Chinese Academy Of Medical Sciences Research Articles

Should lymphadenectomy be recommended in radical surgery of intrahepatic cholangiocarcinoma patients? A retrospective study

PurposeIntrahepatic cholangiocarcinoma (ICC) is an extremely deadly cancer with high recurrence incidence, particularly in patients with lymph node metastasis (LNM). The necessity of lymphadenectomy including lymph node biology (LNB) and dissection (LND) during ICC radical surgery remains debate.MethodsWe retrospectively analyzed the patients diagnosed with ICC and underwent radical surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences from 2012 to 2023.ResultsA total of 308 ICC patients were involved in this study. pLNM+ group had poorer OS (P < 0.0001) and poorer DFS (P < 0.0001) compared with pLNM− group. Compared to the LN− group, LN+ group exhibited worse OS (P = 0.038) and worse DFS (P = 0.003). After PSM and IPTW, compared with LN− group, LNB exhibited longer operation time (IPTW: P = 0.0024) and longer hospitalization days (IPTW: P = 0.0112) with no significant differences in complications, DFS, and OS. Compared with LN− group, LND group had no better DFS and OS, only more complications (IPTW: P = 0.0191), longer operation time (all P < 0.001), higher risk of bleeding (all P < 0.05), transfusion (IPTW: P = 0.014) and longer hospitalization days (IPTW: P = 0.0044). Compared with LNB group, LND had longer operation time (P = 0.0227), higher risk of bleeding (P = 0.017) and transfusion (P = 0.0321), and more postoperative complications (P = 0.0425), with no difference in DFS and OS.ConclusionLymphadenectomy does not necessarily provide long-term survival or recurrence benefits. LND only achieves the effect of LNB while negatively affects postoperative recovery without survival benefit for ICC patients. LNB can be performed for accurate pathological staging while not all patients may require LND based on their specific circumstances.

Knowledge map and emerging trends of oxidative stress in wound healing: A bibliometric analysis from 2000 to 2023.

The skin's integrity is vulnerable to external elements that can induce injuries, leading to wound formation. It's crucial to comprehend wound healing processes to protect the body when this protective barrier is compromised. Over the last 2 decades, there has been considerable progress in understanding delayed wound healing, with a focus on the mechanisms and microenvironmental factors involved. The connection between oxidative stress and wound healing has recently gained attention, emphasizing the need for in-depth analysis to propel further advancements and interventions in this area. Despite these advancements, there remains a noticeable void in the literature concerning the application of scientometric methods to systematically examine the progression of wound healing research. Additionally, a comprehensive assessment of the research output and effectiveness of various researchers and institutions in this field is lacking. To address these gaps, we analyzed data from the Web of Science Core Collection from January 1, 2000, to December 31, 2023, utilizing relevant keywords. Using CiteSpace, we created visual maps that depict the evolution and structure of keyword clusters, and both CiteSpace and VOSviewer were used to evaluate the performance of research networks across different countries, institutions, and authors. This data was methodically analyzed. The leading institution in this field is the Chinese Academy of Medical Sciences. The key researchers are Bekeschus, Sander; Li, Yang; Bi, Yang; Fan, Daidi; and Zhang, Yu. Our software analysis reviewed 3025 studies, revealing 19 co-citation clusters that highlight current trends in research on oxidative stress and wound healing. Prominent journals, leading institutions, and key researchers were identified. Key emerging research directions include studying the mechanisms linking oxidative stress to wound healing, exploring the use of antioxidant substances in wound dressings, and investigating how nanomaterials in dressings can influence oxidative stress. These focal points emphasize the significance of understanding oxidative stress's impact on wound healing and investigating new methods to enhance therapeutic efficacy. This comprehensive approach not only fills a gap in the current literature but also sets the stage for future research endeavors in this crucial area of health science.

Autologous P63+ lung progenitor cell transplantation in idiopathic pulmonary fibrosis: a phase 1 clinical trial.

In idiopathic pulmonary fibrosis (IPF) patients, alveolar architectures are lost and gas transfer function would decline, which cannot be rescued by conventional anti-fibrotic therapy. P63+ lung basal progenitor cells are reported to have potential to repair damaged lung epithelium in animal models, which need further investigation in clinical trials. We cloned and expanded P63+ progenitor cells from IPF patients to manufacture cell product REGEND001, which were further characterized by morphology and single-cell transcriptomic analysis. Subsequently, an open-label, dose-escalation autologous progenitor cell transplantation clinical trial was conducted. We treated 12 patients with ascending doses of cells: 0.6x, 1x, 2x and 3.3x106 cells/kg bodyweight. The primary outcome was the incidence and severity of cell therapy-related adverse events (AEs); secondary outcome included other safety and efficacy evaluations. P63+ basal progenitor cell was safe and tolerated at all doses, with no dose-limiting toxicity or cell therapy-related severe adverse events observed. Patients in three higher dose groups showed significant improvement of lung gas transfer function as well as exercise ability. Resolution of honeycomb lesion was observed in patients of higher dose groups. REGEND001 has high safety profile and meanwhile encourages further efficacy exploration in IPF patients. National High Level Hospital Clinical Research Funding (2022-PUMCH-B-108), National Key Research and Development Plan (2024YFA1108900, 2024YFA1108500), Jiangsu Province Science and Technology Special Project Funding (BE2023727), National Biopharmaceutical Technology Research Project Funding (NCTIB2023XB01011), Non-profit Central Research Institute Fund of Chinese Academy of Medical Science (2020-PT320-005), and Regend Therapeutics. Chinese clinical trial registry: CTR20210349.

Autologous P63+ lung progenitor cell transplantation in idiopathic pulmonary fibrosis: a phase 1 clinical trial

Background:In idiopathic pulmonary fibrosis (IPF) patients, alveolar architectures are lost and gas transfer function would decline, which cannot be rescued by conventional anti-fibrotic therapy. P63+ lung basal progenitor cells are reported to have potential to repair damaged lung epithelium in animal models, which need further investigation in clinical trials.Methods:We cloned and expanded P63+ progenitor cells from IPF patients to manufacture cell product REGEND001, which were further characterized by morphology and single-cell transcriptomic analysis. Subsequently, an open-label, dose-escalation autologous progenitor cell transplantation clinical trial was conducted. We treated 12 patients with ascending doses of cells: 0.6x, 1x, 2x and 3.3x106 cells/kg bodyweight. The primary outcome was the incidence and severity of cell therapy-related adverse events (AEs); secondary outcome included other safety and efficacy evaluations.Results:P63+ basal progenitor cell was safe and tolerated at all doses, with no dose-limiting toxicity or cell therapy-related severe adverse events observed. Patients in three higher dose groups showed significant improvement of lung gas transfer function as well as exercise ability. Resolution of honeycomb lesion was observed in patients of higher dose groups.Conclusions:REGEND001 has high safety profile and meanwhile encourages further efficacy exploration in IPF patients.Funding:National High Level Hospital Clinical Research Funding (2022-PUMCH-B-108), National Key Research and Development Plan (2024YFA1108900, 2024YFA1108500), Jiangsu Province Science and Technology Special Project Funding (BE2023727), National Biopharmaceutical Technology Research Project Funding (NCTIB2023XB01011), Non-profit Central Research Institute Fund of Chinese Academy of Medical Science (2020-PT320-005), and Regend Therapeutics.Clinical trial number:Chinese clinical trial registry: CTR20210349.

Research progress and frontier analysis of Laugier-Hunziker syndrome at home and abroad based on Citespace

Objective: Analyzing the overview, changing trends, hotspots, and frontiers of the rare oral disease Laugier-Hunziker syndrome (LHS) using bibliometrics. Methods: Search the CNKI (China National Knowledge Infrastructure) and Web of science core collection (WOSCC) databases. The time span for Chinese literature is from January 1992 to December 2023, and for English literature is from January 1986 to December 2023. Utilize Citespace software to conduct visualized analysis on various aspects of the literature, including publication volume, authors, countries, institutions, journals, and keywords. Results: This study included a total of 112 articles (25 in Chinese and 87 in English). The overall publication volume showed a fluctuating slow-growth trend. Foreign authors Lenane P and Powell F had the highest number of publications. The team from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, had the most publications among domestic authors. In terms of international collaboration, the United States demonstrated the highest centrality, but the collaborative network worldwide appeared relatively loose. University College Dublin was the foreign institution with the highest publication volume, while Peking Union Medical College Hospital was the domestic institution with the most publications. The journal with the highest number of foreign publications was the Journal of The American Academy of Dermatology, and the journal with the most domestic publications was the Chinese Leprosy Skin Disease Journal. Research hotspots for Laugier-Hunziker syndrome included lesion sites and differential diagnosis, while the frontiers of research encompassed differential diagnosis, disease management, and clinical manifestations related to oral mucosa. Conclusions: Laugier-Hunziker syndrome research shows a focus on differential diagnosis and symptom management. Future studies should prioritize optimizing treatment methods and emphasizing psychological support, while promoting interdisciplinary collaboration and the integration of global research networks to improve clinical diagnostic and therapeutic outcomes.

The impact of peritoneal cytology test results on the prognosis of patients with uterine serous carcinoma

Objective: To explore the impact of peritoneal cytology (PC) test results on prognosis in patients with uterine serous carcinoma (USC). Methods: Medical record information including history of tubal ligation and preoperative hysteroscopy, pathology, surgery, adjuvant therapy, etc. of USC patients admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from January 2004 to December 2020 was retrospectively collected and the cytological sections of PC were reviewed. Positive peritoneal cytology (PPC) patients were classified as PPC group while negative peritoneal cytology (NPC) patients were NPC group. The survival analyses were performed by Kaplan Meier method and prognostic factors of USC patients were analyzed by Cox proportional hazards regression model. Results: A total of 147 USC patients were included, aged [M(Q1,Q3)] 60 (54, 64) years. There were 43 cases (29.3%) in the PPC group and 104 cases (70.7%) in the NPC group. The follow-up time was [M(Q1,Q3)] 60 (34, 73) months, with 52 cases of USC recurrence and 30 patients deaths. The 5-year progression free survival rate was 66.5% and the 5-year overall survival rate was 79.2%. Both 5-year progression free survival rate (41.2% vs 77.0%) and 5-year overall survival rate (58.6% vs 87.1%) were lower in PPC group than those in NPC group (both P<0.001). In 102 patients without pelvic abdominal involvement (stage Ⅰ, Ⅱ, and stage Ⅲ patients with only lymph node metastasis), PPC was associated with USC recurrence (HR=4.191, 95%CI: 1.729-10.165) and USC patients death (HR=4.306, 95%CI: 1.351-13.731). Among 45 patients with pelvic abdominal involvement, PPC was not associated with USC recurrence (HR=1.450, 95%CI: 0.637-3.303) or patient death (HR=1.520, 95%CI: 0.488-4.730). Conclusions: In USC patients, compared with NPC, PPC patients have poorer prognosis. PPC is a factor for prognosis in USC patients without pelvic abdominal involvement.

Application of pedicle or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery

Objective: To investigate the application of pedicled or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery. Methods: From January 2005 to December 2023, 20 patients with vulvar cancer who underwent extensive episiectomy or extended episiectomy±inguinal lymph node resection+vulvar defect flap transfer were collected in Huanxing Cancer Hospital of Chaoyang District and Cancer Hospital and Peking Union Medical College, Chinese Academy of Medical Sciences. The survival status, appearance structure, sexual function satisfaction, tumor recurrence, and survival were analyzed. Results: (1) The median age of the 20 patients was 59 years (ranged: 29-73 years). There were 14 patients with recurrence and 6 patients with initial treatment. Pathological types: 14 cases of squamous cell carcinoma, 4 cases of Paget's disease, 1 case of malignant melanoma, 1 case of adenoid cystic carcinoma (salivary gland type carcinoma). (2) Among the 20 patients, 6 cases underwent extensive episiotomy and 14 underwent extended episiotomy (1 of them underwent extensive excision of inguinal masses). Simultaneous inguinal lymphadenectomy (or dissection) were performed in 11 cases, including 7 cases of bilateral inguinal lymph node resection (or dissection) and 4 cases of unilateral inguinal lymph node resection (or dissection). Flap source: pedicled flap in 12 cases, perforator flap in 8 cases. All the 20 patients were removed at 10-14 days after operation, and all of them survived with rosy skin color and good elasticity. Seventeen cases of transferred flaps healed at stage Ⅰ, 2 cases healed at about 6 weeks due to incision leakage, and 1 case healed at 6 weeks after incision infection debridement. Six months after the operation, 2 cases felt that the pubic mound was thick and swollen. The other 18 cases showed vulva fullness and elasticity, no displacement of urethral opening, no deviation of urethra during urination, no stenosis of vaginal opening, no vulvar scar pain. In addition to 1 unmarried 29-year-old patient and 6 patients over 65 years old who had no sexual life before and after surgery, the other 13 patients had normal sexual life after surgery. (3) The follow-up period were 6 to 100 months, and 9 cases (45%, 9/20) relapsed during the follow-up period. There were 5 deaths (25%, 5/20), who were due to recurrence of vulvar cancer. The 5-year survival rate of 20 patients was 75%, including 83% in 6 patients with initial treatment and 71% in 14 patients with recurrence and reoperation. Conclusions: The combination of flap transfer for episioplasty with vulvar cancer surgery does not affect the wound healing. Because the external structure of the vulva is repaired, it could effectively improve the local wound healing ability and improve the organ function, and has good clinical application value.

Construction and preliminary validation of machine learning predictive models for cervical cancer screening based on human DNA methylation

Objective: Using methylation characteristics of human genes to construct machine learning predictive models for screening cervical cancer and precancerous lesions. Methods: Human DNA methylation detection was performed on 224 cervical exfoliated cell specimens from the Cancer Hospital of the Chinese Academy of Medical Sciences, Tianjin Central Hospital of Gynecology Obstetrics, Xinmi Maternal and Child Health Hospital of Henan Province, West China Second Affiliated Hospital of Sichuan University, and Heping Hospital Affiliated to Changzhi Medical College collected during April 2014 and March 2015. The hypermethylated gene fragments related to cervical cancer were selected by high-density, high-association, and hypermethylated gene fragment screening and the LASSO regression algorithm. Taking cervical intraepithelial neoplasia grade 2 (CIN2) or more severe lesions as the research outcome, machine learning predictive models based on the random forest (RF), naive Bayes (NB), and support vector machine (SVM) algorithm, respectively, were constructed. A total of 144 outpatient specimens were used as the training set and 80 cervical exfoliated cell specimens from women participating in the cervical cancer screening program were used as the test set to verify the predictive models. Using histological diagnosis results as the gold standard, the detection efficacy for CIN2 or more severe lesions of the three machine learning predictive models were compared with that of the human papilloma virus (HPV) detection and cytological diagnosis. Results: In the training set of 144 cases, there were 34 cases of HPV positivity, with a positive rate of 23.61%. Cytologically, there were 37 cases diagnosed as no intraepithelial lesion or malignancy (NILM), and 107 cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) or above. Histologically, there were 28 cases without cervical intraepithelial neoplasia or benign cervical lesions, 31 cases of CIN1, 18 cases of CIN2, 31 cases of CIN3, and 36 cases of squamous cell carcinoma. Seven hypermethylated gene fragments were selected from 45 genes, and three machine learning prediction models based on the RF, NB, and SVM algorithm, respectively, were constructed. In the validation set of 80 cases, there were 28 cases of HPV positivity, with a positive rate of 35.00%. Cytologically, there were 65 cases diagnosed as NILM and 15 cases as ASC-US or above. Histologically, there were 39 cases without cervical intraepithelial neoplasia or benign cervical lesions, 10 cases of CIN1, 10 cases of CIN2, 11 cases of CIN3, and 10 cases of squamous cell carcinoma. In the validation set, the area under the curve (AUC) values of the RF model, NB model, SVM model, HPV detection, and cytological diagnosis of CIN2 or above were 0.90, 0.88, 0.82, 0.68, and 0.45, respectively. The DeLong test showed that there was no statistically significant difference in the AUC values between the RF, NB, and SVM models (all P＞0.05), and the AUC values of the RF and NB models were higher than that of HPV detection (both P＜0.01), and the AUC values of the RF, NB, and SVM models were higher than that of cytological diagnosis (all P＜0.01). Compared with the NB model, the sensitivity of the RF model was similar (80.65% vs. 77.42%), but the specificity of the NB model was much higher than that of the RF model (93.88% vs. 73.47%). Conclusion: Among the machine learning prediction models for cervical cancer and precancerous lesions constructed based on human DNA methylation, the NB model has good predictive performance for CIN2 and above lesions, and may be used for screening of cervical cancer and precancerous lesions.

ATAD2 is a potential immunotherapy target for patients with small cell lung cancer harboring HLA-A∗0201.

ATAD2 is a potential immunotherapy target for patients with small cell lung cancer harboring HLA-A∗0201.

Clinicopathological features and prognosis of rectal neuroendocrine tumor with grade 2

Objective: To explore the clinicopathological features of rectal neuroendocrine tumor (R-NET) G2, identify prognostic factors, and summarize treatment experience. Methods: The clinical data of patients diagnosed with R-NET G2 by pathological diagnosis admitted to Cancer Hospital of the Chinese Academy of Medical Sciences from January 2003 to September 2023 were retrospectively analyzed. The Fisher's exact test and Kaplan-Meier curves were performed to analyze the association between pathological features and prognosis. Results: A total of 22 patients were enrolled in this study and 21 patients were followed up for a period of 6-98 months with a median follow-up time of 42 months. 5 patients died due to tumor progression during the follow-up period. The 1-, 3-, and 5-year cancer-specific survival (CSS) of the whole group were 100.0%, 92.9%, and 69.6%, respectively. Of the 22 patients, 20 underwent surgical treatment, of which 15 underwent postoperative adjuvant therapy; 2 underwent medical treatment for liver and bone multiple metastases. The 5-year survival rates of patients with tumours ≥2 cm in length, T2-3 stage, lymph node metastasis, and distant metastasis (57.1%, 68.8%, 66.7%, and 63.6%, respectively) were shorter than those of patients with tumours <2 cm in length, T1 stage, no lymph node metastasis, and no distant metastasis (all 100.0%, P＜0.001). In addition, patients with liver metastases had larger primary tumor diameters and higher T-stages compared with those without distant metastasis (P＜0.05). Conclusions: R-NET G2 has a high degree of malignancy compared with G1 and a high propensity for metastasis. Clinicians should formulate appropriate diagnostic and treatment strategies based on factors such as tumor size, depth of invasion, lymph node status, presence of distant metastasis, and the location and extent of distant metastasis.

Clinicopathological factors of ovarian clear cell carcinoma: A single institutional analysis of 247 cases in China.

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer with a poor prognosis that often shows resistance to chemotherapy. This study retrospectively analyzed 247 patients with OCCC who were admitted to the Cancer Hospital of the Chinese Academy of Medical Sciences (CAMS) between August 2007 and August 2023. Univariate and multivariate Cox regression analyses were used to identify clinicopathological factors associated with OCCC, and a nomogram prediction model was developed to predict OCCC patient survival outcomes. Kaplan‒Meier survival analysis was used to compare survival outcomes among patients with recurrent disease. Compared with systemic therapy, secondary debulking surgery significantly improved the postrecurrence survival (PRS) rate (P = 0.006). Subgroup analysis revealed that the survival benefit was more pronounced in patients with recurrence and satisfactory tumor shrinkage (PPRS = 0.01, PPFS2 = 0.047). The multivariate analysis revealed that positive preoperative ascites, incomplete remission following initial treatment, and undergoing more than six cycles of postoperative chemotherapy were independent prognostic factors affecting overall survival (OS). Additionally, patients with a positive PD-L1 test who received immunotherapy did not experience relapse during the follow-up period. In conclusion, the secondary clearance procedure offers significant benefits for patients with recurrent OCCC, and patients may experience a survival benefit from supplemental immune or targeted therapy at the end of chemotherapy. The development of a personalized treatment plan can help achieve precise treatment, improve prognosis, and enhance patients' quality of life.

The Prognostic Value of Peripheral Blood Inflammatory Markers in Hepatocellular Carcinoma Treated with Lenvatinib Combined with PD-1 Inhibitors.

To investigate the prognostic value of inflammatory indexes based on peripheral blood cells in unresectable hepatocellular carcinoma (HCC) patients treated with Lenvatinib combined with PD-1 inhibitors. This study retrospectively collected baseline inflammatory indexes from HCC patients received Lenvatinib and PD-1 inhibitor-based combination therapy at the Cancer Hospital of the Chinese Academy of Medical Sciences between October 2018 and October 2021. The optimal threshold values for inflammatory indexes determined using X-tile. The factors related to treatment response and survival outcomes were analyzed through logistic regression and Cox regression, respectively. A novel preoperative prognostic nomogram was constructed based on inflammatory indexes, and the predictive efficacy of the nomogram and BCLC staging was compared by the area under the ROC curve. 156 eligible patients with unresectable HCC were included, with median OS and PFS of 23.8 and 11.5 months, respectively, and ORR of 48.7%. The baseline SIRI was an independent factor of treatment response, with a significantly higher ORR for patients with a SIRI <0.8 than for patients with a SIRI ≥0.8 (59.7% vs 41.5%, P=0.03). SIRI and PNI were independent prognostic factors of PFS, and SIRI was an independent prognostic factor of OS. The AUC value of nomogram based on baseline SIRI, PNI, and tumor distribution in predicting the 6-,12- and 18-month PFS of patients was significantly higher than that of traditional BCLC stage, and its prediction performance was substantially better than that of BCLC stage system (C-index, 0.730 vs 0.535). The baseline SIRI could be used as a potential non-invasive biomarker to predict the efficacy and survival benefit of immune combination therapy for HCC. The nomogram based on inflammation indexes could achieve better prediction performance and help clinicians to identify high-risk patients and formulate treatment plans.

A comparative study of 4-hook anchor device with methylene blue for preoperative pulmonary nodule localization.

Accurate localization of small pulmonary nodules (SPNs) during video-assisted thoracoscopic surgery (VATS) is challenging due to the small size and deep location. Both the 4-hook wire technique and methylene blue are significant methods for preoperative localization of SPNs. This study aimed to compare the safety of both methods by monitoring and recording any surgery-related complications. Additionally, the effectiveness of both methods was compared by measuring the success rate of localization and the time required for both localization and resection of the nodules. Patients who underwent computed tomography (CT)-guided lung nodule localization before VATS from May 2021 to April 2023 at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were analyzed retrospectively. A total of 75 patients with 84 SPNs were included in this study, comprising 35 4-hook anchor patients with 41 SPNs and 40 methylene blue-marked patients with 43 SPNs. The VATS operative time for SPNs in the 4-hook anchor device group was significantly shorter than that in the methylene blue group (57.4±12.4 vs. 79.5±14.3 minutes; P<0.001). The overall puncture operation time [15.0 (13.0, 16.5) vs. 16.00 (13.8, 21.0); P=0.007] was also significantly different between the 4-hook anchor device group and the methylene blue group. There were no significant differences in localizer depth from the pleura, complications, localization success, hemorrhage, hospital stay, or hospital cost between the two groups (all P>0.05). Compared with the methylene blue technique, the 4-hook anchor device is safe and reliable and offers a shorter VATS operative time.

Efficacy and safety of trastuzumab deruxtecan in Chinese patients with HER2-positive and HER2-low advanced breast cancer: a multicenter, observational, real-world study.

Limited real-world efficacy and safety data exist regarding the use of trastuzumab deruxtecan (T-DXd) in the Chinese population with human epidermal growth factor receptor (HER2)-positive and HER2-low advanced breast cancer (BC). This multicenter, observational, real-world study aimed to evaluate the efficacy and safety of T-DXd for the treatment of Chinese patients with HER2-positive and HER2-low advanced BC. The medical records of 61 patients were collected from The Second Hospital of Dalian Medical University, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing Jingxin Hospital, and Cancer Hospital of the Chinese Academy of Medical Sciences. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to response (TTR), and safety. PFS and OS were analyzed using the Kaplan-Meier method and log-rank test. The primary endpoint, PFS was 10.51 months (95% confidence interval (CI), 3.02-NE) in the HER2-low group and 10.18 months (95% CI, 3.88-NE) in the HER2-positive group. Regarding the secondary endpoints in the HER2-low and HER2-positive groups, OS data were immature, ORR rates were 37.93% and 62.50%, DCR rates were 79.31% and 87.50%, and the median TTR rates were 1.28 and 1.31 months, respectively. In the subgroup analysis, front-line treatment with T-DXd was associated with increased beneficial effects. The primary adverse events (AEs) related to T-DXd treatment were gastrointestinal reactions and bone marrow suppression, which were predominantly grades 1-2, with no severe grade 4/5 AEs reported, only one patient developed infectious pneumonia. This study was the first multicenter, real-world study of T-DXd for advanced BC in China. The findings demonstrated that T-DXd may be an effective antitumor treatment with controllable adverse reactions in patients with advanced BC irrespective of HER2 expression levels.

Clinical characteristics and prognostic analysis of diffuse large B-cell lymphoma with TP53 mutation

Exploring the clinical and pathological characteristics and prognostic factors of diffuse large B-cell lymphoma (DLBCL) patients with TP53 mutation. Data of 86 DLBCL patients with TP53 mutation treated with R-CHOP and 19 DLBCL patients with TP53 mutation treated with R-CHOP like regimen as first-line treatment at the Cancer Hospital of Chinese Academy of Medical Sciences (CAMS) and the Cancer Hospital of the CAMS in Shenzhen, China, from January 2006 to June 2023 were retrospectively analyzed. Multivariate Cox analysis was applied to assess the effects of the factors on survival. Among the 105 DLBCL patients with TP53 mutation, 56 were male (53.3%); the median age was 59 years. There were 54 cases with stage Ⅰ-Ⅱ and 51 cases with stage Ⅲ-Ⅳ diseases. The proportion of B-cell lymphoma 2 (BCL2) gene amplification was 9.5% (10/105). The complete response rate in the whole group of patients treated with the R-CHOP regimen was 28.6% (30/105). The median progression-free survival (PFS) was 10.1 (95%CI: 7.3-13.0) months, and the median overall survival (OS) was not reached. Stage Ⅲ-Ⅳ was a risk factor for OS (HR=2.80, 95%CI: 1.04-7.54), and elevated lactic dehydrogenase (LDH) was a risk factor for PFS (HR=2.86, 95%CI: 1.56-5.26) and OS (HR=2.90, 95%CI: 1.08-7.69). The median PFS was lower in patients with BCL2 amplification than in patients without amplification [4.0 (95%CI: 2.7-5.3) vs 11.3 (95%CI: 8.5-14.1) months, P=0.011]. Thirty-one of the 54 (57.4%) patients with stage Ⅰ-Ⅱ disease received combination therapy based on the R-CHOP protocol. In conclusion, stage Ⅲ-Ⅳ and elevated LDH were associated with poor prognosis in TP53 mutation DLBCL patients, and patients with BCL2 amplification had a poor prognosis. For TP53 mutation DLBCL patients with stage Ⅰ-Ⅱ disease, combination of therapeutic modalities based on the R-CHOP may improve the prognosis.

Analysis of prognostic risk factors for patients with locally advanced gastric cancer in the stage ypT0~2N0M0 after neoadjuvant chemotherapy

Objectives: To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy. Methods: The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival. Results: Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis (P＜0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions: The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.

Clinical characteristics and prognosis analysis in patients with bone marrow invasive follicular lymphoma

Objective: This study aimed to summarize the clinical characteristics and prognosis of patients with bone marrow invasive follicular lymphoma (FL) and discuss the treatment modalities. Methods: This study included 183 consecutive patients with FL accompanied by bone marrow invasion and receiving regular treatment at the Hospital of Hematology, Chinese Academy of Medical Sciences, from January 2013 to December 2022. Clinical data were retrospectively collected and analyzed, and single and multifactorial analyses of survival prognosis were conducted with the Kaplan-Meier method and Cox regression model. Results: The median age was 48 (range: 19 - 78) years, and the male-to-female ratio was 0.9∶1. All of the patients had bone marrow invasion, 27.8% had increased lactate dehydrogenase levels, 42.1% had lymphocyte counts of >5×10(9)/L, 18.4% had abnormal chromosomal karyotypes, and 48.6% had Ki-67 index of ≥30% in lymphoid tissue. Comparison of different subgroups: lymphocyte counts of >5×10(9)/L, number of lymph nodes of ≥5 involved, and proportion of bone marrow chromosomal abnormalities occurring were higher in the anthracycline-intensive treatment group than in the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) protocol and the nucleoside analog (including CD20 monoclonal antibody in combination with fludarabine and bendamustine) groups (all P<0.05). The complete remission rate was 39.1% in the conventional R-CHOP group, which was lower and statistically significant than that in the intensive treatment group (55.1%) and the nucleoside analog group (62.5%) (P=0.042). The multivariate analysis for survival analysis revealed high risk of FLIPI (HR= 1.910, 95% CI 1.036 - 3.522, P=0.036), chromosomal abnormalities karyotype (HR=2.666, 95% CI 1.333-5.331, P=0.006), and conventional R-CHOP treatment (HR=2.287, 95% CI 1.140-4.591, P=0.020) were the independent adverse prognostic factors affecting progression-free survival (PFS), whereas POD24 was the only independent adverse prognostic factor affecting overall survival (OS) adverse prognostic factor (HR=9.581, 95% CI 3.000 - 30.593, P<0.001) . Conclusions: The clinical presentations of patients with bone marrow invasive FL were easy to combine the clinical features, including increased lymphocyte count, chromosomal abnormalities, and Ki-67 index in lymphoid tissues. The FLIPI score, chromosomal abnormal karyotype, and high-lymphoid-tissue Ki-67 index were the poor prognostic factors influencing PFS. R-CHOP therapy demonstrated a poor prognosis in this group of patients.

Patient-Centric Mobile Medical Services Accessed Through Smartphones in the Top 100 Chinese Public Hospitals: Cross-Sectional Survey Study.

Smartphone-based technology has been used to enhance the delivery of health care services to the public in numerous countries. This study aims to investigate the application of patient-centric mobile medical services accessed through smartphones in the top 100 Chinese public hospitals. Data on 124 tertiary public hospitals, ranked among the top 100 by the China Hospital Science and Technology Evaluation Metrics of the Chinese Academy of Medical Sciences (2019) and China's Hospital Rankings of the Hospital Management Institute of Fudan University (2019), were collected from the WeChat platform (Tencent Inc), mobile phone apps, and official websites until February 10, 2021. A total of 124 tertiary public hospitals, all of which were among the top 100 hospitals according to the 2 ranking lists, were selected for this study. Almost all (122/124, 98.39%) of the hospitals offered basic services such as appointment scheduling, registration, and health education. The majority also provided online access to test reports (95/124, 76.61%), consultations (72/124, 58.06%), and prescriptions (61/124, 49.19%). Among the hospitals offering online prescriptions, the majority (54/61, 88.52%) supported home delivery through third-party carriers. Slightly less than half (57/124, 45.97%) used artificial intelligence for medical guidance. Only a small fraction (8/124, 6.45%) managed chronic diseases through online monitoring and supervision by experienced doctors. Approximately half (60/124, 48.39%) of the included hospitals were officially licensed as internet hospitals approved to provide full online services. Hospitals with official internet hospital licenses provided more extensive digital health offerings. A significantly higher proportion of approved hospitals offered online consultations (29.69% vs 88.33%, r=43.741; P<.001), test reports (62.5% vs 91.67%, r=14.703; P<.001), and chronic disease management (1.56% vs 11.67%, r=5.238; P<.05). These officially approved hospitals tended to provide over 6 mobile medical services, mainly in the regions of Shanghai and Guangdong. This geographic distribution aligned with the overall layout of hospitals included in the study. Patient-centric mobile medical services offered by the top 100 Chinese public hospitals accessed through smartphones primarily focus on online appointment scheduling, registration, health education, and accessing test reports. The most popular features include online consultations, prescriptions, medication delivery, medical guidance, and early-stage chronic disease management. Approved internet hospitals offer a significantly greater variety of patient-centric mobile medical services compared with unapproved ones.

Two cases of deficiency in ELF4 gene X-linked and literature review

Objective: To summarize the clinical phenotype and genetic characteristics of deficiency in ELF4 gene X-linked (DEX). Methods: A case series study was conducted to retrospectively analyze the clinical data and genetic testing results of 2 cases of DEX treated at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and the First Hospital of Jilin University from January 2023 to April 2024. And literature up to April 2024 was searched from the PubMed database, as well as CNKI and Wanfang databases, using keywords such as "ELF4 deficiency" "deficiency in ELF4, X-linked""ELF4 gene". The main clinical manifestations and genotypes of DEX were summarized. Results: Both patients were male, with onset ages of 3 months and 3 years, respectively. Both patients presented with recurrent oral ulcers and abdominal pain. And the laboratory examination showed a significant increase in inflammatory markers. Intestinal examinations showed multiple intestinal ulcers, and both patients developed intestinal fistulas. Whole exome sequencing found ELF4 c.799C>T, p Arg267Trp and ELF4 c. 248-7G>A, both maternal variants. Based on clinical and genetic results, DEX were diagnosed. In terms of treatment, both patients underwent surgical treatment during the acute phase of the disease and received anti-tumor necrosis factor α therapy, but recurrent gastrointestinal symptoms were still observed in Patient 1, while the clinical effect in Patient 2 was still acceptable. However, the inflammatory markers in both patients were not normal even after treatment. Literature review found 18 patients including 2 patients in this study, reported in 5 English articles and no Chinese reports. Thirteen patients had disease onset age before 5. The main clinical manifestations were fever (12/17), oral ulcers (14/18), abdominal pain (8/18), diarrhea (6/18), perianal ulcers (5/17), ileum ulcers (6/16), colon ulcers (7/16), skin involvement (7/17) and recurrent infections (7/18); laboratory examinations found increased erythrocyte sedimentation rate (13/15) as well as C-reactive protein (9/9), and anemia (13/15); in terms of immunological function, there is a decrease in natural killer cells (9/15) as well as a decrease in class switching memory B cells (8/9). The main types of gene variantions were missense variantions (6/18), nonsense variantions (4/18) or frameshift variantions (3/18). Conclusions: DEX should be considered when an early-onset male patient manifested with recurrent fever, oral ulcers or mucosal ulcers, with elevated inflammatory markers, with or without recurrent infection. It is recommended to perform lymphocyte subsets analysis, gastrointestinal endoscopy and genetic testing to support the diagnosis.

Machine learning-based radiomics for guiding lymph node dissection in clinical stage I lung adenocarcinoma: a multicenter retrospective study.

Preoperative assessment of lymph node status is critical in managing lung cancer, as it directly impacts the surgical approach and treatment planning. However, in clinical stage I lung adenocarcinoma (LUAD), determining lymph node metastasis (LNM) is often challenging due to the limited sensitivity of conventional imaging modalities, such as computed tomography (CT) and positron emission tomography/CT (PET/CT). This study aimed to establish an effective radiomics prediction model using multicenter data for early assessment of LNM risk in patients with clinical stage I LUAD. The goal is to provide a basis for formulating lymph node dissection strategies before surgery in early-stage lung cancer patients. A total of 578 patients with LUAD from three medical centers [Cancer Hospital, Chinese Academy of Medical Sciences (CCAM), the First Affiliated Hospital of Chongqing Medical University (1CMU), and Beijing Chao-Yang Hospital (BCYH)] who underwent preoperative chest CT were divided into three groups, the training group (n=336), the testing group (n=167), and the independent validation group (n=75). The records of 1,316 radiomics features of each primary tumor were extracted. The least absolute shrinkage and selection operator (LASSO) analysis and multivariable logistic regression were used to reduce the data dimensionality, select features, and construct the prediction models. In the training group, the area under the curve (AUC) for the clinical model, radiomics model, and composite model were 0.820, 0.871, and 0.883, respectively. In the testing group, the AUC for the clinical model, radiomics model, and composite model were 0.897, 0.915, and 0.934, respectively. In the validation set, the AUC of the radiomics model was the highest at 0.870, while the composite model and clinical model had AUCs of 0.841 and 0.710, respectively. The results of the Delong test showed that the AUCs of the radiomics model and composite model were significantly higher than those of the clinical model in both the training and validation groups. The decision curve analysis showed that the radiomics nomogram was clinically useful. This study developed and validated a radiomics prediction model, which enables easy LNM prediction in stage I LUAD patients. This model provides a basis for formulating lymph node dissection strategies before surgery and helps to better determine the tumor node metastasis stage of the early-stage LUAD.