1.Oncocytic mucoepidermoid carcinoma of the parotid gland: a clinicopathological report of two cases and literature review
ZHENG Fang ; NIE Mengdong ; QIANG Jinbiao ; JIN Ronghao ; WANG Dandan ; SHI Ce
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(6):576-584
Objective:
To investigate the clinicopathological characteristics and diagnostic-therapeutic strategies of oncocytic mucoepidermoid carcinoma (OMEC) of the parotid gland, and to enhance awareness of this rare variant among clinicians and pathologists.
Methods:
The clinical data, imaging findings, histopathological features, immunophenotype, and molecular characteristics of two patients with parotid OMEC were retrospectively analyzed, and the relevant literature was reviewed.
Results:
Case 1 was a 50-year-old man who presented with a painless mass behind the right earlobe for more than 2 years. The patient underwent extended parotidectomy with preservation of the facial nerve. Histopathological examination revealed that the tumor was predominantly composed of oncocytic cells with a small proportion of mucous cells. Immunohistochemically, the tumor cells were partially positive for cytokeratin 5/6, cytokeratin 7, and P63. Special staining with alcian blue, periodic acid-Schiff, and phosphotungstic acid hematoxylin yielded positive results. The diagnosis of right parotid OMEC was established. No recurrence or metastasis was observed during a 1 year follow-up. Case 2 was a 61-year-old man with a 3-month history of a mass beneath the left ear. After partial parotidectomy at an outside institution, pathological consultation at the Stomatological Hospital of Jilin University demonstrated that the tumor consisted almost entirely of oncocytic cells, exhibited infiltrative growth, and lacked typical mucous, epidermoid, and intermediate cells. Fluorescence in situ hybridization confirmed positive mastermind-like transcriptional activator 2 (MAML2) gene rearrangement, establishing the diagnosis of left parotid OMEC. The patient subsequently underwent total parotidectomy with preservation of the facial nerve, and no recurrence was detected during a short-term 3 months follow-up. A review of the literature indicated that OMEC most commonly arises in the parotid gland and is generally a low-grade malignancy with favorable prognosis. When tumors are composed exclusively of oncocytic cells, exhibit minimal cytological atypia, and lack the classical cellular components of mucoepidermoid carcinoma, they are highly prone to misdiagnosis as oncocytoma, nodular oncocytic hyperplasia, or other benign oncocytic lesions. Accurate differential diagnosis relies on recognition of infiltrative growth patterns, supportive immunophenotypic markers (e.g., P63 positivity), and detection of characteristic MAML2 gene rearrangement. Complete surgical excision remains the treatment of choice. Conclusion OMEC dominated by oncocytic cells carries a high risk of clinical misdiagnosis. Integrating the assessment
Conclusion
OMEC dominated by oncocytic cells carries a high risk of clinical misdiagnosis. Integrating the assessment of infiltrative histopathological features with immunohistochemistry and molecular detection of MAML2 rearrangement is crucial for accurate diagnosis, appropriate assessment of tumor behavior, and optimal surgical decision making.
2.Current Status and Prospective of Research on Disease-Syndrome Integrated Animal Models of Spleen and Stomach Diseases in Traditional Chinese Medicine
Jiaqi ZHANG ; Lihui FANG ; Yongtian WEN ; Shan LIU ; Zhuo SHI ; Xintong WANG ; Xinyi DAI ; Meiling SHE ; Lanshuo HU ; Yangxi FU ; Zheng WANG ; Fengyun WANG ; Xudong TANG
Journal of Traditional Chinese Medicine 2026;67(5):510-516
Animal model research on spleen and stomach diseases in traditional Chinese medicine (TCM) is of great significance for elucidating the nature of diseases and syndromes and for revealing the mechanisms of action of Chinese herbal medicinals. At present, studies on classical TCM syndrome models of spleen and stomach diseases mainly focus on spleen deficiency syndrome, liver constraint syndrome, and damp-heat syndrome. Model construction is mostly based on the etiological and pathophysiological characteristics of syndrome, and model evaluation primarily involves macroscopic manifestations and physicochemical indicators. This paper summarizes the current research status of animal models integrating disease and syndrome for seven common spleen and stomach diseases, including chronic gastritis and gastric precancerous lesions, gastroesophageal reflux disease, functional dyspepsia, inflammatory bowel disease, irritable bowel syndrome, functional constipation, and functional diarrhea. The modeling methods and characteristics of disease-syndrome combined animal models for each disease are analyzed. It is proposed that future research on disease-syndrome integration in spleen and stomach diseases should move toward syste-matic, precise, and integrative development, and that interdisciplinary and cross-disciplinary research approaches should be adopted to enhance the predictive value and application efficiency of disease-syndrome combined animal models.
3.The Role and Regulatory Mechanisms of FOXO1 in Hepatic Lipid Deposition
Meng JIA ; Fang-Hui LI ; Shi-Zhan YAN ; Ai-Ju LI ; Yi-Le WANG ; Pin-Shi NI ; Jia-Han HE ; Yin-Lu LI
Progress in Biochemistry and Biophysics 2026;53(4):905-919
Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.
4.MRI parameters of carotid artery plaque combined with low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio for predicting ischemic stroke in young adults
Chaoyan LIU ; Xinjing SHI ; Fang CHAI ; Xinying WANG ; Zhilei KANG ; Bing LIU
Chinese Journal of Interventional Imaging and Therapy 2025;22(8):507-511
Objective To explore the predictive value of MRI parameters of carotid artery plaque combined with low density lipoprotein cholesterol/high density lipoprotein cholesterol(LDL-C/HDL-C)ratio for predicting ischemic stroke in young patients with carotid atherosclerosis.Methods Totally 125 young patients with carotid atherosclerosis were prospectively included and divided into stroke group and non-stroke group based on whether ischemic stroke occurred within 3 months.Clinical data,laboratory indicators and carotid plaque-related MRI parameters were compared between groups.Based on carotid plaque-related MRI parameters being statistically different between groups,combined model 1 was constructed using multivariable logistic regression analysis,while combined model 2 was constructed combined with LDL-C/HDL-C ratio.The efficacy of each parameter and model for predicting ischemic stroke in young adults was analyzed.Results There were 48 cases in stroke group and 77 cases in non-stroke group.The levels of glycosylated hemoglobin,LDL-C,LDL-C/HDL-C ratio,carotid artery stenosis rate,plaque eccentricity index and plaque enhancement rate in stroke group were all higher than those in non-stroke group(all P<0.05).The area under the curve(AUC)of LDL-C/HDL-C ratio,carotid artery stenosis rate,plaque eccentricity index,plaque enhancement rate,combined model 1 and 2 for predicting ischemic stroke in young adults was 0.816,0.757,0.768,0.805,0.883 and 0.936,respectively,of combined model 1 was higher than those of single parameter(all P<0.05),while of combined model 2 was higher than that of combined model 1(Z=2.336,P=0.020).Conclusion MRI parameters of carotid artery plaque combined with LDL-C/HDL-C ratio could effectively predict ischemic stroke in young patients with carotid atherosclerosis.
5.The significance of preoperative neck enhanced multidetector computed tomography in predicting the recurrent veins and classifying their courses of the submental flap reflux vein for repair in pharyngeal cancer
Qian SHI ; Jugao FANG ; Qi ZHONG ; Lizhen HOU ; Hongzhi MA ; Ling FENG ; Shizhi HE ; Meng LIAN ; Yanming ZHAO ; Ru WANG ; Yunxia LI ; Xixi SHEN ; Yifan YANG ; Lingwa WANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1208-1214
Objective:To evaluate preoperative high-resolution thin-layer cervical enhanced CT used to predict the venous route of the submental flap reflux vein and its relationship with adjacent structures in order to guide the anatomical understanding and protection of submental flap in pharyngeal cancer surgery.Methods:Sixty consecutive patients with pharyngeal cancer who underwent submental flap repair surgery in our department from March 2022 to December 2024, as well as 60 patients who were accepted neck dissection suffering other cancers, were selected. Before surgery, high-resolution cervical enhanced CT scans were performed, and the position of the transverse section of the facial vein in the venous phase horizontal image gradually variation tendency was focused layer by layer. The direction and adjacent relationship of the submental flap reflux veins were determined and recorded. Combined with 60 patients with other head and neck tumors who underwent neck dissection in our department during the same period (a total of 120 cases, 240 sides), the classification and management of the draining veins of Fang′s mental flap were conducted. Type Ⅰ mainly drains into the internal jugular vein; Type Ⅱ mainly drains into the external jugular vein and Type Ⅲ mainly drains into the anterior jugular vein (often accompanied by an external jugular draining branch). The status and proportion of venous drainage were analyzed.Results:Vascular predictive coincidence rate was 98.3% (59/60) among the 60 patients with pharyngeal cancer. Only one patient was predicted to have a simple return to the external jugular vein. However, during the operation, in addition to the main return to the external jugular vein, a small portion also returned to the internal jugular vein. Submental flap reflux vessels were classified into three types based on intraoperative submental flap venous return in 60 cases of laryngopharyngeal cancer, in conjunction with the analysis of venous return patterns from 240 cervical CT scans. Type Ⅰ mainly refluxed to the internal jugular vein, accounting for 42.1%. Type Ⅱ mainly refluxed to the external jugular vein (47.9%). Type Ⅲ mainly refluxed to the anterior jugular vein (10.0%). The total detection rate of CT reading of 240 venous reflux was 98.7% (237/240). Vascular predictive coincidence rate was 97.9%(235/240).Conclusion:The detailed analysis of submental venous return vessels can accurately predict the direction of reflux veins and its surrounding areas by preoperative high-resolution enhanced CT scan. This provides reliable guidance for the anatomy and protection of the submental flap reflux veins during surgery.
6.Efficacy comparison of subsequent treatment modalities for locally advanced hypopharyngeal cancer with partial response to neoadjuvant chemotherapy
Ru WANG ; Zheng LI ; Jugao FANG ; Junfang XIAN ; Qi ZHONG ; Yang ZHANG ; Lizhen HOU ; Hongzhi MA ; Ling FENG ; Shizhi HE ; Qian SHI ; Yifan YANG ; Haiyang LI ; Lingwa WANG ; Xinyu LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1223-1231
Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.
7.Constructing a risk factor model for intracranial artery stenosis in young patients with acute ischemic stroke based on HR-VWI features
Zhilei KANG ; Xinjing SHI ; Fang CHAI ; Chaoyan LIU ; Xinying WANG
Journal of China Medical University 2025;54(9):808-813,820
Objective To establish a risk factor model for intracranial artery stenosis in young patients with acute ischemic stroke(AIS)based on high-resolution magnetic resonance vascular wall imaging(HR-VWI).Methods Young patients with AIS(n=290)treated at Hengshui People's Hospital between January 2021 and January 2023 were retrospectively analyzed and randomly divided into a modeling set(203 cases)and a validation set(n=87)at a ratio of 7∶3.Patients in the modeling set were divided into the stenosis and non-ste-nosis groups according to whether they had intracranial artery stenosis.Multivariate logistic regression was used to analyze the clinical data and HR-VWI characteristics of the patients in the modeling set to screen for factors influencing intracranial artery stenosis in young patients with AIS.R software was used to construct and verify the risk factor model.Results Among the 290 patients,88 had intracranial artery stenosis(30.34%).The proportions of low-density lipoprotein cholesterol(LDL-C),plaque load,smoking history,hypertension,and eccentric plaques were higher in the stenosis group than in the non-stenosis group(P<0.05),and the minimum lumen area and remode-ling index were lower in the stenosis group than in the non-stenosis group(P<0.05).Multivariate logistic regression analysis showed that smoking history,hypertension,LDL-C level,plaque load,plaque morphology,and remodeling index were all factors influencing intracra-nial artery stenosis in young patients with AIS(P<0.05).Based on the above risk factors,R was used to build a nomogram early warning model.The ROC results showed that the AUC of the nomogram model for predicting intracranial artery stenosis in the modelling and vali-dation sets were 0.872(95%CI:0.815-0.902)and 0.850(95%CI:0.789-0.891),respectively.The Hosmer-Lemeshow test results of the modeling and validation sets were x2=0.589,P=0.571 and x2=0.602,P=0.558,respectively.The calibration curves of the two groups were consistent with the standard curves.Conclusion The risk factor model for intracranial artery stenosis in young patients built in this study based on HR-VWI features exhibits good predictive efficacy,providing a new method for clinical prevention and treatment.
8.circHERC4_041 Inhibits the Fibrotic Phenotype of Cardiac Fibroblasts by Encoding Protein
Yuan GAO ; Chuan-Meng ZHOU ; Hua-Yan WU ; Ya WANG ; Ru-Shi WU ; Pei-Ying GUAN ; Jun-Tao FANG ; Jin-Dong XU ; Yu-Peng LIU ; Zhi-Qin HU ; Zhi-Xin SHAN
Chinese Journal of Biochemistry and Molecular Biology 2025;41(3):393-403
A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P<0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P<0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.
9.Molecular mechanisms and prospects for disease treatment of ciliogenesis and autophagy
Hao-liang HU ; Jin WANG ; Jia-yan LIU ; Shi-fang HUANG ; Yu-ting LI ; Zhe CHEN ; Lin-xi CHEN
Chinese Pharmacological Bulletin 2025;41(4):631-637
Cilia,as cellular sensory organelles,actively partici-pate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mecha-nism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activa-ting cellular autophagy and how autophagy regulates cilia genera-tion and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely asso-ciated with the clinical manifestations and pathogenesis of vari-ous ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small mole-cule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundw-ork for developing highly specific targeted small molecule inhibi-tors of ciliogenesis and for the treatment of ciliopathies and canc-ers.By systematically discussing ciliogenesis,autophagy,disea-ses and drugs,this review offers new insights for further elucida-ting the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and de-veloping therapeutic strategies in the future.
10.Application of percutaneous coronary intraluminal shock wave balloon catheter angioplasty in calcified coronary nodules
Hao JIANG ; Zhi WANG ; Zhen-tao SHI ; Min SUN ; Shi-jie FANG ; Qiang TANG
Chinese Journal of Interventional Cardiology 2025;33(5):260-265
Objective To evaluate the effect of Intravascular lithotripsy(IVL)in the treatment of calcified nodules,and to observe the presence of coronary dissection after IVL treatment.Methods A total of 106 patients with coronary atherosclerotic heart disease(coronary heart disease)admitted to the cardiovascular Department of Shougang Hospital,Peking University from March 2023 to July 2024 were retrospectively analyzed.A total of 106 patients with moderate to severe stenosis accompanied by calcification as detected by coronary angiography were treated with IVL after intravascular ultrasound(IVUS)examination.Patients were divided into two groups according to whether there were calcified nodules in the coronary lesions:39 cases in the calcified nodules group and 67 cases in the non-calcified nodules group.The occurrence of coronary dissection during surgery was observed between the two groups,and other perioperative related complications and major adverse cardiovascular events(MACE)within 1 month after percutaneous coronary intervention(PCI)were compared between the two groups.Results The levels of renal insufficiency(25.6%vs.9.0%,P=0.021)and creatinine[(119.71±134.75)μmol/L vs.(71.82±16.53)μmol/L,P=0.033]in the calcified nodule group were higher than those in the non-calcified nodule group,the difference was statistically significant,and there was no difference in other baseline data.The target vessels in the calcified nodule group were mainly left anterior descending branch and right coronary artery,while those in the non-calcified nodule group were mainly left anterior descending branch,with few circumflex branches in both groups,and there was statistical significance in the distribution of target vessels in the left anterior descending branch and right coronary artery between the two groups(P=0.020).In terms of eccentric calcification(P=0.048)and asymmetric calcification(48.7%vs.28.4%,P=0.035)between the two groups,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P<0.05).In terms of whether more than 20 pulses were needed and whether there was slippage during IVL,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P=0.022).The success rate of interventional therapy was 100%in both groups.After IVL treatment,the calcified nodule group was higher than the non-calcified nodule group in terms of the occurrence of coronary artery dissection,the difference was statistically significant(P<0.009).The MACE of the two groups within 1 month after PCI was slightly higher in the calcified nodule group than in the non-calcified nodule group,but the difference was not statistically significant(P=0.235).Conclusions IVL is feasible and effective for the treatment of calcified coronary nodules.However,in the course of treatment,the occurrence of coronary dissection should be vigilant,identified as early as possible,and treated in time.


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