Cancer of digestive system is one of the most common worldwidely cancers and seriously threats to human health. However its etiology and pathogenesis are still not clear. Toll-like receptor (TLR), a newly discovered transmembrane receptor, plays an important role in innate immunity. Recent researches suggested that TLRs had extensive relationship with inflammation, autoimmune diseases and cancer. A large number of researches indicated that TLRs not only participated in the occurrence, development and immune escape of cancer, but also acted in immunotherapy in digestive system. Further investigation of TLRs may re-veal the effects of TLRs in the development of malignant tumors of digestive system, moreover may find new therputic target for the treatment of cancers. We reviewed the relationship between TLRs and cancers of di-gestive system.

Objective To systematically evaluate the efficacy and safety of combined hepatectomy and splenectomy in hepatocellular carcinoma complicated with hepatic cirrhosis and hypersplenism.Methods Medline (1966-August 2009), Embase (1974-August 2009), Cochrane Library, CBMdisc (1978-August 2009), and Wanfang Database were searched without language limitation. All relevant studies were screened and the data were extracted by two independent reviewers, and the methodological qualities of the included studies were evaluated by the Minors scale. The data were analyzed with the RevMan5 software. Results Five non-randomized comparative studies (NRCs) involving 476 patients (232 in HS group, 244 in control group) were enrolled into the analysis. There was no significant difference in the operative mortalities (OR=0. 57, 95%CI 0. 12-2. 66, P=0. 47) and postoperative morbidities (OR= 0. 93, 95 % CI 0.59- 1.46, P = 0.75) between the two groups. Compared with hepatectomy only, CD4+ T cell (WMD=7.90, 95%CI 7.01-8.79, P＜0.01), CD4+ T cell/CD8+ T cell ratio (WMD=0. 75, 95%CI 0. 70-0.80, P＜0.01), white blood cell count (WMD=5.47, 95%CI 5.13-5.82, P＜0.01) and platelet count (WMD=174.89, 95%CI 116.61-233.18,P＜0.01) were significantly higher, but CD8+ T cell (WMD = - 7.66, 95%CI - 8. 53～ - 6. 79,P＜0. 01) was lower compared with combined hepatectomy and splenectomy. There was no significant difference in the 5-year survival rates (OR= 1.37, 95%CI 0.86-2.18, P=0. 18). Conclusion Combined hepatectomy and splenectomy did not increase the operative mortalities and postoperative morbidities in hepatocellular carcinoma complicated with hepatic cirrhosis and hypersplenism. The white blood cell and platelet counts markedly increased after surgery. There was no evidence to show any improvement in the 5-year survival.

With the increasing learning demand for clinical research among refresher clinicians, the current refresher training system remains incomplete. In response to such demands, we have developed a whole-course mentorship training model, constructed a standardized theoretical training framework, and created diverse learning modules in 2020 in department of anesthesiology, West China Hospital, Sichuan University, thereby establishing a more complete clinical research refresher training program for anesthesiology. Practice has shown that this system effectively addressed the issues such as uneven knowledge levels of refresher clinicians and complex learning objectives and significantly improved their clinical research abilities. 42 refresher clinicians completed a clinical research program independently when they completed the training, and 14 of them published academic papers as the first author, with their supervisors. In the future, we will further optimize the training system and improve the quality of training by enhancing humanities education, enriching assessment dimensions, and establishing a training evaluation mechanism, and in addition, we will attract the clinicians of primary hospitals and support the development of primary hospitals by strengthening the efforts on publicity.

Objective:To observe the changes of arterial blood gas indexes in pigs with the free-field primary blast lung injury (PBLI) model, and to explore the value of arterial blood gas indexes in predicting moderate to severe PBLI.Methods:Nine adult healthy Landrace pigs were selected to construct the pig free-field PBLI model. Arterial blood samples were taken 15 minutes before the explosion (before injury) and 10, 30, 60, 120, and 180 minutes after the explosion (after injury). Arterial blood gas indexes and pulse oxygen saturation (SpO 2) were measured, compare the changes of blood gas analysis indexes and SpO 2 levels at different time points, and observe the changes of gross injury scores and pathological injury scores of lung tissue. Analyze the correlation between the blood gas indicators. Results:As time prolonged, at each time point, pH, arterial partial pressure of oxygen (PaO 2), and SpO 2 were lower than those before the injury, and blood lactic acid (Lac) and arterial partial pressure of carbon dioxide (PaCO 2) were higher than those before the injury. Compared with that before the injury, the pH value in the blood decreased significantly 10 minutes after the injury (7.39±0.06 vs. 7.46±0.02, P < 0.05), and the Lac increased significantly (mmol/L: 3.61±2.89 vs. 1.10±0.28, P < 0.05), and lasts until 180 minutes after injury (pH value: 7.37±0.07 vs. 7.46±0.02, Lac (mmol/L): 2.40±0.79 vs. 1.10±0.28, both P < 0.05); while PaO 2 and SpO 2 decreased significantly at 180 minutes after injury [PaO 2 (mmHg, 1 mmHg = 0.133 kPa): 59.40±10.94 vs. 74.81±9.39, P < 0.05; SpO 2: 0.75±0.11 vs. 0.89±0.08, P < 0.05], PaCO 2 increased significantly (mmHg: 56.17±5.38 vs. 48.42±4.93, P < 0.05). Correlation analysis showed that the gross injury score of lung blast injury animals was positively correlated with the pathological injury score ( r = 0.866, P = 0.005); PaO 2 and SpO 2 were positively correlated ( r = 0.703, P = 0.000); pH value and Lac were negative Correlation ( r = -0.400, P = 0.006); pH value is negatively correlated with PaCO 2 ( r = -0.844, P = 0.000). Conclusion:This study successfully established a large mammalian free-field PBLI model, arterial blood gas analysis is helpful for the early diagnosis of PBLI, whether SpO 2 can be used to evaluate the severity of lung injury remains to be further verified.

Objective Space radiation is an important environmental factor affecting the health and efficiency of astronauts.To explore the effects of radiation on electroencephalogram(EEG)signal,and to provide references for further study of the effects of radiation on Central Nervous System(brain)injury.Methods The resting state EEG of radiotherapy volunteers were collected before and after X-ray exposure.The effects of radiation on EEG was studied by means of spectral analysis,nonlinear dynamic characteristic analysis,correlation coefficient analysis and microstate analysis.Results The results show that radiation induced a"slow wave"phenomenon in the EEG spectrum,with a decrease in Gravity Frequency,Sample Entropy,and Lempel-Ziv Complexity,and an increase in Fatigue Index.The average duration and frequency of EEG microstate C both significantly decreased,and the proportion of time for microstate D decreased,while the average correlation coefficient between microstates A and C increased.Conclusion A decrease was induced by radiation in neuronal excitability,which may affect cognitive brain networks and brain attention.This study can provide reference for the study of radiation damage to the Central Nervous System(brain).

Objective:To evaluate the immunogenicity and protective effect of a multicomponent recombinant protein vaccine EPRHP014 constructed independently and provide a scientific basis for developing new tuberculosis (TB) vaccine and effective prevention and control of TB.Methods:Three full-length Mycobacterium ( M.) tuberculosis protein antigens (EsxH, Rv2628, and HspX) and two epitope-predicted and optimized epitope-dominant protein antigens (nPPE18 and nPstS1) were selected, from which five protein antigens were used to construct a protein antigen composition EPRHP014, including a fusion expression multi-component protein antigen (EPRHP014f) and a multi-component mixed protein antigen (EPRHP014m) formed with the five single protein using clone, purification, and purification respectively. Multicomponent protein vaccines EPRHP014f and EPRHP014m were prepared with aluminum adjuvant, and the BCG vaccine was used as a control. ELISA detected the titer of serum-specific antibodies, the secretion of various cytokines was detected by ELISpot and Luminex, and immune protection was observed by the M.tuberculosis growth inhibition test in vitro. The results were statistically analyzed by t-test or rank sum test, and P<0.05 was considered a statistically significant difference. Results:Mice Immunized with EPRHP014m and EPRHP014f could produce highly effective IgG antibodies and their subtypes IgG1 and IgG2a, and the antibody titers were similar to those of mice immunized with BCG, with no statistical significance ( P>0.05). The number of spot-forming cells (SFC) secreting IFN-γ and IL-4 induced by EPRHP014f group was significantly higher than those by EPRHP014m group and BCG group ( P<0.05), but there was no significant difference in the number of SFC for IFN-γ and IL-4 induced between EPRHP014m group and BCG group ( P>0.05). The secretion levels of GM-CSF and IL-12p70 induced by the EPRHP014m group were higher than those of the BCG group ( P<0.05), but there was no significant difference in the levels of IL-6 and IL-10 induced between EPRHP014m group and BCG group ( P>0.05). There was no significant difference in the secretions of IL-6, IL-10, IL-12, and GM-CSF between the EPRHP014f and BCG groups ( P>0.05). EPRHP014m group, EPRHP014f group, and BCG group had obvious antibacterial effects in vitro, and the difference was insignificant ( P>0.05). Conclusion:Both EPRHP014f and EPRHP014m can induce strong humoral and cellular immune responses in mice after immunization, and have a strong ability to inhibit the growth of M. tuberculosis in vitro, indicating that the antigen composition EPRHP014 has good potential in the development and application of TB vaccine.

Objective:To preliminarily evaluate the immunogenicity and efficacy of two novel tuberculosis vaccine candidates (a fusion multicomponent protein EPDPA015f and a mixed multicomponent protein EPDPA015m) and to provide a new antigen combination for the development of tuberculosis vaccines.Methods:Recombinant plasmids for the expression of EPDPA015f and EPDPA015m proteins were constructed. Six-week-old BALB/c mice were immunized with EPDPA015f or EPDPA015m in combination with aluminium adjuvant (50 μg/mouse) for three times with an interval of 10 d. The mice were sacrificed 10 d after the last immunization to collect blood and spleen samples. Serum antibody titers and cytokine levels were measured by ELISA, Luminex technique and enzyme-linked immunospot assay (ELISPOT). Mycobacterial growth inhibition assay (MGIA) was used to detect the ability of mouse splenocytes to inhibit the growth of Mtb in vitro. One-way analysis of variance and t-test were used for statistical analysis. Results:Both EPDPA015f and EPDPA015m could induce the production of various cytokines and IgG antibodies at a high level. The levels of cytokines related to Th1 (IL-2, TNF-α, IFN-γ), Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) as well as other proinflammatory cytokines (GM-CSF, IL-12) were higher in the EPDPA015f group than in the adjuvant group ( P<0.05). The titer of IgG antibody induced by EPDPA015f was as high as 1∶4×10 6. The results of MGIA showed that the numbers of Mtb (lgCFU) in the PBS, adjuvant, EPDPA015f and EPDPA015m groups were 3.46±0.11, 3.51±0.06, 2.98±0.09 and 3.19±0.08, respectively. The number of colonies in the EPDPA015f group was the least as compared with that in the other three groups ( P<0.001, P<0.001, P<0.01). Conclusions:The vaccine candidate EPDPA015f could elicit more comprehensive and high-level cellular and humoral immune responses, and exhibited superior in vitro inhibitory activity against the growth of Mtb. EPDPA015f had the potential to be used as a preventive vaccine or a booster vaccine

Electrocardiogram (ECG) monitoring owns important clinical value in diagnosis, prevention and rehabilitation of cardiovascular disease (CVD). With the rapid development of Internet of Things (IoT), big data, cloud computing, artificial intelligence (AI) and other advanced technologies, wearable ECG is playing an increasingly important role. With the aging process of the population, it is more and more urgent to upgrade the diagnostic mode of CVD. Using AI technology to assist the clinical analysis of long-term ECGs, and thus to improve the ability of early detection and prediction of CVD has become an important direction. Intelligent wearable ECG monitoring needs the collaboration between edge and cloud computing. Meanwhile, the clarity of medical scene is conducive for the precise implementation of wearable ECG monitoring. This paper first summarized the progress of AI-related ECG studies and the current technical orientation. Then three cases were depicted to illustrate how the AI in wearable ECG cooperate with the clinic. Finally, we demonstrated the two core issues-the reliability and worth of AI-related ECG technology and prospected the future opportunities and challenges.
Humans ; Artificial Intelligence ; Reproducibility of Results ; Electrocardiography ; Cardiovascular Diseases ; Wearable Electronic Devices

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia