Objective To compare the clinical efficacy and safety differences between the triple immunosuppressive regimen of mizoribine (MZR) or mycophenolate mofetil (MMF) combined with tacrolimus (Tac) and glucocorticoids of kidney transplant recipients in one year after transplantation. Methods A single-center retrospective cohort study design was adopted. The clinical data of 156 patients who underwent the first allogeneic kidney transplantation at the Third Hospital of Peking University from January 2022 to December 2024 were included. The patients were divided into the MZR group (78 cases) and the MMF group (78 cases) based on the initial immunosuppressive regimen after transplantation. The baseline data, medication use in one year after transplantation, blood routine indicators, adverse events and clinical outcomes were compared between the two groups. For the repeated-measurement longitudinal data, repeated-measurement analysis of variance was used to evaluate the main effects of the groups, time and their interaction effects. Results At the primary efficacy endpoint, there were no statistically significant differences in the one-year survival rate, graft survival rate and incidence of acute rejection between the two groups (all P > 0.05). In terms of medication patterns and laboratory test indicators, there were significant time main effects and "time × group" interaction effects for Tac dosage (all P < 0.05). The Tac dosage in the MZR group was lower than that in the MMF group from 2 to 3 months after transplantation, and it was higher in the MZR group than in the MMF group from 7 to 12 months and one year after transplantation. White blood cell count in the MZR group was higher at one month after transplantation, and the platelet count was higher one year after transplantation (all P < 0.05). In terms of infection, the incidence of novel coronavirus and Pneumocystis jirovecii pneumonia infections in the MZR group was lower (all P < 0.05). In terms of metabolic indicators, the post-transplantation uric acid level was better in the MZR group than in the MMF group, but the total cholesterol level was higher one year after transplantation (all P < 0.05). In terms of liver function, there was a brief and mild increase in transaminase in the early stage after transplantation in the MZR group. Conclusions During the one-year follow-up after transplantation, both the MZR and MMF regimens demonstrate comparable immunosuppressive efficacy and overall safety in Chinese kidney transplant recipients. The MZR regimen shows clear advantages in reducing specific infection risks, alleviating bone marrow suppression and improving uric acid metabolism, but its potential impact on blood lipids needs to be monitored. Therefore, the MZR regimen may be an effective and safe alternative immunosuppressive option for kidney transplant recipients, especially those with high infection risk, poor hematological tolerance, or comorbid hyperuricemia.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective:To explore the clinicopathological and genetic characteristics of sporadic medullary thyroid carcinoma (MTC) and new therapeutic targets for sporadic MTC.Methods:Based on family and personal disease history, we identified 32 sporadic MTC who underwent surgical resection from Jan 2010 to Dec 2022. Clinicopathological and immunohistochemical features were analyzed in all patients, while 6 of them were subject to the whole exome sequencing (WES).Results:Compared with those of low-grade sporadic MTC, patients with high-grade tumors were more likely to have lymph node metastasis at presentation ( χ2=4.428, P=0.040); less likely to be cured by biochemical treatment ( χ2=4.072, P=0.044). Pathological grading scheme, biochemical cure, and TNM stage were independent risk factors of disease free survival. WES was performed on 6 pairs of normal tissues. We screened RET and RAS as driver mutations, and the mutation ratio was 3/6 respectively. Patients with RET or RAS mutations had no recurrence. In addition, we detected PDGFRA somatic mutation, with a mutation ratio of 1/6. Conclusions:For sporadic MTC cases, the pathological grading system has important prognostic value, and RET and RAS somatic mutations are the main driver mutations. PDGFRA are potential therapeutic targets for sporadic MTC.

Objective:To establish a computer-aided design and 3D printing system for precise implantation of micro implant anchorage, and accurately calibrate the position and direction of micro implant implantation.Methods:A retrospective selection was conducted on 15 patients (30 in total) who underwent micro implant implantation surgery from the Department of Stomatology, the Affiliated Hospital of Jiangnan University from November 2019 to November 2021, including 6 males and 9 females, aged (17.1±6.3)years old. The preoperative patient was photographed with cone beam computed tomography (CBCT) and the collected DICOM data format was output. A 3D scan was performed on the patient′s preoperative analysis model to obtain the STL file of the model scan. The CBCT data and model data were fitted and matched using 3Shape Implant Studio software, and the thickness of the guide plate, the amount of undercut compensation, and the size of the key component collar were designed. The 3D printer was used for printing after resizing. Using the assist method to implant micro implants, CBCT was taken postoperatively to compare the preoperative design with the postoperative results.Results:After fitting the postoperative CBCT with the designed CBCT of the micro implant, it was found that the micro implant was consistent with the preoperative design, maintained a safe distance and parallel to the adjacent tooth root, and did not damage the maxillary sinus and other areas. No detachment of the micro implant anchorage was observed 1 or 3 months after surgery. The application of assisted micro implant anchorage 3D guide plate was reliable, with accurate implantation position and direction, and can be implanted in most parts of the oral cavity.Conclusions:The use of computer-aided design and 3D printing system to create an assistive micro implant anchorage 3D guide plate can accurately locate the position and direction of the micro implant, which is worthy of clinical promotion and application.

OBJECTIVE:To establish a method for the content determination of Esomeprazole sodium for injection. METH-ODS:UPLC-MS/MS was performed. The column of ZORBAX Eclipse Plus C18 with 0.1% formic acid-methanol(73∶27,V/V)at a flow rate of 0.3 ml/min,column temperature was 35℃,analysis time was 5 min,injection volume was 2μl;ionization mode was positive ion mode,ion source temperature was 150 ℃,capillary voltage was 3.0 kV,cone voltage was 50 V,cone flow was 150 L/Hr,desolvation temperature was 450 ℃,desolvation gas flow was 900 L/Hr,nebuliser pressure was 7.0 Bar,parent ion scan range was 100-800 mz/mz,working mode was multiple reaction monitoring mode. RESULTS:The linear range of esomeprazole was 0.2-20.0 ng/ml(r=0.999 7);the limit of quantitation was 50 pg/ml;RSDs of precision,stability and reproducibility tests were lower than 2%;recovery was 99.93%-100.05%(RSD=0.1%,n=9). CONCLUSIONS:The method is simple and accurate,and can be used for content determination of Esomeprazole sodium for injection.

Objective To compare the effects of repetitive transcranial magnetic stimulation (rTMS) at various low frequencies on upper limb function after cerebral infarction.Methods Fifty patients were randomly assigned to a control group (10 cases),a sham rTMS group (10 cases) or an rTMS group which had three sub-groups treated at 0.25 Hz,0.5 Hz and 0.75 Hz with 10 cases in each.All of the patients were treated with conventional medical treatment and rehabilitation training.The sham and true rTMS groups received rTMS applied over the M1 area of the unaffected hemisphere,5 days per week for 4 weeks.Motor evoked potential (MEP) cortical latency,and central motor conduction time (CMCT) were measured and the Fugl-Meyer assessment (FMA),motricity index (MI) and a Hong Kong functional test for the hemiplegic upper extremity (FTHUE-HK) were evaluated beforehand and at Post 1 after 2 weeks of treatment and Post 2 after 4 weeks of treatment.Results The average CMCT and FMA scores of the control and sham rTMS groups both had improved significantly at Post 2.There was no significant difference in any of the indices between those 2 groups at any time point.At Post 1,the average MEP cortical latencies of the 0.25 Hz and 0.5 Hz subgroups had improved to be significantly better than those of the control and sham rTMS groups.The average CMCTs of the 0.25 Hz and 0.5 Hz rTMS subgroups were significantly shorter after treatment,and significantly better than those of the control and sham rTMS groups.At Post 2,the average MEP cortical latency of all groups except the control group showed significant improvement compared with pre-treatment.The 2 indices of the 0.25 Hz and 0.5 Hz subgroups were again significantly shorter than those of the control and sham rTMS groups,and the average CMCTs were significantly better than that of 0.75 Hz subgroup.At Post 1 the average FMA and MI scores of the rTMS subgroups had all improved significantly.In the 0.25 Hz and 0.5 Hz subgroups the average MI scores were significantly higher than those of the control and sham rTMS groups.The FTHUE-HK scores of those 2 subgroups had also improved significantly.At Post 2,the average FMA and MI scores of all groups and the FTHUE-HK scores of rTMS group had improved significantly.In the 0.25 Hz and 0.5 Hz subgroups,all of the indices were significantly better than in the control and sham rTMS groups.The average FTHUE-HK score of the 0.25 Hz subgroup was significantly superior to that of the 0.75 Hz subgroup.In the 0.75 Hz subgroup the average MI score was significantly higher than in the control and sham rTMS groups.Conclusions rTMS at either 0.25 Hz or 0.5 Hz applied to the unaffected hemisphere provides effective treatment for enhancing the excitability of the motor cortex and the motor function of a paretic upper limb after stroke.Compared with others,the total number of stimulus pulse in 0.25 Hz subgroup was the least,and priority consideration should be given to the frequency of 0.25 Hz when using rTMS in clinical treatment of cerebral infarction.

AIM: To explore a relative quantitative method by establishing HPLC digitized fingerprints of Fructus Gardeniae and taking the control medicinal material as a reference substance. METHODS: The chromatographic fingerprints were obtained by injecting the sample solution each time on a CenturySIL C_(18) BDS column (20 cm?4.6 mm,5 ?m) with the gradient elution solvent system composed of 1% acetate acid-water and 1% acetate acid-acetonitrile.The flow rate was 1.0 mL/min,the column temperature was maintained at(30?0.15) ℃ and the detection wavelength was set at 265 nm.The HPLC fingerprints of the control medicinal material for Fructus Gardeniae were obtained under different injection volumes and calculated by "the digitized evaluation system of the traditional Chinese medicine fingerprint with the super-information characteristics".Equivalent regression curves were obained by making linear regression between the fingerprint peak areas and apparent injection amounts.(RESULTS:) 35 co-possessing peaks were selected as the fingerprint peaks of Fructus Gardeniae by taking Geniposide peak as the reference peak.Both the equivalent relation between each of the ten places and control medicinal material of Fructus Gardeniae and the equivalent relation between each fingerprint peak of different places and that of Fructus Gardeniae control medicinal material were calculated by equivalent regression curves. CONCLUSION: This method can be useful in the quality control of Fructus Gardeniae.It is also of importantance in deeply studying the relative amounts of single fingerprint peak,and it provides reference value in extending the quantitative evaluation methods of TCM.

AIM: To develope a reversed-phase high performance liquid chromatographic method for the quantitative determination of chlorogenic acid and caffeic acid in Shegan Kangbingdu Injection. METHODS: The operation was carried out in the Kromasil ODS column with the mobile phase consisting of a mixture of water-methanol-acetonitril aceti acid(95∶10∶5∶2,v/v),in which the flow rate of 1.0 mL/min and UV detection wavelength at 326 nm were set to determine the contents of chlorogenic acid and caffeic acid. RESULTS: There were good linear relations between the concentrations and the peak-areas of chlorogenic acid and caffeic acid.The relative standard deviation of peak areas for chlorogenic acid or caffeic acid were 0.60%,0.32%,respectively.The two kinds of standard solutions were both stable in 16 h(RSD=0.54% for CGA,0.11% for CFA).The average recovery was 100.1%,99.6% for CGA,CFA,repectively.The detectable limit(S/N=3)was 0.012,0.020 mg/L,and the quantitative limit (S/N=10) was 0.037,0.052 mg/L,repectively. CONCLUSION:The method is simple,sensitive,rapid and accurate,and can be used for the quality control of Shegan Kangbingdu Injection

AIM: A capillary electrophoresis fingerprints(CEFP) method of Fructus Gardeniae was established to evaluate its quality. METHODS: The background electrolyte(BGE) was 25 mmol/L sodium borate solution containing 10% acetonitrile.The detection wavelength was 228 nm and 24 kV was applied.Fructus Gardeniae was extracted by water and injectded for 15 s(9 cm).Some parameters were used to evaluate the similarities.(RESULTS): 24 co-possessing peaks were selected as the fingerprint peaks of Fructus Gardeniae taking chlorogenic acid peak as the reference peak.The similarities between each of the ten places and the standard CEFP of Fructus Gardeniae were evaluated both qualitatively and quantitatively.The CEFP was also evaluated by the information index(I) and the relative information index(I_r). CONCLUSIONS: The CEFP has acceptable precision,reproducibility and can be used to control the quality of Fructus Gardeniae.

AIM: A HPLC fingerprint method for the quality control of Fructus Forsythiae has been established. METHODS: The chromatographic fingerprints were determined by injecting 5 ?L of the sample solution each time on a CentriSIL BDS colunm(20 cm?4.6 mm,5 ?m) with the gradient elution solvent system composed of 1% acetate acid water and 1% acetate acid acetonitrile.The flow rate was 1 mL/min,the colunm temperature was maintained at(30?0.15)℃ and the signals were acquired at 265 nm.The chromatographic fingerprints were also evaluated by the chromatographic fingerprint index(F),information index of chromatographic fingerprint(I).(RESULTS:)30 co-possessing peaks were selected as the fingerprint peaks,the similarities among samples of Fructus Forsythiae come from 10 production places and its standard chromatographic fingerprints were calculated taking coffeic acid peak as the reference peak. CONCLUSION: This method with good characteristics and specificity can be used in the quality control of Fructus Forsythiae.