There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Objective:This study aimed to retrospectively analyze the clinical characteristics and prognosis of patients with acute leukemia in the plateau.Methods:The clinical information of patients diagnosed with acute leukemia from February 2010 to April 2023 at the People's Hospital of Tibet Autonomous Region was reviewed and collected, including blood cell count, morphology, immunophenotype, cytogenetics, and molecular data. Survival analysis was conducted to analyze the outcome of patients with acute leukemia.Results:This study enrolled 105 patients with acute leukemia, including 24 with acute lymphoblastic leukemia (ALL), 62 with acute myeloid leukemia (AML), and 19 with acute leukemia without baseline data. Of the patients with ALL, 11 underwent bone marrow testing for immunophenotype, all of whom were B-cell lineage. The main FAB subtype of patients with AML was M 2 (25/57), followed by M 3 (12/57), M 5 (6/57), M 4EO (5/57), M 1 (4/57), M 4 (4/57), and M 0 (1/57). The complete remission rates of patients with ALL, acute promyelocytic leukemia (APL), and AML (non-APL) after one course of induction therapy were 57.1% (8/14), 100% (6/6), and 53.6% (15/28), respectively. The median event-free survival (EFS) and overall survival (OS) for patients with ALL were 2 (95% CI 0-9) and 3 (95% CI 0-9) months, respectively, with a median followup of 37 (95% CI 17-57) months. Patients with APL did not reach median EFS or OS, whereas the median EFS and OS for core binding factor AML (CBF-AML) cases were 10 (95% CI 0-21) months and 13 (95% CI 3-23) months, respectively, and patients with non-CBF-AML had inferior median EFS (2 months, 95% CI 1-3) and OS (2 months, 95% CI 1-3) ( P<0.01). Patients with ALL treated from 2020 to 2023 demonstrated trends toward better EFS ( P=0.16) and OS ( P=0.10) than those treated from 2010 to 2019. Similarly, trends toward superior EFS ( P=0.27) and OS ( P=0.12) were observed in patients with AML treated from 2016 to 2023, in comparison with those treated from 2010 to 2015. Conclusion:Progress in the treatment and prognosis of patients with acute leukemia in the plateau has been observed in recent years, which can be further promoted by precision diagnosis and tailored regimens.

Objective:This study aimed to retrospectively analyze the clinical characteristics and prognosis of patients with acute leukemia in the plateau.Methods:The clinical information of patients diagnosed with acute leukemia from February 2010 to April 2023 at the People's Hospital of Tibet Autonomous Region was reviewed and collected, including blood cell count, morphology, immunophenotype, cytogenetics, and molecular data. Survival analysis was conducted to analyze the outcome of patients with acute leukemia.Results:This study enrolled 105 patients with acute leukemia, including 24 with acute lymphoblastic leukemia (ALL), 62 with acute myeloid leukemia (AML), and 19 with acute leukemia without baseline data. Of the patients with ALL, 11 underwent bone marrow testing for immunophenotype, all of whom were B-cell lineage. The main FAB subtype of patients with AML was M 2 (25/57), followed by M 3 (12/57), M 5 (6/57), M 4EO (5/57), M 1 (4/57), M 4 (4/57), and M 0 (1/57). The complete remission rates of patients with ALL, acute promyelocytic leukemia (APL), and AML (non-APL) after one course of induction therapy were 57.1% (8/14), 100% (6/6), and 53.6% (15/28), respectively. The median event-free survival (EFS) and overall survival (OS) for patients with ALL were 2 (95% CI 0-9) and 3 (95% CI 0-9) months, respectively, with a median followup of 37 (95% CI 17-57) months. Patients with APL did not reach median EFS or OS, whereas the median EFS and OS for core binding factor AML (CBF-AML) cases were 10 (95% CI 0-21) months and 13 (95% CI 3-23) months, respectively, and patients with non-CBF-AML had inferior median EFS (2 months, 95% CI 1-3) and OS (2 months, 95% CI 1-3) ( P<0.01). Patients with ALL treated from 2020 to 2023 demonstrated trends toward better EFS ( P=0.16) and OS ( P=0.10) than those treated from 2010 to 2019. Similarly, trends toward superior EFS ( P=0.27) and OS ( P=0.12) were observed in patients with AML treated from 2016 to 2023, in comparison with those treated from 2010 to 2015. Conclusion:Progress in the treatment and prognosis of patients with acute leukemia in the plateau has been observed in recent years, which can be further promoted by precision diagnosis and tailored regimens.

Objective:To evaluate the clinical efficacy and safety of retrograde intrarenal surgery(RIRS) and miniaturized percutaneous nephrolithotomy(mini-PCNL) in the treatment of lower pole kidney stones with a diameter <1.5 cm.Methods:The data of 95 patients with lower pole kidney stones with a diameter <1.5 cm treated in Renmin Hospital of Wuhan University from June 2017 to October 2020 were retrospectively analyzed. According to different surgical methods, the patients were divided into RIRS group and mini-PCNL group. There were 51 cases in RIRS group and 44 cases in mini-PCNL group. There was no significant difference in age [(48.2±11.4) years vs. (46.4±14.1) years], body mass index [(21.9±2.4) kg/m 2 vs. (20.7±3.2) kg/m 2], gender [male/female: 37/14 vs. 24/20], stone CT [(746.42±164.24)HU vs. (858.62±148.72)HU], creatinine [(71.3±21.6)μmol/L vs. (63.5±20.3)μmol/L], stone location (left/right: 26/25 vs. 23/21), stone diameter [(10.5±2.1) mm vs. (12.5±2.4) mm], infundibulopelvic angle [(43.32±9.42) degrees vs. (43.82±10.34) degrees], infundibular length [(24.92±4.85)mm vs. (24.37±5.26)mm] and infundibular [(9.26±3.04)mm vs.(9.46±2.94)mm] between the two groups ( P>0.05). The operation time, stone-free rate, hospital stay and postoperative complications between the two groups were compared. Results:Compared with the mini-PCNL group, the RIRS group had significantly smaller decrease in postoperative hemoglobin [(1.53±0.92) g/L vs. (4.54±2.46) g/L, P<0.05], the postoperative hospital stay was shorter [(2.52±0.94) d vs. (4.51±1.25)d, P<0.05], and postoperative visual analogue score was lower [(2.43±0.92) vs. (3.24±0.76), P<0.05]. The operation time of the mini-PCNL group was shorter than that of the RIRS group [(42.32±13.28) min vs. (54.24±14.43)min, P<0.05]. There was no significant difference in postoperative complications [5.9% (3/51) vs. 11.4% (5/44), P>0.05], postoperative cveatinine [(71.3±21.6) μmol/L vs. (63.5±20.3) μmol/L, P>0.05], postoperative intestinal function recovery time [(25.46±10.28)h vs. (32.43±9.25)h, P>0.05] and stone-free rate [92.2% (47/51) vs. 97.7% (43/ 44), P>0.05] between the two groups. Conclusions:Both RIRS and mini-PCNL are effective and safe minimally invasive treatments for lower pole kidney stones with a diameter < 1.5 cm. RIRS has shorter operation time, less blood loss, lower pain score and faster postoperative recovery.

AIM: To evaluate the differences of macular vascular network measured by optical coherence tomography angiography(OCTA)between severe non-proliferative diabetic retinopathy(S-NPDR)eyes and health eyes, and explore the changes of these OCTA characteristics in patients with S-NPDR before and after panretinal photocoagulation(PRP).

METHODS: This was a prospective study including 31 eyes from 18 consecutive patients with S-NPDR and 31 eyes of healthy subjects. We measured macular vascular density and foveal avascular zone(FAZ)area and volume by an OCTA device.

RESULTS: Compared to the normal control group, in superficial retinal capillary plexus(SCP), macular vascular density decreased in S-NPDR group, except foveal vascular density unchanged. Consistently, in deep retinal capillary plexus(DCP), macular vascular density was also lower in S-NPDR group. In addition, FAZ area and volume expanded in S-NPDR eyes. At 6mo post-PRP in S-NPDR eyes, foveal SCP and DCP densities increased significantly, while FAZ area and volume decreased. At 3mo post-PRP, only foveal vascular density in DCP increased. The changes of foveal SCP and DCP densities as well as FAZ area and volume were not statically significant at 1mo post-PRP.

CONCLUSION: Macular vascular network was impaired in S-NPDR assessed by OCTA. Although OCTA parameters were not significantly affected by PRP in 1 and 3mo period, at 6mo follow-up parameters became significant after PRP.

Retina and optic nerve both originate in brain, therefore they have the similar structure and functional characteristics of the brain. Exploring the performance of the central optic nervous disorder on the retina will be beneficial to uncovering the interaction mechanism between brain and eye. As an extension of the central nervous system, the retina contains ganglion cell, a special neuron, whose axon form the optic nerve and has access into the central nervous system. Therefore, the retina can be used as a mirror reflecting neurodegenerative diseases structurally and functionally. With the development of imaging technology, optical coherence tomography(angiography)has become the mainstream tool for ophthalmological clinical diagnosis due to its easy operation and low cost. In recent years, discovering biomarkers of neurodegenerative diseases, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis and so on, in the retinal optical coherence tomography images has gradually become an emerging research direction. In this review, we summarized the research progress of neurodegenerative diseases analysis based on the retinal images in the past decade, and provide a prospect to inspire further research as far as possible.