Objective The purpose of this article is to summarize and review the current status of the construction of clinical research evaluation systems in domestic public hospitals,identify existing problems in the evaluation system,and propose development strategies and suggestions.Methods Retrieved relevant articles,dissertations and policies from the past five years(2018-2022),screened the titles,viewed the full texts of 52 selected papers and their references,and summarized them.Results The"five-only"indicators have long been an important indicator for evaluating clinical research in public hospitals,but in today's scientific research environment and policy environment,the"five-only"evaluation system has revealed its utilitarian draw-backs and gradually evolved into a hindrance to scientific research.It is urgent to break through the"five-only"orientation and establish a clinical research evaluation system oriented towards"transforming and applying transformation of scientific research achievements".Conclusion The evaluation system for clinical research should break the previous"five-only"evaluation model based on quantity-oriented scientific research evaluation.We can draw on the framework of the research output,influence,and environment indicators in the UK's REF Excellence Framework model,combine the American APT system and the Chinese STEM indicator dimensions,explore multi-outcome evaluation,integrate developmental indicators,and continuously improve the indica-tor system and application methods in practice to promote the development of clinical research in public hospitals.

Objective To evaluate the efficacy,safety and economics of romiplostim for treating primary immune thrombocytopenia(ITP)by rapid health technology assessment,and to provide an evidence-based basis for policy makers and clinical practice.Methods PubMed,Cochrane Library,Embase,CNKI,WanFang Data and VIP databases and the official websites of health technology assessment agency were electronically searched to collect high-quality clinical evidence and pharmacoeconomics evaluation literature of romiplostim for the treatment of ITP from inception to January 18,2024.Two researchers independently screened the literature,extracted information,and accessed the quality of included the literature,the extracted results were categorized and evaluated.Results A total of 14 literature were included,in which 8 systematic reviews/Meta-analysis and 6 pharmacoeconomic studies.In terms of efficacy,treatment with romiplostim significantly elevated platelet response rate,sustained platelet response rate,and mean platelet count in patients with ITP compared with placebo(P＜0.05).Romiplostim did not show a significant advantage in elevating patients'platelet response rate and sustained platelet response rate compared with other agents used to treat ITP(P＞0.05).In terms of safety,the incidence of serious adverse events was statistically lower with romiplostim compared to placebo(P＜0.05),while no significant differences were seen in the incidence of adverse events,bleeding events and thrombotic events(P＞0.05).There were no significant differences in the incidence of adverse events,serious adverse events,bleeding events,or thrombotic events when comparing romiplostim to other drugs for the treatment of ITP(P＞0.05).From an economic standpoint,most studies considered eltrombopag to be more economic advantages than romiplostim.Conclusion Romiplostim has good efficacy and safety in the treatment of ITP,and no advantage was shown in terms of economy.

Objective:To investigate the effects of different feeding formulas on the feeding and growth and metabolism of premature infants in the early postnatal period.Methods:Eligible premature infants with the gestational age of ≤ 34 weeks hospitalized from March 2023 to March 2024 were selected as per inclusion criteria, excluding those with congenital metabolic diseases, severe congenital heart disease and developmental malformations of digestive tract. According to the feeding formulas within 2 weeks after birth, premature infants were divided into three groups, namely donor human milk (DHM) group, preterm formula (PF) group and extensively hydrolyzed formula (eHF) group. The characteristics of premature infants, perinatal condition, feeding formulas, milk intake on the 7th and 14th day, the time to the daily milk intake of 120ml/kg and 150ml/kg respectively, the time on parenteral nutrition, the length of hospitalization, feeding intolerance, cholestasis, extrauterine growth retardation and biochemical metabolic indexes at 7 days, 14 days and discharge were collected. The differences of feeding and biochemical metabolic parameters were compared across the three groups.Results:A total of 108 cases were enrolled ,of whom 39 were in DHM group, 37 in PF group and 32 in eHF group. There was no significant difference in gestational age, birth weight, head circumference and maternal complications across the three groups. The milk intake in the DHM group was (50.7±29.1) ml/(kg·d) on the 7th day, compared with (34.2±27.3) ml/(kg·d) in PF group ( P=0.031), and (103.1±36.7) ml/(kg·d) on the 14th day, compared with (73.9±39.2) ml/(kg·d) in the PF group. Compared with the PF group, the DHM group reached the daily milk intake of 120 ml/(kg·d) earlier [(18.5±10.4) days vs. (24.1±10.3) days, P=0.020], had shorter duration of parenteral nutrition [(17.9±10.9) days vs. (23.2±11.2) days, P=0.042], and lower incidence of feeding intolerance (28.2% vs. 48.6%). The length of hospitalization in DHM group was shorter than that in PF group [(33.8±15.5) days vs. (37.8±17.6) days], but there was no significant difference ( P>0.05). There was no significant difference between the DHM group and the eHF group in terms of the milk intake on the 7th and 14th day, the time to the daily milk intake of 120 ml/(kg·d), the time on parenteral nutrition, the length of hospitalization and feeding intolerance. At 1 and 2 weeks after birth, alkaline phosphatase in DHM group was higher than that in PF group and eHF group ( P<0.05), but there was no significant difference in biochemical nutritional metabolism parameters (hemoglobin, urea nitrogen, albumin, prealbumin, alkaline phosphatase and total bile acid) across the three groups at discharge( P>0.05). Conclusion:Early use of DHM in premature infants is better tolerated than PF and can help achieve complete enteral nutrition earlier and shorten the use of parenteral nutrition, while not affecting the growth and development of premature infants.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Objective: To investigate the trends in incidence and mortality of stroke in Ningbo City, Zhejiang Province from 2012 to 2021, so as to provide the evidence for improving the stroke control strategy in Ningbo City. Methods: Data pertaining to the stroke incidence and mortality in Ningbo City from 2012 to 2021 were captured from Ningbo Municipal Chronic Disease Collaborative Management System, and the incidence and mortality of stroke was estimated and standardized by the Sixth National Population Census in 2010. The trends in incidence and mortality of stroke were evaluated using annual percent change (APC) in Ningbo City from 2012 to 2021. Results: A total of 185 747 residents with stroke were reported in Ningbo City from 2012 to 2021. The crude incidence of stroke was 312.78/105 in Ningbo City from 2012 to 2021, which appeared a tendency towards a rise (APC=2.429%, t=5.507, P<0.001), and the standardized incidence of stroke was 188.86/105, with no remarkable changes seen (APC=-0.399%, t=-1.544, P=0.161). There were 47 355 deaths due to stroke in Ningbo City from 2012 to 2021, and the crude and standardized mortality rates were 79.74/105 and 42.79/105, which both appeared a tendency towards a decline (APC=-4.778%, t=-6.867, P<0.001; APC=-8.269%, t=-13.729, P<0.001). Higher standardized incidence and mortality were seen among men (226.05/105 and 50.14/105) than among women (153.37/105 and 35.89/105), and the crude incidence and mortality of stroke appeared a tendency towards a rise with age (χ2trend=3 671.325, 1 419.107, both P<0.001). The standardized incidence and mortality of hemorrhagic stroke were 40.38/105 and 18.56/105, both showing a tendency towards a decline (APC=-5.042%, t=-12.958, P<0.001; APC=-11.570%, t=-14.979, P<0.001), and the standardized incidence of ischemic stroke was 143.91/105, appearing a tendency towards a rise (APC=1.254%, t=3.223, P=0.012), while the standardized mortality of ischemic stroke was 19.65/105, with no obvious changes seen (APC=-2.110%, t=-2.150, P=0.064). Conclusions The incidence of stroke appeared a tendency towards a rise and the mortality appeared a tendency towards a decline in Ningbo City from 2012 to 2021. Men and the elderly are at high risk of stroke.

Objective:To evaluate the clinical value of Xing's ureteroileal anastomosis technique in radical cystectomy.Methods:The data of 38 patients who underwent radical cystectomy with Xing's ureteroileal anastomosis technique at Cancer Hospital, Chinese Academy of Medical Sciences and Beijing Chaoyang Hospital from July 2013 to June 2021 were retrospectively reviewed. There were 30 males and 8 females. The mean age was 61.6±15.1 years old. The mean body mass index (BMI) was 25.1±2.7 kg/m 2. The American Society of Anesthesiology (ASA) graded 25 cases as grade 1, 10 cases as grade 2 and 3 cases as grade 3. There were 35 cases with stage cT 2N 0M 0 and 3 cases with cT 3N 0M 0. All patients underwent radical cystectomy and ileal conduit, and the ureteroileal anastomosis was performed using the Xing's ureteroileal anastomosis technique. Afferent loop entry was divided equally into two lumens. After 1.5 cm-long lengthwise incisions, each ureter was directly and end-to-end anastomosed to the aforementioned lumens. Postoperative information was recorded, including ureteric stricture, ureteric reflux, hydronephrosis, anastomotic leakage, renal calculus, urinary tract infection, and pyelonephritis. Results:Ureteroileal anastomosis was performed successfully in 38 cases with 76 units. The median follow-up time was 35.6 (17.0, 46.3) months. Three patients developed unilateral anastomotic stenosis after operation. Five patients had unilateral ureteral reflux. Two patients had unilateral hydronephrosis. No anastomotic leakage, urinary tract infection, or pyelonephritis occurred after the operation. Renal calculus appeared in 3 cases, all on the left unit.Conclusions:Xing's ureteroileal anastomosis technique is a simple method with few postoperative and good functional outcomes.

Serum autoantibody markers have the advantages of easy specimen acquisition, simple detection technology and dynamic real-time monitoring. With the wide application of immune checkpoint inhibitors in the treatment of malignant tumors, autoantibody markers in predicting tumor immune checkpoint inhibitors efficacy and forecasting irAEs (immune related adverse events) show good prediction of potential. This review mainly focused on the progress of autoantibody markers in the prediction of therapeutic effect and the monitoring of irAE in tumor immunotherapy.
.
Humans ; Immune Checkpoint Inhibitors ; Immunotherapy/adverse effects* ; Lung Neoplasms/etiology* ; Neoplasms/drug therapy* ; Prognosis

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective:To explore the difference in the complexity of different treatment planning systems, multi-leaf collimator (MLC) types and treatment sites of volume-modulated arc therapy (VMAT), and propose a complexity score for plan quality control.Methods:Statistical analysis of 12 complexity metrics including Monaco and Eclipse, Agility, Millennium and High-definition MLC, nasopharyngeal, lung and cervical cancer was performed. Spearman correlation coefficient between complexity metrics was calculated. Principal component analysis was conducted to reduce the dimensionality of the original data set to the first two principal components and explain its physical meaning. Complexity score based on the principal components was calculated to establish warning and action thresholds for plan quality control. The correlation between complexity metrics and γ pass rate was analyzed.Results:Except cervical cancer aperture sub-regions metric, other metrics had significant differences between Monaco and Eclipse. Monaco MLC had a more regular field but higher MU, smaller leaf gap, and longer leaf travel distance. High-definition MLC with smaller leaf width significantly added MLC aperture-related metrics. The first two principal components explained over 80% of the total variance of the original dataset, complexity score was weighted average of first two principal components. The distribution of complexity score for different equipment and sites was different. The warning threshold was expressed as the average plus standard deviation, and the action threshold was expressed as the average plus 2 standard deviations. Complexity metrics and complexity scores had small correlation with γ pass rate, showing weak or irrelevant but statistically significant. Conclusions:Different planning systems, MLC types, and treatment site complexity metrics are significantly different. The complexity score is a useful tool for plan quality control.

Background Aluminum can cause synaptic plasticity damage in the hippocampus, probably due to blocked interneuronal signal transmission. MicroRNA-29a (miR-29a) can target phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression and participate in the generation of neuronal networks, and may be involved in the effect of aluminum on the electrical activity of neuronal networks. Objective To study the role and mechanism of miR-29a-targeted PTEN in aluminum-induced neuronal network injury in primary hippocampal neurons of ICR mice treated with maltol aluminum [Al(mal)₃] in vitro. Methods Primary hippocampal neurons of ICR mice born within 24 h were cultured in vitro. The purity of neurons was determined by labeling neuron-specific microtubule-associated protein 2 (MAP2) by immunofluorescence staining on day six of the culture; neurons were treated with different concentrations of Al(mal)₃, and divided into a control group, and 10, 20, and 40 μmol·L⁻¹ Al(mal)₃ groups, and neuronal cell viability was detected by CCK-8 method. Al(mal)₃ at 20 μmol·L⁻¹ was selected for subsequent experiments to establish a neuronal network injury model for intervention. The lentivirus infection method was used to transfect miR-29a into neurons, which were divided into mNG, mNG+20 μmol·L⁻¹ Al(mal)₃, miR-29a, and miR-29a+20 μmol·L⁻¹ Al(mal)₃ groups, and micro-electrode array (MEA) was used to analyze the firing of neuronal network. The expressions of miR-29a and PTEN mRNA in each group were detected by real-time PCR (RT-PCR), and the expression of PTEN protein in each group was detected by Western blotting. Results The purity of primary mouse hippocampal neurons was greater than 90%, and the viability of the neurons was above 80% in all groups. At 48 h of the designed Al(mal)₃ treatments, the changes in spike frequency, burst frequency, network burst frequency, and synchrony index of neurons cultivated on MEA plates in the control group were 207.56%±38.70%, 73.19%±46.43%, 75.42%±33.04%, and 117.13%±15.54%, respectively; the Al(mal)₃ groups’ neuronal network electrical activity showed a decreasing trend. Compared with the control group, the spike frequency, burst frequency, network burst frequency, and synchrony index of the 20 and 40 μmol·L⁻¹ Al(mal)₃ groups significantly decreased (The changes were 171.70%±28.08%, 49.20%±23.23%, 50.20%±18.18%, and 85.45%±20.30%; 150.68%±26.15%, 43.43%±15.54%, 52.05%±26.31%, and 26.80%±8.29%, respectively, P < 0.05). Compared with the control group (1.00), the miR-29a relative expression levels were significantly decreased in the 20 μmol·L⁻¹ Al(mal)₃ group (0.74±0.09) and the 40 μmol·L⁻¹ Al(mal)₃ group (0.62±0.12) (P < 0.05); the relative expression levels of PTEN mRNA were significantly increased in the 20 μmol·L⁻¹ Al(mal)₃ group (1.32±0.12) and the 40 μmol·L⁻¹ Al(mal)₃ group (1.48±0.11) (P < 0.05); the PTEN protein relative expression levels (1.29±0.12 and 1.82±0.10, respectively) were also significantly increased (P < 0.05). By overexpressing miR-29a in mouse primary hippocampal neurons, the spike frequency, burst frequency, and network burst frequency were significantly higher in the miR-29a group compared with the mNG group (The changes were 252.80%±62.03%, 171.65%±56.30%, and 197.75%±27.12%, respectively, P<0.05). The mNG+20 μmol·L⁻¹ Al(mal)₃ group showed a significant decrease in all indicators of neuronal network electrical activity (The changes were 123.28%±47.31%, 66.62%±31.53%, 70.60%±12.48%, and 52.86%±20.26%, respectively, P < 0.05). Compared with the mNG+20 μmol·L⁻¹ Al(mal)₃ group, the electrical activity indicators of neuronal network were significantly higher in the miR-29a+20 μmol·L⁻¹ Al(mal)₃ group (The changes were 161.41%±42.13%, 101.16%±30.63%, 127.02%±29.58%, and 109.73%±15.61%, respectively, P < 0.05). Compared with the mNG group (1.00), the neuronal PTEN mRNA relative expression (0.67±0.11) and the PTEN protein expression (0.75±0.08) were decreased in the miR-29a group (P < 0.05); the PTEN mRNA relative expression (1.32±0.12) and the PTEN protein relative expression (1.46±0.15) in the mNG+20 μmol·L⁻¹ Al(mal)₃ group were increased (P < 0.05). Compared with the mNG+20 μmol·L⁻¹ Al(mal)₃ group, the PTEN mRNA relative expression (0.93±0.06) and the PTEN protein relative expression (0.92±0.09) were decreased in the miR-29a+20 μmol·L⁻¹ Al(mal)₃ group (P < 0.05). Conclusion Aluminum significantly inhibits the electrical activity of hippocampal neuronal networks, and miRNA-29a may be involved in the aluminum-induced impairment of hippocampal neuronal network electrical activity by regulating PTEN expression.