First Hospital of Jilin University

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
\nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794,
\nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727,
\nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986,
\nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409,
\nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368,
\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
\nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997,
\nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798,
\nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909,
\nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336,
\nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419,
\nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490,
\nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401,
\nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880,
\nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913,
\nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381,
\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

BACKGROUND: Olaparib is an oral poly(adenosine diphosphate-ribose) polymerase inhibitor that has promising antitumor activity in patients with metastatic breast cancer and a germline BRCA mutation. METHODS: We conducted a randomized, open-label, phase 3 trial in which olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease. Patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or standard therapy with single-agent chemotherapy of the physician's choice (capecitabine, eribulin, or vinorelbine in 21-day cycles). The primary end point was progression-free survival, which was assessed by blinded independent central review and was analyzed on an intention-to-treat basis. RESULTS: Of the 302 patients who underwent randomization, 205 were assigned to receive olaparib and 97 were assigned to receive standard therapy. Median progression-free survival was significantly longer in the olaparib group than in the standard-therapy group (7.0 months vs. 4.2 months; hazard ratio for disease progression or death, 0.58; 95% confidence interval, 0.43 to 0.80; P<0.001). The response rate was 59.9% in the olaparib group and 28.8% in the standard-therapy group. The rate of grade 3 or higher adverse events was 36.6% in the olaparib group and 50.5% in the standard-therapy group, and the rate of treatment discontinuation due to toxic effects was 4.9% and 7.7%, respectively. CONCLUSIONS: Among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with olaparib monotherapy than with standard therapy. (Funded by AstraZeneca; OlympiAD ClinicalTrials.gov number, NCT02000622 .).

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

BACKGROUND: Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers. METHODS: We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients. RESULTS: Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P = 0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = 0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events. CONCLUSIONS: In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).

BACKGROUND: China has a large population of older people, but has not yet undertaken a comprehensive study on the prevalence, risk factors, and management of both dementia and mild cognitive impairment (MCI). METHODS: For this national cross-sectional study, 46 011 adults aged 60 years or older were recruited between March 10, 2015, and Dec 26, 2018, using a multistage, stratified, cluster-sampling method, which considered geographical region, degree of urbanisation, economic development status, and sex and age distribution. 96 sites were randomly selected in 12 provinces and municipalities representative of all socioeconomic and geographical regions in China. Participants were interviewed to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, and family history, and then completed a neuropsychological testing battery administered by a psychological evaluator. The prevalence of dementia (Alzheimer's disease, vascular dementia, and other dementias) and MCI were calculated and the risk factors for different groups were examined using multivariable-adjusted analyses. FINDINGS: Overall age-adjusted and sex-adjusted prevalence was estimated to be 6·0% (95% CI 5·8-6·3) for dementia, 3·9% (3·8-4·1) for Alzheimer's disease, 1·6% (1·5-1·7) for vascular dementia, and 0·5% (0·5-0·6) for other dementias. We estimated that 15·07 million (95% CI 14·53-15·62) people aged 60 years or older in China have dementia: 9·83 million (9·39-10·29) with Alzheimer's disease, 3·92 million (3·64-4·22) with vascular dementia, and 1·32 million (1·16-1·50) with other dementias. Overall MCI prevalence was estimated to be 15·5% (15·2-15·9), representing 38·77 million (37·95-39·62) people in China. Dementia and MCI shared similar risk factors including old age (dementia: odds ratios ranging from 2·69 [95% CI 2·43-2·98] to 6·60 [5·24-8·32]; MCI: from 1·89 [1·77-2·00] to 4·70 [3·77-5·87]); female sex (dementia: 1·43 [1·31-1·56]; MCI: 1·51 [1·43-1·59]); parental history of dementia (dementia: 7·20 [5·68-9·12]; MCI: 1·91 [1·48-2·46]); rural residence (dementia: 1·16 [1·06-1·27]; MCI: 1·45 [1·38-1·54]); fewer years of education (dementia: from 1·17 [1·06-1·29] to 1·55 [1·38-1·73]; MCI: from 1·48 [1·39-1·58] to 3·48 [3·25-3·73]); being widowed, divorced, or living alone (dementia: from 2·59 [2·30-2·90] to 2·66 [2·29-3·10]; MCI: from 1·58 [1·44-1·73] to 1·74 [1·56-1·95]); smoking (dementia: 1·85 [1·67-2·04]; MCI: 1·27 [1·19-1·36]), hypertension (dementia: 1·86 [1·70-2·03]; MCI: 1·62 [1·54-1·71] for MCI), hyperlipidaemia (dementia: 1·87 [1·71-2·05]; MCI: 1·29 [1·21-1·37]), diabetes (dementia: 2·14 [1·96-2·34]; MCI: 1·44 [1·35-1·53]), heart disease (dementia: 1·98 [1·73-2·26]; MCI: 1·17 [1·06-1·30]), and cerebrovascular disease (dementia: 5·44 [4·95-5·97]; MCI: 1·49 [1·36-1·62]). Nine of these risk factors are modifiable. INTERPRETATION: Dementia and MCI are highly prevalent in China and share similar risk factors. A prevention strategy should be developed to target the identified risk factors in the MCI population to thwart or slow down disease progression. It is also crucial to optimise the management of dementia and MCI as an important part of China's public health system. FUNDING: Key Project of the National Natural Science Foundation of China, National Key Scientific Instrument and Equipment Development Project, Mission Program of Beijing Municipal Administration of Hospitals, Beijing Scholars Program, Beijing Brain Initiative from Beijing Municipal Science & Technology Commission, Project for Outstanding Doctor with Combined Ability of Western and Chinese Medicine, and Beijing Municipal Commission of Health and Family Planning.

Abstract Objective To assess the prevalence of diabetes and its risk factors. Design Population based, cross sectional study. Setting 31 provinces in mainland China with nationally representative cross sectional data from 2015 to 2017. Participants 75 880 participants aged 18 and older—a nationally representative sample of the mainland Chinese population. Main outcome measures Prevalence of diabetes among adults living in China, and the prevalence by sex, regions, and ethnic groups, estimated by the 2018 American Diabetes Association (ADA) and the World Health Organization diagnostic criteria. Demographic characteristics, lifestyle, and history of disease were recorded by participants on a questionnaire. Anthropometric and clinical assessments were made of serum concentrations of fasting plasma glucose (one measurement), two hour plasma glucose, and glycated haemoglobin (HbA 1c ). Results The weighted prevalence of total diabetes (n=9772), self-reported diabetes (n=4464), newly diagnosed diabetes (n=5308), and prediabetes (n=27 230) diagnosed by the ADA criteria were 12.8% (95% confidence interval 12.0% to 13.6%), 6.0% (5.4% to 6.7%), 6.8% (6.1% to 7.4%), and 35.2% (33.5% to 37.0%), respectively, among adults living in China. The weighted prevalence of total diabetes was higher among adults aged 50 and older and among men. The prevalence of total diabetes in 31 provinces ranged from 6.2% in Guizhou to 19.9% in Inner Mongolia. Han ethnicity had the highest prevalence of diabetes (12.8%) and Hui ethnicity had the lowest (6.3%) among five investigated ethnicities. The weighted prevalence of total diabetes (n=8385) using the WHO criteria was 11.2% (95% confidence interval 10.5% to 11.9%). Conclusion The prevalence of diabetes has increased slightly from 2007 to 2017 among adults living in China. The findings indicate that diabetes is an important public health problem in China.

Antibacterial materials are recognized as important biomaterials due to their effective inhibition of bacterial infections. Hydrogels are 3D polymer networks crosslinked by either physical interactions or covalent bonds. Currently, hydrogels with an antibacterial function are a main focus in biomedical research. Many advanced antibacterial hydrogels are developed, each possessing unique qualities, namely high water swellability, high oxygen permeability, improved biocompatibility, ease of loading and releasing drugs, and structural diversity. Here, an overview of the structures, performances, mechanisms of action, loading and release behaviors, and applications of various antibacterial hydrogel formulations is provided. Furthermore, the prospects in biomedical research and clinical applications are predicted.

Since the outbreak of coronavirus disease 2019 (COVID-19) in late December 2019, it has brought significant harm and challenges to over 200 countries and regions around the world. However, there is increasing evidence that many patients with COVID-19 are asymptomatic or have only mild symptoms, but they are able to transmit the virus to others. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. This article reviews the characteristics, treatment, and outcomes of asymptomatic infections with COVID-19, hoping it would be helpful for early prevention and control of this severe public health threat worldwide.

Metal–organic frameworks (MOFs) have been used for photodynamic therapy (PDT) of cancers by integrating photosensitizers, which cause cytotoxic effects on cancer cells by converting tumor oxygen into reactive singlet oxygen (1O2). However, the PDT efficiency of MOFs is severely limited by tumor hypoxia. Herein, by decorating platinum nanozymes on photosensitizer integrated MOFs, we report a simple yet versatile strategy for enhanced PDT. The platinum nanoparticles homogeneously immobilized on MOFs possess high stability and catalase-like activity. Thus, our nanoplatform can facilitate the formation of 1O2 in hypoxic tumor site via H2O2-activated evolvement of O2, which can cause more serious damage to cancer cells. Our finding highlights that the composites of nanozymes and MOFs have the potential to serve as efficient agents for cancer therapy, which will open an avenue of nanozymes and MOFs toward biological applications.

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; Since the publication of &lt;i&gt;Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition)&lt;/i&gt; in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition &lt;i&gt;(2019 Edition)&lt;/i&gt; was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

BACKGROUND: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy. METHODS: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area. RESULTS: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. CONCLUSIONS: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

INTRODUCTION: The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain. METHODS: We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD. RESULTS: The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015. DISCUSSION: China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide.

Importance: Laparoscopic distal gastrectomy is accepted as a more effective approach to conventional open distal gastrectomy for early-stage gastric cancer. However, efficacy for locally advanced gastric cancer remains uncertain. Objective: To compare 3-year disease-free survival for patients with locally advanced gastric cancer after laparoscopic distal gastrectomy or open distal gastrectomy. Design, Setting, and Patients: The study was a noninferiority, open-label, randomized clinical trial at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 2012 to December 2014. Final follow-up was on December 31, 2017. Interventions: Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histology to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy. Main Outcomes and Measures: The primary end point was 3-year disease-free survival with a noninferiority margin of -10% to compare laparoscopic distal gastrectomy with open distal gastrectomy. Secondary end points of 3-year overall survival and recurrence patterns were tested for superiority. Results: Among 1056 patients, 1039 (98.4%; mean age, 56.2 years; 313 [30.1%] women) had surgery (laparoscopic distal gastrectomy [n=519] vs open distal gastrectomy [n=520]), and 999 (94.6%) completed the study. Three-year disease-free survival rate was 76.5% in the laparoscopic distal gastrectomy group and 77.8% in the open distal gastrectomy group, absolute difference of -1.3% and a 1-sided 97.5% CI of -6.5% to ∞, not crossing the prespecified noninferiority margin. Three-year overall survival rate (laparoscopic distal gastrectomy vs open distal gastrectomy: 83.1% vs 85.2%; adjusted hazard ratio, 1.19; 95% CI, 0.87 to 1.64; P = .28) and cumulative incidence of recurrence over the 3-year period (laparoscopic distal gastrectomy vs open distal gastrectomy: 18.8% vs 16.5%; subhazard ratio, 1.15; 95% CI, 0.86 to 1.54; P = .35) did not significantly differ between laparoscopic distal gastrectomy and open distal gastrectomy groups. Conclusions and Relevance: Among patients with a preoperative clinical stage indicating locally advanced gastric cancer, laparoscopic distal gastrectomy, compared with open distal gastrectomy, did not result in inferior disease-free survival at 3 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01609309.

BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the world. Although considerable progress has been made in the diagnosis, treatment and prognosis of CVD, there is still a critical need for novel diagnostic biomarkers and new therapeutic interventions to decrease the incidence of this disease. Recently, there is increasing evidence that circulating miRNAs (miRNAs), i.e. endogenous, stable, single-stranded, short, non-coding RNAs, can be used as diagnostic biomarkers for CVD. Furthermore, miRNAs represent potential novel therapeutic targets for several cardiovascular disorders. In this review we provides an overview of the effects of several CVD; including heart failure, acute myocardial infarction, arrhythmias and pulmonary hypertension; on levels of circulating miRNAs. In addition, the use of miRNA as therapeutic targets is also discussed, as well as challenges and recommendations in their use in the diagnosis of CVD.

Abstract There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow‐up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non‐metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third‐line to the first‐line of treatment for different patient groups with detailed notes are provided.

Low back pain (LBP), a prevalent and costly disease around the world, is predominantly caused by intervertebral disc (IVD) degeneration (IDD). LBP also presents a substantial burden to public health and the economy. IDD is mainly caused by aging, trauma, genetic susceptibility, and other factors. It is closely associated with changes in tissue structure and function, including progressive destruction of the extracellular matrix (ECM), enhanced senescence, disc cell death, and impairment of tissue biomechanical function. The inflammatory process, exacerbated by cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), are considered to be the key mediators of IDD and LBP. IL-1β and TNF-α are the most important proinflammatory cytokines, as they have powerful proinflammatory activities and can promote the secretion of a variety of proinflammatory mediators. They are also upregulated in the degenerative IVDs, and they are closely related to various pathological IDD processes, including inflammatory response, matrix destruction, cellular senescence, autophagy, apoptosis, pyroptosis, and proliferation. Therefore, anti-IL-1β and anti-TNF-α therapies may have the potential to alleviate disc degeneration and LBP. In this paper, we reviewed the expression pattern and signal transduction pathways of IL-1β and TNF-α, and we primarily focused on their similar and different roles in IDD. Because IL-1β and TNF-α inhibition have the potential to alleviate IDD, an in-depth understanding of the role of IL-1β and TNF-α in IDD will benefit the development of new treatment methods for disc degeneration with IL-1β and TNF-α at the core.

Since December 2019, a novel coronavirus has spread throughout China and across the world, causing a continuous increase in confirmed cases within a short period of time. Some studies reported cases of thrombocytopenia, but hardly any studies mentioned how the virus causes thrombocytopenia. We propose several mechanisms by which coronavirus disease 2019 causes thrombocytopenia to better understand this disease and provide more clinical treatment options.

Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract. The absorption of SCFAs is mediated by substrate transporters, such as monocarboxylate transporter 1 and sodium-coupled monocarboxylate transporter 1, which promote cellular metabolism. An increasing number of studies have implicated metabolites produced by microorganisms as crucial executors of diet-based microbial influence on the host. SCFAs are important fuels for intestinal epithelial cells (IECs) and represent a major carbon flux from the diet, that is decomposed by the gut microbiota. SCFAs play a vital role in multiple molecular biological processes, such as promoting the secretion of glucagon-like peptide-1 by IECs to inhibit the elevation of blood glucose, increasing the expression of G protein-coupled receptors such as GPR41 and GPR43, and inhibiting histone deacetylases, which participate in the regulation of the proliferation, differentiation, and function of IECs. SCFAs affect intestinal motility, barrier function, and host metabolism. Furthermore, SCFAs play important regulatory roles in local, intermediate, and peripheral metabolisms. Acetate, propionate, and butyrate are the major SCFAs, they are involved in the regulation of immunity, apoptosis, inflammation, and lipid metabolism. Herein, we review the diverse functional roles of this major class of bacterial metabolites and reflect on their ability to affect intestine, metabolic, and other diseases. Video Abstract.

G Protein Coupled Receptor 109A (GPR109A), which belongs to the G protein coupled receptor family, can be activated by niacin, butyrate, and -hydroxybutyric acid. Here, we assessed the anti-inflammatory activity of sodium butyrate (SB) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mice, an experimental model that resembles Crohn's disease, and explored the potential mechanism of SB in inflammatory bowel disease (IBD). In vivo, experimental GPR109a -/-and wild-type (WT) mice were administered SB (5 g/L) in their drinking water for 6 weeks. The mice were then administered TNBS via rectal perfusion to imitate colitis. In vitro, RAW246.7 macrophages, Caco-2 cells, and primary peritoneal macrophages were used to investigate the protective roles of SB on lipopolysaccharide (LPS)-induced inflammatory response and epithelium barrier dysfunction. In vivo, SB significantly ameliorated the inflammatory response and intestinal epithelium barrier dysfunction in TNBS-induced WT mice, but failed to provide a protective effect in TNBS-induced GPR109a -/-mice. In vitro, pretreatment with SB dramatically inhibited the expression of TNF- and IL-6 in LPS-induced RAW246.7 macrophages. SB inhibited the LPS-induced phosphorylation of the NF-B p65 and AKT signaling pathways, but failed to inhibit the phosphorylation of the MAPK signaling pathway. Our data indicated that SB ameliorated the TNBS-induced inflammatory response and intestinal epithelium barrier dysfunction through activating GPR109A and inhibiting the AKT and NF-B p65 signaling pathways. These findings therefore extend the understanding of GPR109A receptor function and provide a new theoretical basis for treatment of IBD.