Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Purpose/Significance Based on the typical use scenario of sensitive personal information in medical and health institu-tions,the implementation of the secure use of sensitive personal information is explored.Method/Process For user registration,internal utilization and interaction,medical device/wearable device collection and information disclosure and other scenarios,the paper analyzes the risk of sensitive personal information leakage,explores the application scenarios,advantages and disadvantages of various technical means such as identity authentication,access control,data encryption,data desensitization and detection audit.Result/Conclusion The application of technical means can assist medical and health institutions to further protect the security of patients'personal information.

Objective To evaluate the effect of endoscopic laryngeal mask on perioperative airway management and postoperative recovery in patients undergoing gastric endoscopic submucosal dissection(ESD).Methods Ninety patients,aged 18-64 years,BMI 18-25 kg/m2,ASA physical statusⅠorⅡ,who underwent elective gastric ESD were randomly divided into two groups:the endoscopic laryngeal mask group(group E)and the endotracheal tube group(group C),45 patients in each group.After induction of general anesthesia,group E received endoscopic laryngeal mask airway ventilation,and the endoscope was inserted through the endoscopic channel of the laryngeal mask,group C received tracheal intubation,and the endoscopy was inserted through the mouth.The successful time and one-time success rate of intubation,and the insertion time and withdrawal rate of endoscopy were recorded.The operative time,extubation time and PACU residence time were recorded.HR,MAP were recorded when the patient entered the room(T0),at the time of intubating(T1),inserting gastroscopy(T2),exiting gastroscopy(T3),extubation(T4),and leaving PACU(T5).The average airway pressure and peak airway pressure at T1-T3 were recorded.The airway sealing pressure and endoscopic view grading system(EVGS)grading of group E were recorded before and after changing the position,and at the end of surgery.The adverse reactions and the satisfaction of anesthesiologists and gastroenterologists were recorded.Results Compared with T0,HR and MAP were significantly increased at T1 and T4 between the two groups(P＜0.05).Compared with group C,the suc-cessful time of intubation,the extubation time,and PACU residence time were significantly shortened,HR and MAP were significantly decreased at T1 and T4,the incidence of choking cough during extubation,post-operative pharyngeal pain,and hoarseness were significantly decreased(P＜0.05).There were no signifi-cant differences in the one-time success rate of intubation,the insertion time and withdrawal rate of endosco-py between the two groups.Endoscopic laryngeal mask showed good sealing and alignment in group E.Conclusion Endoscopic laryngeal mask could shorten the success time of establishment of artificial airway in patients with gastric ESD,without interfering with digestive endoscopy operations,shorten extubation time and PACU retention time,maintain intraoperative hemodynamic stability,and reduce adverse reactions.

Taking medical statistics major in Binzhou Medical University as an example, based on the outcome-based education theory, in order to enhance the innovation ability of university students, we put forward the systematic second classroom training system, including improving the personnel training system, implementing education, experiment teaching reform, and practice teaching reform. It has achieved outstanding results in the discipline competition, improved social service ability and high degree of employer satisfaction. The systematic second-class talent training system based on the outcome-based education theory can provide reference for other medical colleges and related applied majors.

Objective:To evaluate the efficacy and safety of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) monotherapy for brain metastasis in advanced non-small cell lung cancer (NSCLC), and to explore the timing of immunomonotherapy and the application of hormone on the efficacy of ICI.Methods:By searching literature in CNKI, Wanfang, VIP, PubMed, CBM, Embase, Cochrane Library and Web of Science databases, the advanced NSCLC patients with brain metastasis who received ICI treatment were identified, including patients with symptomatic brain metastasis who had received hormone therapy or brain surgery or radiotherapy. Meta-analysis was performed on the collected data to evaluate the systemic objective response rate (sORR) and intracerebral tumor objective response rate (iORR), the iORR of whether ICI monotherapy was first-line therapy, and the iORR of whether hormone was used were evaluated, and the incidence of adverse reactions was evaluated.Results:Fifteen studies were finally included, with a total of 4 033 patients, including 917 patients with brain metastasis. The iORR of immunomonotherapy was 26% (95% CI 19%-34%) and the sORR was 28% (95% CI 18%-40%). The iORR of first-line immunomonotherapy was 49% (95% CI 39%-58%). The iORR of symptomatic patients with hormone therapy and asymptomatic patients without hormone therapy was 26% (95% CI 20%-33%) and 19% (95% CI 16%-22%), respectively. The overall incidence of grade 3-4 adverse reactions was 14% (95% CI 11%-17%). Conclusions:The efficacy of ICI monotherapy in the first-line treatment of PD-L1-positive NSCLC patients with brain metastasis is better than that in the subsequent line therapy, and the application of hormone does not affect the efficacy of ICI. ICI monotherapy in the treatment of advanced NSCLC patients with brain metastasis is safe.

Objective:To investigate the relationship between the changes of inflammatory cytokine levels and prognosis of patients with critical coronavirus disease 2019 (COVID-19) undergoing invasive mechanical ventilation (IMV).Methods:A retrospective study was conducted. The clinical date of critical COVID-19 patients undergoing IMV who were hospitalized in Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from February 4th to March 25th in 2020 were collected. At the same time, the inflammatory cytokine levels including interleukins (IL-2, IL-4, IL-6, IL-10) and tumor necrosis factor-α (TNF-α) at 48 hours before IMV and 48 hours after IMV of all the patients, as well as the 48 hours after weaning or right before death were recorded. Multivariate unconditional Logistic regression analysis was used to screen the independent risk factors of death during hospitalization.Results:Among the 43 patients, 13 patients improved and 30 died. Compared with the survival group, the patients in the non-survival group were older (years old: 67.6±7.3 vs. 58.5±11.9, P < 0.05), with higher rates of hypertension, diabetes and coronary heart disease (53.3% vs. 15.4%, 63.3% vs. 23.1%, 26.7% vs. 0%, all P < 0.05), and the time from onset to admission to hospital, admission to ICU and IMV were longer (days: it was 9.17±5.00 vs. 5.07±2.49, 17.10±7.11 vs. 12.23±5.05, and 17.90±7.46 vs. 12.61±5.60, respectively, all P < 0.05). The IL-6 and TNF-α levels on 48 hours after IMV in the non-survival patients increased significantly as compared with those before 48 hours and the surviving patients. Especially, the IL-6 levels increased significantly as compared with those at 48 hours after IMV and 48 hours after weaning in the surviving patients [ng/L: 800.00 (194.25, 2 000.00) vs. 22.03 (6.66, 28.21), 3 204.00 (1 264.88, 5 000.00) vs. 5.00 (3.98, 12.27), both P < 0.01]. The IL-10 level before death in the non-survival patients increased significantly as compared with that at 48 hours after weaning in the surviving patients [ng/L: 55.89 (26.07, 100.14) vs. 3.53 (2.76, 12.36), P < 0.05]. There were no significant differences in the levels of IL-2 and IL-4 between the two groups at every time point. The variables of age, basic diseases, the IL-6 level after IMV were included in the multivariate unconditional Logistic regression analysis, which showed that age [odds ratio ( OR) = 0.821, 95% confidence interval (95% CI) was 0.695-0.968], hypertension ( OR = 0.027, 95% CI was 0.002-0.378), diabetes mellitus ( OR = 0.054, 95% CI was 0.005-0.611), coronary heart disease ( OR = 0.042, 95% CI was 0.002-0.968) and the IL-6 level after IMV ( OR = 0.902, 95% CI was 0.819-0.994) were independent risk factors for death during hospitalization in patients with critical COVID-19 undergoing IMV (all P < 0.05). Conclusions:The levels of inflammatory cytokine including IL-6, IL-10, and TNF-α increased significantly with aggravation in critical COVID-19 patients undergoing IMV, especially IL-6. IL-6 was an independent risk factor for death of critical COVID-19 patients undergoing IMV.

Objective To explore the signs of consistent changes of intestinal flora in type 2 diabetes mellitus (T2DM) and diabetes kidney disease (DKD) patients, by studying the key change characteristics of intestinal flora in these patients. Methods Thirty patients with T2DM,twenty-five patients with DKD were involved. Thirty healthy patients with matching age and sex were also involved as the control group. Fecal and serum specimens were collected from both the study group and the control group. High-throughput sequencing technology was used to sequence the 16S rDNA-v4 region of fecal samples;interleukin-6 (IL-6) and C-reactive protein (CRP) were detected by electrochemical luminescence and immunoturbidimetry. Microbiome analysis software QIIME (v1.9.1) was used to analyze the composition and diversity of intestinal flora. Microbial diversity analysis software LEfSe was used to compare intestinal bacteria markers differences between the study group and the healthy control group. The diagnosis model was established by the random forest method. The change characteristics of intestinal flora function were predicted by the PICRUSt. Results The intestinal flora diversity of DM and DKD patients was significantly different from that of the healthy control group (P<0.05). T2DM and DKD patients harbored lots of similar changes. For example, there was a significant decrease in Lachnospira, Faecalibacterium, Roseburia and Coprococcus(P<0.05). However, there was also a disease-specific pattern of imbalance between the two disease. There was a significant increase in Bacteroides in T2DM patients, and in Lactobacillus, Slackia, Anaerotruncus,Haemophilus and Enterococcus in DKD patients. Functional prediction was also confirmed that T2DM and DKD patients had more consistent changes. The correlation analysis between serum inflammatory indicators of T2DM and DKD and bacteria suggested that the decrease of beneficial bacteria in the intestinal tract of T2DM and DKD patients may be the cause of the increase of serum inflammatory indicators. Conclusion T2DM and DKD patients harbored lots of similar changes in intestinal flora, a decrease of bacteria producing butyrate,but there was also a disease-specific change between the two disease,providing a data basis for further studies to evaluate the risk of nephropathy in patients with diabetes by intestinal flora .

Objective To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China. Methods The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient′s stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed. Results (1) The total number of hospitalized patients with stageⅠa2 toⅡa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01). The constituent ratio of patients aged 35 years or younger was significantly greater during 2004—2010 than that during 2011—2016 [12.6% (820/6 484) and 8.5% (1 068/12 557), respectively; χ2=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stageⅠ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05). Conclusions The trend in proportion among hospitalized patients for stageⅠa2 toⅡa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion>1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.

Objective: To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China. Methods: The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient's stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed. Results: (1) The total number of hospitalized patients with stage Ⅰa2 to Ⅱa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01) . The constituent ratio of patients aged 35 years or younger was significantly greater during 2004—2010 than that during 2011—2016 [12.6% (820/6 484) and 8.5% (1 068/12 557) , respectively; χ²=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stage Ⅰ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05). Conclusions The trend in proportion among hospitalized patients for stage Ⅰa2 to Ⅱa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion >1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.

Chronic high-salt diet-associated renal injury is a key risk factor for the development of hypertension. However, the mechanism by which salt triggers kidney damage is poorly understood. Our study investigated how high salt (HS) intake triggers early renal injury by considering the ‘gut-kidney axis’. We fed mice 2% NaCl in drinking water continuously for 8 weeks to induce early renal injury. We found that the ‘quantitative’ and ‘qualitative’ levels of the intestinal microflora were significantly altered after chronic HS feeding, which indicated the occurrence of enteric dysbiosis. In addition, intestinal immunological gene expression was impaired in mice with HS intake. Gut permeability elevation and enteric bacterial translocation into the kidney were detected after chronic HS feeding. Gut bacteria depletion by non-absorbable antibiotic administration restored HS loading-induced gut leakiness, renal injury and systolic blood pressure elevation. The fecal microbiota from mice fed chronic HS could independently cause gut leakiness and renal injury. Our current work provides a novel insight into the mechanism of HS-induced renal injury by investigating the role of the intestine with enteric bacteria and gut permeability and clearly illustrates that chronic HS loading elicited renal injury and dysfunction that was dependent on the intestine.
Animals ; Bacteria ; Bacterial Translocation ; Blood Pressure ; Drinking Water ; Dysbiosis ; Enterobacteriaceae ; Gastrointestinal Microbiome ; Gene Expression ; Hypertension ; Intestines ; Kidney ; Mice* ; Microbiota ; Permeability ; Risk Factors