Retrospective investigation on the normal range of serum alanine aminotransferase levels in healthy adults in Ningbo area / 中华传染病杂志

Objective:To reevaluate the upper limit of normal (ULN) of serum alanine aminotransferase (ALT) by retrospectively analyzing the ALT levels in healthy people in Ningbo area.Methods:A total of 56 140 people who underwent health examination and detection of liver biochemical indexes in the Affiliated Hospital of Medical School of Ningbo University and Yinzhou Huamao Hospital of Ningbo from 2018 to 2020 were enrolled. After excluding relevant factors that may lead to liver injury, 11 411 people were included to compare the difference of serum ALT levels among different genders and age groups (20 to 29 years, 30 to 39 years, 40 to 49 years and 50 to 59 years) to determine the ALT ULN in different gender groups. Statistical methods were performed using two independent samples t test and analysis of variance. Results:The serum ALT of males was (19.20±7.90) U/L, which was higher than that of females ((13.75±6.17) U/L), with statistical significance ( t=41.16, P<0.001). The serum ALT ULN in males and in females were 35 U/L and 26 U/L, respectively. The serum ALT levels of 20 to 29, 30 to 39, 40 to 49 and 50 to 59 years old groups were (15.48±7.61) U/L, (16.21±7.40) U/L, (17.36±7.52) U/L and (18.77±7.57) U/L, respectively.The difference was statistically significant ( F=71.51, P<0.001). Serum ALT level in 50 to 59 years old group was higher than that in 20 to 29 years old group, and the difference was statistically significant ( t=13.11, P<0.01). In males, the ALT ULN of 20 to 29 years old was the lowest of 34.43 U/L, and highest of 35.29 U/L in 40 to 49 years old. In females, the ALT ULN in the 20 to 29 years old group was the lowest of 23.01 U/L, and the ALT ULN in the 50 to 59 years old group was the highest of 30.79 U/L. ALT ULN increased with age in females. The serum ALT of males was higher than that of females in all age groups ( t=29.55, 26.91, 13.43 and 4.62, respectively, all P<0.05). Conclusions:The serum ALT level is significantly correlated to gender and age. The serum ALT ULNs of healthy adult are 35 U/L in males and 26 U/L in females in Ningbo area.

Clinical characteristics of liver function injury in patients with coronavirus disease 2019 / 中华传染病杂志

Objective:To investigate the incidence of liver injury in patients with coronavirus disease 2019 (COVID-19), and to explore its impact on the condition and prognosis of patients.Methods:The medical records of 67 patients with COVID-19 who presented with pneumonia hospitalized at Tongji Hospital, Huazhong University of Science and Technology from February 11 to March 28, 2020 were collected. The results of liver biochemistry and coagulation function test at admission were analyzed. Data were compared by chi-square test, analysis of variance or Kruskal-Wallis H test. Results:Among 67 patients, total bilirubin increased in seven (10.4%) patients, which was slightly abnormal, albumin decreased in 36(53.7%) cases, and was below 30 g/L in 15(22.4%) cases, alanine transaminase (ALT) and aspartate transaminase (AST) were elevated in 19(28.4%) and 12(17.9%) cases, respectively. A total of 22(32.8%) cases had elevated ALT and (or) AST. The incidences with elevated ALT and (or) AST in moderate and severe patients were 33.3%(10/30) and 26.9%(7/26), respectively. Five of 11 critical patients had elevated ALT and (or) AST. There was no significant difference among the three groups ( χ2=1.21, P=0.546). Abnormal alkaline phosphatase and (or) γ-glutamyl transpeptidase were observed in 11(16.4%) cases. The prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT) occurred in 10(14.9%) and 17(25.4%) patients, respectively, while most of them were slightly abnormal. Only one patient presented with prolongation of PT and APTT meeting the standard of liver failure. A total of 61.2%(41/67) and 65.7%(44/67) of cases showed increase of fibrinogen and D-dimer, respectively, and 28.4%(19/67) and 19.4%(13/67), respectively increased to an obvious extent. The albumin levels in moderate, severe and critical patients were (37.85±6.19) g/L, (32.96±4.33) g/L and (33.02±3.63) g/L, respectively, which were significantly different ( F=7.36, P=0.001). There were significant differences in PT, APTT, fibrinogen and D-dimer among the three groups ( F=3.22, 3.31, 4.06 and H=17.63, respectively, all P<0.05). Conclusions:COVID-19 only leads to mild liver injury and has only mild impact on liver function. The decrease of albumin level and the increase of fibrinogen and D-dimer may be early predicting indexes for the disease severity.

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.

Migration characteristics among HIV/AIDS patients reported in Yiwu City from 2016 to 2020 / 预防医学

Objective@#To investigate the migration characteristics and follow-up treatment among HIV/AIDS patients after HIV confirmation in Yiwu City, Zhejiang Province from 2016 to 2020, so as to provide insights into the optimization of the HIV/AIDS control strategy among floating populations.@*Methods@#The reported HIV/AIDS patients' demographics, follow-up and treatment data in Yiwu City from 2016 to 2020 were captured from the HIV/AIDS Prevention and Control Information System of Chinese Disease Control and Prevention Information System. The migration characteristics, antiretroviral therapy and outcomes of HIV/AIDS patients were analyzed after HIV confirmation, and the factors affecting the migration of HIV/AIDS patients after HIV confirmation were identified using a Cox proportional hazard regression model.@*Results@#A total of 1 189 HIV/AIDS patients were enrolled, including 988 men (83.10%) and 806 cases without Zhejiang provincial household registration (67.79%). There were 441 patients (37.09%) migrating out of Yiwu City after HIV confirmation, with a migration rate of 17.73/100 person-years, and there were 366 patients migrating out of Zhejiang Province, with a cross-province migration rate of 30.78%. Among participants without Zhejiang provincial household registration, 395 patients (49.01%) migrated out of Yiwu City, including 337 patients (85.32%) returning to their household registration provinces, which mainly included Yunnan, Sichuan, Guizhou and Hunan. Cox proportional hazard regression analysis showed a high risk of migration among minority ethnic populations (HR=1.375, 95%CI: 1.044-1.811), retires (HR=3.605, 95%CI: 1.771-7.335), students (HR=8.969, 95%CI: 4.095-19.645), patients without Zhejiang provincial household registration (HR=4.545, 95%CI: 3.164-6.529) and patients identified through physical examination of floating populations or employees (HR=1.318, 95%CI: 1.006-1.727), and a low risk among married patients with spouses (HR=0.721, 95%CI: 0.569-0.913) and with an educational level of junior high school and above (HR: 0.428~0.753, 95%CI: 0.280-0.952). Among all floating HIV/AIDS patients, there were 26 cases lost to follow-up (5.90%) and 49 deaths (11.11%). In addition, the proportion of absence of antiretroviral therapy, HIV infection progressing into AIDS patients and failure in HIV inhibition were all greater among floating HIV/AIDS patients than among non-floating patients (P<0.05).@*Conclusions@#A high risk of migration was found among HIV/AIDS patients without Zhejiang provincial household registration, unmarried patients, patients with a low education level, retirees, students, and patients identified through physical examination of floating populations or employees in Yiwu City from 2016 to 2020, and migration does not facilitate the sustainability of antiretroviral therapy and follow-up, which may affect the prognosis of HIV/AIDS.

Effective components and mechanism of Qijiao Shengbai Capsules based on fingerprinting and network pharmacology / 中国中药杂志

Qijiao Shengbai Capsules(QJ) can invigorate Qi and replenish the blood, which is commonly used clinically for adjuvant treatment of cancer and leukopenia due to chemoradiotherapy. However, the pharmacological mechanism of QJ is still unclear. This work aims to combine the high-performance liquid chromatography(HPLC) fingerprints and network pharmacology to clarify the effective components and mechanism of QJ. The HPLC fingerprints of 20 batches of QJ were established. The similarity evaluation among 20 batches of QJ was performed by using Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012), resulting in a similarity greater than 0.97. Eleven common peaks were identified by reference standard, including ferulic acid, calycosin 7-O-glucoside, ononin, calycosin, epimedin A, epimedin B, epimedin C, icariin, formononetin, baohuoside I, and Z-ligustilide. The "component-target-pathway" network was constructed by network pharmacy, and 10 key components in QJ were identified, such as ferulic acid, calycosin 7-O-glucoside, ononin, and calycosin. The components were involved in the phosphoinositide 3 kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and other signaling pathways by regulating potential targets, including EGFR, RAF1, PIK3R1, and RELA, to auxiliarily treat tumors, cancers, and leukopenia. The molecular docking conducted on the AutoDock Vina platform confirmed the high binding activity of 10 key effective components with core targets, with the binding energy less than-5 kcal·mol~(-1). In this study, the effective components and mechanism of QJ have been preliminary revealed based on HPLC fingerprint and network pharmacology, which provided a basis for quality control of QJ and a refe-rence for further study on its mechanism.

Current application and prospect of accurate navigation technology in orthopaedic trauma / 中华外科杂志

In the past decades,a dramatic development of navigation technology in orthopaedic surgery has been witnessed. By assisting the localization of surgical region,verification of target bony structure,preoperative planning of fixation,intraoperative identification of planned entry point and direction of instruments or even automated insertion of implants,its ability and potential to reduce operation time,intraoperative radiation,surgical trauma,and improve accuracy has been proved. However,in contrast to the widespread use of navigation technology in arthroplasty,orthopaedic tumor,and spine surgery,its application in orthopaedic trauma is relatively less. In this manuscript,the main purpose is to introduce the technical principles of navigation devices,outline the current clinical application of navigation systems in orthopaedic trauma,analyze the current challenges confronting its further application in clinical practice and its prospect in the future.

Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial / 中华心血管病杂志

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice / 中国实验血液学杂志

OBJECTIVE@#The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model.@*METHODS@#Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model.@*RESULTS@#On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks.@*CONCLUSION@#Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Effect of sexuality education for parents of preschoolers / 中国学校卫生

Objective@#To evaluate the effect of sexuality education for parents of preschoolers, to provide a basis for sexuality educational programs in rural settings.@*Methods@#This community intervention trial chose four kindergartens in Jiangyang District of Luzhou City as the intervention group and other four kindergartens in Jiangyou City of Mianyang City of Sichuan Province as the control group. Sexuality education for parents was carried out in the intervention group, and the control group received routine arrangement. The baseline survey was conducted from March to May 2019, and the final survey was conducted in December 2019. The investigators conducted a face to face or self filled questionnaires among each parent who agreed to participate in the survey by using the self designed questionnaire "Research on Current Situation and Countermeasures of Early Childhood Sexuality Education in Rural Areas (Parent)".@*Results@#Before the intervention, there was no significant difference in the basic information of parents and their children, and the situation of early childhood sexuality education between the intervention group and the control group( P > 0.05 ). After intervention, parents of the intervention group and the control group showed differences in correct rate of the knowledge regarding early childhood sexuality education (41.5%，32.1%), proportion of recognition of parental responsibility (90.7%， 81.3 %), sexuality education in the family (55.7%，45.9%), sexuality education in schools (70.2%，39.1%) and attitude behavior consistency (28.9%，16.3%) ( χ 2=4.05，8.05，4.17，42.48，9.59， P <0.05).@*Conclusion@#Sexuality education towards parents is effective through improving knowledge, responsibility, the implementation of sexuality education in the family, and attitude behavior consistency among parents.

Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. @*METHODS@#CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. @*RESULTS@#Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). @*CONCLUSION@#Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.

Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma / 中华病理学杂志

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.

Application of CBL in the teaching of knee MRI for orthopedic residents / 中华医学教育探索杂志

Objective:To study the effect of CBL on the teaching of knee magnetic resonance image (MRI) for orthopedic residents.Methods:From September 2015 to March 2018, CBL teaching method was applied in the teaching of knee MRI among 90 orthopedic residents of Arthritis Clinical & Research Center of Peking University People’s Hospital. The teaching effect of CBL was evaluated with questionnaire method. The scores of Knee MRI theoretical knowledge and image diagnosis were statistically compared after CBL teaching. SPSS 19.0 was performed for t test. Results:According to the questionnaire of 90 orthopedic residents, in the teaching of knee MRI, CBL teaching improved the residents' learning interest[77.8%(70/90)], fortified their theoretical knowledge[80.0%(72/90)], and enhanced their diagnosis ability of knee MRI[88.8%(80/90)], diagnosis ability of knee diseases[86.6%(78/90)], autonomous learning ability[84.5%(76/90)], expression ability[83.3%(75/90)], and the ability of creating active classroom atmosphere[51.1%(46/90)]. The performances of knee MRI theoretical knowledge and image analysis were significantly increased after CBL teaching, respectively from (65.35±10.36) points to (89.20±10.55) points and from (66.64±9.88) points to (89.50±10.06) points.Conclusion:CBL teaching can improve independent diagnostic ablity of knee MRI of orthopedic residents and lay a solid foundation of diagnosis and treatment for knee diseases, thus improving their clinical skills.

Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (version 2022) / 中华创伤杂志

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Transcriptome changes upon Toll-like receptor 9 pathway activation in primary renal tubular epithelial cells / 中华危重病急救医学

Objective:To explore the effect of Toll-like receptor 9 (TLR9) signaling pathway activation on the transcriptome in the renal tubular cells.Methods:Mouse primary renal tubular epithelial cells were extracted and cultured. When the degree of cell fusion reached 80%, they were divided into two groups, which were added with 10 μL phosphate buffered saline (PBS, PBS control group) and TLR9 activator cytosine phosphate guanidine oligodeoxynucleotide (CpG-ODN) with a final concentration of 5 μmol/L (CpG-ODN treatment group). The RNA sequencing was performed on the Illumina platform after extraction. DEGseq software was used to analyze the differential expression of genes between the two groups. Goatools and KOBAS online software were used to analyze the differential genes involved signal pathways. Homer software was used to predict transcription factors.Results:Compared with the PBS control group, there were a total of 584 differentially expressed genes in the CpG-ODN treatment group, of which 102 were up-regulated and 482 were down-regulated. The most significantly enriched gene ontology (GO) terms of differentially expressed genes included response to interferon-β, defense response to virus and other inflammatory pathway. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways included 2'-5'-oligoadenylate synthase activity, regulation of ribonuclease activity, negative regulation of virus life cycle, cellular response to interferon-βand defense response to protozoan. The results of transcription factor prediction showed that interferon regulatory factor 3 (IRF3) was the most significantly enriched transcription factor in the promoter sequence of differential genes; the most significant transcription factor downstream of TLR9 was IRF3, and other predicted transcription factors such as transcription factor 21 (TCF21), zinc finger protein 135 (ZNF135), and PR domain containing 4 (PRDM4) might be new candidates for TLR9 signaling pathway.Conclusion:CpG-ODN activates TLR9 signaling pathway, and primary renal tubular epithelial cells can directly respond to CpG-ODN stimulation and undergo transcriptome changes, which provides a basis for further research on the molecular mechanism of TLR9 pathway in sepsis induced acute kidney injury.

A preliminary study on index system construction of the merging reform of doctoral degree education in clinical medicine with the standardized training of specialists / 中华医学教育探索杂志

Objective:To explore the reform plan for the integration of doctoral degree education in clinical medicine and standardized training for specialists.Methods:Using the literature analysis method and expert interview method, the preliminary framework of the merger training program was initially constructed, and Delphi method was used to determine the final index system. Excel 2010 was used to make data entry, and SPSS 19.0 was used for statistical analysis.Results:After two rounds of inquiry, the preliminary framework of the merger training program was finally determined from six aspects: enrollment methods, training resources, training content, training methods, training assessment and quality control, including 6 first-level indicators, 26 second-level indicators and 72 third-level indicators.Conclusion:By scientifically formulating systematic training programs, establishing the core training content and comprehensive evaluation system with post competency, and using flexible academic system, it provides a basis for carrying out the reform of the integration of doctoral education of clinical medicine and standardized training of specialists.

Investigation and analysis of the current situation of public elective courses for medical college students / 中华医学教育探索杂志

Objective:To investigate the importance, satisfaction and influencing factors of college students in a medical university, and to provide reference for the teaching reform of public elective courses.Methods:A questionnaire survey was conducted in this study among Batch 2018 students of Southern Medical University. A total of 691 questionnaires were distributed and 674 valid ones were recovered. The data were analyzed descriptively, and one-way ANOVA analysis and multiple linear regression analysis were carried out by using SPSS 20.0.Results:There were statistical differences between students' objective of elective course, evaluation of teachers, evaluation of courses and harvest of courses and students' satisfaction and attention to public elective courses ( P<0.05). Students who chose courses for improving their comprehensive quality paid more attention to public courses [(4.3±0.73) points] and had higher satisfaction [(4.34±0.69) points] than other options. Students with good evaluation on teachers' teaching paid more attention to public elective courses [(4.32±0.71) points] and their satisfaction [(4.45±0.62) points] was higher than other options. Students with good evaluation on the courses had the highest degree of attention [(4.35±0.71) points] and satisfaction [(4.47±0.63) points]. Students paid the highest attention [(4.75±0.53)points] to and had the highest satisfaction [(4.85±0.36) points] with the public elective courses with more course harvest. The multiple linear regression analysis found that the 5 variables, gender, teaching forms, teaching evaluation, course quality and course harvest had significant differences in the scores of public elective course satisfaction ( P<0.05). Conclusion:The male students, in inquiry teaching form, the higher evaluation on the teacher, the higher the course quality, and the more the course harvest, the higher the students' satisfaction with the public elective courses.

Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx / 中国天然药物

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Comparison of the outcomes between open and hybrid approaches in the treatment of thoracoabdominal aortic aneurysms repair / 北京大学学报(医学版)

OBJECTIVE@#Thoracoabdominal aortic aneurysm is one of the most challenging aortic diseases. Open surgical repair remains constrained with considerable perioperative morbidity and mortality. The emergence of a hybrid approach utilizing visceral debranching with endovascular aneurysm repair has brought an alternative for high-risk patients. This study aimed to compare the short- and long-term outcomes between hybrid and open repairs in the treatment of thoracoabdominal aortic aneurysms.@*METHODS@#In this retrospectively observational study, patients with thoracoabdominal aortic aneurysm treated in a single center between January 2008 and December 2019 were reviewed, of whom 11 patients with hybrid repair, and 18 patients with open repair were identified. Demographic characteristic, operative data, perioperative morbidity and mortality, freedom from reintervention, and long-term survival were compared between the two groups.@*RESULTS@#In the hybrid repair group, the patients with dissection aneurysm, preoperative combined renal insufficiency, and American Society of Anesthesiologists (ASA) score of 3 or more were significantly overwhelming than in the open repair group. The operation time of debranching hybrid repair was (445±85) min, and the intraoperative blood loss was (955±599) mL. There were 2 cases of complications in the early 30 days after surgery, without paraplegia, and 1 case died. The 30-day complication rate was 18.2%, and the 30-day mortality was 9.1%. The operation time of the patients with open repair was (560±245) min, and the intraoperative blood loss was (6 100±4 536) mL. Twelve patients had complications in the early 30 days after surgery, including 1 paraplegia and 4 deaths within 30 days. The 30-day complication rate was 66.7%, and the 30-day mortality was 22.2%. The bleeding volume in hybrid repair was significantly reduced compared with open repair (P < 0.001). Besides, the incidence of 30-day complications in hybrid surgery was significantly reduced (P=0.011). During the follow-up period, there were 4 reinterventions and 3 deaths in hybrid repair group. The 1-year, 5-year, and 10-year all-cause survival rates were 72%, 54%, and 29%, respectively. In open repair group, reintervention was performed in 1 case and 5 cases died, and the 1-year, 5-year, and 10-year all-cause survival rates were 81%, 71%, and 35%, respectively. There was no significant difference between hybrid repair and open repair in all-cause survival and aneurysm-specific survival.@*CONCLUSION@#Hybrid approach utilizing visceral debranching with endovascular aneurysm repair is a safe and effective surgical method for high-risk patients with thoracoabdominal aortic aneurysms. The incidence of early postoperative complications and mortality is significantly reduced compared with traditional surgery, but the efficacy in the medium and long term still needs to be improved.

Analysis of Serum Metabonomics in Patients with Multiple Myeloma Based on Liquid Chromatography-Mass Spectrometry / 中国实验血液学杂志

OBJECTIVE@#To observe the changes of serum metabolites in patients with multiple myeloma (MM) by metabonomics, and explore the potential biomarkers for diagnosis, prognosis, and progression of MM.@*METHODS@#Serum samples were collected from 26 patients with MM and 50 healthy controls. The data detected by liquid chromatography-mass spectrometry (LC-MS) was input into SIMCA-14.0 software for multivariate statistical analysis. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the changes of metabolites.@*RESULTS@#The metabolic change of uric acid and trans-vaccenic acid in serum samples of MM patients was 9.39 times and 2.77 times of these in healthy people, respectively, which were significantly higher than those of healthy people, and the difference was statistically significant(P<0.01).@*CONCLUSION@#Uric acid and trans-vaccenic acid are expected to be important metabolic indicators for the diagnosis, prognosis, and efficacy evaluation of MM, thus providing some clues for the pathogenesis of MM.

Clinical features of children with Guillain-Barré syndrome and the significance of Brighton criteria / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with Guillain-Barré syndrome (GBS) and the significance of Brighton criteria in childhood GBS.@*METHODS@#A retrospective analysis was performed on the medical data of 72 children with GBS. Brighton criteria were used for the grading of diagnostic certainty (level 1 as the highest level, and level 4 as the lowest level). A Spearman's rank correlation analysis was used to evaluate the correlation of auxiliary examinations with the level of diagnostic certainty of Brighton criteria.@*RESULTS@#A total of 72 children with GBS were enrolled, with a mean age of onset of (98±32) months. All children (100%, 72/72) had weakness of bilateral limbs and disappearance or reduction of tendon reflex, and limb weakness reached the highest level of severity within 4 weeks. Of all the 72 children, 68 (94%) had positive results of neural electrophysiological examination and 51 (71%) had positive results of cerebrospinal fluid (CSF) examination, and the positive rate of neural electrophysiological examination was significantly higher than that of CSF examination (@*CONCLUSIONS@#Most of the children with GBS meet Brighton criteria level 1, and the positive results of CSF examination and neural electrophysiological examination play an important role in improving the level of diagnostic certainty of Brighton criteria. Neural electrophysiological examination has a higher positive rate than CSF examination in the early stage of the disease.