Objective: To comprehensively evaluate the clinical efficacy of a single dose of tranexamic acid (TXA) in reducing perioperative blood loss in patients undergoing craniomaxillofacial plastic and cosmetic surgery through meta-regression analysis. Methods: Embase, PubMed, Wanfang Data, VIP database, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect clinical studies evaluating efficacy of perioperative TXA administration in patients undergoing craniomaxillofacial plastic and cosmetic surgery, from inception to August 2024. Quality assessment of randomized controlled trials (RCTs) was performed using Cochrane Collaboration's Risk of Bias Tool. Based on the results of methodological heterogeneity, corresponding meta-analyses were conducted using either random-effects or fixed-effects models in R programming software. Results: Thirty-one articles were included, involving 2 072 patients who underwent craniomaxillofacial plastic and cosmetic surgeries. Among these patients, 1 051 were in the TXA treatment group, and 1 021 were in the control group. The paired meta-analysis showed that compared with the control group, the use of TXA significantly reduced bleeding volume in perioperative patients [standardized mean difference (SMD)=-1.13; 95%CI (-1.47, -0.80), P<0.001]. Subgroup analysis revealed that TXA significantly reduced intraoperative bleeding volume in patients across different surgeries, with the order of efficacy as follows: orthognathic surgery [SMD=-1.44; 95%CI (-2.07, -0.80), P<0.001], cleft palate repair [SMD=-1.32; 95%CI (-2.14, -0.50), P<0.001], rhinoplasty [SMD=-0.97; 95%CI (-1.63, -0.30), P<0.001], and craniosynostosis [SMD=-0.96; 95%CI (-1.40, -0.53), P=0.040]. The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) (P=0.650). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger's test indicated a certain degree of publication bias (Z=-3.40, P<0.001). Conclusion: Existing evidence suggests that TXA effectively reduces perioperative blood loss in patients undergoing craniofacial plastic surgery, regardless of its dosage administered.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

Objective : To investigate the expression and interaction of activating transcription factor 3(ATF3) and smad family member 4(Smad4) in pterygium. Methods: In this study, two sets of data GSE51995 and GSE2513 in NCBI database were analyzed by bioinformatics methods to screen out the key difference-expressed gene ATF3 in pterygium when normal conjunctiva was used as the control. The differential genes identified by bioinformatics analysis were further detected by reverse transcription quantitative polymerase chain reaction(RT-qPCR). Finally, the literatures were searched and The Gene Transcription Regulation Database(GTRD) was used to predict whether there was a target gene Smad4 that might bind to the target gene. The expression of Smad4 in normal conjunctival and pterygium tissues was verified by RT-qPCR, and the interaction between the target protein ATF3 and Smad4 in the pterygium was investigated through Co-Immunoprecipitation(Co-IP). Results : The results of bioinformatics a- nalysis showed that compared with normal conjunctival tissue , there was significantly different expression of ATF3 gene in pterygium tissue (P < 0. 05) . RT-qPCR confirmed that ATF3 was less expressed in pterygium tissue than normal conjunctival tissue (P < 0. 001) . Genomic data from the GTRD database revealed that Smad4 contains two ATF3 binding motifs , suggesting functional interaction potential . Compared with normal conjunctiva , RT-qPCR re- vealed Smad4 downregulation in pterygium tissues (P < 0. 01) ; Co-IP demonstrated enhanced interaction between Smad4 and ATF3 in pterygium tissues following immunoprecipitation with anti-ATF3 antibodies (P < 0. 05) . Conclusion ATF3 interacts with Smad4 in pterygium , and the low expression of both in pterygium tissues and their in- teraction may be associated with the pathogenesis of pterygium .

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

Objective:To comprehensively evaluate the clinical effectiveness with respect to a single dose of tranexamic acid (TXA) given preoperatively for blood loss control in perioperative patients accepted craniomaxillofacial plastic and cosmetic surgery.Methods:Embase, PubMed, WanFang Data, VIP, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect randomized controlled trials (RCTs) related to appraise the efficacy in perioperative craniomaxillofacial plastic and cosmetic surgery patients used TXA from inception to August 2024. Based on the result of methodological heterogeneity, corresponding paired meta-analyses were carried out with a random-effects or fixed-effects model applying R 4.0.4 software. Subgroup analysis was performed based on type of surgery, patient age, regional distribution of patients, and sample size included in the studies. A meta-regression analysis was performed on studies that reported the effect of different doses of TXA on reducing perioperative bleeding. Sensitivity analysis was performed to verify the stability of the meta result. Egger’s test was used to analyze potential publication bias.Results:A total of 31 RCTs were included, involving 2 072 patients, with 1 051 in the TXA group and 1 021 in the placebo group. The paired meta-analysis random-effects model ( I2=90%) showed that compared with the control group, the use of TXA significantly reduced the amount of bleeding in perioperative patients[standardized mean difference ( SMD)=-1.13, 95% CI -1.47 to -0.80, P < 0.01]. Subgroup analysis revealed that TXA had a significant effect on reducing intraoperative bleeding in patients with different surgeries, ages, regions, and sample sizes. The most effective subgroups were cases in orthognathic surgery ( SMD=-1.44, 95% CI -2.07 to -0.80, P< 0.01), less than 30 year-old( SMD=-1.32, 95% CI -1.68 to -0.96, P< 0.01], Asian patients( SMD=-1.29, 95% CI -1.72 to -0.86, P< 0.01), less than 30 individuals ( SMD=-1.16, 95% CI -1.50 to -0.82, P< 0.01). The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) ( P>0.05). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger’s test indicated a certain degree of publication bias ( P < 0.01). Conclusion:Taken as a whole, existing evidence suggests that TXA can effectively reduce perioperative bleeding in patients undergoing craniofacial plastic surgery, regardless of its dosage administered. However, further clinical researches are still needed to provide more baselined data, transfusion-related indicators, and information on adverse events such as vascular embolism, in order to comprehensively evaluate and analyze the efficacy and safety of a single dose of TXA for perioperative blood loss control in patients treated with craniomaxillofacial plastic and cosmetic surgery.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.