A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers / 中华外科杂志

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Clinical efficacy of mild therapeutic hypothermia with different rewarming time on neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical efficacy of mild therapeutic hypothermia (MTH) with different rewarming time on neonatal hypoxic-ischemic encephalopathy (HIE).@*METHODS@#A prospective study was performed on 101 neonates with HIE who were born and received MTH in Zhongshan Hospital, Xiamen University, from January 2018 to January 2022. These neonates were randomly divided into two groups: MTH1 group (n=50; rewarming for 10 hours at a rate of 0.25°C/h) and MTH2 group (n=51; rewarming for 25 hours at a rate of 0.10°C/h). The clinical features and the clinical efficacy were compared between the two groups. A binary logistic regression analysis was used to identify the factors influencing the occurrence of normal sleep-wake cycle (SWC) on amplitude-integrated electroencephalogram (aEEG) at 25 hours of rewarming.@*RESULTS@#There were no significant differences between the MTH1 and MTH2 groups in gestational age, 5-minute Apgar score, and proportion of neonates with moderate/severe HIE (P>0.05). Compared with the MTH2 group, the MTH1 group tended to have a normal arterial blood pH value at the end of rewarming, a significantly shorter duration of oxygen dependence, a significantly higher proportion of neonates with normal SWC on aEEG at 10 and 25 hours of rewarming, and a significantly higher Neonatal Behavioral Neurological Assessment score on days 5, 12, and 28 after birth (P<0.05), while there was no significant difference in the incidence rate of rewarming-related seizures between the two groups (P>0.05). There were no significant differences between the two groups in the incidence rate of neurological disability at 6 months of age and the score of Bayley Scale of Infant Development at 3 and 6 months of age (P>0.05). The binary logistic regression analysis showed that prolonged rewarming time (25 hours) was not conducive to the occurrence of normal SWC (OR=3.423, 95%CI: 1.237-9.469, P=0.018).@*CONCLUSIONS@#Rewarming for 10 hours has a better short-term clinical efficacy than rewarming for 25 hours. Prolonging rewarming time has limited clinical benefits on neonates with moderate/severe HIE and is not conducive to the occurrence of normal SWC, and therefore, it is not recommended as a routine treatment method.

The eye irritation test and pharmacokinetic study of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits / 药学实践杂志

Objective To study the eye irritation and the pharmacokinetics of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits. Methods The eye irritation of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits was observed by histological cross-sections of external ocular tissues stained with HE. The aqueous humor of rabbit eyes was extracted by corneal puncture and analyzed by HPLC-MS for pharmacokinetic study. Results Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had no significant irritation on rabbit eyes. The pharmacokinetic parameter showed that the AUC of tacrolimus-loaded cationic nanoemulsion-based in-situ gel was (128.34±13.09) ng·h/ml, which was 1.13 times of tacrolimus-loaded cationic nanoemulsion (113.61±12.36) ng·h/ml and 1.88 times of Talymus® (68.25±10.82) ng·h /ml. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had the advantages of low irritation, long retention time and high bioavailability in rabbit eyes. It has a good potential for clinical application.

Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis / 中华医学杂志(英文版)

BACKGROUND@#Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.@*METHODS@#A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.@*RESULTS@#The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.@*CONCLUSION@#Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.

AG490 regulates JAK2/STAT3 pathway in M2-like macrophages via promoting the proliferation of gastric cancer cells and inhibiting apoptosis / 西安交通大学学报(医学版)

【Objective】 To investigate the regulatory effect of JAK2/STAT3 signaling pathway inhibitor AG490 on the functional phenotype of M2-like macrophages and its effects on proliferation, apoptosis, migration, and invasion of gastric cancer cells. 【Methods】 Human mononuclear cell line THP-1 was induced to differentiate into M0 macrophages by PMA in vitro. The M1-like phenotype was induced by LPS and IFN-γ, and M2-like phenotype was induced by IL-4 and IL-13, respectively, and identified by immunofluorescence labeling CD68, CD86 and CD206. The mRNA expressions of CD163, Arg1, CCL22, PPARγ, IL-10, IL-20 and TNF-α were determined by RT-qPCR. The expressions of key proteins in JAK2/STAT3 signaling pathway were detected by Western blotting. M2-like macrophages were treated with JAK2/STAT3 inhibitor (AG490) to observe the expression level of marker genes for M2 like phenotype. Macrophages were co-cultured with gastric cancer cells, and the effects of the macrophages on proliferation, migration, invasion, and apoptosis of gastric cancer cells were detected by CCK-8 method, healing assay, transwell intracellular Matrigel invasion assay, and flow cytometry. The xenograft tumor model of MKN45 gastric cancer in nude mice was prepared, and the tumor size and quality were observed for 20 days after the model was established. 【Results】 THP-1 cells were induced into M1-like macrophages and M2-like macrophages. M1-like marker (CD86) and M2-like marker (CD206) were identified by flow cytometry. The P38MAPK, JAK2, p-STAT3/STAT3 protein levels of M2-like macrophages treated with AG490 were significantly reduced. The mRNA expression levels of Arg1, CCL22, PPARγ and IL-10 were significantly reduced in the group of M2-like macrophages treated with AG490. Co-culture of M2-like macrophages with gastric cancer cells could promote gastric cancer cell viability, increase migration and invasion ability, and inhibit apoptosis. When the group of M2-like macrophages treated with AG490 was co-cultured with gastric cancer cells, the proliferation activity of MKN-45 cells and MGC823 was significantly lower than that in M2 group (1.047±0.062 vs. 1.426±0.076, 1.149±0.006 vs. 1.301±0.015). Compared to M2 group, the migration (100.0%±5.73% vs. 72%±3.85%) and invasion ability (100.0%±7.40% vs. 60%±6.54%) of MGC823 gastric cancer cells in AG490 treatment group were significantly reduced. The apoptosis rate of MGC823 cells in the AG490 treated group was significantly higher than that in M2 group (27.51%±0.70% vs. 20.82%±0.92%). In the nude mouse xenograft tumor model, the volume and weight of the transplanted tumor collected at day 20 were significantly lower in AG490 treated group than in M2 group (736.04±182.34 vs. 1 080.5±250.57)mm3, (0.64±0.11 vs. 0.87±0.17)g. 【Conclusion】 AG490 downregulates the activation level of JAK2/STAT3 signaling pathway in M2-like macrophages, inhibits M2-type polarization, partially reverses the cancer-promoting function of M2-like macrophages, inhibits proliferation, migration and invasion of gastric cancer cells, and induces apoptosis. The JAK2/STAT3 signaling pathway can be further studied as a potential therapeutic target for gastric cancer.

Concomitant PIK3CA and TP53 Mutations in Breast Cancer:An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis / 한국유방암학회지

Purpose@#PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC).Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. @*Methods@#We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People’s Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. @*Results@#In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205–13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort. @*Conclusion@#Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.

Mediating effect of self-efficacy on self-management ability and self-management behavior in patients with type 2 diabetes mellitus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests.@*METHODS@#In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years.@*RESULTS@#In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect.@*CONCLUSION@#Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.

Research progress on the expression of the RBM20 gene in dilated cardiomyopathy / 中国当代儿科杂志

Dilated cardiomyopathy (DCM) is a significant contributor to heart failure and can lead to life-threatening cardiovascular events at any stage. RNA-binding motif protein 20 (RBM20) gene mutation is known to be one of the causes of DCM. This mutation exhibits familial aggregation and is associated with arrhythmias, increasing the risk of sudden and early death. This article delves into the characteristics of the RBM20 gene, highlighting its role in regulating alternative splicing of the TTN gene and calcium/calmodulin-dependent protein kinase type II gene. Furthermore, the article provides a summary of treatment options available for DCM caused by RBM20 gene mutations, aiming to enhance clinicians' understanding of the RBM20 gene and provide new ideas for precision medicine treatment.

Optimal processing technology of Zhangbang vinegar-processed Olibanum with multi-indicator-response surface methodology and anticoagulant effect evaluation / 中国中药杂志

This study first optimized the processing technology for Zhangbang vinegar-processed Olibanum and investigated its in vitro anticoagulant activity. A multi-index-response surface methodology was used, with yield, powder yield, and the relative percentage of the content of six non-volatile components [11-keto-boswellic acid(KBA), 3-acetyl-11-keto-boswellic acid(AKBA), β-elemonic acid, α-boswellic acid(α-BA), β-boswellic acid(β-BA), and α-acetyl-boswellic acid(α-BA)] and three volatile components(octyl acetate, incensole, and incensole acetate) as evaluation indicators. Analytical hierarchy process(AHP) combined with coefficient of variation method was used to calculate the weight of each indicator and calculate the comprehensive score(OD). Furthermore, response surface methodology was used to investigate the effects of frying temperature(A), burning time(B), rice vinegar dosage(C), and steaming time(D) on the processing technology of vinegar-processed Olibanum. Vinegar-steamed Olibanum was prepared according to the optimal processing technology for in vitro anticoagulant experiments. The results showed that the weights of octyl acetate, incensole, incensole acetate, KBA, AKBA, β-elemonic acid, α-BA, β-BA, α-ABA, yield, and powder yield were 0.358 2, 0.104 5, 0.146 4, 0.032 9, 0.123 7, 0.044 4, 0.022 1, 0.042 2, 0.110 1, 0.012 2, and 0.0032, respectively. The optimal processing technology for Zhangbang vinegar-processed Olibanum was as follows. Olibanum(50 g) with a particle size of 1-5 mm was continuously stir-fried at a low heat of 150-180 ℃ until in a gel-like state, ignited for burning for 15 s, sprayed with 7.5 g of rice vinegar(15%), and steamed for 3 min without fire. Subsequently, the cover was removed, and the product was continuously stir-fried at 150-180 ℃ until in a soft lump shape, removed, cooled, and crushed. The results of the in vitro anticoagulant experiments showed that compared with the blank group, both Olibanum and vinegar-processed Olibanum significantly prolonged the activated partial thromboplastin time(APTT), thrombin time(TT), and prothrombin time(PT) of rat platelet-poor plasma(PPP), and the effect of vinegar-processed Olibanum was significantly better than that of Olibanum(P<0.05). The optimized processing technology for Zhangbang vinegar-processed Olibanum is stable, feasible, and beneficial for the further development and utilization of Olibanum slices. At the same time, using the content of volatile and non-volatile components, yield, and powder yield as indicators, and verifying through pharmacological experiments, the obtained results are more reasonable and credible, and have positive guiding significance for the clinical application of characteristic processed Olibanum products.

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.

Study on genetics and early diagnosis of early onset epileptic encephalopathy of unknown etiology / 中华实用儿科临床杂志

Objective:To explore the genetic etiology and the value of early diagnosis of early onset epileptic encephalopathy (EOEE) with unknown etiology.Methods:A total of 60 children with EOEE of unknown etiology were prospectively enrolled in the outpatient and inpatient departments of Fujian Provincial Hospital from January 2018 to January 2021.Peripheral blood was collected prospectively for whole-exome sequencing and copy number variation (CNV) detection to analyze the clinical characteristics and genetic sequencing results of the children.Results:Twenty-four patients with EOEE-related pathogenic or suspected pathogenic mutations were detected, including infantile spasms (10 cases), Dravet syndrome (3 cases), pyridoxine-dependent epilepsy (1 case) and ohtahara syndrome (1 case), and unknown epileptic encephalopathy (9 cases). The onset age of EOEE-related patients ranged from 1 day to 11 months (median age was 4.2 months), the treatment age ranged from 2 days to 4 years (median age was 10 months), and the age of diagnosis was controlled within 1 month after treatment.There were 20 cases (33.3%) single gene variants and 4 cases (6.7%) CNV variants.A total of 13 genes were involved: KCNQ2, SCN1A, SCN8A, CACNA1E, CDKL5, PPP3CA, PCDH19, TSC1, TSC2, ZEB2, ALDH7A1, DCX and HNRNPU.The 4 CNV abnormalities were 17p13.3 deletion, 11q23.3q25 deletion, 1q36.31-p36.33 deletion, 1q43-1q44 deletion and Xp22.33 duplication, respectively.Totally, 20 mutations were new loci reported for the first time at home and abroad; 11q23.3q25 deletion that resulted in infantile spasm was first reported at home and abroad.Infantile spasm caused by ZEB2 mutation and epileptic encephalopathy caused by PPP3CA gene were both reported for the first time in China. Conclusions:Gene and CNV are important potential causes of children suffering from EOEE.When the etiology is unclear, the combination of whole-exome sequencing and CNV sequencing technology can improve the diagnosis level of genetic etiology of children with EOEE.The early genetic detection of these children can early diagnose and accurately treat epilepsy.

Discussion on the management of Suspected Unexpected Serious Adverse Reaction reports during clinical trials / 中华医学科研管理杂志

Objective:According to the new GCP regulations issued by national medical products administration, this paper discusses the management mode of Suspected Unexpected Serious Adverse Reaction (SUSAR) reports during clinical trials.Methods:Combined with GCP regulations and working practice, this paper comprehensively analyzes the issues identified and related reasons for the management of SUSAR reports during clinical trials, and propose possible countermeasures.Results:There are some problems in the management of SUSAR reports among different stakeholders during clinical trials, such as defects in the performance of obligations and responsibilities. It is suggested that investigators should be more carefully to fulfill GCP responsibilities; sponsors should be more accurately implement the reporting procedures; institutional and ethical supervision should also be strengthened to assure better conduct of clinical trials.Conclusions:Multi-party collaboration and management mode play crucial roles in conducting high-quality clinical trials.

The characteristics of cortical activation when hemiplegic stroke survivors walk assisted by functional electrical stimulation / 中华物理医学与康复杂志

Objective:To explore the characteristics of cortical activation during the stimulation-assisted walking of hemiplegic stroke survivors using functional near-infrared spectroscopy (fNIRS).Methods:Eight stroke survivors with right hemiplegia (average age 44.4±7.2 years) in a self-controlled study each walked at 2km/h on a treadmill, alone and assisted by functional electronic stimulation (FES). Real-time near-infrared spectroscopic images were recorded. The Matlab NIRS-SPM toolkit was employed to calculate the changes in oxyhemoglobin concentration in different cortical regions. A general linear model was evaluated which integrated the task effects, and version 20.0 of the SPSS statistical software was used to perform single sample or paired sample t-tests of the beta values so as to produce activation hot maps of the significant differences.Results:During unassisted walking channels 8, 10, 11, 13-20, 23-28, 30 and 32-37 were significantly activated. During FES-assisted walking it was the same channels plus channels 9 and 22, 31. The results suggest that in walking the cortical regions activated are mainly located in M1 of the unaffected hemisphere, supplemented by M1 and SMA, PMC and S1 in the affected hemisphere. There were significant differences in the activation of channels 9, 24, 27, 32, 33 between the two walking tasks. FES-assistance enhances S1 activation on the unaffected side, as well as the SMA and PMC of the affected side more significantly.Conclusions:Bilateral asymmetrical activation is found mostly in M1 during walking with or without FES assistance. FES assistance significantly strengthens the compensatory activation of the PMC and SMA of the affected hemisphere while walking for those with hemiplegia.

Reproducibility study of Ovarian-Adnexal Reporting and Data System in describing adnexal masses / 中华超声影像学杂志

Objective:To investigate the intra- and inter-observer agreements of different experiencers using the Ovaria-adnexal Reporting and Data System (O-RADS) in the evaluation of adnexal masses.Methods:Totally 48 patients with adnexal masses (48 masses, mean size 9.5±4.7 cm, range 2.3-18.6 cm) found by ultrasound examination in the Third Affiliated Hospital of Sun Yat-sen University, from May 2019 to March 2020 were retrospectively analyzed. All the masses were confirmed by pathology or surgery. Four observers were divided into 2 senior doctors (Doctor 1 and Doctor 2) and 2 junior doctors (Doctor 3 and Doctor 4). Each observer independently evaluated adnexal masses twice using ultrasound O-RADS before and after systematic training, with an interval of 60 days. The intra-observer and inter-observer agreements were analyzed before and after training.Results:The inter-observer agreement between senior doctors were both excellent before and after systematic training (weight Kappa: 0.833 vs 0.802, percentage of agreement: 83.3% vs 81.3%). Whereas there was difference in the inter-observer agreement between non-experienced observers before and after training (weight Kappa: 0.399 vs 0.824, percentage of agreement: 50.0% vs 77.1%). After training, inter-observer agreement between junior doctors was significantly improved and comparable to senior (weight Kappa: 0.824 vs 0.802, percentage of agreement: 77.1% vs 81.3%). Before and after systematic training, the intra-observer agreements of the same doctor, the senior physicians were better than the junior (weight Kappa: 0.882 and 0.843 vs 0.440 and 0.605; percentage of agreement: 87.5% and 83.3% vs 58.3% and 54.2%).Conclusions:O-RADS risk classification system is a highly reproducible method in the subjective assessment of an adnexal mass among observers with varying levels of expertise. However, systematic training before clinical application is necessary and effective for non-experienced observers.

Research progress of patient-specific organ doses from CT / 中国辐射卫生

@#The radiation risk caused by CT examination is of great concern. Organ dose is considered to be the most significant technical parameter for quantifying the patient radiation dose and assessing the corresponding risk. At present, the methods to obtain patient organ dose caused by CT examination mainly include physical phantom measurement, direct human body measurement, dose conversion coefficient, Monte Carlo simulation, and dose calculation software. Although different methods have their own characteristics and application, the individualization of organ dose is always the goal of radiation protection and dosimetry research. Patient-specific phantom developed with artificial intelligence and GPU-accelerated Monte Carlo simulation make it possible to calculate the patient-specific organ dose, and the patient-specific organ dose extrapolated by the CT detector signal provides a new solution.

Effect of Danggui Niantongtang on Autophagy and Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocyte / 中国实验方剂学杂志

ObjectiveTo explore the effect of Danggui Niantongtang （DGNTT） on cell apoptosis and autophagy in rheumatoid arthritis （RA） fibroblast-like synoviocytes （FLS）. MethodRA-FLS were isolated and cultured from the synovial tissue of RA patients. The cells were treated with 10% blank serum （blank control group）， 10% sera containing low， medium and high doses of DGNTT. Wound healing assa and cell invasion test were applied to observe the effect of RA-FLS invasion technique. The apoptosis and autophagy level of RA-FLS cells was detected by Hoechst33342 method and monodansylcadaverine （MDC） staining. The mRNA and protein expression levels of B cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， microtubule-associated protein 1 light chain 3 （LC3）， autophagy key molecular yeast Atg6 homolog 1 （Beclin1） were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）and Western blot. ResultCompared with the blank control group，each dose of serum could slow down the wound healing and significantly Reduce the number of RA-FLS cells invading the lower chamber（P<0.01），the mRNA and protein expression levels of Bcl-2，LC3，Beclin1 were significantly decreased（P<0.01）， and Bax were significantly increased（P<0.01）. Hoechst33342 results showed that low， medium and high doses DGNTT could promote RA-FLS cell apoptosis. After MDC staining，autophagosome in low， medium and high doses DGNTT decreased significantly（P<0.01）. ConclusionDanggui Niantongtang can effectively inhibit the proliferation of fibroblast-like synoviocytes. Its mechanism may be related to promote apoptosis and inhibit autophagy of fibroblast-like synoviocytes.

Effect of Danggui Niantongtang on Expression of Autophagy-related Proteins LC3， Beclin1 and p62 in Rats with Adjuvant Arthritis Differentiated into Wind-damp-heat Impediment / 中国实验方剂学杂志

ObjectiveTo observe the preventive and control effects of Danggui Niantongtang against adjuvant arthritis differentiated into wind-damp-heat impediment in rats and its influences on the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 （LC3）， homolog of yeast Atg6 （Beclin1） and p62. MethodThe six-week-old male SD rats were randomly divided into the normal group， wind-damp-heat impediment model group， low-， medium-， and high-dose Danggui Niantongtang （5.67， 11.34， 22.68 g·kg-1） groups， and methotrexate （MTX， 1.35 mg·kg-1） group， with 10 rats in each group. A rat model of adjuvant arthritis was established by subcutaneous injection of inactivated Mycobacterium tuberculosis into the tail root， followed by exposure to the manual climatic box for 16 d for inducing the wind-damp-heat impediment. The drugs were administered intragastrically on the day of immunization for 28 d. The general conditions of rats were observed and the swelling degree of toes and arthritis index （AI） were detected. The pathological changes in the synovial tissues of the knee joints were observed by hematoxylin-eosin （HE） staining. The mRNA expression levels of LC3， Beclin1， and p62 in the synovial tissues were measured by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， followed by the assay of their protein expression by Western blot and immunohistochemistry. ResultCompared with the normal group， the wind-damp-heat impediment model group exhibited significantly increased swelling degree of toes （P<0.01）， increased AI （P<0.01）， proliferated synovial cells （P<0.01）， up-regulated LC3 and Beclin1 protein and mRNA expression （P<0.01）， and down-regulated p62 protein and mRNA expression （P<0.01） after 16， 20， 24， 28-d medication. Compared with the wind-damp-heat impediment model group， each medication group displayed alleviated toe swelling and synovial hyperplasia to different degrees， decreased mRNA and protein expression levels of LC3 and Beclin1 （P<0.01）， and increased p62 mRNA and protein expression （P<0.05，P<0.01）， with the best outcomes observed in the medium-dose Danggui Niantongtang group. ConclusionDanggui Niantongtang effectively relieves adjuvant arthritis due to wind-damp-heat impediment in rats， which may be related to its regulation of the expression of autophagy-related proteins LC3， Beclin1， and p62 and the inhibition of autophagy.

Efficacy of relocation and expansion pharyngoplasty by suspension sutures in the treatment of OSAHS with soft palate oropharyngeal obstruction / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the efficacy of relocation and expansion pharyngoplasty by suspension sutures in the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: Seventy-three patients(including 60 males and 13 females) with OSAHS admitted to the department of otorhinolaryngology of our hospital in recent two years were retrospectively analyzed. All the patients had velopharyngeal obstructionevaluated by electronic endoscopic Müller test and were divided into control group (34 cases) and observation group (39 cases). The patients in the control group were performed modified uvulopalatopharyngoplasty, while those in the observation group were performed relocation and expansion pharyngoplasty by suspension sutures.The scores of ESS, AHI and LSaO2 before and after treatment were collected and compared. Results: The total effective rate of the observation group was 94.87%, which was significantly higher than 79.41% of the control group. The AHI was lower and LSaO2 value was higher (χ2=-1. 896,-1. 968,P<0.05)in the observation group. The sleeping symptoms and quality of life of the two groups were significantly improved. The ESS score of the observation group was decreased more significantly than that of the control group after treatment, and the difference was statistically significant (χ2=-1.451,P<0.05). The incidence of foreign body sensation in pharynx of the observation group (89.74%) was higher than that of the control group (55.88%), and the postoperative bleeding and postoperative recurrence rate (0.00%, 2.56%) was lower than that of the control group (8.82%, 14.70%)with statistical significance (χ2=4.738,4.249,4.119,P<0.05).The incidence of transient nasopharyngeal reflux in both groups was low and statistically insignificant (χ2=0.629,P>0.05). Conclusions: Preoperative strict screening of indications plays an important role in the selection of palatopharyngeal surgery methods and curative effect. Relocation and expansion pharyngoplasty by suspension sutures can improve the clinical efficacy of OSAHS with better safety and less recurrence.

Effect of Danggui Niantongtang on Key Factors of Extrinsic and Intrinsic Apoptotic Pathway in Synovial Tissue of Adjuvant Arthritis Rats / 中国实验方剂学杂志

Objective:To observe the effect of Danggui Niantongtang on the protein and mRNA expression of key regulatory factors of the extrinsic and intrinsic apoptotic pathway in synovial tissue of adjuvant arthritis （AA） rats， and to further explore the mechanism of Danggui Niantongtang in the prevention and treatment of rheumatoid arthritis. Method:The general condition of AA rats， including its body weight， were observed. The changes of toe volume were detected by toe volume meter. Histopathological changes of synovium of knee joint were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expression levels of tumor necrosis factor receptor super family 6 （Fas）， Fas-associating protein with a novel death domain（FADD）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cysteinyl aspartate specific proteinase Caspase-3 （Caspase-3） were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with the normal group， the toe volume of the model group increased significantly （<italic>P</italic><0.01）， with significantly proliferated synovial cells， significantly reduced mRNA and protein expression levels of Fas， FADD， Bax and Caspase-3 in synovial tissues（<italic>P</italic><0.05，<italic> P</italic><0.01）， and significantly increased Bcl-2 level （<italic>P</italic><0.01）. Compared with the model group， the swelling degree of toes in Danggui Niantongtang group and Tripterygium group was significantly alleviated （<italic>P</italic><0.01）， with significantly improved synovial hyperplasia， significantly increased mRNA and protein expression levels of Fas， FADD， Bax and Caspase-3 （<italic>P</italic><0.05， <italic>P</italic><0.01）， and significantly decreased expression levels of bcl-2 mRNA and protein （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Danggui Niantongtang can effectively reduce joint swelling and abnormal proliferation of synovial tissue in AA rats. Its mechanism may be related to regulating the expression of Fas， FADD， Bax， Bcl-2 and Caspase-3， and promoting the apoptosis of synovial cells.

Effect of Microelectronic Electromyography Bridge on Motor Function of Extensor Carpi Radialis Longus in Patients with Cervical Spinal Cord Injury / 中国康复理论与实践

Objective:To observe the effect of microelectronic EMG bridge (EMGB) training on the motor function of extensor carpi radialis longus in patients with complete cervical 5 spinal cord injury. Methods:From March, 2016 to March, 2017, 20 patients with complete cervical 5 spinal cord injury were randomly divided into control group (n = 10) and experimental group (n = 10). The control group received routine wrist extensor muscle training, and the experimental group received EMGB training in addition, for 180 days. The motor function of the affected limb was evaluated by sEMG of extensor carpi radialis longus, Manual Muscle Test (MMT), Wolf Motor Function Test (WMFT) and Spinal Cord Lesion Independence Measure (SCIM). Results:After treatment, the peak value and average value of sEMG of extensor carpi longus of both sides increased in both groups (t > 2.510, P < 0.05), the peak value and average value of the left side were higher (t > 2.759, P < 0.05), and the peak value of the right side was higher (t = 2.691, P < 0.05) in the experiment group than in the control group, however, there was no significant difference in average value of the right side between two groups (t = 2.063, P = 0.054). The scores of MMT increased in both groups (t > 2.569, P < 0.05), and were higher in the experimental group than in the control group (t > 2.278, P < 0.05). The scores of WMFT and SCIM increased in both groups (t > 3.839, P < 0.05), however, there was no significant difference between two groups (t < 1.498, P > 0.05). Conclusion:EMGB training could improve the motor function of extensor carpi radialis longus in patients with complete cervical 5 spinal cord injury.