Objective To investigate the effect of carbamazepine (CBZ) on Kv7.4 channels of dopaminergic (DA) neurons in the ventral tegmental area (VTA) of the midbrain of epileptic rats. Methods 50 male Wistar rats were randomly divided into 5 groups: control group, epilepsy group, and low, medium, high concentration CBZ group, 10 in each group. Except control group, rats in other groups were induced epilepsy with lithium chloride and pilocarpine to establish epilepsy rat model. After the model was successfully constructed, the rats in low, medium, and high concentration CBZ groups were given CBZ (10, 30, and 50 mg/kg) by gavage respectively, while rats in control group and epilepsy group were given the same amount of normal saline by gavage once a day for 7 days. The behavior changes of rats were observed. The malondialdehyde (MDA), glutathione (GSH) content and superoxide dismutase (SOD) activity in VTA were determinate by spectrophotometric. The protein expression of tyrosine hydroxylase (TH) and kv7.4 in VTA were detected by immunofluorescence and laser confocal microscopy. Western blotting was used to detecte the TH and Kv7.4 expression. Results No abnormal behavior showed with rats in control group. After pilocarpine injection, rats in epilepsy group experienced symptoms such as convulsions, chewing, and salivation, and the symptoms in low, medium, and high concentration CBZ group were alleviated. Compared with rats in control group, the MDA content of the rats in epilepsy group was significantly increased (P<0.05), the GSH content, SOD activity, number of DA neurons in the VTA region, and the expression of TH and Kv7.4 protein were significantly reduced (P<0.05). Compared with rats in epilepsy group, the seizure latency, GSH content, SOD activity, number of DA neurons in VTA area, and TH and Kv7.4 protein expression levels significantly increased in the low, medium and high concentration CBZ group (P<0.05); seizure rate and MDA content significantly decreased in the medium and high concentration CBZ group (P<0.05). Conclusions CBZ could alleviate oxidative stress response in brain of epileptic rats, promote DA neuron activity at VTA, activate Kv7.4 channels, and relieve epileptic seizures.

Sepsis-associated encephalopathy (SAE) is a complex disease with high mortality, an urgent clinical problem to be solved. The mechanism of SAE has not been fully elucidated and there is no effective treatment. Recent study found that high mobility group box 1 (HMGB1) is a late-stage pro-inflammatory mediator with the effect of activating inflammation, besides, HMGB1 plays important role in tissue repair, as well as in sepsis-induced brain injury. Therefore, In-depth research on the relationship between HMGB1 and SAE is expected to provide a new direction for the diagnosis and treatment of SAE. This review focuses on current status of SAE, HMGB1 and the four aspects of HMGB1, including impairment of blood-brain barrier, dysregulation of immune response, oxidative stress and neuronal apoptosis that involved in brain function impairment and SAE.

Objective To evaluate the therapeutic effect of everolimus on tuberous sclerosis related renal angiomyolipoma (TSC-RAML) based on tumor components, and identify the types of main components in reducing RAML by everolimus. Methods To retrospectiely analyze the clinical data of 47 patients with TSC-RAML who were treated in the Urology Department of the First Affiliated Hospital of the Air Force Medical University and met the diagnostic criteria of ITSCCC from September 2017 to September 2022. According to the attenuation range of CT tissue specific threshold, patients were divided into fat rich group (HU ≤-10, n=26) and fat deficient group (HU ≥30, n=21). Collect patients' baseline CT data and 6 months after treatment, record the average CT value of RAML before and after treatment. Three-dimensional reconstruction of RAML was performed using Mimics software, and record the volume of RAML before and after treatment. The volume of RAML and mean CT value were compared between the two groups before and after treatment. Results No statistical difference existed in baseline characteristics between the two groups (P>0.05). The median reduction of tumor volume in fat rich group and fat deficient group of patients were 4.94 (3.12, 27.23) cm³ and 27.31 (10.83, 40.38) cm³, respectively, and the volume response rates were 11.52%±0.96% and 62.09%±12.60% respectively, the differences were statistically significant (P<0.05). The differences of average CT values between the fat rich group and fat deficient group were (4.23±3.01) HU and (14.52±3.61) HU respectively, and the reduction rates of CT values were 14.25%±11.94% and 29.23%±0.53% respectively, all were statistically significant (P<0.05). After treatment, the average CT value of tumors in fat deficient group decreased significantly compared to that in fat rich group with statistically significant difference (P<0.05). Six months after treatment with everolimus, the composition of high-density cord like vascular tissue in RAML tumors reduced significantly and fat conversion occurred. Conclusions The effect of everolimus on reducing tumor volume and average CT value of tumor in fat deficient RAML is better and significant, which confirmed that the reduction is the high-density component of TSC-RAML mainly composed of vascular components.

Objective To examine the differences between mouse models of classic heat stroke (CHS) with multiple organ dysfunction via two different rising strategies. Methods A total of 66 male C57BL/6J mice were divided into direct heat stroke (DHS) group (n=28), a stepwise heat stroke (SHS) group (n=28), and control group (n=10) using the random number table method. In the first two groups, animals received direct warming at 41 ℃ and stepwise warming from 25.0 ℃ to 39.5 ℃, using a simulated climate chamber, respectively. While the animals were in the climate chamber before reaching the endpoint, we constantly monitored the animal activity, animal consciousness, and rectal temperature. We randomly selected 4 animals from each group and collected the blood samples and organ tissues (liver, kidney, intestine, lung, and spleen) after 24 hours of recovery since the end of heat exposure. We used the automatic biochemical analyzer to measure the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), blood urea nitrogen (BUN), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine kinase isoenzyme MB (CK-MB). We employed multifactorial test kits to detect the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-β. We analyzed the histological sections from each organ and then calculated the pathological injury scores. We saved the remaining mice for the 72 h survival analysis. Results Both heat stroke strategies can establish a stable CHS model of the mouse. In contrast with mice in DHS group, mice in SHS group exposed to heat for a longer time [(181.61±41.88) min vs. (104.72±18.68) min, P<0.001], had a higher percentage of dehydration [(11.59±1.52)% vs. (7.07±1.84)%, P<0.001] and higher 72 h mortality (73.68% vs. 22.22%, P<0.05). After 24 hours' recovery, biochemical indicators (ALT, AST, CREA, BUN) of SHS group were higher than those of DHS group [(875.63±241.24) U/L vs. (139.38±188.22) U/L, P<0.01; (2406.75±1008.69) U/L vs. (208.13±149.23) U/L, P<0.01; (79.88±41.39) U/L vs. (18.75±10.51) U/L, P<0.05; (134.33±52.54) U/L vs. (17.75±7.31) U/L, P<0.01]. The pathological injury scores of each organ tissue of the SHS group were higher than those of the DHS group (P<0.05). The levels of MCP-1 of the SHS group were higher than that of the DHS group [(22.89±1.97) pg/ml vs. (15.97±3.91) pg/ml, P<0.05], and TGF-β of SHS group was lower than that of DHS group [(936.46±30.17) pg/ml vs. (1453.50±129.81) pg/ml, P<0.001]. Conclusions The stepwise warming method had a higher success rate in developing the model, a higher mortality rate within 72 h, and more severe organ damage than the direct warming method. Thus it was a more stable and reliable modeling method that was more consistent with the pathophysiological state of CHS patients at the actual onset of illness.

In military training, when the physiological heat stress load is excessive and cannot be corrected in time, heat illness may occur, and in severe cases, exertional heat stroke may occur, which will seriously affect the combat effectiveness. Rapid, effective and uninterrupted cooling is the key measure to relieve excessive heat stress reaction and prevent heat illness/stroke. Based on nearly 10 years of clinical practice experience, the scientific research achievements in heatstroke prevention areas, as well as domestic and foreign latest evidence, Expert Group of Heat Stroke Prevention and Treatment of the Chinese PLA summarized the temperature monitoring, preventive and therapeutic cooling strategies in the whole process of military training, and widely consulted the opinions of emergency and critical care experts in the military, and finally formed the consensus, thus being intended to provide guidance for the implementation of effective temperature management in military training.

Objective To discuss the correlation between triglyceride-glucose index (TYG) and the major ischemic events in the past year in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary interventions (PCI). Methods The present study is a retrospective analysis based on a single-center registration database. From March 2016 to March 2019, the clinical data of 2203 eligible patients with AMI undergoing primary PCI were collected from the General Hospital of Northern Theater Command, and divided into two groups according to the median TYG index at admission [TYG <9.1047 group (n=1101) and TYG ≥9.1047 group (n=1102)]. The demographic characteristics, risk factors and complication, laboratory test, operation characteristics and medication after discharge were compared between the two groups. Meanwhile, the one-year ischemic events (cardiac death, myocardial infarction and/or ischemic stroke) and all-cause death were compared between the two groups. The Cox regression models were used to analyze the correlation between TYG and main outcomes. To evaluate the predictive value of TYG for one-year ischemic events using the ROC curve. Results Compared with TYG <9.1047 group, patients in TYG ≥9.1047 group were younger, less male, and had a higher proportion of hypertension and diabetes (P<0.05), and higher incidence with significant differences (P<0.05) in the frequency of one-year ischemic events, cardiac death and all-cause death. The TYG showed acceptable performance in prediction of one-year ischemic events and all-cause death with areas under the curve (AUC) of 0.62(95%CI 0.55-0.68) for ischemic events and 0.61(95%CI 0.55-0.68) for all-cause death. The best cut-off point for distinguishing the main end point from one-year ischemic events was 9.5948, the sensitivity was 47.3%, and the specificity was 76.5%. Conclusion Excessive TYG at admission of AMI patients is significantly related to the incidence of one-year ischemic events after PCI.

Virtual reality (VR) technology is a comprehensive multimedia technology. Since its development from the 1950s, VR technology has been widely applied in the field of military medicine. Armed forces around the world utilize VR technology to conduct psychological adjustment and skill training for front-line combat personnel and to educate health service personnel. Meanwhile, the high simulation of the real environment by VR enables rear medical personnel to carry out exposure therapy for patients suffering from post-traumatic stress disorder (PTSD) or other psychological trauma, in a reconstructed virtual environment which is extremely similar to battlefield but with far higher safety. It can also carry out rehabilitation training, health education or combat capability assessment for the wounded with brain injury or disability with higher efficiency. This paper reviews the origin and development of VR, expounds the development and application of VR technology in the field of military medicine, and prospects its possible development in near future.

Objective To investigate the protective function and mechanism of rapamycin on the hypothalamus injury of rats with exertional heat stroke. Methods Eighty male Wistar rats were randomly divided into four groups: control group, rapamycin group (Rapa group), exertional heat stroke group (EHS group), and exertional heat stroke + rapamycin group (EHS+Rapa group), with 20 rats in each group. The rats in Rapa group and EHS+Rapa group were injected intraperitoneally with Rapa (1 mg/kg, once a day) for four consecutive days before modeling. The rats in control and EHS groups were treated with the same dose of 0.9% normal saline. In EHS group and EHS+Rapa group, the rats ran in a climate chamber with a temperature range of (39.5±0.3) ℃ and a humidity range of (55%±5%). After successful modeling, the rats were removed from the climate chamber for cooling at room temperature. The animals in control and Rapa groups ran at the same intensity and room temperature as EHS group. During the establishment of the model, we monitored the general state, measured core temperature, and profiled the survival curve of the rats in each group (11 rats randomly selected from each group). The rats in EHS group and EHS+Rapa group were removed from the chamber after modeling of 80 min, and after 300 min observation, each group of rats was anesthetized. Then we collected the abdominal aorta blood and hypothalamus. The histopathological changes in the hypothalamus were analyzed by HE and Nissl staining. Immunofluorescence was used to determine the apoptosis of hypothalamus. Western blotting was used to detect the expression of mammalian target of rapamycin (mTOR) and phosphorylated mTOR (pmTOR), autophagy effector protein (Beclin-1), ubiquitin-binding protein (p62) and autophagy marker microtubule-associated protein 1 light chain 3(LC3) in the hypothalamus of rats. We calculated the ratios of pmTOR/mTOR and LC3-Ⅱ/LC3-Ⅰ. We measured the expression levels of neuron-specific enolase (NSE), brain active peptide 100β protein (S100β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in arterial serum by ELISA. Results When rats were entered into the climate chamber at 80 min, compared with control group, the core temperature of EHS group was significantly increased (P<0.001); compared with Rapa group, the core temperature of EHS+Rapa group was significantly increased (P<0.001). Compared with the EHS group, the survival rate of EHS+Rapa group was increased (P<0.01). HE and Nissl staining showed severe pathological damage in hypothalamic nerve cells in EHS group. We observed significantly less pathological damage in hypothalamic nerve cells in EHS+Rapa group than EHS group (P<0.001). Immunofluorescence analysis showed substantial cell apoptosis in the hypothalamus of EHS rats compared with control group (P<0.05). EHS+Rapa group had significantly less apoptosis in the hypothalamus than EHS group (P<0.05). Western blotting results showed that compared with control group, the ratio of pmTOR/mTOR, Beclin-1 expression, LC3-Ⅱ/LC3-Ⅰ ratio in the hypothalamus tissue of EHS group increased and p62 expression decreased (P<0.01); compared with EHS group, the ratio of pmTOR/mTOR in the hypothalamus of EHS+Rapa group decreased, Beclin-1 expression increased, LC3-Ⅱ/LC3-Ⅰ ratio increased and p62 expression decreased (P<0.05). ELISA results showed that the expression levels of NSE, S100β protein, and TNF-α in the serum of EHS group were significantly increased (P<0.05), while the expression of IL-6 in EHS group showed no significant difference (P>0.05). Compared with EHS group, the expression levels of NSE, S100β protein, IL-6, and TNF-α in the serum of EHS+Rapa group were significantly decreased (P<0.05). Conclusion Rapa can alleviate the hypothalamus tissue damage caused by exertional heat stroke, improve the function of brain cells, reduce the levels of inflammatory factors and the apoptosis of tissue cells, which is related to the inhibition of mTOR signaling pathway and the enhancement of hypothalamus autophagy level.

Parkinson's disease (PD) is a common chronic inflammatory disease of the nervous system in the middle-aged and elderly. The main pathological basis of PD is the decrease of dopaminergic neurons in the substantia nigra and the formation of Louie bodies. The clinical manifestations of PD are usually quiescent tremor, bradykinesia, enhanced muscle tone and abnormal posture and gait. The pathogenesis of PD is very complex, which may be related to age, environment, heredity, oxidative stress and mitochondrial dysfunction. In this review, we summarized research progress on the mechanisms and treatment methods of α-synuclein, oxidative stress, mitochondrial dysfunction, LRRK2 gene mutation and other factors leading to the degeneration of dopaminergic neurons in PD, in order to provide a reference for basic and clinical research of PD.

Objective To investigate the effects of stem cells from human deciduous teeth (SHED) on temporomandibular joint osteoarthritis (TMJOA) in rats. Methods Sixty 8-week-old male SD rats were randomly divided into control group, sodium iodoacetate (MIA)-induced TMJOA group (MIA group) and SHED treatment TMJOA group (SHED group), 20 rats in each group, and 10 animals were sacrificed in each group 2 and 4 weeks after treatment and were collected. Temporomandibular joint (TMJ) on the left was used for morphological detection, and right TMJ condylar cartilage for molecular biology detection. The degree of cartilage degeneration was evaluated by HE and Saffron O-solid green staining, the expression of type collagen Ⅱ in condylar cartilage was detected by immunohistochemical staining, and the expression changes of cleaved-CASP3, the key molecule of apoptosis, and the pro-inflammatory factor tumor necrosis factor-α (TNF-α), were detected by Western blotting. Results Compared with control group, the arrangement of cells in each layer of condylar cartilage in MIA group was disordered, a large number of cell-free areas were visible, and the fibrous layer was significantly thickened (P<0.001). After SHED treatment, the morphology of SHED group basically returned to normal, and there was no significant difference between SHED group and control group. The histological score of Mankin's osteoarthritis of condylar cartilage in MIA group was significantly higher than that in control group (P<0.001). After treatment, the score decreased significantly in SHED group (P<0.001). The positive area ratio of Saffron-O staining and the percentage of positive area of collagen Ⅱ. Of condylar cartilage in MIA group were significantly lower than those in control group (P<0.001). After treatment, the value increased significantly in SHED group (P<0.01) and there was no significant difference compared with control group. The number of TUNEL-positive cells in the condylar cartilage in MIA group was significantly higher than that in control group (P<0.001). After treatment, this value decreased significantly in SHED group (P<0.001). Western blotting results showed that the protein expression levels of cleaved-CASP3 and TNF-α in the condylar cartilage of MIA group were significantly higher than those in control group (P<0.001). After treatment, this value decreased significantly in SHED group (P<0.001) and there was no significant difference compared with control group. Conclusion Intra-articular injection of SHED can reverse condylar cartilage degeneration induced by MIA.