BACKGROUND:There is a significant correlation between sperm DNA fragmentation index and fertilization,embryonic development potential,embryo implantation,miscarriage,and offspring safety.However,its clinical reference value is affected by many factors,resulting in extremely limited clinical significance.This study took live birth as the outcome,corrected other confounding factors through propensity score matching,constructed the best clinical cutoff value of sperm DNA fragmentation index and live birth,and conducted internal and external tests on it,which has good predictive value and clinical application efficiency. OBJECTIVE:To investigate the reference threshold and offspring short-term security of in vitro fertilization-embryo transfer sperm DNA fragmentation index based on live birth. METHODS:A total of 1 921 patients who received in vitro fertilization and embryo transfer in Changzhou Maternal and Child Health Area Hospital from May 2019 to May 2021 were selected.On the basis of tendency matching tolerance of 0.02 and propensity score matching of 1:1,540 cases were successfully matched in each live birth group and non-live birth group,and the model group was established.135 patients who received in vitro fertilization and embryo transfer in Nanxishan Hospital of Guangxi Zhuang Autonomous Region were selected as the external validation group.The optimal clinical cutoff value of sperm DNA fragmentation index for live birth was investigated by the receiver operating characteristic curve.The accuracy and clinical application efficacy of the cutoff value were evaluated by restricted cubic spline curve,standard curve,clinical decision curve,clinical impact curve and internal and external validation tests. RESULTS AND CONCLUSION:(1)The DNA fragmentation index of sperm in the non-live birth group was significantly higher than that in the live birth group and had a significant negative correlation with live birth(r=-0.444,P<0.001).(2)Receiver operating characteristic curve results showed that the optimal cut-off value of DNA fragmentation index for live birth was 24.33%;the area under the curve was 0.775(0.746,0.804);the specificity was 72.60%;the sensitivity was 78.90%,and the accuracy was 75.70%.(3)Restricted cubic spline curve fitting the results of Logistic regression showed that when the sperm DNA fragmentation index was greater than 24.57%,the risk of clinical non-live birth increased.(4)The probability of Logistic regression analysis results showed that sperm DNA fragmentation index was a risk factor for live birth[OR(95%CI)=0.916(0.904,0.928),P<0.001],and when sperm DNA fragmentation index was greater than 27.78%,the probability of clinical live birth would be less than 50%.With the increase of sperm DNA fragmentation index by 1 unit,the probability of a live birth fell by 8.4%.(5)Internal and external to the validation of the clinical cutoff value showed that the cutoff point had certain clinical predictive value and accuracy.(6)Clinical decision curve and clinical impact curve results exhibited that the prediction model based on the clinical cut-off value had the maximum clinical net benefit value when the threshold probability was 0.22-0.73,and the ratio of loss to gain within the threshold probability range was always less than 1,which confirmed that the prediction model had good clinical application effectiveness.(7)The results of sperm DNA fragmentation index and offspring short-term security analysis showed that sperm DNA fragmentation index had no significant differences with preterm birth,body weight,deformity and sex.(8)These findings suggest that the optimal clinical cut-off value of sperm DNA fragmentation index for in vitro fertilization-embryo transfer live birth was 24.33%.The established clinical prediction model has good differentiation,accuracy and clinical application effectiveness.Sperm DNA fragmentation index has no significant impact on offspring short-term security,but large samples and long-term follow-up evaluation are still needed.

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

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Objective:To explore the efficacy and safety of restylane volyme cross-linked sodium hyaluronate gel injection via dual-plane technique for cheek depression and mild to moderate skin laxity in the mid-lower face.Methods:The data of patients with cheek concavity accompanied by mild to moderate skin laxity in the mid-lower face treated at Jinan MeiAo Plastic Surgery Hospital from February 2023 to January 2024 were retrospectively collected. The treatment was injection of cross-linked sodium hyaluronate gel via double-plane technique, with needle insertion points located 1-2 cm anterior to the tragus. After insertion, a 23 G blunt needle was used to fanwise inject the subcutaneous fat (superficial layer) and the subcutaneous (deep layer) fat compartments in the concave area of the cheek, and a suitable amount of subcutaneous injection was administered below the zygomatic arch to soften the prominent zygomatic arch and achieve natural smoothness of the filling area. The total volume injected per side ranged from 1.5 to 3.5 ml. The patient’s skin condition was closely observed during the injection process, followed by gentle compression after injection. Patient images were collected preoperatively, immediately postoperatively, and at 6 months postoperatively. Blind evaluator used the facial laxity rating scale (FLRS) and medicis midface volume scale (MMVS) to evaluate the improvement in facial laxity and fullness. A higher rating/score of the scale indicates greater laxity or worse fullness of the face, and a decrease of 1 grade/point postoperatively compared to preoperative status was considered effective, while a decrease of ≥2 grades/points was considered significantly effective. Patients used the global aesthetic improvement scale (GAIS) to self-assess the improvement in facial appearance before and after treatment, with a maximum score of 5 points indicating the most noticeable improvement. Patient satisfaction and effect durability were investigated using a self-made satisfaction scale. The occurrence of patient complications was recorded. Data were analyzed using SPSS 26.0 statistical software, with measurement data expressed as Mean±SD, and paired t-tests used for comparison of GAIS scores immediately postoperatively and at 6 months postoperatively within the same patient. Categorical data were presented as cases (%). Results:A total of 80 female patients aged 30 to 50 years were included, all of whom were followed up for over 6 months. The FLRS grades showed that compared with preoperative status, all patients immediately postoperatively were rated as effective (69 cases, 86.3%) or significantly effective (11 cases, 13.8%). Compared with immediately postoperatively, 74 cases (92.5%) had no change in rating at 6 months postoperatively, while 6 cases (7.5%) experienced a 1-grade increase, indicating a slight reduction in treatment efficacy. The MMVS scores of the right and left facial sides of patients showed that compared with preoperative status, all patients immediately postoperatively achieved effective (right side: 55 cases, 68.8%; left side: 69 cases, 86.2%) or significantly effective (right side: 25 cases, 31.2%; left side: 11 cases, 13.8%) improvement in facial fullness. Compared with immediately postoperatively, at 6 months postoperatively, right side of 70 cases (87.5%) and left side of 77 cases (96.2%) had no change in grading, the other 12 patients (13 sides) increased by 1 point, indicating that the treatment effect was slightly weakened. All patients believed that their facial appearance improved after treatment, with GAIS scores of 4.5±0.5 immediately after treatment, while of 4.4±0.5 at 6 months postoperatively, the difference was not statistically significant ( t=1.08, P=0.280). The satisfaction rate (very satisfied+ satisfied) immediately postoperatively was 97.5% (78/80). Seventy-two (90.0%) cases expressed willingness to undergo secondary treatment. At 6 months post-treatment, the satisfaction rate (very satisfied+ satisfied) with treatment improvement and maintenance was 98.8% (79/80). Sixty-eight (85.0%) cases believed the treatment improvement effect could be maintained for about 6 months. One patient experienced mild redness and slight swelling in the injection area immediately postoperatively, which subsided after icing. No other obvious adverse reaction occurred. Conclusion:The use of double-plane technique injection of cross-linked sodium hyaluronate gel can safely and effectively improve cheek concavity, alleviate mild to moderate skin laxity in the mid-lower face, and maintain treatment efficacy for approximately 6 months.

Objective:To explore the efficacy and safety of restylane volyme cross-linked sodium hyaluronate gel injection via dual-plane technique for cheek depression and mild to moderate skin laxity in the mid-lower face.Methods:The data of patients with cheek concavity accompanied by mild to moderate skin laxity in the mid-lower face treated at Jinan MeiAo Plastic Surgery Hospital from February 2023 to January 2024 were retrospectively collected. The treatment was injection of cross-linked sodium hyaluronate gel via double-plane technique, with needle insertion points located 1-2 cm anterior to the tragus. After insertion, a 23 G blunt needle was used to fanwise inject the subcutaneous fat (superficial layer) and the subcutaneous (deep layer) fat compartments in the concave area of the cheek, and a suitable amount of subcutaneous injection was administered below the zygomatic arch to soften the prominent zygomatic arch and achieve natural smoothness of the filling area. The total volume injected per side ranged from 1.5 to 3.5 ml. The patient’s skin condition was closely observed during the injection process, followed by gentle compression after injection. Patient images were collected preoperatively, immediately postoperatively, and at 6 months postoperatively. Blind evaluator used the facial laxity rating scale (FLRS) and medicis midface volume scale (MMVS) to evaluate the improvement in facial laxity and fullness. A higher rating/score of the scale indicates greater laxity or worse fullness of the face, and a decrease of 1 grade/point postoperatively compared to preoperative status was considered effective, while a decrease of ≥2 grades/points was considered significantly effective. Patients used the global aesthetic improvement scale (GAIS) to self-assess the improvement in facial appearance before and after treatment, with a maximum score of 5 points indicating the most noticeable improvement. Patient satisfaction and effect durability were investigated using a self-made satisfaction scale. The occurrence of patient complications was recorded. Data were analyzed using SPSS 26.0 statistical software, with measurement data expressed as Mean±SD, and paired t-tests used for comparison of GAIS scores immediately postoperatively and at 6 months postoperatively within the same patient. Categorical data were presented as cases (%). Results:A total of 80 female patients aged 30 to 50 years were included, all of whom were followed up for over 6 months. The FLRS grades showed that compared with preoperative status, all patients immediately postoperatively were rated as effective (69 cases, 86.3%) or significantly effective (11 cases, 13.8%). Compared with immediately postoperatively, 74 cases (92.5%) had no change in rating at 6 months postoperatively, while 6 cases (7.5%) experienced a 1-grade increase, indicating a slight reduction in treatment efficacy. The MMVS scores of the right and left facial sides of patients showed that compared with preoperative status, all patients immediately postoperatively achieved effective (right side: 55 cases, 68.8%; left side: 69 cases, 86.2%) or significantly effective (right side: 25 cases, 31.2%; left side: 11 cases, 13.8%) improvement in facial fullness. Compared with immediately postoperatively, at 6 months postoperatively, right side of 70 cases (87.5%) and left side of 77 cases (96.2%) had no change in grading, the other 12 patients (13 sides) increased by 1 point, indicating that the treatment effect was slightly weakened. All patients believed that their facial appearance improved after treatment, with GAIS scores of 4.5±0.5 immediately after treatment, while of 4.4±0.5 at 6 months postoperatively, the difference was not statistically significant ( t=1.08, P=0.280). The satisfaction rate (very satisfied+ satisfied) immediately postoperatively was 97.5% (78/80). Seventy-two (90.0%) cases expressed willingness to undergo secondary treatment. At 6 months post-treatment, the satisfaction rate (very satisfied+ satisfied) with treatment improvement and maintenance was 98.8% (79/80). Sixty-eight (85.0%) cases believed the treatment improvement effect could be maintained for about 6 months. One patient experienced mild redness and slight swelling in the injection area immediately postoperatively, which subsided after icing. No other obvious adverse reaction occurred. Conclusion:The use of double-plane technique injection of cross-linked sodium hyaluronate gel can safely and effectively improve cheek concavity, alleviate mild to moderate skin laxity in the mid-lower face, and maintain treatment efficacy for approximately 6 months.

Objective:To investigate the prognostic value of enteroscopic grading for the prognostic assessment of patients with malignant hematological diseases who developed intestinal acute graft-versus-host disease (IT-aGVHD) after unrelated cord blood transplantation (UCBT) .Methods:Fifty patients with IT-aGVHD who developed hormone resistance after UCBT from June 2016 to June 2023 at Anhui Provincial Hospital were collected to compare the effective and survival rates of IT-aGVHD treatment in the group with milder enteroscopic mucosal injury (27 cases, enteroscopic grading of Ⅰ and Ⅱ) and the group with more severe injury (23 cases, enteroscopic grading of Ⅲ and Ⅳ) and to retrospectively analyze the factors affecting patients’ prognosis.Results:Patients in the mild and severe groups had an effective rate of 92.6% and 47.8% at 28 days after colonoscopy ( P<0.001), 81.5% and 39.1% at 56 days after colonoscopy ( P=0.002), with optimal effective rate of 92.6% and 65.2% ( P=0.040), respectively, and the differences were statistically significant. The multifactorial analysis found that enteroscopic grading was an independent risk factor affecting the effective rate of IT-aGVHD treatment. The overall survival rate at 2 years after colonoscopy was 70.4% (95% CI 52.0% -88.8% ) and 34.8% (95% CI 14.8% -54.8% ) for patients in the mild and severe groups, respectively, and the difference was statistically significant ( P=0.003). Multifactorial analysis revealed that enteroscopic grading, cytomegalovirus infection status, second-line treatment regimen, and patients’ age were independent risk factors for survival. Conclusion:The treatment efficacy and prognosis of patients in the group with less severe enteroscopic injury (grades Ⅰ and Ⅱ) were better than those in the group with more severe injury (grades Ⅲ and Ⅳ) .

Objective:To summarize the clinical and genetic characteristics of mental retardation disorder (MRD) with TRIO gene variant in children.Methods:Case series study. The data of 9 children with TRIO gene variants were collected retrospectively from August 2019 to March 2024 in Department of Neurology, Beijing Children′s Hospital, Capital Medical University and Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University. The data included gender, age, intellectual and motor development, appearance, seizures, neuroimaging and genetic results. The clinical features and genotype-phenotype correlations were summarized.Results:Of the 9 children, 6 boys and 3 girls, 4 MRD63 children presented with moderate to severe developmental delays accompanied by macrocephaly; 5 MRD44 children had mild to moderate developmental delays with microcephaly. A total of 5 children had dysmorphic facial features (flat occiput, thick eyebrows, unibrow, large ears, short fingers, pale skin, yellow hair, and strabismus), 2 children experienced seizures (1 child with myoclonic seizure and 1 with absence seizure), 4 children had feeding difficulties, 1 child had congenital cataracts, 1 child had congenital heart disease, 1 child had recurrent infections, and 1 child had tiger-striped changes in the fundus examination. TRIO gene variants carried by the 9 children were all de novo, involving 8 variant sites, including 7 missense variants and 1 frameshift variant, c.3232C>T/p.R1078W (2 cases), c.3920A>G/p.Y1307C, c.4112A>T/p.H1371L, c.4283G>T/p.R1428L, c.4394A>G/p.N1465S, c.6041T>C/p.I2014T, c.6821G>A/p.R2274H, c.7027delC/p.Q2343Sfs*70. Among them, 2 sites are located in the Spectrin domain, 4 sites are in the GEFD1 domain, 2 sites are in the GEFD2 domain, and 1 site (frameshift variant) is in the PH2-SH3 domain. The individual with frameshift variant exhibit absence seizures, mild developmental delay, and the mildest phenotype. The child with myoclonic seizures was treated with valproic acid and levetiracetam for seizure control, while the child with absence epilepsy was treated with valproic acid and lamotrigine for seizure control. All 9 children underwent regular rehabilitation exercises, making slow progress.Conclusions:TRIO gene related MRD is characterized by varying degrees of developmental delay, and often accompanied by macrocephaly or microcephaly, dysmorphic facial features, and with or without seizures. The main variant types are missense variants, which are mostly concentrated in the Spectran domain and GEFD domain. p. R1078W may be a relative hotspot variant. The phenotype caused by the frameshift variant is relatively milder.

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Objective To prepare a national reference standard for the quantification of HEK293 cell DNA content,so as to provide a support for the determination of residual DNA in HEK293 cells in the industry.Methods HEK293 cell DNA prepared using Genomic-tip 500/G and genomic DNA purification reagents was used as source materials,and the purity and content were assessed using ultraviolet spectrophotometry and agarose gel electrophoresis.After dilution to approximately 100 ng/μL,the DNA was aliquoted at 160 μL/tube.Five different laboratories were organized for collaborative calibration by using ultraviolet spectrophotometry, and the stability and applicability were evaluated.Results The HEK293 cell DNA national reference standard exhibited A_(260)/A_(280) ratios between 1.8 and 2.0 and displayed a single band on electrophoresis,meeting the specified criteria.Collaborative calibration across five laboratories yielded 78 valid data points with an average content of 104.8 ng/μL,a relative standard deviation(RSD) of 4.2%.The 95% confidence interval for the mean was 103.8—105.8 ng/μL,and the 95% reference range for single measurements was 96.0—113.6 ng/μL.The average confidence limit rate was 1.0%,and the recommended storage condition was-80 ℃.Applicability studies were conducted using two different models of fluorescence quantitative PCR instruments.The reference standard exhibited good applicability within the range of 0.3—3 000 pg/reaction,with amplification efficiencies of 101% and 95%,and R~2 values of 0.999 2 and 0.999 5 for the standard curves,respectively.Conclusion This batch of HEK293 cell DNA national reference standard meets all required specifications and can be utilized as a national reference standard for fluorescence quantitative PCR detection,with a certified content of 104.8 ng/μL,assigned batch number 270039-202301.