{"title":"Fungal mycobiome dysbiosis in choledocholithiasis concurrent with cholangitis.","authors":"Zhiyuan Hao, Yiting Lu, Yarong Hao, Yuanyuan Luo, Kaiming Wu, Changpeng Zhu, Peimei Shi, Feng Zhu, Yong Lin, Xin Zeng","doi":"10.1007/s00535-024-02183-y","DOIUrl":"10.1007/s00535-024-02183-y","url":null,"abstract":"<p><strong>Background: </strong>The gut mycobiome might have an important influence on the pathogenesis of choledocholithiasis concurrent with cholangitis (CC). The aim of this study was to characterize the fungal mycobiome profiles, explore the correlation and equilibrium of gut interkingdom network among bacteria-fungi-metabolites triangle in CCs.</p><p><strong>Methods: </strong>In a retrospective case-control study, we recruited patients with CC (n = 25) and healthy controls (HCs) (n = 25) respectively to analyze the gut fungal dysbiosis. Metagenomic sequencing was employed to characterize the gut mycobiome profiles, and liquid chromatography/mass spectrometry (LC/MS) analysis was used to quantify the metabolites composition.</p><p><strong>Results: </strong>The Shannon index displayed a reduction in fungal α-diversity in CCs compared to HCs (p = 0.041), and the overall fungal composition differed significantly between two groups. The dominant 7 fungi species with the remarkable altered abundance were identified (LDA score > 3.0, p < 0.05), including CC-enriched Aspergillus_niger and CC-depleted fungi Saccharomyces_boulardii. In addition, the correlations between CC-related fungi and clinical variables in CCs were analyzed. Moreover, the increased abundance ratio of Basidiomycota-to-Ascomycota and a dense linkage of bacteria-fungi interkingdom network in CCs were demonstrated. Finally, we identified 30 markedly altered metabolites in CCs (VIP > 1.0 and p < 0.05), including low level of acetate and butyrate, and the deeper understanding on the complexity of bacteria-fungi-metabolites triangle involving bile inflammation was verified.</p><p><strong>Conclusion: </strong>Our investigation demonstrated a distinct gut fungal dysbiosis in CCs and proposed that, beyond bacteria, the more attention should be paid to significantly potential influence of fungi and bacteria-fungi-metabolites triangle interkingdom interactions on pathogenesis of CC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"340-355"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryoichi Miura, Atsushi Ono, Hikaru Nakahara, Yuki Shirane, Kenji Yamaoka, Yasutoshi Fujii, Shinsuke Uchikawa, Hatsue Fujino, Eisuke Murakami, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Takeshi Kishi, Waka Ohishi, Naoya Sakamoto, Koji Arihiro, Clair Nelson Hayes, Shiro Oka
{"title":"Serum IL-6 concentration is a useful biomarker to predict the efficacy of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.","authors":"Ryoichi Miura, Atsushi Ono, Hikaru Nakahara, Yuki Shirane, Kenji Yamaoka, Yasutoshi Fujii, Shinsuke Uchikawa, Hatsue Fujino, Eisuke Murakami, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Takeshi Kishi, Waka Ohishi, Naoya Sakamoto, Koji Arihiro, Clair Nelson Hayes, Shiro Oka","doi":"10.1007/s00535-024-02185-w","DOIUrl":"10.1007/s00535-024-02185-w","url":null,"abstract":"<p><strong>Background: </strong>This study aims to identify biomarkers for treatment response of atezolizumab plus bevacizumab (Atezo+Bev) in patients with hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>96 patients who received Atezo+Bev or lenvatinib as a first-line systemic therapy were enrolled as the training group after propensity score matching (PSM), and 42 patients treated with Atezo+Bev were enrolled as the validation group. 17 serum cytokines were measured by Luminex multiplex assay at the start of treatment. For further assessment of the association between cytokine levels and the tumor microenvironment (TME), immunohistochemistry (IHC) was performed on pre-treatment liver biopsy specimens.</p><p><strong>Results: </strong>In the derivation set, multivariate analysis identified elevated IL-6 as an independent risk factor in the Atezo+Bev group (HR 5.80: p<0.01), but not in the lenvatinib group; in a subset analysis of patients with low IL-6, PFS was longer in the Atezo+Bev training group than in the lenvatinib group (p = 0.02). A validation study also showed a significantly longer prognosis in the low IL-6 group for both PFS (p = 0.0001) and OS (p = 0.03). Serum IL-6 had a positive correlation with tumor IL-6 expression (ρ = 0.56, p < 0.0001) and an inverse correlation with the CD8/CD163-positive cell count ratio (ρ = -0.4, p < 0.01).</p><p><strong>Conclusion: </strong>Serum IL-6 levels are thought to be involved in the suppression of tumor immunity and are useful in predicting the therapeutic effect of Atezo+Bev treatment.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"328-339"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy of liposomal irinotecan + 5-FU/LV vs. S-1 in gemcitabine-refractory metastatic pancreatic cancer: a real-world study using inverse probability of treatment weighting.","authors":"Hiroshi Imaoka, Masafumi Ikeda, Satoshi Kobayashi, Akihiro Ohba, Masayuki Ueno, Yuko Suzuki, Hidetaka Tsumura, Nana Kimura, Shinya Kawaguchi, Yasuyuki Kawamoto, Kohei Nakachi, Kunihiro Tsuji, Noritoshi Kobayashi, Reiko Ashida, Naohiro Okano, Kumiko Umemoto, Gou Murohisa, Ayumu Hosokawa, Akinori Asagi, Hiroko Nebiki, Rei Suzuki, Takeshi Terashima, Ryusuke Shibata, Kazuhito Kawata, Toshifumi Doi, Hiroshi Ohyama, Yohei Kitano, Kazuhiko Shioji, Hiroyuki Okuyama, Atsushi Naganuma, Yuji Negoro, Yasunari Sakamoto, Satoshi Shimizu, Chigusa Morizane, Makoto Ueno, Junji Furuse, Hiroaki Nagano","doi":"10.1007/s00535-024-02186-9","DOIUrl":"10.1007/s00535-024-02186-9","url":null,"abstract":"<p><strong>Background: </strong>S-1 monotherapy had previously been widely used as a second-line treatment for pancreatic cancer (PC) after gemcitabine-based chemotherapy mainly in Japan. Based on the results of the NAPOLI-1 trial, the recommended second-line therapy is now liposomal irinotecan plus fluorouracil/folinic acid (nal-IRI + 5-FU/LV). However, there have been no studies comparing nal-IRI + 5-FU/LV therapy with S-1 monotherapy.</p><p><strong>Methods: </strong>The main objective of this study was to compare overall survival (OS) in patients treated with nal-IRI + 5-FU/LV and those treated with S-1 monotherapy as second-line treatments, using the inverse probability of treatment weighting (IPTW) method. This study was conducted in 31 institutions participating in Japan Oncology Network in Hepatobiliary and Pancreas. To minimize potential biases due to the retrospective design, IPTW analysis was performed with multiple imputation, and imputed IPTW-adjusted hazard ratios and corresponding 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model and combined into pooled estimates.</p><p><strong>Results: </strong>A total of 463 metastatic PC patients were enrolled in this study (257 in the S-1 monotherapy group and 206 in the nal-IRI + 5-FU/LV group). The median OS was 7.50 months (95% CI 4.18-12.69 months) in the nal-IRI + 5-FU/LV group and 5.72 months (95% CI 2.76-10.79 months) in the S-1 monotherapy group. In the IPTW-adjusted Cox proportional hazards model, nal-IRI + 5-FU/LV was associated with a significant OS benefit (pooled IPTW-adjusted hazard ratio, 0.779; 95% CI 0.399-0.941; p = 0.025).</p><p><strong>Conclusion: </strong>These findings support the use of nal-IRI + 5-FU/LV as standard second-line treatment for PC patients after gemcitabine-based chemotherapy.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"356-367"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical factors to predict changes of esophagogastric varices after sustained viral response with direct-acting antiviral therapy.","authors":"Takao Watanabe, Yoshio Tokumoto, Hironori Ochi, Toshie Mashiba, Fujimasa Tada, Atsushi Hiraoka, Yoshiyasu Kisaka, Yoshinori Tanaka, Sen Yagi, Seiji Nakanishi, Kotaro Sunago, Kazuhiko Yamauchi, Makoto Higashino, Kana Hirooka, Masaaki Tange, Atsushi Yukimoto, Makoto Morita, Yuki Okazaki, Masashi Hirooka, Masanori Abe, Yoichi Hiasa","doi":"10.1007/s00535-024-02174-z","DOIUrl":"10.1007/s00535-024-02174-z","url":null,"abstract":"<p><strong>Background: </strong>The clinical course of esophagogastric varices (EGV) after sustained virological response (SVR) with direct-acting antiviral (DAA) therapy has not been clearly elucidated. The predictors for the worsening/improvement of EGV after SVR with DAA therapy were investigated.</p><p><strong>Methods: </strong>Of the cirrhosis patients who achieved SVR with DAA therapy, 328 patients who underwent endoscopic examinations both before and after DAA therapy were enrolled. The predictors of EGV worsening or improvement were investigated.</p><p><strong>Results: </strong>Multivariate analysis identified a history of ascites retention, albumin at baseline, and MELD score at baseline as independent factors that contributed to EGV exacerbation. On multivariate analysis, two factors, BMI and platelet count, were related to EGV improvement. An integrated scoring system was created using these risk factors with or without weighting according to each hazard ratio, and the patients were divided into three groups. A scoring system with weighting of each factor appeared to be more useful, with fewer intermediate patients and more cases classified into the low-risk and high-risk groups.</p><p><strong>Conclusion: </strong>Esophagogastric varices after SVR have a varied clinical course. Using this scoring system that can accurately predict EGV outcomes in clinical settings, it may be feasible to establish a risk-based EGV surveillance plan following SVR.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"222-234"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between homologous recombination deficiency and time to treatment failure to platinum-based chemotherapy for pancreatic cancer by using the C-CAT database.","authors":"Kazunaga Ishigaki, Yurie Tokito, Naminatsu Takahara, Hiroto Nishio, Go Endo, Koshiro Fukuda, Kota Ishida, Rintaro Fukuda, Shinya Takaoka, Hiroki Oyama, Kensaku Noguchi, Tatsunori Suzuki, Tatsuya Sato, Tomotaka Saito, Tsuyoshi Hamada, Koji Miyabayashi, Yasuyoshi Sato, Yousuke Nakai, Hidenori Kage, Katsutoshi Oda, Mitsuhiro Fujishiro","doi":"10.1007/s00535-024-02173-0","DOIUrl":"10.1007/s00535-024-02173-0","url":null,"abstract":"<p><strong>Background: </strong>Since homologous recombination deficiency (HRD) is relatively uncommon in pancreatic cancer (PC), its impact on time-to-treatment failure (TTF) among patients undergoing systemic chemotherapy for unresectable and recurrent PC remains uncertain.</p><p><strong>Methods: </strong>Among patients with unresectable and recurrent PC enrolled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database by July 2023, a total of 1394 patients who underwent first-line chemotherapy with either gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FFX) and received tissue-based CGP tests after disease progression were included in this study. HRD was defined as the presence of germline or somatic genetic mutations in homologous recombination repair (HRR)-related genes such as ATM, BARD1, BRIP1, BRCA1/2, CHEK2, CDK12, PALB, and RAD51C/D. We investigated the correlation between HRD and TTF among patients treated with GnP and FFX.</p><p><strong>Results: </strong>First-line chemotherapy consisted of GnP in 69% of the cases and FFX in 31%. The CGP tests used were NCC OncoPanel and FoundationOne CDx in 26% and 74%, respectively. HRR-related genetic abnormalities were identified in 107 patients (7.6%): BRCA2 (n = 51), ATM (n = 34), BRCA1 (n = 9), PALB2 (n = 9), among others. In the GnP cohort, the median TTF was comparable between the HRD and non-HRD groups (5.3 vs 4.6 months, P = 0.44). Conversely, in the FFX cohort, it was significantly longer in the HRD group compared to the non-HRD group (7.3 vs. 4.7 months, p < 0.01).</p><p><strong>Conclusions: </strong>Our findings suggest that HRR-related genetic abnormalities might be predictive of TTF in platinum-based chemotherapy for PC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"247-256"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel subharmonic-aided pressure estimation for identifying high-risk esophagogastric varices.","authors":"Hidekatsu Kuroda, Tamami Abe, Naohisa Kamiyama, Takuma Oguri, Asami Ito, Ippeki Nakaya, Takuya Watanabe, Hiroaki Abe, Kenji Yusa, Yudai Fujiwara, Hiroki Sato, Akiko Suzuki, Kei Endo, Yuichi Yoshida, Takayoshi Oikawa, Keisuke Kakisaka, Kei Sawara, Akio Miyasaka, Takayuki Matsumoto","doi":"10.1007/s00535-024-02161-4","DOIUrl":"10.1007/s00535-024-02161-4","url":null,"abstract":"<p><strong>Background: </strong>Subharmonic-aided pressure estimation (SHAPE) is a technique for determining changes in ambient pressure. We aimed to analyze a novel SHAPE integrated into ultrasound diagnostic equipment to predict patients with liver cirrhosis at high risk of esophagogastric varices (EV).</p><p><strong>Methods: </strong>This prospective study included 111 patients with liver cirrhosis diagnosed between 2020 and 2023. We obtained liver stiffness measurements (LSM) and spleen stiffness measurements (SSM) using shear wave elastography and hepatic vein-portal vein (HV-PV) gradient using the SHAPE method. The EV risk was determined either as null, low, or high by esophagoscopy and Child-Pugh stage.</p><p><strong>Results: </strong>HV-PV gradient increased concordantly with the increase in EV risk (- 7.0 dB in null-risk, - 4.4 dB in low-risk, and - 2.0 dB in high-risk) with statistically significant difference among any two groups. The most appropriate cut-off value of the HV-PV gradient was - 3.5 dB, and sensitivity, specificity, and positive and negative predictive values were 80.0%, 89.0%, 80.0%, and 88.0%, respectively. The areas under the curve values for predicting the high-risk EV were 0.920, 0.843, and 0.824 for the HV-PV gradient, LSM, and SSM, respectively.</p><p><strong>Conclusions: </strong>The novel SHAPE system demonstrated high accuracy in identifying patients with liver cirrhosis at a high risk of EV.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"187-196"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histological improvement of fibrosis in patients with hepatitis C who achieved a 5-year sustained virological response to treatment with direct-acting antivirals.","authors":"Takayuki Iwamoto, Yasutoshi Nozaki, Takanori Inoue, Takahiro Suda, Rui Mizumoto, Yuki Arimoto, Takashi Ohta, Shinjiro Yamaguchi, Yoshiki Ito, Yoshiko Sudo, Michiko Yoshimura, Machiko Kai, Yoichi Sasaki, Yuki Tahata, Hayato Hikita, Tetsuo Takehara, Hideki Hagiwara","doi":"10.1007/s00535-024-02165-0","DOIUrl":"10.1007/s00535-024-02165-0","url":null,"abstract":"<p><strong>Background: </strong>The histological improvement in liver fibrosis in patients with hepatitis C who achieved a sustained virological response (SVR) to direct-acting antiviral (DAA) treatment has not been comprehensively investigated. Therefore, we assessed the histological changes in liver fibrosis among patients with hepatitis C who underwent long-term follow-up after achieving SVR to treatment with DAA.</p><p><strong>Methods: </strong>This retrospective study enrolled 71 patients with hepatitis C who achieved SVR to treatment with DAA. Changes in histological liver fibrosis and fibrosis biomarkers (hyaluronic acid, type 4 collagen 7S, Mac-2 binding protein glycosylation isomer, autotaxin, and Fibrosis-4 index) were assessed before and 5 years after treatment. Transient elastography using the FibroScan® device was performed 5 years after treatment. Advanced fibrosis and cirrhosis were defined as Ishak fibrosis scores of ≥ 4 and ≥ 5, respectively.</p><p><strong>Results: </strong>Histological liver fibrosis significantly regressed after SVR. Fibrosis biomarkers were significantly reduced after SVR. Transient elastography was the most helpful after evaluating the predictive performance of advanced fibrosis and cirrhosis after SVR, with an area under the receiver operating characteristic curve of 0.965 and a cut-off value of 6.75 kPa. The cut-off values of serum fibrosis biomarkers for identifying advanced fibrosis and cirrhosis after SVR were lower than those before treatment.</p><p><strong>Conclusions: </strong>Long-term SVR to treatment with DAA ameliorated histological liver fibrosis. Noninvasive tests helped predict the degree of liver fibrosis after SVR, but their cut-off values should be redefined to avoid underestimation of liver fibrosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"197-209"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zi Cao, Yichen Yang, Shasha Liu, Lin Sun, Yanxue Liu, Ye Luo, Jian Wang, Yan Sun
{"title":"FGFR2 fusions assessed by NGS, FISH, and immunohistochemistry in intrahepatic cholangiocarcinoma.","authors":"Zi Cao, Yichen Yang, Shasha Liu, Lin Sun, Yanxue Liu, Ye Luo, Jian Wang, Yan Sun","doi":"10.1007/s00535-024-02175-y","DOIUrl":"10.1007/s00535-024-02175-y","url":null,"abstract":"<p><strong>Background: </strong>FGFR2 fusion has become a promising therapeutic target in iCCAs; however, the procedure for screening FGFR2 fusion has not been conventionally developed.</p><p><strong>Methods: </strong>FGFR2 fusion was identified using DNA + RNA-based NGS and FISH, and the concordance between DNA + RNA-based NGS, FISH, and IHC was compared.</p><p><strong>Results: </strong>FGFR2 fusions were detected in 9 out of 76 iCCAs (11.8%). The consistency of FISH and DNA + RNA-based NGS for FGFR2 fusions was high (κ value = 0.867, P = 0.001), while the consistency of IHC and DNA + RNA-based NGS was lower (κ value = 0.464, P = 0.072). All nine FGFR2 fusion-positive iCCAs were MSS with a median TMB of 2.1 mut/Mb, and only one had a CPS (PD-L1) above 5. Two FGFR2 fusion-positive iCCA patients were treated with and benefited from FGFR inhibitor therapy.</p><p><strong>Conclusions: </strong>FGFR2 fusion should be assessed for advanced iCCA patients. We recommend DNA + RNA-based NGS as the preferred option to supply all possible therapeutic targets. FISH should be preferred if the tumor sample is insufficient for NGS or if the patient is inclined to receive FGFR inhibitors promptly. Although IHC is not the preferred method to identify FGFR2 fusion, it might be used as preliminary screening for FGFR2 alterations if the hospital cannot offer NGS or FISH, and the results need to be validated before FGFR2 inhibitors treatment.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"235-246"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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