Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Risk factors of acute kidney injury in children with biliary atresia after liver transplantation / 国际外科学杂志

Objective:To analyze the incidence and risk factors of acute kidney injury in children with biliary atresia after liver transplantation.Methods:The retrospective case-control study was conducted.The clinical data of 115 children with biliary atresia who received liver transplantation for the first time in Beijing Friendship Hospital Affiliated to Capital Medical University from December 2018 to November 2020 were collected.The patients were divided into AKI group ( n=39) and non-AKI group ( n=76) according to the diagnostic criteria of the Kidney Disease Improving Global Outcomes(KDIGO). The differences of clinical indicators between the two groups were compared, and multivariate logistic regression analysis was performed for statistically significant variables ( P<0.05) to further determine the independent risk factors for AKI after liver transplantation. The measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between groups.Measurement data with non-normal distribution were represented by M( Q1, Q3), and Mann-Whitney U test was used for comparison between groups.Count data were expressed as cases and percentage, and comparisons between groups were made using Chi-square test or Fisher′s exact test. Results:The incidence of AKI in biliary atresia patients after liver transplantation was 33.9%. Univariate analysis showed that there were statistically significant differences in age ( OR=0.721, 95% CI: 0.553-0.938, P=0.014), preoperative infection ( OR=3.307, 95% CI: 1.294-8.468, P=0.013), PELD score ( OR=1.065, 95% CI: 1.031-1.101, P<0.001), serum creatinine numerical value ( OR=0.745, 95% CI: 0.657-0.858, P<0.001), intraoperative red blood cell transfusion ( OR=1.034, 95% CI: 1.028-1.051, P<0.001) and intraoperative plasma transfusion ( OR=1.055, 95% CI: 1.025-1.086, P=0.002) between the AKI group and the non-AKI group ( P< 0.05). Multivariate logistic regression analysis was performed on the selected indicators by univariate analysis, and the results showed that preoperative infection ( OR=3.763, 95% CI: 1.185-11.945, P=0.025) and low serum creatinine ( OR=0.685, 95% CI: 0.570-0.823, P<0.001), intraoperative red blood cell transfusion ( OR=1.033, 95% CI: 1.015-1.056, P=0.028) was independently associated with postoperative AKI ( P<0.05). The inpatient treatment time in ICU and in hospital between the two groups were statistically significant ( P<0.05). Conclusions:Preoperative infection, low creatinine numerical value and intraoperative red blood cell transfusion are independent risk factors for postoperative AKI in children with biliary atresia. AKI may prolong the time in ICU and in hospital.

Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study / 中华肝脏病杂志

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022) / 中华肝脏病杂志

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

Long-term clinical outcomes following total knee arthroplasty in patients with hemophilic arthropathy: a single-surgeon cohort after a 10- to 17-year follow-up / 中华医学杂志(英文版)

BACKGROUND@#Total knee arthroplasty (TKA) can reduce severe joint pain and improve functional disability in hemophilia. However, the long-term outcomes have rarely been reported in China. Therefore, this study aimed to evaluate the long-term outcomes and complications of TKA in Chinese patients with hemophilic arthropathy.@*METHODS@#We retrospectively reviewed patients with hemophilia who underwent TKA between 2003 and 2020, with at least 10 years of follow-up. The clinical results, patellar scores, patients' overall satisfaction ratings, and radiological findings were evaluated. Revision surgery for implants during the follow-up period was recorded.@*RESULTS@#Twenty-six patients with 36 TKAs were successfully followed up for an average of 12.4 years. Their Hospital for Special Surgery Knee Score improved from an average of 45.8 to 85.9. The average flexion contracture statistically significantly decreased from 18.1° to 4.2°. The range of motion (ROM) improved from 60.6° to 84.8°. All the patients accepted patelloplasty, and the patients' patellar score improved from 7.8 preoperatively to 24.9 at the last follow-up. There was no statistically significant difference in clinical outcomes between the unilateral and bilateral procedures, except for a better ROM at follow-up in the unilateral group. Mild and enduring anterior knee pain was reported in seven knees (19%). The annual bleeding event was 2.7 times/year at the last follow-up. A total of 25 patients with 35 TKAs were satisfied with the procedure (97%). Revision surgery was performed in seven knees, with 10- and 15-year prosthesis survival rates of 85.8% and 75.7%, respectively.@*CONCLUSIONS@#TKA is an effective procedure for patients with end-stage hemophilic arthropathy, which relieves pain, improves knee functions, decreases flexion contracture, and provides a high rate of satisfaction after more than ten years of follow-up.

Perioperative transfusion analysis and blood ordering schedule update for total knee arthroplasty / 中国输血杂志

【Objective】 To investigate the perioperative rate of allogeneic red blood cell (RBC) transfusion in patients who underwent total knee arthroplasty (TKA) and its risk factors, and to identify its cross-match to transfusion ratio (C∶T ratio). 【Methods】 Anesthetic data of patients who underwent TKA from January 2014 to October 2019 in Peking Union Medical College Hospital were collected and analyzed retrospectively. Perioperative allogeneic RBC transfusion rate was calculated, and binary Logistic regression analysis was performed to identify its risk factors in these patients. The overall C∶T ratio was calculated and divided into subgroups based on surgery type and age group. 【Results】 The study enrolled 2 903 patients. The perioperative rate of allogeneic RBC transfusion in TKA patients was 10.9% (95% CI 9.8%~12.0%) and overall C∶T ratio was 5.6∶1. The independent risk factors leading to perioperative allogeneic RBC transfusion included advanced age(OR=1.025, 95% CI 1.009~1.042, P<0.01), preoperative hemoglobin level(OR=0.966, 95% CI 0.954~0.978, P<0.001), preoperative anemia(OR=3.543, 95% CI 2.052~6.119, P<0.001), hematological diseases(OR=6.462, 95% CI 2.479~16.841, P<0.001), bilateral surgery(OR=7.681, 95% CI 5.759~10.245, P<0.01) and revision surgery(OR=9.584, 95% CI 4.360~21.065, P<0.001). 【Conclusion】 The risk factors for perioperative allogeneic RBC transfusion in TKA patients included advanced age, preoperative low hemoglobin level, preoperative anemia, hematological diseases, bilateral surgery and revision surgery. Only type and screen tests are recommended if patients receiving unilateral primary TKA surgery are less than 75 years old without anemia and hematological diseases, while at least one to four units of blood should be cross-matched if patients are with preoperative anemia and hematological diseases or will receive bilateral and revision arthroplasty.

Interpretation of the 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty / 中华骨科杂志

The American College of Rheumatology (ACR) and the American Association of Hip and Knee Surgeons (AAHKS) convened a writing group to develop a consensus report on the management of anti-rheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty in June 2022. In particular, the consensus provides significant updates on target synthetic disease modifying anti-rheumatic drugs and perioperative medication management in patients with systemic lupus erythematosus, as well as the addition of newly approved antirheumatic medications for administration. This article will interpret the consensus and provide a reference for the perioperative management of antirheumatic medications for hip and knee arthroplasty in patients with rheumatic diseases in China.

Clinical application of serum Golgi protein 73 in patients with chronic liver diseases / 中华肝脏病杂志

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.

Effects of Bushen Yiqi Huoxue Decoction in Treatment of Patients with Diminished Ovarian Reserve: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To explore the therapeutic effect of Bushen Yiqi Huoxue Decoction BYHD) in patients with diminished ovarian reserve (DOR).@*METHODS@#A total of 180 patients with DOR diagnosed from December 2013 to December 2014 were equally assigned into progynova and duphaston (E+D) group, Zuogui Pill group and BYHD group with 60 cases in each by computerized randomization. Patients received E+D, Zuogui Pill or BYHD for 12 months, respectively. Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, endometrial thickness, and the resistance indices (RIs) of ovarian arteries and uterine arteries were observed before and after treatment.@*RESULTS@#Nine women (4 from the E+D group, 3 from the Zuogui Pill group, and 2 from the BYHD group) withdrew from the study. After 6 months, Zuogui Pill and BYHD significantly decreased FSH and LH and increased endometrial thickness and AMH (all P<0.01). BYHD also resulted in E2 elevation (P<0.05), ovary enlargement (P<0.05), AFC increase (P<0.01), and RI of ovarian arteries decrease (P<0.05). After 12 months, further improvements were observed in the Zuogui Pill and BYHD groups (all P<0.01), but BYHD showed better outcomes, with lower FSH, larger ovaries and a thicker endometrium compared with the Zuogui Pill group (all P<0.01). However, E+D only significantly increased endometrial thickness (P<0.01) and no significant improvements were observed in the RI of uterine arteries in the three groups.@*CONCLUSIONS@#BYHD had a favorable therapeutic effect in patients with DOR by rebalancing hormone levels, promoting ovulation, and repairing the thin endometrium. The combination of tonifying Shen (Kidney), benefiting qi and activating blood circulation may be a promising therapeutic strategy for DOR.

Effect of improvement in antibiotic use strategy on the short-term clinical outcome of preterm infants with a gestational age of <35 weeks / 中国当代儿科杂志

OBJECTIVES@#To study the effect of improvement in antibiotic use strategy on the short-term clinical outcome of preterm infants with a gestational age of <35 weeks.@*METHODS@#The medical data were retrospectively collected from 865 preterm infants with a gestational age of <35 weeks who were admitted to the Neonatal Intensive Care Unit of Xiangya Hospital of Central South University from January 1, 2014 to December 31, 2016. The improved antibiotic use strategy was implemented since January 1, 2015. According to the time of implementation, the infants were divided into three groups: pre-adjustment (January 1, 2014 to December 31, 2014; n=303), post-adjustment Ⅰ (January 1, 2015 to December 31, 2015; n=293), and post-adjustment Ⅱ (January 1, 2016 to December 31, 2016; n=269). The medical data of the three groups were compared.@*RESULTS@#There were no significant differences among the three groups in gestational age, proportion of small-for-gestational-age infants, sex, and method of birth (P>0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment Ⅱ groups had a significant reduction in the rate of use of antibiotics and the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days or 4-7 days and a significant reduction in the proportion of infants with a duration of antibiotic use of >7 days in the early postnatal period (P<0.05). Compared with the post-adjustment Ⅰ group, the post-adjustment Ⅱ group had a significant reduction in the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days and a significant reduction in the proportion of infants with a duration of antibiotic use of 4-7 days or >7 days (P<0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment Ⅱ groups had significantly shorter duration of parenteral nutrition and length of hospital stay (P<0.05). There were gradual reductions in the incidence rates of grade ≥Ⅲ intraventricular hemorrhage (IVH) and late-onset sepsis (LOS) after the adjustment of antibiotic use strategy. The multivariate logistic regression analysis showed that the adjustment of antibiotic use strategy had no effect on short-term adverse clinical outcomes, and antibiotic use for >7 days significantly increased the risk of adverse clinical outcomes (P<0.05).@*CONCLUSIONS@#It is feasible to reduce unnecessary antibiotic use by the improvement in antibiotic use strategy in preterm infants with a gestational age of <35 weeks, which can also shorten the duration of parenteral nutrition and the length of hospital stay and reduce the incidence rates of grade ≥Ⅲ IVH and LOS.

Recommendations for diagnosis and treatment of primary biliary cholangitis in China (2021) / 中华内科杂志

Primary biliary cholangitis is a chronic autoimmune cholestatic disease with a progressive course. This disease is not rare in China, but standardized diagnosis and treatment for primary biliary cholangitis are insufficient. Based on the evidence and guidelines from China and other countries, Rheumatology Branch of Chinese Medical Association developed the recommendations of diagnosis and treatment for primary biliary cholangitis in China. The aim is to help clinicians recognize clinical characters, therapeutic selection and prognosis judgement of primary biliary cholangitis, which will contribute to make diagnosis in time, to select treatment properly and to manage follow-up scientifically.

Therapeutic drug monitoring of vancomycin in children after liver transplantation / 中国小儿急救医学

Objective:To understand the vancomycin dose, therapeutic drug monitoring(TDM) situation and therapeutic effect of children after liver transplantation.Methods:A retrospective analysis of the data of 98 children who received intravenous vancomycin treatment after liver transplantation were conducted in the Department of Critical Care Medicine of Beijing Friendship Hospital from January 2017 to June 2019, including demographic data, vancomycin dose, serum trough concentration, drug-related adverse reactions and clinical outcome data.Results:A total of 98 children received intravenous vancomycin treatment and at least one steady-state TDM blood sample was collected.Among them, 53 cases (54.1%) were male, and the median age was 9 months(5 months to 14 years old). The median first daily dose of vancomycin treatment was 50(30-60)mg/(kg·d), and the median duration of treatment was 14(3-54)days.Only 27.5%(27/98)of the children′s initial trough concentration reached the target concentration (10-20 mg/L), while 26 cases(26.5%) did not reach the target after adjusting the treatment.Six children(6.1%)had renal toxicity caused by vancomycin, and two children had skin rash.The effective treatment rate accounted for 51.7%(15/29). The initial trough concentrations of vancomycin in the effective and ineffective groups were(5.92±3.82)mg/L and(10.43±5.37)mg/L, respectively.The difference was statistically significant ( P=0.041). Conclusion:The rate of intravenous vancomycin in children after liver transplantation is low, and the dose needs to be adjusted individually.

Comparison of endogenetic microbial community diversity between wild Cordyceps sinensis,artificial C. sinensis and habitat soil / 中国中药杂志

To obtain the difference of the fungal and bacterial community diversity between wild Cordyceps sinensis, artificial C. sinensis and their habitat soil, Illmina Hiseq high-throughput sequencing technology was applied. The results show that Proteobacteria was the dominant bacterial phylum in C. sinensis, Actinobacteria was the dominant bacterial phylum in soil microhabitat, Ophiocordyceps sinensis was the predominant dominant fungus of C. sinensis. The α diversity analysis showed that the fungal diversity of stroma was lower than other parts, and the fungal diversity of wild C. sinensis was lower than that of artificial C. sinensis. The β diversity analysis showed that the fungal and bacterial community diversity of soil microhabitat samples was significantly different from that of C. sinensis. The fungal community diversity was less different between wild and artificial C. sinensis, especially in sclerotia. LEfSe analysis showed a lot of species diversity between wild and artificial C. sinensis. Those different species between wild C. sinensis, artificial C. sinensis and their habitat soil provide ideas for further research on breed and components of C. sinensis.

Long-term Behavioral Disorder after Hypoxic Ischemic Brain Damage in Newborn Mice / 中国康复理论与实践

Objective:To observe the long-term behavioral changes in movement, emotion, and learning and memory of newborn mice with hypoxic ischemic brain damage (HIBD). Methods:A total of 50 ten-day old newborn C57BL/6 mice were divided into control group (n = 20) and HIBD group (n = 30). The left common carotid artery was ligated in HIBD group and stayed in anoxic chamber for 45 minutes. All the mice were tested with suspension test, light/dark box test, elevated plus maze test, object recognition test and Y maze test two months after surgery. Results:There were 19 mice modeled successfully. Compared with the control group, the suspension test scores decreased (t = 2.785, P < 0.05); the time of latency of light/dark box test increased (t = -4.320, P < 0.001), the time and frequency in light box decreased (t > 2.603, P < 0.05); the time in open arm decreased (t = 4.576, P < 0.001) and the time in close arm increased (t = -3.287, P < 0.01) for the elevated plus maze test; the time nearing old object increased (t = -2.116, P < 0.05) and object recognition index decreased (t = 2.823, P < 0.05) for object recognition test; the time in the initial and novel arms decreased (t > 2.191, P < 0.05) for Y maze test in HIBD group. Conclusion:The long-term disorders of behavior may include disabilities of motor, learning and memory, and disorder of anxiety, in newborn mice with HIBD.

Effect of different tooth preparation designs on the marginal and internal fit discrepancies of cobalt-chromium crowns produced by computer-aided designing and selective laser melting processes

PURPOSE@#To evaluate the impact of five different tooth preparation designs on the marginal and internal fit discrepancies of cobalt-chromium (CoCr) crowns produced by computer-aided designing (CAD) and selective laser melting (SLM) processes. @*MATERIALS AND METHODS@#Five preparation data were constructed, after which design crowns were obtained. Actual crowns were fabricated using an SLM process. After the data of actual crowns were obtained with structural light scanning, intaglio surfaces of the design crown and actual crown were virtually superimposed on the preparation. The fit-discrepancies were displayed with colors, while the root means square was calculated and analyzed with one-way analysis of variance (ANOVA), Tukey’s test or Kruskal-Wallis test (α =.05). @*RESULTS@#The marginal or internal color-coded images in the five design groups were not identical. The shoulder-lip and sharp line angle groups in the CAD or SLM process had larger marginal or internal fit discrepancies compared to other groups (P < .05). In the CAD process, the mean marginal and internal fit discrepancies were 10.0 to 24.2 µm and 29.6 to 31.4 µm, respectively. After the CAD and SLM processes, the mean marginal and internal fit discrepancies were 18.4 to 40.9 µm and 39.1 to 47.1 µm, respectively. The SLM process itself resulted in a positive increase of the marginal (6.0 – 16.7 µm) and internal (9.0 – 15.7 µm) fit discrepancies. @*CONCLUSION@#The CAD and SLM processes affected the fit of CoCr crowns and varied based on the preparation designs. Typically, the shoulder-lip and sharp line angle designs had a more significant effect on crown fit. However, the differences between the design groups were relatively small, especially when compared to fit discrepancies observed clinically.

Analysis of clinical features and prognosis in patients with primary Sjögren's syndrome and autoimmune liver disease / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical features and prognosis in patients with primary Sjögren's syndrome (pSS) and autoimmune liver diseases (ALD).@*METHODS@#A retrospective analysis of clinical manifestation and prognosis was performed in patients with ALD or without ALD during the three years (February 2014 to December 2017).@*RESULTS@#Totally, 203 patients with pSS were included in this study, 68 patients had ALD (31 patients with autoimmune hepatitis, 37 patients with primary biliary cholangitis), while 135 patients did not have ALD. There were no differences between the two groups regarding age, gender, clinical manifestations, such as dry mouth, dry eyes, pain, fatigue, lymphadenopathy, glandular swelling, cutaneous involvement, lung involvement, and renal involvement, and the incidence rate of other autoimmune diseases, such as autoimmune thyroid disease, rheumatoid arthritis, and vasculitis. There were also no differences in the titer of antinuclear antibody (ANA), the positive rates of anti-Sjögren's syndrome A antibody (SSA), SSA52, and anti-Sjögren's syndrome B antibody (SSB), and at the levels of erythrocyte sedimentation rate and C-reactive protein between the two groups. Most importantly, the pSS patients with ALD had a shorter disease course, a higher positive rate of anti-mitochondrial M2 antibody (AMA-M2) and anti-centromere antibody, a higher level of IgG and IgM, a lower level of complement 3, and a decreased number of blood cells. They also had a higher level of liver related serum index, such as alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase and total bilirubin, direct bilirubin, indirect bilirubin, a higher incidence rate of liver cirrhosis, an increased death incident (the mortality was 13.24% in the pSS patients with ALD, while 2.96% in the controls, P=0.013), and a worse prognosis. Binary Logistic regression analysis revealed that liver cirrhosis, the EULAR Sjögren's syndrome disease activity index (ESSDAI) scores and the level of total bilirubin were the prognostic factors of mortality in the pSS patients with ALD. The survival curve was estimated by the Kaplan-Meier method. It demonstrated that the pSS patients with ALD had a lower survival rate when compared with the controls.@*CONCLUSION@#The patients with both pSS and ALD will suffer from a more severe disease and a higher death incident. We should pay more attention to these patients and provide a better symptomatic treatment for them during clinical practice.

Clinical analysis of in-hospital mortality in patients with idiopathic inflammatory myopathies / 中华风湿病学杂志

Objective:To explore the clinical features and risk factors of in-hospital mortality in idiopathic inflammatory myopathies (IIM) patients.Results:We retrospectively analyzed clinical records of polymyositis (PM), classic dermatomyositis (CDM) and clinically amyopathic dermatomyositis (CADM) patients admitted to the First Affiliated Hospital of Zhejiang University from February 2011 to February 2019. The deceased group was defined as the patients who died in hospital or within 2 weeks after hospital discharge, while the survival group was defined as the survival patients. The clinical features were described. Risk factors for deceased patients were identified by logistic regression analysis.Results:The in-hospital mortality rate of IIM patients ( n=424) was 9.4%. The hospitalization time was longer in deceased group ( n=40) [0.9(0.5, 1.0) m vs 0.6(0.4, 1.0) m, Z=-2.159, P<0.05]. Ferritin [1170.8(757.6, 3 759.9) μg/L vs 374.9(182.1, 993.4) μg/L, Z=-4.665], red blood cell distribution width (RDW) [15.2(14.5, 16.3)% vs 14.4(13.5, 15.2)%, Z=-3.066], CRP con-centrations [11.3(4.4, 36.9) mg/L vs 5.1(1.8, 17.2) mg/L, Z=-2.667] and neutrophil-to-lymphocyte ratio (NLR) [10.1(5.5, 18.9) vs 4.2(2.6, 6.5), Z=-5.108] were higher in deceased group ( P<0.05). Proportion of patients with high levels of CEA (45.0% vs 12.5%, χ2=15.745), glutamyl transpeptidase (γ-GT) (55.0% vs 23.8%, χ2=11.578), fucosidase (AFU) (35.0% vs 10.0%, χ2=10.902) and with complications [including pro-gressive in-terstitial lung disease (ILD) (60.0% vs 16.3%, χ2=23.934), pulmonary infection (72.5% vs 20.0%, χ2=31.360), hemophagocytic lymphohistiocytosis (35.0% vs 1.3%, χ2=27.771) and low T3 syndrome (50.0% vs 17.5%, χ2=16.644) were higher in deceased group ( P<0.05). Steroid pulse therapy and intravenous immuno-globulin therapy were more common in deceased group. Higher on-admission disease activity [ OR=1.593, 95% CI(1.255, 2.022), P<0.001], progressive ILD [ OR=5.600, 95% CI(1.510, 20.772), P=0.010] and pulmonary infection [ OR=6.771, 95% CI(2.031, 22.574), P=0.002] were independent risk factors for death in IIM patients. In su-bsection analysis, pulmonary infection and respiratory failure were short-term adverse prognostic factors for IIM patients with progressive ILD, while heliotrope rash, progressive ILD and increased steroid dose therapy were short-term adverse prognostic factors for IIM patients with pulmonary infection. Conclusion:High disease activity at admission, progressive ILD and pulmonary infection are the independent risk factors for death in IIM patients. Therefore, it is necessary to closely monitor above indicators during hospitalization.

The efficacy and safety of iguratimod or leflunomide combined with methotrexate in treating active rheumatoid arthritis (TRANMOD): a multicenter, randomized, double-blinded, double dummy and controlled clinical trial / 中华风湿病学杂志

Objective:The aim of this study was to compare the efficacy and safety of iguratimod (IGU) or leflnomide (LEF) in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA).Methods:This was a multicenter, randomized, double-blinded, double dummy and controlled clinical trial. Patients with moderate or high active RA were randomized in a 1∶1 ratio to receive IGU+MTX (Group A) or LEF+MTX (Group B) treatment. The efficacy and safety were assessed at week 12, 24 and 52, respectively. The primary endpoint was the American Colleague of Rheumatology 20 (ACR20) response rates at the 52th week. Pearson chi square test and two-way Analysis of Variance (ANOVA) were used to compare the improve- ment of ACR20 and DAS28 at 52 weeks. Pearson chi square test or Fisher exact probability test were used to compare the ACR 20 and ACR70 rate between the two groups after treatment. The measurement data of the two groups were compared by independent sample t-test or nonparametric test. Results:A total of 240 RA patients were enrolled in the present study. As a result, 84.1% and 81.0% of patients achieved ACR20 criteria at the 52th week in Group A and Group B, respectively ( χ2=0.35, P=0.56). And the ACR50/70 response rates, disease activity score 28 (DAS28), simplified disease activity index (SDAI) and the absolute decrease of DAS28 from baseline were not statistically different between the two groups at week 12, 24 and 52. The rates of adverse events were lower in Group A than those in Group B (60.0% vs 79.0%, P<0.01). The elevations of glutamic pyruvic transaminase/glutamic oxalacetic transaminase levels, concomitant use of hepatinica and white blood cell decrease were more common in Group B ( P<0.05). Conclusion:IGU in combination with MTX is an efficacious and safe treatment regimen, which is comparable in efficacy in control active RA but superior in safety to LEF combined with MTX.

Overexpression of ribonucleotide reductase small subunit, RNRM, increases cordycepin biosynthesis in transformed Cordyceps militaris / 中国天然药物

Cordycepin was the first adenosine analogue used as an anticancer and antiviral agent, which is extracted from Cordyceps militaris and hasn't been biosynthesized until now. This study was first conducted to verify the role of ribonucleotide reductases (RNRs, the two RNR subunits, RNRL and RNRM) in the biosynthesis of cordycepin by over expressing RNRs genes in transformed C. militaris. Quantitative real-time PCR (qRT-PCR) and western blotting results showed that the mRNA and protein levels of RNR subunit genes were significantly upregulated in transformant C. militaris strains compared to the control strain. The results of the HPLC assay indicated that the cordycepin was significantly higher in the C. militaris transformants carrying RNRM than in the wild-type strain, whereas the RNRML was preferentially downregulated. For the C. militaris transformant carrying RNRL, the content of cordycepin wasn't remarkably changed. Furthermore, we revealed that inhibiting RNRs with Triapine (3-AP) almost abrogated the upregulation of cordycepin. Therefore, our results suggested that RNRM can probably directly participate in cordycepin biosynthesis by hydrolyzing adenosine, which is useful for improving cordycepin synthesis and helps to satisfy the commercial demand of cordycepin in the field of medicine.

Synthesis and biological evaluation of phosphoinositide 3-kinase (PI3K) inhibitors based on a quinoxaline scaffold / 药学学报

Based on the structure of inhibitors XL765 and WR23, the quinoxaline scaffold was selected as an attractive structure for drug design. In this protocol, the 2-position of quinoxaline was modified with a substituted phenoxy fragment. Meanwhile, the linking chain at the 3-position was changed to a sulfonyl hydrazine or was removed. A series of substituent groups were added at the 6-position of the quinoxaline scaffold. Twenty-two quinoline derivatives were designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR, and ESI-MS. All compounds were screened for anti-tumor activity in vitro in A549, MCF-7, HCT-116 and HepG2 cancer cells. The results showed that P6b was effective, P6e and P6f had better activity against HCT116 (IC50 = 3.24, 4.78 and 4.50 μmol·L-1), and P6d had strong inhibitory effect on MCF-7 (IC50 = 0.228 7 μmol·L-1).