Objective To study the mechanism of +Gz environment exposure induced neck muscle injury in rabbits. Methods A total of 20 male rabbits were randomized into the negative control group, +Gz exposure group, +Gz exposure plus neck loading group, and +Gz exposure plus neck loading plus fixation group (5 in each group). The animal centrifuge was used to simulate the +Gz exposure environment. Rabbits in the +Gz exposure group, +Gz exposure plus neck loading group, and +Gz exposure plus neck loading plus fixation group were exposed for 4 weeks in a +6 Gz environment. Before and after the experiment, the rabbits in each group were photographed by X-ray. At the time of 0-, 1-, 2-, 3- and 4-week exposure, ear vein blood was collected from rabbits in each group, and ELISA was performed to detected plasma leveles of lactate dehydrogenase (LDH), creatine kinase (CK) and reactive oxygen species (ROS). After exposure, the trapezius muscle of rabbits was taken for HE staining to detect the muscle morphology.The apoptosis level was detected by TUNEL in the paraffin section of the rabbit trapezius muscle. The expressions of apoptosis-related proteins Bax and Bcl-2 in the trapezius muscle of rabbits were detected by Western blotting. The rabbit's neck trapezius muscle was taken to conduct proteomics testing, select differentially expressed proteins, and perform protein function cluster analysis. Results There was no significant difference in the morphology of the cervical vertebra in each group before and after+Gz exposure. Compared with negative control group, plasma levels of LDH, CK, and ROS in +Gz exposure group, +Gz exposure plus neck loading group, and +Gz exposure plus neck loading plus fixation group significantly increased (P<0.05). Compared with negative control group, the ratio of apoptosis protein Bax/Bcl-2 in +Gz exposure group significantly increased (P<0.05), the number of positive apoptosis cells detected by TUNEL significantly increased (P<0.05). Compared with +Gz exposure group, the+Gz exposure plus neck loading group showed an increased Bax/Bcl-2 ratio (P<0.05) and more TUNEL positive cells (P<0.05).Compared with +Gz exposure plus neck loading group, the ratio of apoptosis protein Bax/Bcl-2 and the positive number of apoptosis were decreased in +Gz exposure plus neck loading plus fixation group, but there were no statistically significant differences (P>0.05).A total of 600 proteins were significantly altered in +Gz exposure group compared to negative control group, and GO functional clustering analysis of the differential proteins revealed significant enrichment of proteins associated with mitochondrial function. Conclusion Exposure to the +Gz environment can cause neck muscle injury and cell apoptosis in rabbits. The muscle injury symptoms can be improved by fixing the stress link of the rabbit neck. Cell apoptosis induced by +Gz exposure may be related to mitochondrial function.

The purpose of Bacillus Calmette-Guérin (BCG) vaccination is to prevent Mycobacterium tuberculosis infection, but studies have shown that BCG activates innate immunity, causes epigenetic reprogramming and metabolic changes of myeloid cells, and forms innate immune memory or trained immunity. When bone marrow-like cells are stimulated by pathogens again, they show enhanced immune response and promote the host's nonspecific defense ability. Innate immune memory is also called training immunity. In recent years, BCG-induced innate immune memory has attracted much attention, and it will guide the design of novel vaccine. This article reviews the application of BCG in prevention and treatment of corone virus disease 2019, the non-specific protection and mechanism of BCG-mediated trained immunity.

Pulmonary arterial hypertension (PAH) is a progressive disease with poor prognosis, which may lead to right heart dysfunction, resulting in a series of clinical symptoms and even death, and there is still a lack of effective treatment. The etiology of PAH is complex, in which epigenetic changes play an important role in its pathogenesis. Histone acetylation modification is one of the most widely and deeply studied epigenetic modifications. The histone acetylation is mainly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), which play a key role in chromatin and gene regulation, and is closely related to the occurrence of PAH. Targeted histone acetylation pathway has a certain therapeutic potential for PAH. This article reviews the research progress on the effect of HDACs on PAH, in order to further understand the pathogenesis of PAH and provide a new direction of treatment.

Objective To analyze the significance and biological role of MAGEA6 expression in gastric cancer. Methods The tissue microarray samples of 90 cases of gastric cancer resected surgically in the hospital sample bank from December 2009 to June 2010 were collected. The expression of MAGEA6 in gastric cancer tissue microarray was detected by immunohistochemical staining, and the relationship between MAGEA6 expression and clinicopathological features of gastric cancer was analyzed.Kaplan-Meier analyzed the relationship between the expression of MAGEA6 and the prognosis of gastric cancer. BGC-823 gastric cancer cell line was cultured in vitro. Set si-MAGEA6 group (transfected with si-MAGEA6) and si-Ctrl group (transfected with vector), the cell proliferation ability and apoptosis rate were detected by CCK-8 and flow cytometry. Western blotting detected the expression of MAGEA6, apoptosis-related proteins [b lymphoma-2 gene (Bcl-2), bcl-2 related X protein (Bax)], autophagy-related proteins [microtubule associated protein light chain 3-Ⅱ (LC3-Ⅱ), p62 protein (p62), autophagy-related gene 5 (Atg5) protein, yeast Atg6 homolog (Beclin 1)], Akt/mTOR signaling pathway-related proteins [protein kinase B (Akt), phosphorylated protein kinase B (p-Akt), mammalian target of rapamycin (mTOR), phosphorylated mammalian target of rapamycin (p-mTOR)]. The autophagy flow and autophagosome formation were observed by laser confocal microscope and electron microscope. Results The immunohistochemical score of MAGEA6 in gastric cancer tissues was higher than that in adjacent tissues [(3.77±1.50) points vs.(2.58±1.11) points, P<0.05]. Patients with high expression of MAGEA6 were significantly related to age and TNM stage (P<0.05).The cell viability of gastric cancer cells in si-MAGEA6 group was lower than that in si-Ctrl group (P<0.05). The apoptosis rate of gastric cancer cells in si-MAGEA6 group was higher than that in si-Ctrl group (14.97%±0.86% vs. 4.63%±0.55%, P<0.05). The protein expression levels of MAGEA6, Bcl-2, p62, p-Akt, and p-mTOR in si-MAGEA6 group were lower than those in si-Ctrl group, the protein expression levels of Bax, Atg5, Beclin 1, and LC3-Ⅰ/LC3-Ⅱ were higher than those in si-Ctrl group (P<0.05). In the si-MAGEA6 group, autophagy bodies increased significantly, and autophagy bodies and lysosomes formed autophagy lysosomes. Conclusions Gastric cancer tissues showed a significantly increased level of MAGEA6. Silencing MAGEA6 expression inhibits the proliferation of gastric cancer cells, suggesting that MAGEA6 may be an effective biomarker and potential therapeutic target for gastric cancer.

Objective To investigate the relationship between autoantibodies and biochemical responses to different doses of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cholangitis (PBC). Methods Clinical data of 122 patients with PBC admitted to the Department of Gastroenterology, the Second Affiliated Hospital of Kunming Medical University from January 2013 to August 2020 were retrospectively analyzed. According to the treatment dose of UDCA, they were divided into >15 mg/(kg.d)UDCA group (n=71)and ≤15 mg/(kg.d) UDCA group (n=51). The relationship between antibody typing and treatment response to different doses of UDCA group and the effects of different doses of UDCA on biochemical indexes and immune indexes of PBC patients were analyzed. Results Baseline anti-SSA positive PBC patients were associated with >15 mg/(kg.d) UDCA response (P<0.05); Pathological stage Ⅱ was associated with ≤15 mg/(kg.d) UDCA response (P<0.05). The level of alanine transaminase (ALT), aspartase aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL), IgM and the positivity rates of antinuclear antibodies (ANA) in>15 mg/(kg.d) UDCA group were significantly decreased after 1 year of treatment, and the pre-albumin was significantly increased (P<0.05).The levels of ALP and GGT and the positivity rates of anti-mitochondrial antibody type 2 (AMA-M2) in UDCA group ≤15 mg/(kg.d)after one year of treatment were significantly lower than those before treatment, and the pre-albumin level was significantly decreased (P<0.05).From the perspective of pathological stages, the >15 mg/(kg.d) UDCA group was dominated by stages Ⅲ and Ⅳ, and the ≤15 mg/(kg.d)UDCA group by stages Ⅰ and Ⅱ. The positivity rate of anti-gp210 was higher in non-response group than that in response group regardless of dose. Conclusions Both large and small doses of UDCA can improve the biochemical and immune indices of PBC patients, but for patients with severe disease and advanced pathological stage, high-dose UDCA therapy is recommended.

Lymph node noncompliance is an indicator. If multiple lymph node stations are not detected in each group of lymph nodes submitted for inspection, the specimen is regarded as lymph node noncompliance. Under the background that the incidence of advanced gastric cancer has been increasing year by year, more and more surgeons have begun to pay attention to the surgical effect of radical gastric cancer surgery and the prognostic quality of life of patients. A large number of domestic and foreign experimental studies have shown that the sequence of lymph node metastasis of gastric cancer is roughly from the lesser curvature of the stomach to the lymph nodes around the abdominal aorta. In addition, during the process of lymph node metastasis, there may be lymph nodes that do not appear in the specified location, or due to the factors such as the patient's advanced age, different surgical procedures, thick abdominal fat, deep tumor invasion, and more intraoperative bleeding, the D2 lymph node may be used for gastric cancer. During the resection operation and postoperative pathological sorting, certain errors occurred. Although radical resection of D2 lymph nodes has become a standard surgical approach for the treatment of advanced gastric cancer, a variety of congenital anatomical factors or human error factors will still cause a decrease in the detection rate of postoperative lymph nodes. Therefore, adequate D2 anatomy is still a research focus and difficulty for surgeons. This article discusses the research progress of lymph node noncompliance in D2 radical resection of advanced gastric cancer.

Female urethral stricture is considered to be one of the important causes of female lower urinary tract symptoms, but it is relatively rare in clinical practice and lacks relevant diagnostic and therapeutic guidelines. In the past, urethral dilation was used as the first-line treatment option for this disease. However, due to its low success rate, high recurrence rate of stricture, and with the development of research on the structure of the female urethra, a variety of urethroplasty procedures have been applied. The success rate of urethroplasty is high, but it is not clear which procedure is more superior. This article reviews the research progress in the etiology, diagnosis and treatment of female urethral stricture to provide a reference for urologists to carry out a variety of treatment methods, and to promote the clinical application of related diagnosis and treatment.

Intracranial aneurysm (IA), characterized by distended blood vessels within the arteries, is a common vascular anomaly that frequently leads to cerebral blood vessel rupture, causing subarachnoid hemorrhage (SAH) with serious consequences.It has been found that, in addition to genetic factors, inflammatory responses induced by altered hemodynamics play a key role in the formation and rupture of IA. Subsequently, vascular inflammation can trigger a series of biochemical responses involving a variety of cells, including vascular smooth muscle cells, macrophages, lymphocytes, mast cells, and neutrophils, and involving several signaling pathways, including the PGE2-EP2-NF-κB signaling pathway, the JAK/STAT3/NF-κB signaling pathway, PI3K/Akt (PKB) signaling pathway, and AMPK/ACC signaling pathway. However, no clear conclusions have been made regarding the specific pathogenesis of IA, and immunotherapies targeting the pathogenesis of IA are still under basic research and not widely used in clinical practice. This review describes the cells, cytokines, and signaling pathways involved in the development of IA, in the hope that it will contribute to the understanding of the pathogenesis of IA and inspire the development and use of immunological drugs.

Objective To explore the promoting effect and its mechanism of shikonin on wound healing and neovascularization of rats with chronic skin ulcer. Methods Fifty of 60 male SD rats were selected to establish the rat model of chronic skin ulcer, of which 40 rats were done successfully and randomly divided into the model group, positive control group, and low- and high-dose shikonin groups (10 rats each). The other 10 rats served as the control group. The wound surfaces in low-and high-dose shikonin group were evenly smeared with 4 mg/cm² and 8 mg/cm² shikonin suspension, in positive control group with 1890 U/cm² recombinant bovine basic fibroblast growth factor gel to smear the wound, and in model group and positive control group were given the equal volume of normal saline for external application. The wound healing was observed on the 3rd,7th and 14th day of intervention. The abdominal aortic blood and wound granulation tissue of rats were taken after intervention, the histopathological changes of wound granulation were observed by HE staining, and the neovascularization was observed by immunohistochemical staining; the content of hydroxyproline (HyP) in granulation tissue was detected by hydrolysis method, the expression of Notch1 pathway related protein in granulation tissue was detected by Western blotting; and the levels of serum inflammatory factors were detected by ELISA. Results The wound healing rate of skin ulcer in each group increased with time and in a time-dependent manner (P<0.05). The wound healing rate decreased in low- and high-dose shikonin groups than in positive control group, and decreased in low-dose shikonin group than in high-dose shikonin group on the 3rd, 7th and 14th day of intervention (P<0.05). HE staining showed that new granulation tissue with a large number of inflammatory cell infiltration could be seen in model group. Compared with model group, old granulation tissue and inflammatory cell infiltration were observed in low- and high-dose shikonin groups and positive control group, and the inflammatory cell infiltration decreased in turn. Compared with that in positive control group, the IOD value of wound granulation tissue decreased in low- and high-dose shikonin groups(104 725.45±2062.45 vs. 197 585.23±2478.42, P<0.05; 149 752.54±2441.86 vs. 197 585.23±2478.42, P<0.05), and the content of HyP decreased [(3.62±0.12) μg/mg vs. (6.48±0.14) μg/mg, P<0.05; (4.94±0.15) μg/mg vs. (6.48±0.14) μg/mg, P<0.05].The IOD value and HyP content of wound granulation tissue were higher in high-dose shikonin group than in low-dose shikonin group (P<0.05). Western blotting results showed that the relative expressions of vascular endothelial growth factor (VEGF) and transforming growth factor β₁ (TGF-β₁) in wound granulation tissue increased, and of Notch1 protein decreased in low- and high-dose shikonin groups than in model group (P<0.05), while the relative expression of VEGF and TGF-β₁ increased and of Notch1 protein decreased in wound granulation tissue of high-dose shikonin group than in low-dose shikonin group (P<0.05). ELISA results showed that the levels of serum IL-8 and TNF-α decreased in positive control group and low- and high-dose shikonin groups than in model group (P<0.05), but increased in low- and high-dose shikonin groups than in positive control group (P<0.05), and decreased in the high-dose shikonin group than in low-dose shikonin group (P<0.05). Conclusion Shikonin may promote the wound healing and neovascularization of rats with chronic skin ulcer by regulating Notch1 signaling pathway.

Objective To report a case of refractory Takayasu arteritis (TAK) treated with tofacitinib (TOF) and evaluated by contrast-enhanced ultrasound, and perform a literature review to better understand this disorder. Methods The data of a case of TAK treated with TOF were analyzed retrospectively, the treatment and follow-up experience summarized by searching the database(CNKI, Wanfang Data, PubMed) and the literature results analyzed comprehensively. Results The patient, a 28-year-old female with a 10-year history of TAK, presented with fever, neck pain and joints pain. Ultrasonography revealed intimal thickening and stenosis of the carotid artery. Laboratory tests demonstrated an elevated erythrocyte sedimentation rate (ESR) and a C-reactive protein (CRP) level. The symptoms were improved after glucocorticoid (GC) treatment. However, it relapsed during the course of GC tapering, even with the combination of disease modifying anti-rheumatic drugs (DMARDs) and tocilizumab. The DMARDs and tocilizumab were not used continuously due to poor response and adverse drug reactions. As disease progressing, left subclavian aneurysm appeared. The treatment of this patient is a big challenge. After adjusting the treatment with tofacitinib (10 mg/d, then adjust to 7.5 mg/d) and GC (methylprednisolone 14 mg/d, then reduce to 8 mg/d), the patient was successfully relieved without any serious adverse events. Contrast-enhanced ultrasound showed that the thickness of arterial wall decreased (the thickness of left common carotid artery decreased from 8.9 mm to 1.2 mm, and the thickness of left subclavian artery decreased from 7.4 mm to 0.8 mm), the contrast intensity decreased (the total score decreased from 5 to 1), and the aneurysm disappeared. By March 2021 (searching CNKI, Wanfang Data and PubMed), a total of 10 cases of TAK patients treated with TOF. Nine patients were women. Seven patients improved and GC reduced. Only one patient had adverse reactions. Conclusions Janus kinase inhibitor is expected to be a new drug for the treatment of TAK. Contrast-enhanced ultrasound can detect the thickness of the vessel wall and the enhancement of the thickened wall in real time. Contrast-enhanced ultrasound will be an effective tool for evaluating vascular inflammation.