Exploring the key anti-fatigue components of American ginseng based on metabolomics and zebrafish models / 药学学报

The aim of this paper is to explore the key anti-fatigue active components in the saponin-like composition of American ginseng. The anti-fatigue activity of western ginseng samples was evaluated using a zebrafish model; metabolomics techniques were used to identify the main saponins in western ginseng from different origins; the active substances and relevant targets of the anti-fatigue effect of western ginseng were initially screened by constructing a PPI protein interaction network between western ginseng saponins and disease targets, and the key active ingredients were screened using a molecular docking method; finally, the anti-fatigue activity of the key active ingredients was evaluated using a zebrafish, animal experiment was approved by the Ethics Committee of Shandong Academy of Medical Sciences (SYXK20220005). The anti-fatigue activity of the key active ingredients was evaluated using a zebrafish model. The results of the zebrafish activity evaluation showed that there were significant differences in the activities of the western ginseng samples from the two origins, and a total of 10 different saponins were identified as possibly related to the anti-fatigue activity after further metabolomic testing and pattern discrimination. The core anti-fatigue targets were screened with the help of component-disease target PPI, combined with pharmacophore-like parameters and molecular docking techniques, and pseudoginsenoside F11 was found to have good binding activity to five of the targets. Finally, the zebrafish model revealed that pseudoginsenoside F11 exhibited significant anti-fatigue activity. This study used metabolomics and zebrafish model to screen the key active substances of pseudoginsenoside F11 for its anti-fatigue activity, which will provide a reference for further research on the anti-fatigue of pseudoginsenosides.

Preparation of Fe3O4@SW-MIL-101-NH2 for selective pre-concentration of chlorogenic acid metabolites in rat plasma,urine,and feces samples / 药物分析学报

An innovative sandwich-structural Fe-based metal-organic framework magnetic material(Fe3O4@SW-MIL-101-NH2)was fabricated using a facile solvothermal method.The characteristic properties of the material were investigated by field emission scanning electron microscopy,transmission electron mi-croscopy(TEM),energy-dispersive X-ray spectroscopy,Fourier transform infrared spectroscopy,X-ray powder diffraction,vibrating sample magnetometry,and Brunauer-Emmett-Teller measurements.Fe3O4@SW-MIL-101-NH2 is associated with advantages,such as robust magnetic properties,high specific surface area,and satisfactory storage stability,as well as good selective recognition ability for chlorogenic acid(CA)and its metabolites via chelation,hydrogen bonding,and π-interaction.The results of the static adsorption experiment indicated that Fe3O4@SW-MIL-101-NH2 possessed a high adsorption capacity toward CA and its isomers,cryptochlorogenic acid(CCA)and neochlorogenic acid(NCA),and the adsorption behaviors were fitted using the Langmuir adsorption isotherm model.Then,a strategy using magnetic solid-phase extraction(MSPE)and ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF MS/MS)was developed and suc-cessfully employed for the selective pre-concentration and rapid identification of CA metabolites in rat plasma,urine,and feces samples.This work presents a prospective strategy for the synthesis of magnetic adsorbents and the high-efficiency pretreatment of CA metabolites.

Development and validation of a prediction model for treatment failure in peritoneal dialysis-associated peritonitis patients: a multicenter study / 南方医科大学学报

OBJECTIVE@#To develop and validate a risk prediction model of treatment failure in patients with peritoneal dialysis-associated peritonitis (PDAP).@*METHODS@#We retrospectively analyzed the data of patients undergoing peritoneal dialysis (PD) in 3 dialysis centers in Jilin Province who developed PDAP between January 1, 2013 and December 31, 2019. The data collected from the Second Hospital of Jilin University and Second Division of First Hospital of Jilin University) were used as the training dataset and those from Jilin Central Hospital as the validation dataset. We developed a nomogram for predicting treatment failure using a logistic regression model with backward elimination. The performance of the nomogram was assessed by analyzing the C-statistic and the calibration plots. We also plotted decision curves to evaluate the clinical efficacy of the nomogram.@*RESULTS@#A total of 977 episodes of PDAP were included in the analysis (625 episodes in the training dataset and 352 episodes in the validation dataset). During follow-up, 78 treatment failures occurred in the training dataset and 35 in the validation dataset. A multivariable logistic regression prediction model was established, and the predictors in the final nomogram model included serum albumin, peritoneal dialysate white cell count on day 5, PD duration, and type of causative organisms. The nomogram showed a good performance in predicting treatment failure, with a C-statistic of 0.827 (95% CI: 0.784-0.871) in the training dataset and of 0.825 (95% CI: 0.743-0.908) in the validation dataset. The nomogram also performed well in calibration in both the training and validation datasets.@*CONCLUSION@#The established nomogram has a good accuracy in estimating the risk of treatment failure in PDAP patients.

Palmitic acid suppresses autophagy in neonatal rat cardiomyocytes via the cGAS-STING-IRF3 pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of palmitic acid (PA) on autophagy in neonatal rat cardiomyocytes (NRCMs) and explore the underlying mechanism.@*METHODS@#NRCMs were isolated and cultured for 24 h before exposure to 10% BSA and 0.1, 0.3, 0.5, or 0.7 mmol/L PA for 24 h. After the treatments, the expressions of Parkin, PINK1, p62, LC3Ⅱ/ LC3Ⅰ, cGAS, STING and p-IRF3/IRF3 were detected using Western blotting and the cell viability was assessed with CCK8 assay, based on which 0.7 mmol/L was selected as the optimal concentration in subsequent experiments. The effects of cGAS knockdown mediated by cGAS siRNA in the presence of PA on autophagy-related proteins in the NRCMs were determined using Western blotting, and the expressions of P62 and LC3 in the treated cells were examined using immunofluorescence assay.@*RESULTS@#PA at different concentrations significantly lowered the expressions of Parkin, PINK1, LC3 Ⅱ/LC3 Ⅰ and LC3 Ⅱ/LC3 Ⅰ+Ⅱ (P < 0.05), increased the expression of p62 (P < 0.05), and inhibited the viability of NRCMs (P < 0.05). Knockdown of cGAS obviously blocked the autophagy-suppressing effect of PA and improved the viability of NRCMs (P < 0.05).@*CONCLUSION@#PA inhibits autophagy by activating the cGAS-STING-IRF3 pathway to reduce the viability of NRCMs.

Early changes within the lymphocyte population are associated with the long term prognosis in severely injured patients / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between early lymphocyte responses and the prognosis in severely injured patients.@*METHODS@#Consecutive patients with severe trauma who were treated in Peking University People's Hospital Trauma Medical Center between June 2017 and June 2020 were enrolled in this restropective chart-review study. According to the responses of lymphocyte after severe injury, the patients were divided into three groups, group 1: lymphopenia-returned to normal; group 2: persistent lymphopenia; group 3: never lymphopenic, and the outcome of 28 d were recorded. Clinical data such as gender, age, base excess, mechanism of injury, Glasgow coma scale (GCS), injury severity score (ISS) and massive blood transfusion were collected. Perform statistical analysis on the collected clinical data to understand the trend of lymphocyte changes in early trauma and the relationship with prognosis. In order to eliminate the interference of age, stratification was carried out according to whether the age was ≥ 65 years old, in different age groups, they were grouped according to whether the length of stay was ≥ 28 d, and the relationship between lymphocyte trend and length of stay was discussed.@*RESULTS@#A total of 83 patients were included, 66 males and 17 females. The main injury mechanisms were traffic accident injuries and high-altitude fall injuries. The average ISS was (30±11) points. 65 patients had lymphopenia on the day of injury, 32 of them returned to normal on the 5th day, and the rest did not recover; the other 18 patients had normal lymphocyte levels after injury. Patients which are failure to normalize lymphopenia within the first 5 days following admission was related with the long hospitalization time and higher 28 d mortality rate. After further stratification by age, failure to normalize lymphopenia within the first 5 days following admission in the elderly group (age ≥65 years) was a risk factor for prolonged hospital stay (≥28 d), P=0.04. While in younger group, a high level of neutrophils within the first 5 d following admission was a risk factor for bad outcome.@*CONCLUSION@#A failure to normalize lymphopenia in severely injured patients is associated with significantly higher mortality and longer hospital stay. This study reveals lymphocytes can be used as a reliable indicator for the prognostic evaluation.

Effects and molecular mechanism of exogenous L-carnitine on excessive endoplasmic reticulum stress-mediated hepatic pyroptosis in severely scald rats / 中华烧伤杂志

Objective: To investigate the effects and molecular mechanism of exogenous L-carnitine on hepatic pyroptosis mediated by excessive endoplasmic reticulum stress in severely scald rats. Methods: The experimental research method was adopted. According to the random number table (the same group method below), fifteen female Sprague Dawley rats aged 6-8 weeks were divided into sham-injury group, scald alone group, and scald+carnitine group (with 5 rats in each group), and full-thickness scald of 30% total body surface area were made on the back of rats in scald alone group and scald+carnitine group, and rats in scald+carnitine group were additionally given intraperitoneal injection of L-carnitine. At post injury hour (PIH) 72, The levels of aspartate aminotransferase (AST) and alanine dehydrogenase (ALT) of biochemical indicators of liver injury were detected by automatic biochemical analyzer with the sample number of 5. At PIH 72, liver tissue damage was detected by hematoxylin-eosin staining. At PIH 72, The mRNA levels of nucleotide-binding oligomerization domain-containing protein-like receptor family pyrin domain containing 3 (NLRP3), cysteine aspartic acid specific protease 1 (caspase-1), gasderminD (GSDMD), and interleukin 1β(IL-1β) in liver tissue as pyroptosis-related markers and glucose regulatory protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in liver tissue as endoplasmic reticulum stress-related markers were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR). Protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue were detected by Western blotting, and the sample numbers were all 5. HepG2 cells as human liver cancer cells were divided into dimethyl sulfoxide (DMSO) group, 0.1 μmol/L tunicamycin (TM) group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group and were treated accordingly. After 24 h of culture, cell viability was detected by cell counting kit 8, and the intervention concentration of TM was screened, and the sample number was 5. HepG2 cells were divided into DMSO group, TM alone group, and TM+carnitine group, and treated accordingly. After 24 h of culture, the protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in cells were detected by Western blotting, and the sample numbers were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference-t test. Results: At PIH 72, the AST and ALT levels of serum in scald alone group were (640±22) and (157±8) U/L, which were significantly higher than (106±13) and (42±6) U/L in sham-injury group, respectively, with t values of -46.78 and -25.98, respectively, P<0.01. The AST and ALT levels of serum in scald+carnitine group were (519±50) and (121±10) U/L, which were significantly lower than those in scald alone group, respectively, with t values of 4.93 and 6.06, respectively, P<0.01. At PIH 72, the morphology of liver tissue of rats in sham-injury group were basically normal with no obvious inflammatory cell infiltration; compared with those in sham-injury group, the liver tissue of rats in scald alone group showed a large number of inflammatory cell infiltration and disturbed cell arrangement; compared with that in scald alone group, the liver tissue of rats in scald+carnitine group showed a small amount of inflammatory cell infiltration. At PIH 72, the mRNA expression on levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 34.42, 41.93, 30.17, and 15.68, respectively, P<0.01); the mRNA levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 34.40, 37.20, 19.95, and 7.88, respectively, P<0.01). At PIH 72, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 12.28, 26.92, 5.20, 10.02, and 24.78, respectively, P<0.01); compared with those in scald alone group, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald+carnitine group were significantly decreased (with t values of 10.99, 27.96, 12.69, 8.96, and 12.27, respectively, P<0.01). At PIH 72, the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 21.00 and 16.52, respectively, P<0.01), and the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 8.92 and 8.21, respectively, P<0.01); the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 22.50 and 14.29, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 14.29 and 5.33 respectively, P<0.01). After 24 h of culture, the cell survival rates of 0.1 μmol/L TM group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group were significantly decreased than that in DMSO group (with t values of 4.90, 9.35, 18.64, and 25.09, respectively, P<0.01). Then 0.8 μmol/L was selected as the intervention concentration of TM. After 24 h of culture, compared with that in DMSO group, the protein expression levels of GRP78 and CHOP in cells in TM alone group were significantly increased (with t values of 10.48 and 17.67, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in TM+carnitine group were significantly lower than those in TM alone group (with t values of 8.08 and 13.23, respectively, P<0.05 or P<0.01). After 24 h of culture, compared with those in DMSO group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM alone group were significantly increased (with t values of 13.44 and 27.51, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05); compared with that in TM alone group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM+carnitine group were significantly decreased (with t values of 20.49 and 21.95, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05). Conclusions: In severely scald rats, exogenous L-carnitine may play a protective role against liver injury by inhibiting the pathways related to excessive endoplasmic reticulum stress-mediated pyroptosis.

Treating children's tic disorder based on " visceral theory" from lung, liver and spleen / 国际中医中药杂志

The pathogenesis of tic disorder in children is closely related to the dysfunction of the internal organs, especially the lung, spleen and liver. The main causes of tic disorder caused by visceral disorders are as follows: lung guard is the main cause of the disease, liver wind is the key to the pathogenesis and spleen deficiency and wind phlegm are the pathological basis. At the same time, the lung, liver, and spleen are mutually restrictive and affect each other. The main manifestations are that if the lung is affected by evil, the wood will punish the gold; if the spleen is insufficiency and the liver is hyperactive, the earth deficiency will be leading to over-restriction by wood. Based on the understanding of the related theories about viscera's disease and viscera's generation, we pay attention to distinguish the etiology and pathogenesis of the viscera, and we treat tic disorders based on syndrome differentiation of lung, liver and spleen with curative effect.

Treatment of cough variant asthma based on the pathogenic characteristics of "wind phlegm and blood stasis" / 国际中医中药杂志

The wind, phlegm, and blood stasis are important pathogenic factors of cough variant asthma in children, and they are also the pathological products in the occurrence and development of this disease. They have typical pathogenic characteristics. The main pathogenesis characteristics of cough caused by wind, phlegm and blood stasis are as follows that external wind attacks the lungs and induces internal wind, phlegm and dampness accumulates in the lungs, and the lungs fail to declare and descend, and blood stasis obstructs the collaterals and stagnation of Qi. The wind, phlegm, and blood stasis have their own pathogenic characteristics, and their cough-causing also have their own pathogenic characteristics and clinical characteristics. Based on the characteristics of wind, phlegm, and blood stasis, the application of medicine based on the differentiation of symptoms and signs can effectively prevent and treat this disease, and provide theoretical basis and treatment ideas for the treatment of cough variant asthma in children with Chinese medicine.

Evaluation of facial soft tissue thickness in asymmetric mandibular deformities after orthognathic surgery / 대한악안면성형재건외과학회지

Objectives@#The purpose of this study was to compare differences in facial soft tissue thickness in three-dimensional (3D) images before and after orthognathic surgery in patients with skeletal Class III malocclusion and to obtain a better understanding of the relationship between hard and soft tissue changes after surgery.Materials and method: The present retrospective study included 31 patients with skeletal Class III malocclusion with mandibular chin deviation greater than 4 mm who had undergone cone-beam computed tomography before and 6 months after surgery. Seven bilateral points were established. Measurements were taken from software-generated multiplanar reconstructions. The predictor variables were timing (pre- and postoperatively) and side (deviated vs.nondedicated). A regression model and correlation analysis were conducted for statistical analysis. @*Results@#The difference of bilateral facial soft tissue thickness was statistically significantly different between deviated and nondeviated sides (P < 0.05), with lower values observed on the deviated side. The soft tissue thickness has become nearly symmetric at local regions of the lower thirds of the face after orthognathic surgery. However, most measurements showed a negative correlation between changes in soft tissue thickness and changes in bone tissues. @*Conclusions@#Skeletal Class III malocclusion with facial asymmetry is accompanied by differences in soft tissue thickness when comparing Dev and N-Dev sides of the posterior region of the mandible, where soft tissues are thinner on the Dev side. Soft tissue thickness can compensate for or camouflage the underlying asymmetric mandible. In addition, the asymmetric soft tissue thickness on the lower third of the face can be partially improved by orthognathic surgery, but the amount of soft tissue thickness change is not consistent with that of hard tissue positional change.

Clinical Significance of Truncated Mutant ΔJBP of TET2 Gene in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML).@*METHODS@#Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion.@*RESULTS@#Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPA@*CONCLUSION@#AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPA

A clinical epidemiological investigation of neonatal acute respiratory distress syndrome in southwest Hubei, China / 中国当代儿科杂志

OBJECTIVE@#To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China.@*METHODS@#According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017.@*RESULTS@#A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66).@*CONCLUSIONS@#Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.

Relationship between TRPV1 gene polymorphism and genetic susceptibility to type 2 diabetes mellitus and intraoperative adverse cardiovascular events / 中华麻醉学杂志

Objective:To determine the relationship between transient receptor potential vanilloid 1 (TRPV1) gene polymorphism and genetic susceptibility to type 2 diabetes mellitus (DM) and intraoperative adverse cardiovascular events (ACVEs).Methods:Eighty-six DM patients and 78 non-DM patients (nDM) undergoing elective knee replacement or posterior lumbar interbody fusion were selected in this study.Real-time fluorescence quantitative polymerase chain reaction was carried out to genotype the rs222747 variant of TRPV1 gene.The ACVEs occurred were recorded during operation, and the risk factors for ACVE developed during operation were identified.Results:Compared with nDM group, the TRPV1 genotype G/G ratio, allele G frequency, and incidence of intraoperative ACVE were significantly increased in DM group ( P<0.05). Aging and TRPV1 genotype GG combined with DM were the risk factors for intraoperative ACVEs occurred ( P<0.05). Conclusion:TRPV1 gene polymorphism is related to the genetic susceptibility to type 2 DM and occurrence of intraoperative ACVEs.

Relationship between perioperative cardiovascular events and serum TRPV1, CGRP and SP concentrations in patients with diabetic peripheral neuropathy / 中华麻醉学杂志

Objective:To evaluate the relationship between perioperative cardiovascular events and serum transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP) and substance P (SP) concentrations in the patients with diabetic peripheral neuropathy (DPN).Methods:Twenty-eight patients with type 2 diabetes mellitus (DM) complicated by DPN undergoing elective non-cardiovascular surgery under general anesthesia, were enrolled in DPN group, and 28 patients with type 2 DM without DPN were included in DM group.Another 28 nondiabetic patients undergoing non-cardiovascular elective surgery under general anesthesia were selected as control group (C group). The patients were 55 to 81 years old and classified as American Society of Anesthesiologists physical status Ⅱ or Ⅲ, regardless of gender.The development of cardiovascular events during surgery and within 24 h after surgery and use of vasoactive drugs were recorded.Venous blood samples were taken at 30 min before anesthesia induction and 24 h after surgery for determination of the concentrations of TRPV1, CGRP, SP and cardiac troponin I (cTnI) in serum using enzyme-linked immunosorbent assay.Results:Compared with group C, the incidence of perioperative cardiovascular events and utilization rate of vasoactive drugs were significantly increased, the preoperative concentrations of serum TRPV1, CGRP and SP were decreased, and the postoperative concentration of serum cTnI was increased in DM and DPN groups ( P<0.05). Compared with DM group, the incidence of perioperative cardiovascular events was significantly increased, the preoperative concentrations of serum TRPV1, CGRP and SP were decreased, the postoperative concentration of serum cTnI was increased ( P<0.05), and no significant change was found in the utilization rate of vasoactive drugs in DPN group ( P>0.05). The postoperative cTnI concentrations in serum were negatively correlated with the preoperative TRPV1, CGRP and SP concentrations in serum in DPN group ( P<0.01). Conclusion:The increased risk of perioperative cardiovascular events may be related to the decrease in serum TRPV1, CGRP and SP concentrations in DPN patients.

Biomechanical analysis and clinical application of 3D printed bone tumor prosthesis of lower limb / 中华骨科杂志

Objective:To design 3D printed prosthesis in an individualized way and explore the short-term clinical efficacy of reconstruction of segmental defect after resection of bone tumor in lower extremities with 3D-printed prosthesis.Methods:From January 2017 to June 2019, 6 patients with lower limb bone tumor who met the inclusion criteria were recruited, including 3 males and 3 females, aged 8.67±1.11 years (range 6-11 years). All 6 cases were primary bone tumors, and the Enneking stages were all IIB, including 3 cases of left tibial tumors, 2 cases of right tibial tumors, and 1 case of right femoral tumor. These 3D-printed prostheses were designed based on the preoperative imaging data. The mechanical stability of the prosthesis was evaluated by three-dimensional finite element analysis. After tumor resection, the 3D-printed prosthesis was installed and fixed to reconstruct the segmental bone defect. All patients were clinically followed up and evaluated by imaging regularly after operation. The functional status was assessed by the Musculoskeletal Tumor Society (MSTS) score. Oncology results and complications were recorded in detail.Results:All operations were successfully performed, including 3 cases underwent left tibial tumor resection, 2 cases underwent right tibial tumor resection, and 1 case underwent right femoral tumor resection. The length of the bone defect after tumor resection was 18.19±3.74 cm, the average operation time was 165.83±54.17 min, and the average intraoperative bleeding was 233.33±133.33 ml. These finite element analysis data show that the overall stress of these prostheses are lower than the maximum mechanical strength of the corresponding materials. These 3D printed prostheses match well with the excision defect and meet the expected effect. There were no adverse reactions during the operation. The mean follow-up period was 16.83±7.17 months. At the last follow-up, all patients survived without tumor recurrence or metastasis. Postoperative imaging results showed that all the implants were stable without complications such as peripheral infection, aseptic loosening, prosthesis fracture. These 3D-printed prostheses composite resulted in substantial bone integration at follow-up. The average MSTS score was 83.67%±9.11%.Conclusion:The individualized 3D printed prosthesis can be used to reconstruct the bone defect after the resection of osteosarcoma in the lower extremities, and the clinical efficacy was satisfactory in the short-term follow-up.

Preliminary study on the a novel individualized 3D printing artificial vertebral body in spine reconstruction / 中华骨科杂志

Objective:To explore the advantages of the novel individualized 3D printing artificial vertebral body in spine reconstruction and to evaluate its clinical effect.Methods:From January 2017 to December 2018, the 15 patients who underwent total vertebrectomy and spine reconstruction with individualized 3D printing artificial vertebral body were analyzed retrospectively. There were 8 males and 7 females, with the mean age 39.5 years (range: 20-57), including 12 primary tumors and 3 metastatic tumors. According to tumor location and surrounding soft tissue invasion range, simple posterior or combined anterior and posterior approach were used for total vertebral resection, and the defection was reconstructed by 3D printing artificial vertebral body. The operation time, intraoperative bleeding volume, postoperative stability of artificial vertebral body and bone ingrowth of adjacent vertebral body, preoperative and postoperative neurological changes, preoperative and postoperative VAS score, local control and survival of patients were analyzed.Results:The mean operation time was 412.0 min (range: 135-740 min), and the mean blood loss was 4 140.0ml (range: 100-14 000 ml). The mean follow-up time was 23.2 months (range: 12-35 months), and no one loss to follow-up. One case had pleural rupture, one case had cerebrospinal fluid leakage and one case had L5 nerve root palsy. All patients recovered after active symptomatic treatment. Compare with the preoperative VAS score (4.7±1.1), the differences of VAS score at 7 d postoperative and last follow-up (1.6±0.6 and 1.0±0.5) were significantly reduced ( P<0.001). Three patients with Frankel grade C gradually recovered to grade D, and no change were found in grade D and Grade E patients, there was no significant improved at last follow-up. Preliminary bone growth was found between the artificial vertebral body and the adjacent vertebral body 3 months after operation. The bone growth was more obvious at 12 months post-operation, and the artificial vertebral body fused with the adjacent vertebral bodies to form bone integration. At 24 months post-operation, the integration of the artificial vertebral body was more accurate. During the follow-up period, there was no loosening or displacement of the artificial vertebral body and no failure of internal fixation. A case of hemangioendothelioma and a case of epithelioid angiosarcoma died at 33 months and 35 months postoperatively. One patient with chondrosarcoma had local recurrence at16 months post-operation. After treated with arotinib, the tumor did not progress. The other 12 patients had no tumor recurrence or distant metastasis. Conclusion:After spinal tumor resection, individualized 3D printing artificial vertebral body can be used to accurate restoration of spinal continuity, and provide nice interface matching and bone growth between artificial vertebral body and the adjacent vertebral endplates. Moreover, the immediate and long-term stability of the artificial vertebral body can meet the needs of spinal reconstruction.

Comparison of orthopedic implants 3D printed with porous titanium versus porous tantalum and prospects of their applications / 中华创伤骨科杂志

3D printing technology used to prepare orthopedic metal implants with complex morphology has advantages of rapidness and efficiency. Titanium and titanium alloys are currently the mainstream raw materials for fabrication of orthopedic implants, because they are characterized by good biocompatibility, high specific strength and low elastic modulus and clinical trials have demonstrated their reliable and good bone-healing effects. Tantalum presents physical and chemical properties similar to those of titanium, but is reported to be osteoinductive. Therefore, in recent years, 3D printed personalized implants with porous tantalum have attracted more attention. However, the related researches are still not enough. This review summarizes the recent researches on porous tantalum and porous titanium at home and abroad, compares their features in manufacturing process, mechanical property, biocompatibility, surface modification, osseointegration and clinical application, and discusses the prospects of their application in the field of 3D printed personalized orthopedic implants.

Safety of protease inhibitors and Arbidol for SARS-CoV-2 pneumonia in Zhejiang Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).

Risk factors for mechanical ventilation in patients with severe multiple trauma / 北京大学学报(医学版)

OBJECTIVE@#To eludicate the risk factors of mechanical ventilation and prolonged mechanical ventilation in patients with severe multiple injuries.@*METHODS@#Consecutive patients with severe multiple injures who were treated in Peking University People's Hospital Trauma Medical Center between December 2016 and December 2019 were enrolled in this restropective chart-review study. According to mechanical ventilation and ventilatory time, the patients were divided into mechanical ventilation (MV) group and non-mechanical ventilation (NMV) groups, prolonged mechanical ventilation (PMV) group and shortened mechanical ventilation (SMV) groups. Clinical data such as gender, age, base excess, mechanism of injury, Glasgow Coma Scale (GCS), abbreviated injury scale (AIS) and injury severity score (ISS) were collected. To indentify the risk factors of mechanical ventilation and prolonged mecha-nical ventilation, univariate and multivariate Logistic analyses were carried out.@*RESULTS@#In the present study, 112 patients (82 male, 30 female) with severe multiple injuries having a median age of 52 (range: 16-89 years) and a median ISS of 34 (range: 16-66) were enrolled. The primary mechanism of injury was traffic accident injury and falling injury. In the study, 62 and 50 patients were assigned to MV and NMV groups, respectively. Logistic analysis showed that GCS (OR=0.72, 95%CI: 0.53-0.92, P=0.03), base excess (OR=0.56, 95%CI: 0.37-0.88, P=0.002) and multiple rib fracture (OR=1.72, 95%CI: 1.60-2.80, P=0.012) were independent significant risk factors for mechanical ventilation after severe multiple injuries. Within the mechanical ventilation group, 38 and 24 patients were assigned to PMV and SMVgroups, respectively. Compared with the SMV group, the PMV group had a higher ISS and higher rate of severe head trauma. The length of hospital stay of PMV group was longer than that of SMV groups. Meanwhile, the incidence of tracheotomy in PMV group was high.@*CONCLUSIONS@#GCS, base excess and rib fracture might be independent risk factors for mechanical ventilation. Higher ISS and lower GCS might prolong the ventilatory time and the length of hospital stay. Meanwhile, the incidence of tracheotomy was high in PMV group because of the longer ventilatory time and poor consciousness.

miR-125a-5p inhibits cancer stem cells phenotype and epithelial to mesenchymal transition in glioblastoma

SUMMARY OBJECTIVE Glioblastoma (GBM) is a common type of cancer with high mortality. Epithelial to mesenchymal transition (EMT) plays a vital role in the development of glioblastoma. The aim of this study is to evaluate the role of miR-125a-5p in glioblastoma and in the tumorigenesis of chemotherapeutic drug-resistant cancer stem-like cells in brain glioma. METHODS The role of miR-125a-5p in the regulation of CSCs, EMT, migration, and invasion in glioblastoma was measured in this study. RESULTS We showed the roles of miR-125a-5p in the regulation of CSCs, EMT, migration, and invasion in glioblastoma. miR-125a-5p can inhibit the CSCs phenotype and EMT in glioblastoma cells. In addition, its over-expression can significantly regulate CSCs-associated genes and EMT-associated gene expression in glioblastoma cells. CONCLUSIONS We concluded that miR-125a-5p is one of the key microRNAs regulating CSCs and EMT programs in glioblastoma. The results suggested that miR-125a-5p might be a novel therapy target for glioblastoma.

RESUMO OBJETIVO O glioblastoma (GBM) é um câncer comum e de alta mortalidade. A transição epitélio-mesênquima (EMT) desempenha um papel vital no desenvolvimento do glioblastoma. O objetivo deste estudo é avaliar o papel do miR-125a-5p no glioblastoma e a tumorigênese de células-troco cancerígenas resistentes a medicamentos quimioterápicos em gliomas cerebrais. METODOLOGIA Os papéis do miR-125a-5p na regulação de células-tronco cancerígenas, EMT, migração e invasão do glioblastoma foram medidos neste estudo. RESULTADOS Mostramos a função do miR-125a-5p na regulação das células-tronco cancerígenas, EMT, migração e invasão do glioblastoma. O miR-125a-5p pode inibir o fenótipo e a EMT de células-tronco cancerígenas em células de glioblastoma. Além disso, a sua superexpressão pode regular de forma significante genes associados às células-tronco cancerígenas e a expressão de genes associados à EMT em células de glioblastoma. CONCLUSÕES Concluímos que o miR-125a-5p é um dos principais microRNAs na regulação de células-tronco cancerígenas e programas de EMT em glioblastomas, e os resultados sugerem que o miR-125a-5p pode ser um novo alvo terapêutico em casos de glioblastoma.

Identification of chemical constituents in Naozhenning granule by UHPLC coupled with hybrid quadrupole-orbitrap MS / 药学学报

Naozhenning granule, which is composed of 11 herbal drugs, is mainly used in the treatment of concussion, cerebral post-traumatic syndrome. As the chemical composition of Naozhenning was complex, the ultrahigh performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry was applied to identify the chemical constituents rapidly in the Naozhenning granule. By analyzing the retention behaviors, accurate molecular weight, the fragmentation pathway, and comparison with the MS data from the standards and references, as well as the automatic identification by the Compound Discover 2.0, a total of 161 compounds were identified or tentatively deduced, and the sources of constituents were also confirmed. The compounds identified in Naozhenning granule included 9 iridoids, 8 butylphthalides, 26 flavonoids and flavonoid glycosides, 8 phenolic acids, 8 monoterpenoid glycosides and 9 alkaloids, as well as the common compounds in the herbal drugs, such as organic acids, amino acids, and sugars. The chemical composition of Naozhenning was studied for the first time, which provides a scientific basis for the quality control and document of effective materials of Naozhenning granule.