Long non-coding RNA MSL3P1 regulates CUL3 mRNA cytoplasmic transport and stability and promotes lung adenocarcinoma metastasis.

Lung adenocarcinoma (LUAD) is the most prevalent histological type of lung cancer. Previous studies have reported that specific long non-coding RNAs (lncRNAs) are involved in cancer development and progression. The phenotype and mechanism of ENST00000440028, named MSL3P1, a lncRNA which we referring to a cancer-testis gene with potential roles in tumorigenesis and progression, have not been reported. We found that MSL3P1 is overexpressed in LUAD tumor tissues, which is significantly associated with clinical characteristics, metastasis, and poor clinical prognosis. MSL3P1 promotes the metastasis of LUAD in vitro and in vivo. The enhancer reprogramming in LUAD tumor tissue is the major driver of the aberrantly expression of MSL3P1. Mechanistically, due to the competitive binding to CUL3 mRNA with ZFC3H1 protein (a protein involved in targeting polyadenylated RNA to exosomes and promoting the degradation of target mRNA), MSL3P1 can prevent the ZFC3H1-mediated RNA degradation of CUL3 mRNA and transport it to the cytoplasm. This activates the downstream epithelial-to-mesenchymal transition signaling pathway, and promote tumor invasion and metastasis. Implications: This study indicates that lncRNA MSL3P1 regulates CUL3 mRNA stability and promotes the metastasis and holds potential as a prognostic biomarker and therapeutic target in LUAD.

CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer.

CYP3A5 is a cytochrome P450 (CYP) enzyme that metabolizes drugs and contributes to drug resistance in cancer. However, it remains unclear whether CYP3A5 directly influences cancer progression. In this report, we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal adenocarcinoma. Multi-omics analysis showed that CYP3A5 knockdown results in a decrease in various glucose-related metabolites through its effect on glucose transport. A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP, a negative regulator of GLUT1. Notably, CYP3A5-generated reactive oxygen species were proved to be responsible for attenuating the AKT-4EBP1-TXNIP signaling pathway. CYP3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic cancer. Taken together, our results, for the first time, reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

Construction of carbon sequestration ecological network in Linyi City based on supply and demand of ecosystem service.

The increasing carbon emissions is one of the important reasons for global warming. As a key area of carbon emissions, carbon sequestration capacity of cities is urgently needed to be improved. Carbon sequestration ser-vices can be transferred between supply and demand areas due to the circulation of atmosphere. With Linyi City as an example, we used the minimum cumulative resistance model to extract the matching path of supply and demand, and constructed a carbon sequestration ecological network. The results showed that the regions with high supply of carbon sequestration services were located in the north and south of the study area, and that current total supply could solve about 60% of the total demand. Although the spatial distribution of supply and demand was uneven, 54% of the areas that could meet the surrounding carbon sequestration demand were still idle. The optimized supply-demand matching paths could maintain good transmission efficiency of material and energy, with lower costs. Paths with strong potential carbon sequestration capacity were located in the central and northwest part of the research area. In the construction of carbon sequestration ecological network, it is necessary to strengthen the protection and restoration of the supply side of carbon sequestration services, realize carbon reduction and strengthen carbon sequestration on the demand side, and optimize the matching path of supply and demand. This method provided services to the demand areas through the oversupply of ecosystem services, optimized the overall resource allocation, which could advance regional carbon sequestration capacity.

Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

A liquid biopsy assay for the noninvasive detection of lymph node metastases in T1 lung adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma (LUAD) is a common pathological type of lung cancer. The presence of lymph node metastasis plays a crucial role in determining the overall treatment approach and long-term prognosis for early LUAD, therefore accurate prediction of lymph node metastasis is essential to guide treatment decisions and ultimately improve patient outcomes. METHODS: We performed transcriptome sequencing on T1 LUAD patients with positive or negative lymph node metastases and combined this data with The Cancer Genome Atlas Program cohort to identify potential risk molecules at the tissue level. Subsequently, by detecting the expression of these risk molecules by real-time quantitative PCR in serum samples, we developed a model to predict the risk of lymph node metastasis from a training cohort of 96 patients and a validation cohort of 158 patients. RESULTS: Through transcriptome sequencing analysis of tissue samples, we identified 11 RNA (miR-412, miR-219, miR-371, FOXC1, ID1, MMP13, COL11A1, PODXL2, CXCL13, SPOCK1 and MECOM) associated with positive lymph node metastases in T1 LUAD. As the expression of FOXC1 and COL11A1 was not detected in serum, we constructed a predictive model that accurately identifies patients with positive lymph node metastases using the remaining nine RNA molecules in the serum of T1 LUAD patients. In the training set, the model achieved an area under the curve (AUC) of 0.89, and in the validation set, the AUC was 0.91. CONCLUSIONS: We have established a new risk prediction model using serum samples from T1 LUAD patients, enabling noninvasive identification of those with positive lymph node metastases.

Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia.

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited. METHODS: In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45+ cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models. RESULTS: Our results characterized the CD45+ cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C+ monocytes and interacted with effector CD4+ T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP. CONCLUSION: Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP's cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets.

Integrating Frailty Assessment to Enhance Care in Cancer Patients with Borderline Eastern Cooperative Oncology Group Performance Status.

BACKGROUND: The (ECOG) performance status (PS) is commonly used to evaluate the functional ability of patients undergoing antitumor therapy. An ECOG PS of 2, indicating patients capable of self-care but restricted strenuous activity, can complicate treatment decisions owing to concerns regarding treatment-related toxicity. We investigated whether frailty assessment could help discriminate treatment tolerance and survival outcomes in patients with an ECOG PS of 2. METHODS: We prospectively included 45 consecutive patients, aged ≥65 years, with an ECOG PS of 2, and newly diagnosed solid cancer scheduled for chemotherapy. Frailty was assessed using an eight-indicator geriatric assessment. The primary outcome was overall survival (OS) based on frailty status; secondary outcomes included treatment tolerance and toxicity. RESULTS: The median patient age was 73 years (range 65-94), and 71% had stage IV disease. Predominant frailty-related deficits were functional decline (96%), malnutrition (78%), and polypharmacy (51%). The median OS was 12.6 months (95% confidence interval [CI]: 6.8-18.4). Patients with 4-6 deficits had significantly lower OS than those with 1-3 deficits (9.9 months vs. 20.0 months, adjusted hazard ratio 2.51, 95% CI: 1.16-5.44, P = .020). Frailty significantly correlated with reduced 12-week chemotherapy competence (52% vs. 85%, adjusted odds ratio [OR] .14, 95% CI: .03-.70, P = .016) and enhanced risk of unexpected hospitalization (60% vs. 20%, adjusted OR 6.80, 95% CI: 1.64-28.1, P = .008). CONCLUSION: Our findings highlight the multifaceted nature of patients with an ECOG PS of 2 and emphasize the importance of frailty assessment for treatment outcomes.

Ankylosing spondylitis status and risk of secondary systemic amyloidosis: A two-sample mendelian randomization study.

OBJECTIVES: There is still controversy regarding the causal relationship between ankylosing spondylitis (AS) and secondary systemic amyloidosis (SSA). This study utilized aggregated data from genome-wide association studies (GWAS) on population cohorts to investigate whether a causal relationship exists between AS and SSA. METHODS: The genetic causal relationship between AS status and SSA was analyzed utilizing a two-sample Mendelian randomization (TSMR). The analyses were conducted using the weighted mode method (WM2), inverse variance weighted method (IVW), simple mode (SM), weighted median method (WM1), and Mendelian randomization Egger regression (MR-Egger). Among these methods, the primary results were based on the IVW approach. The association was evaluated using the odds ratio (OR) along with a 95% confidence interval (95% CI). RESULTS: The IVW analysis revealed a positive causal relationship between AS status and SSA (OR = 1.411, 95 % CI = 1.069, 1.862, P = 0.015). Meanwhile, the WM1 (OR = 1.394, 95 % CI = 1.115, 1.742, P = 0.004) and WM2 (OR = 1.393, 95 % CI = 1.112, 1.743, P = 0.045) methods also identified a positive causal relationship between AS status and SSA. The MR-Egger method did not identify a causal relationship between AS and SSA (OR = 1.175, 95 % CI = 0.888, 1.555, P = 0.342). The SM results demonstrated that the observed genotypes did not exhibit statistically significant differences between AS and SSA (OR = 1.184, 95 % CI = 0.416, 3.366, P = 0.767). The results of the MR-Egger regression suggested that the results were unaffected by bias caused by genetic pleiotropy (Intercept = 0.283, SE = 0.134, P = 0.126). Cochran's Q test did not reveal any significant heterogeneity (Q = 1.759, P = 0.624). The "leave-one-out" analysis further confirmed that the absence of any single SNP did not impact the robustness of our results. CONCLUSION: This study revealed a positive causal relationship between AS status and the occurrence of SSA, providing new insights into the genetic analysis of SSA.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study

ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Surgical outcomes of hepatocellular carcinoma with extrahepatic bile duct tumor thrombus: a multicenter study.

Background: The long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT. Methods: A total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: With a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS. Conclusion: Major hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT.

Frailty assessment by two screening instruments in non-elderly patients with head and neck cancer.

PURPOSE: Frailty assessment is often overlooked in non-elderly patients with cancer, possibly due to the lack of an effective frailty screening tool. This study aimed to evaluate the performance of two modern frailty screening tools, the Flemish version of the Triage Risk Screening Tool (fTRST) and the modified 5-Item Frailty Index (mFI-5), compared to the gold standard comprehensive geriatric assessment (GA) among non-elderly patients with head and neck cancer (HNC). METHODS: We prospectively included 354 consecutive patients aged < 65 years with newly diagnosed HNC scheduled for definitive concurrent chemoradiotherapy (CCRT) at three academic hospitals in Taiwan between January 2020 and December 2022. Frailty assessment using the GA, fTRST, and mFI-5 was performed in all patients to evaluate the relationship between frailty and treatment outcomes. RESULTS: The prevalence of frailty was 27.1%, 37.0%, and 42.4% based on GA, mFI-5, and fTRST, respectively. mFI-5 and fTRST demonstrated good predictive value in identifying frail patients compared to the GA. Patients with frailty, as defined by GA, mFI-5, and fTRST, exhibited higher risks of treatment-related complications, incomplete treatment, and poorer baseline quality of life (QoL). However, only GA showed significant prognostic value for overall survival. CONCLUSIONS: Frailty assessment using fTRST and mFI-5 is valuable for predicting treatment-related adverse events, treatment tolerance, and QoL in non-elderly patients with HNC. Incorporating frailty assessment into the management of non-elderly cancer patients can aid in the identification of high-risk individuals. However, the performance of these tools varies, highlighting the need for further validation and refinement.

Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration.

OBJECTIVE: Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC). METHODS: An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method. RESULTS: We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38. CONCLUSION: Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.

Early Tumor Marker Response Predicts Treatment Outcomes in Patients with Unresectable Hepatocellular Carcinoma Receiving Combined Lenvatinib, Immune Checkpoint Inhibitors, and Transcatheter Arterial Chemoembolization Therapy.

Purpose: Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy. Patients and Methods: This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration >50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991-45.950, p<0.001; high-DCP group: OR: 17.853; 95% CI: 4.478-71.179, p<0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p<0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p<0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p<0.001). Conclusion: After 6 weeks of triple therapy, an AFP or DCP reduction of >50% predicts better treatment outcomes in uHCC patients.

Effect of coexisting adenomyosis on tumour characteristics and prognosis of endometrial cancer: A systematic review and meta-analysis.

To compare clinicopathological features and survival outcomes in patients with endometrial cancer, with and without associated adenomyosis. PubMed, Embase and Scopus databases were systematically searched for relevant observational studies. The pooled effect sizes were reported as either hazards ratio (HR) for survival-related outcomes or as odds ratio (OR) for other categorical outcomes. Weighted mean difference (WMD) was reported for continuous outcomes. All the analyses used the random effects model. A total of 21 studies (N = 46,420) were included. Compared to endometrial cancer patients without adenomyosis, patients with associated adenomyosis had improved overall 5-year survival (OS) (HR 0.62, 95% CI: 0.50, 0.79) and disease-free survival (DFS) (HR 0.60, 95% CI: 0.44, 0.82). Disease-specific survival was statistically similar in patients with and without adenomyosis (HR 0.60, 95% CI: 0.35, 1.05). Among patients with adenomyosis, the risk of having an advanced tumour grade (Grade 2 or 3) was lower (OR 0.51, 95% CI: 0.42, 0.62) and a risk of having International Federation of Gynaecology and Obstetrics (FIGO) stage I or II was higher (OR 2.23, 95% CI: 1.65, 3.01). Patients with adenomyosis had lower risk of tumour invasion of adnexa, cervical stromal invasion, deep myometrial involvement (DMI), lympho-vascular space invasion (LVSI) and peritoneal invasion. Presence of adenomyosis in patients with endometrial cancer is associated with favourable tumour characteristics and may improve the survival.

Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis.

OBJECTIVE: To evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical decision-making. METHODS: Randomized controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation results. RESULTS: A total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (-0.86, 17.75), 5 (-5.01, 11.09), and 6 (-1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, respectively. CONCLUSION: Based on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

Rutaecarpine ameliorates osteoarthritis by inhibiting PI3K/AKT/NF­κB and MAPK signalling transduction through integrin αVß3.

Osteoarthritis (OA) is a chronic progressive articular illness which commonly affects older­aged adults, presenting with cartilage inflammation and degradation. Rutaecarpine (RUT) has been shown to exert promising anti­inflammatory effects; however, the efficacy of RUT in the treatment of OA is debatable. The present study investigated the potential of RUT in alleviating OA in a mouse model. Treatment with RUT inhibited the inflammatory response and extracellular matrix degradation by suppressing process regulators in interleukin (IL)­1ß­stimulated chondrocytes. Moreover, treatment with RUT in vitro upregulated the gene expression of anabolic agents, such as collagen type II, aggrecan and SRY­box transcription factor 9, indicating that RUT contributed to cartilage repair. Additionally, flow cytometric assays, and the measurement of ß­galactosidase levels, autophagic flux and related protein expression revealed that RUT effectively attenuated IL­1ß­induced chondrocyte apoptosis, senescence and autophagy impairment. In addition, bioinformatics analysis and in vitro experiments demonstrated that RUT protected cartilage by mediating the phosphoinositide­3­kinase (PI3K)/Akt/nuclear factor­κB (NF­κB) and mitogen­activated protein kinase (MAPK) pathways. The ameliorative effects of RUT on IL­1ß­stimulated chondrocytes were abrogated when siRNA was used to knock down integrin αVß3. Furthermore, the results of immunohistochemical analysis and microcomputed tomography confirmed the in vivo therapeutic effects of RUT in mice with OA. On the whole, the present study demonstrates that RUT attenuates the inflammatory response and cartilage degradation in mice with OA by suppressing the activation of the PI3K/AKT/NF­κB and MAPK pathways. Integrin αVß3 may play a pivotal role in these effects.

The Clinical Presentations of Liver Abscess Development After Endoscopic Retrograde Cholangiopancreatography with Choledocholithiasis: A 17-Year Follow-Up.

Background: Endoscopic Retrograde Cholangiopancreatography (ERCP), used for choledocholithiasis treatment, carries a risk of pyogenic liver abscess (PLA) due to communication between the biliary system and bowel contents. However, limited data exists on this issue. This study aims to identify the risk factors pertaining to liver abscesses following ERCP lithotomy. Methods: We conducted a retrospective case series across multiple centers to evaluate patients who developed PLA after ERCP for choledocholithiasis. Data was obtained from the Chung Gung Research Database (January 2001 to December 2018). Out of 220 enrolled patients, 195 were categorized in the endoscopic sphincterotomy (ES) group, while 25 were in the non-ES group for further analysis. Results: The non-ES group had significantly higher total bilirubin levels compared to the ES group (4.3 ± 5.8 vs 1.9 ± 2.0, p<0.001). Abscess size, location, and distribution (single or multiple) were similar between the two groups. The most common pathogens were Klebsiella pneumoniae and Escherichia coli. Pseudomonas infection was significantly less prevalent in the ES group compared to the non-ES group (3.6% vs 16.7%, p=0.007). Patients with concurrent malignancies (HR: 9.529, 95% CI: 2.667-34.048, p=0.001), elevated total bilirubin levels (HR: 1.246, 95% CI: 1.062-1.461, p=0.007), multiple abscess lesions (HR: 5.146, 95% CI: 1.777-14.903, p=0.003), and growth of enterococcus pathogens (HR: 4.518, 95% CI: 1.290-15.823, p=0.001) faced a significantly higher risk of in-hospital mortality. Conclusion: PLA incidence was higher in the ES group compared to the non-ES group following ERCP for choledocholithiasis. Attention should be given to significant risk factors, including concurrent malignancies, elevated total bilirubin levels, multiple abscess lesions, and growth of enterococcus pathogens, to reduce in-hospital mortality.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study.

OBJECTIVES: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. MATERIALS AND METHODS: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. RESULTS: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. CONCLUSIONS: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.