Conducting ethical review of investigator-initiated trials （IIT） is one of the important links to ensure the quality of research projects. Currently， the quality of ethical review for IIT projects is greatly influenced by the personal factors of committee members， which to some extent affects the ethical review committee’s judgments of research risks and benefits. Based on the previously developed Risk-Benefit Assessment Scale for Clinical Research， this paper established an ethical review decision-making pathway based on risk-benefit assessment， that is， proposed the “four-step method” for ethical review risk-benefit assessment， including evaluating the research benefits， assessing the research risks， constructing a risk-benefit matrix， and establishing an ethical review pathway. The “four-step method” helps to reduce the impact of committee members’ subjective/intuitive judgments on the quality of ethical review， assists in promoting the implementation of multi-center ethical review policy， narrows the gap in the quality of ethical review among different medical institutions， and provides clearer guidance for the risk judgments of scientific research management and ethical review departments.

Exosomes are extracellular vesicles that facilitate cellular communication by transmitting biomolecules and altering the biochemical characteristics of receptor cells. Mesenchymal stem cell-derived exosomes(MSC-Exos)are lipid bilayer vesicles secreted by mesenchymal stem cells(MSCs). These exosomes have similar functions to MSCs and contain bioactive substances such as proteins, lipids, and nucleic acids. MSC-Exos play a vital role in intercellular communication and are involved in essential physiological processes including immune regulation, tissue damage repair, and angiogenesis promotion. Consequently, they have gained significant attention in research, particularly in the treatment of immune inflammatory diseases, ischemic diseases, and other related fields. This article provides an in-depth analysis of the potential treatment mechanisms for dry eye, focusing on the pathogenesis of the condition, including inflammatory reactions, nerve regeneration, and tissue repair. The objective is to establish a foundation for the application of MSC-Exos in the treatment of dry eye, thereby offering a valuable reference for the future clinical applications.

OBJECTIVE To observe the clinical efficacy and safety of tofacitinib combined with hydroxychloroquine in the treatment of refractory rheumatoid arthritis （RA）. METHODS From January 1， 2021 to January 1， 2022， 120 patients with refractory RA were selected as the study objects. According to the principle of random allocation， the patients were divided into group A， group B and group C， with 40 patients in each group. Group A was given Tofacitinib citrate tablet + Hydroxychloroquine sulfate tablet； group B was given Tofacitinib citrate tablet + Methotrexate tablet； group C was given Tofacitinib citrate tablet + Leflunomide tablet. Three groups were given relevant medicine for 6 months. Therapeutic efficacy and disease activity score 28 （DAS 28） of 3 groups as well as Sharp score， the levels of biochemical indicators [erythrocyte sedimentation rate （ESR）， C- reactive protein （CRP）]， immune indexes [rheumatoid factor （RF）， anti-cyclic peptide containing citrulline （anti-CCP） antibody]， serum cytokine indicators [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] before and after treatment were observed； the occurrence of adverse drug reactions during treatment was recorded. RESULTS After treatment， the proportions of ACR50 and ACR70 patients in group A were significantly higher than groups B and C （P＜0.05）； DAS28 score， Sharp score， biochemical indicators， immune indexes and serum cytokine indicators of 3 groups were significantly lower than before treatment （P＜0.05）， and gradually decreased with prolonged treatment time； after 6 months of treatment， DAS28 score， Sharp score， RF， anti-CCP antibody， the levels of IL-6 and TNF-α in group A were significantly lower than group B and C （P＜0.05）. There was no significant difference in the incidence of diarrhea， nausea and vomiting， leukopenia， rash， abnormal liver and kidney function， or dizziness among 3 groups （P＞0.05）. CONCLUSIONS Tofacitinib combined with hydroxychloroquine shows good efficacy and safety for refractory RA.

Objective To systematically explore the traditional Chinese medicine(TCM)common symptoms,syndrome elements,clinical syndrome differentiation,and medication rules of coronary microvascular disease(CMVD),and to provide a reference for quantitative criteria of clinical differentiation of CMVD,specification of the diagnosis and efficacy evaluation of TCM clinical syndrome,and guidance of clinical medication.Methods The databases including CNKI,Wanfang,VIP,and SinoMed were searched for research papers on the treatment of CMVD by TCM published from database inception to May 16,2023.Relevant information of the included literature was extracted and the database was established.Then,the frequency statistics of symptoms,syndrome elements,syndrome types and Chinese medicinals were carried out.Latent structural models were constructed using Latern 5.0 and Rstudio softwares respectively for comprehensive clustering and association rule analysis,so as to explore the symptom characteristics,syndrome elements distribution,common syndromes and medication rules for TCM treatment of CMVD.Results A total of 107 literature were included,involving 36 syndromes,17 syndrome elements,121 symptoms and 143 Chinese medicinals.It was speculated that the main syndrome element of CMVD was blood stasis,followed by qi deficiency,qi stagnation,phlegm turbidity,yin deficiency and yang deficiency.The main type of syndrome was qi deficiency and blood stasis,followed by heart blood stasis obstruction,qi stagnation and blood stasis,phlegm blended with stasis,qi-yin deficiency,etc..The main medicinals were Chuanxiong Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Angelica Sinensis Radix and Astragali Radix.The medicinals used in the treatment of CMVD were classified as blood-activating and stasis-resolving drugs,deficiency-tonifying drugs,qi-regulating drugs in terms of their efficacy.Conclusion The location of CMVD is in heart,and related to liver and kidney.The syndrome of CMVD is deficiency in origin and excess in superficiality.Blood stasis runs through the development of the disease.The treatment is mainly to activate blood circulation and remove stasis,activate meridians and relieve pain,which should be supplemented with the therapies of tonifying and invigorating qi,soothing the liver and regulating qi,dispelling phlegm and dissipating masses according to the patients'syndromes.

Objective To investigate the expression of serum Maresin 1 and pro-platelet basic protein(PPBP)in patients with diabetes nephropathy(DN)and their correlation with long-term prognosis.Methods A total of 83 patients with diabetes nephropathy admitted to Tangshan Central Hospital from May 2018 to May 2020 were selected as the diabetes nephropathy group.In the same period,60 patients with simple type 2 diabetes were selected as the diabetes group and 60 healthy people as the control group.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of serum Maresin1 and PPBP.Spearman correlation analysis was used to analyze the correlation between the levels of serum Maresin1 and PPBP and renal pathological damage.COX proportional hazard regression analysis was used to analyze the factors influencing the long-term poor prognosis of patients with diabetes nephropathy.ROC curve was used to evaluate the predictive value of serum Maresin1 and PPBP for the long-term poor prognosis.Results The levels of serum Maresin1(15.90±4.53 ng/ml,12.34±4.29 ng/ml,9.65±4.38 ng/ml)in the control group,diabetes group and diabetes nephropathy group were decreased in turn while the levels of serum PPBP(263.45±85.22 pg/ml,349.28±80.49 pg/ml,435.76±87.21 pg/ml)were increased in turn,and the differences were statistically significant(F=35.159,72.678,all P＜0.05).With the increase of IFTA score,interstitial inflammation score,and glomerular grading,serum Maresin1 level was decreased(F=25.838,25.187,9.751,all P＜0.05),while serum PPBP level was increased(F=56.513,92.702,58.137,all P＜0.05),and the differences were statistically significant,respectively.Serum Maresin1 was negatively correlated with IFTA score,interstitial inflammation score,and glomerular grading(r=-0.637,-0.581,-0.594,all P＜0.05),while serum PPBP was positively correlated with IFTA score,interstitial inflammation score,and glomerular grading(r=0.659,0.664,0.608,all P＜0.05),with significant differences.The course of diabetes nephropathy(HR=1.135,95％CI:1.012～1.370),24-hour urinary protein(HR=1.087,95％CI:1.016～1.164),PPBP(HR=1.208,95％CI:1.119～1.365),and IFTA score(HR=1.139,95％CI:1.024～1.219),interstitial inflammation score(HR=1.122,95％CI:1.006～1.249)and glomerular grading(HR=1.139,95％CI:1.052～1.273)were independent risk factors for long-term prognosis of diabetes nephropathy patients,while eGFR(HR=0.934,95％CI:0.892～0.993)and Maresin1(HR=0.903,95％CI:0.816～0.982)were protective factors for long-term prognosis(all P＜0.05).The areas under the curve(AUC)of serum Maresin1,PPBP and two indicators combined to predict the long-term poor prognosis of patients with diabetes nephropathy were 0.781,0.777 and 0.901,respectively.The AUC of two indicators combined was higher than that,and the differences were significant(Z=3.049,3.258,all P＜0.05).Conclusion In patients with diabetes nephropathy,serum Maresin1 was decreased and PPBP was increased,and the two indexes were closely related to the degree of renal injury.The combined test could effectively predict the long-term poor prognosis of patients.

New daily persistent headache(NDPH)is a kind of persistent headache that patients can i-dentify the exact date of the sudden onset.It is one of the rare primary headaches difficult to be cured and may lead to disability,seriously affecting the daily life and work.The exact pathogenesis of NDPH remains unclear,which makes the treatment difficult.Here we report a case of refractory NDPH treated by intravenous injection of esketamine at a sub-anesthetic dose.

This article provides a review of domestic and international research on nursing-sensitive quality indicators (NSQIs) and evaluation systems for acute poisoning patients. It organizes the indicators into three dimensions based on the "structure-process-outcome" framework. The need for establishing a unified, comprehensive, and nationally suitable system of NSQIs in China is emphasized to standardize nursing practices and improve the monitoring of care quality. Although existing indicators possess some scientific validity, they often overlap with emergency nursing quality evaluation systems or are limited to specific types of poisoning. In addition, large-scale clinical trials to test their practical application and accessibility have yet to be conducted. This review aims to consolidate and analyze NSQIs for acute poisoning patients and provide a foundation and reference for improving the quality of nursing care for these patients.

Objective:To prevent postoperative myocardial oedema or other causes of acute heart failure in congenital cardiac disease,anticipating delay sternal closure may reduce the number of children requiring cardiopulmonary resuscitation after surgery.The aim of this study was to describe the rate of delay sternal closure after surgery for congenital cardiac disease and to analyse the risk factors that may be associated with it.Methods:We retrospectively reviewed all surgeries with extracorporeal circulation in the cardiothoracic surgery intensive care unit of Shanghai Children's Medical Center in the past five years,from September 2014 to December 2018.The study cohort was divided into the delay sternal closure group (n=418) and the control group (routine chest closure,n=12 188) according to whether a delay sternal closure was applicated.Risk factors associated with delay sternal closure were identified by multivariate Logistic regression analysis.Results:A total of 12 606 cases were eligible,of which 418 (3.32%) were in the delayed sternal closure group.The most common cardiac diagnosis in the delayed sternal group was transposition of the great arteries (26.8%,112/418),whereas the most common cardiac diagnosis in the control group was ventricular septal defect (45.9%,5 599/12 188).All-cause mortality in children in the delayed sternal closure group was 3.3% (14/418) compared with 0.4% (46/12 188) in the control group,with a statistically significant difference ( P<0.05).Multivariate Logistic regression analysis showed that the need for delayed sternal closure were associated with age ( OR 0.164,95% CI 0.079-0.338, P<0.001),positive intropic support before surgery ( OR 0.42,95% CI 0.252-0.699, P=0.001),sex（ OR 0.742，95% CI 0.648-1.098， P<0.05），mean body weight（ OR 1.192，95% CI 1.078-1.318， P<0.001），positive intropic support before surgery（ OR 0.370，95% CI 0.252-0.699， P<0.001），complicated surgery ( OR 0.241,95% CI 0.159-0.367, P<0.001) and extracorporeal circulation diversion time ( OR 6.412,95% CI 4.339-9.475, P<0.001). Conclusion:Delayed sternal closure is an important management strategy for congenital cardiac surgery in infants and children.Delayed sternal closure is associated with age，sex,mean body weight at the time of surgery,positive intropic support before surgery，complicated surgery and extracorporeal circulation diversion time.

Objective To compare the effect of routine speech training and computer-assisted training on post-stroke dysarthria. Methods From March,2021 to April,2023,72 patients with post-stroke dysarthria in Beijing Bo'ai Hospital were ran-domly divided into control group(n=36)and experimental group(n=36).Both groups received routine rehabili-tation,while the control group received routine speech training,and the experimental group received computer-assisted training,for four weeks.They were assessed with modified Frenchay Dysarthria Assessment(m-FDA)and Speech Intelligibility(SI)before and after intervention. Results Eight cases in the control group and one case in the experimental group dropped down.The scores of m-FDA and SI improved in both groups after treatment(|Z|＞4.183,P＜0.001),and there was no significant difference between two groups(|Z|＜1.598,P＞0.05).Noninferiority of m-FDA was found between two groups(|t|＞3.656,P＜0.001). Conclusion Computer-assisted training could improve the speech function of patients with post-stroke dysarthria,simi-lar to routine speech training.

Objective:Using the established epilepsy patient database to validate the efficacy of the web-based epilepsy diagnosis and anti-seizure medications (ASM) selection tool, EpiPick, for domestic epilepsy patients.Methods:The retrospective collection of clinical data was conducted on patients aged 10 and above who were diagnosed with epilepsy at the Comprehensive Epilepsy Center of the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2020, with regular follow-up and complete information. According to the first ASM recommended by the EpiPick tool and whether they are consistent with the actual ASM used by patients, patients were divided into EpiPick group and clinical group to verify the effectiveness of the EpiPick tool in selecting ASM. The drug retention rate, Engel score, and cumulative probability of no consecutive episodes within 30 months after using the first ASM were compared between the 2 groups, and Kaplan-Meier survival curves were drawn. Finally, the diagnostic results provided by the EpiPick tool were compared with the actual types of epileptic seizures diagnosed clinically, and consistency tests were performed.Results:A total of 364 epilepsy patients were included, including 237 in the EpiPick group and 127 in the clinical group. The ASM retention rates of patients in the EpiPick group and clinical group were 67.9%(161/237) and 56.7%(72/127), respectively, with statistically significant differences (χ2=4.534, P=0.039). Grades Ⅰ, Ⅱ, Ⅲ and Ⅳ according to the Engel scores in the EpiPick group patients who took the first ASM after diagnosis accounted for 47.3%(112/237), 14.8%(35/237), 12.7%(30/237), and 25.3%(60/237), respectively, compared to the clinical group of 32.3%(41/127), 11.8%(15/127), 11.0%(14/127), and 44.9%(57/127), respectively. There was a statistically significant difference in Engel scores between the 2 groups (χ2=14.968, P=0.002). The cumulative seizure-free rates in the EpiPick group at the 1st, 6th, 12th, 30th month and above after starting the first ASM were 73.8%, 61.2%, 53.2%, and 50.6%, respectively, which in the clinical group were 52.0%, 44.1%, 40.2%, and 33.5%, respectively. The logrank test showed a statistically significant difference in the cumulative probability of consecutive seizure freedom between the 2 groups ( HR=0.644 ,95% CI 0.476-0.871 ,P<0.001). After grouping by seizure type [focal seizures (196 cases) and generalized seizures (168 cases)], the cumulative seizure-free rates at the 1st, 6th, 12th, 30th month and above after starting ASM were significantly higher in the EpiPick group than in the clinical group (comparison between the 2 groups in patients with focal seizures: HR=0.654, 95%CI 0.443-0.964, P=0.004; comparison between the 2 groups in patients with generalised seizures: HR=0.586, 95%CI 0.361-0.954, P=0.014). Among 364 patients, 293 cases were clinically diagnosed with seizure classification consistent with the classification results of EpiPick tool. Agreement between the algorithm and the experts in classifying generalized seizures was 83.9%(104/124), which in classifying focal seizures was 78.8%(189/240; Kappa=0.591, P<0.001). Conclusion:Web-based EpiPick tool is suitable to be used to select the first ASM, and is portable for Chinese non-epilepsy specialists to choose ASM for epilepsy patients.