Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.

Objective:To investigate the change trend of hepatectomy for hepatocellular carcinoma and efficacy of fluorescent laparoscopic hepatectomy in a single center from 2014?2023.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 17 232 patients of hepatocellular carcinoma who were admitted to Zhongshan Hospital of Fudan University from January 2014 to December 2023 were collected. There were 14 404 males and 2 828 females, aged 58(range, 11?94)years. Observation indicators: (1) change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014?2023; (2) propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy; (3) intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶3 nearest neighbor matching method, with the caliper value of 0.01. Results:(1) Change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014-2023. Among 17 232 patients of hepatocellular carcinoma, 4 074 cases underwent laparoscopic surgery, and 13 158 cases underwent open surgery or conversion from laparoscopic to open surgery. From 2014 to 2023, the proportions of laparos-copic surgery in hepatectomy were 8.993%(117/1 301), 6.804%(99/1 455), 9.379%(145/1 546), 17.511%(287/1 639), 23.828%(427/1 792), 24.572%(459/1 868), 29.662%(544/1 834), 31.568%(584/1 850), 38.080%(599/1 573), and 34.246%(813/2 374), respectively. The proportions of Grade Ⅲ surgery in laparoscopic hepatectomy were 11.966%(14/117), 7.071%(7/99), 12.414%(18/145), 21.254%(61/287), 28.337%(121/427), 27.887%(128/459), 34.375%(187/544), 34.644%(214/584), 35.726%(214/599), and 42.681%(347/813), respectively. From 2016 to 2023, the proportions of the application of fluorescent laparoscopy in laparoscopic hepatectomy were 2.069%(3/145), 5.923%(17/287), 8.431%(36/427), 10.022%(46/459), 17.647%(96/544), 24.829%(145/584), 9.182%(55/599), and 12.915%(105/813), respectively. (2) Propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy. Among the 4 074 patients who underwent laparoscopic liver resection, 503 cases using fluorescent laparoscopy were assigned to the fluorescent laparoscopy group, 3 571 cases using conventional laparoscopy were assigned to the conventional laparoscopy group. A total of 1 794 patients were successfully matched, with 483 cases in the fluorescent laparoscopy group and 1 311 cases in the conventional laparoscopy group. After propensity score matching, the confounding biases of the maximum tumor diameter and the year of surgery were eliminated, and the two groups were comparable. (3) Intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. After propensity score matching, there was no perioperative death in either the fluorescent laparoscopy group or the conventional laparoscopy group.The operation time of patients in the fluorescent laparoscopy group was 240(150,328)minutes, the portal triad clamping time was 30(15,45)minutes, the volume of intraoperative blood loss was 50(30,100)mL, the number of patients with complication 72, respectively. For patients in the conventional laparoscopy group, the above indicators were 180(131,240)minutes, 23(15,30)minutes, 55(50,100)mL, and 248, respectively. There were significant differences in the above indicators between the two groups ( Z=?7.593, ?7.372, ?4.941, χ2=3.873, P<0.05). Conclusion:The proportion and difficulty level of laparoscopic hepatectomy for hepatocellular carcinoma in Zhongshan Hospital of Fudan University have shown an upward trend during 2014?2023. Compared with conventional laparoscopy, patients undergoing fluorescent laparoscopic hepatectomy have longer operation time and portal triad clamping time, but less intraoperative blood loss and lower iproportion of complications.

Objective:To investigate the change trend of hepatectomy for hepatocellular carcinoma and efficacy of fluorescent laparoscopic hepatectomy in a single center from 2014?2023.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 17 232 patients of hepatocellular carcinoma who were admitted to Zhongshan Hospital of Fudan University from January 2014 to December 2023 were collected. There were 14 404 males and 2 828 females, aged 58(range, 11?94)years. Observation indicators: (1) change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014?2023; (2) propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy; (3) intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶3 nearest neighbor matching method, with the caliper value of 0.01. Results:(1) Change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014-2023. Among 17 232 patients of hepatocellular carcinoma, 4 074 cases underwent laparoscopic surgery, and 13 158 cases underwent open surgery or conversion from laparoscopic to open surgery. From 2014 to 2023, the proportions of laparos-copic surgery in hepatectomy were 8.993%(117/1 301), 6.804%(99/1 455), 9.379%(145/1 546), 17.511%(287/1 639), 23.828%(427/1 792), 24.572%(459/1 868), 29.662%(544/1 834), 31.568%(584/1 850), 38.080%(599/1 573), and 34.246%(813/2 374), respectively. The proportions of Grade Ⅲ surgery in laparoscopic hepatectomy were 11.966%(14/117), 7.071%(7/99), 12.414%(18/145), 21.254%(61/287), 28.337%(121/427), 27.887%(128/459), 34.375%(187/544), 34.644%(214/584), 35.726%(214/599), and 42.681%(347/813), respectively. From 2016 to 2023, the proportions of the application of fluorescent laparoscopy in laparoscopic hepatectomy were 2.069%(3/145), 5.923%(17/287), 8.431%(36/427), 10.022%(46/459), 17.647%(96/544), 24.829%(145/584), 9.182%(55/599), and 12.915%(105/813), respectively. (2) Propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy. Among the 4 074 patients who underwent laparoscopic liver resection, 503 cases using fluorescent laparoscopy were assigned to the fluorescent laparoscopy group, 3 571 cases using conventional laparoscopy were assigned to the conventional laparoscopy group. A total of 1 794 patients were successfully matched, with 483 cases in the fluorescent laparoscopy group and 1 311 cases in the conventional laparoscopy group. After propensity score matching, the confounding biases of the maximum tumor diameter and the year of surgery were eliminated, and the two groups were comparable. (3) Intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. After propensity score matching, there was no perioperative death in either the fluorescent laparoscopy group or the conventional laparoscopy group.The operation time of patients in the fluorescent laparoscopy group was 240(150,328)minutes, the portal triad clamping time was 30(15,45)minutes, the volume of intraoperative blood loss was 50(30,100)mL, the number of patients with complication 72, respectively. For patients in the conventional laparoscopy group, the above indicators were 180(131,240)minutes, 23(15,30)minutes, 55(50,100)mL, and 248, respectively. There were significant differences in the above indicators between the two groups ( Z=?7.593, ?7.372, ?4.941, χ2=3.873, P<0.05). Conclusion:The proportion and difficulty level of laparoscopic hepatectomy for hepatocellular carcinoma in Zhongshan Hospital of Fudan University have shown an upward trend during 2014?2023. Compared with conventional laparoscopy, patients undergoing fluorescent laparoscopic hepatectomy have longer operation time and portal triad clamping time, but less intraoperative blood loss and lower iproportion of complications.

Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Gadoxetate magnetic resonance imaging (MRI) is widely used in clinical practice for liver imaging. For optimal use, we must understand both its advantages and limitations. This article is the outcome of an online advisory board meeting and subsequent discussions by a multidisciplinary group of experts on liver diseases across the Asia-Pacific region, first held on September 28, 2020. Here, we review the technical considerations for the use of gadoxetate, its current role in the management of patients with hepatocellular carcinoma (HCC), and its relevance in consensus guidelines for HCC imaging diagnosis. In the latter part of this review, we examine recent evidence evaluating the impact of gadoxetate on clinical outcomes on a continuum from diagnosis to treatment decision-making and follow-up. In conclusion, we outline the potential future roles of gadoxetate MRI based on an evolving understanding of the clinical utility of this contrast agent in the management of patients at risk of, or with, HCC.

Objective:To explore the risk factors influencing the prognosis for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation and summarize the relevant diagnostic and therapeutic experiences.Methods:The clinicopathological features with diagnosis and treatment plan of 102 recurrent HCC patients fulfilling the Fudan Criteria were compared for survival rate (univariate analysis) and independent prognostic indicators were obtained by Cox multivariate analysis.Results:The 1/3/5-year overall survival rates were 92.2%, 48.6% and 34.6% and the 1/3/5-year survival rates with tumor were 63.2%, 31.0% and 16.7% respectively. Cox regression analysis indicated that patient age, whether tumor can be surgically resected or not and personalized diagnostic & therapeutic plan based upon targeted therapy were independent prognostic factors affecting the overall survival rates and survival rates with tumor.Conclusions:Although HCC recurrence and metastasis after liver transplantation seriously influence patient prognosis, satisfactory outcomes may be obtained for some patients through active, effective and precise managements.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice and has the features of high incidence rate, poor prognosis, and high mortality rate, and its incidence rate and mortality rate rank among the top malignant tumors in the world. High heterogeneity of HCC affects the evolution and therapeutic response of HCC. Since most HCC patients are in the advanced stage at the time of diagnosis, systemic treatment has become the main treatment option. In recent years, remarkable achievements have been made in molecular targeted therapy and immunotherapy for HCC, and the latest NCCN guidelines for the systemic treatment of HCC show that sorafenib, lenvatinib, and atezolizumab combined with bevacizumab are recommended as the first-line treatment of HCC, and regorafenib, cabozantinib, nivolumab, pembrolizumab, and ramucirumab are the second-line treatment options for HCC. In the era of precision medicine, how to select the optimal individualized systemic treatment regimen is the key problem in the systemic treatment of HCC. This article reviews the advances in the systemic treatment of HCC in the era of precision medicine and discusses the development direction of HCC treatment in the future.