Objective:To standardize the management of Investigator-Initiated Trials(IITs) and improve the quality of research projects, this study takes a tertiary hospital in Beijing as an example to analyze the key risk points in the implementation process of IITs and proposes countermeasures based on the issues identified during the management process.Methods:The study analyzed the IITs conducted at in the hospital from 2022 to 2023, focusing on 4 aspects: project classification evaluation and management (risk management), project implementation quality (process management), collaboration and support conditions(contract review and execution), and participant protection (medical ethics). It examined the key points and difficulties in project process management to standardize the quality management of IITs.Results:The implementation process management of IITs in medical institutions was an essential component for standardized clinical research management and an effective means to ensure the scientific nature of clinical research and the quality of data.Conclusions:Medical institutions should establish an effective and feasible IIT quality management system to comprehensively enhance the quality of IIT project, aiming to produce high-quality clinical research outcomes.

Objective:To standardize the management of Investigator-Initiated Trials(IITs) and improve the quality of research projects, this study takes a tertiary hospital in Beijing as an example to analyze the key risk points in the implementation process of IITs and proposes countermeasures based on the issues identified during the management process.Methods:The study analyzed the IITs conducted at in the hospital from 2022 to 2023, focusing on 4 aspects: project classification evaluation and management (risk management), project implementation quality (process management), collaboration and support conditions(contract review and execution), and participant protection (medical ethics). It examined the key points and difficulties in project process management to standardize the quality management of IITs.Results:The implementation process management of IITs in medical institutions was an essential component for standardized clinical research management and an effective means to ensure the scientific nature of clinical research and the quality of data.Conclusions:Medical institutions should establish an effective and feasible IIT quality management system to comprehensively enhance the quality of IIT project, aiming to produce high-quality clinical research outcomes.

Objective To investigate the effect of LAG-3 deficiency (LAG3^-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3^-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3^-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3^-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3^-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3^-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3^-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3^-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

Objective To investigate the effect of transcription factor specific protein5(Sp5)silencing on Wnt signaling pathway correlated factors and cell proliferation ability in mouse embryo palatal mesenchymal cells(mEPMCs).Methods mEPMCs of 14.5 d pregnant C57BL/6J mice were isolated and cultured in vitro.Cell source was identified by immunofluorescence staining.Lentivirus transfection technique was used to silence the expression of Sp5 gene in mEPMCs,and the transfection efficiency was verified by Western blot assay.Follow-up experiments were set up with the blank control group,the no-load virus group and the slience group(the Sp5-shRNA group).The protein and mRNA expression levels of β-catenin,GSK-3β,Wnt3a and CyclinD1 were detected by Western blot assay and RT-qPCR after transfection for 72 h in each group.Cell proliferation capacity was detected by CCK-8.The proliferation rate of 5-Ethynyl-2'-deoxyuridine(EdU)positive cells was detected by immunofluorescence assay.Cell cycle was detected by flow cytometry.Results mEPMCs were successfully isolated,and Sp5 expression was silenced.Western blot and RT-qPCR results showed that the protein and mRNA expressions of β-catenin,GSK-3β,Wnt3a and CyclinD1 were significantly higher in the Sp5-shRNA group than those in the blank control group and the no-loaded virus group(P<0.05).The proliferative ability and the proliferative rate of EdU positive cells were higher in the Sp5-shRNA group than those in the blank control group and the no-loaded virus group(P<0.05).The proportion of mEPMCs in S phase was higher in the Sp5-shRNA group than that in the blank control group and the no-loaded virus group(P<0.05).Conclusion Sp5 in silenced mEPMCs can participate in palate development and promote the proliferation of mEPMCs by regulating Wnt signaling pathway.

Objective:To examine the effects of heart rate control during hospitalization on short-term prognosis of heart failure in elderly patients.Methods:As a prospective study, 150 elderly patients with heart failure were selected from the Department of Geriatrics, Qilu Hospital of Shandong University.The subjects were divided into an experimental group and a control group by digitally generated random numbers, with 75 individuals in each group.Both groups received conventional anti-heart failure therapy during hospitalization, but patients from the control group had doses of heart rate control drugs adjusted every 2-4 weeks, with no special requirement for the heart rate before hospital discharge.In contrast, patients from the experimental group were given heart rate control drugs with timely dose adjustment to achieve more proactive heart rate control, aiming for a rate <70 beat/min, as long as heart failure symptom improvement and good volume management could be maintained.Values of cardiac function indexes were compared between the two groups at discharge and 6 months after discharge.Heart failure readmission rates within 6 months, cardiovascular disease mortality rates and the incidences of composite endpoint events after readmission due to heart failure aggravation were compared between the two groups.Treatment safety was also evaluated.Results:There was no statistical difference in blood pressure, heart rate, N-terminal pro-B-type natriuretic peptide(NT-pro-BNP), left ventricular ejection fraction(LVEF), left ventricular end systolic diameter(LVESD), or left ventricular end diastolic diameter(LVEDD)between the two groups at admission( P>0.05), and there was no statistical difference in the average length of hospitalization between the two groups( P>0.05). The experimental group had a lower average heart rate and diastolic pressure than the control group at discharge and 6 months latter[at discharge: (61.6±4.2)beat/min(1 mmHg=0.133 kPa) vs.(78.0±7.1)beat/min, (62.1±10.4)mmHg vs.(66.1±10.2)mmHg; at 6 months: (64.7±12.1)beat/min vs.(71.8±11.2)beat/min, (62.8±11.2)mmHg vs.(68.6±10.2)mmHg; P<0.05 or P<0.01]. NT-pro-BNP in the experimental group was significantly lower than that in the control group at discharge[(1 706±1 408)ng/L vs.(2 806±3 812)ng/L, P<0.05]. The absolute values of changes in LVEF(ΔLVEF), LVESD(ΔLVESD)and LVEDD(ΔLVEDD)after 6 months in the experimental group were significantly higher than those in the control group[ΔLVEF: (0.08±0.09) vs.(0.02±0.09), P<0.05; ΔLVESD: (-5.82±7.44)mm vs.(-1.63±6.07)mm, P<0.01; ΔLVEDD: (-2.76±5.52)mm vs.(-0.86±4.44)mm, P<0.05]. The rate of readmission and the incidence of composite endpoint events within 6 months in the experimental group were significantly lower than those in the control group[21.3%(16 cases) vs.36.0%(27 cases), P<0.05]; 25.3%(19 cases) vs.44.0%(33 cases), P<0.05.There was no significant difference in all-cause mortality between the two groups( P>0.05). Conclusions:For elderly patients with heart failure, proactive active heart rate control during hospitalization and a rate <70 beat/min before discharge will improve cardiac function indexes and lower the rate of readmission with exacerbation of heart failure, cardiovascular disease mortality and the incidence of composite end-point events after readmission.This strategy has good safety and is beneficial for short-term prognosis.

Objective:To explore the effects and mechanisms of bortezomib on the proliferation and apoptosis of acute T lymphocyte leukemia cell line Jurkat.Methods:MTT assay was used to test the influence of bortezomib on the proliferation of Jurkat cells.Flow cytometry was used to detect the influence of bortezomib on apoptosis of Jurkat cells.Real-time quantitative polymerase reaction(RT-PCR) was used to detect the effects of bortezomib on the expression of Bax, Bcl-2 and Cox-2 genes in Jurkat cells.Results:The inhibition rates of 5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL bortezomib on Jurkat cells at 24h were (13.23±0.71)%, (39.53±0.95)%, (53.07±1.12)%, (60.43±0.75)%, respectively, and the inhibition rates at 48h were (25.20±0.96)%, (52.80±1.30)%, (60.67±0.64)%, (75.10±1.35)%, respectively.The inhibitory rates of proliferation of Jurkat cells at 72h were (38.37±0.93)%, (60.94±0.85)%, (73.83±5.08)%, (88.37±1.55)%, respectively.The inhibitory rates of proliferation of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, and the differences were statistically significant( F=1 602.202, 1 085.089, 181.034, all P<0.05). Bortezomib (5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL) treatment for 24h, 48h and 72h, the apoptosis rate of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, the differences were statistically significant( F=1 288.571, 223.378, 251.175, all P<0.05). The expression of Bax mRNA in Jurkat cells increased with the increase of drug concentration and time( F=258.446, 518.929, 276.764, all P<0.05). The Bcl-2 mRNA and Cox-2 mRNA expression levels decreased with the increase of drug concentration and the prolongation of action time( FBcl-2 mRNA=236.848, 264.849, 343.968, FCox-2 mRNA=679.404, 1288.681, 1541.850, all P<0.05). Conclusion:Bortezomib can inhibit the proliferation and induce apoptosis of Jurkat cells.Bortezomib can increase the expression of Bax mRNA and decrease the expression of Bcl-2 and Cox-2 mRNA, which may be the molecular mechanism of bortezomib to promote apoptosis.

Objective:To summarize the experience of five hospitals in Guangdong Province on successfully transporting retained passengers by chartered flights during the outbreak of the COVID-19.Methods:We retrospectively evaluated the operation and management, cabin arrangement, isolation requirements, and personnel protection in the aspect of epidemic prevention and control.Results:In 11 charter missions, over one thousand "healthy" passengers with potential risk of infections were transported back to China. The medical delivery team and flight crew were kept free of infection, passengers maintained zero cluster infections and no unexpected adverse events during the air transport.Conclusions:Our results indicate how to carry passengers in a scientific and orderly way is crucial for avoiding the transmission risks of the epidemic of COVID-19 among working staffers and passengers during air transportation.

During the COVID-19 epidemic, our national guidelines have suggested that surgical patients should wear a mask to decrease the potential transmission of COVID-19 in the operating room, as long as the condition allows. However, so far, there is no study to discuss the influence of wearing a mask on the ventilation and blood oxygenation status in patients of spontaneous breathing with supplementary oxygen through an anesthetic facemask. This is a before-after study in the same patient, and 10 healthy volunteers were recruited, by testing the arterial blood gas parameters at key time points before and after oxygen inhalation to evaluate the effects of two different supplementary oxygen methods ('disposable medical mask + anesthetic facemask' and 'anesthetic facemask only') on the oxygenation of subjects. Our data demonstrated whether wearing a disposable medical mask or not could effectively increase the oxygen supply of the subjects compared with the basic value before oxygen inhalation; however, compared with the group without mask, the arterial oxygen partial (PaO
COVID-19 ; Healthy Volunteers ; Humans ; Masks ; Oximetry ; Oxygen/blood*

Objective: To explore the correlation between the parameters of the mandible and parameters of cervical vertebrae and craniofacial bone in class Ⅱ skeletal patients in Northeast China and to establish correlation equations expressing the relationship between the mandible and cervical vertebrae and craniofacial bone directly and quantitatively for the clinical diagnosis and treatment of orthodontics and orthognathics and for prediction. Methods : The mandible, cranial facial bone and cervical vertebrae of 201 children and adolescents aged 8 to 20 years were measured using digital cranial lateral tablets. All of the cases were divided into male (n=75) and female (n=126) groups using a sensitivity analysis method based on genetic algorithms to select the craniofacial bone and cervical bone with strong sensitivity to mandible parameters and to establish relevant equations. Results : Through sensitivity analysis, the parameters with the strongest correlation between the measured values of the mandible were H4 and SN, those with a strong correlation were SN-Ar, the anterior and posterior high ratio SGo/NGn, the Y axis angle and mandibular angle Ar-Go-Gn. The established equation was as follows: males: Ar-Pg=28.415+1.818×H4+0.746×SN(r2=0.056 8, P < 0.001); females: Ar-Pg=15.168+1.706×H4+0.675×SN+0.31×SN-Ar-0.29×Y axis angle (r2=0.611, P < 0.001). No significant difference was found between the predicted values obtained by the established equations and measured values (P > 0.05). Conclusion The mandibular length equation established by sensitivity analysis and genetic algorithms is statistically significant and can predict a certain degree of growth and development.

Objective To explore the effect of comprehensive nursing in improving the capacity load,nutritional status and quality of life of patients with peritoneal dialysis.Methods A total of 108 patients underwent peritoneal dialysis were selected as research subjects.All the patients were divided into control group and observation group according to the random number table method,with 54 cases in each group.The patients in the control group were given routine nursing intervention,and the patients in the observation group were treated with comprehensive nursing interventions on the basis of routine nursing.The nutritional status,capacity load and prognostic life quality of the two groups were observed and compared.The complications of dialysis-related infection after 6 months of discharge were observed.Results The blood pressure and body weight of the observation group were lower than that of the control group (P ＜ 0.05).There were no significant differences in the drug types and doses in the two groups (P ＞ 0.05).There was no significant difference in the nutritional status (serum albumin and hemoglobin) between the two groups before treatment (P ＞ 0.05).After comprehensive nursing intervention,the serum albumin and hemoglobin were improved in the two groups,and the improvement of nutritional status in the observation group was better than that in the control group (P ＜ 0.05).The physical function,physical pain,physiological function,vitality,social function,emotional function,mental health and overall health score of the observation group were higher than that of the control group,and the differences were statistically significant (P ＜0.05).The incidence of complication was lower in the observation group than that in the control group after6 months of discharge and (9.3％ vs.29.6％,P＜0.05).Conclusion Comprehensive care intervention for peritoneal dialysis patients can help reduce its capacity load,prevent complications,improve quality of life,and improve nutritional status,so it is worthy of active application and promotion.