Research progress and potential medical applications of anaplastic lymphoma kinase in treatment of non-small cell lung cancer / 中国药理学通报

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

Value of EZSCAN for Screening Mild Renal Impairment / 中山大学学报(医学科学版)

ObjectiveAutonomic dysfunction is a common and serious complication in patients with early chronic kidney disease （CKD）. Sweat gland dysfunction is an initial sign of autonomic dysfunction. Electrochemical skin conductance （ESC） measurement by reverse iontophoresis and chronoamperometry to assess sweat gland function may detect patients with mild renal insufficiency in healthy population for early intervention and treatment to delay further deterioration of renal function. MethodsAn EZSCAN score （0~100） was calculated using a proprietary algorithm based on the chronoamperometry analysis. A total of 6 661 subjects who received physical examination from the physical examination center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to October 2020 were enrolled， including 2 075 （31.15%） subjects with reduced renal function （eGFR < 90 mL·min-1·1.73 m-2） as the case group and 4 586 （68.85%） subjects with normal renal function （90 mL·min-1·1.73 m-2≤ eGFR ≤120 mL·min-1·1.73 m-2） as the control group. Lasso regression was used to screen covariates， and the relationship between the risk score and eGFR was analyzed by loess curve and logistic regression. ResultsAfter multivariate adjustment， the risk score was correlated with the risk of eGFR decline. Compared with the group with the lowest risk value （Q1<24）， the OR（95%CI ）of Q2 （25-27）， Q3 （28-47）， and Q4 （48-75） were 1.85 （1.55， 2.21）， 2.53 （2.13， 3.00）， 2.49 （2.13， 2.93）， respectively. The maximum area under the ROC curve is 0.75（0.74，0.76）， the sensitivity is 73.98%， the specificity is 63%， the positive predictive value is 47.49%， the negative predictive value is 84.25%， and the Youden index is 0.369 72， the optimal cutoff value is 25. ConclusionsEZSCAN could be a useful screening tool to identify healthy individuals at increased risk of renal function decline， and the one with an EZSCAN score of more than 25% should undergo diagnostic laboratory testing.

Level of self-compassion among residents and related influencing factors / 中华医学教育探索杂志

Objective:To investigate the level of self-compassion among residents and related influencing factors, and to help them improve self-compassion ability, achieve learning goals, and increase the degree of satisfaction with learning.Methods:In July 2022, the random sampling method was used to select 330 residents (postgraduate students majoring in clinical medicine after national unified recruitment) from two grade A tertiary hospitals in Shenyang of Liaoning province in China, and Self-Compassion Scale was used for investigation. SPSS software was used to analyze the degree of satisfaction with industry, learning pressure, the balance between learning and life, and occupational burnout among residents and their association with the level of self-compassion through the chi-square test, the one-way analysis of variance, and the multilevel regression analysis.Results:The residents had a mean self-compassion score of (40.90±6.81), and the residents of the second grade had a lower level of self-compassion than those of the other grades. Major satisfaction and balance between learning and life were positively correlated with self-compassion, and occupational burnout was negatively correlated with self-compassion.Conclusion:There is a relatively insufficient level of self-compassion among residents, and improving self-compassion level may effectively regulate occupational burnout, professional satisfaction, and the balance between learning and life, thereby helping to improve learning and mental health.

Genotypic characteristics of thalassemia and evaluation of the effectiveness of blood routine screening in Sanya City / 中华地方病学杂志

Objective:To analyze the mutation types and distribution characteristics of thalassemia gene among high-risk populations in Sanya City, and to evaluate the effectiveness of blood routine screening, in order to provide scientific basis for formulating measures for prevention and control of thalassemia in Sanya City.Methods:Retrospective analysis was used to collect detection results and clinical data from high-risk individuals who completed genetic screening for thalassemia at Sanya Materal and Child Health Hospital from January 2019 to August 2021. Mutation types and distribution characteristics of thalassemia gene were analyzed, and the missed detection rate and sensitivity of blood routine indicators [mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH)] were evaluated based on the results of genetic screening for thalassemia.Results:A total of 5 760 high-risk individuals were included in the screening results of thalassemia genes, and 3 868 samples of thalassemia gene mutations were detected, with a detection rate of 67.15%. Among them, there were 2 979 samples with α-thalassemia genetic mutations, with a detection rate of 51.72%; including 2 966 common genotype samples (99.56%), the main genotype was αα/-α 3.7 (20.14%, 600/2 979); 13 rare genotype samples (0.44%), 4 cases of αα/-- THAI, 3 cases of α CD40(AAG>AA-)α/αα, 2 cases of α PPα/αα, and 1 case of Fusion gene/αα, Fusion gene/α WSα, α WSα/α PPα, and α CD40(AAG>AA-)α/α WSα each. There were 340 samples with β-thalassemia gene mutations, with a detection rate of 5.90%; including 336 common genotype samples (98.82%). The β CD41/42/β N genotype was dominant (57.65%, 196/340); 4 rare genotype samples (1.18%), β CD5(-CT)/β N, β IVS-Ⅱ-2(-T)/β N, β IVS-Ⅱ-761(-T)/β N and β Initiation(ATG>AGG)/β N 1 case each. There were 549 samples of αβ-compound type thalassemia, with a detection rate of 9.53%. The α missing recombination β CD41/42 genotype was dominant (61.02%, 335/549). There were a total of 4 226 samples that could be traced back to MCV and MCH. Among them, 3 007 samples were found to have mutations in thalassemia genes through screening, 2 584 cases were found to have abnormalities in the combination of MCV and MCH indicators, and 423 samples were missed in blood routine screening, with a missed detection rate of 14.07% (423/3 007). The missed samples were mainly α static type, accounting for 89.13% (377/423) of the total missed samples. The screening sensitivity of MCV combined with MCH for α-, β- and αβ-compound type thalassemia was 82.65%, 98.07% and 98.15%, respectively. Conclusion:The types of genetic mutations in thalassemia in Sanya City are complex and diverse, and there are certain omissions in the blood routine screening of MCV combined with MCH.

Three molecular typing methods for Vibrio parahaemolyticus / 中国人兽共患病学报

This study explored three molecular typing methods for Vibrio parahaemolyticus(VP)in Liaoning Province in 2020,to assess the correlation among the three methods and the genetic relationships among between strains;analyze the epi-demic trends and distribution patterns of VPin Liaoning Province;and provide reliable technical support for the prevention and control of foodborne diseases.Serum typing,PFGE,REP-PCR,and ERIC-PCR molecular typing and cluster analysis were performed on 44 VP isolates from Liaoning Province in 2020.A total of 44 isolated strains were divided into 15 serotypes,and 8 isolated strains could not be classified.The serotypes were primarily O3 group,O1 group,and O2 group.Clinical isolates had high molecular similarity,whereas food isolates had low molecular similarity.The resolution(DI)of PFGE was 0.986,that of REP-PCR was 0.947,and that of ERIC-PCR was 0.935.The molecular similarity between serotype O3 and O1 group strains was high.The epidemic serotypes of isolated VP strains in Liaoning Province in 2020 were consistent with those from the past 5 years.The resolution of the PFGE typing method was better than that of REP-PCR and ERIC-PCR;moreover,REP-PCR had better resolution than ERIC-PCR.These three typing methods showed good intercorrelation.The O3 group strains are likely to originate from the O1 group strains.When a foodborne disease outbreak is caused by VP,laboratories with conditions can apply these three methods to trace the source of the pathogenic bacteriaquickly and effectively.

Analysis of clinicopathological features and prognostic factors of breast cancer patients with different molecular subtypes / 肿瘤研究与临床

Objective:To explore the differences in clinicopathological features, survival status and prognostic influencing factors of breast cancer patients with different molecular subtypes, and to provide bases for the prevention and treatment of breast cancer.Methods:The clinicopathological data of new-onset female breast cancer patients hospitalized in Shanxi Province Cancer Hospital from January 2015 to December 2016 were retrospectively analyzed, and patients were followed up. The clinicopathological features of patients with different molecular subtypes were compared. The follow-up was performed until June 30, 2021. Kaplan-Meier method was used to analyze the survival of patients, and Cox proportional hazards model was used to analyze the factors affecting overall survival (OS) of patients with different molecular subtypes.Results:There were 272 (14.9%), 1 005 (55.2%), 277 (15.2%) and 268 (14.7%) patients with subtypes of Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative breast cancer (TNBC), respectively. The differences in the distribution of patients with age at diagnosis, age at menarche, menopausal status, age at menopause, pathological type, longest tumor diameter, T staging, N staging, histological grading, and TNM staging were statistically significant among the four groups (all P < 0.05). At a median follow-up of 60 months, the 5-year OS rates of Luminal A, Luminal B, HER2 overexpression and TNBC subtypes were 93.8%, 89.2%, 77.6% and 78.0%, respectively, and the difference was statistically significant ( χ2 = 58.76, P < 0.001). M staging was an independent influencing factor for OS in patients with Luminal A breast cancer ( HR = 16.789, 95% CI 4.972-56.690, P < 0.001); T staging ( HR = 2.721, 95% CI 1.715-4.319), N staging ( HR = 4.460, 95% CI 2.399-8.291) and M staging ( HR = 3.364, 95% CI 1.988-6.670) were independent influencing factors for OS in patients with Luminal B breast cancer (all P < 0.001); N staging ( HR = 4.428, 95% CI 1.836-10.677) and M staging ( HR = 13.489, 95% CI 6.043-30.107) were independent influencing factors for OS of patients with HER2 overexpression breast cancer (both P < 0.01); T staging ( HR = 3.052, 95% CI 1.575-5.915), N staging ( HR = 2.492, 95% CI 1.298-4.785) and M staging ( HR = 33.012, 95% CI 8.606-126.637) were independent influencing factors for OS of patients with TNBC (all P < 0.01). Conclusions:The clinicopathological features and prognostic influencing factors of breast cancer patients with different molecular subtypes are different, and the prognosis of HER2 overexpression and TNBC patients is poor. Clinicians should provide individualized treatment and follow-up programs for patients with different molecular subtypes of breast cancer.

Cluster characteristics of physical activities among children inside and outside kindergartens and its relationship with athletic abilities / 中国学校卫生

Objective@#Based on physical activity (PA) and sedentary behavior (SB) variables on weekdays and weekends, the study aims to cluster the physical activities inside and outside kindergartens and to explore the cluster characteristics of different children using physical fitness indicators, so as to provide new strategies and methods for early childhood education and health.@*Methods@#From March to June 2019, 291 children aged 3-6 years from 6 kindergartens in Nanchang were recruited by a stratified cluster random sampling method. The ActiGraph GT3X-BT triaxial accelerometer was used to measure and analyze the PA and SB levels inside and outside the kindergarten. A twostep clustering algorithm model was employed for cluster analysis. Physical fitness were measured and evaluated according to the "National Physical Fitness Measurement Standard Manual (Preschool Section)". Differences in physical fitness among different clusters of children were compared, and the cluster characteristics of different children were analyzed.@*Results@#The clustering algorithm model indicated that based on six indicators, including PA and SB inside the kindergarten on weekdays, and PA and SB outside the kindergarten on both weekdays and weekends, children could be divided into three categories:active inside (high PA, low SB inside), active outside (high PA outside), and inactive (low PA, high SB both inside and outside). The average silhouette coefficient of the model was 0.3, indicating good clustering results. Both the active inside and active outside children showed significantly higher PA inside on weekdays, PA outside on weekdays and weekends, daily low intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) than the inactive children ( F=157.91, 80.79 , 95.86, 95.52, 124.74, P <0.05). After adjusting for gender and age, the physical fitness scores of both active outside ( 19.03 ±0.47) and active inside (19.11±0.40) were significantly higher than those of the inactive children (17.94±0.31). Additionally, active inside children (3.91±0.14) also showed significantly better performance in continuous double-leg jumps, compared to inactive children (3.45±0.11) ( P <0.05).@*Conclusion@#Children active inside and those active outside perform well in PA. Future research should focus on the proportion of structured and unstructured PA time to enhance the overall physical fitness of children.

Influencing factors of prognosis of patients with atrial fibrillation and heart failure after rhythm con-trol therapy / 心血管康复医学杂志

Objective:To study influencing factors of prognosis of patients with atrial fibrillation(AF)and heart fail-ure(HF)after rhythm control therapy.Methods:According to rhythm control methods,a total of 379 AF+HF patients treated in our hospital were divided into medication group(n=133)and surgery group(n=246,received catheter ablation of AF);according to AF type,patients were divided into paroxysmal AF group(n=208)and per-sistent AF group(n=171),and general clinical data and rhythm control effect were compared among all groups.According to NYHA cardiac function classification,patients were divided into NYHA classⅡ group(n=160),classⅢ group(n=188)and class Ⅳ group(n=31),and rhythm control effect was compared among above groups.Re-sults:Compared with medication,there were significant reductions in percentage of AF recurrence and LAD after treatment,and significant rise in percentage of heart function improvement in paroxysmal AF group,persistent AF group,NYHA class Ⅱ and Ⅲ group in those underwent surgery(P＜0.05 or＜0.01).Multivariate Logistic re-gression analysis indicated that medication,persistent AF were independent risk factors for AF recurrence and no cardiac function improvement after rhythm control therapy(OR=2.426～7.908,P=0.001 all),and NYHA classⅡ was an independent protective factor for AF recurrence after rhythm control therapy(OR=0.393,P=0.049).Conclusion:Atrial fibrillation catheter ablation can significantly improve prognosis of AF+HF patients.Persistent AF and antiarrhythmic medication are independent risk factors for poor prognosis after rhythm control therapy.

Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

Artesunate inhibits development of breast cancer cells via affecting expression of Skp2 and CDKN1A / 中国药理学通报

Aim To explore the effect of artesunate (ART) on the function of breast cancer cells during the progression of breast cancer and the possible mechanism of action. Methods MCF-7 (30 μmol • L-

Artesunate inhibits development of esophageal squamous cell carcinoma via regulating expression of Skp2 and P21 / 中国药理学通报

Aim To clarify the regulatory effect of Artesunate(ART) on tumor cell function and cell cycle in the pathological process of esophageal squamous cell carcinoma(ESCC). Methods KYSE450 and TE14 cells were treated with different concentrations of ART. The cells treated with 0 mg •L

Correlation between 25(OH)D and metabolically related fatty liver in T2DM population / 中国临床药理学与治疗学

AIM: To investigate the correlation between 25-hydroxyvitamin D and metabolically associated fatty liver disease in type 2 diabetes mellitus. METHODS: A total of 2 406 subjects in Standardized Metabolic Disease Control were recruited from the National Center for Standardized Metabolic Disease Control in The First Hospital of Lanzhou University. The population was divided into Q1, Q2, Q3 and Q4 according to 25(OH)D quartile. The prevalence of MAFLD and related clinical indicators among the four groups were compared, and the influencing factors of MAFLD were analyzed by Logistic regression. Restricted cubic spline (RCS) was used to explore the relationship between 25(OH)D and MAFLD. RESULTS: The prevalence of MAFLD was different with different vitamin D levels. The prevalence of MAFLD was lower in the group with high 25(OH)D level. The level of 25(OH)D in patients with MAFLD was lower than that in patients with T2DM alone, and the number of vitamin D deficiency was relatively higher. Multivariate regression analysis showed that 25(OH)D was not associated with the risk of MAFLD. RCS analysis also suggested that 25(OH)D was not associated with the risk of MAFLD. CONCLUSION: The prevalence of MAFLD is high in people with low vitamin D level, and vitamin D is not associated with the risk of MAFLD after multivariate adjustment.

Glucose and serum deprivation under hypoxia treatment inducing oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells through inhibition of Nrf2 signaling pathway / 解剖学报

Objective To investigate the effects of glucose and serum deprivation under hypoxia(GSDH)treatment on oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells (BMSCs), so to provide an experimental support for improving the therapeutic efficacy of BMSCs. Methods The cell injury model was established by hypoxia (1% O

The value of transanal multipoint full-layer puncture biopsy in determining the response degree of rectal cancer following neoadjuvant therapy: a prospective multicenter study / 中华外科杂志

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ2 analysis, and a paired χ2 test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ2=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ2=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ2=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ2=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ2=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.

Effect of vascular endothelial growth factor-A165 on scleral remodeling of guinea pigs with form-deprivation myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of the intravitreal injection of vascular endothelial growth factor-A165(VEGF-A165)on the scleral remodeling of guinea pigs with form-deprivation myopia(FDM).METHODS: A total of 120 tricolor guinea pigs, aged three weeks, were randomly divided into 6 groups, with 20 in each group. The blank group did not undergo any intervention. In the FDM group, only the FDM model was established. In the phosphate buffer saline(PBS)group, 2.5 μL of PBS was injected into the vitreous cavity before establishing the FDM model. In the 1ng group, 5ng group, and 10ng group, VEGF-A165 was injected into the vitreous cavity at concentrations of 1, 5 and 10ng, respectively, before the establishment of the FDM model. The FDM model was established by covering the right eyes of guinea pigs with translucent balloons for 14d. The diopter and axial length of the right eyes were measured before and after covering. After 14d, the content of dopamine(DA)in retina was measured by high performance liquid chromatography. Additionally, the mRNA and protein expression levels of matrix metalloproteinase-2(MMP-2), tissue inhibitor of matrix metalloproteinase-2(TIMP-2), transforming growth factor(TGF)-β1, TGF-β2 and α-smooth muscle actin(α-SMA)in sclera were detected by reverse transcription polymerase chain reaction(RT-PCR)and Western blot.RESULTS: Before covering, there were no significant differences in the diopter and axial length of the right eyes of guinea pigs in all groups(P&#x003E;0.05). After 14d of modeling, when compared with the blank group, FDM group showed an increase in the degree of myopia in the right eye, a prolongation of the axial length, a decrease in the content of DA in the retina, and an increase in the expression of MMP-2, TGF-β2 and α-SMA in the sclera. Conversely, the expression of TIMP-2 and TGF-β1 were decreased(P&#x003C;0.01). However, in comparison to the FDM group, the degree of myopia in the 1ng, 5ng, and 10ng groups of guinea pigs decreased, the growth trend of axial length slowed, the content of DA in the retina increased, and the expression of MMP-2, TGF-β2 and α-SMA in the sclera decreased. Furthermore, the expression of TIMP-2 and TGF-β1 in the sclera increased(P&#x003C;0.01). As the concentration of intravitreal injection of VEGF-A165 increased, the degree of myopia in the right eye of guinea pigs gradually increased, and the axial length gradually prolonged. The content of DA in the retina gradually decreased, the expression of MMP-2, TGF-β2, and α-SMA in the sclera gradually increased, while the expression of TIMP-2 and TGF-β1 decreased gradually.CONCLUSION: Intravitreal injection of VEGF-A165 can increase the content of DA in the retina of FDM guinea pigs, affect the expression of MMP-2, TIMP-2, TGF-β1, TGF-β2 and α-SMA in the sclera, and inhibit scleral remodeling of guinea pigs. Notably, the VEGF-A165 at the concentration of 1ng showed the most significant efficacy.

Mechanism of Jiaotai Pills in treatment of depression based on quantitative proteomics / 中国中药杂志

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.

Molecular dynamics simulation on the Thermosinus carboxydivorans pfl ZTP riboswitch by ligand binding.

Riboswitches are RNA molecules that can regulate gene expression which is affected by ligand-binding during cotranscriptional folding process. However, the role of ligand during the folding is still unclear. In this study, the pfl domain of Thermosinus carboxydivorans ZTP riboswitch was discussed. The ligand is molecule ZMP. We mainly analyzed the change of ZMP-free and ZMP-bound aptamer domain by the dynamics simulation method. Structural features by calculating their RMSD, RMSF, etc. are analyzed. The results demonstrate that the binding domain require the presence of ZMP to maintain a stable fold. It also suggested that ZMP specificly binding to ZTP can generate more hydrogen bonds in the binding domain. Through the calculation of binding free energy decomposition of each nucleotide, molecule ZMP was found to promote the recognition and binding process of ligands by controlling some special nucleotides in the process of ligand binding. At last, the dynamical correlation and components of conformational motions were both applied to explore the effect of molecule ZMP to ZTP riboswitch. In general, ZMP can effectively affect the motions of the pfl riboswitch and facilitate the folding process of the ZTP riboswitch.These results may provide some new ideas for structural changes in riboswitches and their cotranscriptional folding process.

Analysis of risk factors of extrapulmonary organ dysfunction in children with severe refractory mycoplasma pneumoniae pneumonia / 中华急诊医学杂志

Objective:To analyze the clinical features of severe refractory mycoplasma pneumoniae pneumonia (SRMPP) in children, and explore its risk factors complicated with extrapulmonary organ dysfunction.Methods:The clinical data of children with SRMPP who were admitted to the Department of Critical Care Medicine of Shanghai Children's Hospital from July 2017 to June 2019 were retrospectively summarized. The patients were divided into two groups according to the occurrence of extrapulmonary organ dysfunction: the extrapulmonary organ dysfunction group and the respiratory dysfunction group. The differences of clinical features and laboratory indexes between the two groups were compared, and the risk factors of extrapulmonary organ dysfunction were screened out by logistic regression analysis.Results:A total of 107 cases with SRMPP were admitted to the Pediatric Intensive Care Unit during the past two years, and there were 44 cases (41.1%) complicated with pleural effusion, 17 cases (15.9%) with plastic bronchitis, 104 cases (97.2%) with positive results for macrolide resistance genes (2063, 2064), with an in-hospital mortality rate of 2.8% (3/107). Among 107 children with SRMPP, there were 51 cases (47.7%) with extrapulmonary organ dysfunction, 43 cases (40.2%) with cardiovascular dysfunction, 13 cases (12.1%) with coagulation dysfunction, 11 cases (10.3%) with gastrointestinal dysfunction, 4 cases (3.7%) with renal dysfunction, 4 cases (3.7%) with brain dysfunction, 3 cases (2.8%) with liver dysfunction, and 16 cases (15.0%) with multiple organ dysfunction. Compared with the respiratory dysfunction group, the incidence of capillary leak syndrome was higher (52.9% vs. 17.9%, P < 0.001), the capillary leak index was increased [11.71 (4.63, 27.07) vs. 5.78 (2.07, 15.71), P =0.019], serum albumin was decreased [(32.2 ± 5.6)g/L vs. (34.7 ± 6.7)g/L, P=0. 041], and prothrombin time was prolonged significantly [12.7 (11.7, 13.8)s vs. 12.0 (11.4, 13.0)s, P=0. 009]. Logistic regression analysis showed that capillary leak syndrome ( OR=0. 278, 95% CI 0.102-0.759, P=0. 013) and prolonged prothrombin time ( OR=1. 443, 95% CI 1.018-2.046, P=0. 039) were independent risk factors for SRMPP complicated with extrapulmonary organ dysfunction. Conclusions:Approximately 50% of children with SRMPP have dysfunction of extrapulmonary organs, such as circulation, coagulation and gastrointestinal disorders. Capillary leak syndrome and prolonged prothrombin time are independent risk factors for SRMPP complicated with extrapulmonary organ dysfunction.

Analysis of clinicopathological features and factors influencing the survival of young breast cancer patients / 肿瘤研究与临床

Objective:To explore the clinicopathological characteristics and factors influencing the survival of young breast cancer patients with diagnostic age below 35 years, and to provide the basis for the prevention and treatment of young breast cancer patients.Methods:Epidemiological and clinicopathological data of young female patients with newly diagnosed breast cancer from Shanxi Province Cancer Hospital between January 2015 and December 2016 were retrospectively analyzed. The data included age at diagnosis, reproductive history, history of abortion, menopausal status, and immunohistochemical results. Univariate and multivariate analysis were performed by using Cox regression model.Results:A total of 118 young breast cancer patients were collected, and the median age was 31 years old. Among them, the vast majority of 118 young breast cancer patients were invasive cancer (113 cases, accounting for 95.8%); there were 65 cases (55.1%) with tumor diameter ≤ 20 mm, 61 cases (51.7%) at N 0 stage, and 112 cases (94.9%) at M 0 stage. The positive rates of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) were 73.7% (87/118), 69.5% (82/118) and 28.8% (34/118), respectively. Luminal B breast cancer was the predominant molecular subtype, accounting for 55.1% (65/118). By the end of follow-up (median follow-up period of 60 months), the overall survival rate of young breast cancer patients was 78.8%. Multivariate analysis showed that TNM staging was an independent factor affecting overall survival in young breast cancer patients ( HR = 7.858, 95% CI 2.924-21.120, P < 0.001). Conclusions:Young breast cancer patients have unique clinicopathological features and TNM staging is an independent factor affecting the prognosis. Individualized treatment helps to improve the quality of life and prolong the survival time of patients.

Comparison of the da Vinci Si and Xi surgical systems in robot-assisted laparoscopic adrenalectomy / 中华泌尿外科杂志

Objective:To compare the clinical efficacy and cost of robot-assisted laparoscopic adrenalectomy with da Vinci Xi and Si surgical system in the treatment of adrenal tumors.Methods:The clinical data of 99 patients performing robotic-assisted laparoscopic adrenalectomy in our hospital between June 2019 and December 2020 were retrospective analyzed. Among them, 57 cases were Si system robot assisted laparoscopic adrenalectomy (group Si), 35 male, 22 female; age (45.6±14.0)years; BMI(21.0±1.2); 6 with diabetes, 10 hypertension, 14 with abdominal surgery; 28 left, 29 right; 9 ASA score ≥3; tumor diameter (3.9±1.2)cm. There were 42 cases of Xi system robot-assisted laparoscopic adrenalectomy (group Xi), 21 male, 21 female; age(44.8±14.5)years; BMI(21.4±1.8); 2 with diabetes, 12 hypertension, 11 with abdominal surgery; 15 left, 27 right; 7 with ASA score ≥3; tumor diameter (3.7±1.1) cm. Sex, age, BMI, comorbidities, history of abdominal surgery, lateral division, ASA score, and tumor diameter were not significantly different between the two groups ( P>0.05). Operation method: except for the different docking procedures, the same surgical procedures were roughly performed in the two groups. The docking method of the Si group was the doctor holding the attractor as the guide. The operating room nurse introduced the robot cart under the guidance of the attractor, and then completed the docking.Group Xi docking adoptd the own laser positioning system of the robot system, without manual positioning and guidance; the mechanical arm of the Xi system was also more flexible. Complications were graded according to the Clavien-Dindo grading system. Comparing the treatment effect, safety, and cost of the two groups were compared. Results:The anesthesia times in the Si and Xi groups were (140.0±24.3) min and (125.6±26.4) min ( P=0.006), respectively. The surgical times in the Si and Xi groups were (109.0±18.8) min and (98.8±20.7) min (P=0.013), respectively. The docking times between the Si and Xi groups were (7.8±1.4) min and (5.0±0.9) min ( P<0.001), respectively. The estimated intraoperative blood loss in the Si and Xi groups was (121.5±70.8) ml and (124.7±68.9) ml ( P=0.824), respectively. The postoperative indwelling times of the drainage tube in the Si and Xi groups were (3.4±1.2) d and (3.4±1.3) d ( P=0.892), respectively. Postoperative bed times in the Si and Xi groups were (2.3±1.0) d and (2.5±1.2) d ( P=0.419), respectively. Postoperative hospitalization times in the Si and Xi groups were (6.4±1.5) d and (6.2±1.5) d ( P=0.484), respectively. Post Clavien ≥ grade 3 complications were four and two in groups Si and Xi, respectively ( P=0.642). The total cost during hospitalization in the Si and Xi groups was (51 975.2±7 320.8) Yuan and (56 830.9±8 392.5) Yuan, respectively ( P=0.003). The surgery and consumables costs for the Si and Xi groups were (23 785.3±4 063.1) Yuan and (28 021.2±6 066.8) Yuan ( P<0.001), respectively. Conclusions:Compared with the Si system, the Xi system robot-assisted laparoscopic adrenalectomy can provide similar perioperative results and safety, and shorten the time of anesthesia and surgery, but the total cost of hospitalization is increased.