arterial embolization in hysteromyoma guinea pig models. METHODS: A total of 30 adult female guinea pigs were randomly divided into two groups: pelvic cavity artery moulding group (n=10) was performed pelvic vascular casting mould to demonstrate the anatomical characteristics, such as source, running shape, length, diameter and branches; arterial embolization group (n=20) was induced hysteromyoma model using astrogen-progestogen replacement therapy and performed technical research and pathological analysis by bilateral uterine arterial embolization. RESULTS AND CONCLUSION: The trunks of uterine arteries were erupted from internal iliac arteries. The diameter of the trunks and its arcuate branches were (0.350±0.022) mm and (0.160±0.012) mm, respectively. The 20 guinea pigs of the arterial embolization group were succeeded in operating bilateral arterial embolization. The dosage of 40-120 pm and 100-300 μm trisacryl gelatin microspheras were (0.040t±0.005) mL and (0.017±0.002) mL respectively during the operation. The achievement ratio of establishing model was 75% in the arterial embolization group. On the pathological section, the microspheres could be found in the uterine arterial arcuate branches and second branches within the subsercsa and third branches. The myometrium Was thickening. The cells of the leiomyoma nodules arranged in palisade or weaving shapes. Ischemia and necrosis were evidently present in leiomyomas of guinea pigs after embolization, but the myometria and endometria had no pathological change of ischemia and necrosis. It is feasible to use trisacryl gelatin microspheres to operate uterine arterial embolization for hysteromyoma of guinea pigs and the embolization effects are satisfactory.

BACKGROUND: Currently, the widely used intervertebral disc degeneration models are induced by altering intervertebral disc biomechanics, damaging intervertebral disc structure or changing hereditary features with genetic technique. All these methods are vades from natural duration of intervertebral disc degeneration. OBJECTIVE: To evaluate the feasibility of the establishment of rabbit model of ischemic lumbar vertebrae adjacent to endplate by percutaneous puncture followed by pingyangmycin injection. METHODS: A total of 46 New Zealand white rabbits were selected and two vertebraes were divided as experimental group (L_5) and control group (L_4) in every rabbit. Vertebrae adjacent to endplate was punctured. Pingyangmycin (2 g/L) 1 mL was injected into rabbits in the experimental group. And 1 mL normal sodium was injected into the control group. Lumbar artery angiography was performed in 4 rabbits before operation. Six rabbits were randomly performed MRI and then were executed for vertebral histology at weeks 1,2, 3, 4, 5 and months 2, 3 after operation. Ischemic areas of L_5 were measured by the MRI and histological section at week 4 after operation. RESULTS AND CONCLUSION: MRI and histology of control group had not specific changes. MRI had not significant signal intensity changes in the first 2 weeks in the experimental group. At week 3 after operation, it demonstrated slightly hyperintense signal on T_2-weighted image (T_2WI) and fat-suppression T_2-weighted image (FS T_2WI), while fat-suppression T_1-weighted image (FS T_1WI) was hypointense signal. The signal changed more obviously at week 4. Histology of experimental group had not specific changes in the first 2 weeks. From weeks 3-4, bone trabecula arranged confusedly and disorderly, with gradually decreased osteocyte and marrow haemocytes, while adipocytes increased and coalesced. Cartilage corpuscle of endplate decreased and architecture became disorder. But the anulus fibrosus and nucleus pulposus had no obviously changes. The intervertebral disk of the experimental group degenerated at week 5, and the ischemia of lumbar vertebrae still existed and intervertebral disk degenerated more obviously at months 2-3 after operation. There was significant positive correlation of ischemic areas of experimental group between MRI and histology at week 4 (t-=0.965, P < 0.001). The rabbit model of ischemic lumbar vertebrae adjacent to endplate can be established successfully by peroutaneous puncture vertebrae adjacent to endplate followed by pingyangmycin injection. The operation is minimally invasive, simple and reproducible, with high success rate. This is a fairly ideal animal model to study the degeneration of the lumbar spine and intervertebral disc.