Jounal ofthe National Cancer Center 2 (2022) 1-8 Contents lists available at ScienceDirect Loy a ELSEVIER Journal of the National Cancer Center journal homepage: wivw elsevier comocatelince Cancer incidence and mortality in China, 2016* Rongshou Zheng, Siwei Zhang’, Hongmei Zeng ', Shaoming Wang’, Kexin Sun', Ru Chen', Li Li’, Wengiang Wei, Jie He? ofc oan Reps, National Cancer ener Natonc Cea Rear Cet far Cancer Cance eta, hse Acateny of Me! eer nd Ping nin eat Ce Being 10002, china = Deprten of rae Sarpy, Neal Cancer Cention Cine Rew Cent fr Cancer /Cacer Hap Cnr Accey of Maal cee ened Peg Une dal Coleg, ii 10021, China epee ‘ckgrnind= National Cancer Center (NCO of China anally repos the nationwide Rats for cancer inc Concer ey ence and morality using population based cancer registry data fom all avaiable cancer eeisies in China ostiy “Methods: Thore were a total of 487 regisis whic reported high quality daa of cancer incidence and mortality Ste 2705 Chins in 2016, The nationwide numbers of ew eaneer cases and desths were estimated using the pooled hia cancer regisry dats, which were stratified by area (urban/rural, sex, age group (0, 1-4, 5:9, 1014..85+) and ‘incer site for ineience and morality, and then maitpied by coresponding national popslation, The wor ‘Seg’ population ws applied forthe calculation of agestandarded rates, eau: Abou 4,068,000 new cance cases and 243,50 new cance death occurred in China in 2016, Cancers ‘ofthe hing, colon-rectum, stomach, liver end female breast were the top five common cancers, eccountng for 57-46 of total eaeer new eases. Cancers ofthe ling, ver, stomach, color-rectum and esophagus were the five {incidence res (ASI) stee 298.91 and 186.46 per 100,000 poplin, respectively. The crede mortality ate ‘was 174.55/100,000 and the agestandarized morality rate (ASM) was 105.19/100,000. The ASIR was higher ‘but the ASMR was lower In urban areas than that Ia rural areas. In past decades, the AIR was reatvly sable in sles, bt sgnicanly increased by abou 238 per yea infernal fo overall cancers combined. In conta, the ASME signicantly decreased by abo 1.25 per year for both sexes ding 2000-2016, Notably, the nec. specific ASIR and ASM of esophageal, stomach, and liver eancers decreased significantly, whereas bot rates {or eancers ofthe clon-ectum, prostate, female breast, cervix and thyroid increased significa Conclusions: Cancer remeins a major public health problem in China, which demends longterm collaborative forts of a broad community. Wih dhe nations guideline on cancer prevention and coal, alored eancer prevention and contra programs are needed in different regions to help eee the burden ofthese highly tal {ica in Cina 1, Introduction ‘Cancer is a mejor public health problem and has become one of the ‘most common causes of death in China’. Cancer registries can be used for continuous and dynamic monitoring of eancer incidence and mortal- ity. Cancer Registration isthe fandamental work for formulating cancer prevention and contel strategies, launching comprehensive prevention and control research, and evaluating effects on prevention and control’. CChina has established a nationwide cancer registration and follow-up surveillance system, which can continuously release Cancer Registry An- ‘nual Report. By the end of 2020, cancer registration had covered 1152 counties with a population coverage of 598 million. National Cancer Center (NCC) is responsible for collecting, evaluating, and publishing the national cancer statistics of China. All hospitals and medical and health institutions in the administrative regions are required to submit cancer records to local population-based cancer registries ‘This report provided the latest statistics of new eancer incidence and ‘morality in China in 2016, and comprehensively estimated the overall Given his role a Sitorin-Chie, ie He had no involvement inthe peer-teview of tht atce and had no access to information regarding its peer-review. Full esponsibility forthe editor * Comespondence authors ‘mall edareses: weg elcamsac.cn (W. Wel} protheieG@263.net@. He). ps//dot.ong/10.1016/ ace. 2022.02.002 proces fr this article was delegated to Huan He, Recelved 17 January 2022; Received n ves frm 18 February 2022; Acepted 19 February 2022 2667 004/% 2022 Chinese National Cancer Center. Published by Hlsevier BV. Thi san open aces article under the CC BY Heese (up:/rerentivecommonsorgicenses/by/4.07)hg 5 Zhang Zgetak Jura of Natl Caner Cone 2202) 1-9, Tablet Entmaced numbers of new cancer eases and incidence rates, overall, by sex and cancer ype la China, 2016 cer GG) GI) ewes AO) io") cams") anes als ‘ophagae 2s2s00 1626 131648002505 ‘sone lar S00 [Abeeviation=: ASIRW, agestandardized ineideace rate by word standard popalaton (Seqi's populaony; CNS, ceneal neous systems 1CD-10, Intemational numbers of new cancer cases and deaths in 2016, We further updated the trends of cancer incidence and mortality from 2000 to 2016. This up-to-date nationwide cancer profiles an provide slentfic evidence for cancer prevention and contro in China 2, Materials and methods 2.1. Qualiy conrot [NCC is responsible for data quality control, including assessing the validity, reliability, completeness and comparability ofall cancer seg fatty data based on the criteria of "Guideline for Chinese Cancer Reg- Istation”® and criteria of International Agency for Research on Can cer/International Association of Cancer Registries (IARC/IACR)'". In- exes including mortality to incidence (M1) ratio proportion of cases with morphological verification (MV), percentage of cases with death- certifcatc-only (DCO), percentage of cancer diagnosis with unknown, basis (UB) and the stability of cancer trends aver years were used for quality onto. 22, Data source By 31 December 2019, a total of 682 cancer registries from 31 provinces (autonomous regions and municipalities) and Xinjiang Pro- duction and Construction Corps (not including Hong Kong, Macao Spe- cial Administrative Regions and Taiwan Province) submitted registra tion data of 2016 to National Cancer Center (NCC). All newly diagnosed cancer cases were coded according tothe International Classification of Diseases for Oncology, 3° edition (ICD-0-3) and the International Sta- tistial Classification of Diseases 10! Revision (ICD-10). ‘Temporal trends for age-standardized rates by world standard pop- ulation from 2000 to 2016 for cancer incidence and mortality ofall cancers and selected cancer types were analyzed using data from 22 continuous cancer registries, which represented 3.34% of the Chinese population. More details about those regsties have been reported in a previous study ‘he National Bureau of Statistics of China provided the total nm ber of population of China in 2016, stratified by area (urban/rural) and sex. The age-specific population of 2016 was estimated according to the population structure of the data ofthe fifth and sixth National Census, ‘hich provided the data of the whole population in group (0, 1-4, 584 by 5 years and 85+ years) 23. Statistical analysis Cancer incidence and mortality rates stratified by age (0+ 1-4, 5-84 by 5 years and 854 years), sex (male/female), area (urban/rural) and region (seven administrative regions including North, Northeast, Fas CCenteal, South, Southwest, and Northwest) were calculated using pooled qualified cancer registries’ data. The incidence and mortality rates were ‘multiplied with the population in each strats and then surimed up to ‘obtain the estimated numbers of new cancer cases and deaths. The Seis population was used for age-standardized rates. fa registry is located in a county, it was classified as a rural registry, while it was clas fied as an urban registry if ti located in a cit. The classification of seven administrative regions was based on that of the National Bureau of Statistics All models were restricted co @ maximum of 2 joinpoints ine segments). The annual percent change (APC) and the average ‘Annual Percent Change (AAPC) far three fixed intervals (2000-2016, 2007-2016 anxd 2011-2016) were calculated using Joinpoint Regression Program (version 4.6.0.0) for both incidence and mortality. SAS sof ware (Version 9.4, SAS Institute In. Cary, USA) was used for statistical analysis. 3. Results ‘After data quality control, 487 cancer registries’ data were qualified and included in this analysis, of which 200 rogistries wore from rural areas and 287 were from urban areas, The population covered by thesehg 5 Zhang Zgetak Jura of Natl Caner Cone 2202) 1-9, ‘table ‘Agestandardized inidence rates overall by aren and cancer type by geographic areas covered by 487 eancer registries, 2006 1/10") Geograpticwras Asis Goptagus Stomach Gores her ting Fenalereat Gov Provate Kidney ldier Lymphoma Ukenla ‘arse ase eC aoa te 6a as aaa 30 Ua Wey 82 bs moa joo 820 41a a St fal 162 1800 Ra? 98 mo 4428 aD Be “ North Wo 82 ae ea 28 a0 kD as 61 be aka 89 Northeast wee 46 0 aa Ike tue 381 Me 47 48 to 30 37 fat wes sas 16 43 a7 wor 76 32 Ba 80 Cone m2 43? 1S ks 280 wo 43 ae ae a 83 Nowb (Ur) 18s 43 ns ios a0 00 et es Nowhent (Ub) 1969.4 as 158 26 383 tae 86 Se 82a ee Eee(tte) 196397 14 eo 5 jaz to 40a BN Cova(iew) 161 98 19 2 ns ue 6s Mas ae 53 Souk (Urta) 212348 m1 359 m7 ia loz a2 ayes es Stutinet (Urs) 1664 105103 iso as 210 ue 423 ako ory Nonwest(Uewe) 1765 118280, vs 2 26 aa 6283S a2 Norkus) 1789123 Me Geo at oo 39°42 87a 54 Nowhast urd) 1669 57a ms 393 20 93 2k laa ae Bona) 775169 D7 se m1 ha $200 a4 a8 a CovalGurs) 16174 3 360 57 e232 «2a 58 Sou (kon 1908 S803 goo 331 74 RA 382348 60 Sruwest ue) 1687 164158 wnt ahs 162 me 38018 ay BT ae Nowthose tual) 1702 1398S w0 76 Be 34 23a ae 27 8 cancer registries was 381,565,422 (193,632,325 males and 187,933,009 females), accounting for 27.60% (24.396 for urban areas and 32.0% for ‘ural areas) ofthe national population at the end of 2016. 3.1, Estimated numbers of new cancer cases and cancer incidence rates “Table 1 shows the estimated numbers of new eancer cases and deaths Jn China in 2016. Overall, an estimated numberof 4,064,000 new cancer cases oceurted in 2016. Lung cancer was the most common cancer in ‘men, accounting for about 24.6% ($49,800) ofall new cancer cases, followed by liver, stomach, colorectal and esophageal cancers. These top five eancets accounted for about 68.83 % of all newly diagnosed cancers in men. In women, breast cancer was the most common, accounting for 16.72% (306,000) ofall new eancer cases, followed by lung, colorectal, thycoid and stomach cancers. These fop five cancers accounted for about 56.11% of all new cancer diagnosis in women. “Table 2 displays the ASIRS ofall eancers combined and 12 selected cancer sites in China in 2016. The age-standardized incidence rate Fig. 1. Agespesfe cancer incidence and mar tality by sexi China, 2016. (A) Age-peac ea cer inedence rates and umber of new eases By sex (B) Agespeifie cancer morality rates and deaths by Sox (ASTR) for all cancers combined in urban areas was higher than that {in rural areas (189,7/100,000 vs. 176.2/100,000). South China had the highest ASIR (204.3/100,000), followed by Northeast China and East China, Southwest Chia (167.5/100,000) had the lowest ASIR. The inci- dence rates of cancers of colon-ectum, lung, female breast and prostate Jn urban areas were higher than the rates of those cancers in rural ar. eas, However, the ASIR for some digestive cancers including esophageal cancer, gastric cancer, and liver cancer were lower in urban areas than. ‘that in rural areas 3.2. Estimated numbers of cancer deaths and cancer morality rates “The estimated aumbers of total deaths forall cancers and 26 can- cer types stratified by sex were shown in Table 3. About 2,413,500 people died from cancer in China in 2016, Lung cancer was the most ‘common cause of cancer death for both sexes. For men, lung cancer zg te a" " SS a 3 Se vO ‘ o SKS KH SP sh SPSL SKS Ss Fig 2, Trends in incidence and mortality rates for selected cancers by sex in China, 2000 to 2016 (A) Male incidence (B) Female incidence, (6) Male mortality. (©) Female morality. (4.6%), colorectal eancer (1.3%) and panereatic cancer (1.0%) inereased during this period. The rates of other cancers such as bladder eancer, brain cancer and leukemia remained stable. In women, there was an ‘upward tread of morality rates of cancers of the cervix, thyroid and breast but = downward crend ofthe esophagus, stomach, liver and lung Discussion Cancer is a major public health problem in China. In this study, we analyzed the burden of cancer in China in 2016 using data from 487 ‘qualified cancer registries We estimated that about 4,064,000 new can- cer cases and 2,413,500 cancer deaths in China in 2016. Cancer inci- dence in urban areas was higher than that in rural areas, Lung can- cer was the most common cancer in China as well as the first leading cause of cancer deaths. Age-standardized incidence rates stayed stable in ‘men but inereased by 2.3% per year in women during 2000-2016. Age- standardized mortality rates decreased by 1.2% per year both in men and women. The updated statistics for cancer incidence and mortality ‘overall and by cancer type in China may provide scientific evidence for policymakers, esearchers, and clinicians. ‘The results ofthis study were the estimation for cancer incidence and mortality in China in 2016, For all cancers combined, the numbers ‘of new cases aad deaths in China estimated in this study were relatively low compared with the estimation given by Globoean2020°, the latest alobal cancer prediction from IARC, but closer tothe results of Globocan 2018”. However, the patterns for specific cancer types were quite difer- ent from the Globocan database (Supplementary Table 1 and 2). The methods used to estimate the global cancer incidence and mortality inZhang 5 Zhang Znget ah Trends in incidence rates for selected cancers by sex in Cine, 2000 to 2016, Jura of Natl Caner Cone 2202) 1-9, Alster 20002018 0: (01-03 1601-05) 0601-0) 0101-03) ropa 20002004 5379-25) 20042009 1B EL6-10) 20002016 -ASLST-2A) BNCAT-2H) ISASHAG) ASMST—3A) Stomset 20002004 “A'CS0-333) 2O04Im08 “L1C25-05) 2009.06 SHCA) ouas-25) BMCSA2A) AarCLOW28) Caansecem 20002005 42°G3-50) 20062016 13°.0-1.7) zeaoan Loin “Laon liver 20002005 0920-0.) ogsa0is 0"1as~28) — = ar27-17) 20K35-25) aoreas-29) Posceae — mooanis 107-12) = = rowar-12) Love7-12)LaNa7-1.2) ing 20002016 0102-01) = = biene-an) 9102-01) ‘route 2060-2008 poosanis 4843-53) = 7ime6-77) 4443-33) ‘Biaer 20002005 roosanis Lore1e—04) — = dsar13) aoKisa4 106-04 ‘aia, exS 20002016 a = = 1509-20) 1509-20) 1309-20) teatewia 20002000 poooa016 1628-22) = 19MG6-31) 709-28) 02 e2s-29) Aisies — mopoam6 291-29 = - = aeaias) 2n@i-29) 28eI-29 Fophagus 20002008 -7S'CHAae42) HOOMINI ANH) INOAMG FSS) -BANTI-SO) -GACTESD) FSA) Gaansesrim 20002008 39°0.5-40) doo6am16 BoCo4-a9) = iamas1s) “aacouas) -nocD4-03) ther oooaoes tercas-07 dooea016 arcae=28) Byaa2t) Bacar AMCAs-28) line aooo.oni awras-14) aoiaMe aera) — = Ries) 36G2-47" “Aaranen) Bran 000.2008 6497-55) dnowanIE TaaS-23) = Boats) Lmao) Lanas.a3) Gane agon.a0o? Y4or(190-192) aoePANIG 2eCAW«s) = Rsaiom 21-48) 2901-4) rene ago-anos Ssraa-at) a0osanl6 26-33) Beara) dedaaa dena Bin NS noodle 22-36) aearis) 28a236) 2902-30) Tyre BION IODA SHC. I-187) —_ 200K21G 2418-224) JI°S3-20.2) 2068-224) 2.6°088- 22.4) “The APC is significantly dtferent fom aro (P< 005) Abbreviations: APC, annual percentage change; CNS, central nervous system; ICD-10, Intemational Casiction of Diseases 10 sNevison. ‘Trends in mortality rates for selected cancers by sex in China, 2000 to 2016. sa Sie tan ARGO) Yan —-NCGSNG) Yam ——~AR OSE) _—DooOaNIE —_daoraoTe —_—DoIRDTS Atbiter 20002016 1. 2614-09) 2609) 121408) ADE14-09) phase 20002004 “62°(90-34) 20042009 24¢52-06) 20082016 -A0YS2-26) 4IS2-30) 3TUAIW27) 4045228) Semch 20002004 “s¢74-32) rooeDIe -2ECS2—24) — 2 Saea0-29) 2e(a224 2ea220 Colorect 20002016 1309-17) = = = s0s-17) 1340817) 1309-17) ve 20002016 2731-23) 2731-29) 2731-23) 2MAI-29) Pancess 20002016 LO"G?~14) = = = oma7-14) 1047-14) 1007-14) bing 20002016 -ow"eo9-03) — = = = 06%(09-03) 0649903) As'09-03) Prot 2000016 4649-52) — = = = ‘etas-s2) 464ao-82) 4era9-83) udder 20002016 0308-02) — = = = 0308-02) 03(98-02) -0s08-02) Brain.cxs 20002016 01-06-07) — = = = o1a6-07) o1(a6-07) 0206-07) kena 20002000 21°(.0-33) 20092016 13¢29-04) — = aeiaais 917-07) 1329-04) phage 20002016 BSED) — = = = Gsrlen8) SHC46-89) AaCEG—9) Somach 30002004 “62GR2-0) 20042009 941-03) DoORIMG AOTAI- AO) -A2HEGOA) AMAA) ABSA?) Cairectam 20002004 “o9cat-i) aoo4a009 iscae—a9) a D200 ‘D4lAa-as) -LOrC1S-00) ver 20002008 “20%2b-12) do98AdIE ABSA) — = BaC89—2H) AarlRdma) AMES) fine -«Boooania “oacam-any amaanie amcso—as) — = Dorciso) a(at—ad) aPcso-83) Brest 20002016. L04(04~1.) omGaia) 1040813) 108-13) Gove boonanie. a4s-8a) SHUS89) SaUs5H SAIS) Uren 20002005 3.0-01-63) 20052016 ® aneiean Aacaanie -Leeae) BraincNS 20002016 04 (10-02) aacio-02) ‘o4ttona2) “o4(Lo-02) hyoid 20002015. L6r-28) 0528) 1640626 1806-26) The APC i sgnifceily diferent rom vero (P< 0.05). Abrevatons: APC, annual percentage change; CNS, central nervous system; ICD-10, International Clas 2020 were based on the most recent data supplied by population-based: cancer registries (PBCR) of IARC for Cancer Incidence in Five Conti- ‘ents (G15) Vol. XI (data from 2008 to 2012) §*, Nevertheless, cancer registration work in China in recent years has made great progress and development. With the implementation of Chinese Cancer Registration “Management Regulation‘, preparation and promotion ofthe standard ination of cancer registration work, the population covered by registra sion gradually has expanded and the quality of registration data has been steadily improved. Moreover, China has established more than cation of Diseases 10" revision, 1,600 cancer registries, covering more than 890 million people by the beginning of 2022, The results ofthis study should be more representa tive ofthe actual cancer burden in China compared with the results of Globocan estimates, “The numbers of averall new cases and deaths of cancer in China in 2016 was higher than previous yeas", With the social and economic {evelopment in China, the life expectancy has increased and the popl- Jation structure is aging. Considering aging isan established risk factor for cancer, the increasing cancer burden of China may be partly dve toRh 5 Zhang Zngec ak expanding population during the past decades. Tobacco consumption Js one of the main risk factors for many cancer types including lung cancer, esophageal cancer, stomach cancer, ete, China has the worlds largest smoking population, with an estimated 350 million smokers and 740 million passive smokers'°. Previous studies have shown that smok- Jing accounts for more than 208 of cancer deaths in China“, kffetive tobacco control has been showa to be an effective intervention method. to reduce cancer incidence in western counties. In comparison, only some cties or regions in China such as Beijing and Shanghai have imple- ‘mented a ban on smoking in indoor public places. Nationwide interven tion in smoking control is urgentiy needed and the focus should be put fon the prevention of smoking among women. Although smoking is one of the major risk factors for lung cancer, we should also pay more at- tention Co the continuous inerease in lung eancer incidence rate among, non-smoking female population, especially in rural areas. The incidence rate of lung eancer inereased from 2000 to 2016, and the average ar ‘ual percent change reached 2.1% for women, and even inereased by 4.6% per year inthe last S years. This may be related ta indoor cooking And the ai potution exposure, Similar to the global increases of colorectal eancer and breast can- cer, increasing trends ofthese cancers were also observed in the Chi- ese population. The obesity prevalence in China rose from 3.196 to 8.2% from 2004 to 2018", Given that the proportion af population with obesity and physical inactivity in China is stil increasing, these modifiable isk factors may play 2 roe inthe inerease of colorectal can- cer and breast cancer. Therefore, modifiable risk factors including un- heathy lifestyle, obesity, physical inactivity, and other risk factors con- tributed over 40% ofthe cancer incidence and mortality in China”, s0 the healthy lifestyle promotion is needed fr effective cancer control {in the country. Thyroid cancer experienced the largest increase in in- idence among all cancer types, whereas its mortality remained stable, indicating overdiagnosis may play a part with a rapid transition to a higher socioeconomic level of the country’s economy. On the bright side, our study shoved that esophageal cancer, stomach cancer and liver cancer showed a continuous decreasing trend for age-standardized incl- ddence and mortality rates, The decreasing trends of liver cancer may be attributed to decreased consumption of aflatoxins-contaminated food, Improved quality of water, as well as the Hepatitis B views vaccintio Specially, neonatal Hepatitis B virus vaccination has been made free for all children since 2002, and the vaccination rates reached 99.6% {in 2015” Endoscopic sereening has been shown to be an effective in- tervention method 0 reduce esophageal cancer incidence and mortal- Jig", And we observed a more favorable trend toward eaty-stage diagnosis in the Chinese population especially in the areas with sys tematic esophageal cancer contol programs including primary cancer prevention and cancer screening", The decreasing trends of upper gas- frointestinal cancers in China may further support the pivotal role of endoseopie cancer sereening in high-risk areas. ‘There are several strengths for this analysis. First, this i a system- atic use ofthe most updated and representative data of China, including 487 cancer registries, covering about 381,565,422 population, which accounted for 27.60 % of the national population by the end of 2016. In particular, this study reported the cancer incidence, mortality and tem- poral trend in China by sex, age group and region Detaled information from different perspectives can be provided for cancer prevention and contro ‘There are also some limitations in this study, Firs, the estimations in this analysis relied upon the best available registry data to calculate the Jnckdence and mortality atthe country level, Secondly, there remains a lack of sufficient high-quality data in some areas such as Xinjiang, Tibet, and Qinghai province. However, this estimation was stratified by urban and rural areas, so the poor quality of some provincial data does not affect the national estimation results, Finally, the data sed in the trend analysis section only covered 22 cancer registries, representing a relatively small population and not fully reflecting the overall trend changes in China Joel of be Natonl Caner Cone 2202) 1-9, Inconelusion, the burden of cancer in China s heavy and is expected to continue increasing in the next decade. China has issued 2 series of health polices to prioritize the promotion of cancer control, and the State Counel has established the inter-ministeral joint conference sys tem to prevent and control major chronic diseases. Tis study showed ‘thatthe burden of cancer in China continued to increase mainly de to the aging of the population, but after adjusting the age structure ofthe population, the trend changes are diferent for each cancer site, Some showed an upward trend, some declined or remained stable, but the di- gestive system cancers showed a downward trend regardless ofthe inci- {dence and mortality, indicating thatthe effect of prevention and control ‘measures in China have now taken effect. Specialy, a significant decline in cancer mortality has been observed for the frst time inthis study. Not only should the cancer prevention and control continue maintain ing existing strategies such as targeted prevention and early detection, and treatment programs be carried out to control the inereasing cancer Durden, but also investments should be inereased in elinical treatment and basic research of cancer to accelerate progress against cancer and Jmprove cancer survival in China Declaration of competing interest "The authors declare that they have no confit of interests. Acknowledgements ‘We thank the Bureau of Disease Control, National Health Commis son of the People's Republic of Chinn for their support of this study We sincerely acknowledge stafs of population-based cancer registries forthe effort they put in data collection and éata quality control. The authors take full responsibility of the data analysis and result interpre- tation ofthis paper. Tis study Is supported by National Key RAD Program of Chine (2018YEC1315305), National Science & Technology Fundamental Re- sources Investigation Program of China (2019FY101100), and National Natural Seence Foundation of China (81974499), Author contributions RZ. and W.W. performed the study desiga. RZ., $2. ané SW. per formed the methodology; RZ. and $.W. conducted the data analyses, RZ. drafted the original manuserpt. 8.2, HZ, KS., RC. and W.W. per- formed the revision and edition. W.W. and J. supervised and led the study, Supplementary materials Supplementary material associated with this article can be found, in the online version, at soi:10.1016/)jnee-2022.02.002, References aoresecanisis2 1 Rona anes Gace Chins Gude or Con Regan Ctl, 21 st dha pai, Yay and eines J Cine Iethads Part Conpetenas Bur J Cater 2008-565) 7562704 (an aa sa).208-265 Say Fen. Soejommtare lege Rb Tot A femal A, lobe cane se {nie coun, CA Caner Cin 202686),2g 5. 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