Clinical risk factors analysis of large volume central lymph node metastasis in papillary thyroid carcinoma / 中华内分泌外科杂志

Objective:To investigate the clinical risk factors of large volume lymph node metastasis (LV-LNM) in the central region of papillary thyroid cancer (PTC) .Methods:The clinical data of 1367 PTC patients admitted to the Department of Oncological Surgery, Hangzhou First People’s Hospital, Affiliated to Zhejiang University School of Medicine from Jan. 2016 to Jan. 2019 were retrospectively analyzed. There were 310 males and 1057 females. A total of 1644 cases of central region were included in the study.According to the number of lymph node metastasis in the central area, they were classified into small-volume lymph node metastasis (SV-LNM) group and LV-LNM group.71 cases of LV-LNM, 1573 cases of SV-LNM.The correlation between CLNM and LV-LNM and various clinicopathological features such as the sex, age, tumor size and so on of PTC patients was analyzed by chi-square test and Logistic regression analysis.Results:The proportion of CLNM in the affected side was 35.28% (580/1 644) , and the incidence of LV-LNM in the central area of the affected side was 4.32% (71/1644) . Univariate analysis showed that the LV-LNM in the central region of the affected side was closely correlated with gender, age, bilateral lesions, multiple lesions, size of lesions, membranous invasion and lateral cervical lymph node metastasis on the affected side were closely related ( P<0.05) . Multivariate regression analysis showed that male (OR=2.115, P=0.006) , age < 38 years old (OR=0.586, P=0.004) , multiple lesions on the affected side (OR=2.837, P=0.004) , lesions >7mm on the affected side (OR=1.762, P=0.002) and cervical lymph node metastasis on the affected side (OR=7.023, P<0.001) were independent predictors of LV-LNM in the central region of the affected side ( P<0.001) . The receiver operating characteristic curve (ROC) , sensitivity and specificity of LV-LNM predicted by the model were 0.839, 81.69% and 78.39%. The incidence of ipsilateral cervical lymph node metastasis in the affected central region of LV-LNM was 11.57 times higher than that of SV-LNM. Conclusion:PTC with male, age < 38 years old, multiple lesions on the affected side, lesion >7 mm and lateral cervical lymph node metastasis are prone to LV-LNM in the affected central region.

Altered O-glycosylation Level of SARS-CoV-2 Spike Protein by Host O-glycosyltransferase Strengthens Its Trimeric Structure

The trimeric spike protein (S) mediates host-cell entry and membrane fusion of SARS-CoV-2. S protein is highly glycosylated, whereas its O-glycosylation is still poorly understood. Herein, we site-specifically examine the O-glycosylation of S protein through a mass spectrometric approach with HCD-triggered-ETD model. We identify 15 high-confidence O-glycosites and at least 10 distinct O-glycan structures on S protein. Peptide microarray assays prove that human ppGalNAc-T6 actively participates in O-glycosylation of S protein. Importantly, the upregulation of ppGalNAc-T6 expression can profoundly enhance the O-glycosylation level by generating new O-glycosites and increasing both O-glycan heterogeneity and intensities. Further molecular dynamics simulations reveal that the O-glycosylation on the protomer-interface regions, which are mainly modified by ppGalNAc-T6, can potentially stabilize the trimeric S protein structure. Our work provides deep molecular insights of how viral infection harnesses the host O-glycosyltransferases to dynamically regulate the O-glycosylation level of the viral envelope protein responsible for membrane fusion.

Resveratrol promotes the survival and neuronal differentiation of hypoxia-conditioned neuronal progenitor cells in rats with cerebral ischemia / 医学前沿

Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.

Structural basis for repurposing a 100-years-old drug suramin for treating COVID-19

The COVID-19 pandemic by non-stop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report the discovery of suramin, a 100-year-old drug, as a potent inhibitor of the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) through blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for COVID-19. The 2.6 [A] cryo-EM structure of the viral RdRp bound to suramin reveals two binding sites of suramin, with one site directly blocking the binding of the RNA template strand and the other site clash with the RNA primer strand near the RdRp catalytic active site, therefore inhibiting the viral RNA replication. Furthermore, suramin potently inhibits SARS-CoV-2 duplication in Vero E6 cells. These results provide a structural mechanism for the first non-nucleotide inhibitor of the SARS-CoV-2 RdRp and a rationale for repurposing suramin for treating COVID-19. One Sentence SummaryDiscovery and mechanism of suramin as potent SARS-CoV-2 RNA polymerase inhibitor and its repurposing for treating COVID-19.

Discussion on the necessity of Delphian lymph node dissection for papillary thyroid carcinoma / 中华内分泌外科杂志

Objective:To investigate the clinical significance of Delphian lymph node (DLN) dissection in papillary thyroid cancer (PTC) .Methods:The correlation of DLN detection and metastasis in 208 PTC patients with various clinical and pathological features was analyzed retrospectively. The value of DLN metastasis in predicting PTC high-risk features was evaluated, and the tendency of surgical selection for PTC with DLN metastasis was also discussed.Results:① Of 208 PTC patients, DLN was detected in 144 patients (69.23%) . The detection rate of DLN was related to gender, number of central lymph nodes (excluding DLN) removed and metastasis (all P<0.05) . Male, greater number of nodes in the central compartment (excluding DLN) was more favorable for DLN detection. ② The rate of DLN metastasis was 18.27% (38/208) . In the univariate analysis, DLN metastasis was significantly associated with the following variables:gender, whether it is microcarcinoma, isthmus involvement, number of lesions, extrathyroidal extension, tumor size, number of central lymph nodes (excluding DLN) removed and metastasis (all P<0.05) . In the multivariate analysis, tumor size larger than 1 cm, isthmus involvement and greater number of central lymph nodes (excluding DLN) metastasis were independent risk factors of DLN metastasis ( P<0.05) . ③ The sensitivity of DLN metastasis to predict extranodal invasion, central and lateral lymph node metastasis was 54.54%, 37.36% and 62.86%, with specificity of 78.69%, 92.45% and 55.56%, respectively. ④ Patients with DLN metastasis were more likely to receive total thyroidectomy, bilateral central lymph node dissection, and lateral cervical lymph node dissection. Conclusions:Due to high rate of DLN detected and metastasis, DLN should be routinely dissected. Patients with DLN metastasis predict high risk characteristics of PTC and extensive lymph node metastasis, which is of clinical significance for lymph node dissection.

An interview survey of Beijing′s standardized residency training program since the implementation of the medical education synergy policy / 中华医院管理杂志

Objective:To understand the views of various relevant personnel on the standardized training mode of resident doctors after the implementation of Beijing′s medical education synergy policy, so as to provide references for further improvement of China′s medical education synergy policy.Methods:From January to May 2019, a semi-structured interview method was used to investigate the resident training students, clinical teachers(professional postgraduate tutors and resident training trainees′ guiding doctors)as well as resident training managers in 35 resident training bases in Beijing. The original data of the interviews were sorted out, coded and analyzed by taking root theory and main frame method descriptive analysis.Results:A total of 687 valid interview results were received, of which 71.86% of the resident training managers thought that the mode was more reasonable and the advantages outweighed the disadvantages; 38.07% of the resident training students and 45.45% of the graduate supervisors mentioned that the mode effectively shortened the training time of clinical talents; however, 31.98% of the resident training students and 22.92% of the resident training students′ guiding physicians mentioned it was difficult to balance courses, scientific research and clinical work under this mode, 61.62% of graduate supervisors pointed out that the students were lack of time and energy to engage in scientific research.Conclusions:The training mode of the integration of the standardized training of resident doctors and the postgraduate training of master′s degree in clinical medicine, given its necessity and institutional advantages, is found with room of improvement in its mode setting, arrangement of scientific research courses and clinical rotation, supervision and assessment of the process.

Investigation on the Beijing Standardized Residency Training Program since the implementation of the medical education synergy policy / 中华医院管理杂志

Objective:To understand the status quo and impact of Beijing Standardized Residency Training program following three years of the medical education synergy policy from the perspective of residents.Methods:Online questionnaire was used from April to May 2018 to investigate two types of residents who had completed the program in Beijing in 2018, and a comparison was made with the 2014 training program, activities, evaluation, and support conditions. Statistical descriptions and Wilcoxon signed-rank test were used for analysis.Results:A total of 3 293 residents completed the Beijing Standardized Residency Training, of which 54.75% were resident physicians, and 45.25% were graduate students in clinical medicine. Compared with 2014, the completion rate of the disease types and quantity, clinical operation types and quantity required by the training plan has been significantly improved, with the proportions being 93.77% and 92.80%, respectively. The implementation rate of examinations in 7 departments including Internal Medicine was greater than 90%, which is significantly higher than that in 2014; The conditions for training support had improved significantly.Conclusions:The impact of Beijing Standardized Residency Training Program was already emerging since the medical education synergy policy in place. It was recommended that various measures be taken to steadily improve the quality of the " dual-track system" .

Clinical effects of combined muscle double fixation on blepharoplasty / 中华医学美学美容杂志

Objective:To explore the effect of combined orbicularis muscle double stitch operated on blepharoplasty.Methods:A total of 90 patients, 79 females and 11 males, aged 18-49 years, were treated by using combined orbicularis muscle double stitch procedure, that is, to fix upper lifting muscle, to remove partial fat, and to perform blepharoplasty.Results:All 90 cases＇ incisions were healed at the first phase, no obvious swelling and bleeding. Within 3-24 months follow up, all patients＇ upper eyelids were significantly improved. The skin was smoothy when closing eyes, and eyelash was up when opening eyes, and arc was natural and satisfactory.Conclusions:This method can improve the shape of the upper eyelid swelling and get long-lasting and stable physiological eyelid.

Clinical significance of serum microRNA-222-3p expression in papillary thyroid carcinoma / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the expression of serum miR-222-3p in papillary thyroid carcinoma and its clinical significance.METHODS Total RNA in serum was extracted from 121 patients of papillary thyroid carcinoma and benign thyroid diseases.The reverse transcription quantitative real-time polymerase chain reaction(qRT-PCR) method was used to detect the expression of miR-222-3p,and then the potential correlation between serum miR-222-3p and clinical pathological characteristics of papillary thyroid carcinoma was analyzed.The receiver operating characteristic area under the curve(ROCAUC) and their index for diagnosis evaluation were also calculated.RESULTS The median expression level of serum miR-222-3p in papillary thyroid carcinoma patients was significantly higher than that of control group (2.2188 vs 0.7022,P=0.002).Although the expressions of serum miR-222-3p was not associated with the gender,age,capsule invasion,TNM stage,but it was positively correlated with tumor size,bilateral involvement,lesion quantity and lymph node status.ROC curve analysis showed that the specificity and sensitivity of the miR-222-3p diagnosis of papillary thyroid cancer were 79.75％ and 61.90％,respectively,while the ROC-AUC was 0.717.CONCLUSION The serum miR-222-3p is over expressed in papillary thyroid carcinoma and its expression is significantly correlated with tumor progression.It will be helpful for PTC diagnosis.

Clinical research about level Ⅵ-1 lymph nodes and the lymph nodes posterior to the right recurrent laryngeal nerve of the papillary thyroid carcinoma / 中国耳鼻咽喉头颈外科

OBJECTIVE The objective of this study is to discuss when to dissect the lymph nodes behind the right recurrent laryngeal nerve (LN-prRLN) from the standpoint of the right cervical level Ⅵ-1 (superficial layer to the recurrent laryngeal nerve) lymph nodes in papillary thyroid carcinoma (PTC) patients.METHODS The clinical data of 306 bilateral or right PTC patients from the Hangzhou First People's Hospital who underwent dissection of level Ⅵ-1 lymph nodes and LN-prRLN between March 2014 and September 2015 were analyzed. We measured the number of level Ⅵ-1 metastatic lymph nodes and size of level Ⅵ-1 lymph nodes metastasis loci to predict the metastasis of LN-prRLN.RESULTS The number of level Ⅵ-1 metastatic lymph nodes and size of level Ⅵ-1 lymph nodes metastasis loci were risk factors of LN-prRLN metastasis(P<0.05). When the number of the level Ⅵ-1 metastatic lymph nodes was greater than 1.5, the AUC was 0.813 (the sensitivity was 78.43%, the specificity was 76.65%). The ROC showed that when the size of level Ⅵ-1 lymph nodes metastasis loci were more than 0.45 cm, the AUC was 0.726 (sensitivity was 90.20%, specificity was 48.90%).CONCLUSION In bilateral or right PTC patients with metastasis of level Ⅵ-1 lymph nodes, especially when the number of level Ⅵ-1 metastatic lymph nodes was greater than 2cm and the metastasis loci were more than 0.45 cm, we should dissect the LN-prRLN.

From traditional Chinese medicine syndrome differentiationpoint of view to discuss blood glucose control strategy in patients with different etiological factors and treated by mechanical ventilation / 中国中西医结合急救杂志

Objective From the perspective of traditional Chinese medicine (TCM) syndrome differentiation to investigate the blood glucose control strategies of patients with different etiological factors and treated by mechanical ventilation.Methods One hundred and twenty-six mechanical ventilation patients admitted to the Department of Intensive Care Unit (ICU) of Hangzhou Third People's Hospital from February 2016 to February 2017 were enrolled, they were divided into a heart failure group (64 cases) and a pneumonia group (62 cases) according to the cause of disease. Altogether 4 cases due to death, giving up the treatment or being transferred to other hospital were excluded in each group, thus, 60 cases in heart failure group and 58 cases in pneumonia group were finally enrolled. Both groups received at least 4 days of formal blood glucose monitoring and control program. The differences in TCM syndromes, the number of patients necessary to use insulin to control the blood glucose, the daily use of insulin dosage, the incidence of hypoglycemia and prognosis of patients were compared between the two groups.Results According to TCM syndrome differentiation, deficiency was the primary syndrome in the heart failure group, while in the pneumonia group, excess was the primary syndrome, the proportion of deficiency syndrome in heart failure group was significantly higher than that in the pneumonia group [63.33% (38/60) vs. 31.03% (18/58),P < 0.05]. Within 4 days, the incidence of hyperglycemia [50.0% (29/58) vs. 13.3% (8/60)], daily insulin dose (U/d: 85.35±6.35 vs. 20.13±8.20) in pneumonia group were higher than those in the heart failure group (bothP < 0.05). The incidence of hypoglycemia in heart failure group was higher than that in pneumonia group [16.67% (10/60) vs. 3.45% (2/58),P < 0.01].Conclusions It is necessary to use different blood glucose control strategies in patients with heart failure and pneumonia to undergo mechanical ventilation, and the TCM syndrome differentiation can provide theoretical references.

Progress study of miRNA in papillary thyroid carcinoma / 中华内分泌外科杂志

MiRNAs represent a class of short endogenous non-coding RNAs regulating gene expression at mRNA post-transcriptional level in many biological processes,including differentiation,proliferation,development and apoptosis.The deregulation of miRNA expression is believed to be an important regulator of tumor development.Increasing evidence has revealed the abnormal expression of miRNA in papillary thyroid carcinoma,indicating the important role in PTC invasion mechanism,clinical diagnostic value,efficacy evaluation,recurrence monitoring and prognosis judgement.

A study for the time course of cerebral infarction with diffusion kurtosis imaging / 中华放射学杂志

Objective To investigate the time course of cerebral infarction with diffusion kurtosis imaging-related parameters.Methods According to the time interval from symptom onset to MRI examination, 114 cases of cerebral infarction were divided into five groups:8 cases of hyperacute phase(less than 6 hours), 14 cases of acute(>6-24 h), 60 cases of early subacute(>24 h-7 d), 20 cases of late subacute(>7-14 d), and 12 cases of chronic phase ( >14 d-2 months).They underwent routine diffusion weighted imaging (DWI) and diffusion kurtosis imaging (DKI) scanning, and apparent diffusion coefficient ( ADC) and DKI-derived parameters were obtained from them.The derived diffusion parameters were compared among different phases in the patients , and the percent of changes in the infarcted regions were calculated.Paired t-test was used to compare the difference of each parameter between the infarcted region and contralateral normal region , and their correlation with time interval was tested using Pearson correlation analysis.Results Except for chronic phase , mean kurtosis ( MK) , axial kurtosis ( K∥) , radial kurtosis (K⊥)map showed uneven high signal in the infarcted regions , while mean diffusion(MD), axial diffusion(D∥), radial diffusion(D⊥) showed uniform low signal.MK values in the infarcted regions of hyperacute, acute, early subacute and late subacute phase (1.331 ±0.357,1.578 ±0.453,1.519 ±0.455, 1.403 ±0.275 ) increased significantly , compared with the contralateral normal mirror regions ( 0.850 ± 0.236,0.827 ±0.194,0.865 ±0.144,0.939 ±0.212) (t values were 5.242,6.907,12.416,5.629, respectively.P values were all less than 0.01 ).MK, K∥, K⊥ achieved a peak in the acute and early subacute phase , and showed more amplitude than the decrease of MD , D∥, D⊥.Then they gradually reduced, and tended to normalize.MK, MD, ADC had a significant correlation with the time onset of cerebral infarction ( r was 0.354, 0.747, 0.723, respectively, P values were all less than 0.05 ).Conclusion Diffusion kurtosis imaging can provide more diffusion information than conventional DWI , which can better reflect the microstructure changes in tissue.

Effects of cytochrome P450 isozymes 2A6, 2B6, 2C9 and 2C19 genetic polymorphisms on plasma concentration of sodium valproate / 中华神经科杂志

Objective To investigate the influences of the functional polymorphisms of cytochrome P450 isozymes 2A6 (CYP2A6),2B6 (CYP2B6),2C9 (CYP2C9),and 2C19 (CYP2C19) on plasma concentration of sodium valproate.Methods A total of 131 Chinese children with epilepsy receiving sodium valproate after a period of more than 5 half-time were recruited.The genotypes of CYP2A6 were detected by multiplex polymerase chain reaction (PCR),and the genotypes of CYP2B6,CYP2C9,and CYP2C19 were detected by PCR-ligase detection reaction.Enzyme-multiplied immunoassay technique was used to measure the plasma concentration of sodium valproate.The association between the polymorphisms and the plasma concentration of sodium valproate were analyzed by one-way ANOVA or Student' s t-test.Results Patients were divided into 4 groups according to the genotyping results of CYP2C9 and CYP2C19 (G1:extensive metabolizers in both CYP2C9 and CYP2C19; G2:CYP2C19 intermediate metabolizers; G3:CYP2C19 poor metabolizers; G4:CYP2C9 poor metabolizers),the mean normalized steady-state sodium valproate concentrations were significantly higher in G3 (3.70 ± 0.95) and G4 (4.35 ± 1.48) patients when compared to those in G 1 (2.57 ± 1.30,t =3.056,4.490,both P ＜ 0.01) and G2 (2.76 ± 1.19,t =2.827,4.462,both P ＜ 0.01) patients.The daily doses (mg/d) of sodium valproate received by G3 (19.46 ± 5.20) and G4 (19.30 ±7.67) patients were significantly lower than that of G1 patients(24.10 ±6.97,t =2.359,2.297,both P ＜ 0.05).There were no differences in daily doses or normalized steady-state concentrations of sodium valproate among the CYP2A6* 4 or CYP2B6* 6 genotypic groups.Conclusions The CYP2C9 and CYP2C19 polymorphisms have dramatic effects on the plasma concentration of sodium valproate.The daily doses of sodium valproate in G3 and G4 patients should be lower than usual.

Comparison between standard and high-flexion posterior stabilized (PS) rotating-platform mobile-bearing (RP-MB) total knee system / 中华骨科杂志

Objective To explore the indication and the functional advantages of the high-flexion posterior stabilized (PS) rotating-platform mobile-bearing (RP-MB) total knee system. Methods A prospective randomized, controlled trial was performed. Osteoarthritis was the indicators for total knee arthroplasty.From Feb. 2009 to Apr. 2009, 75 patients (94 knees) were randomly assigned to to receive either a highflexion PS, RP-MB total knee system(PFC sigma RPF) or a standard one (PFC sigma RP). There were no statistical difference in the baselines, the preoperative scores of the Hospital for Special Surgery (HSS) and the knee range of motion (ROM) of both groups. The functional status were assessed with Hospital for Special Surgery and the ROM of the knee at the postoperative 1, 6, 12, 18 months. The satisfaction rates were assessed at the postoperative 18 months. The radiographic measurements were t assessed at the postoperative 3days and 3, 6, 12, 18 months. Results A total of 70 participants (87 knees) completed the 18-month followup. At the time of the final follow-up, the average Hospital for Special Surgery knee score was 92.4±5.0points in the standard group and 94.7±7.0 points in the high-flex ion group. The difference was not statistically significant(P ＞0.05). The average maximal flexion was 131.9±14 degrees in the high-flexion group and 123.0±15.3 degrees in the standard group. There was a statistical difference. But it was not enough to confirm our hypothesis that the difference should be higher than 10 degrees. Moreover, the satisfaction rate were 100% in both groups, and no statistical significant difference was found. Conclusion No significant differences were found between standard and high-flexion posterior-stabilized rotating-platform mobile-bearing total knee prostheses in terms of clinical outcomes or range of motion.

Effect of Psychological Nursing on Anxiety after Spinal Cord Injury / 中国康复理论与实践

@#Objective To observe the effect of psychological nursing on anxiety after spinal cord injury.Methods60 inpatients were divided into group A(normal nursing)and group B(additional psychological nursing).They were evaluated with Self-Rating Anxiety Scale(SAS)when they were hospitalized and 1 month later.ResultsThe scores of SAS obviously decreased in both groups 1 month later(P<0.01),while that of group B were more obviously than group A(P<0.01).ConclusionThe routine nursing could relieve the anxiety symptoms of SCI patients.It is more effective in addition with psychological nursing and healthy education.

Effects of Gross Polysaccharide of Radix Rehmanniae Preparata on Morphology Changes of Thymus and Spleen in Blood Deficiency Model Mice / 中华中医药杂志

Objective: To probe the effects of gross polysaccharide of Radix Rehmanniae Preparata(GPRRP) on the morphology changes of immune organ of blood deficiency model mice.Methods: Using the blood deficiency mice models induced by releasing blood and injection of Cyclophosphamide as the experimental objects,the model animals were divided into 5 groups,that was the large,middle and small dose of GPRRP groups,Danggui Buxue Oral Liquid group,model group,at the same time,giving a blank control group.It was given successively relating drugs to the animals of several groups for 10 days.At the end of the experiment,the hemogram was measured and the thymus and spleen were taken,and making pathological section,then these tissues morphology changes were observed under microscope.Results: GPRRP can obviously resist the atrophy of thymus and spleen induced by the model establishing,can obviously increase the depth of thymus cortex and the number of cortex cells,can enlarge the size of spleen nodules and obviously increase the number of lymphocyte.Conclusion: GPRRP can resist the atrophy of thymus and spleen in blood deficiency model mice.