ObjectiveExploring the role of microRNA126 （miRNA126） in chronic kidney disease combined with atherosclerosis （CKD AS） by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and the mechanism of Shenshuai Xiezhuo decoction in the intervention of CKD AS rats with 5/6 nephrectomy combined with high-fat feeding. MethodA total of 60 SD rats were randomly divided into sham operation group， model group， losartan group， and low， medium， and high dose groups of Shenshuai Xiezhuo decoction. The CKD AS rat model was established by 5/6 nephrectomy combined with high-fat feeding for 10 weeks. The low， medium， and high dose groups （6.0， 12.0， 24.0 g·kg^-1·d^-1） of Shenshuai Xiezhuo decoction and the losartan group （20 mg·kg^-1·d^-1） were gavaged， and the corresponding intervention was carried out for eight weeks. Then， the rats were killed， and samples were collected for corresponding detection. Fully automated biochemical analyzers were used to detect kidney function and blood lipids in rats： blood creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） and Masson staining of aortic tissue and pathological observation under a light microscope were carried out， and autophagosomes and autophagy lysosomes were observed by transmission electron microscopy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA levels of miRNA126， PI3K， Akt， and mTOR in rats， and Western blot was used to determine the protein expression levels of phosphorylated （p）-PI3K， PI3K， p-Akt， Akt， p -mTOR， mTOR， benzyl chloride 1 （Beclin-1）， and microtubule-associated protein light chain 3Ⅱ/Ⅰ （LC3Ⅱ/LC3Ⅰ）. ResultCompared with the sham operation group， the serum SCr， BUN， TC， TG， and LDL-C in the model group were significantly increased （P<0.01）. Compared with the model group， the SCr， BUN， TC， TG， and LDL-C were decreased in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction （P<0.05）. Compared with the sham operation group， thickening plaques， infiltration of mononuclear macrophages， a small number of foam cells， disordered arrangement of smooth muscle fibers in the tunica media， and increased collagen fibers were observed in the model group， and the lesions in the losartan group and Shenshuai Xiezhuo decoction groups were alleviated compared with those in the model group. Compared with the model group， the number of autophagosomes and autophagy lysosomes increased in the medium and high dose groups of Shenshuai Xiezhuo decoction. Compared with the sham operation group， the expression of miRNA126 in the aortic tissue of the model group was significantly decreased （P<0.01）， and the mRNA expressions of PI3K， Akt， and mTOR were significantly increased （P<0.01）. Compared with the model group， the expression of miRNA126 in the aortic tissue of rats in high， medium， and low dose groups of Shenshuai Xiezhuo decoction and losartan group was significantly increased （P<0.01）， while the mRNA expressions of PI3K， Akt， and mTOR were significantly decreased （P<0.01）. Compared with the sham operation group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the model group were significantly increased （P<0.01）， while the protein levels of Beclin-1， LC3Ⅰ， and LC3Ⅱ were significantly decreased （P<0.01）. Compared with the model group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction were decreased （P<0.05）， while the protein levels of Beclin-1 and LC3Ⅱ/LC3Ⅰ were increased （P<0.05）. ConclusionThe expression of miRNA126 is decreased in the aortic tissue of CKD AS rats， and the PI3K/Akt/mTOR pathway is activated to inhibit autophagy flux. Shenshuai Xiezhuo decoction regulates the PI3K/Akt/mTOR signaling pathway through miRNA126， restores the autophagy of aortic endothelial cells， protects the damage of CKD vessels， reduces the formation of As plaques， and slows the development of cardiovascular complications.

Objective:To investigate the pathway of self-disclosure to posttraumatic growth in patients after cervical cancer surgery, and to provide reference for improving the level of posttraumatic growth in patients.Methods:A convenient sampling method was used to investigate 300 patients with cervical cancer after surgery in Shandong Provincial Hospital Affiliated to Shandong First Medical University from June to November 2022 by using general data questionnaire, Distress Disclosure Index (DDI), Connor-Davidson Resilience Scale (CD-RISC), the Shortened Chinese Version of the Family Resilience Assessment Scale (FRAS-C) and the Posttraumatic Growth Inventory (PTGI) in a cross-section study.Results:A total of 290 valid questionnaires were collected, with an effective recovery rate of 96.7%. The patients were aged 23-70(48.13 ± 10.39) years. The scores of self-disclosure, resilience, family resilience and posttraumatic growth were (46.41 ± 9.82), (67.06 ± 14.63), (108.18 ± 11.06) and (58.24 ± 17.86) respectively. The results of pathway analysis showed that self-disclosure could not only directly predict posttraumatic growth, but also indirectly predict posttraumatic growth through the mediating role of resilience and family resilience, and the chain mediating role of resilience and family resilience, respectively. The direct effect of self-disclosure on posttraumatic growth was 0.236(95% CI 0.138-0.335), and the chain mediating effect of family resilience and resilience between self-disclosure and posttraumatic growth was 0.036(95% CI 0.018-0.060). Conclusions:Medical staff should not only consider the direct influence of self-disclosure on posttraumatic growth, but also pay attention to improve the resilience and family flexibility of patients after cervical cancer surgery, so as to promote their posttraumatic growth.

Objective: To explore the independent predictors for recurrence-free survival (RFS) in patients with papillary renal cell carcinoma (PRCC), and establish a nomogram to predict individual 2-year RFS. Methods: The data of patients diagnosed in Xijing Hospital of the Air Force Medical University from June 2009 to May 2018 were retrospectively analyzed. A total of 71 patients with primary T_1-4N₀M₀ unilateral tumor were included in this study. The median age was 54 (range from 25 to 83) years. There were 51 males and 20 females. There were 27 cases of typeⅠ, 44 cases of type Ⅱ, 36 cases of left tumor and 35 cases of right tumor. Patients with clinical Ⅰ, Ⅱ, Ⅲ, Ⅳ stage were 47 cases, 12 cases, 9 cases and 3 cases, respectively. Tumor necrosis occurred in 15 cases (21.1%). The average preoperative alkaline phosphatase (ALP) was 89.0(43.0-217.0) U/L, the average preoperative hemoglobin (Hb) was (132.5±19.9) g/L, with 20 cases (28.2%) of Hb<120 g/L before surgery; the average of preoperative Hb was (132.5±19.9) g/L, among which 20 cases (28.2%) had Hb<120 g/L before surgery; the average of preoperative neutrophils/lymphocytes (NLR) was 2.40 (1.03-6.77); radical nephrectomy was performed in 43 patients and nephrectomy was performed in 28 patients. The 1-, 2-, and 3-year RFS were calculated using Kaplan-Meier method and the differences among different subgroups were assessed using Log-rank test. Univariate and multivariate Cox regression analysis were used to identify the independent predictors for RFS, and the nomogram was developed using R software according to the results of multivariate Cox regression analysis. Furthermore, the predictive ability of the nomogram was internally validated using the Bootstrap method by calculating the C-index and drawing the calibration plot. Results: After a median follow-up of 41 ( range from 25 to 83) months, 16 (22.5%) recurrence occurred, including 4 local recurrence and 12 distant recurrence, and 11 (68.8%) patients relapsed within 2 years after surgery. The 1, 2, and 3-year RFS were 88.6%, 80.4%, and 78.7%, respectively. Clinical stage Ⅱ (HR=3.655, 95%CI 1.036-12.890, P=0.044) and stage ≥Ⅲ(HR=3.654, 95%CI 1.008-13.248, P=0.049), preoperative ALP≥90U/L(HR=3.274, 95%CI 1.044-10.267, P=0.042), preoperative Hb<120 g/L (HR=4.771, 95%CI 1.553-14.660, P=0.006), and preoperative NLR≥2.40(HR=4.701, 95%CI 1.238-17.849, P=0.023) were identified as independent risk factors for RFS. On internal validation, the nomogram which integrates the four predictors of clinical stage, preoperative ALP, preoperative HB and preoperative NLR, has a good predictive performance (C-index =0.829, 95%CI 0.819-0.839). Conclusions In the present study based on single center data, clinical stage Ⅱ and ≥Ⅲ, preoperative ALP≥90 U/L, preoperative Hb<120 g/L and preoperative NLR ≥2.40 were independent predictors for postoperative RFS in patients with PRCC, and a new preoperative nomogram for predicting individual postoperative 2-year RFS was established, which would be helpful for urologists to develop more systematic treatment plans.

Objective To investigate the association between serum total testosterone (TT ) levels and type 2 diabetes(T2DM )and any gender differences in elderly patients. Methods Based on the Aging Health database built from 2008 to 2012 ,935 elderly individuals over 60 years old with a mean age of 65.8 years receiving physical examinations were included.According to the 1999 WHO criteria for diabetes ,participants were assigned into four groups :a T2DM group(n＝298) ,an impaired fasting glucose(IFG)group(n＝26) ,an impaired glucose tolerance(IGT)group(n＝121) ,and a normal glucose regulation(NGR)group(n ＝ 490).We measured serum TT by ELISA and analyzed the distribution patterns in the groups.Furthermore ,we examined the gender-specific correlation of TT with T2DM and homeostasis model assessment of insulin resistance (HOMA-IR). Results The prevalence of T2DM in the participants was 31.9%(298/935).One-way ANOVA analysis showed that the TT level was higher in the NGR group than in the T2DM and IGT groups (PANOVA＝ 0.001) . Logistic regression analysis indicated a significant protective association between TT and T 2DM in the elderly.Every one unit of increase in the SD of the TT level was accompanied by a 23% reduction in the risk for T2DM (P＝ 0.001).Further gender-stratification analysis suggested that the protective role of TT against T2DM only existed in males (OR＝ 0.55 ,95% CI :0.44-0.68 ;P＜ 0.001).After adjustment for age ,blood pressure ,blood lipids ,and waist circumference ,the protective role of TT against T2DM in males still remained (OR ＝ 0.68 ,95% CI :0.53-0.86 ;P ＝ 0.002 ).Pearson correlation analysis also indicated a significant negative correlation between TT and HOMA-IR in older males(P＝0.002).As for older females ,no significant correlation of TT with T2DM and HOMA-IR was found. Conclusions The serum TT level might be an independent protective factor for T 2DM in older males ,as evidenced by its correlation with improved insulin resistance status ,which is not present in older females.

Objective To investigate the risk factors and appropriate screening methods for diabetic peripheral neuropathy (DPN ). Methods This research is a multicenter ,randomized ,cross-sectional study. Questionnaires ,physical examinations and laboratory tests were performed on 1054 elderly diabetic outpatients at 13 hospitals in urban and rural areas of Beijing. Patients were screened for DPN with the five physical examinations recommended by the Diabetes Branch of the Chinese Medical Association. They were divided into a confirmed DPN group(n=449 ,42.6％ ) ,a suspected DPN group(n=276 ,26.2％ ) ,and a non-DPN group(n=329 ,31.2％ ).Multivariate logistic regression was used to analyze risk factors for DPN.The sensitivity ,specificity ,Youden index ,and area under the receiver operating characteristic (ROC)curve were calculated and used for evaluating each test and their combinations in screening DPN and for choosing the opitmal test combination. Results The differences in age ,family income ,duration of diabetes ,glycated hemoglobin(HbA1c) ,hypoglycemia ,and dyslipidemia among three groups were statistically significant (all P<0.01). The decision whether or not to initiate metformin therapy ,metformin doses and DPN prevalence in patients on long-term metformin therapy showed statistically significant differences among three groups (all P<0.01). The differences in the prevalences of cerebral infarction ,diabetic retinopathy ,and peripheral vascular disease among three groups were statistically significant (all P< 0.05).Multivariate Logistic regression analysis suggested that levels of HbA1c ,hypoglycemia ,LDL cholesterol ,whether or not metformin use , metformin dose ,and duration of metformin use were risk factors for DPN in elderly diabetics (all P<0.05) . The combined methods of ankle reflex ,vibratory sensation and temperature sensation used for screening DPN showed the best results with a sensitivity of 94.1％ ,specificity of 75.3％ ,an area under the ROC curve of 0.847 ,and a Yoden index of 0.6945. Conclusions The prevalence of DPN in elderly diabetic outpatients at third-level referral hospitals in Beijing is high. Poor glycaemic control ,repeated episodes of hypoglycemia , metformin use and its daily dose and duration are risk factors for DPN in elderly diabetics.We should focus on strengthening the DPN screening and management of high-risk population.Symptoms of peripheral neuropathy plus ankle reflex ,vibratory and temperature sensations are simple ,rapid and reliable DPN-screening methods ,and can be promoted in outpatient department and primary hospitals.

OBJECTIVE:To provide reference for improving the registration success rate of new drug research and develop-ment(R&D)enterprises after adjusting drug registration system in China. METHODS:The national drug policies,regulations and related documents were comprehensively studied and combed to explore the main contents of drug registration system adjustment and its effects on the R&D forms,drug patent and on-site verification. The suggestions were put forward. RESULTS & CONCLU-SIONS:The adjusted drug management system showed new definitions for new drugs and generic drugs in China,as well as de-tailed requirements and regulations for drug R&D conditions,process and on-site inspection. It enhanced the protection of patents and patentees. The new drugs should be assessed its market value and clinical advantages. Data contents and requirements for drug registration declaration were made the relevant adjustments. New drug R&D enterprises should develop drug listed license manage-ment system as early as possible based on the implementation of listed license management system pilot,improve its efficiency and benefit. The new drug R&D should notice the clinical efficacy and demand of market,focus on the drugs with good clinical effica-cy in common diseases,frequently-occurring diseases and major diseases;and those for treating rare diseases,the elderly and chil-dren disease can use easy access or fast track to accelerate the speed of drug registration. New drug R&D enterprises should im-prove the R&D conditions,and standardize the management of development process to ensure the effective and smooth develop-ment.

Objective To explore the qualitative evaluation of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant thyroid nodules (TNs).Methods Totally 110 outpatients with 132 TNs underwent CEUS were enrolled in this study in Jinling Hospitall Medical School of Nanjing University (Nanjing General Hospital of Nanjing Military).Nanjing General Hospital of Nanjing Military All the nodules underwent ultrasound guided fine needle aspiration biopsy (FNAB).113 TNs were histologically diagnosed,the characteristics of enhancement for each noudle were scored.The characteristicsof enhancement between benign and malignant TNs were compared by chi-square test.The receiver operating characteristic (ROC) curve analysis were conducted to determine the diagnostic values of thyroid CEUS.Results Contrast-enhanced patterns were significantly different between benign and malignant TNs in the degree,homogeneity of enhancement,enhanced ring and boundary,shape and size of the enhanced lesions (x2=23.85,P ＜ 0.001;x2=7.43,P=0.04;x2=34.54,P ＜ 0.001;x2=25.7,P ＜ 0.001;x2=53.10,P ＜ 0.001;x2=22.78,P ＜ 0.001;x2=30.90,P ＜ 0.001).Contrast-enhanced patterns were not significantly different between benign and malignant TNs in the process and completeness of enhancement.Malignant lesions had concentric (79.5％),inhomogeneous (89.0％) and low (71.1％) enhanced with irregular (79.5％) and unclear (64.4％) boundary and bigger size (63.0％).The typical CEUS feature of benign nodules was peripheral ring hyperenhancement (34.7％).According to ROC curve,the cut off value was 3.5 points.The area under the ROC curve (AUC) for CEUS was 0.862 (95％CI:0.797-0.927).The sensitivity,specificity and accuracy for CEUS were 80.8％,79.6％,80.3％ respectively.Conclusion The pattem of CEUS may assist in differential diagnosis of benign and malignant TNs.

Objective: To investigate the prevalence of biting pencils among pupils living in Harbin, Guangzhou, and Beijing and to compare the differences among these cases. Methods: Stratified sampling method was used to select four elementary schools in Harbin and Guangzhou from April 2015 to April 2016. Firstly, Simple random sampling method was used in every grade (grade 1-grade 5) to select 3 or 4 classes (71 classes in total).After the sample selection, questionnaire surveys were conducted among pupils and their guardians (anyone of their guardians) who belonged to these classes. Secondly, the study extracted part of these pupils to conduct a field survey. Every school was classified by grade, and every grade adopted the method of random sampling to select one classes (20 classes in total). Meanwhile, the study randomly selected pupils from 10 classes in 2 elementary schools in Beijing. All together, 1 627 pupils participated in the field survey. The questionnaire included general information about the students and their guardians, the situation of biting pencils, the awareness of the harm of biting pencils, etc.; the field survey considered if participates' pencils have tooth marks and the severity of the marks, etc. χ² was applied to test and compare the differences among pupils of different genders and different cities. The comparison focused on the proportion of students who bited pencils, the proportion of pencils with tooth marks and the proportion of students and guardians already awared of the harm of biting pencils, etc. Results: The number of the valid questionnaires in Harbin and Guangzhou were 1 842, and 1 210, respectively. The occurrence rate of pupils biting pencils in Harbin (18.0% (333/1 842)) was higher than that in Guangzhou (11.3% (137/1 210)) (χ²=29.16, P=0.001). Specifically, in Harbin, the rate of boys biting pencils was 21.9% (212/965), which was higher than girls (13.8% (121/877)) (χ²=27.04, P=0.001). Similarly, in Guangzhou, the rate of boys biting pencils was 14.5% (92/632), which was also higher than girls (7.7% (45/578)) (χ²=15.34, P=0.001). The awareness rate of the harm of biting pencils among students from these two cities were 88.5% (1 611/1 819), and 90.8% (1 098/1 208), respectively, and the difference was statistically significant as well (χ²=4.39, P= 0.020). Compared with these data, the awareness rate of the harm of biting pencils among guardians from these two cities were 74.7% (1 339/1 791), and 79.4% (832/1 047), respectively as well as the statistically significant difference appeared (χ²=9.83, P=0.007). The result of field survey showed the rate of tooth-marked pencils in Harbin, Guangzhou and Beijing was 30.5% (187/613), 14.8% (79/534), and 28.3% (136/480), respectively. The difference was also statistically significant (χ²=42.68, P=0.001). The degree of tooth marks was mainly mild, while the percentage of mild degree in Guangzhou (54.4%(43/79)) and Beijing (41.2% (56/136)) was apparently higher than that of Harbin (39.0% (73/187)). The difference was not statistically significant (χ²=7.01, P=0.136). Conclusion The behavior of biting pencils existed universally among pupils in Harbin, Guangzhou, and Beijing , which the situation of pupils biting pencils in Harbin and Beijing was more serious than that in Guangzhou. Pupils, parents and teachers should pay attention to such a behavior.

Objective To explore the effects ofDanshen Tongluo Detoxication Decoction on the inflammatory response of rats with bone marrow stem cell (BMSC) transplantation in acute myocardial infarction (AMI); To discuss its mechanism of action.Methods The whole bone marrow adherent method was adopted for BMSCs separation and culture. The AMI model was established by closing the left anterior descending coronary artery of SD rats. After the modeling, SD rats were randomly divided into sham-operation group, model group and BMSCs group (BMSCs transplantation group),Danshen Tongluo Detoxication Decoction group, Danshen Tongluo Detoxication Decoction + BMSCs group, 10 rats in each group. BMSCs cell suspension was injected directly into the edge of the myocardial tissue infarction area; Chinese medicine or normal saline were administered for gavage. 4 weeks later, the contents of MCP-1 and sICAM-1 in each group were detected by ELISA. TLR-4 expression was measured by Western blot method, and HE staining was used to observe the myocardial tissue pathological changes.Results Compared with the model group, the contents of MCP-1 and sICAM-1 and the protein expression of TLR-4 in BMSCs group,Danshen Tongluo Detoxication Decoction group, andDanshen Tongluo Detoxication Decoction + BMSCs group decreased, Danshen Tongluo Detoxication Decoction group was better than BMSCs group (P<0.05,P<0.01), andDanshen Tongluo Detoxication Decoction + BMSCs group was better than BMSCs group andDanshen Tongluo Detoxication Decoction group(P<0.05,P<0.01).Conclusion BMSCs transplantation combined withDanshen Tongluo Detoxication Decoction can restrain the inflammatory response of AMI model rats and repair ischemic myocardium issue, which mechanism may be related to regulating TLR-4 induced inflammatory response.

Objective To explore the clinical value of MRI in diagnosing and treating cesarean scar pregnancy (CSP).Methods A retrospective analysis was conducted on the clinical manifestations of 54 patients diagnosed with CSP between January 2009 to January 2013 in Peking University Third Hospital.Based on the patients' MRI image and other clinical datas,we did transvaginal operation on patients with CSP1,and transvaginal combined with abdominal operations on patients with CSP2.The intraoperative blood loss,operation time,postoperative hospital stay,and the length of time required for of serum hCG dropping to normal of the patients were analyzed.Results The average age of the 54 patients was (34±5) years and the average duration of gestation was (56± 16) days,all patients' vital sign were stable,the hCG level was 23-142 962 U/L before treatment.Twelve patients were diagnosed with CSP1 by MRI,and 5 of them had focus of 1-2 cm in diameter,the 5 patients' serum hCG level was 436-1 159 U/L and 23-32 days after drug administration,their hCG level returned to normal; the other 7 patients had focus of 2.0-4.4 cm in diameter,and their hCG level was 2 218-63 446 U/L,lesion resection was done on the 7 patients by hysteroscope or under B-uhrasound monitor.Forty-two patients were diagnosed with CSP2,and their focus were 1.0-7.1 cm in diameter,and serum hCG level were 23-142 962 U/L.We did bilateral uterine artery occlusion by laparoscope or laparotomy during operation for 22 patients or bilateral uterine artery embolization (UAE) before operation for 20 patients,then we did lesion resections.The blood loss during operation of CSP1 or CSP 2 was 50.1,267.2 ml; operation time was 30,128 minutes; postoperative hospital stay was 4.6,6.7 days;their serum hCG returned to normal 13-30 days after the surgery.All the 54 patients' uterus were preserved,and the patients undergoing operations were all cured without the second operation.Conclusion MRI is an effective method to conduct clinical treatment in CSP.