Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Objective:To construct a continuity of care plan for adolescent fixed orthodontic patients based on the theory of timing, and provide systematic and standardized nursing interventions for adolescent fixed orthodontic patients.Methods:Guided by the theory of timing, preliminary plan items were formulated through literature review and questionnaire survey. Using the Delphi method, 15 experts were consulted for two rounds to determine the continuity of care plan for adolescent fixed orthodontic patients from October to December, 2023.Results:The effective response rates of the two rounds of questionnaires were 15/15, respectively. The expert authority levels were 0.93 and 0.94, and the Kendall harmony coefficients were 0.28 and 0.38, respectively. The differences were statistically significant (both P<0.001). The final established plan included 5 primary indicators, 23 secondary indicators, and 47 tertiary indicators. Conclusions:The continuity of care plan for adolescent fixed orthodontic patients based on the timing theory is reliable and scientific, and can meet the continuity of care needs of patients at different stages, providing reliable clinical basis for carrying out continuity of care.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To construct a continuity of care plan for adolescent fixed orthodontic patients based on the theory of timing, and provide systematic and standardized nursing interventions for adolescent fixed orthodontic patients.Methods:Guided by the theory of timing, preliminary plan items were formulated through literature review and questionnaire survey. Using the Delphi method, 15 experts were consulted for two rounds to determine the continuity of care plan for adolescent fixed orthodontic patients from October to December, 2023.Results:The effective response rates of the two rounds of questionnaires were 15/15, respectively. The expert authority levels were 0.93 and 0.94, and the Kendall harmony coefficients were 0.28 and 0.38, respectively. The differences were statistically significant (both P<0.001). The final established plan included 5 primary indicators, 23 secondary indicators, and 47 tertiary indicators. Conclusions:The continuity of care plan for adolescent fixed orthodontic patients based on the timing theory is reliable and scientific, and can meet the continuity of care needs of patients at different stages, providing reliable clinical basis for carrying out continuity of care.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To investigate the effect of the transcription factor TBX1 on the proliferation of colorectal cancer cells and to explore potential molecular mechanisms.Methods:The mRNA and protein levels of TBX1 in colorectal cancer cell lines HCT116, RKO, SW480, HT29, and LOVO were detected by using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Colorectal cancer cell lines HCT116 and SW480 cells with low TBX1 expression were transfected with either a pcDNA3.1 plasmid containing TBX1 mimics (TBX1 overexpression group) or an empty pcDNA3.1 plasmid (the control group). LOVO cells with high TBX1 expression were transfected with small interfering RNA (siRNA) targeting TBX1 including si-TBX1-8604A, si-TBX1-8604B, and a negative control siRNA (si-NC), which were treated as si-TBX1-8604A group, si-TBX1-8604B group, and si-NC group. qRT-PCR was used to detect the expressions of transcriptional level TBX1 and PARK2, and Western blot was used to detect the protein levels of TBX1, PARK2, and key factors in the MAPK and PI3K signaling pathways. Methyl Thiazolyl Tetrazolium (MTT) assay and cell colony formation assay were used to detect the cell proliferation. Combining literatures and the JASPAR database, 2 binding sites of TBX1 in the PARK2 promoter region were predicted. Chromatin immunoprecipitation assay was employed to verify the binding sites of TBX1 to PARK2 in HCT116 and SW480 cells. Dual luciferase reporter gene assay was used to verify the targeting relationship between TBX1 and PARK2. The expression of TBX1 and PARK2 in colon cancer tissues was analyzed by using the Cancer Genome Atlas (TCGA) database (September 2023).Results:High TBX1 expression in HCT116 and SW480 cells transfected with TBX1 mimics plasmid was confirmed by qRT-PCR and Western blot, while TBX1 expression was successfully knocked down in LOVO cells transfected with siRNA targeting TBX1. MTT assay indicated that the absorbance values for HCT116 cells in TBX1 overexpression group on d1, d3, d5, and d7 after inoculation, and for SW480 cells on d3, d5, and d7 after inoculation were lower than those in the control group, and the differences were statistically significant (all P < 0.01). LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group exhibited higher absorbance values than the si-NC group on d1, d3, d5, and d7 after inoculation, and the differences were statistically significant (all P < 0.05). Cell colony formation assay revealed that after 14 d, the colony number of HCT116 cells [(387±9) vs. (843±13)] and SW480 cells [(413±9) vs. (931±15)] in TBX1 overexpression group was lower than that in the control group, and the differences were statistically significant (all P < 0.05). The colony number of LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group was (493±77) and (470±32), respectively, which was higher than that in the si-NC group (349±26), and the differences were statistically significant (all P < 0.05). The protein relative expression levels of p-ERK and p-AKT S473 in HCT116 and SW480 cells in TBX1 overexpression group were lower than those in the control group, while protein relative expression levels of p-ERK and p-AKT S473 in LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group were higher than those in the si-NC group, and the differences were statistically significant (all P < 0.05). The relative expression level of PARK2 mRNA in HCT116 and SW480 cells (all P < 0.01) and the protein level in the overexpression group were higher than those in the control group. Chromatin immunoprecipitation assay demonstrated that the enrichment times of TBX1 binding to 2 sites of PARK2 intron in HCT116 and SW480 cells in TBX1 overexpression group were higher than that in the control group, and the differences were statistically significant (all P < 0.05). Dual luciferase reporter gene assay showed that the relative luciferase activity of HCT116 and SW480 cells co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and pGL3 plasmid containing PARK2 mimics was higher than that of cells co-transfected with empty pcDNA3.1 and pGL3 plasmids, co-transfected with empty pcDNA3.1 plasmid and pGL3 plasmid containing PARK2 mimics, co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and empty pGL3 plasmid, and the differences were statistically significant (all P < 0.05). Spearman analysis showed that there was a positive correlation between transcriptional level TBX1 and PARK2 in colon cancer tissues (288 cases) in TCGA database ( r = 0.226, P < 0.001); and the relative expression level of PARK2 mRNA in colon cancer tissues (383 cases) was lower than that in normal intestinal tissues (50 cases), and the difference was statistically significant ( P < 0.001). Conclusions:Elevated expression of transcriptional factor TBX1 inhibits the proliferation of colorectal cancer cells, potentially by activating the downstream target gene PARK2 and inhibiting the phosphorylation of ERK and AKT in the MAPK and PI3K signaling pathways, ultimately affecting the activation of these pathways.

Argonaute proteins are active throughout the lifetime in a variety of organisms and they bind to small RNAs (sRNAs) to regulate gene expression. The Argonaute proteins of vertebrates can be classified into two clades: the Ago clade and the Piwi clade. Both clades have N, L1, L2, PAZ, MID and PIWI domains. The N domain is involved in the loading of sRNAs. L1 and L2 domains facilitate the linking between domains. The PAZ and MID domains exert functions by anchoring sRNAs. The PIWI domain of some Argonaute proteins has RNase H-like structure and exerts the endonuclease function. Ago proteins regulate gene expression at transcriptional and post-transcriptional levels. Piwi proteins mainly exist in the germ cells, silencing transposons in different ways to keep genome integrality and regulating gene expression. In recent years, great progress has been made in Argonaute proteins in terms of the crystal structures, functions, and expression patterns. By reviewing the relevant studies, we elaborate on the structures, sRNA dependence, gene expression regulation, and biological roles of the Ago and Piwi proteins in vertebrates, aiming to clarify the roles of Argonaute proteins in epigenetic regulation and provide a reference for further research and application of these proteins.
Argonaute Proteins/chemistry* ; Animals ; Vertebrates/metabolism* ; Gene Expression Regulation ; RNA, Small Interfering/metabolism* ; Epigenesis, Genetic ; Humans

【Objective】 To analyze the hepatitis B virus (HBV) infection data of blood donors from 18 domestic blood stations, so as to investigate the HBV infection situation of blood donors. 【Methods】 The positive rate of HBV and its distribution characteristics of regions, the percentage of HBsAg+ ELISA in first-time vs repeated blood donors, and the percentage of HBsAg-/HBV DNA+ blood donors of 18 domestic blood stations during 2017 to 2020 were collected from the Working Platform for Practice Comparison of Blood Centers, and the HBV infection among blood donors were statistically analyzed. 【Results】 From 2017 to 2020, the positive rate of HBV in blood donors among 18 domestic blood stations was 13.48/10 000-144.02/10 000, with the average HBV positive rate in eastern, central and western region at 26.14/10 000, 51.98/10 000 and 41.00/10 000, respectively. The HBsAg+ rate by ELISA among first-time and repeated blood donors was 14.55/10 000-305.39/10 000 vs 1.04/10 000-87.43/10 000 The HBsAg-/HBV DNA+ yield was 1.80/10 000-35.31/10 000. 【Conclusion】 The distribution of HBV infection in blood donors has regional characteristics, and HBV prevalence was low in repeated blood donors. HBsAg ELISA combined with HBV DNA detection can better ensure blood safety.

【Objective】 To study the annual financial expenditure in blood stations with different scales, and to establish the regression equation between blood collection units and total expenditure. 【Methods】 The annual total expenditure, the per capita cost of serving population, as well as the collection units of whole blood and apheresis platelet of 24 blood stations were collected. The financial expenditure required for collecting 10 000U blood was calculated.The statistical analysis was carried out with SPSS statistical software. 【Results】 From 2017 to 2020, the total annual financial expenditure of 24 blood stations showed an upward trend. The total expenditure among blood stations was different. The per capita cost of servicing population in the areas where the 24 blood stations were located had been increasing year by year. The 24 blood stations were divided into two grades according to the blood collection volume as 50 000 U, and the relationship equation between the blood collection volume and the annual total expenditure had been established. After testing, each equation was effective(P<0.05); There was no difference in the financial expenditure required for collecting 10 000U blood among blood stations with different scales. 【Conclusion】 From 2017 to 2020, the blood stations with an annual collection volume more than 50 000 U demonstrated a higher financial expenditure and the per capita cost of serving population than those <50 000 U. The blood collection volume of blood stations is significantly correlated with the annual total expenditure and the per capita cost of serving population.