Medical emergency support for the snowboarding project during the Beijing Winter Olympics / 北京大学学报(医学版)

Objective:To analyze and summarize the medical security situation of the snowmobile,sled,and steel frame snowmobile tracks at the National Sliding Centre,and to provide experience for future event hosting and medical security work for mass ice and snow sports.Methods:Retrospective analysis of injuries and treatment of athletes participating in the International Training Week and World Cup for Ski,Sled,and Steel Frame Ski from October to November 2021(hereinafter referred to as"Inter-national Training Week"),as well as the Ski,Sled,and Steel Frame Ski events at the Beijing Winter Olympics in February 2022(hereinafter referred to as the"Beijing Winter Olympics").We referred to and drew on the"Medical Security Standards for Winter Snow Sports"to develop specific classification standards for analyzing injured areas,types of injuries,and accident locations.Results:A total of 743 athletes participated in the International Training Week and the Beijing Winter Olympics.During the com-petition,there were 58 incidents of overturning,prying,and collision,of which 28(28 athletes)were in-jured,accounting for 48.3％of the total accidents and 3.8％of the total number of athletes.Among them,there were 9 males(32.1％)and 19 females(67.9％),with an average age of(26.3±4.7)years.Among the 28 injured athletes,20 cases(71.4％)received on-site treatment for Class Ⅰ injuries,while 8 cases(28.6％)had more severe injuries,including Class Ⅱ injuries(7 cases)and Class Ⅲ injuries(1 case),which were referred to designated hospitals for further treatment.Among the 28 injured athletes,3 cases(10.7％)experienced multiple injuries,including 2 cases of 2 injuries and 1 case of 3 injuries.The most common injuries were in the ankle and toes(10/32,31.3％).Out of 28 injured athletes,one(3.6％)experienced two types of injuries simultaneously,with joint and/or ligament injuries being the most common(11/29,37.9％).The most accident prone point on the track was the ninth curve(18/58,31.0％).Conclusion:Through the analysis and summary of medical security work,it can provide better experience and reference for the future development of snowmobile,sled,and steel frame snowmobile sports in China,making the National Snowy and Ski Center truly a sustainable Olympic heritage.

Research progress on the relationship between Alzheimer's disease and obstructive sleep apnea / 中华老年医学杂志

Alzheimer's disease(AD)is the most common cognitive disorder in the elderly and manifests primarily as progressive cognitive function decline, neuropsychiatric symptoms and multiple functional impairments.Obstructive sleep apnea(OSA)is a common type of respiratory disorder.Studies have found that AD and OSA are connected in many ways, including the risk of developing these diseases, biomarkers and neuroimaging features.These connections may result from a variety of mechanisms, such as neuropathological protein deposition, exacerbated immune-mediated inflammation, oxidative stress abnormalities, impaired mitochondrial function, and disturbed neurotransmitter systems, among others.This article reviewed the relationship between AD and OSA, the mechanisms linking them and their treatment.

Clinical diagnosis， treatment， and prognosis of gallbladder sarcomatoid carcinoma： An analysis of 16 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinicopathological features， diagnosis and treatment methods， and prognosis of gallbladder sarcomatoid carcinoma （GBSC）. MethodsA retrospective analysis was performed for the clinical data of 16 patients with GBSC who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2015 to April 2023， including general information， clinical manifestations， imaging features， pathological features， and treatment modality， and follow-up was performed for all patients. The Kaplan-Meier method was used to perform the survival analysis and plot the survival curve， and the Log-rank test was used for comparison between groups. ResultsAmong the 16 patients， there were 6 male patients and 10 female patients， with a mean age of 62.9±8.4 years. The main clinical manifestations were right upper abdominal pain in 13 patients （81.3%）， nausea in 5 patients （31.3%）， abdominal distension in 4 patients （25.0%）， poor appetite in 3 patients （18.8%）， weakness in 2 patients （12.5%）， fever in 2 patients （12.5%）， and jaundice in 1 patient （6.3%）， and 3 patients were asymptomatic and were found to have this disease by physical examination. Of all patients， 81.3% （13/16） were in the advanced stage （stage Ⅲ/Ⅳ） at the time of initial diagnosis. Histopathological examination showed that some cancer cells were spindle-shaped under the microscope， with marked nuclear division and noticeable heteromorphism. Immunohistochemistry showed a positive expression rate of 100% （16/16） for Vimentin， AE1/AE3， and CK8/18， and Ki-67 proliferation index was highly expressed in 81.3% （13/16） of the patients （≥50%）， with a median of 70% （range 20%‍ ‍—‍ ‍90%）. All 16 patients underwent surgical treatment， with radical surgery in 11 patients and palliative surgery in 5 patients， among whom 9 received R0 resection， 2 received R1 resection， and 5 received R2 resection， and 7 patients received adjuvant therapy after surgery. Effective follow-up was achieved for all 16 patients， with a follow-up time of 0.5‍ ‍—‍ ‍26.0 months and a median follow-up time of 11.0 months. By the end of follow-up， 2 patients survived and 14 patients died due to tumor recurrence or metastasis， with a median survival time of 10.0 months， and the 1- and 2-year cumulative survival rates after surgery were 31.3% and 8.3%， respectively. The prognostic analysis showed that TNM stage （χ2=6.727， P=0.009）， surgical approach （χ2=7.508， P=0.006）， margin condition （χ2=7.934， P=0.005）， and adjuvant therapy （χ2=4.608， P=0.032） were associated with the prognosis of patients. ConclusionThe clinical manifestations of GBSC lack specificity， and a confirmed diagnosis relies on immunohistochemical analysis. Most patients are in the advanced disease at the time of initial diagnosis and tend to have a poor prognosis. There are currently no targeted therapies for this disease， and radical surgery with negative margins and adjuvant therapy can improve the survival rate of patients.

Correlation between pelvic relapses of rectal cancer after radical and R0 resection: A regression model-based analysis / 中华胃肠外科杂志

Objective: To propose a new staging system for presacral recurrence of rectal cancer and explore the factors influencing radical resection of such recurrences based on this staging system. Methods: In this retrospective observational study, clinical data of 51 patients with presacral recurrence of rectal cancer who had undergone surgical treatment in the Department of Gastrointestinal Surgery, Peking University People's Hospital between January 2008 and September 2022 were collected. Inclusion criteria were as follows: (1) primary rectal cancer without distant metastasis that had been radically resected; (2) pre-sacral recurrence of rectal cancer confirmed by multi-disciplinary team assessment based on CT, MRI, positron emission tomography, physical examination, surgical exploration, and pathological examination of biopsy tissue in some cases; and (3) complete inpatient, outpatient and follow-up data. The patients were allocated to radical resection and non-radical resection groups according to postoperative pathological findings. The study included: (1) classification of pre-sacral recurrence of rectal cancer according to its anatomical characteristics as follows: Type I: no involvement of the sacrum; Type II: involvement of the low sacrum, but no other sites; Type III: involvement of the high sacrum, but no other sites; and Type IV: involvement of the sacrum and other sites. (2) Assessment of postoperative presacral recurrence, overall survival from surgery to recurrence, and duration of disease-free survival. (3) Analysis of factors affecting radical resection of pre-sacral recurrence of rectal cancer. Non-normally distributed measures are expressed as median (range). The Mann-Whitney U test was used for comparison between groups. Results: The median follow-up was 25 (2-96) months with a 100% follow-up rate. The rate of metachronic distant metastasis was significantly lower in the radical resection than in the non-radical resection group (24.1% [7/29] vs. 54.5% [12/22], χ2=8.333, P=0.026). Postoperative disease-free survival was longer in the radical resection group (32.7 months [3.0-63.0] vs. 16.1 [1.0-41.0], Z=8.907, P=0.005). Overall survival was longer in the radical resection group (39.2 [3.0-66.0] months vs. 28.1 [1.0-52.0] months, Z=1.042, P=0.354). According to univariate analysis, age, sex, distance between the tumor and anal verge, primary tumor pT stage, and primary tumor grading were not associated with achieving R0 resection of presacral recurrences of rectal cancer (all P>0.05), whereas primary tumor pN stage, anatomic staging of presacral recurrence, and procedure for managing presacral recurrence were associated with rate of R0 resection (all P<0.05). According to multifactorial analysis, the pathological stage of the primary tumor pN1-2 (OR=3.506, 95% CI: 1.089-11.291, P=0.035), type of procedure (transabdominal resection: OR=29.250, 95% CI: 2.789 - 306.811, P=0.005; combined abdominal perineal resection: OR=26.000, 95% CI: 2.219-304.702, P=0.009), and anatomical stage of presacral recurrence (Type III: OR=16.000, 95% CI: 1.542 - 166.305, P = 0.020; type IV: OR= 36.667, 95% CI: 3.261 - 412.258, P = 0.004) were all independent risk factors for achieving radical resection of anterior sacral recurrence after rectal cancer surgery. Conclusion: Stage of presacral recurrences of rectal cancer is an independent predictor of achieving R0 resection. It is possible to predict whether radical resection can be achieved on the basis of the patient's medical history.

Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome / 中华肝脏病杂志

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.

Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis / 中国中药杂志

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

Equisetin is an anti-obesity candidate through targeting 11β-HSD1

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.

Effects and significance of α-synuclein on β-arrestin 2 expression in Parkinson' disease in a mouse model / 中华老年医学杂志

Objective:To investigate the effects and significance of α-synuclein(α-syn)on the expression level of β-arrestin 2 in Parkinson's disease(PD)in a mouse model.Methods:Twenty-eight C57BL/6J mice with similar motor skills were randomly divided into a model group and a control group, with 14 mice in each group.A PD model was established by injecting preformed fibrils of α-syn into the striatum of the brain, and behavioral changes were monitored after 4 weeks.The expression levels of α-syn, the dopamine receptor(DR), tyrosine hydroxylase(TH), inflammatory factors, β-arrestin 2 and the nuclear transcription factor-κB(NF-κB)signaling pathway-related proteins were determined by Western blotting.The interaction between α-syn and β-arrestin 2 was detected by fluorescence resonance energy transfer(FRET), and the regulation of α-syn on β-arrestin 2 transcriptional activation was detected by the dual luciferase report assay.Results:After 4 weeks of modeling, compared with the control group, the average movement speed of mice in the model group was significantly reduced( t=9.415, P<0.001), the movement track was sparse and concentrated around the open field, and the time needed to climb the pole was significantly prolonged( t=16.412, P<0.001). Compared with the control group, the relative expression of α-synin in astrocytes in the model group increased significantly, the relative expressions of D1DR and TH decreased significantly[(1.14±0.18) vs.(0.53±0.16), (0.67±0.13) vs.(1.15±0.11), (0.46±0.05) vs.(0.81±0.06)]( t=9.810, 10.917 and 17.356, all P<0.001), the relative expression of tumor necrosis factor-α, interleukin-1β, interleukin-6 and NF-κB signaling pathway-related proteins increased significantly( t=3.583, 4.284, 5.396, 11.747, 16.375 and 18.294, all P<0.001), and the relative expression of β-arrestin 2 protein[(0.42±0.11) vs.(1.33±0.14)]in astrocytes decreased significantly( t=19.795, P<0.001). The FRET results suggested a possible direct interaction between α-syn and β-arrestin 2.The results of the dual luciferase report assay showed that the transcription activity of β-arrestin 2 was significantly increased after α-syn gene knockout. Conclusions:The α-syn may induce inflammation in astrocytes by activating the NF-κB signaling pathway and participate in the pathogenesis of PD by reducing dopamine biosynthesis and inhibiting its physiological function through negative regulation of β-arrestin 2.

Clinical study of internal jugular vein dilatation index in predicting septic shock volume responsiveness / 中华急诊医学杂志

Objective:To explore the value of severe ultrasound measurement of internal jugular vein dilation index (ΔIJV) combined with passive leg raising (PLR) in predicting the volume responsiveness of septic shock.Methods:Patients diagnosed with septic shock under complete mechanical ventilation in the ICU of Jinshan Hospital Affiliated to Fudan University from January 2020 to March 2021 were prospectively selected as the research objects. After 500 mL crystals were injected within 30 min, the patients having the "gold standard" left stroke volume (SV) increased by 15% were allocated to the volume response positive group, and patient having an SV increased by less than 15% to the volume response negative group. First, the maximum anterior posterior diameter (IJV max) and the minimum anterior posterior diameter (IJV min) in the respiratory cycle of internal jugular vein were measured by ultrasound, then SV before and after PLR was measured, and finally SV, IJV max and IJV min were measured again after rapid infusion of 500 mL crystals, and ΔIJV=(IJV max-IJV min)/(IJV mean)×100%. The Wilcoxon rank-sum test was used to compare the hemodynamic indexes before and after capacity expansion and PLR. Spearman rank method was used to analyze the change rate of SV (ΔSV) after PLR and the correlation between ΔIJV and ΔSV of the "gold standard". The sensitivity, specificity and relevant cut-off values were obtained by drawing the subject function curve to evaluate the value of ΔIJV and PLR in predicting the volume responsiveness of patients with sepsis. Results:A total of 56 patients were enrolled in the study, and they were divided into two groups: 32 patients in the volume response positive group and 24 patients in the volume response negative group. There was a positive correlation between ΔIJV and ΔSV after capacity expansion ( r=0.778, P<0.01). Taking ΔIJV>17.3% as the threshold, the area under the curve (AUC) was 0.846 (95% CI: 0.716~0.977), the sensitivity was 84.4% and the specificity was 83.3%. PLR was also positively correlated with ΔSV ( r=0.698, P<0.01). Taking ΔSV>15.5% after PLR as the threshold, the AUC was 0.895 (95% CI: 0.796~0.993), the sensitivity was 96.9%, and the specificity was 79.2%. When ΔIJV combined with PLR predicted volume reactivity, the AUC was 0.944 (95% CI: 0.862~1.000), the sensitivity was 99.8% and the specificity was 87.5%. Conclusions:The measurement of internal jugular vein respiratory dilation index by bedside ultrasound is a reliable index to predict volume responsiveness in patients with sepsis. When combined with PLR, the sensitivity and specificity of prediction can be improved.

Anti-obesity effect of 11β-HSD1 inhibitor equisetin on ob/ob mice / 药学学报

Equisetin (EQST) belongs to polyketide (PKS)-nonribosomal peptide synthetase (NRPS) type compound with an inhibitory effect of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) enzyme activity. This study investigated anti-obesity effect and insulin resistance improvement effect of EQST on high-fat diet (HFD)-induced ob/ob mice model. EQST treatment effectively reduced the body weight gain, fat weight gain and blood lipid content of model mice. All animal experiments were approved by the Medical Ethics Committee of Capital Institute of Pediatrics. EQST alleviated adipose tissue expansion and hepatic ballooning degeneration of model mice, and also effectively controlled the blood glucose content after glucose load and insulin load, showed a significant improvement in obesity and insulin resistance. EQST inhibited adipogenic proteins fatty acid-binding protein 4 (FABP4) and peroxisome proliferators-activated receptor γ (PPARγ), and upregulated thermogenic protein (uncoupling protein 1, UCP1) through suppressing 11β-HSD1 protein expression. In addition, EQST widely upregulates mitochondrial respiratory metabolism related proteins in adipose tissue and may improve insulin resistance through phosphatidylinositol-3-kinase (PI3K) pathway. Therefore, EQST plays an anti-obesity role by promoting adipose tissue thermogenesis and improving insulin resistance, which may provide reliable clues for improving obesity and diabetes.

Analysis of Gene Mutation Characteristics and Prognosis of Elderly Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the characteristics of gene mutation in elderly patients with acute myeloid leukemia (AML) and its effect on prognosis.@*METHODS@#The clinical and laboratorial characteristics of 54 AML patients (≥60 years old) in Department of Hematology, Tangdu Hospital were analyzed retrospectively during April 2016 to October 2019. Thirty-four AML/myelodysplastic syndrome/myeloproliferative neoplasm related mutant genes were detected by second-generation sequencing technology, and their clinical characteristics, treatment effect, and influence on prognosis were analyzed.@*RESULTS@#All the patients received DAC+CAG induction treatment, after 1-2 couses of treatment, 36 cases (66.7%) achieved complete response, with a total effective rate of 75.9%, and the median survival time was 17 months. The most frequent mutant genes were TET2 (33.3%), CEBPA (31.5%), DNMT3A (18.5%), ASXL1 (16.7%), NRAS (14.8%), RUNX1 (14.8%), FLT3-ITD (12.9%), TP53 (12.9%), NPM1 (12.9%), and IDH2 (12.9%). Among 7 patients with TP53 mutation, 6 cases obtained complete response after 1-2 courses of induction treatment, but there was no statistically significant difference in the effect on prognosis. Patients with FLT3-ITD and NRAS mutations had shorter overall survival time compared with who had no mutation (P=0.47, P=0.48). Multivariate analysis showed that FLT3-ITD and NRAS mutations were poor prognostic factors.@*CONCLUSION@#The incidence of TET2 gene mutation is high in elderly AML patients. AML patients with TET2 and TP53 mutations may benefit from Decitabine-based chemotherapy. However, patients with FLT3-ITD and NRAS mutations have a short survival time, and may have a poor prognosis.

Wutou Chishizhi Wan Regulates Autophagy and PI3K/Akt/GSK-3β Signaling Pathway in Rats with Myocardial Ischemia-reperfusion Injury / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Wutou Chishizhi Wan in regulating autophagy and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/glycogen synthase kinase-3β （GSK-3β） signaling pathway in rats with myocardial ischemia-reperfusion injury （MIRI）. MethodSixty male SD rats were randomly assigned into the normal group （normal saline）， model group （normal saline）， positive control （trimetazidine， 5.4 mg·kg-1） group， and low-， medium-， and high-dose （1.63， 4.9， 14.7 g·kg-1， respectively） Wutou Chishizhi Wan groups， with 10 rats in each group. The rats in other groups except the normal group underwent left anterior descending coronary artery ligation for modeling. Electrocardiogram was employed to detect the ST-segment elevation to evaluate the modeling. Hematoxylin-eosin （HE） staining was performed to reveal the damage of myocardial tissue. The levels of aspartate aminotransferase （AST） and creatine kinase （CK） were determined by colorimetry， and those of cardiac troponin T （cTnT） and myoglobin （MYO） by enzyme-linked immunosorbent assay （ELISA）. Western blot was carried out to determine the protein levels of microtubule-associated proteins 1 light chain 3 （LC3）， autophagy-related gene Beclin-1， PI3K， Akt， GSK-3β， p-GSK-3β， and p-Akt. ResultCompared with the normal group， the modeling elevated the serum levels of AST， CK， cTnT， and MYO （P<0.01）， destroyed the arrangement of myocardial cells abd nucle， twisted and broken myocardial fibers， up-regulated the protein levels of LC3Ⅱ/Ⅰ and Beclin-1 （P<0.01）， and down-regulated the protein levels of PI3K， p-Akt， and p-GSK-3β （P<0.01）. Compared with the model group， trimetazidine and Wutou Chishizhi Wan （all the doses） lowered the levels of AST， CK， cTnT， and MYO in serum （P<0.01）， restored the arrangement of myocardial cells and muscle fibers， reduced necrosis， down-regulated the protein level of Beclin-1 （P<0.01）， and up-regulated the protein levels of PI3K， p-Akt， and p-GSK-3β （P<0.01）. Additionally， Wutou Chishizhi Wan （all the doses） down-regulated the protein level of LC3Ⅱ/Ⅰ （P<0.05， P<0.01）. Compared with those in the trimetazidine group， the serum AST level rose in the low-dose Wutou Chishizhi Wan group （P<0.05） and declined in the high-dose group （P<0.01）， and the protein level of Beclin-1 was down-regulated in the medium-dose group （P<0.01）. Additionally， the trimetazidine group had higher protein level of LC3Ⅱ/Ⅰ than medium- and high-dose Wutou Chishizhi Wan groups （P<0.05， P<0.01）， higher protein level of PI3K than low-， medium-， and high-dose groups （P<0.01）， lower protein level of p-Akt than low- and medium-dose groups （P<0.01）， and higher p-GSK-3β protein level than the medium-dose group （P<0.01）. ConclusionDifferent doses of Wutou Chishizhi Wan can ameliorate MIRI， and the high dose has the best effect. Wutou Chishizhi Wan can reduce the activity of myocardial injury markers AST， CK， cTnT， and MYO， and alleviate the pathological damage of myocardial tissue. It can down-regulate the protein levels of beclin-1， LC3Ⅱ/Ⅰ， and up-regulate those of PI3K， p-Akt， and p-GSK-3β. In summary， Wutou Chishizhi Wan may inhibit excessive autophagy and regulate the PI3K/Akt/GSK-3β signaling pathway to exert protective effect on MIRI rats.

Influence of LMR and LMR/LDH on Prognosis of Primary Waldeyer's Ring Diffuse Large B-cell Lymphoma / 肿瘤防治研究

Objective To investigate the predictive value of peripheral blood LMR and LMR/LDH on the prognosis of primary Waldeyer's Ring DLBCL patients. Methods We collected 71 patients with primary Waldeyer's Ring DLBCL. The ROC curve was used to determine the optimal critical values of LMR and LMR/LDH before treatment. The chi-square test was used to analyze the constituent ratio and rate of high and low LMR groups as well as high and low LMR/LDH groups. Kaplan-Meier method was used to calculate survival rate. Log rank method and Cox risk regression model were used for univariate and multivariate analyses, respectively. Results The optimal critical values of LMR and LMR/LDH were 2.97 and 1.56, respectively. The prognosis of patients in the high LMR group was significantly better than that in the low LMR group (P < 0.001). The prognosis of patients in the high LMR/LDH group was significantly better than that in the low LMR/LDH group (P < 0.001). Univariate analysis showed that age, B symptoms, clinical stage, treatment efficacy, IPI score, LDH level, LMR and LMR/LDH were important factors that influenced the prognosis of early-stage Waldeyer's Ring DLBCL. Multivariate analysis showed that the age, clinical stage and LMR/LDH were independent prognostic factors. Conclusion LMR and LMR/LDH before treatment may have certain value in predicting the prognosis of Waldeyer's Ring DLBCL patients.

N-glycosylation modification of heat shock protein gp96 affects its immunological function / 生物工程学报

N-glycosylation modification, one of the most common protein post-translational modifications, occurs in heat shock protein gp96. The purpose of this study is to investigate the effect of N-glycosylation modification on immunologic function of the recombinant gp96 using the mutant gp96 in N-glycosylation sites. Firstly, wild-type and mutant gp96 proteins were expressed by insect expression system and their glycosylation levels were detected. To determine the effect of N-glycosylation on gp96 antigen presentation function, the IFN-γ+ CD8+ T cells in gp96-immunized mice and secretion level of IFN-γ were examined by flow cytometry and ELISA. The ATPase activity of gp96 was further detected by the ATPase kit. Finally, the effect of N-glycosylation on adjuvant function of gp96 for influenza vaccine was investigated in immunized mice. It was found that total sugar content of mutant recombinant gp96 was reduced by 27.8%. Compared to the wild type recombinant gp96, mutations in N-glycosylation sites resulted in decreased antigen presentation ability and ATPase activity of gp96. Furthermore, influenza vaccine-specific T cell levels induced by mutant gp96 as adjuvant were dramatically reduced compared to those by wild type recombinant gp96. These results demonstrate that N-glycosylation modification is involved in regulation of ATPase activity and antigen presentation function of gp96, thereby affecting its adjuvant function. The results provide the technical bases for development of gp96- adjuvanted vaccines.

The expression level of β-arrestin 1/2 in mice with Parkinson's disease and its relationship with pathogenesis of Parkinson's disease / 中华老年医学杂志

Objective:To observe the expression level of β-arrestin 1/2 in mice with Parkinson's disease(PD)and its relationship with pathogenesis of PD.Methods:PD model was prepared by using 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride(MPTP). The mice were killed at 3 days after the last administration and the brain tissue was taken for observing brain histopathological changes.The colocalization of β-arrestin1/2 with microglia was detected by using immunofluorescence double-labeling of β-arrestin1/2 and microglia.Tyrosine hydroxylase(TH)and Iba-1 were used to label cells, and then the loss of dopaminergic neurons and the activation of microglia were observed by immunohistochemistry.Results:As compared with the blank control group, the relative expression level of β-arrestin1 protein in brain tissue of PD mice was increased significantly, while the relative expression level of β-arrestin2 protein was decreased significantly( t=11.535, 9.948, both P=0.000), and β-arrestin1/2 shared cell localization with microglia.After MPTP induced PD, the number of Th + neurons in SNc area of midbrain was decreased significantly in β-arrestin1 + /+ group and β-arrestin1 -/- group( t=4.098, 3.571, P=0.000, 0.001), while the number of Iba-1 + cells in SNc area of midbrain was increased significantly( t=10.097、6.448, both P=0.000). After MPTP induced PD, the number of Th + neurons in SNc area of midbrain was decreased significantly in β-arrestin2 + /+ group and β-arrestin2 -/- group( t=3.512, 5.237, P=0.001, 0.000), while the number of Iba-1 + cells in SNc area of midbrain was increased significantly( t=5.816、8.402, P=0.000). Compared with β-arrestin1 + /+ group, the expressions of TRAF6, NF-κB and COX-2 in mouse microglia were significantly increased in β-arrestin1 -/- group( t=5.324, 5.837, 9.350, all P=0.0000). Compared with β-arrestin2 + /+ group, the expressions of TRAF6, NF-κB and COX-2 in mouse microglia were significantly down-regulated in β-arrestin2 -/- group( t=5.094, 6.318, 9.466, all P=0.000). Conclusions:The expression of β-arrestin1 is up-regulated and β-arrestin2 is down-regulated in brain tissue of PD mice.β-arrestin1/2 may affect the proliferation and activation of microglia and the loss of dopaminergic neurons through TRAF6/NF-κB/COX-2 pathway, and participate in the pathological process of PD.

Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with ASXL1 Gene Mutation / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML) patients with ASXL1 mutation.@*METHODS@#The clinical data of 229 newly diagnosed AML patients treated in our hospital from April 2016 to October 2019 were analyzed retrospectively. The next-generation sequencing technology was used to detect gene mutations in all the patients, the clinical characteristics of the patients with ASXL1 mutation were analyzed.@*RESULTS@#ASXL1 gene mutation was detected out in 45 patients(19.6%). Among these patients, the frameshift mutation (n=22,48.9%) was most common, followed by missense mutation (n=15, 33.3%) and nonsense mutation (n=8,17.8%), respectively, all of them were located at exon 12. The median mutation rate was 32.47%(range, 2.74%-53.50%). The median age of the patients with ASXL1 mutation was 54(range, 14-74) years old, and most of the patients were male, and most of them with the history of MDS or MPN, and low white blood cell count at the initial diagnosed (P<0.05). Patients with ASXL1 mutation showed a lower CR rate than that of without ASXL1 mutation. Patients with or without ASXL1 mutation showed a statistically significant difference in survival at 20 months (P=0.042), while there was no significant difference between the patients in the two groups over 20 months (P=0.505). All the 6 patients with ASXL1 mutation in low-risk group were survived, while the median OS time was 16 months in the high-risk group(P=0.034). Multivariate analysis showed that the history of MDS or MPN and CR rate from induction therapy were the independent risk factors affecting survival of the patients.@*CONCLUSION@#Frameshift mutation is commonly in AML patients with ASXL1 gene mutation, and ASXL1 mutation were more often in men, the history of MDS or MPN, and low white blood cell count. The CR rate of the patients with ASXL1 mutation was lower than that of the AML patients without ASXL1 mutations, AML patients with ASXL1 mutation showed poor short-term efficacy, but there was no significant difference between the two groups in long-term survival over 20 months.

The use of miR122 and its target sequence in adeno-associated virus-mediated trichosanthin gene therapy / 中西医结合学报

OBJECTIVE@#Plant-derived cytotoxic transgene expression, such as trichosanthin (tcs), regulated by recombinant adeno-associated virus (rAAV) vector is a promising cancer gene therapy. However, the cytotoxic transgene can hamper the vector production in the rAAV producer cell line, human embryonic kidney (HEK293) cells. Here, we explored microRNA-122 (miR122) and its target sequence to limit the expression of the cytotoxic gene in the rAAV producer cells.@*METHODS@#A miR122 target (122T) sequence was incorporated into the 3' untranslated region of the tcs cDNA sequence. The firefly luciferase (fluc) transgene was used as an appropriate control. Cell line HEK293-mir122 was generated by the lentiviral vector-mediated genome integration of the mir122 gene in parental HEK293 cells. The effects of miR122 overexpression on cell growth, transgene expression, and rAAV production were determined.@*RESULTS@#The presence of 122T sequence significantly reduced transgene expression in the miR122-enriched Huh7 cell line (in vitro), fresh human hepatocytes (ex vivo), and mouse liver (in vivo). Also, the normal liver physiology was unaffected by delivery of 122T sequence by rAAV vectors. Compared with the parental cells, the miR122-overexpressing HEK293-mir122 cell line showed similar cell growth rate and expression of transgene without 122T, as well as the ability to produce liver-targeting rAAV vectors. Fascinatingly, the yield of rAAV vectors carrying the tcs-122T gene was increased by 77.7-fold in HEK293-mir122 cells. Moreover, the tcs-122T-containing rAAV vectors significantly reduced the proliferation of hepatocellular carcinoma cells without affecting the normal liver cells.@*CONCLUSION@#HEK293-mir122 cells along with the 122T sequence provide a potential tool to attenuate the cytotoxic transgene expression, such as tcs, during rAAV vector production.

Clinical features of 3 patients with adrenomyeloneuropathy / 中华神经医学杂志

Objective:To summarize the clinical manifestations, imaging characteristics, and diagnoses basis of adrenomyeloneuropathy (AMN).Methods:The clinical data of 3 patients with AMN, admitted to our hospital from November 2016 to April 2019, were retrospectively collected. The clinical manifestations, imaging features, and diagnostic process of these patients were analyzed.Results:Three young male patients had onset with gradual aggravation of unilateral or bilateral lower limb insufficiency. MR imaging showed symmetrical abnormal signals in brainstem in 2 patients, and atrophy of thoracic spinal cord in 1 patient. By target region capture sequencing, mutations in the ABCD1 gene were found in all 3 patients; 2 underwent pedigree validation; the remaining one patient and his mother had failed Sanger sequencing validation due to pseudogene interference, and elevated plasma level of very long chain fatty acid (VLCFA) was noted in this patient. Conclusions:AMN usually initiates in the adulthood with spastic paraplegia as onset. Symmetrical lesions in brainstem or atrophy of spinal cord can be manifested on MR imaging; some patients may be accompanied by adrenocortical insufficiency. The definite diagnosis mainly depends on genetic screening and determination of VLCFA level in the blood.

Value of plasma soluble leukocyte differentiation antigen 14 subtype combined with neutrophil gelatinase associated lipocalin in early diagnosis and prognostic prediction of sepsis in children / 中国小儿急救医学

Objective:To explore the value of plasma soluble leukocyte differentiation antigen 14 subtype(Presepsin) combined with neutrophil gelatinase associated lipocalin(NGAL) in the early diagnosis and prognosis of sepsis in children.Methods:A total of 94 children with sepsis admitted to our hospital from June 2017 to October 2020 were selected, 41 children with shock were classified as septic shock group, and 53 children without shock were classified as sepsis group.Another 41 healthy children in our hospital during the same period were selected as the control group.The plasma levels of Presepsin, NGAL, procalcitonin(PCT) and C-reactive protein(CRP)were detected in three groups.The pediatric critical illness score and sequential organ failure(SOFA)score of children with sepsis were recorded.According to the mortality of the children within 28 days of admission, they were divided into survival group( n=75)and death group( n=19). The plasma levels of Presepsin, NGAL, PCT and CRP, pediatric critical illness score and SOFA score were compared between the survival group and the death group.Pearson test and receiver operating characteristic curve were used to analyze the correlation between plasma Presepsin, NGAL and pediatric critical illness score, SOFA score, and the predictive value of early diagnosis and prognosis of sepsis in children. Results:The levels of plasma Presepsin, NGAL, PCT and CRP in sepsis group and septic shock group were higher than those in control group, and those in septic shock group were higher than those in sepsis group( P<0.05). The plasma levels of Presepsin, NGAL, PCT, CRP and SOFA scores in death group were higher than those in survival group, and the pediatric critical illness score in death group was lower than that in survival group( P<0.05). Plasma Presepsin and NGAL were negatively correlated with pediatric critical illness score( r=-0.676, P<0.001; r=-0.664, P<0.001), and positively correlated with SOFA score( r=0.781, P<0.001; r=0.749, P<0.001). When the plasma Presepsin level was 468.91 ng/L, the sensitivity of area under curve(AUC) for sepsis diagnosis was 85.6% and the specificity was 77.5%.When the plasma NGAL level was 38.94 ng/mL, the sensitivity of AUC for sepsis diagnosis was 82.4%, and the specificity was 65.8%.The AUC of plasma Presepsin combined with NGAL for early diagnosis of sepsis was 0.912(95% CI 0.865 to 0.959), which was higher than of plasma Presepsin of 0.857(95% CI 0.785 to 0.928) and the AUC of NGAL of 0.761(95% CI 0.680 to 0.841). When the plasma Presepsin level was 816.92 ng/L, the sensitivity for predicting the prognosis of sepsis was 73.2% and the specificity was 76.1%.When the plasma NGAL level was 51.27 ng/mL, the sensitivity for predicting the prognosis of sepsis was 67.4% and the specificity was 68.0%.The AUC of plasma Presepsin combined with NGAL to predict the prognosis of sepsis was 0.891(95% CI 0.816 to 0.966), which was higher than the AUC of plasma Presepsin of 0.795(95% CI 0.698 to 0.892) and NGAL of AUC 0.714(95% CI 0.577 to 0.851). Conclusion:Clinical detection of plasma Presepsin and NGAL levels is helpful to early diagnosis of sepsis and judge the severity of the disease in children, which has guiding significance in evaluating the prognosis, and is beneficial to improve the prognosis.

Research progress in 3Ds nursing intervention of patients with maintenance hemodialysis hyperphosphatemia / 中国实用护理杂志

Hyperphosphatemia is one of the common complications in maintenance hemodialysis patients and is closely related to cardiovascular disease and related death events. Therefore, the effective management of blood phosphorus is an important link to improve the prognosis of patients with maintenance hemodialysis. This study on maintenance hemodialysis patients with hyperphosphatemia 3Ds management including diet, along with the progress of dialysis and drug related nursing intervention were summarized, discuss how to reasonable dietary phosphorus limited, improve the efficiency of dialysis, and the correct use of problems still existing in phosphate binder, in order to reduce hyperphosphatemia to provide the reference for clinical nursing practice.