Stage Invasion Research Articles

Gene mutation, clinical characteristics and pathology in resectable lung adenocarcinoma

ObjectiveWith the wide use of CT scan in clinical practice, more lung cancer was diagnosed in resectable stage. Pathological examination and genetic testing have become a routine procedure for lung adenocarcinoma following radical resection. This study analyzed special pathological components and gene mutations to explore their relationship with clinical characteristics and overall survival.MethodsClinical, pathological, and gene mutation data from 1,118 patients were collected. All patients underwent surgery at the Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University. Patients were grouped based on pathological components and gene mutations. Differences in clinical features and overall survival were analyzed as well.ResultsPatients with mucinous, neuroendocrine, and poor-differentiated components were presented with more prognostic risk factors, including pleural invasion, carcinothrombosis, STAS, and advanced stages, along with varying frequencies of gene mutations. These factors significantly shortened overall survival. ALK and KRAS mutations were also associated with risk factors such as solid nodules, pleural invasion, STAS, and later stages. However, a significant reduction in overall survival was observed only in patients with the KRAS mutation. Relationship between gene mutations and pathological components still requires further investigation.ConclusionSpecial pathological components (mucinous, neuroendocrine, and poor-differentiated) and gene mutations had an influence on biological behavior of tumors, resulting in different clinical characteristics and prognosis.

Is the risk of bank vole infection with cestodes related to the population dynamics regime?

The bank vole (Clethrionomys glareolus (Schreber, 1780)) is the dominant species in the primary fir-spruce forests of the Visim State Biosphere Reserve in the Middle Urals. Here, we studied the long-term population dynamics of small mammals and infection rates with cestode larvae (Cestoida) of bank voles from 1995 to 2021. In addition to the traditionally studied risk factors of parasite infection (e.g., age and sex, phase of population cycle of the host), we assessed the possible influence of the intermediate host population dynamics by contrasting parts of the time series with regular 3-year cyclicity and noncyclic regime. The overall risk of larval cestode infections was 5.0% (95% CI: 4-6%, Ninfected = 97, Ntotal = 1938). The infection rate was associated with the animals' age and, unexpectedly, with the intermediate host population dynamics regime. The odds of finding cestode larvae in overwintered individuals were 4.3 times (2.8-6.6) higher than in young of the year, and in the noncyclic regime, the odds were 2.3 times (1.5-3.5) higher than in the 3-year cyclicity regime. No statistically significant higher risk of infection was found for males compared to females as the infection rate was only 1.4 times (0.9-2.1, ≈ 1) higher. The higher infection rates of overwintered individuals were as expected for individuals associated with longer exposure to the invasive parasite stages. We hypothesised that the noncyclic regime in long-term fluctuations of rodent numbers better resonates with the characteristic period of the cestodes' life cycle, resulting in higher infection rates.

Dual-center retrospective cohort analysis of high-risk cutaneous squamous cell carcinoma tumors.

High-risk cutaneous squamous cell carcinoma (hr-cSCC) tumors exhibit aggressive behavior, leading to local recurrence, metastasis, and mortality. The management of hr-cSCC tumors is not well-defined. To clarify the impact of clinical risk factors and management strategies on disease-related outcomes (DROs) in patients with hr-cSCCs. This dual-center retrospective cohort study reviewed patient records from 2007 to 2023, focusing on hr-cSCC tumors classified as high-risk according to two staging systems. 160 adult patients with hr-cSCC were included. Tumors > 2cm were associated with a higher risk of recurrence, metastasis, and mortality, with greater risk for tumors > 4cm. Nonsurgical therapies were linked to higher recurrence and mortality rates compared to surgical monotherapy. Patients whose initial treatment was delayed > 60 days following biopsy had increased incidence of DROs. Other variables associated with at least one DRO included female sex, higher tumor grade, lymphovascular invasion, and advanced AJCC-8 stages. Limitations of this study include its retrospective design, narrow demographics, and variable follow-up times. This study identifies increased tumor diameter, non-surgical treatments, delayed treatment > 60 days after biopsy, female sex, tumor grade, lymphovascular invasion, and advanced tumor stage as significant risk factors for DROs in hr-cSCC. Importantly, our study provides new clarifying evidence that delayed surgical treatment of hr-cSCCs > 60 days after biopsy is associated with elevated incidence of DROs.

Neoadjuvant Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Chemotherapy for Muscle-Invasive Urothelial Cancer: Large, Single-Center Analysis of Consecutive Patients' Data.

Background/Objectives: Bladder cancer is a significant clinical problem with approximately 500,000 new cases worldwide annually. In approximately 25% of cases, disease is diagnosed at a stage of invasion of the muscle layer of the bladder. The current standard approach in this disease is preoperative chemotherapy followed by radical cystectomy. Dose-dense MVAC (ddMVAC), a two-day chemotherapy regimen, is the reference treatment protocol in this setting. The presented study evaluated the effectiveness and safety of accelerated MVAC (aMVAC) chemotherapy-a one-day regimen given before the resection of the bladder due to muscle-invasive disease. Methods: A retrospective analysis included 119 consecutive patients diagnosed with urothelial muscle-invasive bladder cancer (MIBC) who underwent preoperative chemotherapy with the aMVAC regimen. The planned treatment included 4-6 cycles of preoperative chemotherapy. The analysis of the degree of histopathological response to treatment was based on the three-grade TRG (tumor regression grade) classification. Results: A complete pathological response (TRG1) was observed in 44 patients (36.7%), and a major pathologic response (<ypT2) was achieved in 58 patients (48.7%). A reduction in the cisplatin dose was associated with a statistically significant decrease in the chance of achieving complete pathologic responses (46.1% vs. 10%, RR for TRG1 = 0.69, p = 0.00118). Patients who received at least 4 cycles (compared to ≤3 cycles) of neoadjuvant chemotherapy had a significantly higher chance of achieving a pathological response (partial or complete) to treatment (78.1% vs. 52.2%, RR 0.68, p = 0.0374). Administration of at least five cycles of chemotherapy was associated (compared to four cycles) with a significantly higher likelihood of achieving a complete pathological response (63.2% vs. 33.8%, RR = 1.71, p = 0.0221). The vast majority of adverse events were in grades 1 and 2, according to CTCAE version 5.0. Only five patients experienced grade 3-4 toxicities. The most common adverse event was anemia, which occurred in 66.3% of patients. Conclusions: Our real-world data analysis confirms the activity, safety, and feasibility of the aMVAC regimen as neoadjuvant chemotherapy in patients with urothelial MIBC.

Real-world data on utilization of neoadjuvant chemotherapy for muscle invasive bladder cancer: impact on surgical complications and oncological efficacy.

Recommended treatment of urothelial muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy, but there are challenges with low utilization of NAC. We aimed to evaluate the utilization of NAC, perioperative complications and oncological efficacy in a real-world setting. All patients operated with radical cystectomy at the University Hospital of North Norway during 2011-2021 for MIBC were included. NAC consisted of three cycles of dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (ddMVAC) every second week. Complications after cystectomy (Clavien-Dindo ≥ grade 3 within 30 days), histopathologic NAC response, cancer recurrence, relapse-free survival (RFS), overall survival (OS) and cause of death were reported. We included 124 patients, median observation time of 4 years. Fifty-nine patients (48%) received NAC. Most common causes for not receiving NAC were age ≥ 75 years (n = 38; 31%), cardiovascular disease (n = 7; 5.6%), and reduced kidney function (n = 6; 4.8%). Overall 34 patients (27%) had a ≥ grade 3 complication. The 5-year actuarial OS rate was higher among patients treated with NAC than those without NAC (67% vs. 45%, p = 0.02). Among NAC-treated patients, 29 (49%) were downstaged to non-muscle invasive stage (≤pT1), and the 5-year actuarial RFS and OS were higher among patients with ≤pT1 in the post-cystectomy specimen than those with ≥ pT2 (92% vs. 35%, and 94% vs. 39%, both p < 0.001). The utilization of NAC was high in this real-world setting. Treatment with ddMVAC with achieved downstaging to ≤pT1 was associated with considerably improved RFS and OS.

Preoperative inflammatory burden index for prognostication in esophageal squamous cell carcinoma undergoing radical resection

BackgroundThe Inflammatory burden Index (IBI) is an effective predictor for a range of malignancies. However, the significance of IBI in esophageal squamous cell carcinoma (ESCC) needs to be further verified. The aim of this study was to verify the predictive power of IBI in ESCC undergoing radical resection.MethodsThe current retrospective study, which comprised 408 ESCC patients randomized into either the primary or validation cohort, evaluated the relationships between IBI, clinical characteristics, and cancer-specific survival (CSS). Additionally, the nomogram model was also constructed and verified.ResultsThe IBI is significantly related to tumor length, vessel invasion, perineural invasion, and TNM stage. Compared to other hematological indices, the decision curve analyses (DCA) and receiver operating characteristic curve (ROC) confirmed the higher prognostic value of IBI, indicating the better clinical applicability. In patients with high IBI compared to the low IBI cohort, the 5-year CSS was considerably worse (total: 27.0% vs. 59.1%, P < 0.001; primary: 25.0% vs. 58.9%, P < 0.001; validation: 31.7% vs. 59.7%, P = 0.002). The IBI was shown to be an independent parameter by multivariate analyses (primary: HR = 2.352, P < 0.001; validation: HR = 1.683, P = 0.045). Finally, with the C-index of 0.675 (0.656–0.695) in the primary set and 0.662 (0.630–0.694) in the validation set for CSS in ESCC, an IBI-based nomogram was created and validated.ConclusionThe predictive significance of IBI in ESCC patients undergoing radical resection was validated by this investigation. IBI may be utilized for preoperative evaluation of ESCC as it was found to be substantially correlated with prognosis.

Vaccination with a DNA vaccine cocktail encoding TgROP2, TgROP5, TgROP9, TgROP16, TgROP17, and TgROP18 confers limited protection against Toxoplasma gondii in BALB/c mice.

Toxoplasmosis is a foodborne zoonotic parasitic disease caused by Toxoplasma gondii, which seriously threatens to human health and causes economic losses. At present, there is no effective vaccine strategy for the prevention and control of toxoplasmosis. T. gondii rhoptry proteins (ROPs) are important proteins secreted by the parasite during the early stage of invasion into host cells. In this study, we constructed six individual plasmids (pVAX1-ROP2, pVAX1-ROP5, pVAX1-ROP9, pVAX1-ROP16, pVAX1-ROP17, and pVAX1-ROP18) encoding T. gondii rhoptry proteins and then used an equimolar amount of each as a vaccine cocktail. Following booster immunization, serum antibody levels, splenic lymphocyte proliferation, cytokine production, and survival time after infection with T. gondii RH strain were measured in immunized mice. The results showed that the mice immunized with the DNA vaccine cocktail developed a higher level of the specific anti-T. gondii IgG in serum and the cytokines such as IFN-γ, IL-2, IL-12, and IL-4 (P < 0.01). The stimulation index (SI) of spleen lymphocytes (P < 0.01), the frequencies of CD4+ T lymphocytes (P < 0.01), and the ratio of CD4+/CD8+ T lymphocytes (P < 0.05 or P < 0.01) in the vaccine-immunized mice were significantly increased compared to the control group. After challenge with the virulent T. gondii RH strain tachyzoites, the survival time of mice in the DNA vaccine cocktail group (18.1 ± 1.81 d) was significantly longer (P < 0.01) than that in the control group (8.4 ± 1.02 or 7.9 ± 0.83 d). The results indicated that the DNA vaccine cocktail could elicit strong humoral and cellular immune responses in mice and could also improve the resistance of mice to acute T. gondii infection.

THE STABILITY OF IRANIAN AND CENTRAL ASIAN CIVILIZATION AND IDENTITY DURING THE REIGN OF THE MONGOLS

The cultural life of Iran experienced a decline due to the Mongol invasion in the early stages of the dynasty, then with the establishment of the Ilkhan government in Iran, a period of partial revival of Iranian-Islamic thought and culture began. After all, the Arab invasion of Iran, the collapse of the Sassanids and the rise of Islam weakened the foundations of the political and religious unity of Iranian existence and weakened its integrity. The Islamic government replaced the ethnic and national government of Iran, and the world religion of Islam replaced the Zoroastrian religion of Iran for three centuries. Iranshahr or the Iranian kingdom also collapsed. For several centuries, the political unity of the country of Iran, that is, before the rule of the Ilkhans, and especially before the emergence of the power of the Safavid dynasty, was weakened. The purpose of this article is to consider the rulers of the Ilkhanate as saviors of the Iranian people from the influence of foreign culture and reformers of Iranian national identity. The Ilkhanids used three discursive strategies: Mongol, Iranian and Islamic to legitimize their rule in Iran. In this context, the Ilkhanids played an important role in preserving and modernizing Iran’s intellectual and cultural heritage. For this reason, the Ilkhanate period is considered one of the fundamental aspects of Iranian civilization, which brought about great changes in Iran’s cultural policy. The article uses factorial and textual analysis methods to identify the main elements in the formation of such unique discourses. The results presented in the article allowed the researchers to conclude that for the first time, the Ilkhanid era provided a suitable platform and context for the display of various aspects of Iranian identity. Thus, although the later stages of the Mongol invasion in history were a kind of retreat for Iranian culture and civilization, in reality, under the influence of another language and culture, to consider Iran as having rediscovered itself and become the basis for the reshaping of its forgotten national identity, personalities, languages ​​and cultures is the main idea of the article.

An NIR-driven biosensor based on the metal-enhanced fluorescence effect and a signal amplification strategy for miRNA detection.

Research has shown that the expression level of microRNA-155 (miRNA-155) is positively correlated with clinical stage and depth of invasion in patients with cervical cancer and cervical intraepithelial neoplasia and tends to be highly expressed. Therefore, it is very important to develop sensitive miRNA-155 analysis methods for the early diagnosis, treatment, and prognostic evaluation of cervical cancer. In this study, a near-infrared light-driven fluorescent biosensor based on the metal-enhanced fluorescence effect of polydopamine-coated upconversion nanoparticle (UP/Au) and two toehold-mediated strand displacement (TMSD) steps was constructed for the detection of miRNA-155. The target miRNA-155 can undergo a TMSD1 reaction with single-stranded DNA1 (ssDNA1) modified on wrinkled silica (WSNs) to form the ssDNA1/miRNA-155 complex and expose toehold 2. Through the TMSD2 reaction, ssDNA2 adsorbed on the UP/Au surface reacts with ssDNA1 to form the ssDNA1/ssDNA2 complex, which replaces miRNA-155 and enables the recovery of the UP/Au fluorescence signal. The target miRNA-155 was reacted with the new ssDNA1 to amplify the detection signal, with a detection range of 0.5-20 pM and a detection limit of 19.76 fM for miRNA-155. In addition, the fluorescent biosensor has been applied for the analysis of miRNA-155 in serum samples, indicating its good practicality.

Genocidal Dimensions of the Russo-Ukrainian War: Targeting the People and Cultural Heritage of Ukraine

When the Russian Federation launched a full-scale aggression against Ukraine, it violated the prohibition on the “use of force against the territorial integrity or political independence of any state”, embodied in Article 2, paragraph 4, of the United Nations Charter. The crimes committed by the Russian armed forces since 24 February 2022 in Ukraine constitute the most serious crimes of international concern, as confirmed by the International Criminal Court’s arrest warrant for Russian President Vladimir Putin and the Presidential Commissioner for Children’s Rights Maria Alekseyevna Lvova-Belova in connection with specific acts classified by this court as war crimes. At the same time, to constitute a crime of genocide, there must be a proven intent on the part of the accused to destroy, in whole or in part, a national, ethnical, racial, or religious group. This article examines the war crimes perpetrated by the Russian armed forces against the civilian population of Ukraine during the Russo-Ukrainian war and identifies signs of genocidal intent in these actions. It analyses explicit acts of genocide including killings, causing serious bodily or mental harm, the forced transfer of Ukrainian children to Russia and occupied territories, and the intentional creation of living conditions geared toward the physical destruction of the Ukrainians as a nation. Additionally, the article scrutinises the attacks on the country’s cultural heritage sites, which in turn can be qualified depending on the circumstances, as war crimes (when, inter alia, military necessity is not justified and the principle of distinguishing between military and civilian targets is violated), crimes against humanity (when they are systematic), or genocide (when they are part of a policy of identity destruction). The author demonstrates that Russian aggression against Ukraine not only poses a threat to the territorial integrity and state sovereignty of the country, but also seeks to annihilate – at least partially – the Ukrainian nation, its identity, and its cultural heritage. The Russo-Ukrainian conflict exhibits signs of a genocidal campaign that are recognised by international law under the 1948 Genocide Convention. This is manifested in an attempt to commit genocide, direct and public incitement for genocide, and the commission of genocide in certain territories, specifically in Bucha and Mariupol. However, substantiating and proving the crime across all of Ukraine will be more difficult and may take years. An exception to this challenge is the mass transfer of almost 4,500 Ukrainian orphans to Russia – a crime that concerns the entire country. Additionally, acts of torture and killings that occurred in the early stages of the full-scale invasion (February and March 2022) in the Kyiv and Chernihiv regions exhibit signs of genocide committed in certain territories. At the same time, the existing facts, viewed through a historical prism, indicate that the actions taken by Russian forces in Ukraine embody the characteristics of genocide.

Genocidal Dimensions of the Russo-Ukrainian War: Targeting the People and Cultural Heritage of Ukraine

When the Russian Federation launched a full-scale aggression against Ukraine, it violated the prohibition on the “use of force against the territorial integrity or political independence of any state”, embodied in Article 2, paragraph 4, of the United Nations Charter. The crimes committed by the Russian armed forces since 24 February 2022 in Ukraine constitute the most serious crimes of international concern, as confirmed by the International Criminal Court’s arrest warrant for Russian President Vladimir Putin and the Presidential Commissioner for Children’s Rights Maria Alekseyevna Lvova-Belova in connection with specific acts classified by this court as war crimes. At the same time, to constitute a crime of genocide, there must be a proven intent on the part of the accused to destroy, in whole or in part, a national, ethnical, racial, or religious group. This article examines the war crimes perpetrated by the Russian armed forces against the civilian population of Ukraine during the Russo-Ukrainian war and identifies signs of genocidal intent in these actions. It analyses explicit acts of genocide including killings, causing serious bodily or mental harm, the forced transfer of Ukrainian children to Russia and occupied territories, and the intentional creation of living conditions geared toward the physical destruction of the Ukrainians as a nation. Additionally, the article scrutinises the attacks on the country’s cultural heritage sites, which in turn can be qualified depending on the circumstances, as war crimes (when, inter alia, military necessity is not justified and the principle of distinguishing between military and civilian targets is violated), crimes against humanity (when they are systematic), or genocide (when they are part of a policy of identity destruction). The author demonstrates that Russian aggression against Ukraine not only poses a threat to the territorial integrity and state sovereignty of the country, but also seeks to annihilate – at least partially – the Ukrainian nation, its identity, and its cultural heritage. The Russo-Ukrainian conflict exhibits signs of a genocidal campaign that are recognised by international law under the 1948 Genocide Convention. This is manifested in an attempt to commit genocide, direct and public incitement for genocide, and the commission of genocide in certain territories, specifically in Bucha and Mariupol. However, substantiating and proving the crime across all of Ukraine will be more difficult and may take years. An exception to this challenge is the mass transfer of almost 4,500 Ukrainian orphans to Russia – a crime that concerns the entire country. Additionally, acts of torture and killings that occurred in the early stages of the full-scale invasion (February and March 2022) in the Kyiv and Chernihiv regions exhibit signs of genocide committed in certain territories. At the same time, the existing facts, viewed through a historical prism, indicate that the actions taken by Russian forces in Ukraine embody the characteristics of genocide.

Colorectal Cancer: A Brief and Simplified Analysis of a Complex Disease.

Background and Objectives: This study examined factors influencing the onset and progression of colorectal tumors, including patients' epidemiological data, tumor location (right-sided, left-sided, and rectal), histomorphology, perineural or intraneural invasion, lymph node status, immune reactions, mismatch repair (MMR) status, and commonly observed mutations. Our primary goal was to evaluate their predictive and prognostic value and interactions. Materials and Methods: We analyzed a retrospective cohort of 100 patients with colorectal adenocarcinoma diagnosed between 2020 and 2023, using formalin-fixed paraffin-embedded (FFPE) tumor blocks. The methods included routine H&E microscopy, immunohistochemistry, Next-Generation Sequencing (NGS), and subsequent statistical analysis. Results: The findings showed a median diagnosis age of 70 years, with no gender-specific tumor localization. Right-sided tumors were prevalent, especially among patients with a defective MMR (dMMR), which represented 89% of dMMR cases. MMR status significantly correlated with tumor localization. We observed significant relationships between tumor grade, lymphovascular invasion, and overall tumor stage. Higher tumor grades and stages correlated with increased lymphovascular invasion and lymph node involvement. Interestingly, tumor budding did not correlate with lymph node metastasis but was significantly associated with higher tumor grades. Most BRAF mutations were found in right-sided tumors, indicating a significant correlation with this localization. Conclusions: This study focuses on the diversity of colorectal cancer (CRC) by examining how genetic and histological characteristics vary based on tumor location or other tumor variables.

Constructing a doxycycline-inducible system for an epithelial-to-mesenchymal transition model in MCF10A cells.

Epithelial to mesenchymal transition (EMT) has been shown to play an essential role in the early stages of cancer cell invasion and metastasis. Inducible EMT models can initiate EMT in a controlled manner, thereby providing the opportunity to determine whether a cancer-associated gene influences cancer metastasis by triggering EMT. Moreover, different inducible EMT models enable the investigation of specific mechanisms of EMT modulation by various genes, facilitating a more precise understanding of how these genes influence cancer metastasis through the induction of EMT. Unfortunately, current inducible EMT models still present unmet needs. Therefore, we aimed to establish an inducible EMT model in MCF10A cells, a spontaneously immortalized human fibrocystic mammary cell line, by manipulating the expression of mouse Twist1 (mTwist1). In this study, we first compared the EMT induction capacity between human TWIST1 (hTWIST1) and mTwist1, and selected mTwist1 for further investigation. By monitoring the changes in epithelial and mesenchymal markers at different induction time points, we examined the EMT process in both polyclonal and monoclonal MCF10A cells that express doxycycline (DOX)-inducible mTwist1. Furthermore, our results showed that doxycycline-induced mTwist1 expression triggered EMT at a similar rate to TGFβ1-induced EMT in MCF10A cells. Additionally, this process was reversible upon DOX withdrawal. Thus, we have established a robust inducible EMT model in MCF10A cells, which can be used to further study cancer metastasis-driving genes.

Spatially resolved gene expression profiling of tumor microenvironment reveals key steps of lung adenocarcinoma development

The interaction of tumor cells and their microenvironment is thought to be a key factor in tumor development. We present spatial RNA profiles obtained from 30 lung adenocarcinoma patients at the non-invasive and later invasive stages. We use spatial transcriptome sequencing data in conjunction with in situ RNA profiling to conduct higher resolution analyses. The detailed examination of each case, as well as the subsequent computational analyses based on the observed diverse profiles, reveals that significant changes in the phenotypic appearances of tumor cells are frequently associated with changes in immune cell features. The phenomenon coincides with the induction of a series of cellular expression programs that enable tumor cells to transform and break through the immune cell barrier, allowing them to progress further. The study shows how lung tumors develop through interaction in their microenvironments.

Immunohistochemical Expression of COX2 in Urothelial Carcinoma of the urinary bladder

Background and objectives: Urothelial carcinoma of urinary bladder constitutes 90% of bladder cancer cases. Cyclo-oxygenase 2 as an immune-histochemical marker, is not expressed in normal tissues, while it is expressed in some cancers including urothelial carcinoma. The purpose of this study is detecting the frequency of expression of Cyclo-oxygenase 2 in urinary bladder’s urothelial carcinoma in association with certain clinicopathological variables. Methods: A retrospective study was done on seventy-nine cases (fixed with formalin and embedded in paraffin) of urothelial carcinoma which were chosen haphazardly from a private laboratory in Erbil city over two years (between October 2019 to October 2021). In the present study, Cyclo-oxygenase 2 expression was assessed on the urothelial carcinoma slides. Results: Cyclo-oxygenase 2 was positive in 45.6% of the cases. It was positive in 80% of non-papillary tumors, while it was less expressed (40.6%) in papillary tumors, which means that significant correlation was seen between Cyclo-oxygenase 2 positivity and tumor pattern (papillary vs non-papillary) (p = 0.037). In this study, no important association was found between Cyclo-oxygenase 2 expression and other clinicopathologic features like age (p=0.236), gender (p=517), tumor grade (p=0.106), lymphovascular invasion (p=0.696) and T stage (p=0.061). Conclusion: In this study Cyclo-oxygenase 2 was expressed in less than half of our urothelial tumor samples. A strong association was found between Cyclo-oxygenase 2 positivity and tumor pattern (papillary and non-papillary), but no important association was found between Cyclo-oxygenase 2 positivity and other variables such as age, gender, tumor grade, lymphovascular invasion and tumor stage.

Exploring the optimal threshold of 3D consolidation tumor ratio value segmentation based on artificial intelligence for predicting the invasive degree of T1 lung adenocarcinoma.

The assessment of lung adenocarcinoma significantly depends on the proportion of solid components in lung nodules. Traditional one-dimensional consolidation tumor ratio (1D CTR) based on ideal, uniformly dense solid components lacks precision. There is no consensus on the CT threshold for evaluating invasiveness using the threshold segmentation method. This study aimed to explore the effectiveness of the three-dimensional CTR (3D CTR) calculated by the artificial intelligence threshold segmentation method in predicting invasive stage T1 lung adenocarcinoma and to identify its optimal threshold and cut-off point. Data from 1,056 patients with 1,179 pulmonary nodules confirmed by postoperative pathology were collected retrospectively from two centers, Zhengzhou People's Hospital and Huadong Hospital of Fudan University. Patients were divided into non-invasive [atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA)] and invasive groups [invasive adenocarcinoma (IAC)]. Seven computed tomography (CT) threshold settings (-550 to 0 HU) were used to calculate the 3D CTR via the threshold segmentation method, and differences between the groups were analyzed. Receiver operating characteristic (ROC) curves were plotted to compare predictive performance for invasiveness of stage T1 lung adenocarcinoma, and the optimal threshold and corresponding cut-off value were determined. Subgroup analyses based on nodule size-T1a (≤10 mm), T1b (>10 to 20 mm), and T1c (>20 to 30 mm)-were also conducted. The CT threshold of -150 Housefield unit (HU) showed the highest predictive efficacy for invasiveness of stage T1 lung adenocarcinoma, with an area under the curve (AUC) of 0.901 [95% confidence interval (CI): 0.883-0.919], sensitivity of 86.878%, and specificity of 77.883%. The optimal cut-off point for 3D CTR was 2.75%. In subgroup analyses, -150 HU remained optimal, with predictive performance increasing with nodule size. For the T1a group, the AUC was 0.887 (95% CI: 0.885-0.919), cut-off value was 2.75%, sensitivity was 77.620%, and specificity was 85.714%. For the T1b group, values were 0.903 (95% CI: 0.875-0.931), cut-off value was 5.4%, sensitivity was 87.671%, and specificity was 80.296%. For the T1c group, values were 0.928 (95% CI: 0.893-0.963), cut-off value was 7.1%, sensitivity was 88.043%, and specificity was 81.176%. This study suggests that setting the CT threshold at -150 HU and using the AI-based threshold segmentation method to calculate the 3D CTR effectively distinguishes whether stage T1 lung adenocarcinoma is invasive, with an optimal cut-off point at 2.75%. Under this threshold, for varying nodule sizes, criteria are proposed: for nodules ≤10 mm with a 3D CTR <2.75%; >10 to 20 mm with a 3D CTR <5.4%; and >20 to 30 mm with a 3D CTR <7.1%, these partially solid nodules can be treated as non-IAC.

Potential anti-schistosomal effect of Daflon, a repurposed drug targeting different stages of Schistosome maturity.

Despite the long history of experimental trials to combat schistosomiasis, it remains a significant burden due to drug resistance and the effectiveness of the standard treatment only against the mature stage, while skipping other early developmental stages thus leading to severe permanent pathological sequelae. Therefore, repurposing a commonly used well-known safe drug would be a wise alternative. We investigated the potential anti-schistosomal drug activity of Daflon® (DAF) against different schistosomal developmental stages. DAF was administrated at a dose of 100 mg/kg/mouse on days zero, 21, and 42 post-infection towards the invasive, immature, and mature stages of Schistosoma mansoni respectively in comparison to the standard anti-schistosomal drug (Praziquantel). All mice were sacrificed on day 49 post-infection. DAF induced a significant reduction in the total and female worm count, hepatic granuloma size, and number, the extent of liver parenchymal injury and fibrosis as well as intestinal and hepatic egg count compared to the infected untreated control. Liver malondialdehyde (MDA) levels significantly decreased in all DAF-treated groups. Scanning electron microscope findings revealed edema, tegumental blebs, cracks, and fissures in male tegument in all DAF-treated groups with distortion of the ventral suckers and disarrangement of the spines of the oral sucker. The female worm from DAF-treated groups showed tegumental edema with loss of the spines at the posterior end. Compared to the documented reduction of testosterone levels and distortion of testicular architecture in the S. mansoni-infected untreated group, DAF significantly restored testosterone levels and testicular architecture.

Single-cell RNA sequencing reveals immune microenvironment niche transitions during the invasive and metastatic processes of ground-glass nodules and part-solid nodules in lung adenocarcinoma

BackgroundRadiographically, ground-glass nodules (GGN) and part-solid nodules (PSN) in lung adenocarcinoma (LUAD) have significant heterogeneity in their clinical manifestations, biological characteristics, and prognosis. This study aimed to explore the heterogeneity of LUAD in different radiological phenotypes and associated factors influencing tumor evolution.MethodsWe performed single-cell RNA sequencing (scRNA-seq) on tumor tissues from eight and seven cases of GGN– and PSN–LUAD, respectively, at different disease stages, including minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IAC), and metastatic lung cancer (MLC). Additionally, we analyzed adjacent normal tissues from four cases. Immunohistochemistry, multiplex immunofluorescence, and external scRNA-seq data were employed to confirm the expression of signature genes as well as the distribution patterns of CXCL9 + TAMs and TREM2 + TAMs. A LUAD mouse model was generated using gene editing, organoid culture, and orthotopic transplantation techniques, and comprehensive analyses such as histopathology, RNA sequencing, and Western blotting were performed to validate key pathways.ResultsDiverse cellular compositions were observed in the tumor microenvironment (TME) during GGN– and PSN–LUAD invasion and metastasis. Notably, CXCL9 + and TREM2 + tumor-associated macrophages (TAMs) exhibited the most significant enrichment changes. It was found that GGN–LUAD exhibited a stronger immune response than PSN–LUAD, with increased interaction between CXCL9 + TAMs and CD8 + tissue-resident memory T cells during invasion stage (MIA–IAC). Conversely, greater interactions between TREM2 + TAMs and tumor cells were observed in PSN–LUAD during the MLC stage. Additionally, TREM2 + TAMs were found to differentiate into TREM2 + /SPP1 + and TREM2 + /SPP1– TAMs at different stages, which promotes tumor progression. This study also emphasizes that during the transdifferentiation process of GGN– and PSN–LUAD, IFN-γ activates the STAT1 signaling pathway to regulate the activation of CXCL9 + TAMs, and further recruiting CD8 + Trm cells and activating T cells through MHC class I antigen presentation. The role of the IFN-γ/STAT1 pathway in the occurrence and development of LUAD was further validated by animal experiments.ConclusionsOur findings offer a potential therapeutic strategy to maintain a dynamic balance within the TME and improve the immunotherapy efficacy by modulating the relative proportions and functional states of CXCL9 + TAMs and TREM2 + TAMs.

A colorimetric sensor array combined with a hybrid feature selection approach for discrimination of citrus infested by Bactrocera dorsalis (Hendel)

Changes in citrus volatile organic compounds (VOCs) induced by Bactrocera dorsalis (Hendel) infestation can serve as characteristic identifiers for non-destructive detection of infested citrus. This study proposed an innovative method combining colorimetric sensor array (CSA) technology with machine learning algorithms for the discrimination of B. dorsalis infestation in citrus. Gas chromatography-mass spectrometry (GC-MS) analysis identified key VOCs, including d-limonene, linalool, and decanal, as infestation markers. Subsequently, various porphyrin and metalloporphyrin dyes exhibiting sensitivity to these VOCs were selected to construct the CSA. To enhance detection accuracy, a hybrid feature selection method integrating ReliefF and Particle Swarm Optimization (PSO) was implemented. Subsequently, the optimized features subsets were utilized to develop classification models. Specifically, a binary classification model employing the K Nearest Neighbor (KNN) algorithm achieved a high accuracy of 93.89 % in distinguishing between healthy and infected citrus. Furthermore, a multi-class classification model using KNN was developed to differentiate among invasive, incubation, and infestation stages, attaining a remarkable accuracy of 97.78 %. This approach presents a promising solution for early detection of B. dorsalis infestation in citrus.

An inner membrane complex protein IMC1g in Plasmodium berghei is involved in asexual stage schizogony and parasite transmission.

The malaria parasite's inner membrane complex is critical to maintain its structural integrity and motility. Here, we identified the function of the IMC1g protein, a member of the IMC1 family, in invasive and proliferative stages of P. berghei. We found that the IMCp domain of PbIMC1g is critical for proper IMC targeting, and PbIMC1g interacts with PbIMC1c. Conditional knockdown of PbIMC1g expression affects schizogony, gametogenesis, and ookinete conversion. PbIMC1g interacts with IMC1c to firmly anchor the glideosome to the subpellicular network. Additionally, we confirmed that IMC1g is functionally conserved in Plasmodium spp. These data reveal the function of IMC1g protein in anchoring the glideosome, providing further insight into the mechanism of the glideosome function.