Advances and current research status of early diagnosis for gallbladder cancer.

Gallbladder cancer (GBC) is the most common malignant tumor in the biliary system, characterized by high malignancy, aggressiveness, and poor prognosis. Early diagnosis holds paramount importance in ameliorating therapeutic outcomes. Presently, the clinical diagnosis of GBC primarily relies on clinical-radiological-pathological approach. However, there remains a potential for missed diagnosis and misdiagnose in the realm of clinical practice. We firstly analyzed the blood-based biomarkers, such as carcinoembryonic antigen and carbohydrate antigen 19-9. Subsequently, we evaluated the diagnostic performance of various imaging modalities, including ultrasound (US), endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT) and pathological examination, emphasizing their strengths and limitations in detecting early-stage GBC. Furthermore, we explored the potential of emerging technologies, particularly artificial intelligence (AI) and liquid biopsy, to revolutionize GBC diagnosis. AI algorithms have demonstrated improved image analysis capabilities, while liquid biopsy offers the promise of non-invasive and real-time monitoring. However, the translation of these advancements into clinical practice necessitates further validation and standardization. The review highlighted the advantages and limitations of current diagnostic approaches and underscored the need for innovative strategies to enhance diagnostic accuracy of GBC. In addition, we emphasized the importance of multidisciplinary collaboration to improve early diagnosis of GBC and ultimately patient outcomes. This review endeavoured to impart fresh perspectives and insights into the early diagnosis of GBC.

Deep learning-assisted distinguishing breast phyllodes tumors from fibroadenomas based on ultrasound images: a diagnostic study.

OBJECTIVES: To evaluate the performance of ultrasound-based deep learning (DL) models in distinguishing breast phyllodes tumors (PTs) from fibroadenomas (FAs) and their clinical utility in assisting radiologists with varying diagnostic experiences. METHODS: We retrospectively collected 1180 ultrasound images from 539 patients (247 PTs and 292 FAs). Five DL network models with different structures were trained and validated using nodule regions annotated by radiologists on breast ultrasound images. DL models were trained using the methods of transfer learning and 3-fold cross-validation. The model demonstrated the best evaluation index in the 3-fold cross-validation was selected for comparison with radiologists' diagnostic decisions. Two-round reader studies were conducted to investigate the value of DL model in assisting six radiologists with different levels of experience. RESULTS: Upon testing, Xception model demonstrated the best diagnostic performance (AUC: 0.87, 95%CI: 0.81-0.92), outperforming all radiologists (all p < 0.05). Additionally, the DL model enhanced the diagnostic performance of radiologists. Accuracy demonstrated improvements of 4%, 4%, and 3% for senior, intermediate, and junior radiologists, respectively. CONCLUSIONS: The DL models showed superior predictive abilities compared to experienced radiologists in distinguishing breast PTs from FAs. Utilizing the model led to improved efficiency and diagnostic performance for radiologists with different levels of experience (6-25 years of work). ADVANCES IN KNOWLEDGE: We developed and validated a DL model based on the largest available dataset to assist in diagnosing PTs. This model has the potential to allow radiologists to discriminate two types of breast tumors which are challenging to identify with precision and accuracy, and subsequently to make more informed decisions about surgical plans.

Observation of clinical efficacy of acupuncture combined with bloodletting therapy and Qingwen Xiere decoction in mild to moderate COVID-19 patients. / é’ˆåˆºè”åˆåˆºè¡€åŠæ¸ ç˜Ÿæ³„çƒ­æ±¤å¯¹æ–°åž‹å† çŠ¶ç— æ¯’æ„ŸæŸ“è½»ä¸­åž‹æ‚£è€ ä¸´åºŠç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To evaluate the clinical efficacy and safety of acupuncture combined with bloodletting therapy and Qingwen Xiere decoction in mild to moderate COVID-19 patients. METHODS: A total of 100 mild to moderate COVID-19 patients collected from December 2022 to February 2023 were randomly divided into control and observation groups, with 50 patients in each group. Patients in the control group received oral Qingwen Xiere decoction for 6 days. The observation group received acupuncture combined with bloodletting therapy in addition to oral Qingwen Xiere decoction, with the acupuncture (at Kongzui ï¼»LU6ï¼½, Hegu ï¼»LI4ï¼½, Quchi ï¼»LI11ï¼½, Feishu ï¼»BL13ï¼½, Zhongwan ï¼»CV12ï¼½, Qihai ï¼»CV6ï¼½, Yinlingquan ï¼»SP9ï¼½) administered 30 min each day for 6 days, and bloodletting (at Shaoshang ï¼»LU11ï¼½, Shangyang ï¼»LI1ï¼½, Dazhui ï¼»GV14ï¼½) administered every other day for 3 times. Traditional Chinese medicine syndrome scores and pulmonary CT scores were recorded before and after treatment. Serum contents of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured using ELISA. Anxiety and depression degree were assessed using the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). Safety of the treatments was evaluated in both groups. RESULTS: Compared with before treatment, after treatment, the control group showed improvement in fever, dry cough, sore throat, and total traditional Chinese medicine syndrome scores (P<0.01), but no significant improvement in muscle pain or fatigue；the observation group showed significant improvement in total traditional Chinese medicine syndrome and individual symptoms scores (P<0.01)；both groups demonstrated reductions in pulmonary CT scores, HAMA score, HAMD score and serum contents of CRP and IL-6 (P<0.01)；serum TNF-α content significantly decreased in the observation group (P<0.01). All outcome measures were superior in the observation group to the control group (P<0.01, P<0.05). No adverse reactions were reported in either group. CONCLUSIONS: Acupuncture combined with bloodletting therapy and oral Qingwen Xiere decoction effectively improves clinical symptoms, alleviates pulmonary inflammatory injury, reduces inflammatory cytokine contents, and mitigates anxiety and depression in mild to moderate COVID-19 patients, and without adverse effects.

Suppression of SENP3 enhances macrophage alternative activation by mediating IRF4 de-SUMOylation in ESCC progression.

Esophageal cancer is common worldwide, with ESCC being the most frequent tumor in East Asia. Tumor-associated macrophages are an important component of the ESCC microenvironment. SUMOylation is a post-translational modification of proteins, and SUMO-specific proteases (SENPs) play an important role in de-SUMOylation. In human patients, we discovered that the levels of SENP3 were upregulated in the tumor-associated macrophages. Furthermore, the loss of SENP3 enhanced the alternative activation of macrophages in the 4-NQO-induced ESCC mice model. This is the first study to identify SENP3-mediated macrophage polarization via the de-SUMOylation of interferon regulatory factor 4 (IRF4) at the K349 site. Alternative activation of macrophages increases the migration and invasion potential of ESCC cells and promotes their progression in vivo. Moreover, patients with relatively low SENP3 expression in macrophages exhibit higher primary PET SUVmax value and lymph node metastasis rates. In summary, this study revealed that SENP3-mediated IRF4 de-SUMOylation is crucial for the alternative activation of macrophages and influences the progression of ESCC.

PTEN status determines therapeutic vulnerability to celastrol in cholangiocarcinoma.

BACKGROUND: A balanced protein homeostasis network helps cholangiocarcinoma (CCA) maintain their oncogenic growth, and disrupting proteostasis therapeutically will induce proteotoxic stress. Phosphatase and tensin homolog (PTEN) have been reported to be involved in proteostasis, and PTEN-associated pathways are commonly altered in CCA. Celastrol, a triterpene from plants, exhibits cytotoxic effects in various types of cancer. However, the underlying mechanisms remain unclear. PURPOSE: We investigated the therapeutic effect of celastrol in CCA and identified the molecular characteristics of tumors that were sensitive to celastrol. The target of celastrol was explored. We then evaluated the candidate combination therapeutic strategy to increase the effectiveness of celastrol in celastrol-insensitive CCA tumors. METHODS: Various CCA cells were categorized as either celastrol-sensitive or celastrol-insensitive based on their response to celastrol. The molecular characteristics of cells from different groups were determined by RNA-seq. PTEN status and its role in proteasome activity in CCA cells were investigated. The CMAP analysis, molecular docking, and functional assay were performed to explore the effect of celastrol on proteasome activities. The correlation between PTEN status and clinical outcomes, as well as proteasomal activity, were measured in CCA patients. The synergistic therapeutic effect of autophagy inhibitors on celastrol-insensitive CCA cells were measured. RESULTS: Diverse responses to celastrol were observed in CCA cells. PTEN expression varied among different CCA cells, and its status could impact cell sensitivity to celastrol: PTENhigh tumor cells were resistant to celastrol, while PTENlow cells were more sensitive. Celastrol induced proteasomal dysregulation in CCA cells by directly targeting PSMB5. Cells with low PTEN status transcriptionally promoted proteasome subunit expression in an AKT-dependent manner, making these cells more reliant on proteasomal activities to maintain proteostasis. This caused the PTENlow CCA cells sensitive to celastrol. A negative correlation was found between PTEN levels and the proteasome signature in CCA patients. Moreover, celastrol treatment could induce autophagy in PTENhigh CCA cells. Disrupting the autophagic pathway in PTENhigh CCA cells enhanced the cytotoxic effect of celastrol. CONCLUSION: PTEN status in CCA cells determines their sensitivity to celastrol, and autophagy inhibitors could enhance the anti-tumor effect in PTENhigh CCA.

PA200-Mediated Proteasomal Protein Degradation and Regulation of Cellular Senescence.

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed.

Perioperative outcomes and survival after neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: This study aimed to compare the difference in perioperative outcomes and prognosis between neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. METHODS: The patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunochemotherapy or neoadjuvant chemoradiotherapy were identified from a prospectively maintained database at Zhongshan Hospital of Fudan University between January 2018 and March 2022. Propensity score matching was performed to balance the 2 groups. RESULTS: A total of 124 patient pairs were enrolled in the final analysis. The complete pathological response rate (20.2% vs 29.0%, P = .140) was similar in the 2 groups, whereas the lower major pathological response rate (44.4% vs 61.3%, P = .011) was observed in the neoadjuvant immunochemotherapy group. Neoadjuvant immunochemotherapy was associated with a lower rate of adverse events (42.7% vs 55.6%, P = .047) without additional postoperative complications (38.7% vs 35.5%, P = .693). The neoadjuvant immunochemotherapy group had lower distant metastasis (6.5% vs 16.1%, P = .027) and overall recurrence (11.3% vs 23.4%, P = .019) in the postoperative 1 year. Also, neoadjuvant immunochemotherapy was associated with better progression-free survival (hazard ratio, 0.50; 95% CI, 0.32-0.77; P = .002). Cox proportional hazard analysis showed that neoadjuvant immunochemotherapy (univariable: hazard ratio, 0.55; 95% CI, 0.37-0.82; P = .003; multivariable: hazard ratio, 0.44; 95% CI, 0.29-0.65; P < .001) was one of the independent prognostic factors for progression-free survival. The 2 groups had similar overall survival (hazard ratio, 0.62; 95% CI, 0.36-1.09; P = .094) at the latest follow-up. CONCLUSIONS: This retrospective study showed that neoadjuvant immunochemotherapy was safe and effective for patients with locally advanced esophageal squamous cell carcinoma. Further verification is needed in randomized controlled trials.

The Potential Role of Virus Infection in the Progression of Thyroid Cancer.

Multiple factors have engaged in the progression of thyroid cancer (TC). Recent studies have shown that viral infection can be a critical factor in the pathogenesis of TC. Viruses, such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may play an essential role in the occurrence, development, and even prognosis in TC. This review mainly explored the potential role of viral infection in the progress of TC. The possible mechanisms could be recognizing the host cell, binding to the receptors, affecting oncogenes levels, releasing viral products to shape a beneficial environment, interacting with immune cells to induce immune evasion, and altering the pituitary-thyroid axis. Thus, comprehensive knowledge may provide insights into finding molecular targets for diagnosing and treating virus-related TC.

Bortezomib in previously treated phosphatase and tension homology-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective and single-centre phase II trial.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients. METHODS: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0. CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC. HIGHLIGHTS: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma.

The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8+ T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.

Deep learning-assisted diagnosis of benign and malignant parotid tumors based on ultrasound: a retrospective study.

BACKGROUND: To develop a deep learning(DL) model utilizing ultrasound images, and evaluate its efficacy in distinguishing between benign and malignant parotid tumors (PTs), as well as its practicality in assisting clinicians with accurate diagnosis. METHODS: A total of 2211 ultrasound images of 980 pathologically confirmed PTs (Training set: n = 721; Validation set: n = 82; Internal-test set: n = 89; External-test set: n = 88) from 907 patients were retrospectively included in this study. The optimal model was selected and the diagnostic performance evaluation is conducted by utilizing the area under curve (AUC) of the receiver-operating characteristic(ROC) based on five different DL networks constructed at varying depths. Furthermore, a comparison of different seniority radiologists was made in the presence of the optimal auxiliary diagnosis model. Additionally, the diagnostic confusion matrix of the optimal model was calculated, and an analysis and summary of misjudged cases' characteristics were conducted. RESULTS: The Resnet18 demonstrated superior diagnostic performance, with an AUC value of 0.947, accuracy of 88.5%, sensitivity of 78.2%, and specificity of 92.7% in internal-test set, and with an AUC value of 0.925, accuracy of 89.8%, sensitivity of 83.3%, and specificity of 90.6% in external-test set. The PTs were subjectively assessed twice by six radiologists, both with and without the assisted of the model. With the assisted of the model, both junior and senior radiologists demonstrated enhanced diagnostic performance. In the internal-test set, there was an increase in AUC values by 0.062 and 0.082 for junior radiologists respectively, while senior radiologists experienced an improvement of 0.066 and 0.106 in their respective AUC values. CONCLUSIONS: The DL model based on ultrasound images demonstrates exceptional capability in distinguishing between benign and malignant PTs, thereby assisting radiologists of varying expertise levels to achieve heightened diagnostic performance, and serve as a noninvasive imaging adjunct diagnostic method for clinical purposes.

Image-Guided Thermal Ablation for Hepatic Epithelioid Hemangioendothelioma: A Multicenter Experience.

PURPOSE: To investigate the feasibility, safety, and clinical outcomes of image-guided thermal ablation in patients with hepatic epithelioid hemangioendothelioma (HEHE). MATERIALS AND METHODS: This was a multicenter retrospective investigation of 18 patients (43.9 years [SD ± 14.8]; 6 men) who underwent image-guided thermal ablation for HEHE between January 2013 and February 2023. A total of 31 ablation sessions (24 involving microwave ablation and 7 involving radiofrequency ablation) were evaluated. The rates of technical success, adverse events, and outcomes were assessed. The Kaplan‒Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) rates. The risk factors affecting PFS were investigated using Cox proportional hazard regression analysis. RESULTS: The technical success rate was 93.5% (29/31). No major adverse events occurred. Local tumor progression occurred after 2 sessions (6.5%, 2/31), and intrahepatic distant metastasis occurred after 16 sessions (51.6%, 16/31). During the medium follow-up time of 37.2 months (range, 3-117 months), the OS and PFS rates were 87.6% and 62.2%, respectively, at 1 year; 75.5% and 37.4%, respectively, at 3 years; and 75.5% and 37.4%, respectively, at 5 years. The median OS and PFS were 90.5 months (95% CI: 68.1-112.8) and 23.8 months (95% CI: 15.4-32.2), respectively. According to the multivariate analysis, a larger tumor size (P = .026) was associated with shorter PFS. CONCLUSIONS: Image-guided thermal ablation is a feasible and safe treatment option for patients with HEHE that resulted in local tumor control and a favorable long-term prognosis.

Photooxidation triggered ultralong afterglow in carbon nanodots.

It remains a challenge to obtain biocompatible afterglow materials with long emission wavelengths, durable lifetimes, and good water solubility. Herein we develop a photooxidation strategy to construct near-infrared afterglow carbon nanodots with an extra-long lifetime of up to 5.9 h, comparable to that of the well-known rare-earth or organic long-persistent luminescent materials. Intriguingly, size-dependent afterglow lifetime evolution from 3.4 to 5.9 h has been observed from the carbon nanodots systems in aqueous solution. With structural/ultrafast dynamics analysis and density functional theory simulations, we reveal that the persistent luminescence in carbon nanodots is activated by a photooxidation-induced dioxetane intermediate, which can slowly release and convert energy into luminous emission via the steric hindrance effect of nanoparticles. With the persistent near-infrared luminescence, tissue penetration depth of 20 mm can be achieved. Thanks to the high signal-to-background ratio, biological safety and cancer-specific targeting ability of carbon nanodots, ultralong-afterglow guided surgery has been successfully performed on mice model to remove tumor tissues accurately, demonstrating potential clinical applications. These results may facilitate the development of long-lasting luminescent materials for precision tumor resection.

A multicenter case-controlled study on laparoscopic hepatectomy versus microwave ablation as first-line therapy for 3-5 cm hepatocellular carcinoma in patients aged 60 and older.

BACKGROUND: There is currently a lack of convincing evidence for microwave ablation (MWA) and laparoscopic liver resection (LLR) for patients ≥60 years old with 3-5 cm hepatocellular carcinoma. MATERIALS AND METHODS: Patients were divided into three cohorts based on restricted cubic spline analysis: 60-64, 65-72, and ≥73 years. Propensity score matching (PSM) was performed to balance the baseline variables in a 1:1 ratio. Overall survival (OS) and disease-free survival (DFS) were assessed, followed by a comparison of complications, hospitalization, and cost. RESULTS: Among 672 patients, the median age was 66 (IQR 62-71) years. After PSM, two groups of 210 patients each were selected. During the 36.0 (20.4-52.4) month follow-up period, the 1-year, 3-year, and 5-year OS rates in the MWA group were 97.6, 80.9, and 65.3% and 95.5, 78.7, and 60.4% in the LLR group (HR 0.98, P =0.900). The corresponding DFS rates were 78.6, 49.6, and 37.5% and 82.8, 67.8, and 52.9% (HR 1.52, P =0.007). The 60-64 age cohort involved 176 patients, with no a significant difference in OS between the MWA and LLR groups (HR 1.25, P =0.370), MWA was associated with a higher recurrence rate (HR 1.94, P =0.004). A total of 146 patients were matched in the 65-72 age cohort, with no significant differences in OS and DFS between the two groups (OS (HR 1.04, P =0.900), DFS (HR 1.56, P =0.110)). In 76 patients aged ≥73 years after PSM, MWA provided better OS for patients (HR 0.27, P =0.015), and there were no significant differences in DFS between the two groups (HR 1.41, P =0.380). Taken together, for patients older than 65 years, the recurrence rate of MWA was comparable with LLR. Safety analysis indicated that LLR was associated with more postoperative bleeding ( P =0.032) and hypoproteinemia ( P =0.024). CONCLUSIONS: MWA was comparable to LLR in patients aged 65 years and older. MWA could be an alternative for the oldest old or the ill patients who cannot afford LLR, while LLR is still the first option of treatments for early-stage 3-5 cm hepatocellular carcinoma in capable elderly's.

Liver indicators affecting the relationship between BMI and hypertension in type 2 diabetes: a mediation analysis.

BACKGROUND: Body mass index (BMI) is an important risk factor for hypertension in diabetic patients. However, the underlying mechanisms remain poorly understood. Although liver-derived biological intermediates may play irreplaceable roles in the pathophysiology of diabetes, few studies have explored them in the association between BMI and hypertension in diabetes. OBJECTIVE: To investigate the role of liver enzymes in mediating the relationship between BIM exposure and hypertension in type 2 diabetes mellitus (T2DM). METHODS: We included a total of 1765 participants from the China National Diabetic Chronic Complications Study Cohort. Associations between liver enzymes and hypertension were estimated using multivariable regression models. The function of liver indicators in the relationship between BMI and hypertension was assessed using mediation analysis. Mediation analysis was conducted, taking into account age, diabetes duration, current smoking, fasting plasma glucose level, glycated hemoglobin, anti-diabetic therapy, and family history of diseases, including diabetes, hypertension, obesity, and hyperlipidemia. RESULTS: For men, the association of BMI with hypertension was partially mediated by alanine aminotransferase (ALT), with a proportion of mediation was 68.67%, by aspartate aminotransferase (AST) was 27.02%, and by γ-glutamyltransferase (GGT) was 38.58%, by AST/ALT was 63.35%; for women, the proportion mediated by ALT was 36.93%, and by AST was 37.47%, and GGT was 44.60%, and AST/ALT was 43.73% for BMI (all P < 0.05). CONCLUSION: The effect of BMI on hypertension is partly mediated by liver indicators (ALT, AST, GGT, and AST/ALT) in diabetic patients. Our results may provide opportunities to identify new targets for hypertension interventions.

[Clinical Features and Prognostic Factors of Patients with Primary Cutaneous Lymphoma].

OBJECTIVE: To retrospectively analyze the clinical characteristics and prognostic factors of patients with primary cutaneous lymphoma. METHODS: The clinical data of 22 patients with primary cutaneous lymphoma admitted to Xinjiang Hotan District People's Hospital, Heji Hospital affiliated to Changzhi Medical College and the Fifth Medical Center of PLA General Hospital from January 2013 to June 2021 were retrospectively analyzed. RESULTS: The incidence of primary cutaneous T cell and NK/T cell lymphoma was about 91.9/100 000, and the incidence of primary cutaneous B cell lymphoma was about 14.5/100 000. The overall survival (OS) of patients aged ≥65 years was significantly shorter than that of patients younger than 65 years (P <0.05). Patients with elevated ß2-microglobulin (ß2-MG) had shorter OS and progression-free survival (PFS) (both P <0.05). Patients who achieved complete/partial response after initial treatment had longer OS than those with stable or progressive disease (P <0.05). There were significant differences in OS and PFS among patients with different pathological types of primary cutaneous lymphoma that originated from T and NK/T cells, the OS and PFS of patients with mycosis fungoides were longer than those of patients with other pathological types (both P <0.05). In addition, disease stage might also affect the PFS of the patients (P =0.056). CONCLUSION: The age, disease stage, ß2-MG level, pathological type and remission state after treatment of the patients were related to the clinical prognosis.

Combination therapy of irreversible electroporation and cytokine-induced killer cells for treating mice bearing panc02 pancreatic-cancer xenografts.

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via Panc02 cell-bearing mouse model in vivo. CIK cells were isolated from the spleens of Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model and the proportion of different lymphocytes was also determined. The antitumor effect of the combination of IRE and CIK cells in a PC subcutaneous-xenograft model was also investigated. The proportion of cells that were positive for CD3+CD8+ and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined treatment of IRE and CIK cell significantly inhibited tumor growth and increased the survival rate of Panc02 cell-bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and the regulators of CIK cell proliferation.

Combined conventional ultrasonography with clinicopathological features to predict axillary status after neoadjuvant therapy for breast cancer: A case-control study.

OBJECTIVES: This study aimed to evaluate the value of a model combining conventional ultrasonography and clinicopathologic features for predicting axillary status after neoadjuvant therapy in breast cancer. METHODS: This retrospective study included 329 patients with lymph node-positive who underwent neoadjuvant systemic treatment (NST) from June 2019 to March 2022. Ultrasound and clinicopathological characteristics of breast lesions and axillary lymph nodes were analyzed before and after NST. The diagnostic efficacy of ultrasound, clinicopathological characteristics, and combined model were evaluated using multivariate logistic regression and receiver operator characteristic curve (ROC) analyses. RESULTS: The area under ROC (AUC) for the ability of the combined model to predict the axillary pathological complete response (pCR) after NST was 0.882, that diagnostic effectiveness was significantly better than that of the clinicopathological model (AUC of 0.807) and the ultrasound feature model (AUC of 0.795). In addition, eight features were screened as independent predictors of axillary pCR, including clinical N stage, ERBB2 status, Ki-67, and after NST the maximum diameter reduction rate and margins of breast lesions, the short diameter, cortical thickness, and fatty hilum of lymph nodes. CONCLUSIONS: The combined model constructed from ultrasound and clinicopathological features for predicting axillary pCR has favorable diagnostic results, which allowed more accurate identification of BC patients who had received axillary pCR after NST. ADVANCES IN KNOWLEDGE: A combined model incorporated ultrasound and clinicopathological characteristics of breast lesions and axillary lymph nodes demonstrated favorable performance in evaluating axillary pCR preoperatively and non-invasively.