COSSH score and associated risk stratification in predicting short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure / 中华临床感染病杂志

Objective:To evaluate the prognostic efficacy of the Chinese Group on the Study of Severe Hepatitis B (COSSH) acute-on-chronic liver failure (ACLF) II score (COSSH ACLF IIs) and associated risk stratification in predicting short-term prognosis of patients with hepatitis B virus-related ACLF (HBV-ACLF).Methods:Clinical data of 224 patients with HBV-ACLF admitted to the First Affiliated Hospital of Wannan Medical College and the First Hospital of Quanzhou, Fujian Medical University from January 2018 to December 2021 were retrospectively analyzed. The patients were divided into survival group ( n=171) and fatal group ( n=53) according to 28-day survival status. The values of the COSSH ACLF IIs, the Chronic Liver Failure-Consortium (CLIF-C) ACLF score (CLIF-C ACLFs), the CLIF-C organ failure score (CLIF-C OFs), the Model of End-stage Liver Disease (MELD) score (MELDs), the MELD-sodium score (MELD-Nas), and the Child-Turcotte-Pugh score (CTPs) for 28-day mortality prediction were compared using the area under the receiver operating characteristic curve (AUC). The patients were divided into groups according to COSSH ACLF classification and COSSH ACLF IIs risk stratification, respectively. The differences in 28-day mortality between groups were compared by Kaplan-Meir method, and the consistency of the two ACLF classification systems was compared by Kappa consistency test. Results:The AUC, sensitivity, and specificity of the COSSH ACLF IIs in 28-day mortality prediction were 0.885, 0.981 and 0.731, respectively. For predicting 28-day mortality, the COSSH ACLF IIs achieved a higher AUC than the CLIF-C OFs, the MELDs, the MELD-Nas, and the CTPs ( P<0.01), while there was no significant difference in AUC between the COSSH ACLF IIs and the CLIF-C ACLFs ( Z=1.696, P=0.090). The cumulative 28-day mortality rates significantly increased with the ascending of COSSH ACLF grade and risk strata of the COSSH ACLF IIs (11.7%, 43.5% and 93.3%, P<0.001; 14.2%, 41.0% and 81.3%, P<0.001). The two ACLF grading systems showed a consistency in severity stratification of HBV-ACLF patients (Kappa=0.478, P<0.001). Conclusion:The COSSH ACLF IIs shows an excellent prognostic performance in predicting short-term mortality of HBV-ACLF patients. Using the new risk stratification scale can simplify the severity stratification of HBV-ACLF patients.

Differences in non-suicidal self-injury behaviors between only-child and non-only-child adolescents with mood disorders: a cross-sectional study / 中国当代儿科杂志

OBJECTIVES@#To investigate the differences in non-suicidal self-injury (NSSI) behaviors between only-child and non-only-child adolescents with mood disorders.@*METHODS@#A three-stage sampling method was used to perform a cross-sectional survey of 529 adolescents, aged 12-18 years, who had mood disorders and NSSI behaviors. These adolescents were sampled from the outpatient service of 20 mental hospitals in 9 provinces of China from August to November 2020. A self-made questionnaire was used to collect general demographic data. The Functional Assessment of Self-Mutilation, Beck Scale for Suicide Ideation, Kessler Psychological Distress Scale, Stress Mindset Measure-General, Multidimensional Scale of Perceived Social Support, Multidimensional Students' Life Satisfaction Scales, and Rosenberg Self-Esteem Scale were used to collect the information on self-injury behaviors and psychological factors in these adolescents.@*RESULTS@#A total of 529 adolescents with mood disorders and NSSI behaviors were surveyed, among whom 375 were only-child adolescents and 154 were non-only-child adolescents. Compared with the non-only-child group, the only-child group had a significantly higher total score of Functional Assessment of Self-Mutilation (P<0.05) .The type and frequency of self-injury in the only-child group were significantly higher than those in the non-only-child group (P<0.05). Psychological analysis showed that compared with the non-only-child group, the only-child group had a significantly lower score of self-esteem (P<0.05) and significantly higher scores of psychological distress and depressive symptoms (P<0.05). The multiple linear regression analysis showed that the score of suicidal ideation was positively correlated with the frequency of NSSI behaviors in both only-child and non-only-child adolescents with mood disorders (P<0.05); in the only-child adolescents, the level of self-esteem was negatively correlated with the frequency of NSSI behaviors (P<0.05), and the score of stress perception was positively correlated with the frequency of NSSI behaviors (P<0.05); in the non-only-child adolescents, the score of anxious emotion was positively correlated with the frequency of NSSI behaviors (P<0.05).@*CONCLUSIONS@#Among the adolescents with mood disorders and NSSI behaviors, the only-child adolescents tend to have a higher frequency of self-injury and poorer mental health, and therefore, the only-child adolescents with mood disorders and NSSI behaviors need more attention.

Association between Internet gaming disorder and sleep quality among junior middle school student of Xi an City / 中国学校卫生

Objective@#To investigate the association of Internet gaming disorder (IGD) and sleep quality in adolescents of Xi an, thereby providing theoretical evidence for prevention of IGD and improvement of sleep quality of adolescents.@*Methods@#A total of 1 181 adolescents from 3 middle schools of Xi an were randomly selected between August, 2019 and February, 2020. These adolescents were assessed by a series of questionnaires, including basic information questionnaire, IGD and Insomnia Severity Index (ISI). Univariate analysis and multivariate Logistic regression model were used to evaluate the association between IGD and insomnia.@*Results@#Among 929 junior middle school students who participated in online games and the IGD Diagnostic Questionnaire was filled out in the past 12 months, the prevalence of IGD was 20.0%(186). Univariate analyses indicated that gender,whether single family, whether they living with their parents, whether they were addicted to online games, whether they could control the time of online games, and the severity of insomnia influenced IGD ( χ 2=17.11, 8.33, 202.92, 91.23, 29.06, P <0.05). The multivariate Logistic regression of the total population showed that participating in online games was not associated with the severity of insomnia ( OR = 1.62 , 95% CI =0.92-0.85, P >0.05). The people who participated in online games in the past 12 monthsthe severity of insomnia was positively correlated with the risk of IGD ( OR =3.56，95% CI =1.92-6.61, P <0.01).@*Conclusion@#Internet gaming disorder become a severe situation in the middle school students. The severity of insomnia might become the risk factor of IGD, so social should pay more attention to the prevention of internet addiction.

Association between Internet gaming disorder and sleep quality among junior middle school student of Xi an City / 中国学校卫生

Objective@#To investigate the association of Internet gaming disorder (IGD) and sleep quality in adolescents of Xi an, thereby providing theoretical evidence for prevention of IGD and improvement of sleep quality of adolescents.@*Methods@#A total of 1 181 adolescents from 3 middle schools of Xi an were randomly selected between August, 2019 and February, 2020. These adolescents were assessed by a series of questionnaires, including basic information questionnaire, IGD and Insomnia Severity Index (ISI). Univariate analysis and multivariate Logistic regression model were used to evaluate the association between IGD and insomnia.@*Results@#Among 929 junior middle school students who participated in online games and the IGD Diagnostic Questionnaire was filled out in the past 12 months, the prevalence of IGD was 20.0%(186). Univariate analyses indicated that gender,whether single family, whether they living with their parents, whether they were addicted to online games, whether they could control the time of online games, and the severity of insomnia influenced IGD ( χ 2=17.11, 8.33, 202.92, 91.23, 29.06, P <0.05). The multivariate Logistic regression of the total population showed that participating in online games was not associated with the severity of insomnia ( OR = 1.62 , 95% CI =0.92-0.85, P >0.05). The people who participated in online games in the past 12 monthsthe severity of insomnia was positively correlated with the risk of IGD ( OR =3.56，95% CI =1.92-6.61, P <0.01).@*Conclusion@#Internet gaming disorder become a severe situation in the middle school students. The severity of insomnia might become the risk factor of IGD, so social should pay more attention to the prevention of internet addiction.

Real-world study evaluating the incidence of liver damage conditions in patients with primary liver cancer using immune checkpoint inhibitor-based combination therapy / 中华肝脏病杂志

Objective: To evaluate the incidence of immune checkpoint inhibitor-based combination therapy-induced liver damage in patients with primary liver cancer. Methods: Clinical data of 65 hospitalized cases of primary liver cancer treated with programmed cell death-1 its ligand programmed death-ligand 1 (PD-1/PD-L1) antibody in the Department of Infectious Diseases of the Second Affiliated Hospital of Chongqing Medical University from January 1, 2018 to March 31, 2021 were retrospectively analyzed. The degree of liver injury before and after treatment was assessed according to CTCAE v5.0. Patients were grouped according to gender, age, presence or absence of cirrhosis, baseline Child-Pugh score, BCLC stage, and treatment regimen to compare the incidence of liver injury under different conditions. The χ (2) test or rank-sum test was used for comparison among multiple groups. Results: 46 cases (70.77%) had liver damage of any grade according to the CTCAE V5.0 criteria during the treatment and observation period. All 6 cases who received standardized anti-hepatitis B virus (HBV) treatment developed liver damage. 10 (15.38%), 15 (23.08%), 19 (29.23%), and 2 (3.08%) cases had grade 1, 2, 3, and 4 liver damage respectively. There was no statistically significant difference in the incidence of liver damage between male and female patients (68.33% and 100%, P = 0.180). There was no statistically significant difference in the incidence of liver damage among different age groups (P = 0.245). The incidence of liver damage in cirrhotic and non-cirrhotic group was 72.22%, and 63.64% (P = 0.370), respectively. The incidence of liver damage in patients with baseline Child-Pugh class A, B, and C were 71.43%, 61.11% and 100%, respectively, and the difference was not statistically significant (P = 0.878). The incidence of liver damage was not statistically significantly different under different BCLC stages (P = 1.000). The incidence of liver damage in the PD-1/PD-L1 antibody monotherapy, PD-1/PD-L1 antibody combined with targeted drug therapy, and PD-1/PD-L1 antibody combined with TACE/radiofrequency ablation treatment group were 60.00%, 67.85%, and 86.67%, respectively. There was no statistically significant difference in the incidence of liver damage between the treatment regimen (P = 0.480). Conclusion: Immune checkpoint inhibitor therapy-induced liver damage is common in patients with primary liver cancer; however, it rarely severely endangers the patient's life. Additionally, patient's gender, age, presence or absence of cirrhosis, baseline liver function, BCLC stage and the immunotherapy regimen has no effect on the incidence of immune-related liver damage.

A Case Series of Olfactory Dysfunction in Imported COVID-19 Patients: A 12-Month Follow-Up Study / 生物医学与环境科学（英文）

Objective@#The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases.@*Methods@#A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up.@*Results@#Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases.@*Conclusions@#Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.

Feasibility of Preheating at 41 ℃ to Correct Red Blood Cell Parameters in the Presence of High-titer Cold Agglutinins / 中国医学科学院学报

Objective To explore the feasibility of preheating in 41 ℃ water bath for 30 minutes to correct the red blood cell parameters in the specimens containing high-titer cold agglutinins(CAs). Methods Two specimens containing high-titer CAs were selected during work,and the parameters of complete blood count at room temperature or after preheating in 37 ℃ or 41 ℃ water bath were compared.The smears were stained,and the distribution of red blood cells was observed with a microscope.Further,74 specimens without CAs were collected for complete blood count,and then the test results at room temperature and after preheating at 41 ℃ were compared. Results At room temperature,the specimens containing high-titer CAs showed significantly reduced red blood cell count(RBC)and hematocrit(HCT),abnormally increased mean corpuscular hemoglobin(MCH)and mean cell hemoglobin concentration(MCHC),abnormal percents of hemoglobin(HGB)and RBC,and aggregation of a large number of red blood cells.After being preheated at 37 ℃ for a certain time,the specimens demonstrated obviously improved parameters while still aggregation of a small number of red blood cells.After being preheated at 41 ℃ for 30 minutes,the specimens showed significantly increased RBC,normal HCT,MCH,and MCHC,and evenly distributed red blood cells.The 74 specimens without CAs showed the comparability was ≥80% between room temperature and preheating at 41 ℃ for 30 minutes or 60 minutes. Conclusion We can preheat the specimens containing high-titer CAs in a water bath at 41 ℃ to obtain accurate red blood cell parameters.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China / 中华医学杂志(英文版)

BACKGROUND@#There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.@*METHODS@#From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.@*RESULTS@#Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).@*CONCLUSIONS@#Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

Influencing factors and evaluation methods of skin microchannels formation and closure after microneedles application / 药学学报

As a novel transdermal drug delivery technology of minimally invasive, safe and efficient, microneedles have received increasing attention. The microchannels formation by microneedles onto the skin is a prerequisite and key for microneedles to deliver drugs. However, there is still a lack of systematic evaluation in skin microchannels. This review summarized influencing factors and evaluation methods in microchannels formation and healing by microneedles, including geometric parameters, materials for preparation, drugs, penetration parameters, differences among the skin of subjects, and presence or absence of occlusion. This review provides reference for other scholars to further study the effectiveness and security of microneedle applications.

Effects of metal or dissolving microneedles and its parameters of operation on the formation and closure of skin microchannels / 药学学报

To investigate the influence factors and effects of metal or dissolving microneedles on the formation and healing of skin microchannels, the pencil-shaped or conical stainless steel microneedles with different lengths, tip to tip space and base area, and the pencil-shaped dissolving microneedles with different tip to tip space were used. The microneedles were applied to the skin of epilatory mice and rats, and the effects of various microneedle parameters, application parameters, and animals on the microchannels were explored by the transepidermal water loss (TEWL) and methylene blue staining. Visually observe the skin local irritation caused by the microneedles. The animal experiments were approved by the Animal Experiments Welfare and Ethical Committee of Zhejiang University of Technology. The application time of the microneedle should be maintained at 30 s or more. When the insertion forces were 2, 4, 8 N, and the TEWL initial values of the formed microchannels were 12.9, 33.0, 40.4 g·m-2·h-1, respectively. When the length of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 37.1, 40.4, 49.5 g·m-2·h-1, respectively. When the tip to tip space of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 33.2, 40.4, 55.8 g·m-2·h-1, respectively. When the base area of metal microneedle were 0.16, 0.35, 0.62 cm2, and the TEWL initial values of the formed microchannels were 35.1, 40.4, 67.1 g·m-2·h-1, respectively. The effects of conical and pencil-shaped microneedles are similar. When the tip to tip space of pencil shaped dissolving microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 49.8, 60.5, 70.5 g·m-2·h-1, respectively. The TEWL baseline values of animal skins of different genders and series are different, but the tendency of microchannels formation and closure is similar. Visual inspection revealed that the slight erythema caused by the microneedles subsided within 24 h. Microneedles of different parameters have different effects on microchannels. The microchannels closed within 24 or 48 h, and the skin local irritation caused by microneedle was mild.

Exhaustion of CD8 / 中国实验血液学杂志

OBJECTIVE@#To investigate the changes in function of CD8@*METHODS@#Flow cytometry was used to detect the expressions of PD-1, TIM-3, and LAG-3, which were the markers of exhausted CD8@*RESULTS@#The expressions of inhibitory receptors (PD-1, TIM3 and LAG-3) on CD8@*CONCLUSION@#The exhausted CD8

Research Advance of the Roles of N6-methyladenosine in the Regulation of Hematopoiesis--Review / 中国实验血液学杂志

There are more than 150 types of chemical modifications in RNA, mainly methylation, which are widely distributed in all kinds of RNA, including messenger RNA, transfer RNA, ribosomal RNA, non-coding small RNA and long non-coding RNA. In recent years, the identification of RNA methylation modification enzymes and the development of high-throughput sequencing technology at transcriptome level laid a foundation for revealing the expression and function of genes regulated by chemical modification of RNA. In this review, the most recent advances of RNA methylation, especially N6-methyladenosine (m

Evaluation of adhesive bone conduction hearing aid in pediatric patients with unilateral congenital aural atresia / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the auditory efficacy and subjective satisfaction of adhesive bone conduction hearing aid in children with unilateral congenital aural atresia (UCAA). Methods: Ten subjects (5 males and 5 females) diagnosed with UCAA with an average age of 8.3 years old (ranged from 5 to 15) were included in Beijing Tongren Hospital, Capital Medical University from January to August 2019. The free sound field hearing threshold, word recognition score in quiet, speech reception threshold in noise and sound localization ability (results were measured by RMS error) tests were performed in unaided and aided situation, respectively. Subjective satisfaction questionnaires were also distributed to subjects. Paired t test and Wilcoxon signed rank test were used as statistical analysis methods. Results: The average hearing threshold in aided condition was improved by (21.9±4.4) dB (t=15.8，P<0.05). Speech recognition abilities were generally improved both under quiet and noise (P<0.05);however, when the binaural summation, squelch and head shadow effects were analyzed respectively, the binaural squelch effect was not statistically improved (P>0.05), while the other effects were improved in aided condition (P<0.05). In sound localization test, there was no significant difference of the RMS error value between the unaided and aided situation (P>0.05). The subjects got high satisfaction rates in three subjective questionnaires. Conclusion: The adhesive bone conduction hearing aid can provide significant audiological benefit for children with UCAA as well as raising the quality of their life.

Effect of γ-secretase inhibitor on middle ear ultrastructures in ovalbumin-mediated otitis media with effusion in rats / 中华耳鼻咽喉头颈外科杂志

Objective: To study the effect of the inhibitor of Notch signaling pathway-γ-secretase inhibitor DAPT on the ultrastructures of middle ear in the ovalbumin (OVA)-mediated allergic OME in vivo. Methods: Male Sprague-Dawley (SD) rats, weighing 250-300 g, were completely and randomly divided into three groups (5 rats, 10 ears in each group):(1)Control group(2)OME group(3)OME+DAPT group. Rats in the OME group underwent systemic and local sensitization by intraperitoneal and intratympanic injection of ovalbumin to make the model of OVA-induced OME. Rats in the control group were sensitized with PBS. On the basis of establishing the OME model, OME+DAPT group were intraperitoneal injected with DAPT (10 mg/kg) for seven consecutive days and were administered before intratympanic injection of ovalbumin. After the model was successfully established, endoscopy,H&E staining and scanning electron microscopy were used to study the histology and mucous-ciliary ultrastructures of the non-ciliated and ciliated mucosa in the middle ear of each group. One-way ANOVA and Tukey methods were used for statistical analysis. Results: H&E staining showed that the three groups had statistically significant differences in submucosal thickness both in non-ciliated and ciliated regions (non-ciliated area:(6.83±1.47)μm, (38.58±9.57)μm, (32.17±11.89)μm, respectively. F=107.9;cilia area:(26.69±3.22)μm, (30.41±6.75)μm, (26.76±4.06)μm, respectively. F=5.62,both P<0.01). The thickness of the submucosa in the non-ciliated area and the cilia area of the OME group were significantly thicker than that of control group (F=42.08 and 4.40,both P<0.05); the thickness of the non-ciliated area and the ciliated area in OME+DAPT group were reduced compared to OME group(F=1.55 and 2.77,both P<0.05). Scanning electron microscopy showed that the array of cilia on the middle ear mucosa was disorderly arranged and inversed, this phenomenon was relieved in the OME+DAPT group. The number of goblet cells in the control group, OME group, and OME+DAPT group were 9.87±1.92; 15.67±5.77; 10.33±1.99 respectively and the difference between them was statistically significant (F=11.43, P<0.01). The number of goblet cells in the OME group were significantly higher than those in the control group (F=9.00,P<0.01) and the number of goblet cells in the OME+DAPT group were decreased compared to those of OME group (F=8.41, P<0.01). Conclusions: The study demonstrates the pathological changes of the ultrastructure in middle ear in OVA-induced OME and the effect of the γ-secretase inhibitor on it. In OME group, the cilia are disorderly arranged and inversed, the number of goblet cell is increased and they are swelled which suggest the hypersecretion of the mucus. DAPT can regulate OVA-induced allergic inflammation and relieve pathological changes of ultrastructure in middle ear mucociliary transport system through alleviating submucosal inflammation, reducing the hypersecretion of goblet cell and the morphological damage of cilia through the Notch signaling pathway.

Bonebridge implantation combined with simultaneous bilateral auricle reconstruction for bilateral congenital aural atresia / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the feasibility and safety of auricle reconstruction combined with Bonebridge implantation for bilateral aural atresia patients. Methods: A retrospective analysis was conducted for 36 cases(72 ears) who underwent Bonebridge implantation combined with bilateral auricle reconstruction from February 1, 2017 to January 15, 2020. All cases were bilateral congenital aural atresia and underwent Nagata auricle reconstruction for both sides simultaneously. Bonebridge implantations were performed during the second stage of auricle reconstruction. Results: All 36 patients healed well and had no surgical complications when discharged. The preoperative average bone conduction threshold of the patients was(8.5±5.8) dB HL and postoperative bone conduction threshold was (8.4±5.2) dB HL. There was no significant change after the implantation (P=0.724). The preoperative average air conduction threshold of was(64.9±7.4)dB HL and postoperative air conduction threshold was (24.0±5.3) dB HL, which had a significant change after the implantation (P<0.001). The hearing threshold with Bonebridge significantly decreased by 40.9 dB HL compared with the preoperative air conduction threshold(P<0.001). The speech recognition rate of monosyllable words, disyllabic words and short sentences in quiet environment increased by 62.5%, 63.5% and 72.2% respectively. The differences were statistically significant (P<0.001). The speech recognition rate of monosyllabic words, disyllabic words and short sentences in noise environment were significantly increased by 55.9%, 58.9% and 69.9% respectively (P<0.001). After a follow-up of 18.3 months in average, the hearing results were stable and the aesthetic outcomes were satisfied. One patient had implant rupture and healed after revision surgery. Conclusions: With an integrated surgical procedure, patients with bilateral congenital aural atresia can complete bilateral auricle reconstruction and hearing implantation within six months. This integrated surgical procedure is safe and efficient, with a stable hearing improvement and good appearance.

Research progress on the precancerous lesions of cholangiocarcinoma / 中华肝胆外科杂志

Cholangiocarcinoma is a malignant tumor originating from bile duct epithelium, with insidious onset and high degree of malignancy. Most of the patients were diagnosed at the middle and late stages and the survival rate is very poor. The etiology of cholangiocarcinoma is still unknown. Billary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, biliary mucinous cystic neoplasm and intraductal tubular/tubulopapillary neoplasm of the bile duct are considered as precancerous lesions of cholangiocarcinoma. Improving the understanding of precancerous lesions of cholangiocarcinoma, and early treatment of these lesions are important for enhancingthe patients’ quality of life. However, the current understanding of precancerous lesions of cholangiocarcinoma is limited. Development of molecular diagnostic technology is deeply needed. And sensitive and specific biomarkers are urgently needed for the early diagnosis of the high-risk persons accurately, so as to achieve " early detection, early diagnosis and early treatment" . This article reviews how to recognize and deal with precancerous lesions of cholangiocarcinoma.

Blood-brain barrier and Alzheimer's disease and vascular cognitive impairment / 国际脑血管病杂志

The integrity of the blood-brain barrier (BBB) is important for maintaining the function of the central nervous system. Its leakage can occur prior to structural changes. At present, the role of BBB leakage abnormalities in the occurrence and development of cognitive impairment has attracted attention, and it has been found that Alzheimer's disease and vascular cognitive impairment are related to BBB leakage abnormalities. This article reviews the pathophysiology of BBB leakage in Alzheimer's disease and vascular cognitive impairment.

Establishment of Secondary HLH Mouse Model and Effect of Ruxolitinib on Disease Manifestations of Model Mide / 中国实验血液学杂志

OBJECTIVE@#To establish a secondary hemophagocytic lymphohistiocytosis(HLH) mouse model, and to investigate the effect of ruxolitinib on the disease manifestation of model mice.@*METHODS@#Wild type C57BL/6 mice were randomly divided into 4 groups: two groups of mice were intraperitoneally injected with CpG oligodeoxynucleotide 1826 (CpG-ODN1826) every other day to induce HLH, and other two groups were control groups. One group of the CpG-ODN1826 groups and one of the control groups were given ruxolitinib, and other two groups were given the same amount of PBS. Blood samples, serum ferritin and hepatic/spleen weights of experimental mice were detected and serum cytokine levels were measured by ELISA.@*RESULTS@#Compared with the control groups, the levels of white blood cells, hemoglobin and platelets in the CpG-ODN1826 groups were significantly lower (P＜0.05); and liver/body weight, spleen/body weight, serum ferritin, sCD25, IL-10, IL-1β, IFN-Ƴ, IL-12p70, GM-CSF, TNF-α and IL-18 levels significantly increased (P＜0.05). There was no significant difference in the levels of IL-2, IL-4, IL-5, IL-6, IL-22, IL-13, IL-27 and IL-23 between the two groups (P＞0.05). The spleen in CpG group had disordered internal structure, expanding red pulp and hyperplastic nucleated cells. The liver had severe perivascular inflammations. The spleen/weight of the ruxolitinib-treated mice in the CpG-ODN1826 group was significantly smaller than that of the unapplied ruxolitinib (P＜0.05).@*CONCLUSION@#The CpG-ODN1826 can induce secondary HLH symptoms in wild type C57BL/6 mice. Ruxolitinib can alleviate the symptoms of splenomegaly in HLH model mice.

Effect of Xiao Jianzhongtang on AMPK/PGC1-α Signal Pathway in Skeletal Muscle of Exercise Fatigue Mice / 中国实验方剂学杂志

Objective:To observe the effect of Xiao Jianzhongtang on Adenylate-activated protein kinase/peroxidase proliferation-activated receptor coactivator 1-α （AMPK/PGC1-α） signaling pathway in skeletal muscle of exercise fatigue mice.Method:Forty Kunming mice were randomly divided into normal group， model group， Buzhong Yiqitang group and Xiao Jianzhongtang group， with 10 mice in each group. The model group， Buzhong Yiqitang group and Xiao Jianzhongtang group were trained on the treadmill to establish a fatigue model， and the normal group did not apply any intervention. At the same time as the treadmill training， the model group was given the same amount of normal saline. Xiao Jianzhongtang was administered with 5 g·kg-1 of medicine， and Buzhong Yiqitang was administered with 2.8 g·kg-1 of medicine for 6 days. After the experiment， the weight of each group of mice and the time of running out of exhaustion were measured，the colorimetric method was used to detect the serum urea （UREA）， lactate dehydrogenase （LDH）， muscle glycogen （MG）， and skeletal muscle of each group of mice Na+-K+-ATPase， Ca2+-Mg2+-ATPase content， pathological changes of skeletal muscle of each group were observed by hematoxylin-eosin （HE） staining， Western blot was used to detect the protein expression of AMPK and PGC1-α in skeletal muscle of each group .Result:Compared with normal group， the body weight of model group significantly decreased （P<0.01）， and the contents of Na+-K+-ATPase， Ca2+-Mg2+-ATPase， LDH， and MG significantly decreased （P<0.05，P<0.01）. The content of UREA increased significantly （P<0.01）， and the expression of AMPK and PGC1-α protein increased significantly （P<0.01）. Compared with model group， the mice in the Xiao Jianzhongtang group had significantly increased body weight （P<0.05）， significantly increased the time spent on treadmill exhaustion（P<0.01）， Na+-K+-ATPase， Ca2+-Mg2+-ATPase， LDH， and MG. The content increased significantly（P<0.05， P<0.01）， the content of UREA decreased significantly （P<0.01）， and the expression of AMPK and PGC1-α protein increased significantly （P<0.01）.Conclusion:Xiao Jianzhongtang has an anti-exercise fatigue effect， which may be related to enhancing skeletal muscle AMPK/PGC1-α pathway，enhancing mitochondrial oxidative phosphorylation，reducing accumulation of metabolites，slowing down glycogen consumption and decomposition，and enhancing skeletal muscle energy synthesis.

Mechanism of Chaihu Shugansan on Syndrome of Liver Stagnation / 中国实验方剂学杂志

Chaihu Shugansan is a representative prescription for soothing the liver and relieving depression in traditional Chinese medicine(TCM). Chaihu Shugansan is from Jingyue Quanshu.Chaihu Shugansan has been widely used in clinic since Ming dynasty because of its exact curative effect.Chaihu Shugansan has the effect in soothing the liver and relieving depression through multiple components, multiple ways and multiple targets.At present, the mechanism of Chaihu Shugansan has been interpreted based on its multiple effect on neurotransmitters, cytokines, neuronal injury signal pathways, neuroendocrine, oxidative stress and so on.This paper summarizes the progress of clinical studies on source, pharmacology of single herbs and effective components of Chaihu Shugansan, in aspects of cardiovascular system, neuropsychiatric system, digestive system, reproduction-related systems, analyses and summarizes relevant literatures of Chaihu Shugansan published in recent years, and discusses about current development and shortcomings of Chaihu Shugansan, so as to provide ideas for the studies in the future.Beneficial explorations will be conducted in large-sample-size, standardized, clinical and experimental mutual verification.In proteomics research technology, network pharmacology, supramolecular theory of TCM and other fields, Chaihu Shugansan and liver depression syndrome will be organically connected from the microscopic perspective.And comprehensive studies will be conduct to TCM, metabonomics, proteomics, genomics and other disciplines, in order to clarify Chaihu Shugansan prescriptions, syndromes, therapeutics and its mechanism.