Gliomas are the most common primary neuroepithelial tumors of the central nervous system in adults, of which glioblastoma is the deadliest subtype. Apart from the intrinsically indestructible characteristics of glioma (stem) cells, accumulating evidence suggests that the tumor microenvironment also plays a vital role in the refractoriness of glioblastoma. The primary functions of platelets are to stop bleeding and regulate thrombosis under physiological conditions. Furthermore, platelets are also active elements that participate in a variety of processes of tumor development, including tumor growth, invasion, and chemoresistance. Glioma cells recruit and activate resting platelets to become tumor-educated platelets (TEPs), which in turn can promote the proliferation, invasion, stemness, and chemoresistance of glioma cells. TEPs can be used to obtain genetic information about gliomas, which is helpful for early diagnosis and monitoring of therapeutic effects. Platelet membranes are intriguing biomimetic materials for developing efficacious drug carriers to enhance antiglioma activity. Herein, we review the recent research referring to the contribution of platelets to the malignant characteristics of gliomas and focusing on the molecular mechanisms mediating the interaction between TEPs and glioma (stem) cells, as well as present the challenges and opportunities in targeting platelets for glioma therapy.
Humans ; Glioma/metabolism* ; Blood Platelets/physiology* ; Brain Neoplasms/pathology* ; Tumor Microenvironment

Objective The aim of this study was to explore the acceptance and influencing factors of self-collected urine samples for human papillomavirus(HPV)testing in cervical cancer screening among eligible women,and to provide scientific evidence for promoting this testing in low resource areas.Methods A population-based cross-sectional study was conducted from 2022 to 2023 at the Maternal and Child Health Hospital in Shuangliu district,Chengdu City Sichuan Province.The study subjects were women aged 21 to 69 years old,and a customized questionnaire was used to conduct general information and acceptance surveys on the partic-ipants.Results A total of 2,062 women were included,with an average age of 51.58±9.34 years.Among them,1,501(72.79％)women believed that self-sampling urine was very easy.However,although 1,333(64.65％)women were still willing to accept doctor sampling as a cervical cancer screening method,only 729(35.35％)were more willing to accept self-sampling urine HPV testing.Age,educational level,annual household income,awareness of HPV,HPV vaccination status,and a sense of shame about the doctor's sampling process were all associated with the acceptance of self-collected urine HPV testing among women undergoing cervical cancer screening(P＜0.001).The results of multivariate logistic regression analysis indicated that older women(OR=0.965,95％CI:0.951-0.979)and those who were not familiar with HPV(OR=0.760,95％CI:0.602-0.961)were more likely to undergo self sampling urine HPV testing,while those with junior high school education(OR=1.330,95％CI:1.053-1.682),high school education or a-bove(OR=1.990,95％CI:1.401-2.827),and a sense of shame towards the doctor's sampling process(OR=2.314,95％CI:1.706-3.142)were more likely to undergo self sampling urine for HPV testing.Conclusions Most women believe that self sampling urine for HPV testing is very easy,but compared to doctor sampling,only some women choose to self sample urine for HPV testing.Key health education interventions should be carried out for older and lower educated populations to promote acceptance of urine HPV testing.

Objective The aim of this study was to explore the acceptance and influencing factors of self-collected urine samples for human papillomavirus(HPV)testing in cervical cancer screening among eligible women,and to provide scientific evidence for promoting this testing in low resource areas.Methods A population-based cross-sectional study was conducted from 2022 to 2023 at the Maternal and Child Health Hospital in Shuangliu district,Chengdu City Sichuan Province.The study subjects were women aged 21 to 69 years old,and a customized questionnaire was used to conduct general information and acceptance surveys on the partic-ipants.Results A total of 2,062 women were included,with an average age of 51.58±9.34 years.Among them,1,501(72.79％)women believed that self-sampling urine was very easy.However,although 1,333(64.65％)women were still willing to accept doctor sampling as a cervical cancer screening method,only 729(35.35％)were more willing to accept self-sampling urine HPV testing.Age,educational level,annual household income,awareness of HPV,HPV vaccination status,and a sense of shame about the doctor's sampling process were all associated with the acceptance of self-collected urine HPV testing among women undergoing cervical cancer screening(P＜0.001).The results of multivariate logistic regression analysis indicated that older women(OR=0.965,95％CI:0.951-0.979)and those who were not familiar with HPV(OR=0.760,95％CI:0.602-0.961)were more likely to undergo self sampling urine HPV testing,while those with junior high school education(OR=1.330,95％CI:1.053-1.682),high school education or a-bove(OR=1.990,95％CI:1.401-2.827),and a sense of shame towards the doctor's sampling process(OR=2.314,95％CI:1.706-3.142)were more likely to undergo self sampling urine for HPV testing.Conclusions Most women believe that self sampling urine for HPV testing is very easy,but compared to doctor sampling,only some women choose to self sample urine for HPV testing.Key health education interventions should be carried out for older and lower educated populations to promote acceptance of urine HPV testing.

Objective To investigate the role of member septin family(SEPT12)in human spermatogenesis and its influence on sperm motility and sperm ultrastructure.Methods Whole exome sequencing(WES)was performed on peripheral blood DNA extracted from 375 patients with asthenoteratozoospermia,and a patient with idiopathic in-fertility carrying compound heterozygous mutation of SEPT12 was screened out.Sanger sequencing was performed to verify the mutation,and co-segregation analysis was performed in the family.The morphological abnormalities of sperm were analyzed by hematoxylin-eosin(HE)staining and scanning electron microscopy(SEM),and the ultra-structural defects of sperm were analyzed by transmission electron microscopy(TEM).Then the effects of the muta-tion on the level and position of the protein and the changes of the location and level of the defect structure markers were analyzed by Western blot and immune-fluorescence(IF).Results The compound heterozygous mutations c.C332A(p.Ti111K)and c.406_416 del TGCTCGTATTG(p.q136 VFS*39)in the SEPT12 gene were screened and identified in a patient with asthenoteratozoospermia.The mutations were verified by Sanger sequencing,which was consistent with the co-segregation genetic pattern of the family.The mutations resulted in loss of protein expres-sion,decreased sperm motility and sperm morphological deformities,mainly including short tail,curly tail and ir-regular sperm head.The ultrastructure of sperm showed that the annulus between the mid-piece and the principle-piece was missing,the acrosome membrane of sperm head fell off and the nucleus contained vacuoles.In the mid-piece of sperm flagella,the arrangement of mitochondrial sheath was disordered,most of flagella axoneme central pair was absent,microtubules doublet was missing or disordered,and some radical spoke was absent.By Western blot and IF,the marker proteins of related structural components were detected,and the results showed that the level of SEPT4 protein decreased,SEPT6 protein unchanged,acrosomal related proteins ACTL7A and ACROSIN protein missing,and the expression levels of mitochondrial and axoneme related proteins TOMM20,SPAG6 and RSPH3 protein significantly decreased.Conclusion The deletion of SEPT12 protein caused by SEPT12 gene mu-tation leads to the deletion of the annulus between the mid-piece and the principle-piece,and the abnormal assem-bly of sperm acrosome,mitochondrial sheath and flagella.

Background::With an increasing proportion of multiparas, proper interpregnancy intervals (IPIs) are urgently needed. However, the association between IPIs and adverse perinatal outcomes has always been debated. This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.Methods::We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019. Multivariable Poisson models with restricted cubic splines were used. Each adverse outcome was analyzed separately in the overall model and stratified models. The stratified models included different categories of fertility policy periods (2014–2015, 2016–2017, and 2018–2019) and infant gestational age in previous pregnancy (<28 weeks, 28–36 weeks, and ≥37 weeks).Results::There were 781,731 pregnancies enrolled in this study. A short IPI (≤6 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.63 [1.55, 1.71] for vaginal delivery [VD] and 1.10 [1.03, 1.19] for cesarean section [CS]), low Apgar scores and small for gestational age (SGA), and a decreased risk of diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. A long IPI (≥60 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.18 [1.11, 1.26] for VD and 1.39 [1.32, 1.47] for CS), placenta previa, postpartum hemorrhage, diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes. The estimated risk of preterm birth, low Apgar scores, SGA, diabetes mellitus in pregnancy, and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.Conclusion::For pregnant women with shorter or longer IPIs, more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

Recently, small nucleolar RNAs (snoRNAs) have transcended the genomic "noise" to emerge as pivotal molecular markers due to their essential roles in tumor progression. Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance. Historically, snoRNA research has concentrated on two classical mechanisms: 2'-O-ribose methylation and pseudouridylation. This review specifically summarizes the novel regulatory mechanisms and functional patterns of snoRNAs in tumors, encompassing transcriptional, post-transcriptional, and post-translational regulation. We further discuss the synergistic effect between snoRNA host genes (SNHGs) and snoRNAs in tumor progression. More importantly, snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes. Accordingly, we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.

Recently,small nucleolar RNAs(snoRNAs)have transcended the genomic"noise"to emerge as pivotal molecular markers due to their essential roles in tumor progression.Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance.Historically,snoRNA research has concentrated on two classical mechanisms:2'-O-ribose methylation and pseudouridylation.This review specifically summarizes the novel regulatory mecha-nisms and functional patterns of snoRNAs in tumors,encompassing transcriptional,post-transcriptional,and post-translational regulation.We further discuss the synergistic effect between snoRNA host genes(SNHGs)and snoRNAs in tumor progression.More importantly,snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes.Accordingly,we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.

Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [⁶⁴Cu]DPA and investigated the tumor engagement of [⁶⁴Cu/⁶⁸Ga]DPA in mouse models. Our results revealed that intact [⁶⁴Cu/⁶⁸Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [⁶⁴Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.

Objective:To investigate the clinical outcomes of patients with multiple morphological abnormalities of the flagella (MMAF) caused by CFAP43 or CFAP44 gene mutations following intracytoplasmic sperm injection (ICSI). Methods:Clinical data and genetic information were retrospectively analyzed for 121 MMAF patients who attended Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University during September 2014 to July 2020. Totally 9 MMAF patients were identified to carry CFAP43 or CFAP44 mutations, 5 of them (P3, P5, P7, P8, and P9) received ICSI treatments, the ICSI outcomes were further analyzed. Results:Sanger sequencing validated 9 MMAF patients harboring CFAP43 or CFAP44 biallelic mutations, our study firstly identified a novel homozygous mutation of CFAP43(c.4132delC: p.Arg1378Glufs*10), novel compound heterozygous mutations of CFAP43 (c.3938G>A: p.Arg1313Gln;c.4342G>A:p.Glu1448Lys) and novel compound heterozygous mutations of CFAP44 (c.1718C>A:p.Pro573His; c.4075G>A: p.Glu1359Lys). The 5 MMAF patients underwent 5 ICSI cycles, 4 healthy offspring were obtained. The rate of fertilization of CFAP43- or CFAP44-mutated MMAF patients following ICSI was 76.47% (39/51), 3 patients' wife got clinical pregnancy, 3 patients got live birth delivery, respectively. No significant differences were found in ICSI outcomes among CFAP43-mutated or CFAP44-mutated MMAF patients, DNAH1-mutated MMAF patients, and severe oligoasthenozoospermia group (all P>0.05) .Conclusion:CFAP43 or CFAP44 mutations are responsible for the malformation of sperm flagella and decrease of sperm motility, and validated as the important genetic causes of MMAF. CFAP43- or CFAP44-mutated MMAF patients could have a favorable treatment outcome following ICSI.

Objective::To analyze the temporal trends of maternal mortality ratio (MMR) due to obstetric hemorrhage and its specific causes in Chinese mainland from 2000 to 2019, to identify whether the rate of change has accelerated or slowed down during this period, and to find the prior cause of obstetric hemorrhage that needs to be intervened in the future.Methods::Individual information on maternal deaths and total number of live births from 336 surveillance sites across 31 provinces in Chinese mainland was collected from the National Maternal and Child Health Surveillance System between 2000 and 2019. Maternal death was defined according to the World Health Organization’s criterion. The final underlying cause of death was confirmed by the national review and was coded according to International Classification of Diseases -10. Linear trends for changes in characteristics of maternal deaths were assessed using linear or logistic models with the year treated as a continuous variable. The MMR and 95% confidence intervals ( CI) for regions or causes were estimated by Poisson’s distribution. Joinpoint regression was used to assess the accurate temporal patterns. Results::The national MMR due to obstetric hemorrhage was 18.4 per 100,000 live births (95% CI: 15.0-22.2) in 2000. It peaked in 2001 (22.1 per 100,000 live births, 95% CI: 18.3-26.4) and was lowest in 2019 (1.6 per 100,000 live births, 95% CI: 1.0-2.3). For specific regions, the MMR due to obstetric hemorrhage in rural areas and western regions both experienced a slight rise, followed by a rapid decline, and then a slow decline. For specific causes, no change point was found in joinpoint analysis of the national MMR caused by placenta previa, postpartum uterine atony, and retained placenta (the annual percent change was -12.0%, -10.5%, and -21.0%, respectively). The MMR caused by postpartum hemorrhages (PPH) significantly declined by 8.0% (95% CI: 1.9-13.6) per year from 2000 to 2007. The annual percent change of MMR caused by PPH accelerated further to -25.0% between 2007 and 2011, and then decreased to -7.8% between 2011 and 2019. The proportion of maternal deaths due to antepartum hemorrhages increased from 7.6% (8/105) in 2000 to 14.3% (4/28) in 2019. The changes in the proportion of causes were different for maternal deaths due to PPH. The proportion of postpartum uterine atony increased from 39.0% (41/105) in 2000 to 60.7% (17/28) in 2019, and the proportion of uterine rupture also increased from 12.3% (13/105) in 2000 to 14.3% (4/28) in 2019. However, the proportion of retained placenta decreased from 37.1% (39/105) in 2000 to 7.1% (2/28) in 2019. Conclusion::Over the last 20 years, the intervention practice in China has proved that targeted interventions are beneficial in reducing the MMR due to obstetric hemorrhage. However, the MMR has reached a plateau and is likely to increase for some specific causes such as uterine rupture. China needs to develop more effective interventions to reduce maternal deaths due to obstetric hemorrhage, especially for postpartum uterine atony and uterine rupture.