The aim of this study is to investigate the protective effect of idebenone (IDE) combined with borneol (BO) against Parkinson's disease (PD). In this study, wild-type AB zebrafish and transgenic Tg ( vmat2: GFP) zebrafish with green fluorescence labeled dopamine neurons were used to establish the PD model with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). Following drug treatment, the behavioral performance and dopamine neuron morphology of zebrafish were evaluated, and regulation of dopamine signaling pathway-related genes was determined using RT-qPCR. The results showed that IDE combined with BO improved the behavioral disorders of zebrafish such as bradykinesia and shortening movement distance, also effectively reversed the damage of MPTP-induced dopaminergic neurons. At the same time, the expression of dopamine synthesis and transportation-related genes was up-regulated, and the normal function of the signal transduction pathway was restored. The combination showed a better therapeutic effect compared to the IDE monotherapy group. This study reveals the protective mechanism of IDE combined with BO on the central nervous system for the first time, which provides an important experimental basis and theoretical reference for clinical combination strategy in PD treatment.
Animals ; Zebrafish ; Signal Transduction/drug effects* ; Animals, Genetically Modified ; Dopamine/metabolism* ; Neuroprotective Agents/pharmacology* ; Disease Models, Animal ; Camphanes/pharmacology* ; Ubiquinone/pharmacology* ; Parkinson Disease/drug therapy* ; Dopaminergic Neurons/metabolism*

Objective: To investigate the protective effects of morusin on lipopolysaccharide (LPS)-induced acute liver injury in mice and its underlying mechanisms. Methods: Thirty-two male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups (n = 8 per group): control, LPS, low-dose morusin (morusin-L, 10 mg/kg), and high-dose morusin (morusin-H, 20 mg/kg) groups. The mice in each group were administered the corresponding drugs or normal saline via continuous gavage daily for 16 consecutive days. Except for control group, which received an equal volume of normal saline, other groups were intraperitoneally injected with LPS (5 mg/kg) 2 h after the last gavage to establish the acute liver injury model. Serum and liver tissues were collected for subsequent analysis 6 h after LPS injection. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected with biochemical methods. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in serum were measured by enzyme-linked immunosorbent assay (ELISA). Hepatic pathological changes were evaluated by hematoxylin-eosin (HE) staining. The 16S ribosomal RNA (16S rRNA) sequencing was performed to assess the composition of intestinal flora, linear discriminant analysis effect size (LEfSe) was applied for multi-level species discrimination, and Spearman’s correlation analysis was performed. The liver tissues of mice with acute liver injury were analyzed by RNA sequencing (RNA-seq) technology to identify differentially expressed genes (DEGs), and then enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was conducted. The expression levels of selected genes was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), while immunohistochemistry (IHC) was performed to examine the expression levels of IL-6, myeloid differentiation primary response 88 (MYD88), and toll-like receptor 2 (TLR2). Results: Morusin significantly reduced the serum levels of ALT, AST, and inflammatory factors (TNF-α, IL-6, and IL-1β) (P < 0.05, P < 0.01, or P < 0.001), while alleviating the hepatic pathological damage in mice. Based on efficacy comparisons, morusin-H group was selected for subsequent microbiome and transcriptome analyses. Microbiome analysis revealed that morusin-H effectively mitigated LPS-induced gut dysbiosis and restored the Firmicutes/Bacteroidota balance (P < 0.01). At the genus level, morusin-H significantly reduced the abundances of norank_f_Muribaculaceae, Desulfovibrio, Parabacteroides, and Muribaculum (P < 0.05, P < 0.01, or P < 0.001). At the phylum, family, and genus levels, our findings indicated that morusin-H treatment caused a significant decrease in the abundance of Desulfobacterota, Desulfovibrionaceae, and Desulfovibrio (P < 0.01). Importantly, the abundance of Desulfovibrio was positively correlated with the levels of ALT, AST, TNF-α, IL-1β, and IL-6. Transcriptomic and molecular analyses showed that the therapeutic mechanism of morusin-H involved suppression of the IL-17/TNF signaling pathways and downregulating the mRNA levels of Tlr2, Tlr3, Myd88, Il6, and Cxcl10 (P < 0.05 or P < 0.001), as well as the protein levels of key inflammatory mediators (IL-6, MYD88, and TLR2) (P < 0.001). Conclusion Morusin demonstrates protective effects against LPS-induced acute liver injury, likely through modulation of gut microbiota and suppression of pro-inflammatory factor expression. These findings indicate that morusin exerts its effects through the "microbiota-inflammation-liver" axis, providing a theoretical basis for its use as a multi-target plant-based drug in the treatment of metabolic inflammation-related liver diseases.

Objective To analyze the characteristics of blood lipid metabolism in patients with Wilson's disease(WD)and understand the influencing factors of abnormal blood lipid.Methods The clinical data of 170 patients with WD and 59 healthy people were collected from June 2021 to March 2023,the blood lipids of the two groups were compared.To compare the characteristics of blood lipid metabolism in WD patients with different gender,age,body mass index(BMI)and disease types.According to whether the blood lipid was abnormal or not,WD patients were divided into normal blood lipid group and abnormal blood lipid group,and the biochemical indexes of the two groups were compared.The general situation and biochemical indicators were included in the single factor regression analysis,and the related factors that might affect blood lipid metabolism were screened out.The related factors of single factor screening were included in multivariate Logistic regression analysis to determine the abnormal factors affecting blood lipid.Results The triglyceride(TG)level of WD patients was lower than that of healthy controls,the difference was statistically significant(P<0.05).The rate of dyslipidemia in WD patients was 40.59%.Low density liporotein cholestrol in female WD patients was significantly lower than that in male WD patients(P<0.05).The values of BMI,alanine aminotransferase(ALT)and uric acid(UA)in dyslipidemia group of WD patients were significantly higher than those in normal group(all P<0.05).Multivariate Logistic regression analysis showed that BMI 24～28(OR=4.526,P<0.05),BMI>28(OR=6.360,P<0.05),UA(OR=1.006,P<0.01)and hyaluronic acid(HA)(OR=1.003,P<0.01)were associated with the high risk of dyslipidemia,with statistical significance.Conclusions WD patients have a high incidence of abnormal lipid metabolism,mainly with low high density liporotein cholestrol and high TG.The dyslipidemia in WD patients is affected by many factors.BMI,UA and HA are independent risk factors for dyslipidemia in WD patients.

Objective:To investigate the value of ultrasonic measurement of the ratio of optic nerve sheath diameter (ONSD) to eyeball transverse diameter(ETD) in the diagnosis and prognosis of intracranial hypertension in patients with craniocerebral trauma.Methods:A total of 120 patients with craniocerebral trauma treated in the Xingtai General Hospital of North China Medical and Health Group from December 2021 to January 2023 were perspectively selected, and they were divided into normal intracranial pressure group (73 cases) and intracranial hypertension group (47 cases) according to the results of intracranial pressure measurements, and the intracranial hypertension group was divided into good prognosis group (20 cases) and poor prognosis group (27 cases) according to the follow-up prognosis. The efficacy of ONSD, ETD and ONSD/ETD in intracranial hypertension diagnosis and prognosis assessment were analyzed by receiver operating characteristic (ROC) curve. Kaplan-Meier method was used to evaluate the 6-month risk of adverse prognosis of patients, and the comparison was made by Log-rank test.Results:The levels of intracranial pressure, ONSD, ONSD/ETD in the normal intracranial pressure group were lower than those in the intracranial hypertension group: (130.73 ± 23.63) mmH 2O (1 mmH 2O = 0.009 8 kPa) vs. (270.11 ± 35.78) mmH 2O, (5.47 ± 0.29) mm vs. (5.78 ± 0.44) mm, 0.246 ± 0.018 vs. 0.263 ± 0.018, there were statistical differences ( P<0.05). The scores of Glasgow Coma Scale (GCS), intracranial pressure, ONSD, ONSD/ETD in the good prognosis group were lower than those in the poor prognosis group: (5.50 ± 1.24) scores vs. (6.41 ± 1.34) scores, (256.15 ± 30.23) mmH 2O vs. (280.44 ± 36.56) mmH 2O, (5.62 ± 0.40) mm vs. (5.90 ± 0.44) mm, 0.254 ± 0.014 vs. 0.270 ± 0.017, there were statistical differences ( P<0.05). ROC curve analysis results showed that the area under the curve (AUC) of ONSD and ONSD/ETD for diagnosing intracranial hypertension in patients with craniocerebral trauma were 0.718 and 0.765, respectively, and the critical values were 5.87 mm and 0.263, respectively. The AUC of ONSD and ONSD/ETD predicting prognosis of intracranial hypertension patients was 0.677 and 0.763, respectively, and the critical values were 5.90 mm and 0.267, respectively. Grouped by the threshold of ONSD/ETD for the prognosis of intracranial hypertension (0.267), the incidence of adverse prognosis in ONSD/ETD > 0.267 group was higher than that in the ONSD/ETD≤0.267 group, there was statistical difference ( P<0.05). Conclusions:ONSD/ETD can be used as an index for diagnosis and prognosis of intracranial hypertension.

OBJECTIVE To analyze the influential factors on trough concentration （cmin） and area under the drug concentration time curve （AUC） of voriconazole （VRZ） in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation （HSCT）. METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024. The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated. The factors affecting cmin and AUC of VRZ were analyzed using multiple linear regression. RESULTS A total of 120 cases of VRZ cmin in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L； 46 cases had a cmin in 0.5-5 mg/L（ 38.33%）， 2 cases had a cmin＞5 mg/L（ 1.67%）， and 72 cases had a cmin＜0.5 mg/L. The median AUC of VRZ was 11.68 mg·h/L. The patient’s body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine had significant effects on VRZ cmin （P＜0.05）. Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC （P＜0.05）. CONCLUSIONS The body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine are independent factors affecting VRZ cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.

ObjectiveTo explore the characteristics and associated risk factors of diabetes in patients with schizophrenia living in communities, and to provide a basis for the prevention of diabetes comorbidity in this population. MethodsA stratified cluster sampling was used to randomly select patients with schizophrenia in Shanghai who participated in the free health examination provided by the National Basic Public Health Services in 2020. Statistical methods were employed to analyze the general demographic data, clinical characteristics, and laboratory test results of the study subjects. ResultsThe study included 3 374 individuals with schizophrenia, among which the prevalence of diabetes was 17.01%. Statistically significant differences were observed in terms of age, education level, urban area type, marital status, employment status, duration of illness, blood pressure, body mass index, total cholesterol, and triglyceride levels (all P<0.05). Multivariate logistic regression analysis revealed that living in non-central urban areas (OR=1.76, 95%CI: 1.33‒2.32), disease duration of 6‒ years (OR=2.60, 95%CI: 1.07‒6.32), disease duration of 11‒ years (OR=2.72, 95%CI: 1.17‒6.35), disease duration of 16‒ years (OR=3.38, 95%CI: 1.54‒7.42), hypertension(OR=1.73, 95%CI: 1.27‒2.36), obesity (OR=1.52, 95%CI: 1.15‒2.00), and elevated triglyceride levels (OR=2.78, 95%CI: 2.22‒3.49) were risk factors for diabetes in patients with schizophrenia. ConclusionThe prevalence of diabetes in community-dwelling patients with schizophrenia is higher than that in the general population. It is recommended that appropriate health education and rehabilitation guidance be provided as part of community-based mental health services.

Objective:To investigate the diagnostic value of density features of computed tomography(CT)of the fat around pericoronary artery of dual-source computer tomography angiography(CTA)combined with electrocardiogram(ECG)on the severity of disease condition in patients with coronary heart disease(CHD).Methods:A total of 120 CHD patients who admitted to Shanxi Bethune Hospital from March 2021 to March 2023 were selected,and they were grouped according to the New York Heart Association(NYHA).Among of them,86 cases at grade Ⅱ-Ⅲ were divided into grade Ⅱ-Ⅲ group,and 34 cases at grade Ⅳ were divided into grade Ⅳ group.A dual-source CT was used to detect the densities of different coronary branches of Pericardial Adipose Tissue(PCAT)of average coronary artery of proximal left anterior descending artery(pLAD),mid left anterior descending artery(mLAD),proximal left circumflex artery(pLCX),proximal right coronary artery(pRCA),mid right coronary artery(mRCA)and distal right coronary artery(dRCA)of all patients,and ECG was used to detect and record the value of QRS voltage,QRS time limit value and QTc interval of patients.The mean PCAT densities of pLAD,mLAD,pLCX,pRCA,mRCA and Drca,and the QRS voltage and QRS time limit,as well as QTc interval between the two groups were observed and compared.The receiver operating characteristics(ROC)curve was used to analyze the efficacies of the above indicators in single diagnosis and combined diagnosis for the severity of disease condition of CHD patients.Results:The mean PCAT density of pLAD,mLAD,pLCX,pRCA,mRCA,mRCA and dRCA,and QRS time limit and QTc interval of patients in grade Ⅱ-Ⅲ group were significantly lower than those in grade Ⅳ group,with statistically significant difference(t=58.681,5.097,5.902,13.513,P<0.05),respectively.The area under curve(AUC)values of ROC curves of ECG and CT density of the fat around pericoronary artery of CTA were larger than 0.5 for the severity of disease condition in CHD patients,and the highest AUC value of combined diagnosis was 0.966.The results of Pearson linear correlation analysis showed that there were correlations among mean PCAT density,QRS voltage,QRS time limit and QTc interval,and there were significantly negative correlations between QRS voltage and mean PCAT density,between QRS time limit and QTc interval(r=-0.754,-0.280,-0.452,P<0.05),and there were significantly positive correlations among mean PCAT density,QRS time limit,QTc interval and the severity of the disease condition of CHD patients(r=0.983,0.435,0.547,P<0.05),respectively.There was a significantly negative correlation between QRS voltage and severity of disease condition of CHD patients(r=-0.776,P<0.05).Conclusion:The combination of CT density features of the fat around pericoronary artery of coronary artery CTA and ECG QRS wave group detection is helpful to the diagnosis for the severity of disease condition of CHD patients,which can improve the accuracy of diagnosis and has a certain of application value.

Objective:To investigate the application value of computed tomography (CT) and magnetic resonance imaging (MRI) examination in clinical diagnosis of gallbladder tumor with perigallbladder invasion.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 80 gallbladder tumor patients with perigallbladder invasion who were admitted to 3 medical centers (21 cases in The First Affiliated Hospital of Northwest University, 42 cases in The First Affiliated Hospital of the Air Force Medical University, 17 cases in The First Affiliated Hospital of Dalian Medical University) from January 2021 to December 2022 were collec-ted. There were 45 males and 35 females, aged (56±4)years. Observation indicators: (1) CT and MRI examinations; (2) surgical conditions. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) CT and MRI examinations. Of 80 patients, cases with gallbladder cancer and gallbladder adenoma were 73 and 7, respectively. Cases with endoluminal nodular type, mass type and localized thick-walled type were 33, 39 and 8, respectively, with tumor diameter as 1.55 cm×1.35 cm×1.33 cm, 1.64 cm×1.37 cm×1.36 cm and 5.72 cm×4.07 cm×4.36 cm. Results of CT examination of endoluminal nodular type showed local nodular protrusions into the endoluminal area, and local enhancement on enhanced scanning. Results of CT examination of localized thick-walled type showed the cavity wall of lesion was locally or diffusely irregul-arly thickened, with a thickness of 1.10(range, 1.10-2.21)cm. Of 80 patients, results of CT and MRI examinations showed invasion of liver parenchyma in 68 cases, which was manifested as local mass, blurred demarcation, and abnormal protrusion. The maximum depth was (4.22±0.25)cm, (4.22±0.22)cm, (4.28±0.16)cm of cross-sectional, coronal, sagittal view in CT examination, respectively. The minimum depth was (0.22±0.10)cm, (0.25±0.08)cm, (0.24±0.12)cm. The depth of liver parenchyma invaded was (1.64±1.38)cm, (1.68±1.46)cm, (1.66±1.40)cm. Results of CT and MRI examinations showed invasion of perigallbladder, which was manifested as local invasion of the gastric antrum in 12 cases. (2) Surgical conditions. Of 80 patients, results of CT and MRI examina-tions showed that 60 patients had localized masses in the gallbladder cavity with or without infiltration of surrounding tissues. After confirming the absence of other organs and distant metastasis, cases undergoing radical resection and palliative resection were 44 and 16, respectively. Results of CT and MRI examina-tions showed that 20 patients had malignant gallbladder tumors with peri-pheral liver infiltration and multiple intrahepatic metastases with distant organ metastases, which were unresectable.Conclusion:For patients with gallbladder cancer and perigallbladder invasion, CT or MRI examina-tions can show their structural characteristics.

Objective:To understand the reinfection rate of 2019-nCoV in the previously infected population in Suzhou and compare the illness severity and prognosis of the reinfection cases with the first-time infection cases.Methods:A questionnaire survey was conducted in the persons with previous 2019-nCoV infection reported in Suzhou from January 22, 2020 to November 8, 2022 to collect the information about the incidence of reinfection of 2019-nCoV in this population from December 8, 2022 to January 18, 2023. The persons who were infected with 2019-nCoV for the first time were selected by marching the residence, age and gender at ratio of 1∶2 from 2019-nCoV infection community follow-up cohort of Suzhou. By χ2 test, the clinical symptoms and prognosis of the reinfection case and the first-time infection cases were compared. Results:The reinfection rate of 2019-nCoV was 13.01% (147/1 130) in Suzhou. No reinfection was found within 1-6 months after the first-time infection, the rate of reinfection was 10.59% (95/897) in those with interval of 7-12 months between the reinfection and the first-time infection and 45.61% (52/114) in those with the interval ≥24 months. The lowest reinfection rate was 9.09% (1/11) in those who had completed 4 doses of 2019-nCoV vaccination. The main symptoms of the reinfection cases were similar to those of the first-time infection cases. Except for dry cough, nausea/poor appetite and other symptoms, there were significant differences in other clinical symptoms between the two groups ( P<0.05). In the reinfection cases, fever had shorter duration with lower body temperature. The hospital visit rate in the reinfection cases was 4.08% (6/147), lower than that in the cases with the first-time infection (11.56%, 34/294). The time for negative nucleic acid (antigen) test result and recovery from illness after the reinfection were shorter than those after the first-time infection. Conclusions:Reinfection occurred in some people who had been infected with 2019-nCoV. The interval between the reinfection and the first-time infection and the completion of the 4 doses of booster vaccination were the factors influencing the reinfection rate. The hospital visit rate in the reinfection cases was lower than that in the cases with the first-time infection. The reinfection had similar symptoms and shorter illness duration compared with the first-time infection.

Squalene monooxygenase (SQLE) is the rate-limiting enzyme of cholesterol biosynthesis. It plays a crucial role in regulating cholesterol homeostasis. Increasing evidence shows that SQLE is closely related to the occurrence, development, metastasis, and poor prognosis of various cancers. SQLE can not only promote the proliferation of cancer cells and epithelial-mesenchymal transformation but also play an important role in maintaining the stemness of cancer stem cells and regulating cholesterol homeostasis. SQLE may be a potential molecular target for cancer therapy. In this review, the role of SQLE in regulating cholesterol homeostasis in vivo; its function in the occurrence, development, and metastasis of various cancers; and its molecular mechanism were summarized. Screening new SQLE inhibitors may provide new ideas for targeted cancer therapy.