[Purpose]To analyze the trends of brain tumor incidence and age of onset in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The incidence data of brain tumors from 2009 to 2019 were obtained from 16 national cancer registration areas of Jiangsu Province.The crude incidence rate,age-standardized incidence rate by Chinese standard popula-tion(ASIRC),average age of onset,standardized age-specific incidence rate,and annual average percentage change(AAPC)by sexes and regions were calculated.[Results]The incidence rate of brain tumor in Jiangsu Province from 2009 to 2019 showed an increasing trend(AAPC=4.12％,95％CI:3.31％～4.95％),and the increase in female(AAPC=5.79％,95％CI:4.44％～7.15％)was higher than that in male(AAPC=2.31％,95％CI:1.66％～2.97％);and the increase in urban areas(AAPC=4.84％,95％CI:3.52％～6.18％)was higher than that in rural areas(AAPC=3.04％,95％CI:2.12％～3.98％).The ASIRC also showed an increasing trend(AAPC=2.14％,95％CI:1.27％～3.02％).Birth cohort analysis showed that within the same age group,the incidence rate of brain tumors increased with increasing birth years.The average age of onset for crude incidence showed a delaying trend of 0.43 years old per year(t=7.09,P＜0.001);that for ASIRC was 0.20 years old per year(t=3.33,P=0.009).The proportion of patients in the age group of 60 years old and above increased from 35.79％in 2009 to 44.18％in 2019.[Conclusion]The incidence of brain tumor in cancer registration areas of Jiangsu Province showed an increasing trend from 2009 to 2019 with a delaying trend of average age of onset.

Objective:To investigate and assess the situation of popularization and promotion of domestically innovative medical devices in Liaoning Province,so as to provide a basis for promoting the allocation policy of domestically innovation medical devices.Methods:Self-made questionnaire and on-site filling survey were conducted to implement investigation and analysis for the allocation situation of newly medical equipment of 188 medical institutions in 9 demonstration regions of the Project on Regional Application and Demonstration of Innovative Medical Equipment in Liaoning Province from 2015 to 2020.The allocation data of medical equipment between before(from 2015 to 2017)and after the demonstration projects were implemented(from 2018 to 2020)were compared.The occupancy rate of domestically medical devices(referred as"occupancy ratio of domestic device")was used as an evaluation indicator to assess the status of equipment allocation and application before and after the projects of application and demonstration were implemented in the region of innovative equipment for diagnosis and treatment.Results:In the 9 demonstrational regions of Liaoning province,the number of newly added domestic medical devices during the period from 2018 to 2020 increased from 1,608 units between 2015 and 2017 to 1,703 units.The occupancy ratio of newly added domestic devices increased from 72.7%to 84.9%.The occupancy ratio of domestic devices of newly added key equipment increased from 63.0%to 83.4%,and the growth rate reached 20.4%.In different districts and different grades of medical institution,the increase and application of domestically medical devices appeared difference.Conclusion:The occupancy rate of newly added domestically medical devices in 9 demonstration regions in Liaoning province has generally increased.However,there are still imbalances between different regions and different grades of medical institutions.The manufacturers of domestically medical devices still need strengthen brand building and marketing promotion,so as to further enhance market competitiveness of domestically medical devices.

Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

Environmentally-induced reproductive toxicity is one of the important causes of fertility declines and has become a significant global public health challenge.Elucidating the causal links between exposure to environmental hazards and reproductive damage,unraveling the underlying molecular mechanisms,and establishing precise reproductive injury assessment systems are crucial for development of targeted interventions and safeguarding human reproductive health.In this article,we systematically review the research progress on reproductive toxicity caused by emerging environmental chemical pollutants,common physical factors,and biological factors in the recent 3 years.We summarize the new technologies in the field of toxicology,including novel experimental models,exposomics,and artificial intelligence.We also discuss the potential research directions in risk assessment,prevention and intervention of environmental factors-induced reproductive damage.

Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

Objective To investigate the transgenerational effects of paternal PM2.5 exposure on offspring growth and development,and to preliminarily elucidate the role of sperm DNA methylation modifications in mediating these effects.Methods Eight-week-old male C57BL/6 mice were randomly divided into filtered air(FA),unfiltered air(UA),and concentrated PM2.5(CAP)groups,with 10 animals in each group.The exposure was conducted from November 2019 to April 2020,and then,these male mice were mated with unexposed females to generate F1 offspring,which were bred successively to produce F2 and F3 generations.All the offspring were living in PM2.5-free environment.The birth body weight,birth number,and sex ratio of the offspring were recorded,body weight growth was monitored,and organ coefficients of the heart,liver,lung,and brain were calculated.Whole-genome methylation sequencing was performed on the sperm DNA of the CAP group,FA group,and their F1 generation offspring to screen for differentially methylated regions,and the genes and pathways associated with these regions were analyzed.Results When compared with the F1～F3 offspring of the FA group,the CAP group had significantly reduced birth body weight in the F1 generation(P<0.05),no statistical differences were observed in the birth body weight in the F2 and F3 generations(P>0.05),or either in the sex ratio and birth number among the F1,F2 and F3 generations.Compared with the FA group offspring,the F1～F3 offspring of CAP group exhibited delayed body weight gain,especially in the males(P<0.05),the CAP-F1 male generation had obviously elevated liver organ coefficient(P<0.01),but no statistical changes were observed in the heart,lung,or brain coefficients among the F1～F3 generations.Between the FA group and the CAP group,37 997 differentially methylated regions were detected,with a reduction of approximately 50%in the number of differentially methylated regions in the F1 generation.Differentially methylated genes in F0 and F1 sperm were potentially related to developmental processes,including imprinting genes(Gnas,Igf2)and metabolic genes(Ppard,Rps6kb1).Conclusion Paternal exposure to PM2.5 leads to reduced birth weight and intergenerational growth retardation in offspring.Its impact on phenotypic effects is gradually weakened during intergenerational transmission.Changes in the methylation of development-related genes in sperm may be one of the mechanisms mediating this intergenerational effect.

Objective To explore the biological functions and mechanisms of PIWI-interacting RNA(piRNA)in cervical cancer(CC).Methods RT-qPCR was used to detect the expression level of piRNA-2732 in CC tissue,CaSki cells and End1/E6E7 cells.EpiQuik m6A RNA methylation quantification kit was used to detect the methylation level of m6A RNA in CaSki cells.The expression levels of methyltransferases(METTL3,METTL14 and WTAP)and demethylases(FTO,ALKBH5)mRNA in CaSki cells were detected by RT-qPCR.After culturing CaSki cells to logarithmic growth stage,they were divided into six groups:piRNA-2732 mimic negative control group(mi-NC group),piRNA-2732 mimic group(mi-2732 group),piRNA-2732 inhibitor negative control group(in-NC group),piRNA-2732 inhibitor group(in-2732 group),piRNA-2732 mimic+METTL3 knockdown control group(mi-2732+si-NC group),and piRNA-2732 mimic+METTL3 knockdown group(mi-2732+si-METTL3 group).The viability of CaSki cells was detected by CCK8 assay.Colony formation assay was used to detect the proliferation ability of CaSki cells.Transwell experiment was used to detect the migration and invasion ability of CaSki cells.RT-qPCR and Western blot were used to detect the expression of methyltransferase like protein 3(METTL3).Transfected METTL3 wild-type(METTL3-WT)and METTL3 mutant(METTL3-MUT)in the mi-NC group,mi-2732 group,in-NC group,and in-2732 group respectively,and detected the effect of piRNA-2732 on METTL3 through dual luciferase reporter gene assay.Results Compared with the adjacent tissues,the expression of piRNA-2732(3.84±1.08 vs 1.32±0.53)was significantly higher in the cancer tissues of CC patients,and the difference was statistically significant(t=5.115,P<0.001).Compared with end1/E6E7 cells,the expression of piRNA-2732(1.00±0.13 vs 1.67±0.16)in CaSki cells was significantly higher,and the difference was statistically significant(t=5.632,P<0.01).Compared with mi-NC group,mi-2732 group promoted the viability,proliferation,migration and invasion of CaSki cells,and the differences were statistically significant(t=4.410～11.040,all P<0.01).Compared with mi-NC group,mi-2732 group increased m6A RNA methylation level and METTL3 mRNA and protein,the differences were statistically significant(t=6.176,9.211,12.550,all P<0.05).The results of dual luciferase reporter gene testing showed that compared with the mi-NC+METTL3-WT group,the relative luciferase activity of mi-2732+METTL3-WT group was significantly increased(t=11.850).Compared with mi-2732+METTL3-WT group,the relative luciferase activity of mi-2732+METTL3-MUT group was significantly lower(t=12.740),and the difference was statistically significant(all P<0.000 1).Compared with in NC+METTL3-WT group,the relative luciferase activity of in-2732+METTL3-WT group was significantly lower(t=7.828),compared with in-2732+METTL3-WT group,the relative luciferase activity of CaSki cells in in-2732+METTL3-MUT group was significantly increased(t=8.146),and the difference was statistically significant(all P<0.001).Compared with mi-2732+si-NC group,the expression level of m6A in mi-2732+si-METTL3 group was significantly lower,and the difference was statistically significant(t=7.630,P<0.01).Compared with mi-2732+si-NC group,the proliferation ability,colony number,cell migration and invasion ability of CaSki cells in mi-2732+si-METTL3 group were significantly decreased,and the differences were statistically significant(t=3.695～4.891,all P<0.001).Conclusion piRNA-2732 is overexpressed in CC tissues and cells,and piRNA-2732 promotes tumor development in CC through METTL3 mediated m6A methylation.

Objective:To evaluate the efficacy and safety of intrasaccular flow disruptor in wide-necked intracranial aneurysms.Methods:One hundred and seventeen patients with wide-necked intracranial aneurysms treated with intrasaccular flow disruptor were collected from Department of Neurointervention (First Affiliated Hospital of Zhengzhou University), Department of Neurosurgery (Beijing Tiantan Hospital, Capital Medical University), Department of Cerebrovascular Surgery, Neurosurgery Center (Zhujiang Hospital, Southern Medical University), and Department of Neurosurgery (First Affiliated Hospital of Harbin Medical University) from August 2022 to March 2024. Raymond-Roy Occlusion Classification (RROC) was employed to evaluate aneurysm embolization immediately after procedure; cranial CT or MRI within 48 hours of embolization were performed to identify any new intracranial hemorrhage, subarachnoid hemorrhage, or new symptomatic cerebral infarction related to the intracranial aneurysms. Modified Rankin Scale (mRS) was used to assess the neurological function at discharge. Imaging follow-up and outpatient follow-up were performed at 6 months after embolization to evaluate the aneurysm occlusion degree and complications.Results:A total of 117 intrasaccular flow disruptors were implanted in 117 patients, with a technical success rate of 100%; 115 patients (98.3%) enjoyed successful one-time release of their disruptors, and 2 patients (1.7%) required retrieval and redirection of the disruptors before second successful attempt. Flow disruptor plus stent was performed in 13 patients (11.1%). Immediately after procedure, RROC grading I was noted in 3 patients, grading II in 51 patients and grading III in 63 patients. Cranial CT or MRI within 48 hours of embolization indicated no new intracranial hemorrhage, subarachnoid hemorrhage, or symptomatic cerebral infarction related to the intracranial aneurysms. All patients had mRS score of 0 at discharge. Eighty-three patients completed a 6-month follow-up (RROC grading I in 41 patients, grading II in 33 patients and grading III in 9 patients), without ischemic or hemorrhagic adverse events.Conclusion:The results of this study preliminarily suggest that intrasaccular flow disruptor is effective and safe in wide-necked intracranial aneurysms.