Military traumatic brain injury (TBI) belongs to military psychiatry, which is a new subcategory of psychiatry. Military TBI has become a landmark injury in modern military conflicts, which not only has a high incidence and death rate, but also has many sequelae, bringing heavy burden to patients and society. There have been frequent reports on TBI, but the pathophysiological mechanism of trauma to human brain tissue caused by military action and war has not been extensively studied. In this paper, epidemiological data, pathogenesis, molecular biological diagnosis and research achievements of existing therapeutic techniques related to TBI were reviewed, especially in terms of pathophysiological mechanism, and the pathogenesis, pathophysiological changes, blood-brain barrier injury, neuroinflammation and immune response of military TBI induced concussion and impact brain injury were summarized. It will provide useful reference for further study of military TBI.

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.

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.

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 identify the epidemiological characteristics of tuberculosis in Zigong from 2018 to 2021, and to compare the epidemic situation of tuberculosis before and during the COVID-19 pandemic, so as to provide guidance for further prevention and control. Methods The data of tuberculosis cases reported in Zigong from January 1, 2018 to December 31, 2021 were derived from the "Tuberculosis Information Management System". And further descriptive epidemiological analysis was carried out based on the collected data. Results A total of 5289 tuberculosis cases were reported in Zigong from 2018 to 2021 with the range of reported incidence from 49.29/100 000 to 55.19/100 000, and the average incidence reported was 52.54/100 000. The incidence showed two peaks every year from 2018 to 2021, except for 2020 with only one peak in September. The ratio of male to female patients was 3.14:1 (4010:1279) and farmers were the main occupation of patients (56.06%). Tuberculous pleurisy was the main type of extrapulmonary tuberculosis (69.17%), and diabetes was the main type of comorbidities (74.32%), respectively. Ziliujing district showed the lowest incidence among these districts in Zigong. Newly treated patients have been the main treatment type of tuberculosis patients in Zigong in the past four years with the ratio of newly patients to retreatment patients of 14.60:1(4950:339). There were four types of patients showing high rates of consultation delays, including officers (74.29%), retreatment patients (73.75%), diagnosed (74.95%) and recommended (78.57%) due to symptoms. During the COVID-19 pandemic, while the reported incidence of tuberculosis in Zigong city has decreased, the rate of laboratory positive detection has also decreased. Conclusions Middle-aged male and farmers are still the focus of tuberculosis prevention and treatment in Zigong. The COVID-19 pandemic has little effect on the gender structure of patients. However, the COVID-19 pandemic might cause a slight increase in the number of hidden tuberculosis patients in Zigong. It is suggested to strengthen publicity, education and screening for the target population.

Objective To determine the diversity between the different types of pulmonary tuberculosis, a retrospective analysis was made on the characteristics of medical history, blood indicators and the characteristics of peripheral T cell subsets of these patients. Methods The data of 283 pulmonary tuberculosis patients with full information were analyzed in the Eighth Medical Center of Chinese PLA General Hospital from January 2018 to December 2021, who had definite diagnosis, neither diabetes nor drug resistance, and were all on the initial treatment. The patients were divided into four groups: secondary pulmonary tuberculosis group (PTB group, 186 cases), tracheal and bronchial tuberculosis group (BTB group, 23 cases), tuberculous pleurisy group (TBP group, 42 cases) and hematogenous disseminated pulmonary tuberculosis group (DTB group, 32 cases). The patients' general conditions, medical history characteristics, laboratory indicators and T cell subsets, etc. were analyzed comparatively. Results There were no statistical differences in the age, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leukocyte count, lymphocyte count and hemoglobin level of patients between PTB group, BTB group, TBP group and DTB group(P>0.05). Compared with other groups, the proportion of men (34.8%) and the smoking rate (8.8%) were lower, and the disease course was longer (only 39.1% for the patients less than 3 months) in BTB group (P<0.05); the platelet count [308.00(242.00, 432.75.00)×10⁹/L] and carbohydrate antigen 125 (CA125) level [69.10(40.94, 185.40) U/ml] were higher, the albumin level[34.50(29.60, 39.20) g/L] was lower, and the disease course was shorter (88.1% for the patients less than 3 months) in TBP group;the NK cell count [70.00(33.50, 218.50) cells/μl] and NK cell percentage [7.09%(4.38%, 11.87%)] were lower in DTB group;the differences were statistically significant (P<0.05). Conclusions Male patients are more likely to suffer from TBP and female patients are more likely to suffer from BTB. Platelet counts and CA125 level are higher in patients with TBP, while the counts and proportion of NK cells are lower in patients with DTB.

Objective To evaluate the value of GeneXpert MTB/RIF Ultra (Xpert Ultra) in the early and rapid diagnosis of sputum and bronchoalveolar lavage fluid (BALF) samples in patients with smeared negative tuberculosis. Methods A total of 93 patients with sputum smear-negative suspected pulmonary tuberculosis who were admitted to Shandong Public Health Clinical Center from May 2020 to December 2021 were included in this study. Among them, 57 patients were clinically diagnosed as sputum smear-negative pulmonary tuberculosis and 36 patients were non-pulmonary tuberculosis. Sputum and BALF samples were collected from all patients, and Xpert Ultra, GeneXpert MTB/RIF (Xpert), BACTEC MGIT 960 culture (MGIT 960 culture) were performed. To evaluate the sensitivity, specificity and coincidence rate of various detection methods and their combined detection of sputum and bronchoalveolar lavage fluid samples in the diagnosis of smeared negative pulmonary tuberculosis. Results Taking clinical diagnosis as the reference standard, the sensitivity of sputum samples detected by Xpert Ultra for the diagnosis of smeared negative pulmonary tuberculosis was significantly higher than that of Xpert [56.14% (32/57) vs. 36.84% (21/57), P=0.039] and MGIT 960 culture [56.14% (32/57) vs. 33.33% (19/57), P=0.014]. The sensitivity of BALF samples detected by Xpert Ultra for the diagnosis of smeared negative pulmonary tuberculosis was significantly higher than that of Xpert [75.44% (43/57) vs. 56.14% (32/57),P=0.030] and MGIT 960 culture [75.44% (43/57) vs. 38.60% (22/57), P<0.01]. Three different methods of testing sputum samples, the area under the receiver operating characteristic curve (AUC) was the combination of the three elements (0.807)>Xpert Ultra+Xpert (0.798)>Xpert Ultra+MGIT 960 culture (0.789)>Xpert Ultra method (0.781)>Xpert (0.684)>MGIT 960 culture (0.667);Samples of BALF were examined, the AUC was the combination of the three elements (0.895)=Xpert Ultra+Xpert (0.895)>Xpert Ultra+MGIT 960 culture (0.877)=Xpert Ultra method (0.877)>Xpert (0.781)>culture method (0.693). Rifampicin resistance was not detected in the enrolled samples by the three detection methods. Conclusions Xpert Ultra has high clinical application value in the early and rapid diagnosis of smeared negative pulmonary tuberculosis, and the sensitivity of Xpert Ultra in the detection of BALF is higher than that of sputum sample, so the BALF sample is recommended as prior selection.

Objective To evaluate the immunotherapeutic effect of Bacille Calmette-Guérin (BCG) in type 1 diabetes mellitus (T1DM) mice and explore its mechanism. Methods Fifteen SPF grade male C57BL/6 mice were randomly divided into molding group (n=10, established T1DM model by intraperitoneal injection of streptozotocin 50 mg/kg)and control group (n=5, intraperitoneal injection of equivalent amount of citric acid buffer). Ten mice with random blood glucose≥16.7 mmol/L were divided into T1DM group and BCG group (5 each). Mice in BCG group were then subcutaneously injected with 1×10⁶ cfu/mouse of BCG at an interval of 4 weeks for 2 times, and the other two groups were injected with the same dose of phosphate buffer solution (PBS). During the experimental period (13 weeks), the body weight and food consumption of mice were monitored weekly, and blood glucose levels were measured by tail vein sampling. Oral glucose tolerance test (OGTT) was used to detect the glucose regulation ability of mice after glucose load. HE staining was used to observe the pathological changes of pancreatic tissue. Pancreatic insulin level was detected by immunohistochemistry (IHC). Serum C-peptide levels were detected by enzyme linked immunosorbent assay (ELISA). Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the transcription levels of cytokines in mice spleen. The proportion of regulatory T cells (Treg) in splenocytes was detected by flow cytometry. Results After twice immunization with BCG (13-week), the blood glucose level increased significantly of mice in T1DM group than that in control group (P<0.001); while in BCG group was still higher than that in control group, but was significantly lower than that in T1DM group (P<0.01). The oral glucose tolerance test (OGTT) showed that, the blood glucose levels of mice in the three groups increased rapidly after glucose load, and began to decline at 120 min, and decreased to normal level at 180 min in control group; Compared with control group, the blood glucose levels of mice in T1DM group and BCG group also decreased after 120 min, but were still higher significantly than in control group at 180 min (P<0.001), while the blood glucose level in BCG group was lower than that in T1DM group, but the difference was not statistically significant (P>0.05). At initial immunization (5th-week), compared with control group, the percentage of weight gain decreased in T1DM group and BCG group (P<0.0001), and the food consumption increased significantly (P<0.0001); After twice immunization with BCG (13th-week), compared with control group, the percentage of weight gain in T1DM group was still lower significantly (P<0.0001), and the food consumption was significantly higher (P<0.001).Compared with T1DM group, the percentage of weight gain in BCG group increased (P<0.001), and the food consumption was lower (P<0.001), and there was no significant difference compared with control group (P>0.05). The results of HE staining showed that, compared with control group, the islets of mice in T1DM group had obvious atrophy, while the morphology of islets of mice in BCG group was similar to that in control group, and the number of cells in islets was significantly higher than that in T1DM group.The insulin immunohistochemistry (IHC) staining showed that, compared with control group, the insulin-positive area in pancreas of mice decreased significantly in T1DM group (P<0.01), and although the insulin positive area in BCG group was lower than that in control group (P<0.05), but was still significantly higher than that in T1DM group (P<0.05). ELISA test showed that the contents of serum C-peptide in T1DM group and BCG group decreased obviously than that in control group (P<0.001, P<0.05), however, the content of serum C-peptide in BCG group was significantly higher than that in T1DM group (P<0.05). qRT-PCR showed that, compared with control group, the level of cytokine mRNA in T1DM group did not change (P>0.05); Compared with T1DM group and control group, the mRNA levels of IL-2, IL-10 and transforming growth factor-β (TGF-β) were significantly increased in BCG group (P<0.0001), but there was no change in mRNA level of γ-interferon (IFN-γ) (P>0.05). The results of flow cytometry showed that compared with control group, the percentage of Treg cells in T1DM group decreased (P<0.05), while compared with T1DM group, the percentage of Treg cells in BCG group increased obviously (P<0.05), and there was no statistical difference compared with control group (P>0.05). Conclusion BCG immunotherapy could induce the increase of Treg cells, regulate autoimmune response, and promotes insulin secretion by reducing pancreatic pathological damage and restoring islet cell function, thus reducing the blood glucose level of T1DM mice.

Objective To explore the role of interleukin-18 binding protein (IL-18BP) in alleviating cognitive dysfunction of traumatic brain injury (TBI) rats and the related mechanisms. Methods A total of 120 adult male SD rats were randomly divided into 4 groups (30 each): sham group, TBI group, TBI+IL-18BP group (administered 1.5 mg/kg IL-18BP by tail vein), and TBI+IL-18BP+ADU-S100 group (administered 1.5 mg/kg IL-18BP by tail vein, and 20 mg/kg ADU-S100 by intraperitoneal injection). The rat model of TBI was established using the free falling body method. At 30 d after modeling, cognitive function of rats was measured by Morris water maze test. The serum levels of IL-18 and IL-18BP were detected by ELISA. The integrated fluorescence intensity of GFAP, IL-18 and cleaved-caspase-3 in hippocampus were detected by immunofluorescence. The relative expression levels of stimulator of interferon genes (STING), phosphorylated TANK-binding kinase 1 (p-TBK1), TBK1, phosphorylated interferon regulating factor 3 (p-IRF3), and IRF3 in hippocampus were detected using Western blotting. Results Compared with sham group, rats in TBI, TBI+IL-18BP and TBI+IL-18BP+ADU-S100 groups had longer escape latency and decreased times of crossing the platform and reduced time of acting in the targeted quadrant (P<0.0001), with increased concentration of IL-18 and IL-18BP in the blood, enhanced fluorescence intensity of IL-18 and cleaved-caspase-3, up-regulated expression levels of STING, p-TBK1 and p-IRF3 in the hippocampus (P<0.05); Compared with TBI group, the escape latency was shortened, the times of crossing platform and the percentage of target quadrant activity time were increased in TBI+IL-18BP group (P<0.001), the concentration of serum IL-18 decreased while of serum IL-18BP increased, and the fluorescence intensity of IL-18 and cleaved-caspase-3, the expressions of STING, p-TBK1 and p-IRF3 in the hippocampus were down-regulated significantly in TBI+IL-18BP group (P<0.05); Compared with TBI+IL-18BP group, the latency was significantly prolonged, the platform crossing times remarkably reduced, the time spent in the target quadrant was considerably shortened, the concentration of serum IL-18 increased while of IL-18BP decreased, the fluorescence intensity of IL-18 and cleaved-caspase-3, the expression levels of STING, p-TBK1 and p-IRF3 in hippocampus were increased in TBI+IL-18BP+ADU-S100 group (P<0.05). Conclusion IL-18BP can improve the cognitive function of TBI rats to some extent, and its mechanism may be related to the inhibition of astrocytes apoptosis and STING/TBK1/IRF3 signaling pathway.

Objective To observe the changes in depression-like behavior and cAMP-PKA-CREB-BDNF signaling pathway in the hippocampus of rats with mild brain blast injury (mbTBI) caused by blast shock wave, and to explore the mechanism of neurological dysfunction caused by mbTBI. Methods 44 male SD rats were randomly divided into control group and model group, 22 in each group. The rats in the model group were placed in a gridded iron cage, with the head facing the explosion center and fixed on the ground 15 m away from the explosion center in a fan shape. At the same time, the shock wave intensity at the location of the rats was detected. After the explosion, 7 rats in each group were randomly selected and fed in separate cages. Open field test and elevated plus maze test were used to evaluate the depression-like behavior of rats at 7, 14 and 28 d after exposure. The remaining rats in each group were randomly sacrificed at 7, 14 and 28 d after exposure. The hippocampus was removed and protein extracted. Western blotting was used to detect the relative expression of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (p-CREB), brain-derived neurotrophic factor (BDNF) and oncogenic protein c-FOS. Results After the explosion test, all the rats in the model group survived, but within 24 hours, they were apathetic, slow in action and poor in appetite. After 72 hours, the above symptoms gradually eased. There was no significant difference in body weight between the two groups at each time point (P>0.05). The results of behavioral experiments showed that compared with the control group, the total moving distance, the residence time in the central area, the number of times and the proportion of time entering the open arm of the model group were significantly reduced at 14 d after the explosion test (P<0.05). The results of Western blotting showed that compared with the control group, the expression levels of PKA, CREB, pCREB and BDNF protein in the model group were significantly decreased at 7, 14 and 28 d after explosion test (P<0.05). Compared with the control group, the expression of cAMP and c-FOS in the model group was significantly decreased at 7 and 14 d after the explosion test (P<0.05), and there was no significant difference between the two groups at 28 d(P>0.05). Compared with 7 and 14 d after the explosion test, the expression levels of PKA, CREB and BDNF in the model group were significantly increased at 28 d after the test (P<0.05). Conclusion Single blast shock wave exposure can cause depression-like behavior changes in rats, which may be related to the down-regulation of the cAMP-PKA-CREB-BDNF signaling pathway.