BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.

Objective This study aimed to investigate the effects of silencing Ras homolog family member C(RhoC)on the proliferation,apoptosis,invasion,migration,and epithelial-mesenchymal transition(EMT)of salivary adenoid cystic carcinoma(SACC)and its molecular mechanisms.Methods A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1,2019 to March 1,2024 were selected,and the expression levels of RhoC were detected by Western blot and immunohistochemistry.Three small interfering RNA(siRNAs)were designed to target the RhoC gene sequence,transfected into SACC-LM and SACC-83 cell lines,and evaluated for transfection efficiency.The protein expression levels of RhoC,Rho-asso-ciated protein kinase-1(ROCK1),p38 mitogen-activated protein kinase(p38MAPK),phosphorylated-p38MAPK(p-p38MAPK),twist family bHLH transcription factor 1(TWIST1),E-cadherin,N-cadherin,and Vimentin were com-pared using Western blot.CCK-8 assay,flow cytometry,transwell invasion assay,and wound healing assay were conducted to assess the differences in cell proliferation,apoptosis,invasion,and migration abilities among the groups.Bioinformatics methods were also used to predict possible upstream micro RNAs(miRNAs)of RhoC and their expression levels in SACC.Moreover,dual-luciferase reporter gene experiments were performed to verify the binding sites of miR-138-5p and RhoC.Results RhoC was highly expressed in SACC(P＜0.05).After silencing RhoC,the test group showed a significant decrease in the expression level of ROCK1,p-p38MAPK,TWIST1,N-cadherin,and Vimentin,as well as a significant increase in the expression level of E-cadherin(P＜0.05).No signifi-cant difference in the expression level of p38MAPK was observed(P＞0.05).The cell proliferation,invasion,and mi-gration ability decreased in the test group,whereas the apoptosis rates significantly increased(P＜0.05).miR-138-5p was lowly expressed in SACC,and miR-138-5p mimic can significantly downregulated the luciferase activity of 293T cells after transfection with a RhoC wild-type plasmid(P＜0.05).Conclusion RhoC is highly expressed in SACC,and RhoC silencing may target the downstream ROCK1/p38MAPK/TWISTl signaling pathway,thereby in-hibiting the proliferation,invasion,migration,and EMT of SACC while promoting its apoptosis.On the contrary,miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC,and there may be binding sites between the two genes.

AIM:To investigate the improvement effect of blood flow-limited resistance training on renal fibro-sis in type 2 diabetes mellitus(T2DM)rats and its potential mechanism to attenuate renal fibrosis by inhibiting the trans-forming growth factor β1(TGF-β1)/Smad3 signaling pathway.METHODS:The T2DM model was prepared by combining a high-fat diet and streptozotocin(STZ),and after successful modeling,the rats were randomly divided into a T2DM con-trol group,a low-load resistance training group,a high-load resistance training group,a blood flow restriction group and a blood flow restriction combined with resistance training group for 8 weeks of exercise.The renal index,fasting blood glu-cose(FBG),serum creatinine(SCr),and blood urea nitrogen(BNU)were recorded in each group.The morphological changes of the kidneys were observed by hematoxylin and eosin(HE)and Masson's trichrome staining,and the collagen volume fraction was calculated.The mRNA expression levels of renal Klotho,TGF-β1,and α-smooth muscle actin(α-SMA)were detected by RT-qPCR.The protein expression levels of renal Klotho,TGF-β1,Smad3,phosphorylated Smad3(p-Smad3),α-SMA and connective tissue growth factor(CTGF)were detected using Western blot.RESULTS:Compared with the other groups,FBG,SCr,BNU,and renal collagen volume fraction were significantly decreased in the blood flow restriction combined with resistance training group of rats(P<0.05),Klotho expression was significantly in-creased(P<0.05),and the expression of TGF-β1,p-Smad3,CTGF and α-SMA was significantly decreased(P<0.05),and there was no significant change in the expression level of Smad3(P>0.05).CONCLUSION:Blood flow restriction combined with resistance training attenuates renal fibrosis in T2DM rats,the mechanism of which may be related to the up-regulation of Klotho expression,disruption of the TGF-β1/Smad3 signaling pathway,and inhibition of the deposition of epi-thelial-mesenchymal transformation.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

Objective:To analyze the results of the practice test and formal test of the annual professional proficiency test for residents in 2022, to investigate related influencing factors and the effectiveness of the practice test, and to propose the measures for improving the results of the annual professional proficiency test.Methods:The scores of the annual professional proficiency test were analyzed for 202 residents who participated in the test in 2022, and the data on sex, education background, type of personnel, whether they passed the medical licensing examination, and practice test scores were analyzed to investigate related influencing factors. SPSS 23.0 and GraphPad Prism 8 were used for the chi-square test, the t-test, the one-way of variance, and the Fisher's exact test. A multiple linear regression analysis was used to identify influencing factors, and a Pearson correlation analysis was also performed. Results:The scores of the annual professional proficiency test for 202 residents were normally distributed with the highest number of the residents with a score of 90-99 points and the lowest number of the residents with a score of <70 points. The residents who passed the medical licensing examination had a significantly higher score of the annual professional proficiency test than those who failed the examination ( t=2.87, P=0.005), and the residents who passed the three practice tests had a significantly higher score of the annual professional proficiency test than those who failed the practice tests ( P<0.05). The score of the second practice test, the score of the third practice test, and the passing of medical licensing examination were independent influencing factors for the score of annual professional proficiency test ( R2=0.236, R2=0.201, F=6.60, P<0.05). The correlation analysis showed that the scores of the three practice tests were positively correlated with the final score ( r=0.189, 0.373, and 0.311, P<0.05). Conclusions:Improving the passing rate of medical licensing examination and strengthening pre-examination practice tests can help to improve the score of annual professional proficiency test. At the same time, it is necessary to improve the quality of training through the measures such as strengthening the homogenization management of different types of students, improving the attention and enthusiasm of all levels, and accelerating the construction of question banks.

Aim To explore the correlation between carotid atherosclerosis(CAS)and neutrophil/lymphocyte ratio(NLR)in patients with early morning hypertension,and to construct a line chart model to predict the risk of CAS in patients with hypertension in the morning.Methods 255 patients with early morning hypertension hospitalized in the Affiliated Hospital of Chengde Medical College from October 2019 to November 2022 were collected,and their basic data,blood routine and blood biochemical indexes were collected.All selected patients need to improve 24-hour ambulatory blood pressure monitoring and carotid artery color ultrasound detection.According to the presence or absence of CAS,all selected patients were divided into morning hypertension with CAS group(n=197)and morning hypertension without CAS group(n=58).Multivariate Logistic regression analysis was used to explore the risk factors of early morning hypertension with CAS,and to construct and verify an individual line chart model to predict the risk of early morning hypertension pa-tients with CAS.Results The age,NLR,neutrophils(NE),monocytes(MO),white blood cell(WBC),total cho-lesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDLC)increased in the early morning hyperten-sion with CAS group compared with those in the morning hypertension group without CAS,while the HDLC decreased(P＜0.05).The results of multivariate Logistic regression analysis showed that the age,NLR and TC were higher in the early morning hypertension with CAS group than those in the early morning hypertension without CAS group,while HDLC was lower;Age,NLR and TC were independent risk factors of early morning hypertension with CAS,while HDLC was inde-pendent protective factors of morning hypertension with CAS.Based on the results of multivariate Logistic regression anal-ysis,an individualized line chart model for predicting early morning hypertension with CAS was constructed.The area un-der the ROC curve of the line chart model was 0.853(95％CI:0.802-0.904,P＜0.01).The result of Hosmer Leme-show fit test was x2=1.665(P＞0.05).Conclusions There was a positive correlation between NLR and morning hy-pertension with CAS,and NLR was an independent risk factor for morning hypertension with CAS.The individualized line chart model based on age,NLR,TC and HDLC can effectively predict the risk of hypertension with CAS in the early morn-ing,which provides a theoretical basis for early detection and prevention of atherosclerosis.

Objective:To summarize the clinical phenotype and genetic characteristics of a case of autosomal dominant mental retardation-42 (MRD42) caused by GNB1 gene mutation. Methods:The clinical and genetic data of a case of MRD42 caused by a GNB1 gene missense mutation diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in March 2023 were retrospectively analyzed. The child was followed-up, the child′s data were summarized, and related literature was reviewed. Results:The patient is a 6-month-old female infant, who was admitted to hospital because of "developmental delay for 3 months, intermittent convulsions for 1 month". The clinical manifestations included generalized tonic-clonic seizures, focal seizures, intellectual disability, delayed language and motor development. Long-term video electroencephalogram showed slightly slower background activity, bilateral occipital spike and wave discharges, multispike and wave complexes during sleep. Three focal onset seizures were captured. Cranial magnetic resonance imaging suggested that the subarachnoid space of the bilateral frontotemporal areas was slightly wide. Chromosome karyotype and copy number variation analysis showed no abnormality. The results of whole exon sequencing showed a de novo heterozygous missense mutation in the GNB1 gene [NM_002074:c.155(exon5)G>A;p.Arg52Gln], which had not been reported. The seizure was effectively controlled by function rehabilitation training and anti-epileptic drug therapy. Conclusions:MRD42 is a rare autosomal dominant disorder caused by mutation in the GNB1 gene. The clinical manifestations include infantile-onset seizures, mental retardation, speech and motor development delay, etc. The de novo heterozygous missense mutation in the GNB1 gene c.155G>A(p.Arg52Gln) is the genetic cause of the proband.

Objective:To investigate the hemodynamic characteristics and dynamic cerebral autoregulation(dCA) of patients with severe carotid stenosis before carotid endarterectomy(CEA), and to analyze their correlations with hyperperfusion after CEA.Methods:A total of 63 patients with unilateral severe carotid artery atherosclerotic stenosis who underwent CEA were consecutively recruited prospectively in Xuanwu Hospital, Capital Medical University from January 2021 to August 2021. According to postoperative hyperperfusion, patients were divided into hyperperfusion group (13 cases) and non-hyperperfusion group (50 cases). The general clinical data and hemodynamic parameters were compared between the two groups. The dCA was evaluated by the transfer function analysis that measured the fluctuation amplitude of mean cerebral blood flow velocity(CBFV) with blood pressure change, the time difference of phase with blood pressure change, and the correlation between mean CBFV and blood pressure change. The value of dCA for predicting postoperative hyperperfusion was analyzed through the ROC curve and the area under the curve(AUC).Results:①The proportion of hypertension in hyperperfusion group was higher than that in non-hyperperfusion group ( P<0.05). ②The peak systolic velocity (PSV) at the stenosis lesion of the internal carotid artery, the end-diastolic velocity (EDV) at the stenosis lesion of the internal carotid artery and the ratio of PSV at the stenosis lesion of the internal carotid artery to the distal internal carotid artery in the hyperperfusion group were higher than the non-hyperperfusion group.And the PSV of the ipsilateral middle cerebral artery in the hyperperfusion group was lower than the non-hyperperfusion group (all P<0.05). ③In the very low-frequency and low-frequency region, the phase in the hyperperfusion group was lower than that in the non-hyperperfusion group (all P<0.05), while there was no significant difference in the high-frequency regions( P>0.05). In the three regions of very low-frequency, low-frequency and high-frequency, there were no significant differences in the gain and coherence between the two groups(all P>0.05). ④The best cutoff value of phase in the very low-frequency was 33.28 for predicting hyperperfusion after CEA (AUC=0.766, 95% CI=0.629-0.904, P=0.03), with the specificity of 0.700, and sensitivity of 0.846. Conclusions:There are differences in hemodynamics and dCA between the hyperperfusion group and the non-hyperperfusion group after CEA. The impaired preoperative dynamic cerebral autoregulation is an independent predictor of postoperative hyperperfusion.

Objective:To explore the effectiveness of Acute Care of the Elderly(ACE)model and its existing problems in the clinical practice for older adults with acute clinical conditions.Methods:Using the random number table method, a random number sequence was generated, and the patients admitted to the Department of Geriatrics of Shenzhen Nanshan Hospital due to acute diseases From January 2019 to September 2021 were enrolled in the ACE model intervention group(160 cases)and the control group(77 cases)in a 2: 1 ratio.The inclusion criteria were based on disease severity, frailty assessment, and activity of daily living(ADL)assessment.The intervention time was 1-3 weeks.Outcomes of the patients include ADL, hospitalization days, hospitalization expenses, drug proportion, human resource investments, adverse events, 30-day readmission rate, and 1-year mortality.Results:There were no significant difference in baseline indicators such as frailty index and ADL score between the two groups at admission.The ADL score(Barthel index)of the ACE group was significantly improved compared with the control group at discharge(81.71±14.23 vs.70.9±23.89, P<0.001)and at 30 days after discharge(85.84±15.25 vs.68.29±30.91, P<0.001). The hospital cost[(12 735.81±6 541.41)￥ vs.(16 391.54±12 962.34)￥, P=0.002], drug proportion(21.34% vs.28.93 %, P=0.036)and 30-day readmission rate(13.1% vs.23.4%, P=0.037)of the ACE group were significantly lower compared to the control group.The human resource input(32.97±6.72 vs.25.03±5.31, P=0.008)and patient satisfaction(98.23% vs.90.66%, P=0.031)in the ACE group were significantly higher than those of the control group.(4)The incidence of adverse events during hospitalization was significantly lower in the ACE group than in the control group in terms of aspiration(0.63% vs.20.8%, P<0.001), falls(0 vs.10.4%, P<0.001), incontinence dermatitis(0 vs.3.9%, P=0.033), and 1-year mortality(6.3% vs.24.7%, P<0.001). There was no significant difference in the average length of stay(8.98±4.25 vs.10.03±5.32, P=0.101), pressure sores(13.01±4.77 vs.13.27±4.89, P=0.364), DVT risk score(8.53±2.79 vs.8.89±2.76, P=0.340)and medical staff satisfaction(73% vs.80%, P=0.240)between the two groups. Conclusions:The ACE model helps to reduce the disability rate of elderly patients with frailty, adverse events during hospitalization, save drug costs, and improve patient satisfaction.It is worth promoting in geriatric practice, but its localization management details and processes still face many challenges.

Objective:To understand the effect of standardized residency training for residents with different identity types, and put forward targeted optimization and improvement measures to achieve the homogenization of training effect.Methods:Combined with literature review and expert consultation results, a self-designed questionnaire was conducted for 324 residents who completed their courses in 2019 and 2020. The effective recovery rate of the questionnaire was 87.65%. By comparing the passing rate of first-time medical admission and completion examination of different identity types, and the training standards of six core competencies, the training effect conclusion was drawn. T-test and Fisher exact probability test were also made by SPSS 21.0. Results:The passing rates of first-time doctors and completion examinations were higher in professional masters and units than in the general population, with the highest passing rates reaching 100% (10/10) and 97.3% (72/74) respectively. There was no statistical difference between the passing rates of residents with different identity types. The overall standard of the six core competencies of the integrated professional masters was better than that of the society and unit personnel. There were statistical differences between the groups in the training standards of the four abilities of the residents with different identity types in professional literacy ( P=0.048), patient management ( P=0.030), communication and cooperation ( P=0.026) and learning promotion ( P=0.003). There was no significant difference in professional ability ( P=0.131) and teaching ability ( P=0.061). Conclusion:There is no difference in the passing rate of residents with different identity types in a military hospital, which achieves the goal of homogenization training to a certain extent. However, there are obvious differences in the standards of the six core competencies, and further optimization measures need to be explored.