Objective To investigate the protective effect and regulatory mechanism of ciprofol on Parkinson's disease(PD)rats based on the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α)signaling pathway.Methods Wistar rats were divided into blank control group,model group,ciprofol group,and ciprofol+AMPK inhibitor dorsomorphin group(ciprofol+Dor group),with 10 rats in each group.Except for the blank control group,PD models were estab-lished in the other three groups.Behavioral experiments were used to assess the motor and cognitive functions of rats in each group.Enzyme-linked immunosorbent assay(ELISA)was employed to de-tect the levels of dopamine(DA)and 5-hydroxytryptamine(5-HT)in the rat brain striatum.Immu-nofluorescence staining was conducted to measure the level of tyrosine hydroxylase(TH)in the rat brain substantia nigra.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was applied to detect the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,and Bax in the rat brain striatum.Western blot was used to determine the relative protein expression levels of ULK1,beclin1,Bcl-2,Bax,phosphorylated(p)-AMPK,SIRT1,PGC1α,and the ratio of LC3 Ⅱ to LC3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ)in the rat brain striatum.Results Compared with the blank control group,the motor and cognitive functions of rats in the model group were reduced,the levels of DA and 5-HT in the brain striatum decreased,the fluorescence intensity of TH in the brain substantia nigra weakened,and the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were reduced.In contrast,the relative mRNA expression level of Bax and the relative protein expression level of Bax increased,with statistically significant differ-ences(P＜0.05).Compared with the model group,the motor and cognitive functions of rats in the ciprofol group were improved,the levels of DA and 5-HT in the brain striatum increased,the fluo-rescence intensity of TH in the brain substantia nigra strengthened,and the relative mRNA expres-sion levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were elevated.Meanwhile,the relative mRNA expression level of Bax and the relative protein expression level of Bax decreased,with statistically significant differences(P＜0.05).The comparison between the ciprofol+Dor group and the ciprofol group revealed that the AMPK inhibitor dorsomorphin could re-verse the effects of ciprofol(P＜0.05).Conclusion Ciprofol may exert neuroprotective effects for PD rats by promoting autophagy through activating the AMPK/SIRT1/PGC1α signaling pathway.

Objective To investigate the effects and related molecular mechanisms of esket-amine on the proliferation,epithelial-mesenchymal transition(EMT),and stem cell properties of colorectal cancer(CRC)cells.Methods CRC cell line SW480 was cultured with varying concentra-tions of esketamine,and the cells were divided into blank group(0 μmol/L),low-concentration group(1 μmol/L),medium-concentration group(5 μmol/L)and high-concentration group(10 μmol/L).Cell proliferation activity was assessed using the EdU proliferation assay,cell spheroid-forming ability was evaluated via the spheroid formation assay,cell migration capacity was measured using the scratch assay,cell invasion ability was determined through the transwell assay,and the expression levels of tumor stem cell property markers[NANOG homeobox(NANOG),SRY-box transcription fac-tor(SOX)2,SOX4],the neurogenic locus Notch homolog protein 1(Notch1)receptor and the Notch1 intracellular domain(Notch1 ICD)were detected by western blot.A recovery test was con-ducted by adding the Notch1 receptor agonist Jagged1 to the culture groups with different concentra-tions of esketamine.Results Compared with the blank group,esketamine significantly inhibited the proliferation activity,spheroid-forming ability,migration ability,and invasion ability of CRC cells in a concentration-dependent manner.The intracellular expression levels of SOX2,SOX4,NANOG,and Notch1 ICD proteins were significantly decreased,while the expression level of the Notch1 recep-tor was significantly increased in the esketamine groups(P＜0.05).After the addition of Jagged1,the inhibitory effects of esketamine on the proliferation activity,metastatic ability,and stem cell properties of CRC cells were alleviated.Conclusion Esketamine inhibits CRC cell proliferation,metastasis,EMT,and stem cell properties by reducing the activation level of the Notch1 receptor,demonstrating a potential for clinical anti-tumor applications.

Objective: To analyze the changing trend and distribution characteristics of hepatitis C virus (HCV) infection among blood donors in Hebei, thereby providing data to support strategy and procedure adjustment for blood collection and supply institutions. Methods: Data from 12 blood stations in Hebei Province from 2012 to 2021 were collected. These data were analyzed to determine trends in anti-HCV antibody double reagent reactive rate and to characterize its distribution among different donor categories, genders and birth cohorts. Results: During the period from 2012 to 2021, a total of 7.4576 million samples were tested at 12 blood stations in Hebei Province, with 3.4659 million (46.47%) from first-time donors, and 3.9917 million (53.53%) from repeat donors. The number (of anti-HCV double reagent reactive samples was 7167 (9.61/10 000). The anti-HCV double reagent reactive rate showed a annual downward trend (P<0.05), from 17.40/10 000 at the beginning to 4.95/10 000 at the end of the study period. Additionally, the double reagent reactive rate of repeat blood donors had remained below 1/10 000 since 2017. The double reagent reactive rate of first-time blood donors (19.42/10 000) was higher than in repeat donors (1.09/10 000) (P<0.05), and the double-reagent reactive rate of female first-time blood donors (20.98/10 000) was higher than that of male first-time blood donors (18.49/10 000) (P<0.05). The anti-HCV double reagent reactive rate among first-time donors exhibited two distinct peaks within the pre-1976 and 1989-1994 birth cohorts, with notable gender differences observed in both peak periods. The rate of double reagent reactive in females born before 1976 (52.22/10 000) was higher than that in males (32.28/10 000) (P<0.05), while that of males born in 1989-1994 was higher (25.75/10 000) than that of females (14.28/10 000) (P<0.05). Conclusion: The prevalenc of HCV infection among blood donors in Hebei Province has shown a consistent year-over-year decline over the study period. The majority of infected individuals are found among the first-time blood donors born before 1995. These trends and characteristics provide valuable insights for developing pre-blood collection screening strategies, analyzing nucleic acid test data in blood screening, adjusting blood screening procedures, and provide evidence for targeted screening of high-risk populations as part of public health initiatives to eliminate hepatitis C.

Objective: To design HBV DNA proficiency testing and system comparison samples with different concentration gradients, analyze their detection results in PCR detection systems, evaluate the nucleic acid detection capabilities of laboratories and differences between detection systems, and put forward suggestions for continuous quality improvement to participating laboratories. Methods: Three groups of randomly numbered proficiency testing samples (with HBV DNA reference concentrations of <2, 7.5, and 30 IU/mL respectively) were taken as the detection objects. Using nucleic acid test data from 11 provincial blood station laboratories as the source, the samples were grouped by detection system and laboratory successively, and statistical analysis was conducted. Results: Statistical analysis of the detection data of the three groups of samples based on detection systems and laboratories showed that from low to high concentration, the coincidence rate between the detection results of different detection systems and laboratories and the expected results showed an increasing trend: 38.89%, 85.90%, and 100.00%; the same system exhibited certain differences in performance among different laboratories. Conclusion: Through this proficiency testing and system comparison, it is found that there are certain differences in the detection capabilities of different laboratories and different nucleic acid test systems. Blood station laboratories should standardize processes, strengthen quality management and data analysis on the basis of being familiar with the detection performance of their detection systems, and at the same time strengthen the control of laboratory interference factors to continuously improve the nucleic acid detection capabilities of blood station laboratories.

Objective:Using graph theory analysis, this study compares the topological and node attributes of the brain network to explore the differences in gray matter structural and functional network topological properties between bipolar depression (BD) patients with and without obsessive-compulsive symptoms (OCS).Methods:A total of 90 BD patients (27 males, 63 females; median age 19.0(22.0, 25.0) years) were recruited from the psychiatric outpatient and inpatient departments of the First Affiliated Hospital of Jinan University between March 2018 and December 2022. Fifty healthy controls (19 males, 31 females; median age: 23.0 (20.0, 27.0) years) were also enrolled. The BD patients were divided into two groups based on the presence of OCS: 53 with OCS (OCS group) and 37 without OCS (NOCS group). Resting-state structural and functional MRI data were collected for all participants to construct gray matter structural and functional networks. Graph therory analysis was applied to calculate network topological metrics such as small-world properties. The structural and functional network topological properties were compared among the BD-OCS, BD-nOCS, and control groups. Partial correlation analysis was conducted to examine the association between network topological metrics with significant group differences and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. Support vector machines (SVM) were used with these metrics as classification feature values to improve diagnostic accuracy through pairwise group classification.Results:Structural network analysis of gray matter: compared to HC group, both OCS group and NOCS group showed increased shortest path length and standardized characteristic path length (shortest path length: 0.78 and 0.80 vs. 0.69; normalized characteristic path length: 0.48 and 0.49 vs. 0.43), and decreased global efficiency (0.21 and 0.21 vs. 0.24) compared to the HC group (permutation test, all P<0.05). Compared to NOCS and HC groups, the OCS group showed increased nodal centrality and betweenness centrality in the right rolandic operculum and left superior occipital gyrus (permutation test, all P<0.05). Functional network analysis of gray matter: compared to the NOCS group, the OCS group showed increased node efficiency and decreased betweenness centrality in the cerebellum ( t=2.15, -3.04; all P<0.05); compared to HC groups, the OCS group showed decreased betweenness centrality in the cerebellum and left inferior frontal gyrus, along with increased node centrality and nodal efficiency in the right transverse temporal gyrus ( t=-2.99, -3.61, 3.06, 3.10; all P<0.05). In the OCS group, betweenness centrality in the left inferior frontal gyrus positively correlated with Y-BOCS scale obsessive thinking score ( r=0.303, P=0.034). Nodal centrality and node efficiency of the right transverse temporal gyrus negatively correlated with Y-BOCS total score ( r=-0.301, -0.311) and Y-BOCS obsessional thinking scores ( r=-0.385, -0.380) separately(all P<0.05). SVM classification: the combined network features achieved an area under the curve of 0.80 in distinguising OCS from NOCS patients. Conclusion:BD-OCS and BD-nOCS patients both exhibit consistent changes in gray matter structural network topology, with the OCS group displaying more pronounced nodal topological abnormalities. Multi-network feature integration demostrates potential for diagnostic classfication.

Objective:Using graph theory analysis, this study compares the topological and node attributes of the brain network to explore the differences in gray matter structural and functional network topological properties between bipolar depression (BD) patients with and without obsessive-compulsive symptoms (OCS).Methods:A total of 90 BD patients (27 males, 63 females; median age 19.0(22.0, 25.0) years) were recruited from the psychiatric outpatient and inpatient departments of the First Affiliated Hospital of Jinan University between March 2018 and December 2022. Fifty healthy controls (19 males, 31 females; median age: 23.0 (20.0, 27.0) years) were also enrolled. The BD patients were divided into two groups based on the presence of OCS: 53 with OCS (OCS group) and 37 without OCS (NOCS group). Resting-state structural and functional MRI data were collected for all participants to construct gray matter structural and functional networks. Graph therory analysis was applied to calculate network topological metrics such as small-world properties. The structural and functional network topological properties were compared among the BD-OCS, BD-nOCS, and control groups. Partial correlation analysis was conducted to examine the association between network topological metrics with significant group differences and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. Support vector machines (SVM) were used with these metrics as classification feature values to improve diagnostic accuracy through pairwise group classification.Results:Structural network analysis of gray matter: compared to HC group, both OCS group and NOCS group showed increased shortest path length and standardized characteristic path length (shortest path length: 0.78 and 0.80 vs. 0.69; normalized characteristic path length: 0.48 and 0.49 vs. 0.43), and decreased global efficiency (0.21 and 0.21 vs. 0.24) compared to the HC group (permutation test, all P<0.05). Compared to NOCS and HC groups, the OCS group showed increased nodal centrality and betweenness centrality in the right rolandic operculum and left superior occipital gyrus (permutation test, all P<0.05). Functional network analysis of gray matter: compared to the NOCS group, the OCS group showed increased node efficiency and decreased betweenness centrality in the cerebellum ( t=2.15, -3.04; all P<0.05); compared to HC groups, the OCS group showed decreased betweenness centrality in the cerebellum and left inferior frontal gyrus, along with increased node centrality and nodal efficiency in the right transverse temporal gyrus ( t=-2.99, -3.61, 3.06, 3.10; all P<0.05). In the OCS group, betweenness centrality in the left inferior frontal gyrus positively correlated with Y-BOCS scale obsessive thinking score ( r=0.303, P=0.034). Nodal centrality and node efficiency of the right transverse temporal gyrus negatively correlated with Y-BOCS total score ( r=-0.301, -0.311) and Y-BOCS obsessional thinking scores ( r=-0.385, -0.380) separately(all P<0.05). SVM classification: the combined network features achieved an area under the curve of 0.80 in distinguising OCS from NOCS patients. Conclusion:BD-OCS and BD-nOCS patients both exhibit consistent changes in gray matter structural network topology, with the OCS group displaying more pronounced nodal topological abnormalities. Multi-network feature integration demostrates potential for diagnostic classfication.

Objective:To investigate the dynamic brain function changes in adolescent depression patients with or without suicidal ideation, and to explore the characteristics and the hypothalamus-pituitary-adrenal axis of adrenocorticotropic hormone (ACTH) and the potential correlation between levels of the hormone cortisol.Methods:From March 2018 to January 2021, the First Affiliated Hospital of Jinan University conducted a study involving 48 adolescent patients with major depressive disorder (MDD) who have suicidal ideation(MDD+SI), 38 MDD patients without suicidal ideation(MDD-SI), and 41 healthy control participants(HC). The study utilized resting state functional magnetic resonance imaging (fMRI) to analyze the brain activity of these individuals. The dynamic local consistency (dReHo) and dynamic functional connection (dFC) values for the three groups were computed utilizing a sliding time window analysis technique. Blood samples were obtained within 24 hours following the completion of the MRI scan to quantify ACTH and cortisol levels via direct chemiluminescence. A one-way analysis of covariance was employed to compare the dReHo and dFC values among the three groups, while a one-way analysis of variance was utilized to compare the hormone levels across the three groups. Significant differences in dReHo values among the three groups were identified in specific regions, as well as in dFC values, using the least significant differences method correction following inspection ( P<0.05). Additionally, a partial correlation analysis was conducted to investigate the relationship between these dynamic indexes and hormone levels. Results:The difference of dReHo values among the three groups was found in the right posterior cerebellum (mainly Crus Ⅱ and Crus I) ( F=9.44, P<0.001), and the left precuneus ( F=10.93, P<0.05). There were significant differences in dFC values between the three groups in the left precuneus and left middle temporal gyrus ( F=9.60, P<0.001), and the left precuneus with bilateral precuneus ( F=9.66, P<0.001). The correlation analysis revealed a positive relationship between the decreased dReHo ( r=0.350, P=0.018) variability in the left precuneus, the decreased dFC( r=0.362, P=0.015) variability between the left precuneus and the left middle temporal gyrus (MTG), and the decreased cortisol level( P=0.013, 0.039) in the group of MDD+SI. Conclusion:Adolescents diagnosed with MDD, both with and without suicidal ideation, exhibit dynamic functional alterations in the precuneus and middle temporal gyrus. The cerebellar function changes appear to be unique to those with suicidal ideation. Furthermore, the aberrant dynamic brain function observed in the precuneus and middle temporal gyrus is associated with abnormal cortisol levels in individuals with suicidal ideation.

Objective:To investigate the clinical efficacy of robot-assisted screw fixation for unstable pelvic ring multifocal fractures.Methods:A retrospective analysis was performed on 76 patients with unstable pelvic fractures treated with orthopaedic robot-assisted screw fixation in the Trauma Center of the Affiliated Central Hospital of Shandong First Medical University from January 2015 to June 2022, including 43 males and 33 females, aged 52.53±13.68 years (range, 16-87 years). There were 43 cases of falling injuries from high places, 22 cases of traffic accidents, 11 cases of crushing injuries and heavy objects. Fifty-five patients were employed before the injury, while 21 were not. Fractures were classified according to the Tile classification, with 72 cases classified as type B and 4 cases as type C. Robot-assisted fixation techniques included internal fixator (INFIX), anterior ring screws, sacroiliac screws, and LC-II screws. Intraoperative blood loss, fluoroscopy frequency, surgical time, and the success rate of initial guidewire placement were recorded. Fracture reduction quality was evaluated using the Matta criteria, and postoperative pelvic function recovery was assessed using the Majeed criteria.Results:A total of 150 surgical procedures were performed on 76 patients, including 34 cases of INFIX fixation, 48 cases of anterior ring screws, 61 cases of sacroiliac joint screws, and 7 cases of LC-II screws. The mean intraoperative fluoroscopy frequency was 46.63±17.50 times (range, 15-93 times). Intraoperative fluoroscopy frequency varied among different fixation techniques, with INFIX group at 16.44±4.32 times, LC-II group at 21.59±5.80 times, anterior ring screws group at 29.44±11.65 times, and sacroiliac screws group at 23.10±11.87 times. The intraoperative blood loss was 20 (10, 47.5) ml (range, 5-300 ml), and the surgical time was 105 (86, 150) min (range, 30-290 min). The mean surgical time varied among different fixation techniques. All patients were followed up for an average of 6.46±2.26 months (range, 3-16 months). Clinical healing was achieved in all patients within 6 months, with an average time of 3.14±0.50 months. At the last follow-up, fracture reduction quality assessed by the Matta score was excellent in 21 cases and good in 43 cases, with an excellent/good rate of 84% (64/76). The Majeed score was 81.82±9.14 points (range, 50-92 points). For patients who were employed before the injury, the Majeed score was 86.55±4.85 points (range, 60-92 points), with 49 cases rated as excellent, 5 cases as good, and 1 case as fair. For patients who were not employed before the injury, the Majeed score was 69.43±5.34 points (range, 50-73 points), with 18 cases rated as excellent, 2 cases as good, and 1 case as fair. The overall excellent and good rate was 97% (74/76). Among patients who underwent INFIX internal fixation, 8 cases experienced lateral femoral cutaneous nerve injury postoperatively, all of which recovered sensation after 3 months; 1 case using LC-II screws experienced screw loosening postoperatively and was advised to reduce activity, then the screw was removed after fracture healing at 6 months postoperatively; 1 case using anterior ring channel screws experienced surgical site infection postoperatively, which was controlled after debridement.Conclusion:In the treatment of unstable pelvic ring multiple fractures, robot-assisted screw fixation has less blood loss, less fluoroscopy times, high success rate of planning guide needle, satisfactory reduction quality and postoperative function.

Objective:To investigate the dynamic brain function changes in adolescent depression patients with or without suicidal ideation, and to explore the characteristics and the hypothalamus-pituitary-adrenal axis of adrenocorticotropic hormone (ACTH) and the potential correlation between levels of the hormone cortisol.Methods:From March 2018 to January 2021, the First Affiliated Hospital of Jinan University conducted a study involving 48 adolescent patients with major depressive disorder (MDD) who have suicidal ideation(MDD+SI), 38 MDD patients without suicidal ideation(MDD-SI), and 41 healthy control participants(HC). The study utilized resting state functional magnetic resonance imaging (fMRI) to analyze the brain activity of these individuals. The dynamic local consistency (dReHo) and dynamic functional connection (dFC) values for the three groups were computed utilizing a sliding time window analysis technique. Blood samples were obtained within 24 hours following the completion of the MRI scan to quantify ACTH and cortisol levels via direct chemiluminescence. A one-way analysis of covariance was employed to compare the dReHo and dFC values among the three groups, while a one-way analysis of variance was utilized to compare the hormone levels across the three groups. Significant differences in dReHo values among the three groups were identified in specific regions, as well as in dFC values, using the least significant differences method correction following inspection ( P<0.05). Additionally, a partial correlation analysis was conducted to investigate the relationship between these dynamic indexes and hormone levels. Results:The difference of dReHo values among the three groups was found in the right posterior cerebellum (mainly Crus Ⅱ and Crus I) ( F=9.44, P<0.001), and the left precuneus ( F=10.93, P<0.05). There were significant differences in dFC values between the three groups in the left precuneus and left middle temporal gyrus ( F=9.60, P<0.001), and the left precuneus with bilateral precuneus ( F=9.66, P<0.001). The correlation analysis revealed a positive relationship between the decreased dReHo ( r=0.350, P=0.018) variability in the left precuneus, the decreased dFC( r=0.362, P=0.015) variability between the left precuneus and the left middle temporal gyrus (MTG), and the decreased cortisol level( P=0.013, 0.039) in the group of MDD+SI. Conclusion:Adolescents diagnosed with MDD, both with and without suicidal ideation, exhibit dynamic functional alterations in the precuneus and middle temporal gyrus. The cerebellar function changes appear to be unique to those with suicidal ideation. Furthermore, the aberrant dynamic brain function observed in the precuneus and middle temporal gyrus is associated with abnormal cortisol levels in individuals with suicidal ideation.

Objective:To understand the risk signal of ocular adverse events (AE) related to mycophenolate mofetil (MMF) and to provide reference for the safe clinical use of this drug.Methods:The US FDA Adverse Event Reporting System database was searched, and the AE reports on MMF as the primary suspect drug from the 1st quarter of 2004 to the 3rd quarter of 2022 were collected. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities version 24.0, and ocular AEs were screened out. The ocular AE risk signals were explored using 3 frequency methods, including reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, and Bayesian confidence propagation neural network method, and the multi-item gamma-Possion shrinker (MGPS) method. The information of the ocular AE reports and AE risk signals of MMF were analyzed descriptively. Results:A total of 402 cases of ocular AE with MMF as the primary suspect drug were collected, which involved 402 patients, 31 PTs and 5 SOCs. The 402 AE cases were reported among 33 countries, 283 of which had clinical outcome records, including death in 32 cases (11.3%), disability or blindness in 142 cases (50.2%), life-threatening in 14 cases (4.9%), and hospitalization or prolonged hospitalization in 95 cases (33.6%). Results of the frequency method showed that all 31 PTs were risk signals, while the results of the MGPS method manifested that 22 PTs were risk signals. None of the 31 PTs were recorded in the drug labels. The top 5 PTs in the number of AE reports were blindness (136 cases), cytomegalovirus chorioretinitis (37 cases), uveitis (34 cases), endophthalmitis (29 cases), and necrotising retinitis (22 cases). The ranking of signal intensity showed by the 4 methods was similar. The top 5 PTs with the high signal intensity were orbital apex syndrome [ ROR=55.84, PRR=55.83, information component ( IC)=5.58, empirical Bayesian geometric mean ( EBGM)=47.71], quadrantanopia ( ROR=43.22, PRR=43.21, IC=5.26, EBGM=38.21), retinitis viral ( ROR=40.13, PRR=40.13, IC=5.16, EBGM=35.78), optic discs blurred ( ROR=40.13, PRR=40.13, IC=5.16, EBGM=35.78), and serpiginous choroiditis ( ROR=31.07, PRR=31.07, IC=4.83, EBGM=28.41). Conclusions:The clinical manifestations of ocular AE during MMF treatment are diverse, and none of them are recorded in the drug label. The clinical outcomes are poor and can lead to blindness, which should be vigilant in clinical practice.