Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

OBJECTIVE: To analyze the laboratory detection results of hemolytic disease of the fetus and newborn(HDFN). METHODS: Related test results of 283 newborns and their mothers' blood samples from Kunming Maternal and Child Health Hospital from August 2023 to May 2024 were collected, including mother and child ABO blood group, RhD blood group, as well as 3 tests of HDFN, total bilirubin (TBil) and indirect bilirubin (IBil). RESULTS: 283 were ABO incompatibility, among which 187 were HDFN positive, with a positive rate of 66.08%; the positive rate of HDFN in neonates with antigen-A incompatibility was 74.12%(126/170), the positive rate of HDFN in neonates with antigen-B incompatibility was 53.57%(60/112), which was the highest in neonates with O/A incompatibility ［75.45%(126/167)］, followed by O/B incompatibility［54.55%(60/110)］. Group by age, the positive rates of HDFN in the ≤1 d group, 2 d group, 3 d group, 4 d group, 5 d group and ≥6 d group were 76.03%(111/146), 67.86%(38/56), 57.14%(24/42), 38.46%(5/13), 46.15%(6/13) and 23.08%(3/13), respectively. With the increase of age, the positive rates of HDFN gradually decreased, there was a statistically significant difference between the ≤3 day age group and >3 day age group ( P <0.05). There was no statistically significant difference in TBil and IBil levels between the "direct antibody+indirect antibody+release+" group and the HDFN negative group in newborns. HDFN infants exhibited a rapid increase in bilirubin levels within the first day after birth, with significantly higher TBil and IBil values compared to Non ABO-HDFN infants in the ≤1 day group ( P <0.01). However, the difference of bilirubin levels between the two groups gradually narrowed from 2-6 days after birth, and the difference was not statistically significant (P >0.05). The peak value of TBil and IBil occurred on the 4th day after birth in HDFN infants. CONCLUSION ABO-HDFN is most commonly seen in newborns whose mothers are type-O, and the positive rate was the highest in newborns with O/A incompatibility. The detection rate of HDFN is affected by the age of the newborns, and the two were correlated inversely. ABO-HDFN group developed more rapidly with a higher peak. Therefore, HDFN tests should be carried out as soon as possible for mothers and newborns with incompatible blood types, and appropriate treatment should be provided to prevent complications.
Humans ; Infant, Newborn ; ABO Blood-Group System ; Erythroblastosis, Fetal/epidemiology* ; Female ; China/epidemiology* ; Blood Group Incompatibility ; Male ; Bilirubin/blood*

OBJECTIVE: To evaluate the efficacy and safety of PD-1 inhibitor combined with azacitidine and HAG regimen in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: This study is a prospective, single-arm, phase II clinical trial that included R/R AML patients who met the inclusion criteria and were treated at The First Affiliated Hospital of Soochow University from December 2020 to August 2023. Patients could undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) after salvage therapy. The efficacy and safety were evaluated. RESULTS: Twenty patients were enrolled, including 14 males and 6 females, with an average age of (50.7±15.3) years. The overall response rate (ORR) after one cycle of the treatment was 75.0% (15/20), and 35.0% (7/20) of the patients achieved complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after two cycles of the treatment. Eight patients received allo-HSCT. The main adverse events were hematologic toxicities, and no grade 5 adverse events occurred. CONCLUSION The combination of PD-1 inhibitor, azacitidine, and the HAG regimen is a feasible and relatively safe treatment option for R/R AML, thus, to be worth further study.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Azacitidine/administration & dosage* ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; Hematopoietic Stem Cell Transplantation ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Aged

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To analyze the clinical characteristics of eosinophilic lung diseases(ELD) in children to enhance pediatricians′ understanding of ELD.Methods:In this retrospective cross-sectional study, a total of 149 children with ELD were recruited from Beijing Children′s Hospital, Capital Medical University between April 1, 2007 and March 31, 2022.Chi-square test, Fisher′s exact test, Mann-Whitney U test and Kruskal-Wallis test were used to analyze data and conclude clinical characteristics.Spearman correlation was used to analyze the correlation between eosinophils in peripheral blood and bronchoalveolar lavage fluid.Chi-square test and Kappa consistency test were used to compare the differences and consistency in diagnostic results between bronchoalveolar lavage fluid or lung biopsy and eosinophil elevation with chest imaging abnormalities. Results:(1)The isolated lung involvement was mostly caused by allergic bronchopulmonary aspergillosis(9 patients), and other system involvement by idiopathic hypereosinophilic syndrome(89 patients).(2)The main respiratory manifestations included coughing(90 cases, 60.4%) and expectoration(41 cases, 27.5%), while 23.5%(35 cases) of patients had no respiratory symptoms; 50.3% had digestive system involvement, and 40.9% had skin involvement.These were the two most commonly affected organs.(3)Spearman correlation was performed between eosinophils in peripheral blood and bronchoalveolar lavage fluid( r=0.3, P<0.05).Chi-square test was performed to compare ELD diagnosed by bronchoalveolar lavage fluid or lung biopsy with peripheral blood eosinophilia accompanied by abnormal chest imaging( P<0.05).Kappa consistency test(Kappa<0.2) showed poor consistency between the two diagnostic methods. Conclusions:ELD are present in children, and multiple etiologies may be pathogenic.Among children with ELD, the isolated lung involvement is mainly caused by allergic bronchopulmonary aspergillosis.The digestive system and skin are the most commonly affected organs, except for lungs.The correlation between eosinophil levels in peripheral blood and bronchoalveolar lavage fluid is poor.

In this work,an electrochemical sensor for detection of Rhodamine B(RhB)was constructed by modifying molecularly imprinted polymer(MIP)and carboxylated multi-walled carbon nanotubes(f-MWCNTs)onto the surface of glassy carbon electrode(GCE).The MIP/f-MWCNT/GCE electrochemical sensor demonstrated outstanding performance in detection of RhB due to the excellent conductivity of f-MWCNT and synergistic selectivity of MIP.Under optimal experimental conditions,the sensor had a wide linear response range(0.01?30 nmol/L,30?500 nmol/L),with limit of detection of 0.01 nmol/L.In addition,the sensor exhibited excellent recognition ability to RhB in the presence of other structurally similar compounds(e.g.,Rhodamine 6G,methylene blue,and methyl orange),and common metal ions(K+,Ca2+,Mg2+and Fe3+).Furthermore,the sensor exhibited good stability and reproducibility.Additionally,the electrochemical sensor exhibited good practical adaptability when analyzing RhB in real samples,with recoveries ranging from 99.8%?105.6%for tap water and 99.2%?105.0%for river water samples.