The morbidity and mortality of lung cancer are still the highest among all malignant tumors. Radiotherapy plays an important role in clinical treatment of lung cancer. However, the effect of radiotherapy is not ideal due to the radiation resistance of tumor tissues. Abnormalities in tumor vascular structure and function affect blood perfusion, and oxygen transport is impeded, making tumor microenvironment hypoxic. Tumor hypoxia is the major cause of radiotherapy resistance. By promoting tumor vessel normalization and enhancing vascular transport function, tumor hypoxia can be relieved to reduce radiotherapy resistance and increase tumor radiotherapy sensitivity. In our previous study, a pericytes-targeted tumor necrosis factor alpha (named Z-TNFα) was first constructed and produced by genetically fusing the platelet-derived growth factor receptor β (PDGFRβ)-antagonistic affibody (ZPDGFRβ) to the TNFα, and the Z-TNFα induced normalization of tumor vessels and improved the delivery of doxorubicin, enhancing tumor chemotherapy. In this study, the tumor vessel normalization effect of Z-TNFα in lung cancer was further clarified. Moreover, the tumor hypoxia improvement and radiosensitizing effect of Z-TNFα were emphatically explored in vivo. Inspiringly, Z-TNFα specifically accumulated in Lewis lung carcinoma (LLC) tumor graft and relieved tumor hypoxia as well as inhibited HIF-1α expression. As expected, Z-TNFα significantly increased the effect of radiotherapy in mice bearing LLC tumor graft. In conclusion, these results demonstrated that Z-TNFα is also a promising radiosensitizer for lung cancer radiotherapy.

Isocitrate dehydrogenase 1 mutant (IDH1mut) tumors respond poorly to immunotherapy, but are more sensitive to chemoradiotherapy and poly (ADP-ribose) polymerase inhibition (PARPi). Accordingly, some efforts have aimed to capitalize on the IDH1 mutation rather than reverse it. Moreover, radiotherapy (RT) and PARPi can stimulate antitumor immunity, raising the possibility of reversing the immunosuppression caused by IDH1 mutation while killing the tumor. To assess this possibility, we treated IDH1mut tumors and cells with RT + PARPi. RT + PARPi showed enhanced efficacy over either modality alone both in vitro and in vivo. RT + PARPi induced more DNA damage and activated the cGAS-STING pathway more. IFN beta, CXCL10, and CCL5 were also more highly expressed at both the mRNA and protein levels. In two different tumor models, RT + PARPi increased infiltration and cytolytic function of CD8+ T cells, with one model also showing increased CD8+T cell proliferation. RT+PARPi also increased PD-L1 expression and enhanced checkpoint inhibition. Knocking out cGAS reversed the increased CD8+ T cell infiltration and the antitumor effect of RT+PARPi. We conclude that RT + PARPi reshapes the IDH1mut tumor immunosuppressive microenvironment, thereby augmenting checkpoint inhibition.

Background CLEC4A (C-type lectin domain family 4 member A), a member of the C-type (Ca2+-dependent) lectin (CLEC) receptor, is an immunosuppressant of dendritic cells (DCs) and plays an important role in innate and adaptive immunity, however, its role in lung adenocarcinoma (LUAD) and the potential for immunotherapy remains to be investigated. Methods To achieve our objectives, we conducted a comprehensive analysis of CLEC4A expression and its correlation with clinical factors in LUAD. We utilized publicly available datasets, such as The Cancer Genome Atlas (TCGA) and other relevant resources, to gather gene expression and clinical data from LUAD patients. Furthermore, we investigated the association of CLEC4A expression levels with clinical pathological staging and prognosis of lung adenocarcinoma. The TIMER database was utilized to analyze immune cell infiltration, while the TISIDB database provided insights into lymphocyte infiltration and immune regulatory factors. Results Our analysis revealed a significant correlation between poor prognosis and low CLEC4A expression in LUAD patients. Reduced expression of CLEC4A was associated with adverse clinical factors, indicating its potential as a prognostic biomarker in LUAD. Moreover, we observed a noteworthy relationship between CLEC4A expression and immune cell infiltration. Increased CLEC4A expression was correlated with higher infiltration levels of CD8+ T cells, CD4+ T cells, dendritic cells (DC), and B cells within the tumor microenvironment. This indicates an immunoregulatory role for CLEC4A in modulating immune responses against LUAD. Additionally, our analysis highlighted a positive correlation between CLEC4A expression and the presence of lymphocytes, further emphasizing its potential importance in tumor immunity. Furthermore, the investigation of immune-related factors indicated a potential involvement of CLEC4A in immune regulation within the tumor microenvironment. Conclusion This study provides valuable insights into the expression, prognosis, and potential immunotherapeutic role of CLEC4A in lung adenocarcinoma (LUAD). The identified correlations between CLEC4A expression and clinical characteristics, immune cell infiltration, and lymphocyte infiltration highlight the significance of CLEC4A as a potential biomarker and therapeutic target for LUAD. Further research is warranted to elucidate the underlying mechanisms and capitalize on the therapeutic potential of targeting CLEC4A in LUAD. These efforts could contribute to improving patient outcomes and prognosis in LUAD.

BackgroundSince the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies.MethodsWe searched all the relevant studies in PubMed, Embase and Cochrane Library databases. We also reviewed abstracts of relevant conferences, to prevent omissions. The meta-analysis was performed using Stata version 16.0.ResultsChemoradiotherapy combined with immunotherapy can improve progression-free survival (PFS) (HR: 0.60, 95%CI :0.55-0.60) and overall survival (OS) (HR: 0.59, 95%CI :0.53-0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5%-52.7%) and 71.3% (95% CI, 67.3%-75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95%CI, 51.0%-70.3%) and 77.4% (95%CI, 73.2%-81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95%CI, 31.3%-39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95%CI, 31.9%-51.9%). The pooled rate of pneumonitis >= grade 3 was 6.7% (95%CI, 5.0%-8.5%). The incidence of pneumonitis >= grade 3 after 1 year of immunotherapy is 4.8% (95%CI, 3.1%-6.5%). The incidence of pneumonitis >= grade 3 after 2 years of immunotherapy is 5.1% (95%CI, 2.9%-7.3%).ConclusionsProlonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit.

Background: With the widespread application of immune checkpoint inhibitor (ICI) combined with radiotherapy (RT) for the treatment of lung cancer, increasing attention has been paid to treatment-related pneumonitis. The effect of the treatment sequence on the incidence of pneumonitis remains unclear. Methods: We searched databases including PubMed, Embase, and ClinicalTrials.gov, meeting abstracts, and reference lists of relevant review articles for literature published on radio- and immunotherapy in lung cancer. Stata software (version 16.0) was used for meta-analysis. Data on the incidence of any grade and >= grade 3 pneumonitis was pooled using the random effects model. Bayesian network meta-analysis was used for arm-based pairwise comparisons. Subgroup analyses were performed to identify the potential influencing factors. Results: Thirty-eight studies met our inclusion criteria. The network meta-analysis showed no significant difference between the incidence of pneumonitis in concurrent ICI with RT (concurrent arm) and RT followed by ICI (RT-first arm) (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.10-4.81). In the meta-analysis of single group rates, RT following ICI (ICI-first arm) exhibited higher incidence of any grade pneumonitis compared with concurrent- and RT-first arms, with 0.321 (95% CI: 0.260-0.386) for programmed cell death protein 1 (PD-1) inhibitors from clinical trials, and 0.480 (95% CI: 0.363-0.598) for PD-1 inhibitors from real-world retrospective data, respectively. Conclusion: No significant difference in the incidence of any grade and grade >= 3 pneumonitis was found between RT-first and concurrent arms. The ICI-first arm exhibited a higher incidence of pneumonitis, which needs to be further confirmed by follow-up studies.

Uterine arteriovenous malformation (UAM) is a rare medical condition. Even though UAM can cause abnormal and life-threatening uterine hemorrhage, there is no consensus on the clinical guideline on its treatments, most likely due to its low incidence, unknown etiology, and distinct fertility demands by different patients. Here, we present one elderly woman with uncommon UAM. We first discuss our experience regarding the diagnoses and treatments of UAM and then propose a hypothesis for the pathogenesis of UAM.

Immune dysregulation has long been proposed to be associated with adenomyosis, but the underlying mediators and mechanisms remain largely unexplored. Here, we used flow cytometry to investigate the alterations in immune cell subsets in adenomyotic uteri and analyze the phenotype and function of abnormal immune cells. We found that an increase in cluster of differentiation (CD)8+ T-cell number was the predominant alteration in ectopic lesions in patients with adenomyosis and was significantly associated with the severity of adenomyosis. Importantly, we identified an exhausted natural killer group protein 2A (NKG2A)+CD8+ T-cell subset that was associated with the severity of adenomyosis and found that the number of these cells was significantly increased in the eutopic endometrium and ectopic lesions. In addition, the increases in the expression of NKG2A ligand histocompatibility leucocyte antigen E and interleukin-15 in glandular epithelial cells in the adenomyotic microenvironment might contribute to CD8+ T-cell exhaustion by promoting NKG2A expression on CD8+ T cells or inhibiting the effector function of these cells. In conclusion, our data revealed a previously unrecognized role for NKG2A+CD8+ T-cell exhaustion in the pathogenesis of adenomyosis, indicating that therapeutic interventions designed to target and reinvigorate exhausted CD8+ T cells may be beneficial for patients with adenomyosis.

Human epidermal growth factor receptor 2 (Her2) is abundantly expressed in various solid tumors. The Her2-specific Affibody (Z(Her2:2891)) has been clinically tested in patients with Her2-positive breast cancer and is regarded as an ideal drug carrier for tumor diagnosis and targeted treatment. Indocyanine green (ICG) can be used as a photosensitizer for photothermal therapy (PTT), in addition to fluorescent dyes for tumor imaging. In this study, a dimeric Her2-specific Affibody (Z(Her2)) based on Z(Her2:2891) was prepared using the E. coli expression system and then coupled to ICG through an N-hydroxysuccinimide (NHS) ester reactive group to construct a novel bifunctional protein drug (named ICG-Z(Her2)) for tumor diagnosis and PTT. In vitro, ICG-Z(Her2)-mediated PTT selectively and efficiently killed Her2-positive BT-474 and SKOV-3 tumor cells rather than Her2-negative HeLa tumor cells. In vivo, ICG-Z(Her2) specifically accumulated in Her2-positive SKOV-3 tumor grafts rather than Her2-negative HeLa tumor grafts; high-contrast tumor optical images were obtained. However, Her2-negative HeLa tumor grafts were not detected. More importantly, ICG-Z(Her2)-mediated PTT exhibited a significantly enhanced antitumor effect in mice bearing SKOV-3 tumor grafts owing to the good photothermal properties of ICG-Z(Her2). Of note, ICG-Z(Her2) did not exhibit acute toxicity in mice during short-term treatment. Overall, our findings indicate that ICG-Z(Her2) is a promising bifunctional drug for Her2-positive tumor diagnosis and PTT.

Background BANF1 is well known as a natural opponent of cyclic GMP-AMP synthase (cGAS) activity on genomic self-DNA. However, the roles of BANF1 in tumor immunity remain unclear. Here, we investigate the possible impact of BANF1 on antitumor immunity and response to immunotherapy.Methods The Cancer Genome Atlas public data were analyzed to evaluate the relevance of the expression of BANF1, patients' survival and immune cell infiltration. We monitored tumor growth and explored the antitumor efficacy of targeting tumor-intrinsic BANF1 in combination with anti-programmed cell death protein-1 (PD-1) in MC38 or B16F10 tumor models in both immunocompetent and immunodeficient mice. Flow cytometry, immunofluorescence and T cells depletion experiments were used to validate the role of BANF1 in tumor immune microenvironment reprogramming. RNA sequencing was then used to interrogate the mechanisms how BANF1 regulated antitumor immunity.Results We show that upregulated expression of BANF1 in tumor tissues is significantly associated with poor survival and is negatively correlated with immune cell infiltration. Deficiency of BANF1 in tumor cells markedly antagonizes tumor growth in immunocompetent but not immunocompromised mice, and enhances the response to immunotherapy in murine models of melanoma and colon cancer. In the immunotherapy clinical cohort, patients with high BANF1 expression had a worse prognosis. Mechanistically, BANF1 knockout activates antitumor immune responses mediated by cGAS-synthase-stimulator of interferon genes (cGAS-STING) pathway, resulting in an immune-activating tumor microenvironment including increased CD8(+) T cell infiltration and decreased myeloid-derived suppressor cell enrichment.Conclusions BANF1 is a key regulator of antitumor immunity mediated by cGAS-STING pathway. Therefore, our study provides a rational that targeting BANF1 is a potent strategy for enhancing immunotherapy for cancer with BANF1 upregulation.

PURPOSE:Hematologic toxicities (HTs) are among the most common toxicities of combined immunotherapy and radiation therapy (RT). It remains essential to prevent RT-induced HTs because they can cause treatment discontinuation (influencing antitumoral effects) and because lymphopenia might dampen the effects of immunotherapy. To date, there are no studies examining the effect of thoracic vertebral body (TVB) RT dose on HTs in patients with non-small cell lung cancer receiving combined lung RT and programmed cell death (ligand) 1 immunotherapy. METHODS AND MATERIALS:For standardization, all doses were reported as 2-Gy equivalents (EQD2). Mirroring publications before the immunotherapy era, TVB volumes referred to T1-T10, and specific dosimetric parameters (DmeanEQD2, V5EQD2-V60EQD2) were analyzed. Logistic regression estimated associations between grade ≥3 HTs (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability (NTCP) models were constructed by logistic regression analysis modeling for HT3+. Receiver operating characteristic (ROC) analysis delineated TVB dosimetric thresholds, the stratification of which was able to evaluate post-RT absolute lymphocyte count and immunotherapy responses. Areas under the curve (AUCs) for NTCP models were corroborated by bootstrapping (optimism-corrected) methodology. RESULTS:In 132 patients, there were 26 (19.7%) instances of HT3+. On multivariate analysis, DmeanEQD2 and V5EQD2 to V20EQD2 were associated with HT3+ (P < .05 for all). The NTCP models illustrated a 50% probability of HT3+ at a DmeanEQD2 = 39.8 Gy, V5EQD2 = 87.4%, V10EQD2 = 77.0%, and V20EQD2 = 68.4%. ROC analysis delineated optimal thresholds of HT3+ with DmeanEQD2 ± 30.2 Gy, V5EQD2 ± 69.1%, V10EQD2 ± 64.6%, and V20EQD2 ± 53.5%. Patients treated with values above those cutoffs had over double the risk of HT3+, with significant differences in post-RT absolute lymphocyte count and immunotherapy responses (P < .05 for all). AUCs for each individual parameter ranged from 0.743 to 0.798, and combining all 4 aforementioned cutoffs into a ROC curve resulted in a qualitatively higher AUC (0.836). CONCLUSIONS:This hypothesis-generating work suggests that TVB dosimetry may equate with HT3+ in patients with non-small cell lung cancer undergoing combined lung RT/immunotherapy. Applying TVB dose constraints in this population could reduce HT3+ and avoid dampening of immunotherapy responses, but prospective validation is required.

Selenium, a non-metallic element, is a micronutrient essential for the biosynthesis of selenoproteins containing selenocysteine. In adults, the thyroid contains the highest amount of selenium per gram of tissue. Most known selenoproteins, such as glutathione peroxidase, are expressed in the thyroid and are involved in thyroid hormone metabolism, redox state regulation, and maintenance of cellular homeostasis. Some clinical studies have shown that lack of selenium will increase the prevalence of several kinds of thyroid diseases. Selenium treatment in patients with Graves’ orbitopathy has been shown to delay disease progression and improve the quality of life. Selenium supplementation in Hashimoto’s thyroiditis was associated with the decreased levels of anti-thyroid peroxidase antibody and improved thyroid ultrasound structure. In thyroid cancer, various selenium supplements have shown variable anticancer activity. However, published results remain the conflicting and more clinical evidence is still needed to determine the clinical significance of selenium. This article reviews the strong association between selenium and thyroid disease and provides new ideas for the clinical management of selenium in thyroid disease.

OBJECTIVE:To introduce a case of removing heterotopic cervical pregnancy while preserving the normal gestational sac in the uterine cavity by hysteroscopic surgery under ultrasound guidance. DESIGN:Video description of the case and surgical procedure. SETTING:Hospital affiliated to a university. PATIENT:A 35-year-old woman with G7P1A5L1 was admitted with a heterotopic cervical pregnancy 21 days after in vitro fertilization and embryo transfer (the corrected gestational age was 5+2 weeks). The serum β-human chorionic gonadotropin level was 24,530 mIU/mL at the corrected gestational age of 5+3 weeks. Ultrasound examination on the day of admission showed that there was a gestational sac in the cervical canal (1.5 × 0.8 × 0.5 cm, yolk sac visible) and another in the intrauterine cavity (1.2 × 1.2 × 1.1 cm, yolk sac visible). The pregnant woman and her partner strongly urged to remove the cervical gestational sac and continue the intrauterine pregnancy to term. INTERVENTION:After the Institutional Review Board approval was obtained, hysteroscopic surgery with bipolar resectoscope and transabdominal ultrasound guidance was used to resect the heterotopic cervical pregnancy while preserving the intrauterine gestational sac. MAIN OUTCOME MEASURES:The heterotopic cervical pregnancy was completely resected by hysteroscopy, and the normal gestational sac in the uterine cavity was successfully preserved. RESULTS:Ultrasound-guided hysteroscopic surgery allowed us to successfully preserve the intrauterine pregnancy while removing the cervical pregnancy completely. During the operation, the dilation pressure and the flow rate of the dilation fluid was kept as low as possible to avoid excessive intrauterine pressure and excessive dilation fluid entering the intrauterine cavity, which could have had adverse effects on the intrauterine pregnancy sac. No surgical- or anesthesia-related complications occurred. The pathological results confirmed placental villi and decidual tissue. The one-month follow-up ultrasonography showed a live single intrauterine pregnancy with cardiac activity. CONCLUSION(S):Hysteroscopic removal of a heterotopic cervical pregnancy under ultrasound guidance can be safely performed while successfully preserving an ongoing intrauterine pregnancy.

At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). He-matopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy.

Accumulation of senescent cells in the elderly impairs bone homeostasis. It is important to alleviate cell senescence and scavenge excessive oxidative stress for enhanced bone fracture healing in elderly patients. In this study, resveratrol (RSV), an antioxidant drug, was encapsulated in a biocompatible zeolitic imidazolate framework-8 (ZIF-8) nanoparticle to protect it from oxidation and improve its bioavailability. Cells responsible for bone healing, including osteoblasts, bone marrow-derived mesenchymal stem cells (BMSCs), macrophages, and endothelial cells, were used to evaluate the regulatory role of the nanoformulation in the alleviation of cellular senescence and promotion of cell functions. It was proved that the nanoformulation sustainably released RSV with well-preserved bioactivity and improved bioavailability. Cell experiments confirmed that ZIF-8/RSV was capable of alleviating the senescence of cells [human osteoblasts (HOBs), BMSCs, H2O2-induced senescent vascular endothelial cells (HUVECs)] and scavenging excessive intracellular reactive oxygen species (ROS). Excitingly, the ZIF-8/RSV improved the osteogenic ability of senescent osteoblasts and promoted macrophage M2 polarization. In addition, the ZIF-8/RSV also enhanced the angiogenic function of senescent HUVECs. More importantly, the ZIF-8/RSV nanoformulation outperformed the REV alone, indicating the critical role of encapsulation using ZIF-8. These findings suggest that the ZIF-8/RSV nanoformulation exhibits potential for bone fracture treatment in elderly patients.

Background Although preoperative radiotherapy (PORT) is a promising therapeutic option for stage III non-small cell lung cancer (NSCLC), the efficacy of this treatment remains controversial. The positive lymph node ratio (PLNR) is recognized as an independent prognostic factor for survival. However, no previous studies have focused on the association between PLNR and PORT in stage III NSCLC. Methods Data were collected from the Surveillance, Epidemiology and End Results (SEER) database, and all patients enrolled in this analysis were diagnosed during 2010–2015. The primary endpoint was overall survival (OS). Univariate and multivariate Cox regression analysis was used to identify factors associated with survival before and after case-control matching. PLNR was defined as the ratio of the number of positive lymph nodes to the total number of retrieved or examined lymph nodes. A cutoff value for PLNR was calculated using an X-tile model. Results Overall, 391 patients with PORT and 2814 patients without PORT were enrolled in this study. The cohort after 1:1 case-control matching included 322 patients who received PORT and 322 patients without PORT. PORT was not associated with a significant effect on OS (HR = 1.14; 95% CI: 0.91–1.43; P = 0.825). Multivariate Cox regression analysis showed that PLNR ( P < 0.001) was independently associated with OS in patients with stage III NSCLC. An X-tile model was used to identify a cutoff value for PLNR: the risk of death was significantly lower in patients with PLNR ≤0.41 who received PORT than in those with PLNR >0.41 who received PORT (HR = 0.59; 95% CI: 0.38–0.91; P = 0.015). Conclusion PLNR may be a prognostic factor for survival in patients with stage III NSCLC who undergo PORT. Lower PLNR is a predictor of better OS and thus warrants further study.

AimsResistance to thyroid hormone (RTH) and pituitary tumors are both rare diseases, and the differential diagnosis of these two diseases is difficult in some cases. There are also patients who have both conditions, making diagnosis more difficult. To better understand this aspect, we analyzed the clinical characteristics and gene mutations of RTH coexisting with pituitary tumors.MethodsDatabase retrieval was conducted in the PubMed, Cochrane Library, and SinoMed databases, and the search contents were case reports or case series of patients with RTH coexisting with pituitary tumors. The demographic, clinical manifestations, and imaging characteristics of pituitary tumors and gene mutations were summarized.ResultsThirteen articles involving 16 patients with RTH coexistent with pituitary tumors, consisting of 13 female patients, one male patient, and two patients with unknown sex, were included. The patients were 10 to 79 years old and most patients were 41-55 years old (43.75%). The 16 patients were from seven different countries and three continents (Asia, the Americas, and Europe). All the patients showed an abnormal secretion of TSH, and five patients underwent transsphenoidal surgery. Finally, four patients were pathologically confirmed to have TSHoma. A total of 11 different mutations occurred at nine amino acid sequence sites (251, 310, 344, 347, 383, 429, 435, 438, and 453). Two different mutations occurred in both the no. 435 and no. 453 amino acid sequences. Fourteen patients provided their treatment histories, and all had undergone different treatment regimens.ConclusionsPatients with both RTH and pituitary tumors had multiple clinical manifestations and different thyroid functions, imaging characteristics of pituitary tumors, genetic mutations of THRβ, and treatments. However, due to the limited number of cases, the patients were mainly women. Further studies with more cases that focus on the mechanism are still needed.

Abstract Background: Ovarian cancer (OV) is a highly aggressive and often fatal disease that frequently goes undetected until it has already metastasized. The classic treatment for ovarian cancer involves surgery followed by chemotherapy. However, despite the effectiveness of surgery, relapse is still a common occurrence. Unfortunately, there is currently no ideal predictive model for the progression and drug sensitivity of postoperative ovarian cancer patients. Cell death patterns play an important role in tumor progression and have the potential to be used as indicators of postoperative OV prognosis and drug sensitivity. Materials and methods: A total of 12 PCD patterns were employed to construct novel classification and prognosis model. Bulk transcriptome, single-cell transcriptome, genomics, and clinical information were collected from TCGA-OV, GSE9891, GSE26712, GSE49997 and GSE63885. In addition, single-cell transcriptome data GSE210347 was procured from the Gene Expression Omnibus (GEO) database for subsequent analysis. Results: In this study, a novel PCD classification has been employed to phenotype postoperative ovarian cancer patients, revealing that patients in cluster 1 exhibit heightened sensitivity to immune-based therapies. Meanwhile, a programmed cell death index (PCDI) was established using an 8-gene signature with the help of a machine learning algorithm. The PCDI was validated in four independent datasets, and it was found that patients with high-PCDI had a worse prognosis after surgery in OV. The investigation also revealed that PCDI is associated with chemokines, interleukins, interferons, and checkpoint genes, as well as important components of the immune microenvironment, as determined through a comprehensive analysis of bulk and single-cell transcriptomes. In addition, we also found that patients with low-PCDI values may exhibit sensitivity to immunotherapy, while those with high PCDI values may display increased responsiveness to tyrosine kinase inhibitors. Conclusion: This study provides new insights into the significance of programmed cell death (PCD) patterns in ovarian cancer patients following surgery. Through a comprehensive analysis of different cell death patterns, we have developed a novel PCD model and nomogram that can effectively predict the clinical prognosis and drug sensitivity of OV patients post-surgery.

Metabolic Reprogramming is a sign of tumor, and as one of the three major substances metabolism, lipid has an obvious impact. Abnormal lipid metabolism is related to the occurrence of various diseases, and the proportion of people with abnormal lipid metabolism is increasing year by year. Lipid metabolism is involved in the occurrence, development, invasion, and metastasis of tumors by regulating various oncogenic signal pathways. The differences in lipid metabolism among different tumors are related to various factors such as tumor origin, regulation of lipid metabolism pathways, and diet. This article reviews the synthesis and regulatory pathways of lipids, as well as the research progress on cholesterol, triglycerides, sphingolipids, lipid related lipid rafts, adipocytes, lipid droplets, and lipid-lowering drugs in relation to tumors and their drug resistance. It also points out the limitations of current research and potential tumor treatment targets and drugs in the lipid metabolism pathway. Research and intervention on lipid metabolism abnormalities may provide new ideas for the treatment and survival prognosis of tumors.

AbstractBackground Ovarian cancer (OV) is a highly aggressive and often fatal disease that frequently goes undetected until it has already metastasized. The classic treatment for ovarian cancer involves surgery followed by chemotherapy. However, despite the effectiveness of surgery, relapse is still a common occurrence. Unfortunately, there is currently no ideal predictive model for the progression and drug sensitivity of postoperative ovarian cancer patients. Cell death patterns play an important role in tumor progression and have the potential to be used as indicators of postoperative OV prognosis and drug sensitivity. Materials and methods A total of 12 PCD patterns were employed to construct the model. Bulk transcriptome, single-cell transcriptome, genomics, and clinical information were collected from TCGA-OV, GSE9891, GSE26712, GSE49997 and GSE63885. In addition, single-cell transcriptome data GSE210347 was procured from the Gene Expression Omnibus (GEO) database for subsequent analysis. Results In this study, a programmed cell death index (PCDI) was established using an 8-gene signature with the help of a machine learning algorithm. The PCDI was validated in four independent datasets, and it was found that patients with high-PCDI had a worse prognosis after surgery in OV. The investigation also revealed that PCDI is associated with chemokines, interleukins, interferons, and checkpoint genes, as well as important components of the immune microenvironment, as determined through a comprehensive analysis of bulk and single-cell transcriptomes. In addition, we also found that patients with low-PCDI values may exhibit sensitivity to immunotherapy, while those with high PCDI values may display increased responsiveness to tyrosine kinase inhibitors. Conclusion This study provides new insights into the significance of programmed cell death (PCD) patterns in ovarian cancer patients following surgery. Through a comprehensive analysis of different cell death patterns, we have developed a novel PCD model that can effectively predict the clinical prognosis and drug sensitivity of OV patients post-surgery.