Short-term outcomes and long-term quality of life after undergoing radical proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis for Siewert type II and III adenocarcinoma of the esophagogastric junction: A propensity score matching analysis / 中华胃肠外科杂志

Objective: To evaluate the effects on short-term clinical outcomes and long-term quality of life of laparoscopic-assisted radical proximal gastrectomy with esophageal gastric tube anastomosis versus total gastrectomy with Roux-en-Y anastomosis for adenocarcinoma of the esophagogastric junction. Methods: This was a propensity score matching, retrospective, cohort study. Clinicopathological data of 184 patients with adenocarcinoma of the esophagogastric junction admitted to two medical centers in China from January 2016 to January 2021 were collected (147 in the First Affiliated Hospital of Xiamen University and 37 in the Affiliated Hospital of Qinghai University). All patients had undergone laparoscopic-assisted radical gastrectomy. They were divided into two groups based on the extent of tumor resection and technique used for digestive tract reconstruction. A proximal gastrectomy with reconstruction by esophageal gastric tube anastomosis group comprised 82 patients and a total gastrectomy with reconstruction by Roux-en-Y anastomosis group comprised 102 patients. These groups differed significantly in the following baseline characteristics: age, preoperative hemoglobin, preoperative albumin, tumor length, tumor differentiation, and tumor TNM stage (all P<0.05). To eliminate potential bias caused by unequal distribution between the two groups, 1∶1 matching was performed by the nearest neighbor matching method. The 13 matched variables comprised sex, age, height, body mass, body mass index, preoperative glucose, preoperative hemoglobin, preoperative total protein, preoperative albumin, neoadjuvant radiotherapy, tumor length, degree of differentiation, and pathological TNM stage. Postoperative complications, postoperative nutritional status, incidence of reflux esophagitis 1 year after surgery, and quality of life were compared between the two groups. Results: After propensity score matching, 60 patients each were enrolled in the proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis groups. The baseline characteristics were comparable between these groups (all P>0.05). There were no significant differences between the two groups in operative time, intraoperative bleeding, time to semifluid diet, postoperative hospital days, tumor length, and total hospital costs (P>0.05). Patients in the proximal gastrectomy with esophageal gastric tube anastomosis group had earlier postoperative gastric tube and abdominal drainage tube removal time than those in the total gastrectomy with Roux-en-Y anastomosis group (t=-2.183, P=0.023 and t=-4.073, P<0.001, respectively). In contrast, significantly fewer lymph nodes were cleared and significantly fewer lymph nodes were positive in the proximal gastrectomy with esophageal gastric tube anastomosis group than in the total gastrectomy with Roux-en-Y anastomosis group (t=-5.754, P<0.001 and t=-2.575, P=0.031, respectively). The incidence of early postoperative complications was 43.3% (26/60) in the total gastrectomy with Roux-en-Y anastomosis group; this is not significantly higher than the 26.7% (16/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=3.663，P=0.056). The incidences of pulmonary infection (31.7%, 19/60) and pleural effusion (30.0%, 18/60) were significantly higher in the total gastrectomy with Roux-en-Y anastomosis group than in the proximal gastrectomy with esophageal gastric tube anastomosis group (13.3%, 8/60 and 8.3%, 5/60, respectively); these differences are significant (χ2=8.711, P=0.003 and χ2=11.368, P=0.001, respectively). All early complications were successfully treated before discharge. The incidence of long-term postoperative complications was 20.0% (12/60) in the total gastrectomy with Roux-en-Y anastomosis group and 35.0% (21/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this difference is not significant (χ2=3.386，P=0.066). The incidence of reflux esophagitis was 23.3% (14/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this is significantly higher than the 1.7% (1/60) in the total gastrectomy with Roux-en-Y anastomosis group (χ2=12.876, P<0.001). Body mass index had decreased significantly in both groups 1 year after surgery compared with preoperatively; however, the difference between the two groups was not significant (P>0.05). The differences in hemoglobin and albumin concentrations between 1 year postoperatively and preoperatively were not significant (both P>0.05). Quality of life was assessed using the Visick grade. Visick grade I dominated in both groups. The percentage of patients with Visick II and III in the total gastrectomy with Roux-en-Y anastomosis group was 11.7% (7/60), which is significantly lower than the 33.3% (20/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=8.076, P=0.004). No patients in either group had a grade IV quality of life. Conclusions: Both proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis laparoscopic-assisted radical surgery for adenocarcinoma of the esophagogastric junction are safe and feasible. However, both procedures have their own advantages and disadvantages in terms of postoperative complications. The incidence of reflux esophagitis is higher after proximal gastrectomy with esophageal gastric tube anastomosis, whereas the long-term quality of life is lower than that of patients after total gastrectomy with Roux-en-Y anastomosis.

Meta-analysis of Simotang Oral Liquid in treatment of functional dyspepsia in adults / 中国中药杂志

This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. "Simotang Oral Liquid" "Simotang" "Si Mo Tang" "Si Mo Tang Oral Liquid" were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.

Effect of wheat-grain moxibustion on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition, and to explore the possible mechanism of wheat-grain moxibustion in treating bone marrow inhibition.@*METHODS@#Forty-five SPF male CD1(ICR) mice were randomly divided into a blank group, a model group and a wheat-grain moxibustion group, 15 mice in each group. The bone marrow inhibition model was established by intraperitoneal injection of 80 mg/kg of cyclophosphamide (CTX). The mice in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), 3 moxa cones per acupoint, 30 s per moxa cone, once a day, for 7 consecutive days. The white blood cell count (WBC) was measured before modeling, before intervention and 3, 5 d and 7 d into intervention. After intervention, the general situation of mice was observed; the number of nucleated cells in bone marrow was detected; the serum levels of interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were measured by ELISA; the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc in bone marrow cells was measured by Western blot and real-time PCR method.@*RESULTS@#Compared with the blank group, the mice in the model group showed sluggish reaction, unstable gait, decreased body weight, and the WBC, number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were decreased (P<0.01), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was decreased (P<0.01). Compared with the model group, the mice in the wheat-grain moxibustion group showed better general condition, and WBC, the number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were increased (P<0.01, P<0.05), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion shows therapeutic effect on bone marrow inhibition, and its mechanism may be related to activating Wnt/β-catenin signaling pathway in bone marrow cells, improving bone medullary hematopoiesis microenvironment and promoting bone marrow cell proliferation.

Experience in Diagnosis and Treatment of Oculomotor Nerve Palsy based on Channel Pattern Differentiation / 中医杂志

It is believed that the basic pathogenesis of oculomotor nerve paralysis （ONP） is qi and blood depletion and channel obstruction. Taking channel pattern differentiation as the core， it is recommended to use acupuncture mainly based on location， syndrome and channel deficiency-excess differentiation. Location and channel tropism differentiation mainly follows the principle of “where the channels and collaterals pass， the main treatment can reach”， and commonly uses acupuncture points on Dumai （督脉）， the hand Shaoyang （少阳） Sanjiao （三焦） channel， the hand Taiyang （太阳） small intestine channel， three yang channels of the foot， the hand Shaoyin （少阴） heart channel， the foot Jueyin （厥阴） liver channel， and others， and combines scalp acupuncture with electro-acupuncture to enhance channel stimulation. Pattern and channel tropism differentiation is to differentiate the entered channel according to clinical symptoms and zang-fu patterns. The differentiation of deficiency-excess should be payed attention to， and the principle of “supplementing the deficiency， and draining the excess” should be followed. The supplementing and draining method should be used rationally by considering the differences in the supplementing and draining acupoints themselves， as well as the actual condition of the patients. Simultaneously， it is suggested to combine manipulation and stimulation amount and effect in clinical practice.

Clinical research progress on brain natriuretic peptide and amino-terminal pro-brain natriuretic peptide / 中国胸心血管外科临床杂志

@#Brain natriuretic peptide (BNP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were the main members of the natriuretic peptide family. BNP has the effects of diuretic sodium, reducing sympathetic nervous system activity, dilating blood vessels, and improving the pathological remodeling of heart. Plasma BNP/NT-proBNP levels have been widely used in the diagnosis, severity assessment, prognosis prediction and treatment guidance of heart failure. In recent years, BNP/NT-proBNP has become a research hotspot in the diagnosis and and prognosis judgment of atrial fibrillation, recurrence of atrial fibrillation after radiofrequency ablation and cardioversion and congenital heart disease in infants and children, prediction of postoperative complications, and drug development. This article reviews the latest advances in clinical application and research progress on BNP/NT-proBNP.

Primary ovarian squamous cell carcinoma: clinicopathological features and prognostic analysis of fifteen cases / 中华病理学杂志

Objective: To assess the clinical features and treatment outcomes in patients with primary ovarian squamous cell carcinoma (POSCC). Methods: Fifteen patients with primary ovarian squamous cell carcinoma diagnosed from January 2009 to December 2018 in Cancer Hospital of the University of Chinese Academy of Sciences were collected. The expression of p16, hMLH1, hMSH2, hMSH6 and PMS2 in POSCC was detected by immunohistochemistry, and the status of high-risk human papillomavirus (HPV) by RNAscope test. Results: Squamous cell carcinoma with different degrees of differentiation was found in 15 cases, including three cases with high differentiation and 12 cases with medium to low differentiation. There were four cases with in situ squamous cell carcinoma, four cases with teratoma, one case with endometrial carcinoma/atypical hyperplasia, and one case with endometriosis. p16 was expressed in five cases (5/15), indicating coexisting high-risk HPV infection. There was no high-risk HPV infection in the remaining 10 cases, and p16 staining was negative. There was no deficient mismatch repair protein in all cases. The overall survival time (P=0.038) and progression free survival (P=0.045) of patients with high-risk HPV infection were longer than those without HPV infection. Conclusions: POSCC is more commonly noted in postmenopausal women and often occurs unilaterally. Elevated serological indexes CA125 and SCC are the most common finding. Morphologically, the tumors show variable degrees of differentiation, but the current data suggest that the degree of differentiation cannot be used as an independent prognostic index. High-risk HPV infection may be associated with the occurrence of POSCC, and that the prognosis of POSCC patients with HPV infection is better than that of patients without infection.

Outcomes and prognosis of radical surgery in patients with stageⅠb2 and Ⅱa2 cervical squamous cell carcinoma / 中华妇产科杂志

Objective:To evaluate the survival, complications and prognostic factors in patients with stageⅠb2 and Ⅱa2 cervical squamous cell carcinoma treated by primarily radical surgery with or without postoperative adjuvant therapy.Methods:The clinical and pathological data of patients with stageⅠb2 and Ⅱa2 cervical squamous cell carcinoma treated in the Cancer Hospital of the University of Chinese Academy of Sciences from January 2015 to January 2018 were retrospectively analyzed. All patients underwent Querleu-Morrow classification (Q-M classification) C2 radical surgery, including extensive hysterectomy+pelvic lymphadenectomy with or without adjuvant therapy based on postoperative risk factors. Survival rate was calculated by Kaplan-Meier method and survival curve was drawn. Univariate analysis was performed by using the log-rank test to analyze the clinicopathological factors related to the prognosis of patients. Multivariate analysis was performed by using Cox regression method to analyze independent risk factors affecting survival prognosis.Results:(1) The median age of 643 patients with cervical squamous cell carcinoma was 50 years old (45-58 years old). Clinical stage: 260 cases (40.4%, 260/643) of stage Ⅰb2, 383 cases (59.6%, 383/643) of stage Ⅱa2. (2) Among 643 cases underwent Q-M classification C2 surgery, 574 cases (89.3%, 574/643) of them received adjuvant therapy and 184 cases (28.6%, 184/643) of them had grade 3-4 complications after treatment, including 134 cases (20.8%, 134/643) early complications and 66 cases (10.3%, 66/643) late complications. The incidence of grade 3-4 complications in 574 patients received postoperative adjuvant therapy was 30.1% (173/574), which was significantly different from that in 69 patients who received surgery alone (15.9%, 11/69; χ2=6.08, P=0.014). (3) All 643 cases were followed up, and the median follow-up time was 40 months (3-76 months). During the follow-up period, 117 cases (18.2%, 117/643) recurred, including 45 cases (7.0%, 45/643) of local recurrence, 54 cases (8.4%, 54/643) of distant metastasis, and 18 cases (2.8%, 18/643) of local recurrence and distant metastasis. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates of patients with stage Ⅰb2 and Ⅱa2 cervical squamous cell carcinoma were 79.9% and 85.5%, respectively. Univariate analysis showed that pelvic lymph node metastasis, para-aortic lymph node metastasis, deep stromal infiltration, and lymph-vascular space invasion were significantly associated with 5-year PFS in patients with stage Ⅰb2 and Ⅱa2 cervical squamous cell carcinoma (all P<0.05). The maximum diameter of tumor, pelvic lymph node metastasis and para-aortic lymph node metastasis were significantly associated with the 5-year OS of cervical squamous cell carcinoma in stages Ⅰb2 and Ⅱa2 (all P<0.05). Multivariate analysis showed that pelvic lymph node metastasis and para-aortic lymph node metastasis were independent factors affecting 5-year PFS and 5-year OS in patients with stage Ⅰb2 and Ⅱa2 cervical squamous cell carcinoma (all P<0.01). Conclusion:Radical surgery is a feasible and effective primary treatment for stagesⅠb2 and Ⅱa2 cervical squamous cell carcinoma, with a high 5-year survival rate and an acceptable complication rate.

Global characterization of modifications to the charge isomers of IgG antibody / 药物分析学报

Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quanti-tatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fraction-ated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor ac-counting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

Clinical observation on plastic splint treatment of middle clavicle fracture based on a new classification / 中国骨伤

OBJECTIVE@#According to 73 patients with middle clavicle fracture treated conservatively, a new classification of middle clavicle fracture was proposed, and the clinical effect of plastic splint in the treatment of middle clavicle fracture was observed.@*METHODS@#Total 73 patients with middle clavicle fracture treated with plastic splint from September 2018 to August 2020 were analyzed retrospectively. All the patients were divided into 4 types according to the degree of fracture displacement. There were 16 cases of typeⅠ, including 7 males and 9 females, ranging in age from 18 to 37 years old, with a mean of (28.6±7.8) years old;12 cases of mild disease, 3 cases of moderate disease and 1 case of severe disease. There were 16 cases of type Ⅱ, including 6 males and 10 females, ranging in age from 25 to 49 years old, with a mean of (37.3±9.4) years old;5 cases of mild disease, 8 cases of moderate disease and 3 cases of severe disease. There were 7 cases of type Ⅲ, including 4 males and 3 females, ranging in age from 33 to 57 years old;2 cases of mild disease, 3 cases of moderate disease and 2 cases of severe disease. There were 34 cases of type Ⅳ, including 16 males and 18 females, ranging in age from 48 to 82 years old, with a mean of(66.4±14.9) years old;7 cases of mild disease, 17 cases of moderate disease and 10 cases of severe disease. All patients received plastic splint external fixation for 4 weeks. Visual analgue scale (VAS) and Constant-Murley shoulder scores before treatment and 1, 3 and 9 months after treatment were observed and recorded to evaluate the change of pain degree and shoulder function recovery before and after treatment. The patients' satisfaction with the appearance after treatment was recorded at the latest follow-up. The X-ray findings at the latest follow-up were used to judge whether the patient had fracture nonunion. And according to the fracture healing time and imaging findings, the excellent and good rate of clinical curative effect in patients with different types was obtained.@*RESULTS@#All patients were followed up, and the duration ranged from 9 to 11 months, with a mean of (9.8±0.7) months. The VAS scores of typeⅠ, typeⅡand type Ⅳ before treatment were 2.88±0.83, 3.67±0.80 and 6.92±1.71 respectively, which were decreased to 0.54±0.19, 0.77±0.25 and 1.18±0.17 respectively after 9 months of treatment. The Constant-Murley shoulder scores of typeⅠ, typeⅡand type Ⅳ were 65.81±2.09, 63.50±2.22 and 47.93±2.91 respectively before treatment, and increased to 88.56±2.11, 85.12±2.23 and 71.25±2.16 respectively after 9 months of treatment. Five patients were not satisfied with the appearance after treatment;6 patients had no obvious continuous callus passing through after 9 months of treatment, which was fracture nonunion.@*CONCLUSION@#The classification of middle clavicle fracture is more appropriate to the clinic, which has a certain clinical guiding significance for the selection of treatment methods and prognosis of middle clavicle fracture. Plastic splint is effective in the treatment of middle clavicle fracture without obvious displacement and overlapping displacement, and the incidence of complications is low. It can be popularized in clinic.

Correlative analysis of cervical curvature and atlantoaxial instability / 中国骨伤

OBJECTIVE@#To investigate the correlation between the changes of cervical curvature and atlantoaxial instability.@*METHODS@#The correlation between the changes of cervical curvature and atlantoaxial instability was retrospectively studied in 50 outpatients with abnormal cervical curvature (abnormal cervical curvature group) from January 2018 to December 2019. There were 24 males and 26 females in abnormal cervical curvature group, aged from 18 to 42 years old with an average of(30.62±5.83) years. And 53 patients with normal cervical curvature (normal cervical curvature group) during the same period were matched, including 23 males and 30 females, aged from 21 to 44 years with an average of(31.98±6.11) years. Cervical spine X-ray films of 103 patients were taken in lateral position and open mouth position. Cervical curvature and variance of bilateral lateral atlanto-dental space(VBLADS) were measured and recorded, Pearson correlation coefficient analysis was used to study the correlation between the changes of cervical curvature and atlantoaxial instability.@*RESULTS@#Atlantoaxial joint instability accounted for 39.6%(21/53) in normal cervical curvature group and 84.0%(42/50) in abnormal cervical curvature group. There was significant difference between two groups(P<0.01). VBLADS in abnormal cervical curvature group was (1.79±1.01) mm, which was significantly higher than that in normal cervical curvature group(0.55±0.75) mm(P<0.01). Pearson correlation coefficient analysis showed that the size of cervical curvature was negatively correlated with VBLADS.@*CONCLUSION@#Cervical curvature straightening and inverse arch are the cause of atlantoaxial instability, the smaller the cervical curvature, the more serious the atlantoaxial instability.

A prediction model of pathological complete response in patients with locally advanced rectal cancer after PD-1 antibody combined with total neoadjuvant chemoradiotherapy based on MRI radiomics / 中华胃肠外科杂志

Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.

Study on NAEK-labelled HiD-Hin47 fusion protein as a carrier for pneumococcal polysaccharide conjugate vaccine / 中华微生物学和免疫学杂志

Objective:To develop an unnatural amino acid-labelled HiD-Hin47 fusion protein as a novel carrier.Methods:Twenty versions of the fusion protein were designed, each of which contained a different amino acid site replaced by an azide-bearing amino acid, N6-(2-azidoethoxy) (carbonyl)-L-Lysine (NAEK). These fusion proteins were constructed, expressed and purified, and the yield were evaluated by SDS-PAGE. Based on the highest protein yield, which was approximately 70% of the wild-type yield, the fusion protein with the unnatural amino acid in E677 site was selected. The pneumococcal polysaccharides of serotype 3 (F3) and serotype 6B (F6B) were coupled to the selected fusion protein through a "click" reaction. The conjugates were purified and compared in animal studies with other F3 and F6B conjugates that were coupled to CRM197, tetanus toxoid (TT) and HiD by conventional methods.Results:The immunogenicity of F3 conjugate using HiD-Hin47 as carrier (F3-HiD-Hin47) was slightly better than that of other F3 conjugates. F6B-HiD-Hin47 was significantly better than F6B-TT and F6B-HiD in terms of immunogenicity, but showed no significant difference with F6B-CRM197.Conclusions:NAEK-labelled HiD-Hin47 had the potential as a carrier for pneumococcal polysaccharide conjugate vaccine and was worthy of further study.

Preparation and immunogenicity evaluation of recombinant poliomyelitis type 2 virus-like particles / 中华微生物学和免疫学杂志

Objective:To express virus-like particles of poliovirus type 2 (PV2-VLP) in insect cells using a recombinant baculovirus expressing P1 and 3CD and to preliminarily evaluate its immunogenicity.Methods:Based on the codon preference of High 5 cells, the sequences of P1 gene and 3CD gene of PV2 were optimized and inserted into pUC57-Amp to construct pUC57-PV2-P1 and pUC57-PV2-3CD. UC57-PV2-P1s mutant that carried P1 gene mutation affecting thermostability was then constructed. Recombinant baculovirus strains of rBac-PV2-P1s-3CD and rBac-PV2-P1-3CD (wild type) were constructed using homologous recombination. The expression of target proteins was detected by Western blot. PV2-VLP was purified by ion exchange chromatography. The structure of VLP was observed under transmission electron microscopy to evaluate the assembly efficiency. The immunogenicity of PV2-VLP was assessed in a rat model.Results:The recombinant baculovirus with stable expression of P1s and 3CD proteins was successfully constructed. Western blot results showed that the yield of VLP was higher after thermostability mutation than that of the wild type. A three-dimensional structure with a diameter of about 30 nm was observed under electron microscopy, indicating that the VLP was successfully assembled. Animal experiment showed that the recombinant PV2-VLP had immunogenicity and could effectively induce the production of neutralizing antibodies.Conclusions:Effective VLP vaccines could be successfully prepared using the insect cell-baculovirus expression system, which provided reference for the development of polio VLP vaccine.

Effects of broad-spectrum antibiotics on the efficacy of 5-fluorouracil treatment of CT26 tumor-bearing mice / 中华微生物学和免疫学杂志

Objective:To study the effects of broad-spectrum antibiotics and induced antibiotic-resistant bacteria on the efficacy of 5-fluorouracil (5-FU) chemotherapy for mice with colon cancer and to investigate the underlying mechanisms associated with anti-tumor immune responses.Methods:BALB/c mice were subcutaneously injected with CT26 colon cancer cells and randomized into four groups: tumor-bearing control group, antibiotic group treated with ampicillin, streptomycin and colistin, 5-FU group and anitibiotic+ 5-FU group. Tumor volumes and body weights were measured and recorded. Seven days after the last 5-FU treatment, the percentages of splenic immune cell subpopulations and proliferated CD8 + T cells after co-culturing with CT26 were analyzed by flow cytometry. Gut microbiota composition was detected by 16S rRNA sequencing and the bacteria in mesenteric lymph nodes (mLN) were isolated and cultured. Bone marrow-derive macrophages were stimulated with identified bacteria and the expression of M1 and M2 polarization markers were assessed by quantitative PCR. The proliferation of CD8 + T cells co-cultured with bacteria-treated macrophages was analyzed by flow cytometry. In addition, tumor-bearing mice were treated with 5-FU and oral gavage of bacteria isolated from antibiotic+ 5-FU group or PBS. Tumor volumes, gut microbiota composition and the percentages of proliferated CD8 + T cells co-cultured with CT26 were assessed. Results:Tumor volumes were larger and body weights were lower in the antibiotic+ 5-FU group than in the 5-FU group. The percentages of CD4 + T cells, CD8 + T cells and neutrophils did not varied significantly after using antibiotics, however, the percentage of monocytes was increased in the antibiotic group. The percentage of proliferated tumor-specific CD8 + T cells in the antibiotic+ 5-FU group was decreased compared with that in the 5-FU group. Compared with the control group and 5-FU group, antibiotic usage was associated with the changes in gut microbiota composition with decreased α diversity indexes. Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis were isolated from mLNs of the antibiotic group, 5-FU group and antibiotic+ 5-FU group, respectively. Bone marrow-derived macrophages stimulated with Proteus mirabilis expressed arginase at a high level, which was a M2 polarization marker of macrophage, and associated with the decreased percentage of proliferated CD8 + T cells after co-culturing. Bacteria of the genus Proteus were enriched in the gut microbiota of 5-FU-treated tumor-bearing mice with the oral gavage of Proteus mirabilis. Although no significant inhibitory effect on tumor growth was observed, the oral gavage of Proteus mirabilis was associated with the decreased percentage of proliferated tumor-specific CD8 + T cells in vitro. Conclusions:Broad-spectrum antibiotics inhibited the efficacy of chemotherapy and the proliferation of tumor-specific CD8 + T cells, in which antibiotic-resistant bacteria might be involved.

Analysis of related risk factors for the refracture of adjacent vertebral body after percutaneous kyphoplasty / 中国骨伤

OBJECTIVE@#To investigate the risk factors of vertebral refracture after percutaneous kyphoplasty (PKP) for osteoprotic vertebral compression fractures (OVCFs), and to provide reference for clinical prevention.@*METHODS@#A retrospective analysis of 228 OVCFs patients who met the inclusion criteria admitted from November 6, 2013 to December 14, 2018. There were 35 males and 193 females, with a male-to-female ratio of 3∶20, and aged 58 to 91 years with an average of (69.70±7.03) years. All patients were treated with PKP and had complete clinical data. According to whether refracture occurred after operation, they were divided into refracture group (24 cases) and non refracture group (204 cases). Factors that may be related to refracture (including gender, age, surgical segment, number of vertebral bodies in the surgical segment, whether combined with degenerative scoliosis, whether anti-osteoporosis treatment) were included in the univariate analyses, and the single factor analysis of statistically significant risk factors was carried out with multiple Logistic regression analysis to further clarify the independent risk factors for vertebral body refracture after PKP. Survival analysis was performed using the time of vertebral refracture after PKP as the end time of follow up, the occurrence of refracture after PKP as the endpoint event, and the presence or absence of degenerative lateral curvature as a variable factor.@*RESULTS@#All 228 patients were followed up for 1.8 to 63.6 months with an average of (28.8±15.6) months, and the refracture rate was 10.5%(24/228). There were statistically significant differences between two groups in age, number of operative vertebral bodies, whether combinedwith degenerative scoliosis and whether anti osteoporosis treatment (@*CONCLUSION@#Combined scoliosis is an independent risk factor for refracture after OVCFs vertebroplasty, and it is also a possible high-risk factor for refracture after surgery.

Application of clinical flow examination scale in standardized residency training of anesthesiology / 中华医学教育探索杂志

Objective:The clinical flow examination (CFE) scale was used to evaluate the effect of standardized residency training in the department of anesthesiology in West China Hospital of Sichuan University.Methods:Using the CFE scale, 98 students were tested three times consecutively, and then satisfaction surveys were conducted on the assessment tutors and students respectively. IBM SPSS software was used to test the reliability and validity of the CFE scale, and then the scores and satisfaction were statistically analyzed. SPSS 23.0 was used for t test and chi-square test. Results:The CFE scale had high reliability and validity, and the results of 95 students were included for analysis. The 95 students had a very high rate of excellence in basic, professional and final grades. Except that the basic, professional and final overall scores of the female group were higher than those of the male group ( P < 0.05), the differences between the other groups were not statistically significant ( P > 0.05). Results of the CFE satisfaction survey showed that the satisfaction of students and instructors was 98.9% and 100%, respectively. Conclusion:CFE scale can be well used to evaluate the effect of standardized residency training, and the training effect of anesthesiology department in our hospital is good and basically homogeneous, while there is still room for further improvement.

The Results of ABO/RhD Blood Group and Comparative Analysis Detected by Two Methods in Infants Younger than 6 Months / 中国实验血液学杂志

OBJECTIVE@#To detect the ABO / RhD blood type of infants younger than 6 months in different gestational age and month old with automatic microcolumn glass sphere and tube method, and compare the result of the two methods.@*METHODS@#The data of 896 samples of infants younger than 6 months from January 2018 to February 2019 was collected. The two methods were used to detect ABO/RhD blood type in all samples and compare the detection rate of ABO/RhD antigen and ABO reverse typing and agglutination intensity of the two methods.@*RESULTS@#Three hundred and eight cases of type A (34.4%), 281 cases of type B (31.4%), 210 cases of type O (23.4%), 97 cases of type AB (10.8%), and 896 positive cases of RhD blood type were detected out by two methods. There were no significant differences of ABO/RhD antigen agglutination intensity between two methods (P > 0.05). Except for type AB, the detection rate of ABO reverse typing in infants with type B was significantly higher than that with type A and type O (P < 0.05). The agglutination intensity of type A reverse cell was higher than type B reverse cell (P < 0.05). The fully automatic microcolumn glass sphere method exhibited higher detection rate of ABO reverse typing in the samples of type A and type O group and agglutination intensity of ABO reverse typing in all types as compared with the tube method (P < 0.05). The detection rate and agglutination intensity of ABO reverse typing in term group were significantly higher than those in preterm group (P < 0.05). The fully automatic microcolumn glass sphere method exhibited higher detection rate of ABO reverse typing and agglutination intensity compared with the tube method between two groups (P < 0.05). The detection rate and agglutination intensity of ABO reverse typing in group IV (4-6 months old) were significantly higher than those in groups I, II and III (young than 3 months old) (P < 0.05). The fully automatic microcolumn glass sphere method exhibited higher detection rate of ABO reverse typing in I, II, III groups and agglutination intensity of ABO reverse typing in the 4 groups compared with the tube method (P < 0.05).@*CONCLUSION@#ABO / RhD blood group antigen can be accurated detected in majority of infants, but the detection rate of ABO antibody is related to gestational age and month age of infants. The detection rate and agglutination intensity of the fully automatic microcolumn glass sphere method in ABO reverse typing are higher than those of the tube method, especially for premature infants and children within 3 months old.

Road traffic injury mortality and morbidity by country development status, 2011-2017 / 中华创伤杂志(英文版)

PURPOSE@#This research examined road traffic injury mortality and morbidity disparities across of country development status, and discussed the possibility of reducing country disparities by various actions to accelerate the pace of achieving Sustainable Development Goals target 3.6 - to halve the number of global deaths and injuries from road traffic accidents by 2020.@*METHODS@#Data for road traffic mortality, morbidity, and socio-demographic index (SDI) were extracted by country from the estimates of the Global Burden of Disease study, and the implementation of the three types of national actions (legislation, prioritized vehicle safety standards, and trauma-related post-crash care service) were extracted from the Global Status Report on Road Safety by World Health Organization. We fitted joinpoint regression analysis to identify and quantify the significant rate changes from 2011 to 2017.@*RESULTS@#Age-adjusted road traffic mortality decreased substantially for all the five SDI categories from 2011 to 2017 (by 7.52%-16.08%). Age-adjusted road traffic mortality decreased significantly as SDI increased in the study time period, while age-adjusted morbidity generally increased as SDI increased. Subgroup analysis by road user yielded similar results, but with two major differences during the study period of 2011 to 2017: (1) pedestrians in the high SDI countries experienced the lowest mortality (1.68-1.90 per 100,000 population) and morbidity (110.45-112.72 per 100,000 population for incidence and 487.48-491.24 per 100,000 population for prevalence), and (2) motor vehicle occupants in the high SDI countries had the lowest mortality (4.07-4.50 per 100,000 population) but the highest morbidity (428.74-467.78 per 100,000 population for incidence and 1025.70-1116.60 per 100,000 population for prevalence). Implementation of the three types of national actions remained nearly unchanged in all five SDI categories from 2011 to 2017 and was consistently stronger in the higher SDI countries than in the lower SDI countries. Lower income nations comprise the heaviest burden of global road traffic injuries and deaths.@*CONCLUSION@#Global road traffic deaths would decrease substantially if the large mortality disparities across country development status were reduced through full implementation of proven national actions including legislation and law enforcement, prioritized vehicle safety standards and trauma-related post-crash care services.

Meta-analysis of efficacy and safety of Shexiang Tongxin Dripping Pills combined with conventional therapy of coronary heart disease / 中国中药杂志

The aim of the research was to evaluate the efficacy and safety associated with Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD). We searched 8 electronic databases up to November 2020, including PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP and SinoMed. Eligible studies were clinical trials of Shexiang Tongxin Dropping Pills combined with conventional therapy used in the treatment of coronary heart disease(CHD). The Meta-analysis was performed using STATA 15 software. A total of 21 RCTs(n=2 186) were shortlisted for the Meta-analysis. The results of efficacy evaluation showed that the total effective rate of Shexiang Tongxin Dropping Pills combined with conventional therapy was higher than that of conventional therapy of coronary heart disease(RR=1.20, 95%CI[1.15, 1.26], Z=8.63, P<0.001). Furthermore, Shexiang Tongxin Dripping Pills combined with conventional therapy had better effect on electrocardiogram efficacy(RR=1.24, 95%CI[1.16, 1.34], Z=5.98, P<0.001) and the number of angina attacks(SMD=-2.30, 95%CI[-3.47,-1.14], Z=3.88, P<0.001), the duration of angina attack(SMD=-2.31, 95%CI[-3.07,-1.55], Z=5.97, P<0.001), with lower levels of LDL-C(SMD=-0.73, 95%CI[-1.32,-0.14], Z=2.42, P=0.016), TC(SMD=-1.16, 95%CI[-1.35,-0.96], Z=11.56, P<0.001) and TG(SMD=-0.87, 95%CI[-1.06,-0.68], Z=8.97, P<0.001), and higher levels of HDL-C(SMD=0.87, 95%CI[0.02, 1.71], Z=2.00, P=0.045). The results of safety evaluation showed that the incidence of adverse reactions of Shexiang Tongxin Dropping Pills combined with conventional therapy was lower than that of conventional therapy of coronary heart disease(RR=0.45, 95%CI[0.22, 0.91], Z=2.23, P=0.026). There were significant differences in the above outcome indexes between the two groups. After the Harbord method test, the total effective rate outcome index has publication bias, but the sensitivity analysis of the cut-and-fill method suggested that the result was stable. In general, limited by the quantity and quality of included literature, more high-quality studies are needed to further verify the conclusions of this study.

Pharmacoeconomic evaluation of Suhuang Zhike Capsules using Markov model for inpatients with acute exacerbation of chronic obstructive pulmonary disease / 中国中药杂志

To evaluate the economics of Suhuang Zhike Capsules in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) for inpatients. Based on the published clinical research data, cost-utility analysis was used in this study to evaluate the pharmacoeconomics of Suhuang Zhike Capsules in treatment of AECOPD inpatients from the perspective of medical insu-rance. The test group was treated with Suhuang Zhike Capsules combined with conventional Western medicine, and the control group was treated with conventional Western medicine alone. Treeage software was used to construct a pharmacoeconomic model and perform simulation analysis. The results showed that the cost and output of Suhuang Zhike Capsules combined with the conventional Western medicine were 60 010.18 yuan and 1.92 quality adjusted life year(QALYs), respectively in the simulated 3 years of disease treatment. The cost and output of the conventional Western medicine were 96 730.60 yuan and 1.90 QALYs respectively. Suhuang Zhike Capsules combined with conventional Western medicine required lower cost but achieved higher output, showing cost-utility advantages, so this drug combination was a plan with pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is believed that as compared with the conventional Western medicine, Suhuang Zhike Capsules combined with conventional Western medicine have lower cost and higher output for the treatment of AECOPD inpatients, and it is a treatment plan with pharmacoeconomic advantages.