1.Therapeutic effects of adipose-derived mesenchymal stem cells and their exosomes on dexamethasone-induced sarcopenia in mice
Weiyuan YUAN ; Qinhui LEI ; Xiuqi LI ; Tiezhu LU ; Ziwen FU ; Zhili LIANG ; Shaoyang JI ; Yijia LI ; Yu REN
Chinese Journal of Tissue Engineering Research 2026;30(1):58-67
BACKGROUND:Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass,strength,and/or physical function.Currently,effective treatments for sarcopenia remain limited.A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.OBJECTIVE:To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice.METHODS:Mesenchymal stem cells were isolated and cultured from canine adipose tissue,and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis,adipogenesis,and chondrogenesis.Subsequently,exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy,western blot assay,and nanocoulter tracking analysis.In vitro,the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models.In vivo,a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells.Therapeutic efficacy was assessed through mouse rotarod performance,histopathological analysis,and muscle atrophy-related genes testing.RESULTS AND CONCLUSION:(1)The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73,CD90,and CD105,and lowly expressed MHC-Ⅱ,CD14,CD19,CD34,and CD45,and successfully differentiated into osteoblasts,adipocytes,and chondrocytes in vitro.(2)The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size,electron microscopy morphology,and positive expression of specific markers.(3)Compared to the dexamethasone-induced C2C12 atrophy group,treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes,inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1.(4)Compared to the aging C2C12 group,adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells.(5)Compared to the control group,the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased(P<0.01).After 7 days(P<0.01,P<0.01)and 10 days(P<0.01,P<0.05)of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection,rotarod time was significantly increased,respectively.After 14 days,all treatment groups showed longer rotarod times than the model group,although with no significant differences between them.(6)Compared to the control group,the cross-sectional area of anterior tibial muscle in the model group was significantly reduced(P<0.01),and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells(P<0.05,P<0.01).(7)Compared to the model group,intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes(P<0.01,P<0.01,P<0.01,P<0.01).The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes,and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice.
2.Therapeutic effects of adipose-derived mesenchymal stem cells and their exosomes on dexamethasone-induced sarcopenia in mice
Weiyuan YUAN ; Qinhui LEI ; Xiuqi LI ; Tiezhu LU ; Ziwen FU ; Zhili LIANG ; Shaoyang JI ; Yijia LI ; Yu REN
Chinese Journal of Tissue Engineering Research 2026;30(1):58-67
BACKGROUND:Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass,strength,and/or physical function.Currently,effective treatments for sarcopenia remain limited.A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.OBJECTIVE:To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice.METHODS:Mesenchymal stem cells were isolated and cultured from canine adipose tissue,and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis,adipogenesis,and chondrogenesis.Subsequently,exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy,western blot assay,and nanocoulter tracking analysis.In vitro,the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models.In vivo,a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells.Therapeutic efficacy was assessed through mouse rotarod performance,histopathological analysis,and muscle atrophy-related genes testing.RESULTS AND CONCLUSION:(1)The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73,CD90,and CD105,and lowly expressed MHC-Ⅱ,CD14,CD19,CD34,and CD45,and successfully differentiated into osteoblasts,adipocytes,and chondrocytes in vitro.(2)The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size,electron microscopy morphology,and positive expression of specific markers.(3)Compared to the dexamethasone-induced C2C12 atrophy group,treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes,inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1.(4)Compared to the aging C2C12 group,adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells.(5)Compared to the control group,the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased(P<0.01).After 7 days(P<0.01,P<0.01)and 10 days(P<0.01,P<0.05)of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection,rotarod time was significantly increased,respectively.After 14 days,all treatment groups showed longer rotarod times than the model group,although with no significant differences between them.(6)Compared to the control group,the cross-sectional area of anterior tibial muscle in the model group was significantly reduced(P<0.01),and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells(P<0.05,P<0.01).(7)Compared to the model group,intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes(P<0.01,P<0.01,P<0.01,P<0.01).The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes,and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice.
3.Cage design-centric glider approach to full-endoscopic lumbar fusion: optimizing nerve root protection in facet-sparing and facet-resecting techniques
Yu-Chia HSU ; Hao-Chun CHUANG ; Yuan-Fu LIU ; Chao-Jui CHANG ; Yu-Meng HSIAO ; Yi-Hung HUANG ; Keng-Chang LIU ; Chien-Min CHEN ; Hyeun-Sung KIM ; Cheng-Li LIN
Asian Spine Journal 2026;20(2):343-353
Endoscopic transforaminal lumbar interbody fusion (TLIF) offers substantial advantages in the management of degenerative spinal diseases, including accelerated postoperative recovery. However, its technical complexity and steep learning curve pose risks for nerve root injury. Optimizing nerve root protection in full-endoscopic facet-sparing TLIF (FE fs-TLIF) and full-endoscopic facet-resecting TLIF (FE fr-TLIF) is essential for enhancing surgical safety. This study aimed to improve the nerve root protection in FE fs-TLIF and FE fr-TLIF by optimizing cage glider selection and insertion techniques based on the specific cage shape—banana-shaped or bullet-shaped. The goal was to ensure safe cage positioning and mitigate nerve root injury during discectomy, endplate preparation, and cage insertion. These strategies were validated through cadaveric simulations and clinical implementation. In FE fr-TLIF utilizing bullet-shaped (straight) cages, one-tip and two-tip cage gliders effectively protected the traversing nerve root by facilitating medial cage entry, thereby minimizing irritation of the exiting nerve root. Conversely, in FE fr-TLIF with banana-shaped cages, the lateral tilt of the cage holder during implantation required the use of a two-tip cage glider to protect the traversing and exiting nerve roots, thereby mitigating the potential risk of nerve irritation. In FE fs-TLIF, a one-tip cage glider is preferred for safeguarding the exiting nerve root, while the traversing root is inherently protected by the medial wall of the facet joint. The use of a two-tip cage glider in FE fs-TLIF can cause injury to the nerve root during glider insertion. In addition to the selection of cage gliders, improper cage insertion steps can also contribute to postoperative neurapraxia. The appropriate selection of cage gliders with corresponding insertion techniques is critical for nerve root protection in endoscopic TLIF. Tailoring these choices to the specific approach (FE fs-TLIF or FE fr-TLIF) and cage type (banana or bullet) enhances surgical safety and clinical outcomes.
4.Aerobic Exercise and MOTS-c Ameliorate Hepatic Oxidative Stress and Metabolic Disorder in Type 2 Diabetes via The NRF2/PPARγ Axis
Fei-Long CHEN ; Zhi-Yu LI ; Tu-Tu WANG ; Yu FU ; Lei LÜ ; Cheng-Yuan XING ; Shun-Chang LI
Progress in Biochemistry and Biophysics 2026;53(8):2071-2090
ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.
5.Differentiation and Treatment of Coronary Heart Disease from the Perspective of "Guarding the Channel Passages" Based on Circadian Rhythm
Jingjing ZHAO ; Yuanyuan CHEN ; Lanlan LI ; Xiaoqing ZHANG ; Ran ZHAO ; Shujuan XU ; Han PENG ; Lingmei LI ; Hao GUO ; Jianhua FU
Journal of Traditional Chinese Medicine 2026;67(18):1977-1981
Coronary heart disease (CHD) has a distinct circadian rhythmicity in its onset, which is closely related to the waxing and waning of qi and blood in the channel passages of the human body. Grounded in the circadian rhythm theory of "correspondence between heaven and humankind", this paper explores the pathogenic evolution rules of qi-blood disharmony, channel obstruction, interacting as cause and effect with circadian rhythm disorders in CHD. Clinically, CHD can be observed to attack in the early morning, at night, in the afternoon, and at fixed or unfixed circadian intervals. The pathogenesis rhythms at different time nodes can correspondingly reflect the susceptibility tendencies and pathological stress responses of the human body to core pathogeneses such as yang deficiency with cold congelation, yin deficiency with yang floating, qi and yin deficiency, and liver constraint with qi stagnation under specific temporal states. Treatment should be adapted to the season and time, regulating yin and yang in accordance with biological rhythms. It is recommended to regulate qi during the daytime by promoting ascending and dispersing to unblock the channel passages, and select the appropriate timing for administration to harness natural timing. At the Mao (卯) hour, yang ascends while yin descends, and taking medication at this time conforms to the ascending of yang qi. At the Wu (午) hour, the heart meridian is active, and taking medication at this time warms the channel passages and assists heart yang, which can be treated with modified Buzhong Yiqi Decoction (补中益气汤) or Shengyang Yiwei Decoction (升阳益胃汤). At night, blood should be harmonized, when the channel passages are unblocked through nourishing, restraining, and searching, with Lianmei Decoction (连梅汤) combined with Dahuang Zhechong Pill (大黄䗪虫丸). Following the temporal rhythm, the focus is put on the transitional time of day and night and the four seasons to treat disease before it arises, resonating and corresponding with the natural rhythm.
6.Transthoracic Echocardiography-guided Double Cavity Permanent Pacemaker Implantation in Pregnant Women:Two Cases Report
Huayuan YUAN ; Mingpeng FU ; Yulong GUO ; Jian LI ; Zhiling LUO ; Yu QIAO ; Guodong NIU ; Tao GUO
Chinese Circulation Journal 2025;40(9):922-925
X-ray is usually used to determine anatomy and localization during conventional permanent pacemaker implantation.But X-ray exposure might induce radiation injury to fetus.In this paper,we reported 2 cases successful double cavity permanent pacemaker implantation in pregnant women woman at 13 weeks of gestation under the guidance of transthoracic echocardiography.The postoperative pacing parameters were good,the whole process was finished with zero radiation,and there were complications during pregnancy.Both cases resulted in full-term pregnancies and the natural delivery of healthy newborns.Pacemaker electrodes were in normal position as confirmed by post-delivery X-ray examinations.
7.Expert consensus on clinical treatment of acute radiation syndrome from external irradiation
Li LIANG ; Long YUAN ; Changlin YU ; Qingjie LIU ; Yulong LIU ; Wenfeng YANG ; Jin WANG ; Weixu HUANG ; Ying LIU ; Cuiping LEI ; Huifang CHEN ; Ximing FU ; Baoshan CAO ; Mopei WANG ; Zhaohui ZHANG ; Yu XIAO ; Yamei CHEN ; Quanfu SUN
Chinese Journal of Radiological Medicine and Protection 2025;45(9):827-839
China emerges as a major country in nuclear energy development and the application of nuclear and radiologic technology. The diagnosis and treatment of acute radiation syndrom (ARS) caused by external irradiation represent a core function in the country′s medical rescue of nuclear and radiological emergencies. Clinically, ARS manifests hematopoietic, gastrointestinal, cutaneous, and central nervous system syndromes, with specific clinical manifestations, signs, severity, and prognosis strongly correlated with radiation dose. China has established a number of national and provincial centers for treating radiation-induced damage. Nevertheless, most medical staff have limited experience in ARS treatment. This consensus presents a summary of recent experience in treating ARS of China. In combination with recommendations from international organizations such as the World Health Organization (WHO), this consensus proposes key evidence of critical clinical issues of ARS, covering all links in the rescue of external irradiation-induced ARS. Initially, clinical diagnosis, syndromes, and severe degrees should be determined based on clinical symptoms and dose estimates. It is necessary to normalize clinical treatment measures for hematopoietic recovery, gastrointestinal injury treatment, infection control, symptomatic treatment, and multi-organ function preservation. To this end, this consensus offers cautions. This consensus provides principles of treatment with traditional Chinese medicine, psychological intervention, and follow-up. Additionally, it highlights multidisciplinary collaboration. It is recommended that this consensus be applied in relevant treatment centers.
8.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
9.Improved YOLOv8 algorithm-based detection of pulmonary nodules in CT images
Chinese Medical Equipment Journal 2025;46(8):1-10
Objective To propose an improved YOLOv8 algorithm based on polarized self-attention(PSA)and deformable attention(DAT)so as to enhance the detection of pulmonary nodules in CT images.Methods A basic framework was established with a YOLOv8 model consisting of a backbone network(Backbone),a neck module(Neck)and a head module(Head).PSA was introduced into the end of the spatial pyramid pooling-fast(SPPF)of Backbone to construct a YOLOv8-PSA algorithm,and DAT was involved in the medium-scale feature layer P4 in Head to form a YOLOv8-DAT algorithm.The YOLOv8-PSA and YOLOv8-DAT algorithms were trained and validated using the CT image dataset of pulmonary nodules from public platforms,and compared with the original YOLOv8 algorithm for the detection of pulmonary nodule lesions in CT images.Results When used for pulmonary module detection of CT images,the YOLOv8-DAT algorithm had the mean average precision(mAP)in case of intersection over union threshold of 0.5(mAP50),mAP in case of intersection over union threshold of 0.5 to 0.95(mAP50-95)and precision ratio being 0.918,0.588 and 0.960 respectively,which gained advantages over the YOLOv8-PSA algorithm with mAP50,mAP50-95 and precision ratio being 0.914,0.583 and 0.945 respectively,and over the original YOLOv8 algorithm with mAP50,mAP50-95 and precision ratio being 0.911,0.564 and 0.952 respectively.Conclusion The YOLOv8-DAT algorithm detects pulmonary modules in CT images effectively,and facilitates early screening and diagnosis of pulmonary modules clinically.[Chinese Medical Equipment Journal,2025,46(8):1-10]
10.Trend Analysis and Future Forecast of Thyroid Cancer Incidence by Sex in China from 1990 to 2021
Xiangrui FU ; Wen LI ; Yurong LIU ; Xuan ZHANG ; Wenli LU ; Yuan WANG
China Cancer 2025;34(10):804-812
[Purpose]To analyze the changes in the incidence trend of thyroid cancer from 1990 to 2021,and to predict the future incidence from 2022 to 2030.[Methods]We collected data related to the incidence of thyroid cancer among Chinese residents from 1990 to 2021 in the Global Bur-den of Disease 2021(GBD 2021)study,analyzed the trend of thyroid cancer incidence using the Joinpoint regression model,and constructed a Bayesian age-period-cohort(BAPC)model to pre-dict the future incidence of thyroid cancer during the years of 2022-2030,based on the inci-dence data during the years of 1990-2021.[Results]From 1990 to 2021,the age-standardized incidence rate(ASIR)of thyroid cancer in China showed a fluctuating upward trend,and the ASIR of thyroid cancer in China in 2021 was 2.47/105,slightly lower than the global average(2.91/105)in the same year.In 2021,there were significant differences in new cases and incidence rate of thyroid cancer between men and women,with the incidence rate of women being higher than that of men.Among them,the number of new cases in women was 27 915,the crude incidence rate was 4.02/105,and the ASIR was 2.87/105;in men,the number of new cases was 20 189,the crude incidence rate was 2.77/105,and the ASIR was 2.11/105.Between 1990 and 2021,the increase in the number of new cases,the crude incidence rate,and the ASIR of men in China was much larger than that of women.The ASIR of thyroid cancer in both male and female showed an in-creasing trend,while the average annual percentage change(AAPC)in female was lower than that in male.There were significant gender differences in the age-specific incidence rates of thyroid cancer.In 2021,the incidence rate of women was higher than that of men in the Chinese population<75 years old,whereas the incidence rate of men was higher than that of women in the population≥75 years old.From 1990 to 2021,the incidence rates of the Chinese male population aged 45~59 years old and ≥75 years old increased significantly;and the incidence rate of the Chinese fe-male popu-lation aged 50~74 years old increased significantly.Projections showed that the ASIR of overall,male and female standardized incidence rates in 2030 increased to 2.90/105,2.44/105 and 3.26/105 respectively.[Conclusion]The incidence rate of thyroid cancer in China is on the rise,with the incidence rate of women being higher than that of men,but the incidence rate of men has increased more than that of women,and the gap between the incidence rates is narrow-ing,and the peak age of incidence of men is mostly in the senior age group.

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