The epidemiology of traumatic brain injuries in the fastest-paced city in China: a retrospective study.

Introduction: Traumatic brain injury (TBI) seriously affects the quality of human health and the prognosis of the patient, but the epidemiological characteristics of TBI can vary among populations. Numerous changes have occurred in the epidemiological characteristics of individuals with TBI in the fast-paced city of Shenzhen, China. However, little is known about these characteristics. This study aimed to investigate the changes in TBI epidemiology, help clinicians improve medical treatment. Methods: In this retrospective cross-sectional analysis, we collected the data of 4,229 patients with TBI admitted to 20 hospitals in Shenzhen in 2017. We collected data on age, gender, cause and severity of the injury, eventual diagnosis, time from injury to admission in a neurosurgery department, and patient outcomes. Two neurosurgeons simultaneously collected the data. We compared these results with a similar study conducted in Shenzhen during the period from 1994 to 2003 to clarify and explain the changes in the epidemiological characteristics of TBI. Results: The majority of respondents were men [2,830 (66.9%)]. The mean age was 32.5 ± 21.4 years. The youngest patient was less than 1 year old, and the oldest patient was 101 years old. A total of 3,947 (93.3%) patients had a favorable outcome, 219 (5.2%) had an unfavorable outcome, and 63 (1.5%) died. The predominant external cause was falls (1,779 [42.1%]); this was the most common cause of TBI in children and older adults. Riders of electric bicycles (423 [29.0%]) were the most vulnerable to traffic accident-related injuries. Time greater than 50 h from injury to admission to a neurosurgical department had a significant effect on prognosis (p < 0.001). Conclusion: The epidemiological characteristics of TBI have changed significantly over the past 20 years. Falls, rather than traffic accidents, were the most common cause of TBI. Further research is needed to devise solutions to decrease the incidence of falls and improve the outcomes of TBI.

An Empirical Analysis of the Effects of Physical Exercise on Adolescent Mental Health and Its Mediating Mechanisms.

The use of physical exercise for the purpose of maintaining adolescents' mental health is an important topic of psychological research. However, there is no unified conclusion on the effect of physical exercise time on the level of mental health. This paper investigates the causal effect of physical activity on adolescent mental health using a multilayer linear modeling approach and a Bootstrap method to test for possible mediating effects. The results of the study showed that there was a nonlinear inverted U-shaped relationship between physical activity time and adolescent mental health, with a threshold value of 105 min, and the results of the mediating effect analysis showed that self-assessment of health, self-confidence, academic stress, peer relationships, and positive peer behaviour were important mediating mechanisms between physical activity and mental health. The results of the mediation effect analysis showed that physical exercise was an important mediating mechanism between self-assessment, confidence, academic stress, peer relationship, and positive peer behaviour.

Wires with Continuous Sabal Leaf-Patterned Micropores Constructed by Freeze Printing for a Wearable Sensor Responsible to Multiple Deformations.

The design of porous structure in wearable sensors is very important for the detection of mechanical signals. However, it remains challenging to construct a porous structure capable of detecting all kinds of mechanical signals. Here, round wire with long-range orientated micropores (RW-LOM) is fabricated by a newly established freeze printing technique and constructed into a wearable sensor by the incorporation of carbon nanotubes and polydimethylsiloxane. The Sabal leaf-like lamellar structure in RW-LOM is realized and can be tuned by the proper coordination of slurry concentration and the printing parameters. The fine structures in RW-LOM allow the wearable sensor to detect compression, stretching, twisting, and bending with a high sensitivity, stability, and broad detecting range. This work not only provides a wearable sensor with high stability and high sensitivity but also establishes a technique to construct porous wires that could find applications in the fields like intelligent industry and healthcare.

Serum Levels of MMP-8 and MMP-9 as Markers in Chronic Subdural Hematoma.

Chronic subdural hematoma (CSDH) is a common neurological disease that involves the collection of blood products in the subdural space. The progression of CSDH is an angiogenic and inflammatory process, but the multifactorial mechanisms underlying CSDH are still not fully understood. We aimed to identify one or more factors that may play an important role in the development of CSDH. We enrolled 83 patients with CSDH, including 17 postoperative patients, and analyzed 20 markers in the hematoma fluid and peripheral blood of each patient. Overall differential gene expression was examined to identify the representative markers. The concentration of MMP-8 was significantly lower in the postoperative group than in the preoperative group. The concentration of MMP-9 was significantly higher in the postoperative group than in the preoperative group. These findings indicate that MMP-8 and MMP-9 may play important roles in the pathophysiology of CSDH. Understanding the pathways associated with CSDH may provide insights for improving disease outcomes.

Knockdown of rno_circRNA_009194 Improves Outcomes in Traumatic Brain Injury Rats through Inhibiting Voltage-Gated Sodium Channel Nav1.3.

Excessive activation of voltage-gated sodium channel Nav1.3 has been recently reported in secondary traumatic brain injury (TBI). However, the molecular mechanisms underlying regulating voltage-gated sodium channel (Nav1.3) have not been well understood. The present study used a TBI rat model induced by a fluid percussion device and performed a circular RNA (circRNA) microarray (n = 3) to profile the altered circRNAs in the hippocampus after TBI. After polymerase chain reaction (PCR) validation, certain circRNAs were selected to investigate the function and mechanism in regulating Nav1.3 in the TBI rat model by intracerebroventricular injection with lentivirus. The neurological outcome was evaluated by Morris water maze test, modified Neurological Severity Score (mNSS), brain water content measurement, and hematoxylin and eosin staining. The related molecular mechanisms were explored with PCR, Western blotting, luciferase reporter, chromatin immunoprecipitation assay, and electrophoretic mobility shift assay (EMSA). A total of 347 circRNAs were observed to be differentially expressed (fold change [FC] ≥ 1.2 and p < 0.05) after TBI, including 234 up-regulated and 113 down-regulated circRNAs. Among 10 validated circRNAs, we selected circRNA_009194 with the maximized up-regulated fold change (n = 5, FC = 4.45, p < 0.001) for the in vivo functional experiments. Down-regulation of circRNA_009194 resulted in a 27.5% reduced mNSS in rat brain (n = 6, p < 0.01) after TBI and regulated the expression levels of miR-145-3p, Sp1, and Nav1.3, which was reversed by sh-miR-145-3p or Sp1/Nav1.3 overexpression (n = 5, p < 0.05). Mechanistically, circRNA_009194 might act as a sponge for miR-145-3p to regulate Sp1-mediated Nav1.3. This study demonstrated that circRNA_009194 knockdown could improve neurological outcomes in TBI in vivo by inhibiting Nav1.3, directly or indirectly.

Long-standing overt ventriculomegaly in adulthood with primary presentation of psychiatric disturbance: A case report.

RATIONALE: Hydrocephalus is a common disease in neurosurgery. The typical symptoms of hydrocephalus include urinary incontinence, gait instability, and cognitive decline. Irritability rarely occurs in patients with hydrocephalus. Irritability rarely occurs in patients with hydrocephalus, especially in long-standing overt ventriculomegaly of adulthood (LOVA). PATIENT CONCERNS: A 30-year-old female was admitted to our hospital because of mental retardation and unstable gait for more than 15 years. She had undergone ventriculoperitoneal shunt 15 years prior due to ventriculomegaly and related symptoms. However, the shunt catheter was removed shortly after surgery because of blockage, with no further postoperative treatment. DIAGNOSIS: The patient was diagnosed with long-standing overt ventriculomegaly according to her head circumference and clinical symptoms, including adult hydrocephalus development, overt triventriculomegaly and absence of a secondary cause for aqueductal stenosis in adulthood. INTERVENTIONS: After considerable discussion, she underwent ventriculoperitoneal shunt placement and showed dramatic and sustained improvement. OUTCOMES: The patient has been followed at 3-month intervals for over 2 years since discharge, and both the patient and family have reported a significant change in their daily life. She was able to live independently and control her emotions. Slight epilepsy was noted approximately 5 months after surgery but recovered 2 months later. LESSONS: It is difficult to decide whether to treat LOVA when the in patients whose symptoms are not significant. We believe that early diagnosis and positive treatment can help improve outcomes and would recommend ventriculoperitoneal (VP) shunting in patients with LOVA.

UPLC-Q-TOF/MS based fecal metabolomics reveals the potential anti-diabetic effect of Xiexin Decoction on T2DM rats.

Xiexin Decoction (XXD), a traditional Chinese medicine prescription composed of Rhei rhizome (RR), Scutellaria radix (SR) and Coptidis rhizome (CR), has been used to cure diabetes in clinical practices for thousands of years, but its mechanism is not clear. Our previous study indicated that XXD could significantly ameliorate the symptom of type 2 diabetes mellitus (T2DM) rats by shifting the composition of gut microbiota. However, the effect of XXD on the metabolic activity of gut microbiota is not clarified. In this study, the underlying mechanism of XXD on the amelioration of T2DM was explored by fecal metabolic profiling analysis based on ultra performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC-Q-TOF/MS). The disordered metabolic profiles in T2DM rats were notably improved by XXD. Ten potential biomarkers, which were mainly involved in arachidonic acid metabolism, amino acid metabolism, bile acid metabolism, glycolysis and gluconeogenesis, were identified. Furthermore, these metabolites were closely related to SCFAs-producing and anti-inflammatory gut microflora. After XXD intervention, these biomarkers restored to the normal level at some extent. This study not only revealed potential biomarkers and related pathways in T2DM rats affected by XXD, but also provided a novel insight to uncover how traditional herb medicines worked from fecal metabolomics.

A Powerful HPLC-ELSD Method for Simultaneous Determination of Fecal Bile Acids in T2DM Rats Interfered by Sanhuang Xiexin Tang.

Bile acids (BAs) as important endogenous ligands can activate farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) signaling to regulate glycolipid metabolism. In this study, a simple, reliable and sensitive analysis method for simultaneous determination of four BAs from rat feces based on high-performance liquid chromatography with evaporative light scattering detector (HPLC-ELSD) was developed. Chromatographic analysis was performed with the mobile phases of acetonitrile and 0.2% formic acid. All the standard curves exhibited good linearity (R2 ≥ 0.99). The relative standard deviations of precision, stability and repeatability varied from 1.27 to 3.96%, 2.20 to 3.89% and 3.00 to 4.31%, respectively. The validated method was successfully applied to investigate the variation of four BAs in feces from T2DM rats after oral administration of Sanhuang Xiexin Tang (SXT). Data showed that SXT could remarkably increase the contents of conjunct BAs and decrease the contents of free BAs, which might contribute to ameliorate the symptoms of T2DM rats.

Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis.

Ulcerative colitis (UC), a nonspecific inflammatory disease, is characterized by inflammation and mucosal damage in the colon, and its prevalence in the world is increasing. Nevertheless, the exact pathogenesis of UC is still unclear. Accumulating data have suggested that its pathogenesis is multifactorial, involving genetic predisposition, environmental factors, microbial dysbiosis, and dysregulated immune responses. Generally, UC is aroused by inappropriate immune activation based on the interaction of host and intestinal microbiota. The relationship between microbiota and host immune system in the pathogenesis of UC is complicated. However, increasing evidence indicates that the shift of microbiota composition can substantially influence intestinal immunity. In this review, we primarily focus on the delicate balance between microbiota and gut mucosal immunity during UC progression.

Protective effects of Lizhong decoction on ulcerative colitis in mice by suppressing inflammation and ameliorating gut barrier.

ETHNOPHARMACOLOGICAL RELEVANCE: Lizhong Decoction (LZD) is a classical prescription firstly recorded in "Shanghan Lun". It has been used to clinically treat ulcerative colitis (UC) for thousands of years. However, its mechanism is not clear up to now. AIM OF THE STUDY: The goal of this study was to assess the amelioration of LZD on dextran sodium sulfate (DSS)-induced colitis in mice and further clarify its mechanism. MATERIALS AND METHODS: The ulcerative colitis model induced by DSS was successfully established and applied to evaluate the intervention effect after oral administration of LZD. Furthermore, the expression of key targets in inflammatory signaling pathways and intestinal tight junction proteins were investigated by enzyme-linked immunosorbent assay (ELISA) and quantitative real time polymerase chain reaction (qPCR) analysis. RESULTS: The results showed that all doses of LZD could notably improve DSS-induced colon lesions, reduce histological scores, prolong colon length and increase body weight. Colonic inflammation in UC mice was significantly alleviated by inhibiting the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), reducing the yield of nitric oxide (NO) and inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and along with promoting the production of anti-inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10) after LZD treatment. Furthermore, LZD remarkably down-regulated the level of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) mRNA and up-regulated the expression of tight junction proteins (zonula occluden-1, occludin and claudin-1) in UC mice. CONCLUSION: In summary, this study indicated that LZD could notably improve UC symptoms by suppressing inflammation and ameliorating gut barrier, which provided scientific basis for its clinical application in the future.

Lizhong decoction ameliorates ulcerative colitis in mice via modulating gut microbiota and its metabolites.

Ulcerative colitis (UC), a kind of inflammatory bowel disease, is generally characterized by chronic, persistent, relapsing, and nonspecific ulceration of the bowel, which is widespread in the world. Although the pathogenesis of UC is multifactorial, growing evidence has demonstrated that gut microbiota and its metabolites are closely related to the development of UC. Lizhong decoction (LZD), a well-known classical Chinese herbal prescription, has been used to clinically treat UC for long time, but its mechanism is not clear. In this study, 16S rRNA gene sequencing combining with untargeted metabolomics profiling was used to investigate how LZD worked. Results indicated that LZD could shape the gut microbiota structure and modify metabolic profiles. The abundance of opportunistic pathogens such as Clostridium sensu stricto 1, Enterobacter, and Escherichia-Shigella correlated with intestinal inflammation markedly decreased, while the levels of beneficial bacteria including Blautia, Muribaculaceae_norank, Prevotellaceae UCG-001, and Ruminiclostridium 9 elevated in various degrees. Additionally, fecal metabolite profiles reflecting microbial activities showed that adenosine, lysoPC(18:0), glycocholic acid, and deoxycholic acid notably decreased, while cholic acid, α-linolenic acid, stearidonic acid, and L-tryptophan significantly increased after LZD treatment. Hence, based on the systematic analysis of 16S rRNA gene sequencing and metabolomics of gut flora, the results provided a novel insight that microbiota and its metabolites might be potential targets for revealing the mechanism of LZD on amelioration of UC.Key Points • The potential mechanism of LZD on the amelioration of UC was firstly investigated.• LZD could significantly shape the structure of gut microbiota.• LZD could notably modulate the fecal metabolic profiling of UC mice. Graphical abstract.

Scutellariae radix and coptidis rhizoma ameliorate glycolipid metabolism of type 2 diabetic rats by modulating gut microbiota and its metabolites.

Scutellariae radix (Scutellaria baicalensis Georgi, SR) and coptidis rhizoma (Coptis chinensis Franch, CR) are both widely used traditional Chinese medicines and have been used together to treat T2DM with synergistic effects in the clinical practices for thousands of years, but their combination mechanism is not clear. Accumulating evidences have implicated gut microbiota as important targets for the therapy of T2DM. Thus, this study aimed to unravel the cooperation mechanism of SR and CR on the amelioration of T2DM based on the systematic analysis of metagenome and metabolome of gut microbiota. Bacterial communities were analyzed based on high-throughput 16S rRNA gene sequencing. Furthermore, ultra high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze variations of microbial metabolites in feces and the contents of short chain fatty acids (SCFAs) in the cecum were determined by a gaschromatography-flame ionization detector (GC-FID). 16S rRNA gene sequencing results revealed that T2DM rats treated with SR, CR, and the combination of SR and CR (SC) exhibited changes in the composition of the gut microbiota. The SCFAs-producing bacteria such as Bacteroidales S24-7 group_norank, [Eubacterium] nodatum group, Parasutterella, Prevotellaceae UCG-001, Ruminiclostridium, and Ruminiclostridium 9 in T2DM rats were notably enriched after treatment with SR, CR, and their combination. In contrast, secondary bile acid-producing bacteria such as Escherichia-Shigella strongly decreased in numbers. The perturbance of metabolic profiling in T2DM rats was obviously improved after treatment, exhibiting a lower level of secondary bile acids and a numerical increase of microbially derived SCFAs. Moreover, the correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes. The findings indicated that the crosstalk between microbiota-derived metabolites and the host played an important role in the progress of T2DM and might provide a novel insight regarding gut microbiota and its metabolites as potential new targets of traditional Chinese medicines. Furthermore, this work also suggested that the integration of various omics methods and bioinformatics made a useful template for drug mechanism research.

Xiexin Tang ameliorates dyslipidemia in high-fat diet-induced obese rats via elevating gut microbiota-derived short chain fatty acids production and adjusting energy metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbal medicine has been taken as a new and effective approach to treat many chronic diseases. Xiexin Tang (XXT), a compound recipe composed of Dahuang (Rheum palmatum L.), Huangqin (Scutellaria baicalensis Georgi) and Huanglian (Coptis chinensis Franch.), has been reported to have hypoglycemic and hypolipidemic effects, but its mechanism remains unclear. Our previous study found that Xiexin Tang markedly ameliorated the composition of the gut microbiota, especially for some short chain fatty acids (SCFAs) producing bacteria, and then notably increased SCFAs production. However, the mechanism of XXT on the fermentation of gut bacteria and further improvement of obesity is not yet clear. AIM OF THE STUDY: This study aimed to unravel the molecular mechanism of XXT on the amelioration of obesity. MATERIALS AND METHODS: Here, high-fat diet-induced obese rat model was established to investigate the intervention efficacy following oral administration of XXT. Additionally, the expressions of key enzymes of gut microbe-derived SCFAs biosynthesis and key targets in the signaling pathway of energy metabolism were investigated by ELISA and qPCR analysis. RESULTS: Results showed that XXT could notably correct lipid metabolism disorders, alleviate systematic inflammation, improve insulin sensitivity and reduce fat accumulation. Additionally, XXT could increase gut microbiota-derived SCFAs-producing capacity by enhancing mRNA levels and activities of SCFA-synthetic key enzymes such as acetate kinase (ACK), methylmalonyl-CoA decarboxylase (MMD), butyryl-CoA: acetate CoA transferase (BUT) and butyrate kinase (BUK), which markedly decreased the adenosine triphosphate (ATP) contents, elevated adenosine diphosphate (ADP) and adenosine monophosphate (AMP) levels and further lowered the energy charge (EC) in obese rats via activating peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/uncoupling protein-2 (UCP-2) signaling pathway. What's more, XXT could notably ameliorate dyslipidemia via increasing the gene expression of 5'-AMP-activated protein kinase (AMPK) and blocking mammalian target of rapamycin (mTOR) signaling pathway. CONCLUSIONS: Taken together, our data provided a novel insight into the role of XXT in losing weight from energy metabolism regulation, which unraveled the molecular mechanism of XXT on the alleviation of dyslipidemia and fat heterotopic accumulation. The study provided useful information for XXT in clinical application to treat obesity.