ObjectiveTo elucidate the potential mechanisms by which the classic prescription Anmeidan alleviates cognitive impairment in insomnia model rats through metabolic profiling. MethodsA total of 60 SD rats were randomly divided into six groups： blank group， model group， low-， medium-， and high-dose Anmeidan groups， and the Suvorexant group， with 10 rats in each group. Except for the blank group， the insomnia model was established in all other groups via intraperitoneal injection of para-chlorophenylalanine. The Suvorexant group was administered Suvorexant solution （30 mg·kg^-1·d^-1） by gavage， while the low-， medium-， and high-dose Anmeidan groups received Anmeidan decoction （4.55， 9.09， 18.18 g·kg^-1·d^-1） by gavage. The blank group received an equivalent volume of normal saline. The open field test was used to assess spatial exploration and anxiety/depressive-like behaviors in rats. Serum levels of epidermal growth factor （EGF）， brain-derived neurotrophic factor （BDNF）， and vasoactive intestinal peptide （VIP） were measured using enzyme-linked immunosorbent assay （ELISA）. Untargeted metabolomics was employed to identify differential metabolites in rat serum， and systematic biological methods were applied to analyze the potential targets and pathways of Anmeidan. ResultsCompared to the blank group， the model group exhibited significant reductions in total distance traveled， average speed， number of entries into the central area， time spent in the central area， and frequency of upright events （P<0.01）， along with significant decreases in VIP， EGF， and BDNF levels （P<0.05，P<0.01）. A total of 100 differential metabolites were identified between the model and blank groups. Compared to the model group， the low-， medium-， and high-dose Anmeidan groups showed significant increases in total distance traveled， average speed， number of entries into the central area， time spent in the central area， and frequency of upright events （P<0.05，P<0.01）， as well as a significant increase in VIP levels （P<0.05，P<0.01）. Anmeidan significantly reversed abnormal changes in 67 metabolites compared to the model group. A combined analysis identified 134 potential targets of Anmeidan， with network topology analysis suggesting that Caspase-3， B-cell lymphoma 2 （Bcl-2）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-2 （IL-2）， matrix metalloproteinase-9 （MMP-9）， and Toll-like receptor 4 （TLR4）， among others， may serve as key targets of Anmeidan. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis revealed major enriched pathways， including the cyclic adenosine monophosphate （cAMP） signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， and IL-17 signaling pathway. ConclusionThis study demonstrates that Anmeidan can recalibrate abnormal metabolic profiles in insomnia model rats to mitigate cognitive impairment， with its mechanisms of action potentially involving the regulation of immune-inflammatory responses， energy metabolism， and apoptosis-related pathways.

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*

Objective We conduct a systematic review and meta-analysis to evaluate the efficacy and safety of Suanzaoren decoction for post-stroke insomnia.Methods We conducted a comprehensive literature search,including PubMed,EMbase,CNKI,WanFang Data and so on,from the database creating to September 15th 2023.Our systematic review only included randomized controlled trials(RCTs)concerning with Suanzaoren decoction in treating post-stroke insomnia.Two reviewers independently screened the literature,extracted the data,and assessed the risk of bias for included studies.We used RevMan 5.3 software to perform Meta-analysis.Results A total of 13 RCTs were included,involving 1002 patients.The meta-analysis results showed that the clinical effective rate of the Suanzaoren decoction group was higher than the control group(OR=4.25,95%CI 2.79 to 6.46,P<0.00001).The Suanzaoren decoction group(combined with other treatments)reduced the Pittsburgh sleep quality index(PSQI)score more significantly than the control group(MD=-2.78,95%CI-3.24 to-2.33,P<0.00001).The Suanzaoren Decoction group was better than the control group in reducing the score of the National Institute of Health Stroke Scale(NIHSS)and improving neurological impairment(MD=-1.58,95%CI-1.95 to-1.21,P<0.00001).The incidence of adverse events in Suanzaoren Decoction group was lower than that in the control group(OR=0.38,95%CI 0.20 to 0.71,P=0.003).Conclusion Suanzaoren decoction can enhance the clinical efficacy and improve the degree of neurological defect of post-stroke insomnia patients,Suanzaoren decoction(combined with other treatments)can improve the sleep quality.The incidence of adverse events is lower.However,the efficacy and safety of Suanzaoren decoction for post-stroke insomnia still need to be further verified by more high-quality RCTs.

Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.

Objective:To investigate the diagnostic efficacy of MRI-based or CT-based measurements and the combined evaluation methods for preoperative bone quality assessment in patients with cervical degenerative diseases.Methods:Patients who underwent spine surgery for cervical degenerative diseases at the Department of Orthopedics, Huashan Hospital, Fudan University from September 2020 to March 2022 with available preoperative X-ray, CT, MRI and dule energy X-Ray absorptiometry (DEXA) data were included in this study. Vertebral bone quality score (VBQ) based on MRI T1-weightedimages and CT Hounsfiled unit (HU) values of the cervical spine were measured, and a combined diagnostic formula based on the binary logistic regression was constructed. The patients were divided into normal bone mass (T≥-1.0) and osteopenia/osteoporosis groups (T<-1.0). The student's t-test and Chi-square test were performed for comparisons between groups. The Pearson correlation coefficient was also used to investigate the correlation between DEXA-T scores, cervical VBQ and CT HU values. In addition, receiver operating characteristic curve (ROC) were plotted to explore the diagnostic efficacy of VBQ, CT HU and their combined diagnosis. Meanwhile, the corresponding sensitivity and specificity were obtained. Results:A total of 71 patients were included in this study (17 in the normal group and 54 in the osteopenia/osteoporosis group). The student's t-test showed that VBQ (2.90±0.70 vs. 3.83±0.83, t=4.23, P<0.001) and CT HU values (370.26±85.38 vs. 295.20±67.96, t=3.73, P=0.002) were significantly different between the two groups. The area under the ROC curve (AUC) for VBQ and CT values of the cervical spine were 0.81 and 0.75, respectively, and the AUC for the combined diagnostic value constructed on the basis of both was 0.85. Applying VBQ scores alone had a diagnostic sensitivity of 80% and a specificity of 70%, and the combined diagnosis with VBQ and CT HU had a sensitivity of 90% and a specificity of 75%. Person correlation analysis showed a significant correlation between DEXA T value, cervical VBQ value and CT HU value. The detailed formula was: DEXA T score=-0.63×cervical VBQ+0.64 ( r=-0.55, P<0.001), CT HU value=-40.20×cervical VBQ+458.40 ( r=-0.45, P<0.001), DEXA T score=0.006×CT HU-3.47 ( r=0.45, P<0.001). Conclusion:This study confirmed the feasibility of using cervical VBQ values, CT HU values and combined diagnostics for preoperative bone density screening in patients with degenerative cervical spine diseases. This method allows surgeons to perform an initial preoperative bone density screening based on the patient's existing imaging data, and thus could aid in confirming the indication and scheme of surgery. The method could be a powerful tool for preoperative bone density assessment screening in patients with cervical degenerative diseases.

Objective:To investigate the correlation between paraspinal muscle atrophy, morphological changes of facet joints and adjacent segment disease (ASDis) after lumbar fusion operation.Methods:A retrospective study was conducted among 195 patients who underwent posterior lumbar fusion again for ASDis at this institution from January 2014 to December 2020, including 29 patients with ASDis whose initial surgical fusion segment was L 4,5. According to Roussouly's staging, there were 5 cases of type I, 9 cases of type II, 10 cases of type III, and 5 cases of type IV. Another 29 cases were selected from patients without ASDis after lumbar fusion as a control group. The control group was paired 1∶1 with the ASDis group according to gender, fusion segment, and Roussouly typing of the lumbar spine. The cross-sectional area (CSA) and fat infiltration (FI) of paravertebral muscle, facet joint angle (F-J) and pedicle facet (P-F) angle before the first (second) operation were measured and compared between the two groups. Then logistic regression analysis was used to determine the predictors of ASDis after posterior lumbar fusion. Finally, the receiver operation characteristic (ROC) curve was described, and the area under the curve (AUC) and cut-off point were calculated. At the same time, the paraspinal muscle atrophy before the second operation in ASDis group was measured. Results:The average follow-up time of 98 patients was 59.25±6.38 months (range, 49-73 months). The average body mass index (BMI) of ASDis group was 24.76±3.64 kg/m 2, which was higher than that in control group (22.24±2.92 kg/m 2) ( t=2.481, P=0.041). The average CSA and relative cross-sectional area (rCSA) of paraspinal muscle in ASDis group were 3 214.32± 421.15 mm 2 and 1.69±0.36 respectively, which were less than 3 978.91±459.87 mm 2 and 2.26±0.29 in control group ( t=10.22, P=0.012; t=9.47, P=0.038). The FI degree of paraspinal muscle in ASDis group (21.95%±5.89%) was significantly higher than that in control group (14.64%±7.11%) ( t=7.32, P=0.002). The F-J angle in ASDis group was 35.06°±3.45°, which was less than 38.39°±4.67° in control group ( t=4.76, P=0.027). The P-F angle in ASDis group was 117.39°±8.13°, which was greater than 111.32°±4.78° in control group ( t=5.25, P=0.031). Multivariate logistic regression analysis showed that higher BMI ( OR=1.34, P=0.038), smaller rCSA of paraspinal muscle ( OR=0.02, P=0.017) and higher FI of paraspinal muscle ( OR=1.58, P=0.032) were the risk factors of postoperative ASDis. The ROC curve showed that the AUC of BMI was 0.680 and the cut-off point was 22.58 kg/m 2; The AUC of the FI of paraspinal muscle was 0.716 and the cut-off point was 15.69%; The AUC of rCSA of paraspinal muscle was 0.227 and the cut-off point was 1.92. For ASDis patients, the paraspinal muscle before the second operation had a higher degree of FI (25.47%±6.59% vs. 21.95%±5.89%, t=3.99, P=0.042) and a smaller rCSA (1.52±0.28 vs. 1.69±0.36, t=3.85, P=0.038) than that before the first operation. The difference between the FI degree of paraspinal muscle before the second operation and the first operation was negatively correlated with the occurrence time of ASDis ( r=-0.53, P=0.039) , and the difference of rCSA was positively correlated with the occurrence time of ASDis ( r=0.64, P=0.043) . Conclusion:When BMI >22.58 kg/m 2, FI of paraspinal muscle >15.69%, and rCSA of paraspinal muscle <1.92, it suggests that ASDis is more likely to occur after operation. And the more obvious paraspinal muscle atrophy after the first operation, the earlier ASDis may occur. Morphological changes of facet joints cannot be used as an index to predict the occurrence of ASDis.

Objective To explore the effect of " hospital informationized blood glucose management" on perioperative diabetic patients. Methods Three hundred patients with type 2 diabetes mellitus, who underwent selective operations from orthopedics, general surgery, urological surgery, and thoracic surgery were divided into two groups: 150 cases of blood glucose information management group and 150 cases of traditional blood glucose monitoring and management group. The blood glucose on target rate, percent of hypoglycemic events, percent of hyperglycemic events, the blood glucose level on the first postoperative day, the average hospitalization day, perioperative infection rate were evaluated for efficacy. Results The blood glucose on target rate in informationized blood glucose management group was significantly higher than that of the control group [(52.52 ± 18.31)%vs (14.88 ± 8.39)%, P＜0.01]. The frequency of hyperglycemia, the average daily blood glucose, the average blood glucose on fasting, after three meals and at night, the fasting and postprandial blood glucose level on the first postoperative day in informationized blood glucose management group were significantly lower than that of the control group [( 45. 31 ± 18.87)%vs (84.41±8.86)%, (8.59±1.34 vs 12.47±2.37) mmol/L, (7.33±1.41 vs 10.01±1.99)mmol/L, (8.89 ±2.34vs13.61±3.47)mmol/L,(9.47±1.94vs13.46±2.77)mmol/L,(9.40±2.72vs13.28±2.94)mmol/L, (8.28±2.11vs11.31±2.89)mmol/L,(8.29±2.51vs11.58±3.52)mmol/L,(8.25±3.67vs17.65±19.68) mmol/L, all P＜0.01]. In addition, the average hospitalization day of the informationized blood glucose management group was significantly shorter than that of the control group [(16±7 vs 21±15)d, P＜0.05]. The infection rate of the management group and the control group were 41. 2% and 58. 8% respectively. There was no significant difference between two groups (P＞0.05). Conclusion The " hospital informationized blood glucose management" is simple and practical, which may significantly improve the rate of blood glucose control in each period, reduce the average hospitalization day, and decrease perioperative infection tendency.

OBJECTIVECombined the optical principle with automatic control technology and computer real-time image detection technology to develop a non-contact system for noninvasive esophageal varices pressure measurement.

METHODSThe system included the adjustable air pump, laser device, image collection and analysis program. The feasibility and accuracy of the system were verified by in vitro experiments.

RESULTSThe bionic vascular pressure measured by this system had good correlation and repeatability with the actual pressure.

CONCLUSIONSThis system is accurate, feasible and has good application prospects.

Objective Combined the optical principle with automatic control technology and computer real-time image detection technology to develop a non-contact system for noninvasive esophageal varices pressure measurement.Methods The system included the adjustable air pump, laser device, image colection and analysis program. The feasibility and accuracy of the system were verifi ed by in vitro experiments.Results The bionic vascular pressure measured by this system had good correlation and repeatability with the actual pressure.Conclusions This system is accurate, feasible and has good application prospects.

Ring dermoid of cornea (RDC) is an autosomal dominant disorder of cornea. The previous study identified a G185A mutation of PITX2 gene in a Chinese family with RDC. To investigate the pathological mechanism of PITX2 R62H mutation, a PITX2 prokaryotic expression plasmid were constructed and GST-PITX2 fusion protein were purified. EMSA was further conducted. The DNA-banding ability of PITX2 R62H was similar to that of the wild type PITX2 were found. The cell lines stably expressed PITX2 was also generated, and cell cycle were analyzed by flow cytometry, and the expression of ?-catenin and Cyclin D1 were detected by quantitative Real-time PCR. The results showed that proliferating ability of cells expressing PITX2 R62H was lower than that of cells expressing PITX2 WT, as well as ?-catenin and Cyclin D1 mRNA level. These findings revealed that PITX2 R62H mutation affected the Wnt/?-catenin→PITX2 pathway, promoted the genes expressing abnormally, and led to abnormal cell proliferation and the formation of RDC, which may play an important role in pathogenesis of RDC.