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:To investigate the correlation between the clinical features and endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) in patients with cirrhosis.Methods:A total of 148 patients with cirrhosis and portal hypertension who underwent EUS-PPG measurement at the Third Xiangya Hospital of Central South University from March 15, 2022 to June 20, 2023 were selected. The clinical data of patients collected before EUS-PPG measurement were analyzed. Variations in the EUS-PPG across different clinical data subgroups were analyzed. Multivariate linear regression analysis was used to explore the independent factors influencing EUS-PPG.Results:The EUS-PPG was significantly elevated in patients exhibiting red signs (16.62±5.33 mmHg VS 13.44±5.34 mmHg, t=3.616, P<0.001), gastroesophageal varices (15.78±5.30 mmHg VS 9.70±4.77 mmHg, t=4.247, P<0.001), hepatic encephalopathy (20.83±7.52 mmHg VS 14.92±5.35 mmHg, t=2.606, P=0.010), thrombocytopenia (15.66±5.39 mmHg VS 13.29±5.83 mmHg, t=2.136, P=0.034), hypoproteinemia (16.13±5.86 mmHg VS 14.12±5.03 mmHg, t=2.230, P=0.027), and an increased international normalized ratio (16.25±6.00 mmHg VS 14.40±5.11 mmHg, t=2.022, P=0.045). Conversely, the EUS-PPG was significantly reduced in patients with a history of splenectomy and devascularization (13.17±5.88 mmHg VS 15.73±5.34 mmHg, t=-2.379, P=0.019). The EUS-PPG in patients with varying degrees of ascites (no VS slight VS moderate or severe: 13.40±5.48 mmHg VS 15.90±5.49 mmHg VS 16.69±5.17 mmHg, F=5.188, P=0.007) and different Child-Pugh classifications (A VS B VS C: 14.07±5.05 mmHg VS 15.69±5.74 mmHg VS 17.64±5.99 mmHg, F=3.066, P=0.049) increased gradually. Multivariable linear regression analysis showed that red signs ( β=2.44, t=2.732, P=0.007), gastroesophageal varices ( β=4.45, t=2.990, P=0.003), ascites ( β=1.75, t=2.368, P=0.019), and hepatic encephalopathy ( β=5.82, t=2.644, P=0.009) were independent factors for the elevated EUS-PPG. Conclusion:There is a significant correlation between EUS-PPG and the clinical features related to the severity of cirrhotic portal hypertension, which indicates the feasibility of EUS-PPG in evaluating cirrhotic portal hypertension.

To analyze the clinical data of 2 neonates with Langerhans cell histiocytosis (LCH). The rashes appeared in both cases shortly after birth.Case 1 had both rashes and neonatal sepsis, and no other tissues and organs were involved.After anti-infective treatment, the rashes gradually disappeared.Case 2 had secondary pneumonia, abnormal coagulation function and gastrointestinal bleeding.Both cases were positive for CD1a and S-100 by immunohistochemical staining of skin biopsy, and they were diagnosed as multi system-LCH.The early diagnosis of LCH is particularly important.The detection methods of skin or lymph node biopsy like immunohistochemistry, need to be performed as early as possible.Because the course of the disease is not clear, a close monitoring and follow-up are needed.

Objective: To improve the diagnosis and therapy of childhood pulmonary thromboembolism (PTE) by analyzing the clinical features of this rare condition. Methods: A total of 8 pediatric patients (4 males, 4 females) with PTE diagnosed in the Children′s Hospital of Zhejiang University School of Medicine from March, 2014 to March, 2019 were enrolled. The clinical manifestation, laboratory results, imaging findings, diagnosis and treatment were summarized. Results: Among these 8 cases, aged from 9 hours to 14 years and 10 months. Fever was found in 4 cases, cough aggravation in 4, short of breath in 3, chest pain in 2, abdominal and back pain in one, hemoptysis in 2, cyanosis in 1, and edema of lower extremities in 2. Physical examination found decreased breath sound in 2 cases, phlegm rale in 3, and pleural friction rub in one. Pleural effusion was found in 5 cases by ultrasound. Plasma D-dimer increased in 6 cases (0.66-9.96 mg/L) and hypersensitive C-reactive protein elevated in 5 cases (10.78-78.00 mg/L). Chest enhanced CT showed pulmonary artery or venous filling defects, including pulmonary artery embolism in 7 cases and pulmonary vein embolism in one. The primary disease of these patients included Mycoplasma Pneumoniae pneumonia in 4 cases, nephritis in 2 and postoperative congenital heart disease in 2. Apart from one case who withdrew the treatment and was discharged, the other 7 patients received anticoagulant treatment had good outcome. Conclusions For children with Mycoplasma pneumoniae pneumonia, immune disorders, long-term hormone therapy, cardiovascular invasive operation or other high-risk factors, PTE should be considered when fever, cough aggravation, short of breath, chest and back pain with pleural effusion are present. Chest enhanced CT scan should be performed as soon as possible, and anticoagulation should be started once the diagnosis is confirmed.

Objective:To investigate the operational impact of the curve laterality of degenerative lumbar scoliosis on oblique lateral lumbar interbody fusion (OLIF).Methods:Data of 40 cases with degenerative lumbar scoliosis and 20 cases without degenerative lumbar scoliosis treated in our hospital from January to December 2017 were retrospectively analyzed. There were 20 cases in left convex group (male 5, female 15, 70.62±5.45 years old) and 20 cases in left concave group (male 3, female 17, 69.73±7.24 years old), and there were 20 cases of lumbar degenerative diseases without scoliosis (lumbar spinal stenosis 13 cases, lumbar disc herniation 7 cases; male 5, female 15, 71.48±5.73 years old). The following OLIF operation-related anatomical parameters were measured on MR axial T2 weighted image and lumbar spine X-ray image: distance from the left edge of the abdominal aorta to the anterior medial edge of the left psoas muscle; distance from the left edge of the abdominal aorta to the left lumbar sympathetic trunk; distance from the anterior medial edge of the left psoas muscle to the transverse axis of the vertebral body; distance between the midpoints of adjacent vertebral bodies in L 2-5; angle of rotation of the vertebral body and angle of the OLIF operating channel. One-way analysis of variance(ANOVA) and least significant difference (LSD) were used for statistical analysis of measurement parameters of different groups. Results:There were statistically significant differences between the distance from the left edge of the abdominal aorta to the anterior medial edge of the left psoas muscle, and the distance from the left edge of the abdominal aorta to the left lumbar sympathetic trunk in the three groups of cases (All P<0.05). The L 2, 3 segment (24.41±9.54 mm, 18.18±7.1 mm) and L 3, 4 segment (18.54±7.94 mm, 13.73±6.73 mm) in the left concave group were significantly larger than those in the no scoliosis group; and the above values of the L 4, 5 segment of the left convex group (19.16±7.04 mm, 11.67±3.63 mm) were significantly larger than those in the no scoliosis group. For the distance from the anterior medial edge of the left psoas muscle to the transverse axis of the vertebral body, the values of L 2, 3 and L 3, 4 (13.76±2.98 mm, 15.87±3.53 mm) in the left convex group were significantly greater than those in the no scoliosis control group; but in the left concave group, the corresponding values (9.97±3.14 mm, 10.75±5.03 mm) were significantly smaller than those in the no scoliosis group. The distances between the midpoints of adjacent vertebral bodies of L 2, 3 and L 3, 4 (37.67±3.45 mm, 38.18±3.54 mm) in the left convex group were greater than those in the no scoliosis group and left concave group, and the differences between the three groups were statistically significant ( P<0.05). Pearson correlation analysis between the absolute value of vertebral rotation angle and OLIF surgical passage angle showed that there was a negative correlation between them in the left convex group and a positive correlation in the left concave group. Conclusion:The curve laterality of degenerative lumbar scoliosis had a certain influence on the anatomical parameters of oblique lateral lumbar interbody fusion. It was recommended to design and adjust the operation skills according to the curve laterality before surgery.

To investigate the influence of Angelica Four Inverse Decoction on diabetic peripheral neuropathy (DPN) nerve conduction velocity and advanced glycation end products (AEGs), Cystatin C (Cys-C) and homocysteine (Hcy) levels, 78 cases of DPN patients admitted in our hospital from March 2015 to January 2017 were selected and divided into two groups by random number table method. The two groups adopted the same basic treatment, on the basis of which, the control group was added mecobalamin tablets treatment, while the observation group was given Angelica Four Inverse Decoction. The curative effect of Chinese medicine syndrome, the scores of toronto clinical scoring system (TCSS), nerve conduction velocity and the change of serum AEGs, Cys-C and Hcy levels before and after treatment were recorded and compared between the two groups and then the safety of medicine were evaluated between the two groups. 4 weeks after the treatment, the total effective rate of the observation group was 89.7％, significantly higher than 71.8％ of the control group (P ＜ 0.05) . Compared with those before receiving treatment, the SNCV and MNCV values of the common peroneal nerve and median nerve both significantly increased in the two groups 4 weeks after the treatment (P ＜ 0.01); the improvement of nerve conduction velocity of the observation group was significantly better than that of the control group (P ＜ 0.01) . 4 weeks after the treatment, TCSS score and serum AEGs, Cys-C, Hcy levels were all significantly lower than those before receiving the treatment in the two groups (P ＜ 0.01); compared with that of the control group in the same time period, the improvement effect of TCSS score and serum AEGs, Cys-C, Hcy levels were more significant in the observation group 4 weeks after the treatment (P ＜ 0.01) . There were no obvious adverse reactions in the two groups. As a result, Angelica Four Inverse Decoction applied to DPN patients can more effectively relieve clinical symptoms and signs, improve nerve conduction velocity, reduce the level of AEGs, and improve microcirculation with remarkable curative effect and high safety.

Objective To investigate the mechanisms of sacroiliac joint pain after lumbar fusion surgery and to present the clinical outcomes after a combining intra-and peri-articular injection.Methods Totally 20 male and 15 female patients (48-75 years old) from January 2013 to December 2016 were retrospectively included in the present study.The patients were all with sustained low back and hip pain after prior posterior lumbar interbody fusion surgery.Nine cases were diagnosed with lumbar disc herniation,22 cases with lumbar stenosis,and 4 cases with degenerative lumbar spondylolisthesis.Ten cases were performed with single level fusion,16 cases with two level fusion,9 cases with 3 or more level fusion.Autogenous iliac bone graft was not applied in any of those patients.The pain of the patients was confirmed from the sacroiliac joint through specific symptoms and signs.They were divided into two groups and were treated with either standard intra-articular injection (17 cases) or a combine of intra-and peri-articular sacroiliac injection (18 cases).Peri-articular injection was conducted at 1 cm above the inferior margin of the sacroiliac joint.Recover ratios of visual analogue scale (VAS) and Oswestry disability index (ODI) at 2 weeks post-operatively were recorded and were compared between the two groups.Results No statistical difference was found in gender,fusion location,fusion levels,pre-operative VAS and ODI score between the two groups (P ＞ 0.05).The combination of intra-and peri-articular sacroiliac injection showed significantly better results than the single intra-articular injection in VAS score immediately after injection (t=2.159,P=0.038),VAS score at 2 weeks after injection and ODI score at 2 weeks after the injection (t=2.705,P=0.011;t=2.156,P=0.039,respectively).Conclusion Both intra-and extra-sacroiliac joint diseases may lead to sacroiliac joint pain after lumbar fusion surgery.A single intra-articular sacroiliac injection could not provide optimistic outcomes.Further extra-articular injection is required at approximate 1 cm above the inferior margin of the sacroiliac joint.The technique combining intra-and peri-articular injection could guarantee improved early clinical outcomes.

Objective To assess the risk of sympathetic nerve injury in oblique lumbar interbody fusion (OLIF) in different lumbar spine segments based on anatomical study.Methods Twenty-four healthy adult volunteers (12 male and female) were selected and routine lumbar spine scanning was performed with MAG MAGOMOM Verio 3.0 T.The anatomical structures of left lumbar sympathetic trunk,abdominal aorta and left psoas muscle were identified on T2 images of L2,3,L3,4,L4,5 intervertebral space.And the anatomical parameters of the OLIF operation approach and the anatomical parameters of the left sympathetic trunk and adjacent structures were measured.The t-test was used to compare the parameters between the different sexes.The comparison of the data between the different segments was performed by the least significant difference (LSD) single factor analysis of variance.Results From the L2,3 to L4,5 segments,the anatomical parameters of the OLIF operation approach and the anatomical parameters of the left sympathetic trunk and the adjacent structures showed regular changes.The distances between the anterior margin of the left psoas muscle and the abdominal aorta from L2,3 to L4,5 were 13.65±4.10 mm to 9.42 ± 4.00 mm in adult healthy male individuals,and 13.89±3.18 mm to 8.38 ± 3.33 mm in female individuals,showing a significant downward trend.The distances between the left sympathetic trunk and the abdominal aorta from L2,3 to L4,5 were 10.76±3.89 mm to 6.68±3.39 mm in adult healthy male individuals,and 11.52±3.02 mm to 6.12±2.95 mm in female individuals,also showing a significant downward trend.There were significant differences in the operation area of OLIF surgery between different segments.The operation area of OLIF surgery was relatively large in L 2,3 segment,and the risk of sympathetic nerve injury was relatively small.The left lumbar sympathetic trunk in the L3,4 intervertebral space was walking front and inside,and there was a greater risk of injury in the OLIF surgery.Conclusion The left lumbar sympathetic trunk located in or close to OLIF surgery operation field in L2-L5 segments.There was a certain risk of sympathetic nerve injury in OLIF surgery,and the risk of sympathetic nerve injury was different in L2,3,L3,4,L4,5 segments.

We report two rare cases of spinal intraosseous schwannoma (SIS) with sustained myelopathy symptoms and provide an updated review regarding SIS in the literature. A 71-year-old man experienced right lumbocrural pain and gait disturbance accompanied with paresthesia and right leg weakness. Imaging examinations revealed a mass with lesions in L4 vertebral body causing bone destruction and spinal cord compression. Complete resection of the well-demarcated tumor and posterior fusion were performed. A 54-year-old female reported bilateral gait disturbance, paresthesia, and numbness without weakness, and imaging revealed a posterior mass from T9 causing spinal cord compression and bone erosion. The tumor was completely separated from the spinal nerve root. The tumors from both patients were confirmed as schwannomas. Tumor recurrence was not observed at the 2-4 year follow-up. Although rare, SIS should be considered during differential diagnosis and can affect treatment planning. SIS symptoms vary depending on tumor location, and fusion is frequently necessary for spinal reconstruction after complete tumor resection.
Aged ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Gait ; Humans ; Hypesthesia ; Leg ; Middle Aged ; Neurilemmoma* ; Paresthesia ; Recurrence ; Spinal Cord Compression ; Spinal Cord Diseases ; Spinal Nerve Roots