Objective To evaluate the protective effect of Rhubarb on vascular endothelial cell function in the sepsis patients. Methods We carried out a prospective, single-center, randomized controlled study based on 41 patients with sepsis who admitted to the Intensive Care Unit of the 908th Hospital of PLA. The patients were randomly divided into Rhubarb treatment group (n=20) and control group (n=21). Blood samples were collected before, 24 h and 72 h after the medication. Conventional coagulation tests [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, thrombin time (TT), fibrin degradation products (FDP), D-dimer, antithrombin (AT-Ⅲ), platelet count, platelet distribution width] and coagulation molecular markers including thrombomodulin (TM), tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin- antithrombin complex(TAT), plasmin-α₂ antiplasmin complex (PIC) were detected and statistically analyzed. Results The fibrinogen level [(3.5±1.0) g/L] at the 72 h after administration in Rhubarb treatment group was significantly higher than that in control group [(2.7±0.8) g/L] and Rhubarb treatment group before administration [(2.7±0.9) g/L] (P<0.05). Compared with the serum TM [19.0(15.5,22.6) TU/ml] and t-PAIC [15.4(9.7, 20.9) ng/ml] levels before treatment in control group, the TM [27.3(20.8, 31.2) TU/ml] and t-PAIC [22.2 (15.5, 38.6) ng/ml] at the 72 h after administration in control group significantly increased (P<0.05). Compared with TM [27.3(20.8, 31.2) TU/ml] and t-PAIC [22.2(15.5, 38.6) ng/ml] of control group, the TM [13.2(10.9, 18.0) TU/ml] and t-PAIC [9.2(7.3, 23.1) ng/ml] at the 72 h after administration in Rhubarb treatment group were significantly decreased (P<0.05).Compared with the serum TM [19.7(17.1, 23.4) TU/ml] levels before treatment and the TM [18.6(15.3, 21.1) TU/ml] at the 24 h after administration in Rhubarb treatment group, the TM at the 72 h after administration were significantly decreased (P<0.05).Kaplan-Meier analysis revealed that there was no statistically significant difference in 14-day survival rate between the two groups(P>0.05). Conclusion Chinese Rhubarb can down-regulate TM and t-PAIC levels and improve vascular endothelial cell function in patients with sepsis.

Objective To investigate the effects of different arterial partial pressure of carbon dioxide (PaCO₂) on regional cerebral oxygen saturation (rScO₂) in robot assisted laparoscopic pyeloplasty (RALP) in children. Methods Forty-five children who received RALP in Pediatric Urology Department of the Seventh Medical Center of Chinese PLA General Hospital from February 2019 to February 2020 were selected as the study subjects, by adjusting tidal volume and respiratory rate maintained PaCO₂ at 35-45 mmHg (group N), 30-34 mmHg (group M) and 25-29 mmHg (group L) with 15 patients in each group. Before anesthesia (T₀), 10 min after endotracheal intubation (T₁), before lateral decubitus surgery (T₂), 30 min after pneumoperitoneum(T₃), 10 min after pneumoperitoneum (T₄), and 10 min after recumbent position (T₅), rScO₂ of affected side, percutaneous pulse oxygen saturation (SpO₂), heart rate (HR), mean arterial pressure (MAP), pharyngeal temperature (T), pH and hemoglobin (Hb)were recorded respectively. Arterial blood was extracted for blood gas analysis, and PaCO₂ was recorded, operation time was recorded after operation. Results Compared with T₀, rScO₂ in the three groups was increased significantly at T₁, and decreased significantly at T₃ in group L (P<0.05); compared with T₂, rScO₂ in group L at T₃ was significantly lower (P<0.05); compared with T₃, rScO₂ in group L was increased significantly at T₄ and T₅ (P<0.05). Compared with group N, rScO₂ in group L was decreased significantly at T₃ (P<0.05). Two-factor ANOVA showed that there was no interaction between group and pneumoperitoneum at T₂ and T₃, T₃ and T₄ in the three groups (P>0.05); compared with T₂, rScO₂ at T₃ in group L was significantly lower (P<0.05); compared with T₃,rScO₂ at T₄ in group L was significantly increased (P<0.05). There were no significant differences in SpO₂, HR, MAP, T, pH and Hb among the threes groups at each time point of T₀-T₅. Conclusion Pneumoperitoneum resulted in a significant decrease in rScO₂ on the affected side when PaCO₂ was within 25-29 mmHg during pediatric RALP and the risk of the cerebral oxygen supply-demand unbalance increased.

Nuclear transcription factor TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA binding protein commonly expressed and highly conserved in evolution. In physiological state, TDP-43, when localized mainly in nucleus and cytoplasm (no more than 30%), may play a physiological role, such as participating in mRNA transcription, splicing, translation, transport and maintaining the stability of mRNA, while its mislocalization in mitochondria might play a corresponding pathological role. Recent researches found that, in addition to produce a marked effect in neurodegenerative diseases, TDP-43 also plays an important role in the pathological process of tumors, male infertility, osteoarthritis (OA) and other diseases. Therefore, the gene expression, subcellular organelle translocation, function and the relationship with diseases of TDP-43 have attracted more and more attention. The research progress of pathological effects of TDP-43 has been reviewed in present paper, so as to provide more help for diagnosis and treatment of related diseases.

It is a common phenomenon that the working ability of the people from moderate temperature areas generally decreases after entering high temperature areas, while heat acclimatization can improve the heat tolerance of human. This review summarized the molecular mechanism of the formation of heat acclimatization and the specific key markers produced after heat acclimatization from the perspectives of physiological function, biochemical metabolism and epigenetics. In addition, Genome-Wide Association Study (GWAS) strategy in exploring the main genetic differences among people with different heat adaptation was also discussed. Heat acclimatization changes the sensitivity of central and peripheral thermal effectors, reduces heart rate and increases stroke volume by regulating myocardial autonomic nerve tension to reduce endogenous heat production and accelerate exogenous heat dissipation. Heat acclimatization enhances the secretion of H₂O and sodium retention hormones such as aldosterone and arginine vasopressin and the enrichment of NaCl in diet, which expands the plasma volume to maintain cardiovascular stability. The transcriptional activity of heat shock protein (HSP) and the calcium release of mitochondrial respiratory chain increases after heat acclimatization, in which HSP70 is a potential key genetic marker to distinguish between those with good heat adaptation (hot zone soldiers, firefighters, athletes, etc.) and those with poor heat adaptation. Moderately high concentration of Na⁺, Cl^–, Ca²⁺ and low concentration of K⁺ in plasma can help to enhance heat tolerance and promote the formation of heat acclimatization, which can be used as potential markers for the study of heat acclimatization. Furthermore, heat acclimatization effect in the population has great heterogeneity. How heat acclimatization enhances human's heat tolerance and the balance between the plasticity of this heat tolerance and congenital genetic and acquired epigenetic modification need to be further explored.

Dystonia is a type of movement disorder disease characterized by abnormal movements and postures, which seriously affects patients' social life and quality of life. However, there are certain difficulties in positioning judgment of early intervention, efficacy analysis and prognostic evaluation at present. Resting state functional magnetic resonance imaging (rs-fMRI)is an advanced technique for measuring the brain's spontaneous nerve activity at rest. It is widely used in the study of dystonia due to its advantages of non-invasiveness, simplicity and ease of use, and diverse analysis methods. Studies have shown that dystonia is not simply a basal ganglia dysfunction, but a neural network disorder. This article briefly describes the principle and clinical application of rs-fMRI, focusing on the research progress of rs-fMRI in various dystonia diseases, which will help to further understand the pathogenesis of focal dystonia to provide functional imaging basis for the development of more effective therapeutic drugs.

Sepsis and its development of multiple organ dysfunction pose a serious threat to human life and health. Sepsis is a hot issue that experts in the critical field are committed to solve. It is a heterogeneous, infection-induced systemic inflammatory response syndrome based on endothelial dysfunction, and it is still a huge burden on the global health system. As a well recognized immune cell, the endothelium is the primary site of attack by pathogens, toxins, or endogenous injury signals, which cause activation of endothelial cells and consequently damage to their function or structure. Although the latter may help to eliminate the infection and limit the dissemination of the infection to some extent, the excessive and persistent inflammatory response will also lead to a subsequent storm of cytokine and organ damage, causing irreversible damage to the organism. Glycocalyx is the first barrier on the surface of endothelial cells, it is also the first line of defence for endothelial cells under attack in sepsis, which has a great significance on endothelial function. Many studies have found that a variety of immune inflammatory responses involving the glycocalyx also play a key role in the development of sepsis. This review will give a brief overview of the factors, mechanisms and various treatments targeting glycocalyx injury in sepsis at present.

Glioma is of the most common malignant tumors in the central nervous system. The prognosis of patients is poor, and its effective treatment has always been a major clinical challenge. In tumor cells, genetic instability often leads to a large number of mutations. The expression of nonsynonymous mutations can produce tumor-specific antigens, called neo-antigens, which have high immunogenicity. They could activate specific T cells to produce an immune response and become a new tumor immunotherapy target. Among the tumor vaccines targeting neo-antigens, the mRNA tumor vaccine has obvious advantages: easy access, low cost, high safety, and great stability. Therefore, a neo-antigen mRNA vaccine is likely to become an effective treatment for glioma. At present, some clinical trials have proved the safety and effectiveness of these vaccines. This article reviews the research progress of the neo-antigen tumor mRNA vaccine and its application in glioma therapy, and predict the direction of future research.

Objective To investigate the expression and subcellular localization of long non-coding RNA (lncRNA)COL11A1-208, as well as the effect on the proliferation and invasion of oral squamous cell carcinoma (OSCC) cells. Methods The differential expression of COL11A1-208 in seven OSCC cell lines compared with primary cultured normal oral epithelial cells was detected by quantitative real-time PCR (qPCR), and the subcellular localization of COL11A1-208 was evaluated by cell nuclear/cytoplasmic fractionation and fluorescence in situ hybridization (FISH). CAL27 and HN4 cells were respectively transfected with COL11A1-208 Smart Silencer (SS-COL11A1-208 group) and negative control (NC) Smart Silencer (SS-NC group), while HN4 and HN6 cells were stably infected by COL11A1-208 lentivirus overexpression vector (LV-COL11A1-208 group) and NC lentivirus overexpression vector (LV-NC group). Cell proliferation in each group was detected by CCK-8 assay and plate colony formation assay, while cell migration and invasion ability in each group were detected by Transwell assays. Then, the expression of COL11A1 were detected by qPCR and Western blotting assays, while the protein expression of E-cadherin and vimentin was detected by Western blotting assay. Finally, the effect of COL11A1-208 on OSCC cells in vivo was studied by xenograft formation assay. Results COL11A1-208 was highly expressed in OSCC cell lines compared with the normal cells (P<0.05). The results of nuclear and cytoplasmic RNA isolation assay showed that the nuclear proportion of COL11A1-208 in CAL27, HN4 and HN6 cells was significantly higher than that in cytoplasm (P<0.01); similarly, FISH results showed that COL11A1-208 was primarily localized within the nucleus of OSCC cells. The relative expression of COL11A1-208 in SS-COL11A1-208 group was significantly lower than that in the SS-NC group (CAL27: 0.225±0.030 vs. 1.000±0.000; HN4: 0.393±0.028 vs. 1.000±0.000; P<0.01). Compared with the SS-NC group, proliferation activity, colonizing ability, migration and invasion abilities of SS-COL11A1-208 group decreased significantly (P<0.05). The relative expression of COL11A1-208 in LV-COL11A1-208 group was significantly higher than that in the LV-NC group (HN6: 6524.216±3395.926 vs. 1.000±0.000; HN4: 3486.230±743.908 vs. 1.000±0.000; P<0.05).Compared with the LV-NC group, proliferation activity, colonizing ability, migration and invasion abilities of LV-COL11A1-208 group were significantly increased (P<0.05). Compared with the SS-NC group, the relative expression of COL11A1 protein in SS-COL11A1-208 group decreased significantly (P<0.05), while the relative expression of COL11A1 protein in LV-COL11A1-208 group increased significantly than that in the LV-NC group (P<0.01). In addition, compared with the SS-NC group, the relative expression of E-cadherin in SS-COL11A1-208 group increased significantly (P<0.05), and the relative expression of vimentin decreased significantly (P<0.05). In LV-COL11A1-208 group, the relative expression of E-cadherin decreased significantly (P<0.05),and the relative expression of vimentin increased significantly (P<0.01). In vivo experiments showed that the xenograft tumor weight and volume of ASO-COL11A1-208 group were significantly reduced (P<0.05), while the xenograft weight and volume of LV-COL11A1-208 group were significantly enhanced (P<0.05). Conclusion COL11A1-208 could facilitate the cell proliferation and invasion of OSCC, which plays an important role in the development and progression of OSCCs.

Objective To investigate the role and significance of abdominal paracentesis drainage (APD) to pyroptosis in the pancreas of rats with severe acute pancreatitis (SAP), which is mediated by NLRP3 inflammasome-activated-caspase-1. Methods A total of 48 healthy male SD rats were randomly divided into three groups: sham operation (Sham) group, SAP group, and APD group, with 16 rats in each group. 5% sodium sulfonate was retrogradely injected into the pancreaticobiliary duct to establish the SAP model. In the APD group, besides the SAP induction, a drainage tube was placed on the right lower abdomen for drainage. Serum and pancreatic tissue were collected 12 hours after modeling. We examined the activities of serum lipase and amylase using an automatic biochemical analyzer and evaluated pancreatic damage through HE staining. In addition, we quantified the expression of serum inflammatory factors by ELISA and measured the expression level of genes and proteins related to caspase-1 mediated pyroptosis in pancreatic tissue using RT-PCR and Western blotting. Lastly, we observed the structural changes of the subcellular organelles and the characteristic changes of pyrolysis in pancreatic acinar cells using transmission electron microscopy. Results Compared with the SAP group, the pancreas tissue in the ADP group showed alleviated damages with a much lower pathological score; the levels of serum lipase, amylase, tumor necrosis factor(TNF)-α, Interleukin(IL)-6, IL-1β, and IL-18 also showed significant reduction (P<0.05).Compared with the Sham group, the expression levels of NLRP3, ASC, Caspase-1, cleaved caspase-1, GSDMD, and cleaved-GSDMD were all significantly up-regulated in the pancreas in the SAP group. After APD treatment, the expression of these Caspase-1-mediated pyrolysis pathway key genes in pancreatic tissue was significantly down-regulated. In addition, the expression levels of IL-1β and IL-18 mRNA in pancreatic tissue were also significantly reduced (P<0.05). Transmission electron microscopy showed that the SAP group had endoplasmic reticulum and mitochondrial expansion, chromatin condensation, and the characteristic change of pyrolysis, namely the formation of membrane pores in the cell membrane. In the APD group, we observed reduced chromatin condensation in the nucleus and less expansion in the endoplasmic reticulum and mitochondrial. Conclusion SAP showed activated Caspase-1-mediated pyroptosis. Early treatment with APD can alleviate the severity of SAP, possibly by inhibiting the activation of Caspase-1-mediated pyroptosis, thereby reducing local and systemic inflammatory reactions.

Objective To construct a PAEH/PEG DA hydrogel sustained-release system containing combined Pseudomonas aeruginosa (PA) outer membrane protein F (OprF) and Pseudomonas V antigen (PcrV) gene DNA vaccine, and evaluate the in vivo immune efficacy of the system. Methods The PAEH/PEG DA hydrogel containing combined PA DNA vaccine was prepared with a simple mixing method. The gelation time was tested, and the cytotoxicity (DC 2.4), degradation and cumulative release rate in vitro of the hydrogel were evaluated. Nine mice were randomly divided into 3 groups (3 each): 30 min group, 2 d group and 7 d group, the in vivo degradability and security of the hydrogel were evaluated by gelation volume changes at the injection site and histopathological sections of the skin, respectively. Eighteen mice were randomly divided into 6 groups (3 each): control group (PBS),hydrogel group (Gel), En/pVAX1-OprF group (O), En/pVAX1-PcrV group (P), En/(pVAX1-OprF+pVAX1-PcrV) group (OP), and hydrogel + En/(pVAX1-OprF+pVAX1-PcrV) group (GOP). Mice were immunized 3 times with a 10-day interval, then sacrificed 2 weeks after last immunization. The levels of serum specific IgG antibody, splenic lymphocyte stimulation index (SI) and interferon-γ(IFN-γ) in the supernatant of splenic lymphocytes were detected. Results The PAEH/PEG DA hydrogel sustained-release system required only about 30 min to form a gelation state. There was no significant toxicity to DC 2.4 cells in vitro, and approximately 85%of plasmid DNA was released after 36 hours of in vitro release. The degradation time of the hydrogel was nearly the same in vitro and in vivo. It could be almost completely degraded in about 7 days, and had good in vivo biodegradability and biosafety. The results of in vivo immune test showed that, compared with PBS group, no significant changes existed in the levels of specific IgG antibodies,splenic lymphocyte SI and IFN-γ in the Gel group (P>0.05). Compared with the corresponding DNA vaccine groups (O group or P group) and PBS group, the specific IgG antibody levels, spleen lymphocyte SI and IFN-γ level increased obviously in OP group and GOP group (P<0.05, P<0.01). While compared with OP group, the levels of specific IgG antibodies, splenic lymphocyte SI and IFN-γ increased markedly in GOP group (P<0.05, P<0.01). Conclusion The PAEH/PEG DA hydrogel sustained-release systems containing PA OprE and PcrF gene combined DNA vaccines, which can slowly release the combined DNA vaccine and further enhance the immune efficacy of combined DNA vaccine, are one of the promising strategies for the development of PA vaccines.