ObjectiveTo observe the clinical efficacy and relative mechanism of the Modified Wenshen Yixin Formula （温肾益心方加减， MWYF） as an auxiliary treatment of coronary heart disease （CHD） complicated with hypothyroidism of spleen-kidney yang deficiency. MethodsA total of 135 CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency were included and divided into control group （67 cases） and experimental group （68 cases） according to the patients' wishes of herbal medicine administration. The control group was given conventional western medicine， while the treatment group was additionally given MWYF， 1 dose per day； both groups were treated for 8 weeks. The traditional Chinese medicine （TCM） syndrome scores， angina scores， SF-36 scores， thyroid function indicators including thyroid stimulating hormone （TSH）， thyroxine （T4） and triiodothyronine （T3）， as well as serum cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， monocyte chemoattractant ligand 2 （CCL2）， and tumor necrosis factor-related activator protein （CD40L） levels before and after treatment were compared between the two groups. The dosage and reduction and discontinuation rate of thyroid hormone preparations after treatment were compared between the two groups. The effectiveness regarding TCM syndrome and angina pectoris was evaluated， and the safety was assessed. ResultsBias was adjusted by matching on propensity score， and 102 cases were finally included in the statistical analysis， with 51 cases in each group. The total effective rate regarding TCM syndrome ［94.12% （48/51） versus 64.71% （33/51）］， the total effective rate regarding angina pectoris ［80.39% （41/51） versus 62.75% （32/51）］， and the reduction and discontinuation rate of thyroid hormone preparation ［39.21% （20/51） versus 5.88% （3/51）］ were significantly higher in the experimental group than those in the control group （P＜0.05 or P＜0.01）. After treatment， the total TCM syndrome score， individual scores of major symptoms ， the major symptoms score， the secondary symptoms score， angina pectoris score， and TSH level were significantly reduced （P＜0.01）， while all dimensions of SF-36 scores， T4， T3， and cAMP levels significantly increased in both groups （P＜0.05 or P＜0.01）. The dosage of thyroid hormone preparations and the levels of cGMP， CCL2， and CD40L in the experimental group significantly decreased after treatment （P＜0.01）. When compared between the two groups after treatment， the total TCM syndrome score， the major symptoms score， the scores of individual major symptom （chest tightness， chest pain， fear of cold， cold limbs， waist and kness soreness and weakness）， the secondary symptoms score， angina pectoris score， TSH， cGMP， CCL2， and CD40L levels of the experimental group were significantly lower than those of the control group （P＜0.05 or P＜0.01）， while all dimension scores of SF-36， T4， T3， and cAMP levels were significantly higher （P＜0.01）. A total of three adverse events occurred during treatment， none of which were judged to be related to the interventions of this study. ConclusionMWYF can significantly ameliorate the TCM syndrome， angina pectoris， quality of life and thyroid function in CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency， and can promote the reduction and disconti-nuation of thyroid hormone preparations. The mechanism may be related to the regulation of cAMP/cGMP balance， the regulation of hypothalamic-pituitary-thyroid metabolic axis and the reduction of immune inflammation.

Objective:To explore the relationship between liver iron deposition and steatosis in patients with non-alcoholic fatty liver disease (NAFLD) through MRI.Methods:163 cases of liver biopsy underwent MRI examination. R2* was used to measure liver iron content. Dixon-based proton density fat fraction (PDFF) was used to measure liver fat content. One-way ANOVA, r-correlation, ROC curve, and others were used to assess the relationship between clinical case data, serological indices, and imaging results in accordance with the pathological results of the liver biopsy.Results:R2* gradually increased as the pathological steatosis grade rose. The R2* that corresponded to no steatosis (< 5%), mild steatosis (14.95%±8.55%), moderate steatosis (46.30%±9.32%), and severe steatosis (73.86%±6.35%) were 27.56±4.40, 31.06±5.95, 38.06±4.80, and 48.10±5.55 ( P < 0.001), respectively. There was a positive correlation between R2* and liver steatosis content ( r= 0.769, P < 0.05). The area under the ROC curve and cut-off value were 0.88 and 31.77, respectively, and there was no distinct relationship with liver inflammation or fibrosis. Conclusion:R2* can quantitatively and non-invasively evaluate liver iron deposition in patients with NAFLD. A distinct relationship exists between liver steatosis and iron deposition, and iron deposition tends to increase as the steatosis aggravates.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) for quantitative determination of liver fat and iron content through a rat model of non-alcoholic fatty liver disease (NAFLD) induced by methionine-choline deficient (MCD) diet.Methods:Sixty SD rats were randomly divided into experimental (MCD-diet group, n = 30) and normal control group (normal diet, n = 30). Rats were subjected to special MRI examinations at the ends of 2, 4, and 8 weeks. Proton density fat fraction (PDFF) and R2* value were obtained, and then the rats were sacrificed. The liver tissues were stained with HE, Prussian blue, etc. Liver tissue non-heme iron (NHI) homogenate was determined by flame atomic absorption spectrometry. According to different data, one-way analysis of variance, t-test or χ2 test was used for statistical analysis. Results:PDFF and R2 * values in the MCD diet group at 2, 4 and 8 weeks were 23.37% ± 9.20%, 28.07% ± 6.84%, 25.40% ± 7.04% ( P < 0.01) and 90.58 ± 15.92, 104.12 ± 13.47, 106.35 ± 15.76 ( P < 0.05), respectively, which were significantly higher than the normal control group PDFF (2.39% ± 0.50%, 2.45% ± 0.45%, 3.26% ± 0.80%) and R2* (48.93 ± 7.90, 54.71 ± 5.91, 64.25 ± 15.76). Additionally, with the disease progression, R2 * had gradually increased, which was consistent with the NHI trend in liver tissue homogenates of each group. Conclusion:MRI, as a non-invasive quantitative method, can accurately assess liver fat and iron content in fatty liver disease, and with the degree of severity of fat changes, iron deposits tend to increase.

Objective:To analyze the correlation between serum ferritin and steatosis in non-alcoholic fatty liver disease.Methods:Data of 167 cases who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were collected. Hydrogen proton magnetic resonance spectroscopy were performed within one week. The pathological results of liver biopsy were used as the gold standard to analyze the case data, serological indicators, magnetic resonance spectroscopy-proton density fat fraction.Results:Pathological monitoring result showed that the serum ferritin in patients without steatosis, and with mild, moderate and severe steatosis were (206.20 ± 189.83), (286.65 ± 200.80), (326.55 ± 214.71), (391.50 ± 184.93) ng/ml, respectively, P < 0.005. Serum ferritin was correlated to body mass index, PDFF, alanine aminotransferase, gamma glutamyltransferase, low-density lipoprotein, high-density lipoprotein. The area under ??the receiver operating characteristic curve with ferritin for the diagnosis of non-alcoholic fatty liver disease was 0.716, and the optimal diagnostic threshold was 214.56 ng/ml. The sensitivity and specificity were 80.1%, and 68.8%, respectively. There was no statistically significant difference between the intralobular inflammation, fibrosis, and ferritin. Prussian blue iron staining had no apparent deposition of iron particles. Conclusion:Ferritin has significant positive correlation with the results of pathological and magnetic resonance imaging for liver steatosis. Therefore, it can be used as a non-invasive diagnostic method for liver steatosis evaluation.

Objective:To evaluate the prognostic effects of gradient boosting machine (GBM) model on the short-term effects of percutaneous endoscopic lumbar discectomy (PELD) in the treatment of lumbar disc herniation.Methods:Clinical data and outcomes of 475 patients who underwent PELD surgery for single-segment lumbar disc herniation from October 2016 to March 2018 were retrospectively collected. The lumbar JOA score was used as a reference for the evaluation of curative effects. The improvement rate ≥50% was considered as good curative effects, while <50% was considered as poor curative effects. GBM model and multivariate Logistic regression model were utilized to screen out the influencing factors of the short-term clinical effects of PELD. Prognostic models were established, receiver operating characteristic (ROC) curves were drawn and compared. Sensitivity, specificity and Youden index were compared to evaluate the predictive performance of GBM model.Results:A total of 395 patients were followed up effectively for 24 months. There were 347 patients (87.8%) with good curative effects. However, forty-eight patients (12.2%) had poor curative effects. There were statistically differences in the lumbar JOA score improvement rates between the groups in regards to age, location and type of herniated disc, degeneration level of intervertebral disc and facet joint in surgical segment, sagittal diameter of the protrusion and whether or not there was calcification, onset time to the surgery time period and degeneration level of intervertebral disc in adjacent segment ( P<0.05). The results of multivariate analysis showed that patients with age ≥60 [ OR=9.15, 95% CI(4.04, 20.73), P<0.001] and with larger sagittal diameter of the protrusion [ OR=1.37, 95% CI(1.18, 1.58), P<0.001] were more likely to have a poor prognosis. Patients with unilateral disc herniation had a better prognosis than the extreme lateral type [ OR=0.17, 95% CI(0.06, 0.55), P=0.003]. The prognoses of patients with grade Ⅲ intervertebral disc degeneration in surgical segment were worse than those with grade Ⅱ [ OR=0.17, 95% CI(0.04, 0.70), P=0.014]. The prognoses of patients with grade Ⅲ intervertebral disc degeneration in adjacent segment were worse than those with grade Ⅱ [ OR=0.29, 95% CI(0.10, 0.81), P=0.018]. The AUC predicted by GBM model was 0.92 [95% CI(0.77, 0.96)] with 93.46% sensitivity, 83.33% specificity and 0.77 Youden index. The above parameters were higher than those by the Logistic regression model. The predictive effects of the two models were both statistically significant ( P<0.001). The AUC values of the two models were also statistically significant ( Z=0.11, P<0.001). Conclusion:GBM model is better than multivariate logistic regression analysis model in predicting the short-term clinical effects of PELD in treating lumbar disc herniation.

OBJECTIVETo report on prenatal diagnosis and follow up of two patients with paternal uniparental disomy of chromosome 6 (pUPD6).

METHODSFetal cells were subjected to in situ culturing and G-banded chromosomal analysis. DNA samples of the fetuses and their parents were also analyzed with single nucleotide polymorphism microarray (SNP array).

RESULTSBoth fetuses had a normal male karyotype. SNP array analysis showed both have carried pUPD6.

CONCLUSIONpUPD6 can lead to transient neonatal diabetes mellitus type 1. Homozygous status of recessive mutations, disorder of gene imprinting, and its influence on placental function are the main factors to be considered during prenatal diagnosis and genetic counseling for pUPD6.

Objective: We aimed, in our prospective study, to assess the predictive value of serum non-invasive and biochemical markers for clinical diagnosis of significant fibrosis (including early stages). Methods: We measured sH2a levels in serum, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of hepatitis B patients without non-alcoholic fatty liver disease(NAFLD), which had histological grades of liver fibrosis, with NAFLD individuals and CHB with NAFLD patients. Statistical analysis was by Student′s t test, and receiver-operating characteristic (ROC) curves were drawn. Results: ROC curves showed that serum sH2a had greater diagnostic performance than routine liver function markers compared with histological grades of liver fibrosis(S0, S1-2, S3-4). ROC curves showed that using a sH2a cut-off point of 0.79 was with highest sensitivity as 63% and highest specificity as 80%. And sensitivity as 96.7% and specificity as 75.5% when using a sH2a cut-off point of 0.77. Conclusions sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function.

Objective: To investigate the role of neutrophil elastase inhibitor, sivelestat, in preventing and treating nonalcoholic steatohepatitis (NASH) and its underling mechanisms. Methods: A total of forty 4-week-old male C57BL/6J ApoE-/-mice were equally divided into the following four groups: standard chow (SC)+isotonic saline; SC+sivelestat; high-fat, high-cholesterol (HFHC) diet+isotonic saline; and HFHC+sivelestat. These mice were treated with above methods for 12 weeks. Blood and liver tissue samples were collected to measure biochemical parameters, hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) activity score (inflammation) were evaluated by oil red O staining and HE staining, respectively. The mRNA and protein expression levels of hepatic inflammatory cytokines, CD68, and F4/80 were determined by quantitative RT-PCR and immunohistochemistry, respectively. Comparison of means between the four groups was made by one-way analysis of variance, and comparison between any two groups was made by the LSD or SNK method (for data with homogeneity of variance) or the Tamhane or Dunnett method (for data with heterogeneity of variance). Results: Mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH compared with those fed with SC. Compared with mice fed with HFHC diet without sivelestat, those treated with HFHC and sivelestat exhibited the following features: (1) significantly reduced fast blood glucose, blood cholesterol, and hepatic biochemical parameters, as well as increased insulin sensitivity; (2) significantly reduced NAFLD activity score (5.71±1.11 vs 3.16±1.16, P < 0.05); (3) reduced monocyte chemoattractant protein-1 and tumor necrosis factor -α; (4) significantly reduced mRNA levels of CD68 and F4/80; and (5) reduced expression of CD68 in the liver. Conclusion Sivelestat alleviates the hepatic steatosis and inflammation of NASH in mice by inhibiting the activation of Kupffer cells.

Objective: To investigate the value of 1H-magnetic resonance spectroscopy (¹H-MRS) in determining the content of liver triglyceride in patients with fatty liver disease (FLD), as well as its influencing factors. Methods: A total of 124 patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis B (CHB), or hepatitis B complicated by FLD who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were enrolled, and the clinical data, serological markers, FibroScan results, and ¹H-MRS results were collected. A correlation analysis was performed with the results of liver biopsy as the gold standard, and the influence of factors including hepatitic B virus (HBV) infection and obesity on accuracy was analyzed. A one-way analysis of variance was used for comparison of means between the three groups, and the LSD or SNK test (for homogeneity of variance) or the Tamhane’s or Dunnett’s test (heterogeneity of variance) was used for comparison between any two groups. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data. The MRS-PDFF receiver operating characteristic (ROC) curve was plotted, the area under the ROC curve (AUC) was calculated, the optimal cut-off points for the diagnosis of NAFLD were estimated, and sensitivity and specificity were calculated. Results: The NAFLD group (42 patients) and the CHB + NAFLD group (40 patients) had a significantly higher proton density fat fraction (PDFF, the content of triglyceride in the liver) than the CHB group (42 patients) (16.84±9.76/9.39 ± 5.50 vs 3.45 ± 1.63, P < 0.001). The results were significantly correlated with the degree of steatosis confirmed by liver biopsy (P < 0.001), but it was not significantly correlated with inflammation or fibrosis grade. The correlation analysis showed that the MRS-PDFF value measured by 1H-MRS was significantly correlated with body mass index (BMI), blood lipids, alkaline phosphatase, and blood glucose, while it was not significantly correlated with age, sex, or the presence or absence of hepatitis B. The ROC curve analysis showed that the AUCs of PDFF measured by 1H-MRS were 0.93, 0.974, and 0.976, respectively, for the diagnosis of steatosis S1(≥5%), S2(≥34%), and S3(≥66%), and the corresponding optimal thresholds were 5.14%, 11.16%, and 16.7%, respectively. Conclusion 1H-MRS has a high diagnostic value in quantitative evaluation of the degree of liver steatosis in patients with FLD and is not affected by the factors such as HBV infection, age, and sex, while it is correlated with BMI and lipid metabolism.