The ethical review of clinical research on rare diseases is crucial in ensuring the scientific validity of the research and the rights and interests of the subjects. Starting from the definition of rare diseases， this paper analyzed the current situation of domestic and international regulations and ethical review in clinical research on rare diseases. It also explored the key elements of ethical review from the two dimensions of scientific and ethical aspects of clinical research， including research objectives， methods， risk and benefit assessment， researcher qualifications， research infrastructure， informed consent process， data security and privacy protection， and protection of vulnerable groups such as children. Regarding the ethical review of clinical research on rare diseases， strategies can be adopted such as strengthening the training of ethics review personnel， conducting multi-center collaborative reviews， and focusing on the long-term safety of trials， to improve the quality of ethical review， protect the safety of the subjects， and ensure the efficiency and quality of clinical research.

Objective: To evaluate the safety and efficacy of ABO non-identical platelets with reduced plasma (ABO-NPRP) transfusion in patients with hematological diseases. Methods: A retrospective analysis was conducted on 52 therapeutic doses of apheresis platelets with reduced plasma prepared at Chongqing Blood Center of the Chinese People's Liberation Army. The transfusion efficacy (24 h CCI) and the transfusion adverse reactions of these apheresis platelets were also observed in 35 patients with hematological diseases in First Affiliated Hospital of Army Medical University. Comparisons were made with a control group consisting of patients who received only identical apheresis platelets during the same period. Meanwhile, the effect of ABO-NPRP on the subsequent platelet transfusion efficacy was observed. Results: There was no statistically significant difference in PDW, MPV, and PLCR before and after the preparation of apheresis platelets with reduced plasma (P>0.05), while the difference in platelet count was statistically significant [(2.86±0.34)×10 per therapeutic dose vs (2.46±0.28)×10 per therapeutic dose, P<0.001]; there was no statistically significant difference in the 24 h CCI transfusion efficacy between conventional identical apheresis platelets and ABO-NPRP, with transfusion efficacy rates of 76.60% and 78.85%, respectively (P>0.05); there was no statistically significant difference in platelet transfusion efficacy between the group with ABO-NPRP and the group without ABO-NPRP (completely identical transfusion group), with transfusion efficacy rates of 77.78% and 75.25%, respectively (P>0.05). Conclusion: ABO-NPRP transfusion is safe, effective, demonstrating comparable efficacy to conventional identical transfusion. It can serve as an important complementary strategy to optimize the utilization of blood resources.

Objective: To evaluate the safety and efficacy of ABO non-identical platelets with reduced plasma (ABO-NPRP) transfusion in patients with hematological diseases. Methods: A retrospective analysis was conducted on 52 therapeutic doses of apheresis platelets with reduced plasma prepared at Chongqing Blood Center of the Chinese People's Liberation Army. The transfusion efficacy (24 h CCI) and the transfusion adverse reactions of these apheresis platelets were also observed in 35 patients with hematological diseases in First Affiliated Hospital of Army Medical University. Comparisons were made with a control group consisting of patients who received only identical apheresis platelets during the same period. Meanwhile, the effect of ABO-NPRP on the subsequent platelet transfusion efficacy was observed. Results: There was no statistically significant difference in PDW, MPV, and PLCR before and after the preparation of apheresis platelets with reduced plasma (P>0.05), while the difference in platelet count was statistically significant [(2.86±0.34)×10 per therapeutic dose vs (2.46±0.28)×10 per therapeutic dose, P<0.001]; there was no statistically significant difference in the 24 h CCI transfusion efficacy between conventional identical apheresis platelets and ABO-NPRP, with transfusion efficacy rates of 76.60% and 78.85%, respectively (P>0.05); there was no statistically significant difference in platelet transfusion efficacy between the group with ABO-NPRP and the group without ABO-NPRP (completely identical transfusion group), with transfusion efficacy rates of 77.78% and 75.25%, respectively (P>0.05). Conclusion: ABO-NPRP transfusion is safe, effective, demonstrating comparable efficacy to conventional identical transfusion. It can serve as an important complementary strategy to optimize the utilization of blood resources.

AIM: To systematically evaluate the efficacy and safety of low-concentrations atropine eye drops in controlling adolescent myopia.METHODS:A computer search was conducted on Wanfang Data, CNKI, VIP, PubMed, Cochrane Library, and Embase databases from January 2010 to March 2024 on clinical studies on low-concentration atropine eye drops for controlling adolescent myopia. Two researchers independently screened trials, extracted data, evaluated risk of bias and quality, and used Review Manager5.4 software to perform Meta-analysis.RESULTS:A total of 17 articles, involving 3 764 cases and 3 952 eyes, were included. The Meta-analysis showed that compared with the control group, low concentrations of atropine could effectively slow down the growth of axial length [MD=-0.15, 95% CI(-0.20, -0.10), P<0.00001], significantly controlled the changes in spherical equivalent [MD=0.39, 95% CI(0.29, 0.48), P<0.00001], and had a significant effect on pupil diameter [MD=0.80, 95% CI(0.33,1.28), P=0.0010] and amplitude of accommodation [MD=-2.54, 95%CI(-4.49, -0.60), P=0.01].CONCLUSION:Low-concentrations atropine are effective in controlling spherical equivalent and axial length of myopia in adolescents, significantly affecting pupil diameter and amplitude of accommodation, and effectively delaying the progression of myopia.

Objective To explore whether Yes-associated protein(YAP)affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition(EMT).Methods In a 8-week-old C57BL/6 mouse model of CCl4-induced liver fibrosis,the effect of verteporfin(a YAP inhibitor)intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting.Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis.Serum levels of YAP,N-cadherin,vimentin and Twist were examined in 60 healthy individuals,60 patients with chronic hepatitis B(CHB),and 60 patients with HBV-related liver cirrhosis.In another 24 C57BL/6 mice,the effects of Twist inhibitor alone or in combination with harmine(a YAP activator)on CCl4-induced liver fibrosis were evaluated by histopathological examination and Western blotting.Results The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules,and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice.Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP.Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis.In patients with CHB and liver cirrhosis,serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin,vimentin and Twist levels.In mice with liver fibrosis,inhibiting Twist effectively improved liver inflammation and fibrosis,while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and α-SMA expressions.Conclusion EMT is an important pathogenic mechanism of liver fibrosis,and inhibiting YAP can alleviate liver fibrosis by reducing EMT.

Objective To explore the effect of glioma stem cells with high expression of protein tyrosin phosphatase receptor type Z1 (PTPRZ1 )on the phenotypic polarization and phagocytosis of tumor-associated macrophages and its regulatory mechanism.Methods GSCs and non-stem tumor cells (NSTCs) were screened out from human glioblastoma (GBM) specimens using flow cytometry,and the PTPRZ1 expression in paired GSCs and NSTCs were detected.Human peripheral blood mononuclear cells (PBMC)-derived CD14+monocytes were exposed to the conditioned medium from glioma cells or recombinant chemokine C-C motif ligand 20 (CCL20)for TAM polarization.Stable PTPRZ1 knockout GSCs (PTPRZ1-KO GSCs) were constructed using CRISPR/Cas9. TAM phagocytosis to GSCs,NSTCs,PTPRZ1-Control GSCs (PTPRZ1-Ctrl GSCs)and PTPRZ1-KO GSCs and the expression of immunosuppressive phenotype (M2) polarization marker CD163 were examined using flow cytometry.Differentially expressed genes (DEGs ) between paired GSCs and NSTCs were determined using a bulk RNA-sequencing dataset (GSE54791 )from Gene Expression Omnibus (GEO).A gene set informing worse outcome of patients with GBM was generated using The Cancer Genome Atlas (TCGA)-GBM cohort.By intersecting the aforementioned gene set with the gene set that encodes for human membrance proteins,the PTPRZ1 gene is obtained.Gene set enrichment analysis (GSEA)was used for pathway enrichment analysis to compare the differentially regulated pathways between GBMs with high or low PTPRZ1 expression.Bulk RNA sequencing,qRT-PCR and Western blotting were used to identify the DEGs between PTPRZ1-KO GSCs and PTPRZ1-Ctrl GSCs.Results GSCs were more capable of escaping from TAM phagocytosis than NSTCs (P<0.05 )and had specifically up-regulated PTPRZ1 expression.PTPRZ1-KO significantly suppressed GSCs escaping from TAM phagocytosis (P<0.01 ). GBMs with high PTPRZ1 expression showed significant inhibition of pathways mediating phagocytosis (P<0.05).The expression of CCL20 as a M2 TAM polarization chemokine was significantly down-regulated in PTPRZ1-KO GSCs (P<0.05 ).Treatment with recombinant CCL20 up-regulated the expression of CD163 as a M2 TAM marker in TAM.Conclusion PTPRZ1+GSCs mediate M2 TAM polarization and inhibit TAM phagocytosis,which may be related to the up-regulation of CCL20 in PTPRZ1+GSCs.

Objective:To evaluate the efficacy of Yiqi Yangyin Jiedu Decoction in the treatment of patients with pulmonary nodules and qi-yin deficiency syndrome after early lung cancer surgery.Methods:Randomized controlled trial was conducted. A total of 76 patients with lung nodules and qi-yin deficiency syndrome after early lung cancer surgery at the Oncology Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March to September 2020 were selected and randomly divided into two groups using a random number table method, with 38 cases in each group. The control group received symptomatic treatment, while the treatment group took Yiqi Yangyin Jiedu Decoction from the first day after enrollment. Both groups were treated for 6 months and followed up for 2 years. TCM syndrome scores before and after treatment were evaluated; the patients' activity status was evaluated using the Eastern Oncology Collaborative Group Activity Status (ECOG PS) score in the United States, and electrochemiluminescence was used to detect carcinoembryonic antigen (CEA) and neuron specific enolase (NSE). Flow cytometry was used to detect the percentage of T lymphocyte subsets CD3 +and CD4 +, and ELISA was used to detect TGF-β Horizontal. The patients' weight was recorded and their weight changes after treatment were observed. Adverse reactions during treatment were observed and recorded, the efficacy of TCM syndromes and pulmonary nodules was evaluated. Results:During the observation period, one case was lost to follow-up in the treatment group and three cases were lost to follow-up in the control group. Finally, 37 cases in the treatment group and 35 cases in the control group completed the observation. After the treatment, the panting (0.27±0.07 vs. 0.68±0.12, t=17.66), spontaneous sweating and night sweating (0.16±0.16 vs. 0.79±0.16, t=16.55) score of the treatment group were lower than those in the control group ( P<0.01); insomnia (0.15±0.08 vs. 0.54±0.13, t=15.52) score of the control group was lower than that of the treatment group ( P<0.01). The effective rate of TCM syndrome in treatment group was 81.08% (30/37), higher than 54.29% (19/35) in control group ( Z=-2.00, P=0.040). After the treatment, the ECOG PS score stability rate in the treatment group was 89.19% (33/37), higher than 82.86% (29/35) in control group, without statistical significance ( χ2=0.19, P>0.05). The increase and stable rate of body weight was 88.10% (32/37) in treatment group and 62.86% (22/35) in control group ( χ2=5.36, P<0.05). After 2-year follow-up, the control rate of pulmonary nodules in the treatment group was 91.89% (34/37), while in the control group it was 65.71% (23/35). The difference between the two groups was statistically significant ( χ2=7.47, P<0.01). After the treatment, the level of NSE [(12.54±2.52)ng/L vs. (13.85±2.71)ng/L, t=-2.12], TGF-β [(218.38±102.63)ng/L vs. (301.24±193.69)ng/L, t=-2.29] in treatment group were lower than those in the control group ( P<0.05), and the level of CD3 +T cells [(70.60±7.90)% vs. (65.99±9.27)%, t=2.32] in treatment group was higher than that of the control group ( P<0.05). Conclusion:Yiqi Yangyin Jiedu Decoction can delay the development of pulmonary nodules in patients after early lung cancer surgery, increasing the body weight of patients, relieving the TCM syndromes and improve the immune function of patients, with the potential to prevent and treat the occurrence and development of early lung cancer.

Objective To study the effect of naringenin(NAR)on myocardial fibrosis in rats with chronic heart failure(CHF)and its mechanism.Methods The rat model of CHF was established and randomly divided into CHF model group(CHF),NAR low dose group(L-NAR),medium dose group(M-NAR)and high dose group(H-NAR),with 10 rats in each group.In addition,sham operation group(Sham)was set up.The cardiac function of rats was detected by ultrasonic electrocardiogram.HE staining and Masson staining were used to observe the pathological changes of myocardium.The content of hydroxyproline(HYP)in myocardium was determined by alkaline hydrolysis method,and the content of collagen was calculated.The mRNA expression levels of activin A(Act A)and follistatin(FS)in myocardium were detected by qRT-PCR.The protein expression levels of Act A,FS,Collagen Ⅰ,Collagen Ⅲ,Smad2,Smad3,p-Smad2 and p-Smad3 were detected by Western blot.Results Compared with Sham group,the arrangement of muscle fibers in CHF group was disordered,cells were swollen,and the degree of fibrosis was higher.The left ventricular end diastolic dimension(LVEDD),left ventricular end systolic dimension(LVESD),collagen content,and the expression levels of Act A,Collagen I,Collagen Ⅲ,p-Smad2/Smad2,and p-Smad3/Smad3 ratios were significantly increased(P<0.05),The left ventricular ejection fraction(LVEF)and FS expression level were significantly decreased(P<0.05).Compared with CHF group,the pathological changes and fibrosis degree of myocardial tissue in M-NAR group and H-NAR group were improved.LVEDD,LVESD,collagen content and the expression levels of Act A,Collagen Ⅰ,Collagen Ⅲ,p-Smad2/Smad2,and p-Smad3/Smad3 ratios were significantly decreased(P<0.05),while LVEF and FS expression levels were significantly increased(P<0.05).Compared with L-NAR group,medium and high-dose NAR intervention was more effective in improving myocardial fibrosis and Act A/FS system disorder in CHF rats(P<0.05).Conclusion NAR can inhibit myocardial fibrosis in CHF rats,and its mechanism may be related to the regulation of Act A/FS system.

Objective To explore whether Yes-associated protein(YAP)affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition(EMT).Methods In a 8-week-old C57BL/6 mouse model of CCl4-induced liver fibrosis,the effect of verteporfin(a YAP inhibitor)intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting.Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis.Serum levels of YAP,N-cadherin,vimentin and Twist were examined in 60 healthy individuals,60 patients with chronic hepatitis B(CHB),and 60 patients with HBV-related liver cirrhosis.In another 24 C57BL/6 mice,the effects of Twist inhibitor alone or in combination with harmine(a YAP activator)on CCl4-induced liver fibrosis were evaluated by histopathological examination and Western blotting.Results The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules,and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice.Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP.Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis.In patients with CHB and liver cirrhosis,serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin,vimentin and Twist levels.In mice with liver fibrosis,inhibiting Twist effectively improved liver inflammation and fibrosis,while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and α-SMA expressions.Conclusion EMT is an important pathogenic mechanism of liver fibrosis,and inhibiting YAP can alleviate liver fibrosis by reducing EMT.

Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.