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 investigate the molecular mechanism and identify potential drugs for subthreshold depression (SD), and elucidate the detalied mechanism of Danzhi Xiaoyao powder (DZXY) in SD. Methods: Using RNA-sequencing, we identified differentially expressed genes (DEGs) in leukocytes of SD compared to healthy controls, deciphered their functions and pathways, and identified the hub genes of SD. We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELiS platform. The Connectivity Map database was retrieved to screen candidate drugs for SD. Based on network pharmacology, we elucidated the “multi-component, multi-target, and multi-pathway” mechanism of DZXY in the treatment of SD. Results: We identified 1080 DEGs (padj <0.05 and |log2 (fold change)| ≥ 1 & protein coding) in the leukocytes of patients with SD. These DEGs, including hub genes, were primarily involved in immune and inflammatory response-related processes. Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells. Connectivity Map analysis identified 28 potential drugs for SD treatment, particularly SB-202190 and TWS-119. Constructing the “Direct Compounds-Direct Targets-Pathways” network for DZXY and SD revealed the curative mechanisms of DZXY in SD, primarily including inflammatory response, lipid metabolism, immune response, and other processes. Conclusion These results provide new insights into the characteristics and functional changes of leukocytes in SD, partially illustrate the pathogenesis of SD, and suggest potential drugs for SD. The curative mechanisms of DZXY in SD are also partially elucidated.

Objective To explore the application of hydrogen-rich drinking water combined with hydrogen inhalation in marine personnel with hyperuricemia.Methods A total of 110 marine personnel with hyperuricemia who recuperated in the Lintong Rehabilitation and Recuperation Center of Joint Logistic support Force from July 2022 to September 2023 were randomly divided into intervention group and control group,with 55 cases in each group.All the participants were given health education,diet management and exercise management for one month.And the intervention group was additionally given hydrogen-rich drinking water and hydrogen inhalation.Clinical effective rate and the levels of blood uric acid,blood urea nitrogen and serum creatinine were compared between the two groups.Results The clinical effective rate of the intervention group was significantly higher than that in the control group after one month treatment(78.18%[43/55]vs.50.91%[28/55],P<0.05).The levels of blood uric acid,blood urea nitrogen and serum creatinine were significantly decreased after treatment in both groups,and the levels of blood uric acid and serum creatinine in the intervention group were significantly lower than those in the control group(P<0.05).However,there was no satistically significant difference in blood uren nitrogen between before and after intervention.Conclusion The hydrogen-rich drinking water combined with hydrogen inhalation can effectively reduce the level of blood uric acid in marine personnel with hyperuricemia,improving the therapeutic effect and renal function,so it is worthy of further promotion.

Objective:To compare the efficacy of pars plana vitrectomy (PPV) and nonvitrectomizing vitreous surgery (NVS) in the treatment of idiopathic epimacular membrane (IMEM).Methods:A prospective , randomized and comparative clinical study. From April 2019 to May 2020, 21 eyes of 21 patients with IMEM diagnosed in Chongqing Aier Eye Hospital were included in the study. Among them, 11 males had 11 eyes, and 10 females had 10 eyes. Best-corrected visual acuity (BCVA), optical coherence tomography angiography (OCTA), and corneal, intraocular, and global aberration measurements were performed in all eyes. The international standard logarithmic visual acuity chart was used for BCVA examination, and the visual acuity was converted into logarithm of minimum angle of resolution (logMAR) during statistics. The iTrace visual function analyzer was used to measure the corneal, intraocular and whole ocular aberrations, and the dysfunction lens index (DLI) was calculated. Lens density in Scheimpflug images was calculated using Pentacam three-dimensional anterior segment analysis and diagnosis system. The 6 mm×6 mm area of the macular area was scanned by OCTA, which was divided by the software automatically into three concentric circles with the fovea as the center, namely the central area with a diameter of 1 mm, the inner ring area with a diameter of 1-3 mm, The outer ring area of 3-6 mm was used to measure the superficial vessel density (SVD) and superficial perfusion density (SPD) of the entire macular area, the central area, the inner ring area, and the outer ring area. The patients were divided into PPV combined with epimacular membrane (MEM) peeling group (PPV group) and NVS direct peeling MEM group (NVS group) by random number table method, 10 cases with 10 eyes and 11 cases with 11 eyes, respectively. The age of the two groups ( t=-0.72), logMAR BCVA ( t=-0.98), lens density ( t=-1.10), DLI ( t=1.15), SVD ( t=0.82) and SPD ( t=1.19) of entire macular area, corneal aberration ( t=0.45), intraocular aberration ( t=-0.22), and whole eye aberration ( t=0.83), there was no significant difference ( P>0.05). All eyes were operated on with a 27G vitrectomy system. The MEM was removed from the eyes of the NVS group under NVS condition, and the MEM was removed from the eyes of the PPV group under the condition of PPV, and the operation time was recorded at the same time. The follow-up period after surgery was 12 months. Relevant examinations were performed using the same equipment and methods before surgery. Taking the last follow-up as the time point for efficacy judgment, the BCVA, lens opacity, DLI, visual quality, SVD, SPD and MEM recurrence in the macula were compared between the two groups. The two groups were compared by paired t test. Results:The operation time of eyes in PPV group and NVS group was 20.81±3.52 and 5.70±1.30 min, respectively, and the difference was statistically significant ( t=7.23, P<0.001). At the last follow-up, the logMAR BCVA of PPV group and NVS group were 0.65±0.25 and 0.44±0.20, respectively, and the difference was statistically significant ( t=-2.16, P=0.04); compared with before operation, the BCVA of eyes of the two groups was significantly improved, and the difference was statistically significant. ( t=2.52, 4.41; P=0.033, P<0.001). The lens density and DLI of the affected eyes in the PPV group and NVS group were 10.64±1.58, 6.24±3.99 and 5.77±1.63, 7.74±1.55, respectively, and the differences were statistically significant ( t=-3.90, 2.85; P<0.05). The macular area SVD ( t=1.03), SPD ( t=1.77), corneal aberration ( t=-0.42), intraocular aberration ( t=-1.10), and whole-eye aberration ( t=-1.17) of eyes of the two groups, the difference was not statistically significant ( P>0.05). During the follow-up period, there were 2 eyes with MEM recurrence, 1 eye in the PPV group and 1 eye in the NVS group; there was no significant difference in the recurrence rate of MEM between the two groups ( χ2=0.005, P=0.94). Conclusion:Compared with PPV combined with MEM stripping, the BCVA after NVS surgery increases more, has a better protective effect on the lens, and has a shorter operation time.

Objective:To investigate the relationship between embryo implantation site and adenomyotic lesions in pregnant patients with adenomyosis and its effects on pregnancy outcomes.Methods:Between January 2018 and December 2020, the clinical data of 95 pregnant patients with adenomyosis who were hospitalized in the Women′s Hospital, School of Medicine, Zhejiang University, which could identify the implantation site of embryo or placenta (≥11 weeks of pregnancy) through the nuchal translucency test under ultrasonography were analyzed retrospectively. According to the relationship between embryo implantation site and adenomyotic lesions, 95 patients were divided into two groups:short-distance group ( n=59, the embryo or placenta implantation was very close to or over the adenomyotic lesion), and long-distance group ( n=36, the implantation site of embryo or placenta was far away from the lesion, or the implantation site and the adenomyotic lesion were on different sides of the uterus). Next, taking 28 weeks of pregnancy as cut-off value, 95 patients were divided into <28 weeks of pregnancy group (pregnancy was terminated because of adverse pregnancy outcome before 28 weeks) and ≥28 weeks of pregnancy group (pregnancy lasted to 28 weeks and later), the differences of pregnancy outcomes between the two groups in different gestation times were analyzed. Results:(1) The age of 95 pregnant patients with adenomyosis was (34.8±3.5) years. There were no significant differences with regard to age, uterine size before pregnancy, the proportions of primipara, assisted reproductive technology conception, endometriosis, history of estrogen and progesterone treatment, diffuse adenomyotic lesions between the short-distance group and the long-distance group (all P>0.05). (2) Among the 95 patients, 12 patients (13%, 12/95) had adverse pregnancy outcomes before 28 weeks of pregnancy (i.e. pregnancy <28 weeks), including 11 cases (19%, 11/59) in the short-distance group and 1 case (3%, 1/36) in the long-distance group, there was significant difference between the two groups ( χ2=5.100, P=0.027). Among the 11 patients with adverse pregnancy outcomes at <28 weeks of gestation in the short-distance group, 1 case had threatened rupture of uterus before delivery of twin pregnancy at 26 weeks of gestation, 5 cases had intra uterine fetal death in the second trimester of pregnancy, 4 cases had late inevitable abortion, and 1 case had live birth of singleton at 26 weeks of gestation. In the long-distance group, one patient with adverse pregnancy outcome less than 28 weeks of pregnancy was late inevitable abortion. (3) Of the 95 patients, 83 cases were pregnant for ≥28 weeks (48 cases in the short-distance group and 35 cases in the long-distance group), and their final pregnancy outcome was all live birth. Compared with the long-distance group, the incidence of placental abnormalities (60% vs 14%), fetal distress (27% vs 6%), preterm delivery (67% vs 23%) and intrapartum bleeding [median 350 ml (range: 100-1 500 ml) vs 300 ml (range: 100-800 ml)] in the short-distance group were significantly higher (all P<0.05). While the gestational weeks in the short-distance group [median 37 weeks (range: 30-41 weeks) vs 38 weeks (range: 28-41 weeks)] and neonatal birth weight [median 2 790 g (range: 1 170-4 040 g) vs 3 010 g (range: 980-4 320 g)] decreased significantly (all P<0.05), compared with those in the long-distance group. Conclusion:Patients with pregnancy complicated with adenomyosis are prone to adverse pregnancy outcomes if the embryo implantation is located on or very close to adenomyotic lesions, so close monitoring and early intervention should be carried out to improve pregnancy outcomes.

Objective: To study on the mRNA expression level of IN1 gene associated with the clinical efficacy and prognosis of hepatoblastoma(HB) in children and to elucidate the early warning value of IN1 gene for prognosis and chemotherapy sensitivity. Methods: Forty HB patients were selected based on primary diagnosis and treated from January 2015 to May 2018 in Tongren Hospital Affiliated to Capital Medical University. The expression level of INI1 gene was detected by using fluorescence immuno-PCR. Clinical data of children with HB were collected, including staging, grouping, risk, efficacy and prognosis of chemotherapy. The relationship between the mRNA expression of IN1 gene and clinical data was analyzed by SPSS 21.0 software. Results: (1)Clinical characters: the medium age of 40 HB patients was(30.50±2.39) months, male 29 cases (72.5%), and female 11 cases (27.5%). There was 1 case (2.5%) of stage Ⅱ HB, 13 cases (32.5%) of stage Ⅲ HB, and 26 cases (65.0%) of stage Ⅳ. The low-and intermediate- risk group had 12 cases (30.0%) of HB, and the high-risk group had 28 cases (70.0%) of HB.(2)Clinical efficacy and prognosis: by July 1^st, 2018, the medium following-up time was (12.2±10.1) months, 4 patients (10%) were treated by chemotherapy without surgery, and 36 patients (90%) were treated by surgery .All patients (100%) received chemotherapy.The average cycle of chemotherapy lasted(13.17±0.02). Ten patients were dead and 30 patients survived till following-up.The overall survival (OS) rates were 75% and the event-free survival rates were 50% (20 patients with HB). (3) IN1 gene mRNA expression: The average PCR quantitative of IN1 gene mRNA of 40 HB patients(2^-ΔCT)was 0.31±0.70.The average mRNA quantitative of HB patients (2^-ΔCT)with high-risk and low/intermediate-risk group was 0.23±0.43 and 0.48±1.13(t=6.363, P=0.05). According to histology diagnosis, the average mRNA quantitative of small cell undifferentiated (SCU) type (12 cases)and other type (25 cases) was 0.09±0.11 and 0.43±0.86(t=4.533, P=0.04). The average mRNA quantitative of patients with or without radical surgery was 0.04±0.03 and 0.34±0.74 (t=2.935, P=0.022). The data of children with poor chemotherapy sensitivity(19 cases)and those sensitive to chemotherapy (21 cases) were 0.03±0.04 and 0.30±0.82, and the difference was statistically significant (t=5.688, P=0.018). Conclusions Poor therapeutic effect results in low mRNA expression of IN1 gene in children of HB.The IN1 gene expression could be an early warning factor for treatment sensitivity and prognosis.

Objective To explore the treatment and prognosis of advanced stage childhood hepatoblastoma with pulmonary metastasis.Methods Fifty-six cases of advanced stage hepatoblastoma with pulmonary metastasis diagnosed through pathology from April 2006 to June 2014 in Department of Pediatrics,Beijing Tongren Hospital Affilia-ted to Capital Medical University were enrolled,among them 33 cases were males and 23 cases were females,and the median age was 2.33 years old(1 month-15 years and 1 month old).The clinical effects of multidisciplinary therapy were analyzed.Results (1)Follow-up studies were conducted till December 2016,in which 21 cases of 56 children achieved complete remission,the complete remission rate was 37.5%(21/56 cases),while 12 cases were partial re-mission and 14 cases were deceased,and the effective rate reached 58.9%(33/56 cases).The follow-up period of 41 children were over 24 months,in which the 2-year free event survival(EFS)rate was 37.5%,2-year overall survi-val(OS)rate was 75.0%,5-year survival rate was 42.4%,and the 95% average survival confidence interval was 35.7-55.9 months.(2)The OS rate of children with small age(≤3 years old)was 88.1%(36/42 cases),the ove-rall prognosis was better than that of >3 years old children(35.7%,5/14 cases)(P=0.003).The survival rate of children with complete tumor resection[OS rate was 89.2%(33/37 cases)]was significantly higher than that of the incomplete excision[OS rate was 47.4%(9/19 cases)],and the difference was statistically significant(P=0.001). The prognosis of epithelial type cases was better than that of other types,and the difference was statistically significant (P<0.05),while the fetal type prognosis was the best,and the difference was statistically significant(χ2=8.56,P=0.014).The growth of alpha fetoprotein was negatively correlated with the clinical efficacy and prognosis(r=-0.468, P=0.023).Conclusions Lung is the most common metastatic site of hepatoblastoma,and the marginal lung metasta-sis is more common.With insidious onset and poor prognosis.Therefore,it should be treated with early diagnosis and multidisciplinary therapy to improve prognosis.

To investigate the effect of combination of schisandrin B and doxorubicin on the pharmacokinetic behavior of doxorubicin in SD rats. An LC-MS/MS method was established for the determination of doxorubicin and its main metabolite doxorubicinol in SD rats plasma. Separation was performed on Agilent Eclipse XDB-C18 column(100 mm×2. 1 mm, 3. 5 μm)using 0. 1% formic acid solution and acetonitrile as mobile phase with a liner gradient program. The ion transitions were performed under ESI position model at m/z 544. 2→397. 3(doxorubicin), m/z 546. 2→399. 2(doxorubicinol), m/z 528. 2→381. 2(daunorubicin, internal standard). Calibration curves of doxorubicin(0. 500-500 ng/mL)and doxorubicinol(0. 200-50. 0 ng/mL)showed good linear regression. The precision and accuracy met the requirements. The variation coefficient of extraction recovery and matrix effect was less than 15%. The AUC0-t of doxorubicin were(605. 69±145. 84)and(564. 53±23. 99)ng ·h/mL in alone and combined group, respectively. The AUC0-t of doxorubicinol were(26. 69±13. 41)and(29. 00±2. 78)ng ·h/mL, respectively. Results indicated that, schisandrin B had not affected the pharmacokinetic behavior of doxorubicin in SD rats.