Objective:To explore the expression level of m6A methyltransferase ZC3H13 gene in primary acute myeloid leukemia(AML)and its relationship with clinical features and prognosis.Methods:A total of 131 newly diagnosed AML patients and 12 controls were enrolled from July 1,2018 to December 1,2021 in the Hematology Department of the Second Hospital of Shanxi Medical University.RT-qPCR technology was used to detect the expression level of ZC3H13 mRNA in bone marrow(BM)samples.A retrospective analysis was conducted to examine the correlation between ZC3H13 expression level and clinical indicators,gene mutations,and prognosis.Results:The expression level of ZC3H13 mRNA in primary AML patients was significantly higher than that in the control group(P＜0.001).The white blood cell count,proportion of BM blast cells,and relapse rate in the high ZC3H13 expression group were higher than those in the the low ZC3H13 expression group(all P＜0.05),while the Th/Ts ratio was lower(P＜0.01).Univariate survival analysis showed that patients with high expression of ZC3H13 had shorter median overall survival(OS)and disease-free survival(DFS)than those with low expression of ZC3H13(both P＜0.05).The results of multivariate Cox regression analysis showed that high-risk stratification(OS:HR=1.612,95％CI:1.151-2.257,P=0.005;DFS:HR=1.551,95％CI:1.031-2.335,P=0.035)and high ZC3H13 expression(OS:HR=1.756,95％CI:1.028-2.999,P=0.039;DFS:HR=1.935,95％CI:1.018-3.678,P=0.044)were both independent risk factors for OS and DFS in AML patients.Conclusion:The expression of ZC3H13 in AML patients may be related to tumor burden and immune function.Patients with high expression of ZC3H13 have poor prognosis,and high expression of ZC3H13 is an independent risk factor for the prognosis of AML patients.

Objective To analyze the risk factors of delayed wound recovery after Meek skin grafting in patients with extensive deep burn and its predictive efficiency.Methods A total of 100 patients with extensive deep burn who underwent Meek skin grafting from August 2018 to November 2024 were selected,and they were divided into the normal group(n=79)and the delayed group(n=21)according to the wound healing time.The clinical data of all patients were collected,and the influencing factors of delayed wound recovery after Meek skin grafting in patients with extensive deep burn were analyzed by Logistic regression model,and the efficiency of the model was analyzed by the receiver operating characteristic(ROC)curve and the Hosmer-Lemeshow goodness-of-fit test,respectively.Results There were statistically significant differences in the body mass index,hospitalization time,burn index,burn area,donor skin area,number of postoperative dressing change,postoperative nutritional support,postoperative pain scores,and hospitalized blood glucose levels between the two groups(P<0.05).Logistic regression analysis showed that high burn index(OR=1.086,β=0.082),large burn area(OR=1.155,β=0.144),fewer postoperative dressing change(OR=0.746,β=-0.293),lack of postoperative nutritional support(OR=6.439,β=1.862),high postoperative pain score(OR=4.483,β=1.500),and high level of hospitalized blood glucose(OR=2.251,β=0.811)were the influencing factors for delayed wound recovery after Meek skin grafting in patients with extensive deep burn(P<0.05).The ROC curve revealed that the combined prediction of the above six influencing factors for delayed postoperative wound recovery had an area under the ROC curve(AUC)of 0.896,with a sensitivity and specificity of 88.00%and 89.10%,respectively;and the Hosmer-Lemeshow test result showed:χ2=10.641,and P=0.223,indicating a high predictive efficacy and a certain calibration ability of the model.Conclusion The high burn index,large burn area,fewer postoperative dressing change,lack of postoperative nutritional support,high postoperative pain score and hospitalized blood glucose level were the influencing factors for delayed wound recovery after Meek skin grafting in patients with extensive deep burn,and the prediction model constructed by the above factors has good predictive ability,which can provide a reference for clinical treatment.

Objective:To observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type Ⅰ and Ⅱ patients. Methods:A family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks.Results:Among the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type Ⅰ (proband of families 1 and 2) and 2 cases of type Ⅱ (proband of families 3 and 4). The diopters ranged from -8.00 to-18.00 D. BCVA ranged from no light perception to 0.6 -. There were 2 cases each of vitreous membrane-like and "bead-like" opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains Conclusion:The COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type Ⅰ in families 1 and 2, and type Ⅱ in families 3 and 4.

Objective:To explore the expression level of m6A methyltransferase ZC3H13 gene in primary acute myeloid leukemia(AML)and its relationship with clinical features and prognosis.Methods:A total of 131 newly diagnosed AML patients and 12 controls were enrolled from July 1,2018 to December 1,2021 in the Hematology Department of the Second Hospital of Shanxi Medical University.RT-qPCR technology was used to detect the expression level of ZC3H13 mRNA in bone marrow(BM)samples.A retrospective analysis was conducted to examine the correlation between ZC3H13 expression level and clinical indicators,gene mutations,and prognosis.Results:The expression level of ZC3H13 mRNA in primary AML patients was significantly higher than that in the control group(P＜0.001).The white blood cell count,proportion of BM blast cells,and relapse rate in the high ZC3H13 expression group were higher than those in the the low ZC3H13 expression group(all P＜0.05),while the Th/Ts ratio was lower(P＜0.01).Univariate survival analysis showed that patients with high expression of ZC3H13 had shorter median overall survival(OS)and disease-free survival(DFS)than those with low expression of ZC3H13(both P＜0.05).The results of multivariate Cox regression analysis showed that high-risk stratification(OS:HR=1.612,95％CI:1.151-2.257,P=0.005;DFS:HR=1.551,95％CI:1.031-2.335,P=0.035)and high ZC3H13 expression(OS:HR=1.756,95％CI:1.028-2.999,P=0.039;DFS:HR=1.935,95％CI:1.018-3.678,P=0.044)were both independent risk factors for OS and DFS in AML patients.Conclusion:The expression of ZC3H13 in AML patients may be related to tumor burden and immune function.Patients with high expression of ZC3H13 have poor prognosis,and high expression of ZC3H13 is an independent risk factor for the prognosis of AML patients.

Objective To analyze the risk factors of delayed wound recovery after Meek skin grafting in patients with extensive deep burn and its predictive efficiency.Methods A total of 100 patients with extensive deep burn who underwent Meek skin grafting from August 2018 to November 2024 were selected,and they were divided into the normal group(n=79)and the delayed group(n=21)according to the wound healing time.The clinical data of all patients were collected,and the influencing factors of delayed wound recovery after Meek skin grafting in patients with extensive deep burn were analyzed by Logistic regression model,and the efficiency of the model was analyzed by the receiver operating characteristic(ROC)curve and the Hosmer-Lemeshow goodness-of-fit test,respectively.Results There were statistically significant differences in the body mass index,hospitalization time,burn index,burn area,donor skin area,number of postoperative dressing change,postoperative nutritional support,postoperative pain scores,and hospitalized blood glucose levels between the two groups(P<0.05).Logistic regression analysis showed that high burn index(OR=1.086,β=0.082),large burn area(OR=1.155,β=0.144),fewer postoperative dressing change(OR=0.746,β=-0.293),lack of postoperative nutritional support(OR=6.439,β=1.862),high postoperative pain score(OR=4.483,β=1.500),and high level of hospitalized blood glucose(OR=2.251,β=0.811)were the influencing factors for delayed wound recovery after Meek skin grafting in patients with extensive deep burn(P<0.05).The ROC curve revealed that the combined prediction of the above six influencing factors for delayed postoperative wound recovery had an area under the ROC curve(AUC)of 0.896,with a sensitivity and specificity of 88.00%and 89.10%,respectively;and the Hosmer-Lemeshow test result showed:χ2=10.641,and P=0.223,indicating a high predictive efficacy and a certain calibration ability of the model.Conclusion The high burn index,large burn area,fewer postoperative dressing change,lack of postoperative nutritional support,high postoperative pain score and hospitalized blood glucose level were the influencing factors for delayed wound recovery after Meek skin grafting in patients with extensive deep burn,and the prediction model constructed by the above factors has good predictive ability,which can provide a reference for clinical treatment.

Objective:To observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type Ⅰ and Ⅱ patients. Methods:A family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks.Results:Among the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type Ⅰ (proband of families 1 and 2) and 2 cases of type Ⅱ (proband of families 3 and 4). The diopters ranged from -8.00 to-18.00 D. BCVA ranged from no light perception to 0.6 -. There were 2 cases each of vitreous membrane-like and "bead-like" opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains Conclusion:The COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type Ⅰ in families 1 and 2, and type Ⅱ in families 3 and 4.

Objective:To analyze the occurrence of concomitant gene mutations in cytogenetically normal acute myeloid leukemia(CN-AML)patients with CEBPA mutation and its impact on the clinical characteristics and prognosis of the patients.Methods:151 newly diagnosed patients with CN-AML in the Second Hospital of Shanxi Medical University from June 2013 to June 2020 were analyzed retrospectively.34 common genetic mutations associated with hematologic malignancies were detected by next-generation sequencing technology.The occurrence of concomitant gene mutations in patients with CEBPA positive and negative groups was compared,and the correlation between concomitant mutations in different functional groups and the clinical characteristics and prognosis of CN-AML patients with CEBPA mutation was analyzed.Results:In 151 patients with CN-AML,55(36.42％)were positive for CEBPA mutation(including 36 cases of CEBPAdm and 19 cases of CEBPAsm),of which 41(74.55％)had co-mutations with other genes.The main mutated genes were GATA2(25.45％,14/55),TET2(21.82％,12/55),FLT3(20.00％,11/55),NRAS(12.73％,7/55)and WT1(9.09％,9/55),etc.Some cases had two or more concomitant gene mutations.Grouping the mutant genes according to their functions showed that CEBPA+group had lower mutation rates of histone methylation(P=0.002)and chromatin modification genes(P=0.002,P=0.033),and higher mutation rates of transcription factors(P=0.037)than CEBPA-group.In 55 patients with CEBPA+CN-AML,the platelet count at diagnosis in signaling pathway gene mutation-positive group was lower than that in the mutation-negative group(P=0.005),the proportion of bone marrow blasts in transcription factor mutation-positive group was higher than that in the mutation-negative group(P=0.003),and the onset age in DNA methylation gene mutation-positive group and chromatin modifier mutation-positive group was older than that in the mutation-negative group,respectively(P=0.002,P=0.008).DFS of CEBPA+CN-AML patients in signaling pathway gene mutation group was shorter than that in signaling pathway gene mutation-negative group(median DFS:12 months vs not reached)(P=0.034).Compared with DNA methylation gene mutation-negative group,CEBPA+CN-AML patients with DNA methylation gene mutation had lower CR rate(P=0.025)significantly shorter OS and DFS(median OS:20 months vs not reached,P=0.006;median DFS:15 months vs not reached,P=0.049).OS in patients with histone methylation gene mutation was significantly shorter than that in the histone methylation gene mutation-negative group(median OS:12 months vs 40 months)(P=0.008).Multivariate analysis of prognostic factors showed that the proportion of bone marrow blasts(P=0.046),concomitant DNA methylation gene mutation(P=0.006)and histone methylation gene mutation(P=0.036)were independent risk factors affecting the prognosis.Conclusion:CN-AML patients with CEBPA mutation have specific concomitant gene profile,and the concomitant mutations of different functional genes have a certain impact on the clinical characteristics and prognosis of the patients.

Eight compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Rubus pirifolius Smith by AB-8 macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as 1D/2D NMR, MS, UV, IR and by comparison with literature information as rubussecotriterpene A (1), rubussecotriterpene B (2), cecropiacic acid (3), cecropiacic acid 3-methyl ester (4), alphitolic acid (5), betulinic acid (6), betulin (7), and obtusalin (8). Compounds 1 and 2 are new compounds, and compounds 3-8 were isolated from this plant for the first time.

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --^SEA, followed by 5.70% for -α^3.7, and 0.24% for --^Thai. Among 32 α-thalassemia genotypes, the most common five were --^SEA/αα, -α^3.7/αα, α^CSα/αα, -α^4.2/αα and α^WSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --^Thai/αα. A total carrying rate of 13 kinds of β-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 β-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining β-thalassemia genotypes, the most common were --^SEA/αα, -α^3.7/αα combining CD41-42/N and --^SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --^SEA/-α^3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α^3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of α^WSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --^SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --^SEA/αα in α-thalassemia and CD41-42/N in β-thalassemia, and deletion genotype --^Thai is not rare. There is a certain incidence of intermediate and severe β-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Dipeptidyl Peptidase 4/genetics* ; China/epidemiology* ; Genotype ; Mutation

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m² and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m² or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.