Cathepsins,the most abundant hydrolases in lysosomes,are responsible for the degradation of various substrates.Increasing evidence suggests that cathepsins play important roles in neurodegenerative diseases.Cathepsins affect the progression of diseases by regu-lating the aggregation of abnormal proteins(e.g.α-synuclein,amyloid β-protein,huntington).Abnormal expression levels and activity and gene mutations of cathepsin B,D,and L in the nervous system can lead to the occurrence and development of neurodegenerative diseases.This review summarizes the research progress on cathepsins in neurodegenerative diseases in recent years,with a view to providing a basis for the early diagnosis and treatment of these diseases.

Objective To analyze the risk factors and the prognosis in patients with cerebral venous sinus thrombosis(CVST)accompanied by early-onset seizures.Methods A retrospective study was conducted on 163 patients with CVST admitted to the Department of Neurology and Neurosurgery of Shengjing Hospital of China Medical University during August 2011 to November 2022 as the study subjects.Based on whether they had concurrent seizures within 14 days after diagnosis CVST,the patients were divided into the early-onset seizures group(42 cases)and the non-early-onset seizure group(121 cases).Clinical data were collected,including general clinical data,imaging data,laboratory test results,and treatment plans,etc.The general clinical data involves gender,age,suspected etiology(infection[such as mastoiditis,otitis media,sinusitis,etc.],oral contraceptives/estrogen,pregnancy/puerperium,anemia and other factors that can lead to changes in blood composition,hyperhomocysteinemia),clinical manifestations(including headache,dizziness,disturbance of consciousness,nausea and vomiting,limb numbness,hemiplegia,tinnitus,aphasia,diplopia,mental abnormalities,unresponsiveness,isolated intracranial hypertension[papilledema],etc.).Imaging data includes involved venous sinus location,multiple venous sinuses(involving ≥ 2 venous sinuses)and intracranial changes(intracranial hemorrhage,venous cerebral infarction,subarachnoid hemorrhage).All patients were tested for D-dimer on the second day of admission.Patients with intracranial hypertension were examined with spinal puncture and measured cerebrospinal fluid pressure,with elevated cerebrospinal fluid pressure defined as the pressure＞180mmH2O.The patients were followed up by telephone 2 months after discharge,and the modified Rankin scale(mRS)was used to assess the prognosis of the patients(mRS score ≤2 points as good prognosis,mRS score＞2 points as poor prognosis).The mortality rate of patients was measured.The clinical data,imaging data,laboratory test results,treatment and follow-up results of the two groups were compared.The correlation variables with P＜0.05 in the univariate analysis were included in the multivariate Logistic regression model to analyze the independent risk factors of CVST accompanied by early-onset seizures.Results(1)Compared with the non-early-onset seizure group,the proportion of pregnant/puerperal females in the early-onset seizure group was higher(33.3％vs.13.2％,P=0.004),the proportion of patients with hemiplegia was higher(23.8％vs.6.6％,P=0.005),and the proportion of patients with CVST imaging combined with intracranial hemorrhage was higher(40.5％vs.13.2％,P＜0.01),with all the differences were statistically significant.There was no significant difference in other baseline clinical data between the two groups(all P＞0.05).(2)Further multivariate Logistic regression analysis showed that pregnancy/puerperium(OR,4.854,95％CI 1.917-12.290,P=0.001),hemiplegia(OR,3.871,95％CI 1.246-12.028,P=0.019)and intracranial hemorrhage(OR,5.005,95％CI 2.038-12.288,P＜0.01)were independent risk factors for CVST with early-onset seizures.(3)There were 3 patients(7.1％)in the early-onset seizure group and 6 patients(5.0％)in the non-early-onset seizure group dead,and there was no significant difference in the proportion of death between the two groups(P=0.887).The proportion of patients with good prognosis in the early-onset seizure group was lower than that in the non-early-onset epilepsy group(81.0％vs.92.6％),and the difference between the groups was statistically significant(P=0.043).Among the patients treated with anticoagulation alone,the good prognosis rate of non-early-onset seizures group(99/106,93.4％)was higher than that of the early-onset seizure group(32/40,80.0％),and the difference was statistically significant(P=0.029).Conclusions For CVST patients,especially females during pregnancy or postpartum period,clinical manifestations accompanied by hemiplegia,and with intracranial hemorrhage on imaging,the risk of seizures within 14 days of the diagnosis of CVST should be vigilant.The prognosis of CVST patients with early-onset seizures is worse than that of patients without early-onset seizures.

Objective To explore the application effect of healthcare failure mode and effect analysis (HFMEA) in nursing risk management of emergency surgery for patients with traumatic brain injury (TBI). Methods Taking the HFMEA model as the theoretical framework, the emergency surgical process of TBI was analyzed, a flow chart was drawn, and the potential risk factors were analyzed. Corresponding intervention programs were adopted for high-risk failure modes, and 80 patients from November 2022 to April 2023 were conducted with routine management before implementation of HFMEA (control group), the other 80 patients from May to October 2023 were conducted with management after implementation of HFMEA (observation group). The surgical efficiency (preoperative waiting time, surgical preparation time, anesthesia induction time, postoperative handover time), the incidence rates of adverse events in the operation room (incomplete preparation of supplies, contamination of surgical drapes, insufficient or defective intraoperative instruments, errors in writing nursing records, incorrect or missing items in handover information), the incidence rates of perioperative complications (low intraoperative body temperature, pressure injury, abnormal fluctuations in vital signs during surgery, wound infection, lung infection) and satisfaction degree of surgical doctors to nurses for current operations (itinerant nurses, instrument nurses) were compared between two groups. Results The observation group had significantly shorter preoperative waiting time, surgical preparation time, anesthesia induction time, and postoperative handover time compared to the control group (P < 0.01). The incidence rate of adverse events in the operation room for the observation group was 16.25%, which was significantly lower than 46.25% of the control group (P < 0.01). The incidence rate of complications was 8.75% in the observation group, which was significantly lower than 26.25% in the control group (P < 0.01). Satisfaction degree of the doctors to nurses for the current operation in the observation group was significantly higher than that in the control group (P < 0.05). Conclusion Application of the HFMEA model in the perioperative nursing management of patients with emergency surgery for TBI can effectively improve surgical efficiency, reduce the incidence rates of nursing-related adverse events and complications, and enhance satisfaction degree of doctors to nurses in operation room.

Objective:To evaluate the safety and effectiveness of transjugular intrahepatic portosystemic shunt (TIPS) in hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT).Methods:Data of 15 patients undergoing TIPS for HCC with Vp4 PVTT and portal hypertension (PTN) in Peking University First Hospital from July 2018 to February 2023 were retrospectively analyzed, including 14 males and 1 female, aged (61.5±11.1) years old, ranging from 40 to 78 years old. The success rate of TIPS, portal pressure gradient (PPG) before and after procedure, perioperative adverse effects and complications were recorded. The survival status of patients was followed up by telephone review after surgery. Kaplan-Meier method was used for survival analysis.Results:The procedure of TIPS was performed uneventfully in all patients, with a technical success rate of 100% (15/15). PPG before and after TIPS were (31.73±5.48) mmHg (1 mmHg=0.133 kPa) and (17.60±3.66) mmHg, respectively, and the difference was statistically significant ( P<0.001). No perioperative death, hepatic artery or bile duct injury, acute liver failure or other major complications occurred. Compared with the preoperative status, the performance status scores [0(0, 0) vs. 3(3, 3)] and Child-Pugh scores [6(5, 8) vs. 9(8, 10)] were lower in patients one month after TIPS (all P<0.05). The median survival time was 228 d. Kaplan-Meier curves showed that the cumulative survival rates at 3, 6, 12 and 24 months after TIPS were 100%, 64.3%, 32.7% and 8.2%, respectively. Conclusion:TIPS could be safe and effective for HCC with Vp4 PVTT and severe PTN.

Objective:To learn about the infection and gene polymorphisms of hepatitis E virus (HEV) in murine-shaped animals of plague foci in Yunnan Province.Methods:From July to August 2019, around 16 natural villages (4 in Mile City, 6 in Mangshi and 6 in Lianghe County), which were the foci of domestic plague in Yunnan Province, the murine-shaped animals were captured by the night-time method. The liver RNA was extracted, and the target gene of rat HEV was detected by one-step real-time fluorescence quantitative PCR, and the positive rate of rat HEV was calculated. The rat HEV positive samples were amplified by PCR for further clone sequencing, and the resulting sequences were compared with the HEV sequences registered in the GenBank and a phylogenetic tree was constructed by using MegAlign and MEGA 7.0.Results:A total of 491 murine-shaped animals were captured from 3 orders, 5 families, 8 genera, 15 species, and the positive rate of rat HEV was 4.89% (24/491). Among them, the positive rate of Rattus tanezumi and Niviventer fulvescens was 9.39% (23/245) and 1/3, respectively; and other species were negative. There was a statistically significant difference in the positive rate of rat HEV between different habitats ( P = 0.014), and the positive rate of rat HEV in the habitats near the dwellings was higher than that in other habitats ( P < 0.05). The sequence comparison analysis showed that the gene sequence of P018 from Lianghe County was 100.0% homologous to the MG813927.1 sequence of the first patient with rat HEV in Hongkong, and it was clustered into the same branch with the sequences of MG813927.1 and LC549185.1 from rat, was the type HEV C. G024 from Mangshi shared a low homology (20.7% - 31.5%) with other virus strains, and it was clustered into the same branch with a HEV sequence from an avian (AY535004.1). Conclusions:Rat HEV is prevalent in murine-shaped animals of plague foci of Yunnan Province, and there may be gene polymorphisms of rat HEV. In addition, the difference infection rate may be related to the habitats.

Objective:To explore the practical effect of applied talent training model based on the"Four Combinations"among students majoring in Traditional Chinese Medicine in a Medical College.Methods:The undergraduate students majoring in Traditional Chinese Medicine at a medical college from grade 2021 and 2022 were selected as the research subjects and divided into two groups.Experimental group were students who had participated in various extracurricular competitions and innovation and entrepreneurship projects,while control group were students who had not participated in any competitions or projects.The final intellectual education scores of the two groups of students were compared(excluding the scores of Marxist basic principles).A questionnaire survey was conducted on the satisfaction of talent cultivation models among the above undergraduate students,and the validity and satisfaction analysis of the survey results were conducted.Results:The experimental group had significantly higher intellectual education scores than the control group(P＜0.05).The results of factor analysis indicated that the sample suitability and the questionnaire validity seem plausible(KMO=0.874).The overall satisfaction score of students towards the"Four Combinations"talent cultivation model was 4.16±0.2(out of 5),reflecting their high recognition of the model.Conclusion:The construction of a"Four Combinations"characteristic Traditional Chinese Medicine applied talent cultivation model is beneficial for improving the quality of cultivating high-quality and composite applied talents in Traditional Chinese Medicine,so as to provide high-quality applied talents with solid theoretical foundation and practical innovation capabilities for the Liaoshen region.

OBJECTIVETo explore the role of silent information regulator 1 (SIRT1) signaling pathway in mediating the effect of dexmedetomidine (DEX) to alleviate postoperative cognitive dysfunction (POCD) in aged rats.

METHODSSeventy-two healthy male Sprague-Dawley rats aged 18-20 months (weighing 500-700 g) were randomized equally into normal control group, POCD model group, DEX pretreatment group, and DEX and SIRT1 inhibitor (EX527) pretreatment group. In the latter 2 groups, DEX (25 μg/kg) was injected intraperitoneally in the rats 30 min before the operation, and normal saline was injected instead in the other 2 groups; in EX527 group, EX527 (1 μg/kg) was injected intravenously 5 min before the operation. In all but the control group, the rats were subjected to laparotomy lasting 30 min, and on days 1, 3, and 5 following the operation, 6 rats were randomly selected from each group for Morris water maze test to evaluate their cognitive functions. Immediately after the test, the rats were sacrificed and the hippocampus was collected for determination of the levels of tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) using ELISA; Western blotting was used to detect the expression of SIRT1 and nuclear factor- κB (NF-κB) in the hippocampal neurons.

RESULTSCompared with the control rats, the rats in POCD group and EX527 group showed significantly prolonged escape latency, decreased frequency of crossing the original platform, increased TNF- and IL-6 levels, lowered SIRT1 expression in the hippocampal neurons, and increased NF-κB expression ( < 0.05), and these parameters were comparable between POCD group and EX527 group ( > 0.05). DEX pretreatment significantly alleviated cognitive dysfunction and attenuated the changes in TNF-, IL-6, SIRT1, and NF-κB expressions induced by the operation ( < 0.05), and EX527 pretreatment of the rats obviously blocked the effects of DEX ( < 0.05).

CONCLUSIONSDEX alleviates POCD in aged rats probably via SIRT1 signaling pathway.

OBJECTIVE To obser ve the efficacy and safety of rimazo lom for painless gastroscopy sedation in outpatients. METHODS Totally 84 patients who underwent painless gastroscopy were collected from the outpatient department of the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from March to June in 2021. By random number table method combined with envelope allocation concealment method ，they were randomly divided into observation group and control group ，with 42 cases in each group. The patients in the observation group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+Rimazole toluenesulfonate for injection 0.2 mg/kg. Patients in the control group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+ Propofol emulsion injection 2 mg/kg. Gastroscopy was performed after the patient ’s consciousness disappeared. The sedative efficiency，sedative onset time ，recovery time and the occurrence of adverse drug reaction were observed in 2 groups. The heart rate（HR），mean arterial pressure （MAP），pulse oxygen saturation （SpO2），modified observer ’s assessment of alertness/sedation （MOAA/S）score and Narcotrend score were recorded in 2 groups after entering the room （T0），after anesthesia induction （T1）， when gastroscope entered the throat （T2），at the end of gastroscope withdrawal （T3），5 min after gastroscopy （T4）. RESULTS There was no significant difference in the effective rate of sedation （100％），the incidence of respiratory depression ， nausea and vomiting between the two groups （P＞0.05）. The qq.com onset time of sedation in the observation group was longer than control group ，and the recovery time and the incidence ofhypotension，hypotension to be tre ated，injection pain and bradycardia in observation group were significantly shorter or lower than control group （P＜0.05）. At T 0，there was no significant difference in HR ，MAP，SpO2，MOAA/S score or Narcotrend score between two groups （P＞0.05）. From T 1 to T 4，the HR of control group was significantly lower than that of the same group at T 0，and significantly lower than observation group at the same time（P＜0.05）. From T 1 to T 3，the MAP of two groups were significantly lower than the same group at T 0（P＜0.05），but there were no significant differences between two groups and between T 4 and T 0（P＞0.05）. There was no significant difference in SpO 2 at different time points between two groups and HR at different time points in observation group （P＞0.05）. From T 1 to T 3，MOAA/S score and Narcotrend score of two groups were significantly lower than the same group at T 0，while the MOAA/S score and Narcotrend score at T 1 and T 3 and Narcotrend score at T 3 of observation group were significantly higher than control group at the same time （P＜0.05），and the Narcotrend score of observation group at T 2 was significantly lower than control group at the same time（P＜0.05）；at T 4，there were no significant differences in MOAA/S score and Narcotrend score between two groups （P＞ 0.05）. CONCLUSIONS Remazolam shows good sedative effect and safety for painless gastroscopy.