1.Variability of remnant cholesterol inflammation index exhibits a dose-response relationship with stroke risk:Evidence from the Chinese Kailuan cohort
Liuliu CAO ; Man LI ; Zhaohui WU ; Maolin ZHAO ; Baohua WANG ; Li ZHANG ; Peng LI ; Yongna YANG ; Weiguo ZHENG ; Haiyan ZHAO ; Shuohua CHEN ; Shouling WU ; Lixia SUN
Journal of Army Medical University 2025;47(22):2847-2857
Objective To investigate the association between the variability of remnant cholesterol inflammatory index(RCII),a novel composite biomarker,and the risk of stroke,in order to provide a theoretical basis for stroke prevention.Methods A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006,2008,and 2010.These subjects were grouped based on the quartiles of RCII variability,which was represented by standard deviation(SD)and average real variability(ARV),and were followed up every 2 years,with the occurrence of stroke(including ischemic and hemorrhagic strokes),death,or the end of follow-up on December 31,2022 as the endpoints.Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups,and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group.Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.Results Among the 38 659 participants,a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years.After adjusting confounding factors,when the participants were grouped by the quartiles of RCII-SD,the hazard ratio(HR)for stroke was 1.034(95%CI:0.917~1.167,P=0.584),1.146(95%CI:1.018~1.290,P=0.025),and 1.209(95%CI:1.066~1.370,P=0.003),respectively in the Q2,Q3,and Q4 groups,when compared with the Q1 group(Ptrend<0.05).When they were grouped by the quartiles of RCII-ARV,the HR for stroke was 1.008(95%CI:0.894~1.136,P=0.901),1.109(95%CI:0.986~1.248,P=0.085),and 1.152(95%CI:1.018~1.303,P=0.025),respectively,in the Q2,Q3,and Q4 groups,when compared with the Q1 group.Furthermore,both sensitivity and stratified analyses yielded similar results.Conclusion RCII variability is significantly associated with stroke,and the risk of stroke is gradually increasing with increment of the variability.Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism,strengthening lifestyle interventions,and standardizing dietary,exercise,and weight management in order to suppress the index fluctuations.The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.
2.A comparative study of ultra-high-resolution CT and multi-slice spiral CT showing the key sound transmission structures of the middle ear
Yufei SUN ; Ruowei TANG ; Heyu DING ; Ning XU ; Zhaohui ZHONG ; Zhenghan YANG ; Zhenchang WANG ; Pengfei ZHAO
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(4):225-228,233
OBJECTIVE To compare the ability of ultra-high-resolution CT(U-HRCT)and multi-slice spiral CT(MSCT)to display key vocal transmission structures in the middle ear.METHODS Subjects with normal middle ear structures who underwent 0.1 mm layer thickness U-HRCT and 0.625 mm layer thickness MSCT scans at the same time in Beijing Friendship Hospital affiliated to Capital Medical University from December 2019 to August 2024 were retrospectively enrolled.Two experienced head and neck radiologists reconstruct standard transsectional,coronal images based on the thinnest layer thickness.According to the 5-point method,16 key sound transmission structures of the middle ear,including malleus,incus and stapes,as well as joints,ligaments and tendons,were evaluated for image quality scoring.The standard deviation(SD)value,signal noise ratio(SNR),and contrast noise ratio(CNR)of bone in the malleus region and intratympanic gas were measured and calculated on the two examination images.RESULTS Thirty patients(47 sides)with normal middle ear structure were included,including 18 males and 12 females.The two physicians compared the results of U-HRCT in showing malleus head,malleus neck,malleus handle,incus body,long process,and short process,5 points accounted for 100%,and the 5-point scores of incudomalleolar joint space,incudostapedial joint space,stapes footplate and annular ligament were 100%,98.29%,75.83%and 77.83%,respectively,which were significantly higher than those of MSCT(P<0.001).In addition,U-HRCT showed higher scores for lenticular process,stapes head,anterior arch of stapes,posterior arch of stapes,annular ligament,stapes muscle,and tendo musculi tensoris tympani than MSCT(P<0.001),and the lenticular process showed a 100%display rate.There was no significant difference in the SNR between the two groups(P>0.05),but the SD value of the malleus in U-HRCT was 161.6±36.4,which was significantly lower than that in MSCT(297.8±128.1),and the difference was statistically significant(P<0.001).CONCLUSION U-HRCT can clearly visualize the key sound transmission structures of the middle ear,and its visualization ability is significantly better than that of MSCT.
3.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.
4.Preliminary study on the biological role of EF-hand domain-containing protein 2 in hepatocellular carcinoma
Yanmei ZHANG ; Xiao LI ; Xueqiang JIA ; Juanzi LIU ; Wanqing LI ; Junfeng XUAN ; Shiyu FENG ; Zhaohui SUN ; Weiyun ZHANG
Chinese Journal of Preventive Medicine 2025;59(8):1224-1231
This study investigates the expression pattern and functional significance of EF-hand domain-containing protein 2 (EFHD2) in hepatocellular carcinoma (HCC), with particular focus on its regulatory effects on tumor proliferation, migration, and invasion. Cellular experimental study was completed from June 2024 to January 2025 in the Basic Laboratory of the General Hospital of Southern Theater Command. TCGA database to determine EFHD2 expression and its clinicopathological correlations. GSCA database to assess methylation patterns and immune infiltration. Model of transient overexpression and knockdown of EFHD2 was constructed in hepatocellular carcinoma cells Hep3B, then RT-qPCR and Western blot were applied to verify the transfection efficiency. CCK-8 and colony formation assays for proliferation assessment, Transwell chambers for migration/invasion quantification. Protein-protein interaction networks were constructed via STRING, followed by GO/KEGG enrichment analysis. Statistical analysis was performed using the two independent samples t-test. The results showed that EFHD2 demonstrated significant upregulation in HCC tissues versus normal controls ( P<0.05). Elevated EFHD2 expression correlated with advanced clinical stage ( P<0.05) and poor differentiation ( P<0.05). In the CCK-8 assay, the EFHD2 overexpression group demonstrated significantly higher cell viability than the control group, as evidenced by 450 nm relative absorbance values on Day 1 (0.529±0.019 vs. 0.515±0.016, F=0.041, P=0.320), Day 2 (1.356±0.019 vs. 1.094±0.042, F=3.833, P<0.001), Day 3 (2.817±0.049 vs. 2.143±0.124, F=3.833, P<0.001), and Day 4 (3.848±0.015 vs. 3.430±0.021, F=0.469, P<0.001). The EFHD2 knockdown group showed reduced cell viability compared to controls: Day 1 (0.541±0.020 vs. 0.552±0.015, F=0.098, P=0.423), Day 2 (1.154±0.009 vs. 1.326±0.029, F=2.485, P<0.001), Day 3 (2.453±0.041 vs. 2.653±0.031, F=0.479, P<0.001), and Day 4 (3.685±0.038 vs. 3.836±0.021, F=6.804, P<0.001). In colony formation assays, the overexpression group displayed a significant increase in colony numbers (254.667±23.861 vs. 186.000±16.703, F=0.865, P=0.015), whereas the knockdown group exhibited decreased colony formation (229.000±24.637 vs. 306.667±36.501, F=0.988, P=0.038). In Transwell assays, the EFHD2 overexpression group revealed enhanced migratory capacity [ (605.000±72.670) cells vs. (472.667±28.095) cells, F=2.462, P=0.042] and invasive potential [(767.333±21.221) cells vs. (414.333±16.623) cells, F=0.331, P<0.001]. The knockdown group showed attenuated migration [(311.000±71.084) cells vs. (479.667±50.846) cells, F=0.718, P=0.029] and invasion [(247.667±48.263) cells vs. (345.667±32.130) cells, F=0.727, P=0.043] compared to controls. The network of EFHD2-interacting proteins was further constructed by the STRING database, and the GO and KEGG analysis were used to perform bioinformatics analysis reveal that EFHD2 is mainly involved in actin cytoskeleton regulation. In conclusion, EFHD2 is highly expressed in HCC and is involved in the process of proliferation, migration and invasion of HCC.
5.First ATG101-recruiting small molecule degrader for selective CDK9 degradation via autophagy-lysosome pathway.
Ye ZHONG ; Jing XU ; Huiying CAO ; Jie GAO ; Shaoyue DING ; Zhaohui REN ; Huali YANG ; Yili SUN ; Maosheng CHENG ; Jia LI ; Yang LIU
Acta Pharmaceutica Sinica B 2025;15(5):2612-2624
Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.
6.Clinical analysis of radical resection of thyroid carcinoma through lateral neck small incision sternocleidomastoid intermuscular approach
Jiahui WANG ; Zhaohui WANG ; Yibo CHEN ; Yixin SUN
Chinese Journal of Endocrine Surgery 2025;19(1):40-44
Objective:To investigate the feasibility and safety of radical thyroidectomy through a small incision in the side neck of the sternocleidomastoid intermuscular approach.Methods:Clinical data of newly treated patients with papillary thyroid carcinoma admitted to the Department of Thyroid-Otolaryngology and Head and Neck Surgery,Sichuan Cancer Hospital from Feb. 2022 to Mar. 2024 were collected. They were divided into SMIA group and LACA group according to surgical methods. In the SMIA group, 52 cases were treated by the sternocleidomastoid intermuscular approach with a small incision on the side of the neck. In the LACA group, 100 cases were treated by the cervical white line approach with a low cut incision on the front of the neck. Clinical data of the two groups, such as perioperative related indicators,postoperative aesthetic effects and postoperative complications were collected. Independent sample t test or Mann-Whitney U test were compared between the measurement data groups. Chi-square test was used for comparison between data sets. Results:There was no significant difference in demographic and clinical characteristics of tumor between the two groups. Compared with the control group,the operation time of the observation group was longer (83.85±18.72minvs71.33±15.50min, t=4.39, P<0.001) , the total postoperative drainage volume was significantly reduced (61.29±41.80ml vs. 99±35.80ml, Z=-4.65, P<0.001) , and the extubation time was significantly shortened (2.81±0.82d vs. 3.19±0.66d, Z=-3.31, P<0.001) , and the difference was statistically significant. There was no difference in postoperative transient hoarseness between the two groups ( χ 2=0.01, P=0.932) . Patient’s self-feeling was followed up one month after surgery. The number of patients with swallowing discomfort in the SMIA group was significantly lower than that in the LACA group ( χ2=4.30, P=0.017) . There was no significant difference between the two groups in neck stiffness ( χ2=3.16, P=0.075) , scar hyperplasia ( χ2=0.04, P=0.840) , and incision aesthetic effect score ( Z=-0.73, P=0.468) . Conclusions:Radical thyroidectomy through a small incision in the side neck of the sternocleidomastoid muscle is a safe, feasible and aesthetic mode of operation. It’s worth promoting in clinical practice,especially for patients with unilateral tumor and early tomur T stage.
7.Predictive value of serum sEC and COX-2 levels for postoperative recurrence and metastasis of breast cancer
Zhaohui ZHU ; Xu QIAN ; Meiling XUE ; Aijun SUN ; Weimin SUN
Chinese Journal of Endocrine Surgery 2025;19(5):671-677
Objective:To explore the value of serum soluble E-cadherin (sEC) and cyclooxygenase-2 (COX-2) levels in predicting postoperative recurrence and metastasis of breast cancer.Methods:198 female breast cancer patients who underwent surgical treatment in Huai’an Hospital Affiliated to Xuzhou Medical University (Huai’an Second People’s Hospital) From Mar. 2023 to Mar. 2025 were selected and followed up for 3 years. The recurrence and metastasis were counted. Patients with recurrence and metastasis were included in the poor prognosis group, and patients without recurrence and metastasis were included in the good prognosis group. The general data, preoperative serum sEC and COX-2 levels were compared between the two groups. The influencing factors of recurrence and metastasis of breast cancer after operation were analyzed. The dose-response relationship and predictive value of serum sEC and COX-2 levels with recurrence and metastasis were analyzed. Logistic regression equation (LR) model 1 was constructed according to conventional influencing factors, and LR model 2 was constructed according to conventional influencing factors combined with serum sEC and COX-2. The predictive efficacy and accuracy of the two models were analyzed by receiver operating characteristic curve (ROC) and calibration curve. According to the ratio of 7∶3, another 85 female breast cancer patients who underwent surgical treatment in Huai’an Hospital Affiliated to Xuzhou Medical University (Huai’an Second People’s Hospital) from May. 2023 to May. 2025 were selected for external validation (validation set) .Results:Among 198 breast cancer patients who underwent postoperative follow-up for 3 years, 3 cases were lost to follow-up, and the recurrence and metastasis rate among the 195 patients who completed the 3-year postoperative follow-up was 26.15% (51/195). In the good prognosis group, the proportion of TNM stage III was 20.14%, the proportion of lymph node metastasis was 11.81%, the preoperative serum carbohydrate antigen 153 (CA153) level was (54.19±10.84) U/mL, the carbohydrate antigen 125 (CA125) level was (46.03±10.27) U/mL, the sEC level was (1987.65±191.37) ng/mL, and the COX-2 level was (17.85±5.21) ng/mL. In the poor prognosis group, the proportion of TNM stage III was 45.10%, the proportion of lymph node metastasis was 35.29%, the preoperative serum CA153 level was (65.87±12.23) U/mL, the CA125 level was (57.76±11.51) U/mL, the sEC level was (2 295.37±261.48) ng/mL, and the COX-2 level was (10.42±3.16) ng/mL. Compared with the good prognosis group, they were increased ( t/χ 2=12.00, 14.11, 6.39, 6.79, 8.92, 12.00, P<0.05). Multivariate Logistic regression analysis showed that TNM stage III ( OR=2.078, 95%CI =1.569-2.751, P<0.05), lymph node metastasis ( OR=2.435, 95 %CI=1.843-3.216, P<0.05), serum CA153 ( OR= 1.180,95 %CI=1.026-1.357, P<0.05), CA125 ( OR=1.206,95 %CI=1.033-1.408, P<0.05), sEC ( OR=1.011,95 %CI= 1.007-1.015, P<0.05), COX-2 ( OR=1.378,95 %CI=1.128-1.683, P<0.05) were independent risk factors for postoperative recurrence and metastasis of breast cancer. Restricted cubic spline (RCS) analysis showed that serum sEC and COX-2 levels were positively correlated with the risk of recurrence and metastasis of breast cancer ( P<0.05). ROC analysis showed that serum sEC (AUC=0.762,95 %CI=0.696-0.820, P<0.05) and COX-2 (AUC=0.757,95 %CI=0.691-0.815, P<0.05) could be used as biological indicators to predict postoperative recurrence and metastasis of breast cancer. The AUC of LR model 1 in predicting postoperative recurrence and metastasis of breast cancer was 0.862 (95 %CI=0.805-0.907, P<0.05). The AUC of LR model 2 in predicting postoperative recurrence and metastasis of breast cancer was 0.965 (95 %CI= 0.891-0.983, P<0.05), which was significantly larger than that of LR model 1 ( Z=2.015, P<0.05). The calibration curve analysis showed that the calibration degree of LR model 1 in predicting postoperative recurrence and metastasis of breast cancer was good, and the prediction results were in good agreement with the actual observation results. The calibration degree of LR model 2 was high, and the prediction results were in good agreement with the actual observation results. The results of external validation showed that the sensitivity of LR model 2 in predicting postoperative recurrence and metastasis of breast cancer was 82.61%, the specificity was 93.55%, the accuracy was 90.59%, and the Kappa value was 0.762 (95 %CI: 0.549-0.974) . Conclusions:Preoperative serum sEC and COX-2 levels are independent risk factors for postoperative recurrence and metastasis of breast cancer. They can be used as biological indicators to predict postoperative recurrence and metastasis of breast cancer. Combined with conventional indicators, they can significantly improve the predictive efficacy.
8.Survival Analysis of Colorectal Cancer in Jiashan County,Zhejiang Province from 1991 to 2020
Feng XUE ; Xinglin FEI ; Jing SUN ; Zepeng ZHANG ; Zhaohui ZHANG
China Cancer 2025;34(1):32-36
[Purpose]To analyze the survival of colorectal cancer patients in Jiashan County of Zhejiang Province from 1991 to 2020.[Methods]The data of newly reported cases of colorectal cancer were collected in Jiashan County from January 1,1991 to December 31,2020,and pa-tients were followed-up till December 2023.The observed survival rate(OSR)and relative survival rate(RSR)were calculated using the life table and Ederer Ⅱ method with 5-year intervals.Rela-tive survival was adjusted using the International Cancer Survival Standards.The Joinpoint re-gression model was used to calculate the average annual percentage change(AAPC)to analyze the change trend of survival rate.[Results]The 5-year RSR of colorectal cancer increased from 21.7%during 1991 to 1995 to 73.4%during 2016 to 2020,showing an increasing trend(AAPC=4.6%,P<0.05),for men it increased from 17.7%to 72.7%and for women it increased from 30.0%to 74.3%,with AAPCs of 3.9%and 4.3%,respectively(P<0.05).The 5-year RSR of colorectal can-cer in all age groups showed an increasing trend(P<0.05 for all age groups,except for 75+),and the highest increase was found in the age group of 65~74 years old(AAPC=4.9%).[Conclusion]From 1991 to 2020,the 5-year survival rate of colorectal cancer in Jiashan County showed a steady increase,for women and those aged 65~74 years old the increase was more significant.The cancer screening of high-risk groups should be focused on to improve colorectal cancer survival rate.
9.2024 Update of Chinese Guidelines for the Management of Hyperuricemia and Gout Part Ⅱ: Recommendations for Patients with Common Comorbidities
Changgui LI ; Mingshu SUN ; Zhen LIU ; Detian LI ; Changqian WANG ; Zibin TIAN ; Yuxiang DAI ; Zhe FENG ; Chengfu XU ; Dongbao ZHAO ; Feng WEI ; Bo BAN ; Chao XIE ; Zhenmei AN ; Jia LIU ; Zhuo LI ; Yuwei HE ; Xinde LI ; Fei YAN ; Lin HAN ; Lidan MA ; Xiaoyu CHENG ; Tian LIU ; Xufei LUO ; Lingling CUI ; Ying GONG ; Can WANG ; Yaolong CHEN ; Zhaohui LYU ; Yip Ronald ML ; Jiajun ZHAO
Chinese Journal of Endocrinology and Metabolism 2025;41(11):918-929
The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.
10.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.

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