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 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.

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.

Objective:To analyze the medication characteristics of ancient prescriptions for pediatric epilepsy (PE) through data mining; To summarize the compatibility law; To provide a reference for the treatment selection of Chinese materia medica and the development of patent drugs related to PE in clinic.Methods:Those with definite composition, dosage and efficacy for the treatment of PE was screened from the data of TCM prescription designed by Institute of Traditional Chinese Medicine Information, China Academy of Traditional Chinese Medicine. Excel 2013 was used to analyze the frequency of Chinese materia medica and its flavor and meridian tropism in the included prescriptions. The arules package in R 3.6.3 was used for association analysis based on Apriori algorithm. The sankey package and ggraph package of R 3.6.3 were used to draw the network diagram of the property, taste, meridian tropism and association rules of high-frequency Chinese medicine, so as to realize data visualization.Results:A total of 360 ancient prescriptions for the treatment of PE were included, and the dosage form was mainly pills. Most of the prescriptions were composed of 1 to 10 kinds of Chinese materia medica, with a total of 192 (53.33%, 192/360) prescriptions. 152 kinds of Chinese materia medica were included. The most commonly used types of Chinese materia medica were Glycyrrhizae Radix et Rhizoma, Moschus, Saposhnikoviae Radix, Gastrodiae Rhizoma, and Aconiti Lateralis Radix Praeparata. The properties of high-frequency Chinese materia medica (frequency≥30) were characterized by warm and mild, and the tastes were mainly pungent, bitter and sweet, and the meridians were mainly spleen and liver meridians. Through Apriori association analysis, the commonly used combination drugs were Bovis Calculus-Moschus, Ginseng Radix et Rhizoma-Poria and Saposheikovize Radix-Glycyrrhizae Radix et Rhizoma. Similarly, the commonly used triple drugs included Gastrodiae Rhizoma-Aconiti Lateralis Radix Praeparata-Bombyx Batryticatus, Poria-Glycyrrhizae Radix et Rhizoma-Ginseng Radix et Rhizoma, and Moschus-Bovis Calculus-Realgar.Conclusions:The ancient prescriptions for the treatment of PE is mainly composed of wind-calming, resuscitation and tonifying drug. The core prescription ideas of the ancient prescriptions are as follows: dispelling phlegm and dispelling wind, warming the meridian and dispelling yang, resuscitating and relieving spasms, clearing heat and reducing depression, and tonifying qi and blood.

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.

BACKGROUND:Due to the mismatch between the design of the proximal femoral nail antirotation Asian version(PFNA-Ⅱ)and Asian population,extrusion of the proximal femoral intertrochanteric nail may occur in the treatment of femoral intertrochanteric fractures.The influence of the protruding length on the curative effect of the operation needs to be further discussed. OBJECTIVE:To quantitatively measure the protruding length of the proximal trochanter of the femur with intramedullary nail after PFNA-Ⅱ,and to analyze the effect of protruding length on the efficacy of PFNA-Ⅱ in the treatment of femoral intertrochanteric fractures. METHODS:Totally 68 patients with femoral intertrochanteric fractures treated with PFNA-Ⅱ internal fixation in the First Affiliated Hospital of Anhui Medical University were selected.The extramedullary process of the proximal trochanter of the femur was quantitatively measured on the anterior and posterior X-ray films of the hip joint within 6 months after operation.According to the existence of extrusion of the proximal trochanter intramedullary nail,the patients were divided into protruding group and non-protruding group.The data of sex,height,fracture type,length and diameter of the intramedullary nail,the position of screw blade in the femoral neck and protruding length of proximal greater trochanter were collected.The postoperative curative effect was judged by visual analog scale pain score and hip joint Harris score at 6 months after operation.The influence of protruding proximal trochanter of the PFNA-Ⅱ intramedullary nail on the operative effect was observed. RESULTS AND CONCLUSION:(1)There were significant differences in sexual characteristics between the protruding group and the non-protruding group(P=0.001).(2)According to AO/OTA classification,there were no significant differences in fracture type between the protruding group and the non-protruding group(P=0.289).(3)There was no significant difference in the length and diameter of the intramedullary nail between the two groups(P=0.067,P=1.000).(4)There was no significant correlation between the height of all patients and the length of the intramedullary nail(P=0.510),but there was a significant correlation between height and protruding length(P=0.034).There was no significant correlation between screw blade position and protruding length(P=0.968).(5)Six months after operation,there was no significant difference in the hip Harris score(P=0.373),but the visual analog scale pain score was significantly higher in the protruding group than that in the non-protruding group(P=0.000).(6)The results suggest that nail extrusion often occurs in the proximal greater trochanter when PFNA-Ⅱ is used in the treatment of intertrochanteric fractures in Asians.When the nail extended into the proximal soft tissue of the greater trochanter,patients complained of proximal greater trochanteric pain and the visual analog scale score of proximal greater trochanter pain in the patient was significantly higher than that in the non-protruding group.To be more suitable for the Asian population,we suggest that the PFNA-Ⅱ should be improved to further shorten the proximal nail end to obtain better clinical results of femoral intertrochanteric fracture fixation.

Objective:To discuss the clinical characteristics of autosomal recessive spinocerebellar ataxia type 16 patients caused by STUB1 gene mutation, in order to improve the clinical doctors′ understanding of the disease. Methods:The clinical manifestations, auxiliary examinations and genetic testing of 1 autosomal recessive spinocerebellar ataxia type 16 patient caused by STUB1 gene variants diagnosed in Qilu Hospital of Shandong University in May 2022 were collected, and the relevant literature was reviewed to summarize the clinical and genetic characteristics of this type of disease. Results:The proband was a 35-year-old male presenting with unsteady walk and dysarthria. Magnetic resonance imaging showed cerebellar atrophy. Next generation sequencing revealed compound heterozygous c.322dupG (p.Glu108Glyfs *4) and c.433A>C (p.Lys145Gln) variants in the STUB1 gene (according to the transcript NM_005861.4), and the c.322dupG (p.Glu108Glyfs *4) variant was a novel variant. Pedigree verification revealed the 2 variants were respectively inherited from the proband′s healthy parents. A total of 12 foreign literatures reported 32 autosomal recessive spinocerebellar ataxia type 16 patients. The main clinical manifestations were ataxia, dysarthria and tendon hyperreflexia. Besides, nystagmus, spasticity, action tremors, and myoclonus can be present. Magnetic resonance imaging predominantly showed cerebellar atrophy. Conclusions:The patient with autosomal recessive spinocerebellar ataxia type 16 caused by STUB1 gene variant is rare in China. The main clinical manifestation is cerebellar ataxia, and brain imaging reveals remarkable cerebellar atrophy. Genetic testing is helpful for definite diagnosis.

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.