Objective To investigate the expression levels and prognostic value of preoperative serum exosomes micro RNA(miR)-193a and micro RNA(miR)-208b in patients with gastric cancer(GC).Methods A total of 132 patients who underwent GC radical gastrectomy in the First Affiliated Hospital of Xinjiang Medical University from March 2018 to March 2020 were regarded as the GC group,while 132 healthy individuals who underwent physical examination were selected as the control group.Their clinical and pathological data were collected and compared.The relative expression levels of miR-193a and miR-208b in serum exosomes were detected using quantitative real-time polymerase chain reaction(qRT-PCR)method.Pearson method was used to analyze the correlation between miR-193a and miR-208b.The correlation between the expression of miR-193a and miR-208b in preoperative serum exosomes of GC patients and postoperative prognosis was analyzed using Kaplan-Meier method.Univariate and multivariate COX regression were applied to analyze the influencing factors of prognosis.Results The expression level of miR-208b in the serum exosomes of the GC group was higher than that of the control group(1.77±0.14 vs 1.02±0.01),while the expression level of miR-193a was lower than that of the control group(0.52±0.06 vs 1.01±0.01),and the differences were statistically significant(t=92.551,61.392,all P<0.05).The expression levels of miR-193a and miR-208b in GC patients before surgery were negatively correlated(r=-0.409,P<0.05).The low expression rate of miR-193a and high expression rate of miR-208b in patients with TNM stage Ⅰ+Ⅱ,no lymph node metastasis,and no distant metastasis were lower than those in patients with TNM stage Ⅲ+Ⅳ,lymph node metastasis,and distant metastasis,and the differences were statistically significant(χ2=5.008,4.397;7.142,4.688;4.407,5.189,all P<0.05).The 3-year cumulative survival rate of patients with low expression of miR-193a(30.43%)was lower than that of patients with high expression(60.32%)(χ2=17.861,P<0.001),while the 3-year cumulative survival rate of patients with high expression of miR-208b(27.14%)was lower than that of patients with low expression(64.52%)(χ2=16.340,P<0.001).The independent prognostic factors included serum levels of exosomes miR-193a(HR=0.493,95%CI:0.323～0.753)and miR-208b(HR=2.697,95%CI:1.382～5.262)(all P<0.05).Conclusion The preoperative serum miR-193a level in the exosomes was decreased and miR-208b level was increased,and their expression levels were related to the prognosis of patients undergoing GC radical gastrectomy.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

Objective:To design an improved lamina hook system and compare its biomechanical properties with traditional lamina hook system in fixation of lumbar spondylolysis.Methods:The thin layer CT data of the lumbosacral vertebrae of 20 healthy young male servicemen who underwent physical examination in the outpatient department of the 940th Hospital of Joint Logistics Support Force of PLA from January 2021 to August 2022 were collected. The age of the subjects was 20-30 years [(25.0±3.0)years]. A 3-dimensional model of the L 5 vertebral body was constructed using the 3-dimensional modeling software. The new improved lamina hook was designed according to the measurements including the thickness of the middle area, the longest longitudinal diameter, the curvature radius of the lower edge, the angle between the upper and lower tail ends, the thickness of the lower edge, and the longest diameter of the lower edge of the bilateral L 5 vertebral plates. One serviceman was selected from the aforementioned group to construct a linear finite element model of segments L 4-S using the 3-dimensional virtual software (normal model, model A), based on which, the L 5 bilateral spondylolysis model (model B), improved lamina hook model (model C) and traditional lamina hook models (model D) were designed. By constraining both sides of the sacrum and applying a longitudinal load of 400 N on the L 4 vertebral body, the upper 1/3 gravity of the body was simulated, and with a bending moment of 10 N·m along the X, Y, and Z directions, motions of forward flexion, backward extension, lateral bending, rotation, etc were simulated. The range of motion of segment L 4/5 and L 5/S 1 of model A was evaluated and compared with the findings of the previous researches to verify its effectiveness. The overall range of motion of models A, B, C, and D, the range of motion of segment L 4/5 and L 5/S 1, the maximum overall displacement, the maximum displacement and stress of the isthmus, the stress distribution and maximum stress of internal fixation of models C and D, and the stress distribution and maximum stress of the vertebral body of models C and D were compared. Results:(1) During forward flexion, backward extension, lateral bending and rotation, the range of motion of model A was 5.01°, 4.03°, 3.91° and 1.42° in segment L 4/5, and was 4.62°, 2.51°, 2.40° and 1.23° in segment L 5/S 1. (2) The overall range of motion, range of motion of segment L 4/5 and L 5/S 1 and maximum overall displacement of models A, C, and D were similar in axial compression, forward flexion, backward extension, left bending, and left rotation, while those of model B were significantly increased. (3) There was no significant difference in the maximum displacement of the isthmus of models A, C, and D under different motion modes, while the maximum displacement of model B in the isthmus was significantly larger than that of models A, C, and D, especially during rotation, increased by 295%, 277%, and 276% respectively. The maximum stress of the isthmus of model C was 0.938 MPa, 1.698 MPa, 0.410 MPa, 2.775 MPa, and 1.554 MPa respectively. The maximum stress in the isthmus of model D was 0.590 MPa, 1.297 MPa, 0.520 MPa, 3.088 MPa, and 2.072 MPa respectively. The maximum stress of the isthmus of models C and D was similar during axial compression and forward flexion, while the stress of the isthmus of model C was smaller than that of model D during backward extension, lateral bending, and rotation, decreased by 21.1%, 10.2%, and 25.0% respectively compared with model D. (4) The maximum stress of internal fixation in models C and D during forward flexion, backward extension, left bending, and left rotation was 135.220 MPa, 130.180 MPa, 200.940 MPa and 306.340 MPa respectively, and was 131.840 MPa, 112.280 MPa, 349.980 MPa and 370.140 MPa respectively. The maximum stress of internal fixation in the two models of internal fixation during forward flexion and backward extension was similar, while it was decreased by 42.6% and 17.2% in model C during left bending and left rotation, compared with model D. (5) The maximum stress of the vertebral body during forward flexion, backward extension, left bending, and left rotation was 79.787 MPa, 36.857 MPa, 37.943 MPa and 96.965 MPa respectively in model C, but was 80.104 MPa, 64.236 MPa, 196.010 MPa and 193.020 MPa respectively in model D. The maximum stress of models C and D was all distributed in the contact area with the internal fixation, and especially during backward extension, left bending, and left rotation, when it was reduced by 42.6%, 80.6%, and 49.8% of model C respectively, compared with that of model D. Conclusions:The improved laminar hook is more consistent with the Chinese anatomized structure of the lamina. Compared with the traditional lamina hook system, the improved lamina hook system can effectively reduce the displacement in all directions and range of motion of lumbar spondylolysis, therefor can significantly reduce the stress of internal fixation and vertebral body and has better biomechanical performance.

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (M^pro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 M^pro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 M^pro inhibitors.

As a common protease with high similarity among coronavirus species, the main protease (M^pro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

Humans ; Otitis Media, Suppurative ; Chronic Disease ; Biofilms ; Otitis Media

Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with 30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.

OBJECTIVE: To investigate the effect of kaempferol on proliferation of acute myeloid leukemia (AML) KG1a cells and its mechanism. METHODS: Human AML KG1a cells in logarithmic growth stage were taken and set at 25, 50, 75 and 100 μg/ml kaempferol group, another normal control group (complete medium without drug) and solvent control group (add dimethyl sulfoxide) were also set. After 24 and 48 hours of intervention, the cell proliferation rate was detected by CCK-8 assay. In addition, interleukin-6 (IL-6) combined with kaempferol group (Plus 20 μg/l IL-6 and 75 μg/ml kaempferol) was set up, 48 hours after culture, the cell cycle and apoptosis of KG1a cells were detected by flow cytometry, the mitochondrial membrane potential (MMP) of KG1a cells was detected by MMP detection kit (JC-1 method), and the expression of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway related proteins in KG1a cells were detected by Western blot. RESULTS: The cell proliferation rate of 25, 50, 75 and 100 μg/ml kaempferol group decreased significantly (P<0.05), and with the increase of kaempferol dose (r_{24 h}=-0.990, r_{48 h}= -0.999), the cell proliferation rate decreased gradually (P<0.05). The inhibitory effect of 75 μg/ml kaempferol on cell proliferation reached half of effective dose after 48 hours of intervention. Compared with normal control group, the G₀/G₁ phase cell proportion and apoptosis rate of cells in 25, 50 and 75 μg/ml kaempferol group increased, while the S phase cell proportion, MMP, phosphorylated JAK2 (p-JAK2)/JAK2 and phosphorylated STAT3 (p-STAT3)/STAT3 protein expression decreased in a dose-dependent manner (r=0.998, 0.994, -0.996, -0.981, -0.997, -0.930). Compared with 75 μg/ml kaempferol group, the G₀/G₁ phase cell proportion and apoptosis rate of cells in IL-6 combined with kaempferol group decreased, while the S phase cell proportion, MMP, p-JAK2/JAK2 and p-STAT3/STAT3 protein expression increased significantly (P<0.05). CONCLUSION Kaempferol can inhibit KG1a cell proliferation and induce KG1a cell apoptosis, its mechanism may be related to the inhibition of JAK2/STAT3 signal pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-6/metabolism* ; Kaempferols/pharmacology* ; Signal Transduction ; Apoptosis ; Janus Kinase 2 ; Cell Proliferation ; Leukemia, Myeloid, Acute

Objective: To investigate the differences in clinical characteristics, diagnosis, and treatment of pediatric septic shock in pediatric intensive care unit (PICU) among hospitals of different levels. Methods: This retrospective study enrolled 368 children with septic shock treated in the PICU of Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital from January 2018 to December 2021. Their clinical data were collected, including the general information, location of onset (community or hospital-acquired), severity, pathogen positivity, consistence of guideline (the rate of standard attainment at 6 h after resuscitation and the rate of anti-infective drug administration within 1 h after diagnosis), treatment, and in-hospital mortality. The 3 hospitals were national, provincial, and municipal, respectively. Furthermore, the patients were divided into the tumor group and the non-tumor group, and into the in-hospital referral group and the outpatient or emergency admission group. Chi-square test and Mann-Whitney U test were used to analyze the data. Results: The 368 patients aged 32 (11, 98) months, of whom 223 were males and 145 females. There were 215, 107, and 46 patients with septic shock, with males of 141, 51, and 31 cases, from the national, provincial, and municipal hospitals, respectively. The difference in pediatric risk of mortality Ⅲ (PRISM Ⅲ) scores among the national,provincial and municipal group was statistically significant (26(19, 32) vs.19(12, 26) vs. 12(6, 19), Z=60.25,P<0.001). The difference in community acquired septic shock among the national,provincial and municipal group was statistically significant (31.6%(68/215) vs. 84.1%(90/107) vs. 91.3%(42/46), χ²=108.26,P<0.001). There were no significant differences in compliance with guidelines among the 3 groups (P>0.05). The main bacteria detected in the national group were Klebsiella pneumoniae (15.4% (12/78)) and Staphylococcus aureus (15.4% (12/78)); in the provincial group were Staphylococcus aureus (19.0% (12/63)) and Pseudomonas aeruginosa (12.7% (8/63)), and in the municipal group were Streptococcus pneumoniae (40.0% (10/25)) and Enteric bacilli (16.0% (4/25)). The difference in the proportion of virus and the proportion of 3 or more initial antimicrobials used among the national,provincial and municipal group was statistically significant (27.7% (43/155) vs. 14.9% (13/87) vs. 9.1% (3/33), 22.8%(49/215) vs. 11.2%(12/107) vs. 6.5%(3/46), χ²=8.82, 10.99, both P<0.05). There was no difference in the in-hospital mortality among the 3 groups (P>0.05). Regarding the subgroups of tumor and non-tumor, the national group had higher PRISM Ⅲ (31(24, 38) vs. 22 (21, 28) vs.16 (9, 22), 24 (18, 30) vs. 17(8, 24) vs. 10 (5, 16), Z=30.34, 10.45, both P<0.001), and it was the same for the subgroups of in-hospital referral and out-patient or emergency admission (29 (21, 39) vs. 23 (17, 30) vs. 15 (10, 29), 23 (17, 29) vs. 18 (10, 24) vs. 11 (5, 16), Z=20.33, 14.25, both P<0.001) as compared to the provincial and municipal group. There was no significant difference in the in-hospital mortality among the 2 pairs of subgroups (all P>0.05). Conclusion: There are differences in the severity, location of onset, pathogen composition, and initial antibiotics of pediatric septic shock in children's hospitals of different levels, but no differences in compliance with guidelines and in-hospital survival rate.
Female ; Male ; Humans ; Child ; Retrospective Studies ; Shock, Septic/therapy* ; Hospitalization ; Intensive Care Units, Pediatric ; Hospitals, Pediatric

Mice ; Animals ; Tandem Mass Spectrometry ; Alpha-Amanitin ; Chromatography, Liquid ; Metabolomics ; Chromatography, High Pressure Liquid/methods*