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 influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

In the era of rational molecular design of fusion proteins,linker selection has garnered significant attention as a critical determinant of construct functionality.Suboptimal selection of linkers may result in such structural perturbations as protein misfolding,reduced expression yields,and compromised bioactivity.Consequently,the strategic selection of linkers tailored to specific objectives of molecular design by optimizing spatial orientation,maintaining domain autonomy or enabling post-translational modifications has emerged as a pivotal research frontier.Given these challenges,this review outlines the common properties of linkers,ways of classification,and the functional-structural interplay in current applications.Furthermore,we propose context-dependent selection frameworks for therapeutic proteins,biosensors,and enzyme cascades,which can serve as a systematic methodology to guide linker optimization in next-generation fusion protein engineering.

Objective To establish, optimize and validate a method for determining the selective proliferative activity of oncolytic virus using recombinant human herpes simplex virus-1(rhHSV-1) as the oncolytic virus, so as to apply it to the quality evaluation of oncolytic virus-related products. Methods Normal cells and tumor cells were infected with rhHSV-1 at the same MOI respectively. Afteracertainperiodofculture,theviralnucleicacidwasextractedandusedastemplateforqPCRamplification. The copy number of virus genome was obtained, and the virus proliferation ratio was calculated, which was used as an evaluation index for selective proliferative activity. The cell types(normal cells: MRC-5, HEK-293; tumor cells: Hep3B, Fadu), MOI(0. 1, 0. 01, 0. 001, 0. 000 1, 0. 000 01) and culture time(2 h and 2, 3, 4 d) were optimized, and the precision and specificity of the method were verified. The selective proliferative activity of oncolytic virus rhHSV-1 working seed lot was detected by using the established method. Results Using Hep3B as tumor cells and MRC-5 as normal cells, rhHSV-1 had the best proliferation effect with the optimal MOI of 0. 000 1, and the optimal culture time was 72 h. The proliferation ratios of rhHSV-1 in three repeated tests by the optimized method were 260. 68, 336. 65 and 259. 14 respectively, with all of them more than 100 and a CV of 15. 52%. Using the optimized method, rhHSV-1 had significant amplification, but human cytomegalovirus(HCMV) and adenovirus 5(Ad5) showed no obvious amplification. The proliferation ratio of oncolytic virus rhHSV-1 working seed lot was 727. Conclusion The established method for determining the selective proliferative activity of rhHSV-1 has good precision and specificity, and can be used to evaluate the selective proliferative activity of oncolytic viruses

The"season-visceral-related"theory originated from Huangdi Neijing,and its content contains the"holism of five viscera"and"correspondence between nature and humans"in the theoretical system of traditional Chinese medicine(TCM).Recently,the prevalence of post-stroke cognitive impairment(PSCI)has gradually increased with the increasing incidence of stroke.TCM believes that PSCI is located in the brain,however,the causative factors such as phlegm,depression,deficiency,and stasis are caused by the lesions of the five zang viscera.Therefore,PSCI can not be treated with the brain alone.Based on the"season-visceral-related"theory,this article discusses the etiology,pathogenesis,and treatment ideas for PSCI from the four seasons and five zang viscera.Xiaoyao Pill was selected as a treatment for patients with qi imbalance in spring to disperse stagnated liver qi to relieve qi stagnation.Tianwang Buxin Dan was selected as a treatment for patients with blood loss and spirit injury in the summer to nourish the blood and calm the heart and brain.Kaixin Powder was selected as a treatment for patients with spleen deficiency and phlegm blockage in late summer to strengthen the spleen,awaken the mind,and remove stasis.Wenfei Jiangzhuo Decoction was selected as a treatment for patients with qi deficiency and spirit departure in autumn to nourish the lungs,reduce turbidity,and nourish the mind.Dihuang Yinzi was selected as a treatment for patients with marrow reduction and internal toxin in winter to expel phlegm and fill the mind.Treating PSCI using the"season-visceral-related"theory reflects the overall concept of TCM and the hypothesis of syndrome differentiation and treatment and provides novel method for treating PSCI.

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.

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.