OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

Objective: To investigate the attention cognitive function and symptom correlations of school aged children with attention deficit hyperactivity disorder (ADHD)using event related potential (ERP) technology, so as to provide references for the early diagnosis of children with ADHD. Methods: A total of 52 school aged children diagnosed with ADHD at the outpatient department of the Third Affiliated Hospital of Zhengzhou University from September 2022 to September 2024 and 50 age /sex matched healthy controls were selected. The ERP experiment adopted the auditory Oddball task to conduct comparative analyses of the amplitude and latency of the mismatch negative(MMN) at the Fz, Cz, and Pz points of the scalp electrode and the P3a component respectively. The symptom assessment scales adopted the Swanson,Nolan,and Pelham-Ⅳ Rating Scale (SNAP-Ⅳ) and the Parent Symptom Questionnaire (PSQ), which were filled out by the parents. Spearman correlation analysis was used to analyze the correlation between ERP components and symptoms in schoolaged children with ADHD. Results: The latency of MMN components in the healthy control group on the Fz lead was (188.30±2.06)ms, and the amplitude was (-15.54±1.35)μV; the latency of the P3a component on the Pz lead was (312.82±7.80)ms, and the amplitude was (3.80±0.18)μV. The latency of MMN components in the ADHD group on the Fz lead was (188.94±1.39)ms, and the amplitude was (-14.78±1.40)μV; the latency of the P3a component on the Pz lead was (317.21±5.65)ms, and the amplitude was (3.70±0.13)μV. Compared with normal children, the MMN of children with ADHD had smaller amplitudes in the Fz and Cz leads, and the P3a had greater latency and smaller amplitudes in the Cz and Pz leads ( t =2.79,2.20；-2.04，-3.25；2.35,3.21， P <0.05). Correlation analysis showed that the latency of MMN in children with ADHD was positively correlated with the inattention score in the SNAP-Ⅳ( r =0.22), and the amplitude of MMN was negatively correlated with the inattention score in the SNAP-Ⅳ and the learning problem score in PSQ ( r = -0.26 , -0.34)( P <0.05). The latency of P3a was positively correlated with the scores of inattention in the SNAP-Ⅳ and the score of learning problems in the PSQ ( r =0.26 ,0.24); the amplitude of P3a was negatively correlated with the scores of attention deficit and hyperactivity/impulsivity in the SNAP-Ⅳ and the scores of learning problems and impulsivity/hyperactivity in the PSQ( r = -0.26 , -0.22, -0.25,-0.32)( P <0.05). Conclusions School aged ADHD children exhibit abnormal MMN/P3a components, indicating attention related cognitive dysfunction. Symptoms such as inattention, learning problems and hyperactivity/impulsivity in children with ADHD are related to abnormal components of MMN and P3a.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Abstract Obesity is characterized by a body weight exceeding a certain range and a corpulent physique, often accompanied by symptoms such as dizziness and fatigue, lack of energy and motivation to speak, reduced physical activity, and shortness of breath. The core pathogenesis of obesity lies in the dysfunction of the spleen and stomach in transporting and transforming nutrients, leading to abnormal metabolism of water and grain essences and the subsequent accumulation of pathological substances such as phlegm-dampness and "Gaozhuo" (greasy-turbid substances). Traditional Chinese Medicine emphasizes that "spleen deficiency is the root cause, while phlegm-dampness and Gaozhuo are the manifestations", forming a dialectical system encompassing theories on spleen-stomach transportation and transformation, phlegm-dampness pathogenesis, Gaozhuo pathogenesis, and constitutional differentiation. Traditional Chinese Medicine plays a crucial role in preventing and treating obesity through interventions such as herbal medicine, external therapies, and dietary adjustments. This article systematically reviews classical Chinese medical texts, focusing on the etiology, pathogenesis, theoretical origins, and prevention and treatment methods of obesity, so as to provide references for modern Traditional Chinese Medicine approaches to obesity prevention and treatment.

Objective:To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve.Methods:The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People′s Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method .Results:Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P>0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t=2.38, P=0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t=8.77, P=0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t=6.96, P=0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t=3.43, P=0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t=4.58, P=0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t=2.43, P=0.007; DID for plum blossom pile bean clamping=58.42, t=3.03, P=0.013; DID for ferrule positioning=28.33, t=2.83, P=0.031; DID for threading with both hands=48.89, t=2.10, P=0.042; DID for sewing and knotting=54.78, t=3.57, P=0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs. 4 class hours; ferrule positioning: 4 class hours vs. 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t=-2.85, P=0.004; threading with both hands: t=-2.66, P=0.008). Conclusion:The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Objective:To investigate the short-term outcomes of robot-assisted pancreato-duodenectomy (RPD) performed by one single surgeon.Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 240 patients who were performed RPD by one single surgeon at The First Affiliated Hospital of Sun Yat-sen University from July 2016 to October 2023 were collected. There were 130 males and 110 females, aged 59(19)years. All RPD were performed by the same surgeon. Observation indicators: (1) surgical situations; (2) postoperative pathological examination and outcome of patients. Measurement data with normal distribution were expressed as Mean± SD, and measurement data with skewed distribution were expressed as M(IQR). Count data were expressed as absolute numbers or percentages. Results:(1) Surgical situations. Of 240 patients, 15 cases underwent combined vascular resection and reconstruction, and 13 patients were combined with other operations simultaneously. Of 240 patients, 4 cases converted to open surgery, with the conversion rate as 1.67%. The operation time of 240 patients was 458(152)minutes, volume of intraopera-tive blood loss was 50(50)mL, intraoperative erythrocyte transfusion was required in 17 patients. The R 0 resection rate was 99.17%(238/240), the number of lymph nodes harvested was 10(6) and duration of postoperative hospital stay was 17(12)days. (2) Postoperative pathological examination and outcome of patients. Of 240 patients, 51 cases were pancreatic ductal adenocarcinoma, 41 cases were ampullary carcinoma, 41 cases were neuroendocrine neoplasms, 35 cases were pancreatic cystic neoplasms, 28 cases were duodenal carcinoma and 44 cases were other pathologic types. Of 99 patients with major complications, there were 57 cases with clinically relevant postoperative pancreatic fistula, 44 cases with postoperative delayed gastric empty, 11 cases with postoperative biliary fistula, 8 cases with postoperative chyle fistula, 14 cases with incision infec-tion, and 24 cases with postoperative hemorrhage. Multiple complications might occur to the same patient. Reoperation was performed in 6 of the 240 patients. One patient died within 30 days after surgery. Twenty-four patients returned to hospital within 30 days after discharge. Conclusions:RPD performed by one single surgeon is safe and feasible, with favorable short-term outcomes, which can be performed in medical centers with experiences in robot-assisted pancreatic surgery.

This paper reviews the main symptom clusters, assessment tools, influencing factors, intervention and prospect for the management of symptom clusters associated with chimeric antigen receptor T cell immunotherapy in adult patients with hematological malignancies, in order to provide references for medical staff to enhance the scientificity of symptom management and nursing service quality.

Objective:To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve.Methods:The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People′s Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method .Results:Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P>0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t=2.38, P=0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t=8.77, P=0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t=6.96, P=0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t=3.43, P=0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t=4.58, P=0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t=2.43, P=0.007; DID for plum blossom pile bean clamping=58.42, t=3.03, P=0.013; DID for ferrule positioning=28.33, t=2.83, P=0.031; DID for threading with both hands=48.89, t=2.10, P=0.042; DID for sewing and knotting=54.78, t=3.57, P=0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs. 4 class hours; ferrule positioning: 4 class hours vs. 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t=-2.85, P=0.004; threading with both hands: t=-2.66, P=0.008). Conclusion:The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Objective:To study the relationship between the absorptive capacity of inpatients with infectious diseases and the structure of diseases in 65 secondary and tertiary general hospitals in Beijing,and to objectively analyze the current situation of space utilization of inpatients with infectious diseases,so as to provide data support for the formulation of relevant policies.Methods:The variability of spatial absorption capacity indicators for secondary and tertiary general hospitals in 6 urban districts and 10 suburbs were compared separately,and the correlation between the spatial absorption capacity of secondary and tertiary general hospitals and the structure of disease types was visualized and analyzed using quadrant bubble charts.Results:In terms of spatial absorption capacity,there was a statistically significant difference in the proportion of patients from suburban districts treated in the secondary and tertiary general hospitals in 6 urban districts of the Beijing(P=0.003),while there was no statistically significant difference in the proportion of patients from other districts treated in the secondary and tertiary general hospitals in 10 suburbs(P=0.336).The spatial absorption capacity and disease structure of the secondary and tertiary hospitals in 6 urban districts and the tertiary hospitals in 10 suburbs showed significant correlation,while the secondary hospitals in 10 suburbs showed no significant correlation.Conclusion:The tertiary general hospitals in 6 urban districts have superior infectious disease type structure indicators,with significantly stronger spatial absorption capacity and stronger correlation between these two,which plays the function of inpatient service of difficult and severe infectious diseases.Only the district hospitals in the outer suburbs can provide inpatient services for infectious diseases,and the number of cases admitted is large,which meets the needs of inpatient diagnosis and treatment of common infectious diseases in the district.It is necessary to strengthen the investment of infectious disease medical resources and capacity building in 10 suburban districts according to the actual situation.