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.

ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Objective:To analyze the genetic and molecular characteristics of H9N2 subtype avian influenza viruses from external environment and humans in Anhui Province from 2013 to 2022.Methods:Environmental samples and human samples were collected from Anhui influenza surveillance network laboratory. Sixty-three strains of virus were isolated in chicken embryos. RT-PCR was used to amplify the virus and whole genome sequencing was performed. To construct gene evolutionary tree and analyze its genetic characteristics and potential glycosylation sites.Results:The hemagglutinin (HA) gene belongs to the 9.2.4.5 clade, and the protein cleavage sites are mostly " PSRSSR\GL". The neuraminidase (NA) gene, basic protein-1(PB1) gene, acidic protein (PA) gene, non-structural protein (NS) gene and nucleoprotein (NP) gene belong to the F/98 clade, the matrix protein (MP) gene belongs to the G1/97 clade, and the basic protein-2 (PB2) gene belongs to the ST/7488 clade. Mutations of T155N, R164Q, H183N, T189D/V, A190V/T and Q226L occurred in HA protein, deletion of NA protein occurred at 62-64 sites, and mutations of T271A, I292V/M and E627V/L occurred in PB2 protein. At the same time, mutations of K356R and S409N occurred in the PA protein.Conclusions:The H9N2 subtype avian influenza viruses collected from external environment and human sources in Anhui province from 2013 to 2022 belong to the same evolutionary branch, and amino acid site mutations suggest that the virus shows a tendency to gradually adapt to the mammalian host environment. Therefore, further studies on the adaptive evolution of the virus and related monitoring work are needed.

The rates of recovery of spontaneous circulation, admission survival, and discharge survival of out-of-hospital cardiac arrest (OHCA) patients in China are much lower than the world and Asian averages, and the data on the survival of in-hospital cardiac arrest (IHCA) patients are also less favorable. The variable quality of cardiopulmonary resuscitation (CPR) and the low percentage of bystander CPR participation are the main reasons for these phenomena. Real-time feedback devices are an effective strategy to address these issues and have been recommended for use in several guidelines. However, the existing CPR feedback devices have the problems of being inconvenient to operate and expensive to popularize. Therefore, members of the CPR training team of Loudi Central Hospital designed a CPR real-time feedback APP device, which has been granted the right of National Invention Patent of China (patent number: ZL 2021 1 1118500.1). The device consists of a feedback device and a mobile device (there are two versions: healthcare professionals and non-healthcare professionals). The feedback device consists of a pressing plate and a soft rubber plate. The inner side of the soft rubber plate is covered with sensor monitoring points. On each sensor monitoring point, there are micro pressure sensors and micro acceleration sensors. When performing chest compressions, the sensors will transmit the relevant data to the cell phone feedback APP. By sampling and analyzing the data and building a three-dimensional dynamic model, the feedback APP accurately judges the effect of chest compressions based on factors such as the strength of the compressions, the frequency of the compressions and the depth of the compressions, corrects and provides voice guidance for the subsequent CPR process in real time, guides the rescuers to follow the standardized procedures for rescue, and improves the survival rate and neurological recovery of the CPR patients. The device improves CPR with exact effect, real-time accuracy, simple operation, easy to promote, and applicable to all populations. It has good clinical application and socialization popularization value, and can be equipped in medical institutions and public places.

Objective:To report a large family of epileptic seizures caused by DEPDC5 gene variation, and to conduct a clinical genetic analysis on a proband in this family with both DEPDC5 gene mutation and a de novo GABRA1 gene mutation. Methods:The medical records of a family suffering from epilepsy due to a newly identified DEPDC5 gene variant were compiled from cases admitted to Hebei General Hospital in January 2024. The relevant genetic detection was carried out by sampling the peripheral blood of the family members. The whole exome sequencing techniques were employed for the identification of pathogenic mutation sites in the proband. The next generation sequencing technology was utilized for other family members to identify disease-causing mutation sites associated with the clinical phenotype of patients, and these findings were confirmed using first-generation Sanger sequencing technology. Results:The proband, who experienced seizures in early childhood and harbored two gene mutation sites, exhibited an early onset age along with significant delays in both intellectual and motor development. The primary clinical manifestations included focal seizures, myoclonus, and tonic-clonic symptoms. When compared with other family members who had the onset of epilepsy during adolescence, carried only one mutation site, and had generalized epileptic seizures and mostly accompanied by attention deficit hyperactivity disorder, the proband showed obvious clinical heterogeneity. The results of whole exome sequencing indicated that the proband had both GABRA1 c.640C>T(p.Arg214Cys) and DEPDC5 c.4348A>T(p.Lys1450 *) mutations inherited from the father. The mutation inherited from the father was reported here for the first time and had not been reported before, with the paternal mutation traceable to the proband's grandfather, while the proband's mother and grandmother were found to be devoid of the mutation. In this family, 5 patients with similar seizure phenotype all had pathogenic mutations at the same locus of the DEPDC5 gene(c.4348A>T, p.Lys1450 *), and the remaining 3 patients with seizure symptoms were not tested. Conclusions:The DEPDC5 gene mutation is the cause of the disease in this family, and the c.4348A>T is the newly discovered mutation site. The proband carries the mutation sites of both GABRA1 gene and DEPDC5 gene. The clinical manifestations of proband are significantly heterogeneous compared with those of his family members.

Objective:To analyze the clinical characteristics and risk factors of acute kidney injury (AKI) in portal venous hypertension patients undergoing transjugular intrahepatic portosystemic shunt (TIPS).Methods:It was a retrospective observational study. In this study, the clinical data of portal venous hypertension patients undergoing TIPS at Beijing Shijitan Hospital, Capital Medical University from October 16, 2020 to March 30, 2022 were collected retrospectively. According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI, patients were divided into AKI group and non-AKI group. The clinical characteristics of the patients were compared between the two groups, and multivariate logistic regression was used to analyze the risk factors of AKI.Results:A total of 384 patients undergoing TIPS were included in this study, whose age was (53.17±13.35) years. Among them, 122 (31.8%) were female, and 32 patients (8.3%) had AKI. Compared to the non-AKI group, the proportion of patients with diabetes mellitus, baseline estimated glomerular filtration rate (eGFR) <60 ml·min -1·(1.73 m 2) -1 and intraoperative hypotension, Child-Pugh score of liver function, preoperative serum creatinine, preoperative blood uric acid, and postoperative portal venous pressure gradient (PPG) were higher in AKI group (all P<0.05), while the levels of hemoglobin and serum albumin were lower (both P<0.05). Multivariate logistic regression results showed that combined diabetes ( OR=3.728, 95% CI 1.262-11.013, P=0.017), baseline eGFR<60 ml·min -1·(1.73 m 2) -1( OR=3.571, 95% CI 1.356-9.400, P=0.010), decreased serum albumin ( OR=0.847, 95% CI 0.738-0.972, P=0.018), increased PPG after TIPS ( OR=1.096, 95% CI 1.002-1.200, P=0.045) and intraoperative hypotension ( OR=7.006, 95% CI 2.023-24.195, P=0.002) were independently associated with postoperative AKI in portal venous hypertension patients undergoing TIPS. Until discharge, 6 patients with AKI (18.8%) had complete renal function recovery, 24 patients (75.0%) partially recovered, and 2 patients (6.3%) did not recover. The length of hospital stay, hospitalization costs, and all-cause mortality in AKI patients were significantly higher than those in the non-AKI group ( P<0.05, respectively). Conclusions:AKI is not uncommon in patients receiving TIPS. The classical risk factors of AKI, such as diabetes and baseline renal dysfunction, and the factors affecting volumes like lower serum albumin level, hypotension during the operation, and higher PPG level are closely related to the incidence of AKI in these patients. AKI significantly increases the all-cause mortality and medical expenses, which is worth early prevention and treatment by clinicians.

Objective:To investigate the changes and associated factors of cerebral blood flow in middle-aged and elderly patients undergoing maintenance hemodialysis (MHD).Methods:This was a prospective observational study. End-stage renal disease (ESRD) patients undergoing MHD aged over 50 years at Beijing Shijitan Hospital, Capital Medical University from January 2023 to June 2023 were included. General clinical data of the selected individuals were collected, and dialysis related indicators were recorded and calculated. Mean flow velocity (MFV) of the middle cerebral arterial was measured by transcranial Doppler sonography (TCD) to represent cerebral blood flow throughout dialysis. Hemodialysis-related variables were collected. The MFV values of bilateral middle cerebral artery were measured through temporal windows at 7 time points: 15 minutes before dialysis (T1), 15 minutes (T2), 30 minutes (T3), 60 minutes (T4), 120 minutes (T5), 180 minutes (T6) during dialysis, and the endpoint of dialysis (T7), and the average values were recorded. The ΔMFV was calculated as pre-minus endpoint values of MFV. The Spearman rank correlation method was used to analyze the correlations between ΔMFV and dialysis-related variables, and multiple linear regression method was used to analyze the related factors of the changes in MFV.Results:This study included a total of 123 patients undergoing MHD, aged (63.63±8.44) years (range 50-85 years), including 99 males (80.5%). TCD examination demonstrated a decline trend in MFV throughout dialysis. The MFV at T7 was significantly lower than that at T1 ( Z=-7.650, P<0.001). The Spearman correlation analysis showed that the decline in MFV was correlated with ultrafiltration volume ( r=0.356), ultrafiltration rate ( r=0.371), the difference in systolic pressure (pre-analysis minus post-dialysis, r=0.251), the difference in mean arterial pressure (pre-dialysis minus post-dialysis, r=0.194), combined diabetes ( r=0.293), dialysis vintage ( r=0.220), Kt/V ( r=0.287), and serum albumin ( r=-0.295). Multiple linear regression analysis showed that combined with diabetes ( B=3.889, 95% CI 1.373-6.405, P=0.003), decreased serum albumin ( B=-0.456, 95% CI -0.877--0.036, P=0.034), increased ultrafiltration rate ( B=11.099, 95% CI 6.402-15.797, P<0.001) and the decline in systolic pressure ( B=0.062, 95% CI 0.008-0.116, P=0.026) were significantly associated with the decline in MFV throughout dialysis. Conclusions:In middle and elderly patients with ESRD undergoing hemodialysis, there is a decline trend in cerebral blood flow during hemodialysis. The combination of diabetes, lower serum albumin, higher ultrafiltration rate, and intradialytic systolic pressure decline are the risk factors influencing the intradialytic decline of cerebral blood flow.

Objective To explore the relationship between serum leucine 2-rich glycoprotein 1(LRG1),lactate dehydrogenase(LDH)with periodontal indicators and periodontal lesions degree in patients with type 2 diabetes mellitus(T2DM)and chronic periodontitis(CP).Methods 112 patients with T2DM combined with CP admitted to our hospital from July 2022 to July 2023(T2DM combined with CP group)were selected and catego-rized into mild,moderate,and severe groups according to the degree of periodontal pathology;112 patients with CP alone(CP group)were selected from our hospital during the same period,and then 112 patients with T2DM alone(T2DM group)were selected;and LRG1,LDH,and periodontal indexes were measured;Pearson method was applied to analyze the correlation between serum LRG1,LDH,and periodontal indicators.The influencing factors of severe T2DM combined with CP were analyzed using multivariate logistic regression.ROC curve was plotted to analyze the diagnostic value of serum LRG1 and LDH for severe T2DM combined with CP.Results The levels of LRG1 and LDH in the CP group,T2DM group,and T2DM combined with CP group increased sequentially(P＜0.05).The levels of serum LRG1,LDH,AL,PD,and BI increased sequentially in the mild,moderate,and severe groups(P＜0.05).According to Pearson correlation analysis,serum LRG1 was positively correlated with LDH(P＜0.05).Serum LRG1 and LDH were positively correlated with AL,PD,and BI(P＜0.05).According to logistic regression analysis,LRG1,LDH,AL,PD,and BI were all factors for severe T2DM combined with CP(P＜0.05).According to the ROC curve,the AUC for the combined diagnosis of serum LRG1 and LDH in severe T2DM with CP was 0.910,and the combination of the two was better than their individual diagnosis(Z combination vs LRG1=2.659,Z combination vs LDH=2.627,P＜0.05).Conclusion LRG1 and LDH are greatly elevated in the serum of patients with T2DM combined with CP,and they are related to periodontal indicators and the periodontal lesions degree.

Objective To explore the relationship between hyperkalemia and adverse outcomes in elderly maintenance hemodialysis(MHD)patients.Methods A retrospective cohort trial was conducted on 177 MHD patients aged≥60 years in the hemodialysis center of Beijing Shijitan Hospital,Capital Medical University.Baseline data were collected.The mean age was(77.28±14.25)years,among them 109 cases were males(61.6%).According to the peak serum potassium within 4 months,patients were divided into the K+＜5.0 mmol/L group(38 cases,21.5%),the 5.0-5.5 mmol/L group(42 cases,23.7%)and the K+≥5.5 mmol/L group(97 cases,54.8%).Based on the frequency of hyperkalemia within 4 months,patients were divided into the 0,1-2 and 3-4 frequency groups.All of patients were followed up for 1 year.The end point events were all-cause mortality and cardiovascular disease(CVD)mortality.Kaplan-Meier survival analysis was used to compare the cumulative survival rate between the 3 groups.A multivariate Cox regression model was employed to analyze the relationship between the degree and frequency of hyperkalemia with all-cause and CVD mortality.Results The mean follow-up time of 177 patients was 12(1-12)months,20(11.3%)patients died of all-cause death and 14(7.9%)of CVD death.Kaplan Meier survival curve showed cardiovascular mortality rate and all-cause mortality were significantly increased in the K+5.0-5.5 mmol/L group and the K+≥5.5 mmol/L group(both P＜0.05).Multivariate Cox regression analysis indicated that,as a continuous variable,peak potassium levels were independently associated with an increased risk of all-cause death and CVD death(P＜0.001).As a categorical variable,the all-cause mortality risk and CVD mortality risk were significantly higher in both the K+5.0-5.5 mmol/L group and the K+≥5.5 mmol/L group than those in the K+＜5.0 mmol/L group(P＜0.05),and those were significantly higher in the 1-2 and 3-4 frequency groups than those in the 0 frequency group of hyperkalemia(P＜0.05).Conclusion Serum potassium>5.0 mmol/L in elderly MHD patients is an independent risk factor for all-cause and CVD mortality.It is recommended to adjust the upper limit of the normal range of serum potassium to 5.0 mmol/L.