Effect of the protein kinase RNA-like endoplasmic reticulum kinase pathway in endoplasmic reticulum stress on hepatic stellate cell activation and collagen type I expression / 临床肝胆病杂志

ObjectiveTo investigate the effect of the protein kinase RNA-like endoplasmic reticulum kinase （PERK）/eukaryotic initiation factor 2α （eIF2α） pathway in endoplasmic reticulum stress on the activation of hepatic stellate cells （HSC）. MethodsPathological sections of normal liver tissue after surgery were collected from 11 patients with hepatic fibrosis （S1-S4） and 9 patients with hepatic hemangioma and hepatic adenoma confirmed by liver biopsy， and immunohistochemistry was used to measure the protein expression levels of PERK， eIF2α， and C/EBP homologous protein （CHOP）. Human HSC-LX2 cells were treated with different concentrations of the endoplasmic reticulum stress inducer thapsigargin （0， 125， 250， 500， and 1 000 nmol/L）， and qRT-PCR was used to measure the mRNA expression level of PERK， while Western blot was used to measure the protein expression levels of PERK， inositol requiring protein 1 （IRE1）， activating transcription factor 6 （ATF6）， CHOP， and α-smooth muscle actin （α-SMA）. The method of lentivirus transfection was used to construct a PERK stable overexpression LX-2 group and a control group； qRT-PCR was used to measure the mRNA expression levels of PERK， eIF2α， and α-SMA， Western blot was used to measure the protein expression levels of PERK， phosphorylated eIF2α （p-eIF2α）， and α-SMA， and immunofluorescence assay was used to measure the expression of collagen type I alpha 1 （COL1A1）. The independent samples t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with normal liver tissue， the liver tissue of patients with hepatic fibrosis had significantly higher expression levels of PERK， eIF2α， and CHOP （Z=-3.56， t=-5.75， Z=-3.52， all P<0.001）. Compared with the solvent group， the groups treated with different concentrations of thapsigargin had significant increases in the expression levels of the endoplasmic reticulum-associated proteins PERK， CHOP， IRE1， ATF6， and α-SMA （all P<0.05）. Compared with the control group， the PERK stable overexpression group had significant increases in the mRNA expression levels of PERK， eIF2α， and α-SMA and the protein expression levels of PERK， p-eIF2α， and α-SMA （all P<0.05）， and immunofluorescence assay showed a significant increase in the expression level of COL1A1 in the PERK stable overexpression group （P<0.05）. ConclusionPERK overexpression can induce the expression of α-SMA and COL1A1 in LX-2 cells， suggesting that the PERK signaling pathway might be one of the important mechanisms of HSC activation.

Association of intestinal microecology with the development and progression of autoimmune hepatitis / 临床肝胆病杂志

Autoimmune hepatitis （AIH） is an autoimmune disease characterized by chronic liver inflammation， with a gradually increasing incidence rate， and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years， it has been believed that changes in intestinal microecology can cause changes in autoimmune state， microbial metabolites， and intestinal barrier， which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients， elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH， and briefly describes related treatment regimens from the perspective of intestinal microecology， so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis， diagnosis， and treatment of AIH.

Associations of sex hormone levels with body mass index (BMI) in men: a cross-sectional study using quantile regression analysis / 亚洲男科学杂志(英文版)

Body mass index (BMI) has been increasing globally in recent decades. Previous studies reported that BMI was associated with sex hormone levels, but the results were generated via linear regression or logistic regression, which would lose part of information. Quantile regression analysis can maximize the use of variable information. Our study compared the associations among different regression models. The participants were recruited from the Center of Reproductive Medicine, The First Hospital of Jilin University (Changchun, China) between June 2018 and June 2019. We used linear, logistic, and quantile regression models to calculate the associations between sex hormone levels and BMI. In total, 448 men were included in this study. The average BMI was 25.7 (standard deviation [s.d.]: 3.7) kg m-2; 29.7% (n = 133) of the participants were normal weight, 45.3% (n = 203) of the participants were overweight, and 23.4% (n = 105) of the participants were obese. The levels of testosterone and estradiol significantly differed among BMI groups (all P < 0.05). In linear regression and logistic regression, BMI was associated with testosterone and estradiol levels (both P < 0.05). In quantile regression, BMI was negatively associated with testosterone levels in all quantiles after adjustment for age (all P < 0.05). BMI was positively associated with estradiol levels in most quantiles (≤80th) after adjustment for age (all P < 0.05). Our study suggested that BMI was one of the influencing factors of testosterone and estradiol. Of note, the quantile regression showed that BMI was associated with estradiol only up to the 80th percentile of estradiol.

Serum lipoprotein-associated phospholipase A2 level is positively correlated with the recurrence risk of acute ischemic cerebral infarction in hypertensive patients / 南方医科大学学报

OBJECTIVE@#To explore the relationship between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and the risk of acute ischemic stroke (AIS) recurrence in hypertensive patients.@*METHODS@#This retrospective case-control study was conducted among 211 hypertensive patients with AIS treated in Foshan First People's Hospital, including 35 patients with recurrence of AIS during the 1-year follow-up as confirmed by head CT/MR. In the overall patients, 60 had grade 1 hypertension (including 5 recurrent cases), 76 had grade 2 hypertension (with 11 recurrent cases), and 75 had grade 3 hypertension (with 19 recurrent cases). Univariate analysis, multivariate logistic regression analysis, trend analysis, and smooth curve fitting analysis were performed to explore the correlation between serum Lp-PLA2 level within 24 h after admission and the risk of AIS recurrence. The predictive efficacy of serum Lp-PLA2 level for AIS recurrence in different hypertension grades was evaluated using ROC curve analysis.@*RESULTS@#Serum Lp-PLA2 level, age, NIHSS score at admission, mRS scores at 7 days, homocysteine level and smoking status differed significantly between patients with and without AIS recurrence (P < 0.05). After adjustment for confounding factors, multivariate regression analysis showed that the highest tertile of Lp-PLA2 level was associated with a 4.13-fold increase of AIS recurrence risk compared with the lowest tertile (OR=5.13, 95% CI: 1.35-19.40), and each 1 ng/mL increase of Lp-PLA2 level was associated with a 1% increase of AIS recurrence risk (OR= 1.01, 95% CI: 1.01-1.02). Serum Lp-PLA2 level was shown to positively correlate with AIS recurrence risk, and in patients with grade 3 hypertension, its areas under the ROC curve for predicting AIS recurrence was 0.869 with a specificity of 0.893 and a sensitivity of 0.737.@*CONCLUSION@#Serum Lp-PLA2 concentration is an independent risk factor and potentially an effective predictor for AIS recurrence in patients with grade 3 hypertension.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Perioperative management of cerebral revascularization of moyamoya disease / 临床外科杂志

Moyamoya disease(MMD)is a bilateral stenosis occlusional disease that selectively affects the superior segment of clinoid of the internal carotid artery with secondary abnormal vascular network formation at the base of the skull.Intracranial and extracranial vascular reconstruction is the main treatment of moyamoya disease.However,moyamoya disease revasectomy still faces many challenges,with high requirements of surgical techniques and high risk of complications.In this paper,the perioperative management of cerebrovascular reconstruction in moyamoya disease was discussed in terms of surgical indications,surgical timing,patient management,surgical methods of cerebrovascular reconstruction and postoperative complications,so as to provide reference for improving the prognosis of patients.

Research progress of Gasdermin D / 中国药理学通报

Pyroptosis is a novel process of programmed inflammatory necrosis, which is closely related to microbial infections and autoimmune diseases. In recent years it has been proved that Gasdermin D is an executive protein of pyroptosis. Cleaved Gasdermin D leads to the formation of pores in cell membrane to induce pyroptosis, and the release of inflammatory factors such as IL-1β and IL-18 aggravates the occurrence of inflammatory responses. With the deepening of Gasdermin D research, it is gradually clear its protein structure and activation sites, which has other activation pathways apart from inducing inflammasome activation. Activation of Gasdermin D does not necessarily mean cell death, even if it could induce the formation of pores in cell membrane and regulation of inflammatory cytokine secretion. These findings offer insight into Gasdermin D function and change our understanding of pyroptosis and programmed necrosis. The recent progress of Gasdermin D is highlighted in this review.

The research of liver-targeted drugs based on asialoglycoprotein receptor / 药学学报

Asialoglycoprotein receptor (ASGPR) is highly expressed on the surface of parenchymal liver cells. It can specifically recognize and bind to desialylated glycoproteins which contain terminal galactose or N-acetylgalactosamine residues, and endocytosed by clathrin-mediated endocytosis, transported and then degraded in lysosome. Based on this character, ASGPR mediated liver-targeted drug delivery is likely to increase drug distribution, reduce potential side effects and lower dose. This article reviewed the expression, structure, ligand binding and endocytosis of ASGPR, and summarized the design and optimization of ASGPR ligands and the release strategies. Finally, we put forward some expects about the clinical drug development for ASGPR.

Relationship between nutrient-related dietary pattern and mild cognitive impairment in middle-aged and elderly people in 15 provinces of China / 中华流行病学杂志

Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q4 dietary score group than in Q1 dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q2, Q3 and Q4 dietary score groups compared with the Q1 dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q1 dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q1 dietary score group, those with sleep duration of 8 hours per day in Q2 and Q3 dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.

Advancements in virtual screening techniques for study of enzyme inhibitor compounds / 中国中药杂志

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.

Effect of miR-22 Targeting FMNL2 on Cell Migration and Apoptosis in Childhood Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of miR-22 targeting formin-like protein 2 (FMNL2) on the migration and apoptosis of childhood acute myeloid leukemia (AML) cells.@*METHOD@#Peripheral blood samples from 11 children with AML, 10 children with immune thrombocytopenia, human AML cell lines TF-1a, HL-60, THP-1 and human bone marrow stromal cells HS-5 were used as the research objects. UniCel DxH 800 automatic hematology analyzer detected platelet count, hemoglobin, and white blood cell count in peripheral blood samples, and RT-qPCR detected miR-22 expression in peripheral blood samples and AML cells. HL-60 cells were transfected with LipofectamineTM 2000 kit, the experiments were divided into seven groups: blank (no cells transfected), miR-NC, miR-22 mimics, si-NC, si-FMNL2 , miR-22 mimics+OE-NC and miR-22 mimics+OE-FMNL2 . RT-qPCR was used to detect the expression of miR-22 in each group. Transwell was used to detect cell migration. Flow cytometry was used to detect cell apoptosis. Dual-luciferase reporter gene detection experiments verified the targeting relationship between miR-22 and FMNL2 . Western blot was used to detect the expression of FMNL2 protein.@*RESULTS@#Compared with the control group, the number of leukocytes in the peripheral blood of children with AML was significantly increased (P <0.001), while the concentration of hemoglobin and the number of platelets were significantly decreased P <0.001). The expression level of miR-22 in peripheral blood of children with AML was significantly lower than that in control group (P <0.001). Compared with HS-5 cells, the expression levels of miR-22 in TF-1a, HL-60, and THP-1 cells were significantly decreased (P <0.05), and in HL-60 cells was the lowest. Therefore, HL-60 cells were selected for subsequent experiments. Up-regulation of miR-22 or silencing of FMNL2 could reduce the number of migrating cells and increase apoptosis rate (P <0.05). MiR-22 targeted and negatively regulated the expression of FMNL2 . FMNL2 overexpression reversed the effects of up-regulated miR-22 on migration and apoptosis of HL-60 cells.@*CONCLUSION@#MiR-22 can inhibit the migration and promote apoptosis of HL-60 cells by down regulating the expression of FMNL2 .

Independent prognostic value of the congestion and renal index in patients with acute heart failure / 老年心脏病学杂志（英文版）

BACKGROUND@#Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF.@*METHODS@#We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes.@*RESULTS@#A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system.@*CONCLUSIONS@#In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

Clinical progress of 3D printing technology in treatment of distal tibial epiphyseal fractures in adolescents / 局解手术学杂志

The distal tibial epiphyseal fractures is a common type of fracture in adolescents.The distal tibia is adjacent to the ankle joint,where the epiphysis is fragile and easily damaged when the fracture occurs,resulting in ischemic necrosis of the epiphysis and impaired bone growth,and the degree of damage and treatment effect directly influence the shape and function of the ankle joint,seriously affect the prognosis and quality of life of adolescents.Therefore,anatomical reduction should be achieved after injury as much as possible to achieve stable fixation.For stable fractures of the distal tibial epiphysis(such as Salter-Harris type Ⅰ or Ⅱ fractures),the conservative treatment can be used;whereas for unstable fractures,especially Salter-Harris type Ⅲ and Ⅳ fractures with a high risk of displacement,surgical treatment is preferred.However,due to the physiological characteristics of the epiphysis of adolescents,the distal tibia grow and develop differently,the individualized treatment plans should be developed according to the situation of adolescents.3D printing technology combined with imaging technologies including CT and MRI can print complex shapes of geometric structures to meet individual needs,and play an important role in the surgical treatment of distal tibial epiphyseal fractures,especially Salter-Harris type Ⅲ and Ⅳ fractures,which can contribute to formulating individualized surgical plans,improving the success rate of surgery,reducing the incidence of long-term complications,and greatly improving the prognosis of adolescents.Based on the literature reports in the past decade,this paper reviews the research progress of the application of 3D printing technology in the diagnosis and treatment of distal tibial epiphyseal fractures in adolescents.

Effect assessment of pneumatic limb circulation promoting device in postoperative swelling reduction of lower limb fracture / 中国医学装备

Objective:To explore the application effect of pneumatic limb circulation promoting device in postoperative swelling reduction of lower limb fracture.Methods:A total of 48 patients with lower limb fractures who admitted to hospital were selected.According to the random number table method,they were divided into an observation group(n=24)and a control group(n=24).All patients received routine rehabilitation treatment,and the control group conducted routine swelling reduction treatment,and the observation group used LymphaTouch device to conduct swelling reduction treatment.The visual analogue scale(VAS)was applied to compare the change of pain intensities of two groups between before and after treatment,and the modified Barthel index was used to evaluate the ability of daily living,and the simplified formula for evaluating quality of life(short form-36,SF-36)was used to evaluate the life quality of patient.The differences of the muscle circumferences between two groups after treatment were compared,and the swelling conditions of affected limbs of the patients were evaluated.And then,the incidences of complications of two groups were compared.Results:There were no statistically significant differences in VAS scores between the two groups of patients before and 3 days after treatment,and the VAS scores of two groups of patients decreased significantly at the 5th d and 7th day after treatment(t=26.046,t=25.255,P<0.05).The differences of the difference values of muscle circumferences of the two groups of patients between before and 3 days after treatment were not statistically significant.The difference values of muscle circumferences of the two groups of patients decreased at the 5th d and 7th day after treatment,and the differences were statistically significant(t=26.046,t=25.255;P<0.05),respectively.After treatment,the modified Barthel indexes and SF-36 scores increased in both groups of patients,and the observation group was significantly higher than the control group,with a statistically significant difference(t=2.970,t=3.433,P<0.05).The incidence of complications in the observation group was significantly lower than that in the control group,and the difference was significant(x2=4.550,P<0.05).Conclusion:The addition of pneumatic limb circulation promoting device after the surgery of lower limb fracture and the application of LymphaTouch device in treatment can relieve the intensity of postoperative pain and the degree of limb swelling,and improve the ability of daily life and quality of life,and reduce the incidence of complications of patients.

Research progress on the relationship between HIV infection, antiretroviral therapy, and diabetes mellitus / 中华流行病学杂志

The expectancy and quality of life among people with HIV have improved remarkably with the widespread use of antiretroviral therapy (ART). In the meantime, the risks for HIV-related metabolic diseases have increased significantly, in particular diabetes mellitus. Multi-factors coeffect to increasing the risk of diabetes mellitus among HIV patients. Recently, growing of research has reported an association between HIV infections and ART and the development of diabetes mellitus. In this article, we summarize the recent studies investigating HIV infection and ART in diabetes mellitus to clarify their mechanism on the development of diabetes.

Effectiveness of precise prevention and control strategies of dynamic zero COVID-19 in Ningbo, Zhejiang province / 中华流行病学杂志

Objective: To evaluate effectiveness of the precise prevention and control strategies of dynamic zero COVID-19 in Ningbo, Zhejiang province. Methods: Based on the incidence data of COVID-19 and case epidemiological survey report in Ningbo in December 2021, the incidence curve of COVID-19 was generated and a dynamics model was developed to estimate the case number of under different intervention measures. The basic reproduction number (R0) and real-time reproduction number (Rt) were calculated to evaluate intervention effect. Results: A total of 74 cases of COVID-19 had been confirmed in Ningbo as of 17 December, 2021. The R0 was estimated to be 4.3. With the strengthening of prevention and control measures, the Rt showed a gradual downward trend, dropping to below 1.0 on December 11 and 0.4 on December 14. The model fitting results showed that the actual case number was close to the estimated case number (76 cases) when the effectiveness of intervention was 90%. The number of cases decreased by 98.4% compared with that if no intervention was taken. Conclusion: The precise prevention and control strategies of dynamic zero COVID-19 have obvious effect, which can facilitate the rapid control of COVID-19 epidemic in Ningbo.

Changes in Intestinal Microflora and Lipid Metabolism in Ovariectomized Rats and Regulatory Effect of Erxian Decoction / 中国实验方剂学杂志

ObjectiveTo explore the intervention effect of Erxian decoction on intestinal microflora after ovariectomy in rats by 16S rRNA gene sequencing. MethodThirty-two female healthy SD rats were randomly divided into a Sham operation （Sham） group， a model （OVX） group， an estrogen （E） group， and an Erxian decoction （EXD） group， with 8 rats in each group. The rats in the E group and the EXD group received 1.8×10-4 g·kg-1 estradiol valerate solution and 9 g·kg-1 Erxian decoction， respectively， and those in the Sham group and the OVX group received an equal volume of distilled water once a day for 16 weeks. After 16 weeks， the levels of serum estrogen and blood lipid were detected. The fecal DNA was extracted， followed by 16S rRNA gene sequencing and analysis. ResultCompared with the Sham group， the OVX group showed reduced serum estrogen level （P<0.01） and increased serum levels of total cholesterol （TC） and low-density lipoprotein cholesterol （LDL-C） （P<0.05）. Compared with the OVX group， the E group and the EXD group showed increased serum estrogen level （P<0.01） and reduced TC and LDL-C （P<0.05）. Alpha diversity showed that there was no significant change in intestinal microflora diversity after ovariectomy. Beta diversity showed that there were significant differences in the structure of intestinal microflora in the four groups. The intervention of Erxian decoction could improve the changes in intestinal microflora after ovariectomy. LEfSe was used to analyze the differential flora in the four groups. The results showed that the Sham group and the OVX group had 3 differential bacterial phyla and 18 differential bacterial genera， the OVX group and the E group had 1 differential bacterial phylum and 12 differential bacterial genera， and the OVX group and the EXD group had 3 differential bacterial phyla and 5 differential bacterial genera. Estrogen intervention could reverse the change trend of Ruminococcus 1， Anaerovibrio， and Turicibacter in the OVX group. Erxian decoction intervention could reverse the change trend of Bacteroidetes， Firmicutes， Prevotella 9， Ruminococcaceae UCG-014， Ruminococcus 1， and Fusicatenibacter in the OVX group. ConclusionThe structure and function of intestinal microflora in ovariectomized rats changed obviously， and Erxian decoction could ameliorate the change.

A prospective multicenter and real-world study on the diagnostic value of combination of number connection test-B and line tracing test in mild hepatic encephalopathy / 中华消化杂志

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Research progress on pharmacological effect of evodiamine / 中国药理学通报

Evodiamine(EVO)is an indoloquinazoline alkaloid isolated from the fruits of Euodia rutaecarpa,which has long been used in traditional Chinese medicine to treat various diseases.Modern medical research shows that evodiamine has various pharmacological activities and extremely high medicinal value such as anti-inflammation,anti-tumor,losing weight,treating Alzheimer's,and antibacterium.Evodiamine can interact with a variety of proteins.For example,the interaction between evodiamine and TRPV1 induces its activation to exert anti-inflammatory and losing weight; the interaction with DNA topoisomerase I inhibits its function and thus inhibit bacterial proliferation; the interaction with tubulin promotes NLRP3 inflammasome activation,and exerts anti-tumor and anti-inflammatory functions.In recent years,with the in-depth study of evodiamine,pharmacological research and mechanism of evodiamine has significant improvement.Recent progress of pharmacological effect of evodiamine is highlighted in this review.

Hypoxic pretreatment enhancing the angiogenesis of aged human bone marrow mesenchymal stem cells through hypoxia inducible factor-1α / 解剖学报

Objective To investigate the effect of hypoxic pretreatment on the angiogenesis of aged human bone marrow mesenchymal stem cells (hBMSCs), so to provide experimental support for more effective autologous stem cell transplantation therapy in aged patients with ischemic myocardial injury. Methods The aged hBMSCs were cultured in a hypoxic incubator, and then the cell morphology was observed under inverted phase-contrast microscope, the surface markers were detected by flow cytometry, and the differentiation potential was detected by osteogenic and adipogenic differentiation. Subsequently, the conditioned medium (CM) of young hBMSCs under normoxic culture (norCM), the conditioned media of aged hBMSCs under normoxic and hypoxic culture(hypoCM) were collected respectively. They were named as norCM-young, norCM-old and hypoCM-old. The equal volume of medium, which was not treated with stem cells, was set as control group. Human umbilical vein endothelial cells (HUVECs) were treated with 4 conditioned media, the cell survival rate was detected by CCK-8 assay, and the tube formation experiment was used to detect the angiogenesis ability in vitro. The BCA method was used to detect the total protein concentration of the conditioned medium of each group, and the Western blotting was used to detect the expression of hypoxia inducible factor-1α (HIF-1α) in the cells and the conditioned media. Results There was not significant effect of hypoxic pretreatment on the morphology, surface markers and differentiation ability of aged hBMSCs (P > 0. 05. n ≥ 3). Compared with the norCM-old group, hypoCM-old group significantly improved the survival of HUVECs under hypoxia-reoxygenation condition (P < 0. 05, n = 5), and the tube formation ability of it (P<0. 01, n = 5). The total protein concentration of hypoCM-old group was significantly higher than that of norCM-old group (P<0. 05, n = 3). The expression of HIF-1α in hBMSCs of hypo-old group was significantly higher than that of nor-old group (P<0. 05,n = 3), while the content of HIF-1α in conditioned medium of hypoCM-old group was significantly higher than that in norCM-old group (P<0. 01,n = 3). Conclusion The aged hBMSCs pretreated with hypoxia can promote the survival and tube formation of HUVECs through paracrine in vitro, which is HIF-1α-related.