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.

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.

Objective To explore the protective mechanism of RNA binding protein LIN28 on diabetic nephropathy(DN).Methods LIN28 was overexpressed or knocked down by adenovirus in HEK 293T cells.The gene and functional signaling pathway significantly changed after overexpression of LIN28 were obtained through RNA Seq transcriptome sequencing and bioinformatics analysis.HEK 293T cells were divided into the Control group,the Treatment group,the Adv-LIN28-OE+D-ribose group and the Adv-LIN28-NC+D-ribose group in in vitro LIN28 overexpression studies.And HEK 293T cells were divided into the Control group,the Treatment group,the Adv-shRNA LIN28+D-ribose group and the Adv-shRNA NT+D-ribose group in in vitro LIN28 knockdown studies.ELISA was used to detect the levels of human advanced glycation end products(AGEs)of cells supernatants in the above groups.Western blot was used to detect the expression levels of RAGE,NF-κB and MMP-2 of cells in the above groups.Results The results of RNA-Seq transcriptome sequencing,GO analysis and KEGG analysis showed that overexpression of LIN28 resulted in a significant down-regulation of AGE-RAGE signaling pathway in HEK 293T cells(P<0.05).The results of ELISA showed that compared with the Control group,the cell in the Treatment group produced a large amount of AGEs(P<0.05);compared with the Treatment group,the AGEs level of cells in the Adv-LIN28-OE+D-ribose group was significantly decreased(P<0.05),while the AGEs level of cells in the Adv-shRNA LIN28+D-ribose group was increased(P>0.05).The results of Western blot showed that compared with the Control group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Treatment group were significantly increased(P<0.05);compared with the Treatment group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-LIN28-OE+D-ribose group were significantly decreased(P<0.05),while the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-shRNA LIN28+D-ribose group were significantly increased(P>0.05).Conclusion Overexpression of LIN28 by adenovirus at the cellular level in vitro can lead to significant differential expression of thousands of genes.In particular,it can inhibit the diabetes and complications-related AGE-RAGE signaling pathway,which is critical in the progression of DN disease,and play a role in protecting DN.

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ²=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ²=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ²=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ²=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.
Child ; Female ; Male ; Humans ; Hodgkin Disease ; Retrospective Studies ; Neoplasm Recurrence, Local ; China ; Antineoplastic Combined Chemotherapy Protocols ; Prognosis ; Disease-Free Survival

Objective:By observing the changes of hyperthermia on serum carbohydrate antigen 125(CA125),human epididymal protein 4(HE4),chitinase protein(YKL) and immune function index effects,to investigate its effect on cancerous ascites and its antitumor effect of cytoreductive surgery combined with intraperitoneal hyperthermic perfusion chemotherapy and in elderly patients with advanced ovarian cancer.Methods: A total of 72 elderly patients with advanced ovarian cancer were enrolled in the study.They were randomly divided into contrast treatment group and combined treatment group,36 cases in each group.The patients in contrast treatment group were treated with cytoreductive surgery combined with intraperitoneal hyperthermic perfusion chemotherapy.The combined treatment group was treated with partial radiofrequency hyperthermia on the basis of the treatment of the control group.The efficacy was evaluated after 2 courses.The changes of CA125,HE4 and YKL contents and T cell subsets were compared between the two groups before and after treatment,and the safety was evaluated.Results: There was no difference in the operation between the two groups.The total effective rate was 80.0% in combined treatment group,which was significantly better than 55.6% in contrast treatment group(χ2=5.175,P<0.01).The effective rate of ascites control was 80.6% in combined treatment group,which was significantly higher than that in contrast treatment group 52.4%(χ2=3.962,P<0.05).After treatment,the levels of CA125,HE4 and YKL in the two groups were significantly lower than those before treatment,and the decrease of the combined treatment group was more significant than contrast treatment group(P<0.05).After treatment,the levels of CD3+,CD4+,CD4+/CD8+in both groups were lower than those before treatment,CD8+was lower than that before treatment,and the improvement of the indexes in combined treatment group was more significant than contrast treatment group(P<0.05).There was no significant difference between the two groups in the adverse effects of bone marrow suppression,gastrointestinal reaction and liver and kidney dysfunction(P> 0.05).Conclusion: CRS combined with IPHC and hyperthermia can significantly improve the immunosuppression of ovarian cancer,reduce the level of CA125,HE4,YKL, improve clinical efficacy of elderly patients with advanced ovarian cancer.

OBJECTIVETo screen serum peptide associated with renal impairment in patients with multiple myeloma(MM) and search early biomarker of MM renal impairment.

METHODSThe weak cation exchange magnetic bead combined with matrix assisted laser desorption/ionization time of flight mass spectrometry was used to compare and analyze serum peptidome of MM with or without renal impairment.

RESULTSThere were 18 peptide peaks with statistical significance in the molecular weight range from 700 to 10 000 Da(P<0.05), among them 7 peptides were upregulated and 11 were downregulated. The Quick Classifier diagnostic model composed of 3 peptides, which can strongly distinguish MM patients with or without renal impairment by means of Embedded Software. Its sensitivity and specificity were 97.14% and 94.12%, respectively. Peptides with molecular weight of 3908.85 Da and 3216.06 Da were significantly upregulated in MM patients with renal impairment, while the peptide with molecular weight of 2990.08 Da was significantly downregulated in MM patients with renal impairment.

CONCLUSIONPeptides associated with MM renal impairment obtained by serum peptidome technology can provide a new clue for early assessment and diagnosis of clinical MM renal impairment.

OBJECTIVETo explore the effectiveness and safety of combined chemotherapy with pegasparaginase (PEG-Asp) for treatment of patients with acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin's lymphoma (T-NHL) patients.

METHODSA total of 62 ALL or T-NHL patients were diagnosed and treated in our department and were enrolled in this study. Among them, 22 patients received the combined chemotherapy with PEG-Asp, while the other 40 patients received the standard chemotherapy with L-asparaginase (L-Asp) as the control. Therapeutic effectiveness, adverse effects, duration and expense of hospitalization, treatment-related mortality and survival were evaluated and compared in 2 different groups.

RESULTSIn group of combined chemotherapy with PEG-Asp, the overall response rate was 90.91% (20 cases), among them CR rate and PR rate are 77.27% (17 cases) and 13.64% (3 cases), respectively. In the group of standard chemotherapy with L-Asp, the overall response rate was 87.5% (35 cases), among them CR rate and PR rate were 72.5% (29 cases) and 15% (6 cases), respectively. The difference neither between PEG-Asp and L-Asp chemotherapy groups nor between ALL and T-NHL subgroups was significant (P > 0.05). The 6-month and 12-month overall survival rates were not significantly different between the PEG-Asp and L-Asp chemotherapy groups, respectively (P > 0.05). The adverse effects were identified as degree 1-2 according to the WHO criteria of drug toxicity. Neither the adverse effects identified as degree 3-4 nor the treatment-related death were observed. Expect for allergy and hyperglycaemia, the difference of side-effect incidence between the two groups were not significant (P > 0.05). The treatment for all the patients in PEG-Asp chemotherapy group was completed, while the treatment with L-Asp was completed only in 29 cases. Moreover, both average duration and expense of hospitalization after the combined chemotherapy were less than the control.

CONCLUSIONWith higher response rate, lower drug toxicity and allergy incidence, the combined chemotherapy with PEG-Asp can replace the standard chemotherapy with L-Asp in the treatment of ALL and T-NHL. The optimization of the combined chemotheropeutic protocols for more cases and long-term survival rates need to further and deeply explorate.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Asparaginase ; therapeutic use ; Humans ; Lymphoma, T-Cell ; drug therapy ; Polyethylene Glycols ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Survival Rate

OBJECTIVETo explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest.

METHODSProtein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence- associated-β-galactosidase (SA-β-gal) staining combined with Ki67 staining, a cell proliferation marker.

RESULTSAccompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells.

CONCLUSIONOur results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2-arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis.

Cell Cycle Checkpoints ; radiation effects ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; DNA Damage ; Down-Regulation ; Fibroblasts ; metabolism ; radiation effects ; Gene Expression Regulation ; radiation effects ; Humans ; Mitosis ; radiation effects ; RNA Interference ; RNA, Small Interfering ; Radiation, Ionizing ; Up-Regulation

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications