ObjectiveTo sort out the pre-ethical review status of drug clinical trials in a tertiary A hospital， summarize practical experience， and provide references for pre-ethical review. MethodA retrospective analysis was conducted on the ethical review of pre-ethical projects in a tertiary A hospital from 2018 to 2023. ResultsFrom 2018 to 2023， a total of 285 pre-ethical projects were reviewed in this tertiary hospital， including 79 projects where it served as the leading unit. Among these， 279 clinical trials ultimately received approval of the ethical review committee， while 6 projects were not approved due to sponsors’ refusal to modify study protocols. In terms of trial phases， phase III clinical trials constituted the largest proportion， and the oncology center was the department with the highest number of projects. In 2023， the average time for pre-ethical review projects from submission to approval was 43 calendar days， 3 days longer than for other project types. In 2023， this hospital reviewed 75 pre-ethical review projects， including 58 where it served as a participating unit. Among these， 42 projects received approval later than the leading unit， while 9 projects were approved earlier than the leading unit’s ethical approval date. Among the pre-ethical review projects applied in 2023， 70 projects obtained drug clinical trial notifications from the National Medical Products Administration， while 5 projects had unknown notification status due to the lack of ethical approval or discontinuation. Of the projects receiving approval notifications， 16 were annotated with matters requiring enhanced attention during clinical trials， and 7 necessitated protocol improvements. ConclusionThis tertiary A hospital has implemented multiple measures to optimize the management of pre-ethical review. This ethical review model does not compromise the quality of ethical review and contributes to accelerating the initiation of clinical trials. Notably， it is crucial to construct a patient-centered drug development system. Clinical trials guided by this concept align with ethical values， laying the foundation for the smooth conduct of clinical trials， assisting in the drug development process， and safeguarding patients’ medication needs.

Background::Acute pulmonary embolism (APE) is a fatal cardiovascular disease, yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs. A simple, objective technique will help clinicians make a quick and precise diagnosis. In population studies, machine learning (ML) plays a critical role in characterizing cardiovascular risks, predicting outcomes, and identifying biomarkers. This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods::This is a single-center retrospective study. Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets. A total of 8 ML models, including random forest (RF), Na?ve Bayes, decision tree, K-nearest neighbors, logistic regression, multi-layer perceptron, support vector machine, and gradient boosting decision tree were developed based on the training set to diagnose APE. Thereafter, the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies, including the Wells score, revised Geneva score, and Years algorithm. Eventually, the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic (ROC) analysis.Results::The ML models were constructed using eight clinical features, including D-dimer, cardiac troponin T (cTNT), arterial oxygen saturation, heart rate, chest pain, lower limb pain, hemoptysis, and chronic heart failure. Among eight ML models, the RF model achieved the best performance with the highest area under the curve (AUC) (AUC = 0.774). Compared to the current clinical assessment strategies, the RF model outperformed the Wells score ( P = 0.030) and was not inferior to any other clinical probability assessment strategy. The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726. Conclusions::Based on RF algorithm, a novel prediction model was finally constructed for APE diagnosis. When compared to the current clinical assessment strategies, the RF model achieved better diagnostic efficacy and accuracy. Therefore, the ML algorithm can be a useful tool in assisting with the diagnosis of APE.

OBJECTIVE: To explore the changes of serum procalcitonin (PCT) level in patients with moderate and severe acute respiratory distress syndrome (ARDS) after cardiac surgery under cardiopulmonary bypass (CPB), and try to find out the best cut-off of PCT to predict the progression to moderate and severe ARDS. METHODS: Medical records of patients undergoing cardiac surgery with CPB in Fujian Provincial Hospital from January 2017 to December 2019 were retrospectively analyzed. Adult patients who were admitted in intensive care unit (ICU) for more than 1 day and had PCT values on the first postoperative day were enrolled. Clinical data such as patient demographics, past history, diagnosis, and New York Heart Association (HYHA) classification, and the operation mode, procedure duration, CPB duration, aortic clamp duration, intraoperative fluid balance, calculation of 24 hours postoperative fluid balance and vasoactive-inotropic score (VIS); 24 hours postoperative C-reactive protein (CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP) and PCT levels were collected. Two clinicians independently made the diagnosis of ARDS according to the Berlin definition, and the diagnosis was established only in patients with a consistent diagnosis. The differences in each parameter were compared between patients with moderate to severe ARDS and those without or with mild ARDS. Analysis of the ability of PCT to predict moderate to severe ARDS was evaluated by receiver operator characteristic curve (ROC curve). Multivariate Logistic regression was conducted to determine the risk factors of the development of moderate to severe ARDS. RESULTS: 108 patients were finally enrolled, including 37 patients with mild ARDS (34.3%), 35 patients with moderate ARDS (32.4%), 2 patients with severe ARDS (1.9%), and 34 patients without ARDS. Compared with patients with no or mild ARDS, patients with moderate to severe ARDS were older (years old: 58.5±11.1 vs. 52.8±14.8, P < 0.05), with a higher proportion of combined hypertension [45.9% (17/37) vs. 25.4% (18/71), P < 0.05], longer operative time (minutes: 363.2±120.6 vs. 313.5±97.6, P < 0.05), and higher mortality (8.1% vs. 0, P < 0.05), but there were no differences in the VIS score, incidence of acute renal failure (ARF), CPB duration, aortic clamp duration, and intraoperative bleeding, transfusion volume, and fluid balance between the two groups. Serum PCT and NT-proBNP levels in patients with moderate to severe ARDS at postoperative day 1 were significantly higher than those in patients with no or mild ARDS [PCT (μg/L): 16.33 (6.96, 32.56) vs. 2.21 (0.80, 5.76), NT-proBNP (ng/L): 2 405.0 (1 543.0, 6 456.5) vs. 1 680.0 (1 388.0, 4 667.0), both P < 0.05]. ROC curve analysis showed that the area under the curve (AUC) for PCT to predict the occurrence of moderate to severe ARDS was 0.827 [95% confidence interval (95%CI) was 0.739-0.915, P < 0.05]. When PCT cut-off value was 7.165 μg/L, the sensitivity was 75.7% and the specificity was 84.5%, for differentiating patients who developed moderate to severe ARDS from who did not. Multivariate Logistic regression showed that age and the elevated PCT concentration were independent risk factors for the development of moderate to severe ARDS [age: odds ratio (OR) = 1.105, 95%CI was 1.037-1.177, P = 0.002; PCT: OR = 48.286, 95%CI was 10.282-226.753, P < 0.001]. CONCLUSIONS Patients with moderate to severe ARDS undergoing CPB cardiac surgery have a higher serum concentration of PCT than patients with no or mild ARDS. Serum PCT level may be a promising biomarker to predict the development of moderate to severe ARDS, the cut-off value is 7.165 μg/L.
Adult ; Humans ; Cardiopulmonary Bypass ; Procalcitonin ; Retrospective Studies ; Heart ; Respiratory Distress Syndrome

Due to the physiological peculiarities of pregnant women, general clinical studies exclude pregnant women. Therefore, there is a lack of evidence of precise medication for pregnant women with diseases worldwide, which poses a significant risk for them to use medication during pregnancy. Whether to include pregnant women as subjects in clinical research has always been a focus of ethical discussion. By providing a broad overview of pregnant women’s participation in clinical research from an ethical perspective, this paper explored the risks and challenges faced by pregnant women’s participation in clinical research, and provided theoretical basis and thinking paths for how to fairly and effectively include pregnant women as subjects and promoting clinical research on pregnant women.

End-stage renal disease (ESRD) patients undergoing outpatient hemodialysis (HD) and home peritoneal dialysis (PD) are high risk population of severe and critical types caused by SARS-CoV-2 infection. In order to improve the quality of diagnosis and treatment in dialysis patients with SARS-CoV-2 infection, we wrote this recommendation for primary care clinicians. During the epidemic period of SARS-CoV-2 infection, all patients should be instructed to strengthen self-management. Once the SARS-CoV-2 infection was found in dialysis patients, early stratified management should be carried out within 72 hours after the first positive nucleic acid or antigen test results, which includes early antiviral therapy, early recognition, and transferring severe patients from community or primary hospital to a referral hospital promptly. Guidance for dietary and sports rehabilitation after SARS-CoV-2 infection should also be started as soon as possible.

Objective:To observe the differences of macular microvascular structure between recurrent and non-recurrent macular edema (ME) secondary to central retinal vein occlusion (CRVO) after intravitreal injection of ranibizumab (IVR), and to preliminarily analyze the correlation between recurrence and ME.Methods:A prospective clinical observational study. Forty-five patients (45 eyes) diagnosed as CRVO with ME were included in this study in Tianjin Medical University Eye Hospital from January 2020 to December 2021. There were 22 males (22 eyes) and 23 females (23 eyes). All cases were unilateral. The average age was 61.11±10.88 years old. All patients received IVR treatment once a month for 3 consecutive months. ME were regressive after the initial three treatments. The patients were divided into recurrent group (21 cases, 21 eyes) and non-recurrent group (24 cases, 24 eyes) based on ME recurrence at 6 months after ME resolution. All patients underwent best corrected visual acuity (BCVA), intraocular pressure, and optical coherence tomography angiography (OCTA). OCTA was used to scan the macula in the area of 3 mm×3 mm, and the vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP), fovea and parafovea before and after treatment was measured. Foveal retinal thickness, foveal avascular zone (FAZ) area, perimeter of FAZ (PERIM), avascular index of FAZ (AI), VD within 300 μm width of FAZ range (FD-300). Foveal VD included superficial and deep retinal VD (SFVD, DFVD); parafoveal VD included superficial and deep retinal VD (SPFVD, DPFVD). Taking the initial three treatments as the observation time point, the changes of the parameters of the two groups were compared. Comparison between the recurrent and non-recurrent group was performed by two independent sample t-tests. Receiver operating characteristic (ROC) curve analysis was used to measure the area under the curve (AUC) of VD for predicting the recurrence of ME. Results:There were no significant differences in age ( t=1.350), IOP ( t=1.929), SFVD ( t=-1.716), DFVD ( t=-1.143), CRT ( t=-1.207) and AI ( t=1.387) between the recurrent and non-recurrent group ( P>0.05). There were significant differences in times of anti-VEGF therapy ( t=5.912), BCVA ( t=5.003), SVD ( t=-4.617), SPFVD ( t=-4.110), DVD ( t=-5.503), DPFVD ( t=-4.772), FAZ area ( t=2.172), PERIM ( t=2.606) and FD-300 ( t=-3.501) between the recurrent and non-recurrent group ( P<0.05). ROC curve analysis showed that the AUC of DVD in predicting the recurrence of ME was highest, with 0.921, and the threshold was 37.65%. The sensitivity and specificity were 91.7% and 85.7%, respectively. Conclusions:The SVD, SPFVD, DVD, DPFVD and FD-300 in the recurrence group are significantly lower than those in the non-recurrence group, while the FAZ area and PERIM are significantly higher than those in the non-recurrence group. DVD≤37.65% can be used as the best threshold for predicting the recurrence of ME.

Objective Based on the existing clinical drainage device, two novel mechanisms were designed for the connection between the drainage tube of the patient and the drainage tube of the drainage bag, so as to compare such two mechanisms and validate whether the mechanisms can meet the design requirements for clinical use. Methods Mechanism 1 used the method of electromagnetic drive to pull in and Mechanism 2 used the magnetization method of permanent magnet to pull in. The finite element model of static electromagnetic field was established. The force of the two mechanisms under different currents was compared, and the distribution of magnetic field lines and magnetic induction intensity was analyzed. Simulation experiments were designed for preliminary experimental research. Results Under the pull-in state, the maximum magnetic induction of Mechanism 1 and Mechanism 2 at the closed end surface was found in contact area of the two iron cores. The suction force of Mechanism 1 could be adjusted by the current. When the current was 1 A, the maximum magnetic induction intensity at the closed end was 0.76 T, the electromagnetic force measured by the experiment was 6.08 N, the magnetic force of Mechanism 2 was 6.68 N, which was smaller than the 8 N suture tension. Mechanism 2 was separated by supplying the driving coil with a reverse magnetic field. Conclusions When the current was 1 A, Mechanism 1 could meet the magnetic attraction requirements, and Mechanism 2 could be separated when the current reached 1.8 A. Both mechanisms met the requirements of clinical design, but Mechanism 2 was more secure in the process of application. The feasibility of the mechanism structure was verified by finite element analysis and experimental test.

Objective:To observe the relationship between the response to anti-vascular endothelial growth factor (VEGF) drug treatment and single nucleotide polymorphism (SNP) genotype in patients with wet age-related macular degeneration (wAMD).Methods:A retrospective clinical study. From August 2019 to September 2020, 103 eyes of 103 wAMD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 59 males (57.28%, 59/103) and 44 females (42.72%, 44/103); the average age was 68.74±7.74 years. The standard logarithmic visual acuity chart was used to detect the Best Corrected Visual Acuity of the affected eye and converted to the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. Optical coherence tomography was used to detect the central retinal thickness (CRT) of the affected eye. At the same time, the patient's high-density lipoprotein cholesterol (HDL-C) was tested. All eyes were treated with intravitreal injection of anti-VEGF drugs once a month for 3 months. Before the initial treatment, peripheral venous blood from the patient were collected. Interleukin-8 ( IL-8), complement C3 gene ( C3), complement factor H ( CFH), liver lipase ( LIPC), cholesterol ester transfer protein ( CETP), ATP binding cassette subfamily a member 1 ( ABCA1), lipoprotein lipase ( LPL), fatty acid desaturation gene cluster ( FADS1) SNP. According to gene frequency, genotypes are divided into wild type and mutant type were detected. Qualitative data such as the frequency difference of the genotype distribution in the clinical phenotype and the Hardy-Weinberg equilibrium of the genotype distribution were compared with the Chi-square test or Fisher's exact test. Results:There were fewer CRT responders in IL-8 rs4073 mutant (TA+AA) patients than wild-type (TT) [odds ratio ( OR)=0.310, 95% confidence interval ( CI) 0.106-0.910, P<0.05). Among them, after the drug stratification test, the proportion of patients with IL-8 rs4073 locus TT genotype in the conbercept treatment group was less CRT non-responders ( OR=0.179, 95% CI=0.034-0.960, P=0.033). Patients with LIPC rs2043085 mutant (CT+TT) with BCVA increased ≥0.2 logMAR are more likely than wild-type (CC) ( OR=3.031, 95% CI 1.036-8.867, P<0.05); HDL-C level was significantly lower Compared with wild type (CC), the difference was statistically significant ( t=2.448, P=0.016). There was no significant difference in logMAR BCVA and CRT between IL-8 rs4073, LIPC rs2043085 mutant and wild-type patients before treatment ( IL-8 rs4073: Z=-0.198, -1.651; P=0.843, 0.099; LIPC rs2043085: Z=-0.532, -0.152; P=0.595, 0.879). C3 rs 225066, CFH rs800292, CETP rs708272, ABCA1 rs1883025, FADS1 rs174547, LPL rs12678919 have no correlation with anti-VEGF drug treatment response. Conclusions:Patients with wAMD are treated with anti-VEGF drugs. Those with IL-8 rs4073 locus A genotype may be less responsive to CRT. LIPC rs2043085 locus T genotypes may be relatively more responsive to BCVA.

Objective:To investigate the association between early central venous pressure (CVP) measurement and mortality in patients with sepsis.Methods:The adult patients with sepsis were identified from the health data of Medical Information Mart for Intensive Care-Ⅲ v1.4 (MIMIC-Ⅲ v1.4). Data of all adult patients with sepsis were collected, including gender, age, comorbidities, length of survival, total length of hospital stay and intensive care unit (ICU) stay, sequential organ failure assessment (SOFA) score, vital signs, laboratory test results on the first day, vasoactive agents usage, fluid input, urine output and fluid balance on the first day, need for renal replacement therapy and mechanical ventilation, diagnosis of sepsis, and the time and value of the first CVP measurement in the ICU. Patients were divided into early measurement and control groups based on whether or not they had a CVP measurement within the first 6 hours of ICU stay. According to the time of the first CVP measurement, the patients were subdivided into four subgroups: ≤ 3 hours, 4-6 hours, 7-12 hours and no measurement within 12 hours. The primary endpoint was 28-day mortality. The relationship between initial CVP and mortality was analyzed by Lowess smoothing method. Kaplan-Meier survival analysis and Log-Rank test were performed for univariate analysis. Cox regression analysis was performed for multivariate analysis to estimate the relationship between timeliness of CVP measurement and mortality.Results:A total of 4 733 sepsis patients were enrolled, 1 673 of whom had CVP measured within 6 hours of admission to the ICU, and the other 3 060 patients served as the control group. There were no differences in demographic characteristics and underlying diseases between the two groups, except that the early CVP measurement group had less underlying renal failure compared with control group. The early CVP measurement group had higher lactic acid (Lac) levels and SOFA scores, indicating worse severity of disease as compared with control group. The 28-day mortality in the early CVP measurement group was significantly lower than that in the control group (34.2% vs. 40.7%, P < 0.01). The early CVP measurement group had shorter length of total hospitalization and longer length of ICU stay, higher rate of mechanical ventilation and vasoactive agents dependent, and more fluid input and fluid balanced in the first day of ICU stay compared with control group. Lowess smoothing analysis showed that a "U"-shaped relationship between initial CVP and mortality was identified, suggesting that too high or too low initial CVP was associated with worse survival. Kaplan-Meier survival analysis showed that compared with the patients without early CVP measurement within 12 hours, the cumulative survival rate of patients with CVP measured within 3 hours was significantly higher (66.7% vs. 59.1%; Log-Rank test: χ2 = 15.810, adjusted P < 0.001); while no significant difference was found in patients with CVP measured between 4 hours and 6 hours and between 7 hours and 12 hours compared with the patients without early CVP measurement within 12 hours (64.4%, 60.3% vs. 59.1%; Log-Rank test: χ2 values were 5.630 and 0.100, and adjusted P values were 0.053 and > 0.999, respectively). Cox multivariate analysis showed that the Cox proportional risk model was established by taking patients without CVP measurement within 12 hours as reference, timely CVP measurement after ICU admission was associated with reduced 28-day mortality of patients with sepsis [≤3 hours: hazard ratio ( HR) = 0.65, 95% confidence interval (95% CI) was 0.55-0.77, P < 0.001; 4-6 hours: HR = 0.72, 95% CI was 0.60-0.87, P = 0.001; 7-12 hours: HR = 0.80, 95% CI was 0.66-0.98, P = 0.032] after the confounding variables (gender, age, SOFA score, initial Lac, renal failure, maximal blood glucose and white blood cell count, and minimal platelet count within 24 hours) were adjusted. Conclusions:Early CVP measurement is associated with decreased 28-day mortality in patients with sepsis. CVP should be considered as a valuable and easily accessible safety parameter during early fluid resuscitation.

Objective:To explore the significance of multimodal monitoring in the monitoring and treatment of neurocritical care patients.Methods:104 neurocritical care patients admitted to the department of Critical Care Medicine of Fujian Provincial Hospital from March 2019 to January 2020 were enrolled. Patients were randomly assigned into two groups, with 52 in each group. In the routine monitoring treatment group, heart rate, blood pressure, respiratory rate and the changes in consciousness and pupils were monitored after operation. The patients were treated with routine medicine to reduce intracranial pressure (ICP), maintain proper cerebral perfusion pressure (CPP), balance fluid intake and output, and maintain the airway clear. Patients in the multimodal monitoring treatment group were treated with invasive ICP monitoring, ultrasound to assess brain structure, ultrasound to measure optic nerve sheath diameter (ONSD), transcranial color doppler (TCCD), internal jugular venous blood oxygen saturation monitoring, near-infrared spectroscopy (NIRS), non-invasive cerebral blood oxygen saturation monitoring and quantitative electroencephalogram monitoring. According to the monitoring results, the patients were given targeted treatment with the goal of controlling ICP and improving brain metabolism. The length of intensive care unit (ICU) stay, the incidences of neurological complications (secondary cerebral infarction, cerebral hemorrhage, high intracranial pressure, etc.), and the incidences of poor prognosis [6 months after the onset of Glasgow outcome score (GOS) 1 to 3] were compared between the two groups. Spearman rank correlation analysis of the correlation between invasive ICP and the ICP value which was calculated by TCCD. The receiver operating characteristic (ROC) curve of invasive ICP and pulsatility index of middle cerebral artery (PI MCA) were used to predict poor prognosis. Results:The length of ICU stay in the multimodal monitoring treatment group was significantly shorter than that of the routine monitoring treatment group (days: 6.27±3.81 vs. 9.61±5.09, P < 0.01), and the incidence of neurological complications was significantly lower than that in the routine monitoring treatment group (9.62% vs. 25.00%, P < 0.05). In the multimodal monitoring treatment group, 37 cases had a good prognosis and 15 cases had a poor prognosis, while the routine monitoring treatment group had a good prognosis in 27 cases and a poor prognosis in 25 cases. The incidence of poor prognosis in the multimodal monitoring treatment group was lower than that of the routine monitoring treatment group (28.85% vs. 48.08%, P < 0.05). In the multimodal monitoring treatment group, the invasive ICP and PI MCA of patients with good prognosis were significantly lower than those of patients with poor prognosis [invasive ICP (mmHg, 1 mmHg = 0.133 kPa): 16 (12, 17) vs. 22 (20, 24), PI MCA: 0.90±0.33 vs. 1.39±0.58, both P < 0.01]. There was no significant difference in resistance index of the middle cerebral artery (RI MCA) between the good prognosis group and the poor prognosis group (0.63±0.12 vs. 0.66±0.15, P > 0.05). There was a positive correlation between the invasive ICP and the ICP value which was calculated by TCCD ( r = 0.767, P < 0.001). ROC curve analysis showed that the area under ROC curve (AUC) of invasive ICP for poor prognosis prediction was 0.906, the best cut-off value was ≥ 18 mmHg, the sensitivity was 86.49%, and the specificity was 86.67%. The AUC of PI MCA for poor prognosis prediction was 0.759, the best cut-off value was ≥ 1.12, the sensitivity was 81.08%, and the specificity was 60.00%. The AUC of invasive ICP was greater than PI MCA ( Z = 2.279, P = 0.023). Conclusion:Comprehensive analysis of multimodal monitoring indicators for neurocritical care patients to guide clinical treatment can reduce the length of hospital stay, and reduce the risk of neurosurgery complications and disability; invasive ICP can predict poor prognosis of neurocritical care patients.