MARCH5 promotes hepatocellular carcinoma progression by inducing p53 ubiquitination degradation.

BACKGROUND: Human MARCH5 is a mitochondria-localized E3 ubiquitin-protein ligase that is essential for the regulation of mitochondrial dynamics. A large body of evidence suggests that imbalances in mitochondrial dynamics are strongly associated with cancer. However, the expression, biological function and prognostic significance of MARCH5 in hepatocellular carcinoma (HCC) have not been determined. MATERIALS AND METHODS: The mRNA and protein expression of MARCH5 in HCC cell lines and tumor tissues was assessed by real-time quantitative PCR, Western blot analysis and immunohistochemistry. The clinical prognostic significance of MARCH5 was evaluated in 135 HCC patients. Knockdown or overexpression of MARCH5 in HCC cells was determined by in vitro cell proliferation, migration and invasion assays, and in vivo tumor growth and metastasis assays. In addition, the intrinsic mechanisms by which MARCH5 regulates HCC cell growth and metastasis were explored. RESULTS: MARCH5 was significantly overexpressed in HCC cells and was closely associated with patients' poor postoperative prognosis. In vivo and in vitro experiments revealed that MARCH5 significantly promoted the increase and invasive and migratory ability of hepatocellular carcinoma cells, which was mainly due to the promotion of autophagy by MARCH5. Mechanistic studies revealed that MARCH5 promoted autophagy through ubiquitination degradation of p53 leading to malignant progression of hepatocellular carcinoma. CONCLUSION: Our findings suggest that MARCH5 plays a critical oncogenic role in HCC cells, which provides experimental evidence for the use of MARCH5 as a potential target for HCC therapy.

One-day examination of triple nuclear medicine imaging and application in evaluating transarterial embolization.

A diagnosis based on multiple nuclear medicine imaging (NMI) was more comprehensive in approaching the nature of pathological changes. In this research, a method to realize triple NMIs within one day was developed based on the reasonable arrangements of 68Ga-RGD PET/CT specialized on neovascularization, 99mTc-HL-91 SPECT/CT specialized on hypoxia and 18F-FDG PET/CT specialized on tumor metabolism. Feasibility was verified in evaluating the therapeutic effects of transarterial embolization (TAE) performed on rabbit models with VX2 tumor. Radiation dosimetry was carried out to record the radiation exposure from multiple injections of radiopharmaceuticals. In results, the one-day examination of triple NMIs manifested the diversity of the postoperative histological changes, including the local neovascularization induced by embolization, hypoxic state of embolized tissues, and suppression of tumor metabolism. More importantly, radiation dosage from radiopharmaceuticals was limited below 5.70 ± 0.90 mSv. In conclusion, the strong timeliness and complementarity of one-day examination of triple nuclear medicine imaging made it clinically operative and worthy of popularizing. There was flexibility in combining distinct NMIs according to the clinical demands, so as to provide comprehensive information for diagnosis.

Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase (G6PD) by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis.

Betaine-homocysteine methyltransferase (BHMT) regulates protein methylation and is correlated with tumorigenesis; however, the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored. Here, we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma (HCC) using tissue samples from 198 patients. BHMT was to be frequently found (86.6%) expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC. Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo, whereas complete knockout of Bhmt (Bhmt-/-) produced the opposite effect. We combined proteomics, metabolomics, and molecular biological strategies and detected that Bhmt-/- promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models. In contrast, restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis. Additionally, coimmunoprecipitation identified monomethylated modifications of the G6PD, and BHMT regulated the methylation of G6PD. Protein sequence analysis, generation and application of specific antibodies, and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246. Furthermore, we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD, thereby inhibiting G6PD activity, which in turn suppressed hepatocarcinogenesis. Taken together, this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency, suggesting a potential therapeutic strategy for HCC treatment.

Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study.

BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.

Regional delivery of mesothelin-targeted chimeric antigen receptor T-cell effectively and safely targets colorectal cancer liver metastases in mice.

Background: Liver metastasis is the major cause of colorectal cancer related death. Mesothelin (MSLN)-targeted chimeric antigen receptor (CAR) T-cell therapy has been illustrated effective and safe through regional delivery of breast cancer, ovarian cancer and malignant mesothelioma tumors. Herein, we investigated the safety, efficacy, and immune microenvironment of regional delivery of MSLN (CAR) T-cell in the treatment of colorectal carcinoma liver metastases (CRLM). Methods: Second-generation MSLN CAR T-cells were administered by portal vein (PV) or caudal vein (CV, systemic administration) delivery in an orthotopic MSLN+ CRLM nonobese diabetic (NOD)/severe combined immunodeficient (SCID)/γc-/- (NSG) mouse model. A total of 20 mice were randomly divided into control group, non-transduced T cell (NT)-CV group, NT-PV group, MSLN CAR T-cell CV (MSLN-CV) group, and MSLN CAR T-cell PV (MSLN-PV) group, with each group containing four mice to examine the safety and efficacy. The bioluminescence intensity (BLI) of tumor burden, tumor tissue macroscopic and microscopic observation were used to evaluate treatment efficacy. The safety was examined by body weight, survival time, and vital organ damage of mice. CAR T-cell infiltration and cytokine concentration were analyzed by flow cytometry, and immunostaining. The change of immune microenvironment between regional delivery and systemic delivery was investigated on an immune reconstructed CRLM patient-derived xenograft (PDX) model. Additionally, T cell subsets and immunosuppressive markers were examined. Results: PV administration of 1×107/100 µL MSLN CAR T-cells in 20 NSG mice was well tolerated, and no overt toxicity was observed. The tumor burden in the PV group was obviously alleviated. The BLI was (0.73±0.52)×109 in PV group and (1.97±0.11)×109 in CV group (P<0.05), CD8+ granzyme B (GB)+ T cell percentage (MSLN-CV 4.42%±0.47% vs. MSLN-PV 13.5%±4.67%, P<0.01) and cytokine concentration were obviously increased in the MSLN-PV group. In the immune reconstituted CRLM PDX model, intratumor (IT) delivery of MSLN CAR T-cells exhibited much more infiltration of CD4+ and CD8+ T cells accompanied with elevated expression levels of PD-1, LAG-3, and TIM-3. Conclusions: Regional delivery of MSLN-targeted CAR T-cell therapy has encouraging results in the orthotopic CRLM NSG mouse model and PDX model, and converts the tumor microenvironment from cold to hot. This study may provide a new therapeutic approach for CRLM. Further clinical study is needed.

[Research Progress in the Role of Liquid-Liquid Phase Separation in Human Cancer]. / 液-æ¶²ç›¸åˆ†ç¦»åœ¨è‚¿ç˜¤ä¸­ä½œç”¨çš„ç ”ç©¶æ–°è¿›å±•.

Liquid-liquid phase separation (LLPS) is a reversible process, during which biological macromolecules, including proteins and nucleic acids, condense into liquid membraneless organelles under the influence of weak multivalent interactions. Currently, fluorescence recovery after photobleaching is the primary method used to detect the phase separation of biological macromolecules. Recent studies have revealed the link between abnormal LLPS and the pathogenesis and development of various human cancers. Through phase separation or abnormal phase separation, tumor-related biological macromolecules, such as mRNA, long noncoding RNAs (lncRNAs), and tumor-related proteins, can affect transcriptional translation and DNA damage repair, regulate the autophagy and ferroptosis functions of cells, and thus regulate the development of various tumors. In this review, we summarized the latest research findings on the mechanism of LLPS in the pathogenesis and progression of tumors and elaborated on the promotion or inhibition of autophagy, tumor immunity, DNA damage repair, and cell ferroptosis after abnormal phase separation of biomolecules, including mRNA, lncRNA, and proteins, which subsequently affects the pathogenesis and progression of tumors. According to published findings, many biological macromolecules can regulate transcriptional translation, expression, post-transcriptional modification, cell signal transduction, and other biological processes through phase separation. Therefore, further expansion of the research field of phase separation and in-depth investigation of its molecular mechanisms and regulatory processes hold extensive research potential.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

Hypoxia-activated cascade nanovaccine for synergistic chemoembolization-immune therapy of hepatocellular carcinoma.

In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells. Moreover, a porous microcarrier, approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy.

Pneumothorax and pulmonary hemorrhage after C-arm cone-beam computed tomography-guided percutaneous transthoracic lung biopsy: incidence, clinical significance, and correlation.

OBJECTIVE: This study aimed to assess the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after percutaneous transthoracic lung biopsy (PTLB) guided by C-arm cone-beam computed tomography (CBCT). Furthermore, this study aimed to examine the relationships between PTX and PH with demographics, clinical characteristics, imaging, and PTLB parameters. METHODS: A retrospective analysis was conducted on 192 patients who underwent PTLB at our hospital between January 2019 and October 2022. Incidences of PTX and PH were recorded. PTX was considered clinically significant if treated with chest tube insertion (CTI), and PH if treated with bronchoscopes or endovascular treatments. The various factors on PTX and PH were analyzed using the Chi-squared test and Student t-test. Logistic regression analyses were then used to determine these factors on the correlation to develop PTX and PH. RESULTS: PTX occurred in 67/192 cases (34.9%); CTI was required in 5/67 (7.5%). PH occurred in 63/192 cases (32.8%) and none of these cases required bronchoscopes or endovascular treatments. Lesion diameter (ORPTX = 0.822; ORPH = 0.785), presence of pulmonary emphysema (ORPH = 2.148), the number of samples (ORPH = 1.834), the use of gelfoam (ORPTX = 0.474; ORPH = 0.341) and ablation (ORPTX = 2.351; ORPH = 3.443) showed statistically significant correlation to PTX and PH. CONCLUSIONS: CBCT-guided PTLB is a safe and effective method for performing lung biopsies. The use of gelfoam has been shown to reduce the occurrence of PTX and PH. However, caution should be exercised when combining radiofrequency ablation with PTLB, as it may increase the risk of PTX and PH.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Effects of HepaSphere microsphere encapsule epirubicin with a new loading method transarterial chemoembolization: in vitro and in vivo experiments.

METHODS: HS microspheres were loaded in a solution of hypertonic saline and contrast medium at different ratios. Morphology, size distribution, and drug loading capacity of the microsphere were evaluated. Rabbits with hepatic VX2 tumors underwent conventional TACE, drug-eluting beads TACE with HS microsphere loading epirubicin by recommended method (dTACE) or a new loading method (ndTACE). The plasma and tissue epirubicin concentration, tumor necrosis, and the microsphere distribution within the tumor were assessed. RESULTS: It was found that the mean diameter of HS microspheres was effectively reduced to 102 ± 14 µm after loading with 10.0% NaCl and Ultravist (370 mg I /mL) at a ratio of 2: 8 ml. The loading capacity reached 78.7%. It was noted that the concentration of tumor epirubicin was significantly higher (p = 0.016) in the ndTACE group (11,989.8 ± 5776.6 ng/g) than the concentration in the dTACE (6516.5 ± 3682.3 ng/g) and in cTACE groups (1564.1 ± 696.1 ng/g, p < 0.001). Further, the tumor necrosis in group with the new loading method (ndTACE) was 92.4%. CONCLUSIONS: The size of HS microsphere can be effectively reduced when it is loaded with a mixture of hypertonic saline and non-ionic contrast material. HS microsphere loaded with epirubicin using the new method (ndTACE) can increase the drug concentration in tumor and hence exert better improved antitumor effect.

Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition).

Background: Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

Efficacy and Safety of Transarterial Chemoembolization with a Three-Stage Mixed Chemoembolic Regimen for Large Unresectable Hepatocellular Carcinoma.

Objective: This study aimed to assess the treatment response, survival outcomes, and safety of a novel transarterial chemoembolization (TACE) technique with a three-stage mixed chemoembolic regimen (M-TACE) in patients with large unresectable hepatocellular carcinoma (HCC) measuring more than 5 cm in maximum diameter. Methods: Between January 2017 and March 2023, a total of 82 patients were enrolled in this retrospective cohort study. Treatment response was assessed in the first month after M-TACE; progression-free survival and overall survival (OS) were evaluated. The prognostic factors associated with patient survival were statistically analyzed by the Cox regression model. Adverse events were recorded. Results: The maximum diameter of the tumors ranged from 5.3 cm to 20.0 cm (mean 10.71 cm). The objective response (OR) and disease control rates were 74.4 and 92.7%, respectively, at 1-month follow-up. The median survival time was 22 months (95% CI, 13.10-30.90 months). The OS rates were 82.0% at six months, 62.5% at one year, and 43.0% at two years. Targeted therapy and/or immunotherapy (P=0.001) and tumor response at one month (P=0.020) were protective factors for OS. In terms of safety, no major complications occurred and the only observed decrease within the normal range occurred in albumin and platelet levels one month after the embolization procedure. This decrease in levels did not show a significant relationship with the OR rates. Conclusion: M-TACE demonstrated a promising objective tumor response, making it a viable and effective treatment option for patients with large unresectable HCC.

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers.

Aims: To determine the safety and efficacy of microwave ablation (MWA) and transarterial chemoembolization (TACE) with doxorubicin hydrochloride liposome (DHL) in patients with primary liver cancer (PLC) and metastatic liver cancer (MLC). Materials and methods: The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed. Treatment-related adverse events (AEs) were recorded. Local tumor response was evaluated according to the modified RECIST criteria. Local tumor progression-free survival (LTPFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Altogether, 96 patients with liver cancer were included (PLC, n â€‹= â€‹45; MLC, n â€‹= â€‹51). Forty (41.7%) patients experienced AEs during treatment, and eight (8.3%) patients developed grade 3 AEs. Compared to before treatment, the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment. The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC. The median OS was not reached in patients with PLC or MLC. The 1-month and 3-month disease control rates reached more than 80% in both groups. Conclusion: MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.

Pectolinarigenin attenuates hepatic ischemia/reperfusion injury via activation of the PI3K/AKT/Nrf2 signaling pathway.

Hepatic ischemia/reperfusion (I/R) injury is an unavoidable complication of liver hepatectomy, transplantation, and systemic shock. Pectolinarigenin (Pec) is a flavonoid with many biological activities, which include anti-inflammatory, anti-apoptotic, and antioxidant stress. This study explored whether Pec pretreatment could reduce hepatic I/R injury and the potential mechanisms at play. After pretreatment of mice and AML12 cells with Pec, I/R and hypoxia/reoxygenation (H/R) models were established. By examining markers related to liver injury, cell viability, oxidative stress, inflammatory response, and apoptosis, the effect of Pec on important processes involved in hepatic I/R injury was assessed. Protein levels associated with the PI3K/AKT/Nrf2 pathway were analyzed by relative quantification to investigate possible pathways through which Pec plays a role in the I/R process. Pec treatment corrected abnormal transaminase levels resulting from I/R injury, improved liver injury, and increased AML12 cell viability. Moreover, Pec treatment inhibited oxidative stress, inflammation and apoptosis and could activate the PI3K/AKT/Nrf2 pathway during I/R and H/R. Further studies found that LY294002 (PI3K inhibitor) suppressed the protective effect of Pec on hepatic I/R injury. In summary, our results show that Pec inhibits oxidative stress, inflammatory responses, and apoptosis, thereby attenuating I/R-induced liver injury and H/R-induced cell damage via activation of the PI3K/AKT/Nrf2 pathway.

Hepatocellular Carcinoma with Radiological Progression: Lenvatinib Plus PD-1 Inhibitor Combined with Microwave Ablation and Synchronous Transarterial Chemoembolization.

Purpose: To determine the clinical outcomes of lenvatinib plus PD-1 inhibitor combined with microwave ablation (MWA) and synchronous transarterial chemoembolization (TACE) in patients with progressive hepatocellular carcinoma (pHCC). Materials and Methods: This retrospective study enrolled pHCC patients who underwent lenvatinib plus PD-1 inhibitor combined with MWA and TACE (LP-MT) or lenvatinib combined with MWA and TACE (L-MT) from January 2019 to December 2022. Treatment-related adverse events (AEs) were recorded during the follow-up. Progression-free survival (PFS) and overall survival (OS) were the primary outcomes. The prognostic analyses for survival were performed using Cox proportional hazard regression model. Results: In total, 90 eligible patients with pHCC who received combination therapy were included in the study. Among them, 42 patients received LP-MT and 48 patients received L-MT. There were no significant differences in the baseline characteristics between the two groups. Patients who underwent lenvatinib plus PD-1 inhibitor combined with MWA and TACE had better PFS (median, 10.0 vs 7.4 months, P = 0.03) than those who underwent combination therapy without PD-1 inhibitor, although no significant difference was found in OS (median, 22.5 vs 20.0 months, P = 0.19) between the two groups. The disease control rate of LP-MT group was higher than that of L-MT group (88.1% vs 64.6%, P = 0.01), especially in patients with BCLC stage C (89.3% vs 70.0%, P = 0.03). Univariate and multivariate analyses indicated that treatment method and Child-Pugh class were independent prognostic factors for PFS. The AEs of LP-MT group were comparable and tolerable to those of L-MT group (Any grade, 78.6% vs 62.5%, P = 0.10; Grade 3, 23.8% vs 12.5%, P = 0.16). Conclusion: Lenvatinib plus PD-1 inhibitor may be slightly superior to lenvatinib alone when combined with local interventional therapy for progressive HCC, especially in patients with BCLC stage C.

[Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study]. / é‡ç»„äººç”Ÿé•¿æ¿€ç´ æ²»ç–—ä¸åŒåž‚ä½“å‘è‚²çŠ¶å†µç”Ÿé•¿æ¿€ç´ ç¼ºä¹ç—‡æ‚£å„¿ç–—æ•ˆçš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS: In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.

Comparison of intraluminal brachytherapy combined with and without stent placement for treatment of obstructive jaundice induced by tumor thrombus.

PURPOSE: To compare the safety and efficacy of intraluminal brachytherapy with iodine-125 (125I) seed strand implantation combined with and without stent placement to treat patients with obstructive jaundice induced by tumor thrombus. METHODS: Between January 2018 and June 2022, 42 patients with malignant obstructive jaundice (MOJ) induced by tumor thrombus were included. 20 patients received 125I seed strand implantation and stent placement (group A). The remaining 22 patients, implanted 125I seed strands only, served as control (group B). The two groups' overall survival and jaundice-free survival were compared using the Kaplan-Meier method and log-rank test. RESULTS: During the follow-up period, the mean survival time of group A was 38.0 ± 4.1 months (95%CI, 30.0-46.1 months), while that of group B was 25.1 ± 2.8 (95% CI, 19.5-30.6 months) (p = 0.406). The mean survival rates of 12 months for all patients, group A, and group B was 66.7%, 65%, and 68%, respectively. The mean jaundice-free survival of group A and group B were 34.0 ± 3.6 months (95% CI, 27.9-41.2months) and 22.9 ± 2.7 months (95%CI, 17.5-28.2months) (p = 0.254), respectively. Two PTBD drainage tube infection cases occurred in group A and group B separately. CONCLUSIONS: 125I intraluminal brachytherapy is an effective and safe therapy for treating patients with obstructive jaundice induced by tumor thrombus.

Role of epithelial sodium channel-related inflammation in human diseases.

The epithelial sodium channel (ENaC) is a heterotrimer and is widely distributed throughout the kidneys, blood vessels, lungs, colons, and many other organs. The basic role of the ENaC is to mediate the entry of Na+ into cells; the ENaC also has an important regulatory function in blood pressure, airway surface liquid (ASL), and endothelial cell function. Aldosterone, serum/glucocorticoid kinase 1 (SGK1), shear stress, and posttranslational modifications can regulate the activity of the ENaC; some ion channels also interact with the ENaC. In recent years, it has been found that the ENaC can lead to immune cell activation, endothelial cell dysfunction, aggravated inflammation involved in high salt-induced hypertension, cystic fibrosis, pseudohypoaldosteronism (PHA), and tumors; some inflammatory cytokines have been reported to have a regulatory role on the ENaC. The ENaC hyperfunction mediates the increase of intracellular Na+, and the elevated exchange of Na+ with Ca2+ leads to an intracellular calcium overload, which is an important mechanism for ENaC-related inflammation. Some of the research on the ENaC is controversial or unclear; we therefore reviewed the progress of studies on the role of ENaC-related inflammation in human diseases and their mechanisms.