Trauma-induced hypercoagulopathy is a hypercoagulable phenotype of trauma-induced coagulopathy (TIC) characterized by vascular endothelial injury, excessive release of procoagulants, hyperfibrinogenemia, platelet hyperactivity, anticoagulant pathways impairment and fibrinolysis shutdown. Recent studies have found that the incidence, mortality and disability rate of trauma-induced hypercoagulopathy increased significantly with the severity of trauma. Therefore, the People's Liberation Army Professional Committee of Critical Care Medicine and China Medical Education Association Professional Committee of Thrombosis, Hemostasis and Critical Care Medicine jointly formulated Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy published in Military Medical Research in April, 2021. In present paper, the main contents of the consensus were interpreted from the definition, pathophysiological mechanism, assessment, prevention, and treatment of trauma-induced hypercoagulopathy.

Objective To understand the effect of resveratrol (RSV) on vascular repair after the common carotid balloon injury in rats. Methods Forty SD rats were randomized into four groups (n=10): sham group, model group, solvent control group(DSMO group) and RSV group. After establishing the carotid artery balloon injury model, the rats in model group had no special treatment, while the rats in DMSO group and RSV group were given the same dose of DMSO or RSV respectively at the outside of the adventitia of carotid balloon injury segments. The rats in sham group received external carotid artery ligation. Fourteen days after the surgery, excessive anesthesia was applied to rats. The injured segments of the carotid arteries were collected, followed by HE staining to observe the degree of vascular intimal hyperplasia and stenosis. The expression of CD31 using immunohistochemical staining was detected to evaluate the degree of the re-endothelialization, and Western blotting was used to detect the expression levels of vascular endothelial growth factor (VEGF) in the arterial tissues. Results HE staining results showed that there was no significant difference in EEL circumference, EEL area and IEL area between groups (P>0.05); compared with sham group and DMSO group, the lumen area of RSV group decreased significantly (P<0.05). Compared with sham group, the degree of intimal hyperplasia increased in model group and RSV group (P<0.05); compared with model group, the degree of intimal hyperplasia decreased in DMSO group (P<0.05); compared with DMSO group, the degree of intimal hyperplasia increased in RSV group(P<0.05). Compared with sham group, the degree of stenosis in model group and RSV group were significantly higher (P<0.05); compared with model group, the degree of stenosis in DMSO group decreased significantly (P<0.05); compared with DMSO group, the degree of stenosis in RSV group was significantly higher (P<0.05). CD31 immunohistochemical staining results showed that the expression of CD31 in model group was significantly lower than that in sham group (P<0.05), and the expression of CD31 in RSV group was significantly higher than that in model group (P<0.05). Western blotting results showed that the expression of VEGF in model group significantly decreased than that in sham group (P<0.05); compared with model group and DMSO group, the expression of VEGF in RSV group significantly enhanced (P<0.05). Conclusion RSV can promote vascular repair and intimal hyperplasia, and enhance re-endothelialization after the common carotid balloon injury in rats, and the mechanism may be related to the proliferation and migration of adjacent resident endothelial cells and the recruitment of bone marrow endothelial cells or circulating endothelial cells.

Objective To explore the effect of propofol on human gastric cancer transplant BALB/c mice model treated with oxaliplatin. Methods We established a human gastric cancer model in the BALB/c mice using MGC 803 cells subcutaneous transplantation. Then the mice were randomly divided into control group (n=6), propofol group (n=6, 5 mg/kg propofol), oxaliplatin group (n=6, 6 mg/kg oxaliplatin), and propofol with oxaliplatin group (n=6, 5 mg/kg propofol+6 mg/kg oxaliplatin). The mice in each group received a total of 3 consecutive drug administrations through intraperitoneal injection once every 3 days. Mice were sacrificed two days after the last injection. Blood samples were then collected. The tumor volume and mass tumor inhibition rates were analyzed, respectively. The histological features of the tumor were evaluated with HE staining. The expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum were quantified using ELISA. In addition, the expression levels of epidermal growth factor (EGF), matrix metal protease-2 (MMP-2) and MMP-9 proteins in transplanted tumor tissue were quantified using ELISA. Results Compared with control group, the volume tumor inhibition rates (F=248.717, P<0.05) and mass tumor inhibition rates (F=376.205, P<0.05) of propofol group, oxaliplatin group, and propofol+oxaliplatin group were significantly reduced. The tumor volume inhibition rate and mass tumor inhibition rate of propofol+oxaliplatin group were significantly lower than those of oxaliplatin group, and the differences were statistically significant (tumor volume inhibition rate: 82.44%±4.69% vs.47.18%±5.71%, P<0.05; mass tumor inhibition rate: 77.95%±3.64% vs. 46.43%±3.99%, P<0.05). Compared with control group, cancer cell volume was reduced to varying degrees as well as the number of cancer cells was decreased in the remaining drug-treated groups using HE staining. In addition, the most significant decrease in cancer cell number happened in propofol+oxaliplatin group.The cell nucleus shrinks into a uniform blue-black dense body with an increased cytoplasmic density, increased cancer cell nuclear fragments, and large areas of necrosis. ELISA results showed that the levels of TNF-α and IL-6 in serum and EGF, MMP-2 and MMP-9 in transplanted tumor tissues of propofol group, oxaliplatin group and propofol+oxaliplatin group were significantly lower than those in control group, and those in propofol+oxaliplatin group were significantly lower than those in oxaliplatin group, and the differences were statistically significant (P<0.05). Conclusion Propofol can increase the sensitivity of gastric cancer cells to oxaliplatin, inhibit the proliferation, invasion and metastasis of gastric cancer cells, and enhance the anti-tumor effect of oxaliplatin.The mechanism may be related to the inhibition of inflammatory response by propofol and the regulation of EGF expression.

Objective To explore the effect and mechanism of carbazochrome sodium sulfonate on acute lung injury in septic rats. Methods Healthy male Wistar rats were randomized into 5 groups: sham group (n=25), sepsis group (n=25), low dose group (carbazochrome sodium sulfonate: 8 mg/kg)(n=25), middle dose group (carbazochrome sodium sulfonate: 40 mg/kg)(n=25), and high dose group (carbazochrome sodium sulfonate: 80 mg/kg)(n=25). Two additional groups, the autophagy inhibition group(3-MA)(n=10) and the sepsis middle dose group (carbazochrome sodium sulfonate: 40 mg/kg)(n=10), are also included in this study. After the preparation of septic rats by cecal ligation and puncture, the different doses of carbazochrome sodium sulfonate or 3-MA were given by intraperitoneal injection. The survival curve is drawn. After CLP 24 hours, the lung Micro-CT of those survival rats were examined. The arterial blood gas, pulmonary index and vascular permeability of lung tissue were measured. Pathological changes of lung tissues were observed by HE staining. The level of autophagic marker (LC3-Ⅱ/LC3-Ⅰ) of lung tissue was measured by Western blotting. Results Compared with sepsis group, the survival rate of the rats of carbazochrome sodium sulfonate groups increased, the arterial blood oxygen partial pressure and oxygenation index increased, the pulmonary index and vascular permeability decreased, and the differences were statistically significant (P<0.05). Both lung Micro-CT and HE staining showed that the lung lesions were more serious in sepsis group, while carbazochrome sodium sulfonate alleviated these lesions. Western blotting results showed that, the ratio of LC3-Ⅱ/LC3-Ⅰ in lung tissue of septic rats was higher than sham group (5.1±2.7 vs. 2.7±0.7, P<0.05), while the ratio of LC3-Ⅱ/LC3-Ⅰ in lung tissue in the low dose and middle dose carbazochrome sodium sulfonate groups was further increased than sepsis group (6.8±2.6, 8.9±1.4 vs. 5.1±2.7, both P<0.05). The value of LC3-Ⅱ/LC3-Ⅰ in the lung tissue of rats in 3-MA group was significantly lower than that in the middle dose carbazochrome sodium group (3.1±1.7 vs. 8.7±1.6), and the difference was statistically significant (P<0.05). Conclusion The mechanism by which carbazochrome sodium sulfonate-alleviating lung injury is related to the up-regulation of autophagy level in septic rats.

Objective To investigate the effect and mechanism of Z-guggulsterone (Z-GS) on removing slough and promoting muscle growth in skin ulcer of diabetic rats by extracellular regulated protein kinase (ERK)/mitogen activated protein kinase (MAPK) pathway. Methods Ten of the 65 rats were selected as healthy group, and the rest were used to establish the diabetic skin ulcer model. Removing 11 rats died during modeling, 44 successful modeling rats were randomly divided into model group, Z-GS group, inhibitor+Z-GS group and positive control group (11 each). No intervention was given to the rats in healthy group, the model groups were treated with vaseline gauze to cover the wounds. Z-GS was used in Z-GS group, PD98059+Z-GS was used in inhibitor+Z-GS group, and compound sulfadiazine zinc gel was used in positive control group, the treatment lasted for 4 weeks. The changes of healing rate of skin ulcer within 4 weeks after intervention in the model groups were recorded. The changes of serum inflammatory factors were detected by ELISA. HE staining was used to observe the histological structure of skin ulcer. The microvessel density (MVD) in wound tissue was detected by immunohistochemistry. Western blotting was used to detect the expression levels of ERK/MAPK pathway related proteins in the model group, inhibitor+Z-GS group and Z-GS group. Results From model group to inhibitor+Z-GS group, Z-GS group and positive control group, the wound healing rate of rats in turn increased in a time-dependent manner (P<0.05), while the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α)decreased in turn (P<0.05). Compared with model group, the new skin structure was nearly complete, inflammatory cell infiltration was rare, capillary content was abundant and collagen fibers were thicker in positive control group; the epidermis was obviously thickened, and the wound coverage was thicker scab, inflammatory cell infiltration decreased, capillary content was abundant and collagen fibers were small in inhibitor+Z-GS group and Z-GS group; compared with that in positive control group, the new skin was less complete, the inflammatory cell infiltration relatively increased, and the capillary blood vessels and collagen fibers were not abundant in inhibitor+Z-GS group and Z-GS group. From model group, inhibitor+Z-GS group to Z-GS group, the expression levels of phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated MAPK (p-MAPK) protein in wound tissue of rats increased in turn (P<0.05). Conclusion Z-GS may play the role of removing slough and promoting muscle growth by activating ERK/MAPK pathway in diabetic rats with skin ulcer.

Objective To explore the effect and mechanism of ivermectin (Ive) in enhancing oxaliplatin (L-OHP) against colon cancer HCT116/L-OHP cells. Methods In vitro establishment of colon cancer HCT116/L-OHP cells model with L-OHP low-concentration gradient increasing and low-concentration L-OHP (4 μmol/L) continuous culture. Set control group, L-OHP 25 μmol/L group, and L-OHP 25 μmol/L combined with 1, 2, 4, and 8 μmol/L Ive groups, and used MTT assay to detect cell viability. Set control group, L-OHP 25 μmol/L group, L-OHP+Ive 2 μmol/L group, and L-OHP+Ive 4 μmol/L group, and use cloning experiment to detect cell clone formation ability and flow cytometry apoptosis and cell cycle distribution, Western blotting was used to detect the expression levels of nuclear factor κB p65 (NF-κB p65), pregnane X receptor (PXR) and P-glycoprotein (P-gp). The colon cancer HCT116/L-OHP cells model with high expression of NF-κB p65 was constructed by LPS induction(setting control group, LPS group, LPS+L-OHP group, LPS+L-OHP+Ive 2 μmol/L group and LPS+L-OHP+Ive 4 μmol/L group), using lentiviral transfection to construct a colon cancer HCT116/L-OHP cells model with high PXR expression (setting control group, Ad-PXR group, Ad-PXR+L-OHP group, Ad-PXR+L-OHP+Ive 2 μmol/L group and Ad-PXR+L-OHP+Ive 4 μmol/L group), Western blotting was used to detect the expressions of NF-κB p65, PXR and P-gp protein levels. Twenty nude mice were injected subcutaneously with HCT116/L-OHP cells to establish a colon cancer drug-resistant cell transplantation tumor model and were divided into control group, L-OHP group, Ive group and Ive+L-OHP group, 5 mice in each group, and the tumor volume was calculated, the tumor weight was measured, and use immunohistochemistry to detect the expression of NF-κB p65, PXR and P-gp protein in the tumor tissues. Results Ive can potentiate L-OHP to inhibit colon cancer HCT116/L-OHP cells proliferation and clone formation (P<0.05), and promote colon cancer HCT116/L-OHP cells apoptosis and cell cycle S phase block (P<0.05).Western blotting showed that, in colon cancer HCT116/L-OHP cells, the expression levels of NF-κB p65, PXR and P-gp proteins in L-OHP+Ive 2 μmol/L group and L-OHP+Ive 4 μmol/L group were lower than those in control group, those in L-OHP+Ive 4 μmol/L group were lower than in L-OHP group (P<0.05). In the HCT116/L-OHP cells model with high NF-κB p65 expression, the expression levels of the NF-κB p65, PXR and P-gp protein in LPS+L-OHP+Ive 2 μmol/L group and the LPS+L-OHP+Ive 4 μmol/L group were lower than those in LPS group (P<0.05). In HCT116/L-OHP cells model with high PXR expression, the expression levels of the NF-κB p65, PXR and P-gp protein in Ad-PXR+L-OHP+Ive 2 μmol/L group and Ad-PXR+L-OHP+Ive 4 μmol/L group were lower than those in Ad-PXR group and Ad-PXR+L-OHP group, those in Ad-PXR+L-OHP+Ive 4 μmol/L group were lower than those in Ad-PXR+L-OHP+Ive 2 μmol/L group (P<0.05). In vivo experimental results showed that Ive can cooperate with L-OHP to inhibit the growth of HCT116/L-OHP cells xenograft tumors (P<0.05). The results of immunohistochemistry showed that the relative expression density of NF-κB p65, PXR and P-gp protein in the tumor tissues of Ive group, L-OHP group and Ive+L-OHP group was lower than that of control group. The L-OHP group and Ive+L-OHP group were lower than those in Ive group, and the Ive+L-OHP group were lower than those in L-OHP group (P<0.05). Conclusion Ive can enhance the effect of L-OHP against colon cancer HCT116/L-OHP cells, and its potential mechanism of action is to reduce the mediating effect of P-gp protein on L-OHP resistance by inhibiting the expression of NF-κB p65/PXR signaling pathway.

Objective To study the effect of Streptococcus pneumoniae pneumonia (S.pp) on the lung structure and function of mice. Methods Fifty neonatal BALB/c mice (1-week-old) were randomly divided into S.pp group and control group (25 each).Mice in S.pp group were infected intranasally with 2×10⁷ cfu of S. pneumoniae (D39) in 5 μl to establish the S.pp model, same dosage of PBS were used synchronously to treat the mice in control group. Three and five weeks after treatment, lung tissues and bronchoalveolar lavage fluid (BALF) of the two groups were collected, HE staining was performed to detect the pathological changes of lung tissue and alveolar structure; the collagen fiber deposition around alveoli was identified by Masson staining; the levels of IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) in BALF were examined by ELISA. Five weeks after the infection, lung resistance was evaluated by EMKA pulmonary system. Results HE staining showed that, compared with control group, the radial alveolar count (RAC) decreased significantly in infancy and adult S.pp group (8.00±1.10 vs. 3.53±0.35, P=0.018; 13.73±2.49 vs.4.02±0.21, P=0.018), the mean linear intercept (MLI) increased obviously (88.99±5.55 vs. 127.10±9.54, P=0.006; 74.45±4.84 vs. 131.30±17.86, P=0.020), and the alveolar septum thickness increased markedly [(2.38±0.18) μm vs. (3.28±0.13) μm,P=0.002; (3.41±0.60) μm vs. (5.78±0.75) μm, P=0.023]. Compared with control group, the mean alveolar diameter (MAD)increased significantly in infancy S.pp group [(167.00±8.85) μm vs. (193.40±5.14) μm, P=0.042], but no significant difference existed between control group and adult S.pp group. The infiltration of inflammatory cells around alveoli increased obviously in infancy and adult S.pp group compared with that in control group (1.68±0.24 vs. 0.72±0.12, P=0.002; 1.88±0.30 vs.0.67±0.23, P=0.006). Compared with control group, the concentrations of IL-25, IL-33 and TSLP in BALF of adult S.pp group increased significantly [(36.16±2.80) pg/ml vs. (45.16±1.74) pg/ml, P=0.024; (52.06±1.70) pg/ml vs. (61.42±1.50) pg/ml,P=0.004; (13.32±0.74) pg/ml vs. (16.71±0.54) pg/ml, P=0.007]; Collagen fiber deposition around alveoli increased markedly[(0.01±0.01) mm² vs. (0.44±0.01) mm², P<0.001], and the airway resistance increased significantly when the concentration of inhaled aerosolized methacholine reached to 12.5–50.0 mg/ml in adult S.pp group mice (P<0.001). Conclusion Streptococcus pneumoniae pneumonia may induce the decrease of mean alveolar count, the increase of MLI, the alveolar septum thickness and airway resistance in BALB/c mice, thus lead to abnormal lung tissue structure and function.

Objective To investigate the alterations of hepatokines fatty acid binding protein 1 (FABP1) in patients with dyslipidemia and their correlation with dyslipidemia. Methods The clinical data of 122 patients hospitalized in the Department of Cardiovascular Medicine of General Hospital of Western Theater Command during March to October 2020 were analyzed retrospectively. According to the blood lipids level and the criteria of inclusion and exclusion, 72 patients with abnormal blood lipids level (abnormal blood lipid group) and 50 patients with normal blood lipids level (normal blood lipid group) were identified. General information of all subjects was collected, including gender, age, height, weight, smoking and drinking habits, etc. Blood lipid, blood glucose, angiopoietin like protein (ANGPTL)3, ANGPTL4, ANGPTL6, FABP1 were detected. Propensity score matching (PSM) method was used to balance the confounding factors in the baseline data for comparing the alterations of hepatokines between the two groups. Binary logistic regression was used to analyze the risk factors of dyslipidemia, and multiple linear regression was used to analyze the correlation between FABP1 and blood lipid components. Results After balancing confounding factors by PSM method, no statistically significant difference existed in age, gender, tobacco and alcohol addiction, BMI and blood glucose between the two groups (P>0.05). The level of HDL-C was significantly lower, and the levels of TC, LDL-C and TG were significantly higher in abnormal blood lipid group than in normal blood lipid group (P<0.05). FABP1 level was significantly higher in abnormal blood lipid group than that in normal blood lipid group (P<0.05), while no statistical difference existed between the two groups in the serum levels of ANGPTL3, ANGPTL4 and ANGPTL6 (P>0.05). Binary logistic regression analysis showed that FABP1 was an independent risk factor for dyslipidemia (OR=1.011, P<0.05). Multiple linear regression analysis showed that a significant positive correlation existed between TG and FABP1 (β=0.291, P<0.05), and a significant negative correlation existed between TC+LDL-C and FABP1, as well as blood glucose and FABP1 (β=–0.443 and β=–0.268, P<0.05). Conclusion FABP1 is closely related to dyslipidemia, especially to the abnormal metabolism of triglyceride.

Objective To analyze the peripheral 1-de-amino-8-D-arginine vasopressin (hereinafter referred as DDAVP)irritant test as the best cut-off point for the differential diagnosis of Cushing's disease and ectopic adreno-cortico-tropic-hormone(ACTH) syndrome (hereinafter referred as EAS), so as to explore the value of peripheral DDAVP irritant test in differential diagnosis of ACTH-dependent Cushing's syndrome. Methods The clinical data of 102 cases with ACTH-dependent Cushing's syndrome, diagnosed in the Endocrinology Department of the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2019, were retrospectively analyzed, including 93 cases with Cushing's disease (Cushing's disease group) and 9 cases with EAS (EAS group). Based on the ROC curve, the blood ACTH level after stimulation was used as the detection variable, and the diagnosis result of Cushing's disease was used as the status variable to search the best cut-off point for the diagnosis of Cushing's disease. The sensitivity and specificity were analyzed of the peripheral DDAVP irritant test in the differential diagnosis of EAS and Cushing's disease at different cut-off points. Results Compared with Cushing's disease group, the course of disease was shorter and the basic blood cortisol and ACTH values were higher in EAS group with statistical significance (P<0.05). On the ROC curve, taking the increase by 33.6% of ACTH after stimulation as the cut-off point, the sensitivity and specificity for Cushing's disease and EAS were 98.9% and 55.6%, respectively, which were the best cut-off point. With the increase of blood ACTH value after stimulation, the sensitivity for diagnosing Cushing's disease decreased. If the increase by 20.0% of blood cortisol value after stimulation as the cut-off point simultaneously, then, the sensitivity for diagnosing Cushing's disease decreased and the specificity not increased. Thus, the blood ACTH was more specific than the blood cortisol. If taking the increase by 33.6% of the blood ACTH after peripheral DDAVP stimulation test, as well as the greater than or equal to 50.0% of the blood cortisol suppression ratio (or urinary free cortisol suppression ratio) in classical high-dose dexamethasone suppression test (HDDST) were taken as cut-off points, the sensitivity and specificity for identifying ACTH dependent Cushing's syndrome were 73.3% and 87.5%, respectively. Conclusion When taking the increase by 33.6% of blood ACTH after peripheral DDAVP stimulation as the cut-off point, the sensitivity was the highest in diagnosing Cushing's disease, so this method can be used as a screening test for and improve the detection rate of Cushing's disease.

Objective To explore the diagnostic value of thrombomodulin (TM) for sepsis-induced coagulopathy. Methods A prospective study was conducted on 172 hospitalized patients with sepsis from intensive care units (ICU) of the 908th Hospital of Chinese PLA Logistical Support Force between May 2018 and October 2019. All the subjects were divided into sepsis-induced coagulopathy (SIC) group (n=68) and sepsis alone (SA) group (n=104) according to the diagnostic criteria of International Society on Thrombosis and Haemostasis. Baseline characteristics [gender, age, acute physiology and chronic health evaluationⅡ (APACHE Ⅱ), sequential organ failure assessment (SOFA), mean arterial pressure (MAP), lactate (Lac), comorbidity, ICU mortality and length of stay in ICU], coagulation tests [prothrombin time (PT), international normalized ratio (INR), platelet count (PLT)] and molecular markers of coagulation [tissue plasminogen activator-inhibitor complex (t-PAIC), TM, thrombin-antithrombin complex (TAT), plasmin-α₂-plasmin inhibitor complex (PIC)] were compared. Multivariate logistic regression analysis was used to identify risk factors for SIC. The effectiveness of TM in diagnosing SIC was analyzed by ROC curve analysis. Kaplan- Meier analysis was used to analyze the cumulative survival rate. Results Compared with TM [10.5(7.8-14.9) TU/ml], TAT[8.6(4.8-18.0) ng/ml] and t-PAIC [11.6(7.1-22.2) ng/ml] in SA group, TM [15.0(10.5-25.9) TU/ml], TAT [15.1(5.7-34.6) ng/ml]and t-PAIC [22.1(11.0-39.1) ng/ml] in SIC group were significantly increased (P<0.05). Multivariate logistic regression analysis showed that TM and Lac were the independent risk factors for SIC. The area under the curve of TM for diagnosing SIC was 0.685 and its diagnostic threshold was 11.5 TU/ml. Its diagnostic sensitivity, specificity, positive predictive value and negative predictive value were 72.1%, 61.5%, 55.2% and 77.1%, respectively. Kaplan-Meier analysis revealed that the death risk of patients with sepsis in TM >11.5 TU/ml group was 3.61 times higher than TM ≤11.5 TU/ml group. The mortalities of patients who met or didn't meet the ISTH-SIC diagnosis criteria were respectively 47.1%(32/68) and 21.2%(22/104). The mortality of patients with SOFA≥2 and TM>11.5 TU/ml was 47.2%(42/89), while the other patients was 14.5%(12/83). Conclusions Elevated serum TM level could be found in patients with SIC. SOFA combined with TM has a better diagnostic efficacy for SIC.

4D printing, which distorts smart materials under specific stimulation, is emerging as a kind of modern fabrication technology. Underpinned by computer science and materialogy, 4D printing combines a wide range of disciplines including physics, bioengineering, medicine with manufacturing industry, and creates three-dimensional solid objects by adding smart materials layer by layer. Compared with 3D printing, 4D printing is functional demand-oriented, and the geometric structure formed by intelligent materials folds, bends, expands or shrinks under specific stimuli such as temperature and water, thus realizing the change of the performance of the object itself, such as hardness, stiffness, permeability and so on. 4D printing would serve as a new way of digital intelligent manufacturing, which emphasizes the need to consider the dynamic tissue healing and regeneration processes within human body. In addition, it can effectively realize the self-repair of the tissue and complete the bionics from structure to function, so it more truly simulates the dynamic evolution of human micro-environment. In this review, we collect the latest cases of 4D printing in biomedicines at home and abroad and then the potential advantages and challenges of 4D printing in practical application will be analyzed. Finally, we propose future directions and perspectives to further promote intelligentized 4D bioprinting technology in imitating architectures and function of native human tissues.

High-altitude pulmonary edema (HAPE) is a plateau-specific disease caused by low-pressure hypoxia in the plateau, which seriously threatens the quality of life and operational ability and, in severe cases, life in healthy people who have sharply advanced to the plateau. Although the treatment of the disease has been significantly improved, there are still some existing issues in the treatment. For instance, how to balance diuretic use, the effective blood volume supplementation, the timing of hyperbaric oxygen chamber application, and mechanical ventilation parameter settings in pulmonary edema, etc. This review reflects on the typology, pathogenesis, clinical manifestations, prevention and treatment considerations in plateau pulmonary edema.

Atherosclerosis is the basis of a variety of cardiovascular and cerebrovascular diseases, which may further lead to myocardial infarction, cerebral infarction and other life-threatening diseases. At present, the main therapy for atherosclerosis is to control the levels of cholesterol and low density lipoprotein. High density lipoprotein (HDL) is one of the main protective factors of cardiovascular disease. In recent years, more and more studies have revealed the relationship among atherosclerosis, HDL and immune system. The inhibitory effect of HDL on immuno-inflammatory responses could be one of the targets for treatment of atherosclerosis. The mechanism of HDL involved in the regulation of immuno-inflammatory responses of atherosclerosis was summarized in present paper for providing a new idea on treatment of atherosclerosis

A variety of mechanisms help tumor escape from the recognition and killing by the body immune system. In recent years, the adenosine pathway has been found to play an important role in tumor immune evasion. Adenosine is produced from extracellular adenosine triphosphate (ATP) in the presence of two ectonucleotidases (CD39 and CD73), and exerts specific functions through binding to its receptors [mainly adenosine A2A receptor (A2AR)]. Studies have suggested that the adenosine pathway can be over-activated in the tumor micro-environment, and thus promoting tumor development and progression by generating the immuno-suppressive signals. This review talked about the role of the adenosine pathway in regulating tumor immunity and its potential clinical application value. At the same time, the latest research evidence of adenosine-pathway-related targeted drugs is evaluated and summarized to provide a comprehensive reference for understanding the significance of the adenosine pathway in cancer management.

Periodontitis is a typical osteoimmune disorder characterized by inflammatory absorption of alveolar bone, and is the main cause for loose and fall off teeth in adults. Bacterial antigens stimulate the osteoclasts and aggravate periodontal inflammation, so it is of great significance for treatment of periodontitis to control inflammation and block the resorption of alveolar bone. Milk fat globule epidermal growth factor 8 (MFG-E8), as a lipophilic glycoprotein on the cell membrane, is expressed in multiple organs and histiocytes and participates in the bone immune response. MFG-E8 is involved in the development of osteoinflammatory diseases including periodontitis, so can be used as a new marker for the diagnosis of periodontal disease, and also has the potential of targeted therapy for periodontitis with the aggravation of osteoinflammatory diseases, the decreased expression of MFG-E8, reduction of osteoclasts formation and inhibition of alveolar bone resorption. MFG-E8 may be committed to early diagnosis and intervention to control the disease in order to reduce the economic burden of patients and improve the quality of life, and may become a hot spot for the treatment of periodontitis and other osteoinflammatory diseases in the future. Therefore, the research progress of MFG-E8-mediated osteoimmunology in periodontitis has reviewed in present paper to provide new ideas for clinical diagnosis and treatment of periodontitis.

By April 19, 2021, the ongoing coronavirus disease 2019 (COVID-2019), which is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has infected more than one hundred and fourty million individuals across more than 200 countries or territories and killed more than three million twenty-six thousand individuals worldwide. There are currently no specific drugs available for patients with COVID-19 infection, but a number of potential drug targets have been identified with the further understanding of the virological characteristics and pathogenesis of SARS-CoV-2. Some candidate drugs have shown good antiviral activity against SARS-CoV-2 in preclinical or clinical trials. This paper summarizes the current status of potential therapeutic drugs for COVID-19 in order to provide references for future COVID-19 therapy.