a-surgical-procedure-for-thyroidectomy-para-tracheal-capsular

A Surgical Procedure for Thyroidectomy: Para-Tracheal Capsular Dissection and its Benefit in the Protection of the Parathyroid Gland

Para-tracheal capsular dissection, conducted adjacent to the trachea, is postulated to mitigate the risk of parathyroid gland injury. This study compares ...

Shanghai Jiao Tong University School of Medicine

Multidrug resistance to chemotherapeutic drugs is one of the major causes for the failure of cancer treatment. Therefore, there is an urgent need to develop anticancer agents that can combat multidrug-resistant cancers effectively and mitigate drug resistance. Here, we report a rational design of anticancer heterochiral β-peptide polymers as synthetic mimics of host defense peptides to combat multidrug-resistant cancers. The optimal polymer shows potent and broad-spectrum anticancer activities against multidrug-resistant cancer cells and is insusceptible to anticancer drug resistance owing to its membrane-damaging mechanism. The in vivo study indicates that the optimal polymer efficiently inhibits the growth and distant transfer of solid tumors and the metastasis and seeding of circulating tumor cells. Moreover, the polymer shows excellent biocompatibility during anticancer treatment on animals. In addition, the β-peptide polymers address those prominent shortcomings of anticancer peptides and have superior stability against proteolysis, easy synthesis in large scale, and low cost. Collectively, the structural diversity and superior anticancer performance of β-peptide polymers imply an effective strategy in designing and finding anticancer agents to combat multidrug-resistant cancers effectively while mitigating drug resistance.

Heterochiral β-Peptide Polymers Combating Multidrug-Resistant Cancers Effectively without Inducing Drug Resistance.

The high mortality rate of invasive fungal infections and quick emergence of drug-resistant fungal pathogens urgently call for potent antifungal agents. Inspired by the cell penetrating peptide (CPP) octaarginine (R8), we elongated to 28 residues poly(d,l-homoarginine) to obtain potent toxicity against both fungi and mammalian cells. Further incorporation of glutamic acid residues shields positive charge density and introduces partial zwitterions in the obtained optimal peptide polymer that displays potent antifungal activity against drug-resistant fungi superior to antifungal drugs, excellent stability upon heating and UV exposure, negligible  and  toxicity, and strong therapeutic effects in treating invasive fungal infections. Moreover, the peptide polymer is insusceptible to antifungal resistance owing to the unique CPP-related antifungal mechanism of fungal membrane penetration followed by disruption of organelles within fungal cells. All these merits imply the effectiveness of our strategy to develop promising antifungal agents.

An Effective Strategy to Develop Potent and Selective Antifungal Agents from Cell Penetrating Peptides in Tackling Drug-Resistant Invasive Fungal Infections.

Radiation resistance is the leading cause of radiotherapy failure in patients with cancer. Enhanced DNA damage repair is the main reason for cancer cells to develop resistance to radiation. Autophagy has been widely reported to be linked to increased genome stability and radiation resistance. Mitochondria are highly involved in the cell response to radiotherapy. However, the autophagy subtype mitophagy has not been studied in terms of genome stability. We have previously demonstrated that mitochondrial dysfunction is the cause of radiation resistance in tumour cells. In the present study, we found that SIRT3 was highly expressed in colorectal cancer cells with mitochondrial dysfunction, leading to PINK1/Parkin-mediated mitophagy. Excessive activation of mitophagy enhanced DNA damage repair, therefore promoting the resistance of tumour cells to radiation. Mechanistically, mitophagy resulted in decreased RING1b expression, which led to a reduction in the ubiquitination of histone H2A at K119, thereby enhancing the repair of DNA damage caused by radiation. Additionally, high expression of SIRT3 was related to a poor tumour regression grade in rectal cancer patients treated with neoadjuvant radiotherapy. These findings suggest that restoring mitochondrial function could be an effective method for increasing the radiosensitivity of patients with colorectal cancer.

Radiation resistance of cancer cells caused by mitochondrial dysfunction depends on SIRT3-mediated mitophagy.

Thyroid fine needle aspiration biopsy (FNAB) remains indeterminate in 16%-24% of the cases. Molecular testing could improve the diagnostic accuracy of FNAB. This study examined the gene mutation profile of patients with thyroid nodules and analyzed the diagnostic ability of molecular testing for thyroid nodules using a self-developed 18-gene test. Between January 2019 and August 2021, 513 samples (414 FNABs and 99 formalin-fixed paraffin-embedded (FFPE) specimens) underwent molecular testing at Ruijin Hospital. Sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. There were 457 mutations in 428 samples. The rates of BRAF, RAS, TERT promoter, RET/PTC, and NTRK3 fusion mutations were 73.3% (n=335), 9.6% (n=44), 2.8% (n=13), 4.8% (n=22), and 0.4% (n=2), respectively. The diagnostic ability of cytology and molecular testing were evaluated in Bethesda II and V-VI samples. For cytology alone, Sen, Spe, PPV, NPV, and accuracy were 100%, 25.0%, 97.4%, 100%, and 97.4%; these numbers were 87.5%, 50.0%, 98.0%, 12.5%, and 86.2% when considering positive mutation, and 87.5%, 75.0%, 99.0%, 17.6%, and 87.1% when considering positive cytology or and positive mutation. In Bethesda III-IV nodules, when relying solely on the presence of pathogenic mutations for diagnosis, Sen, Spe, PPV, NPV, and AC were 76.2%, 66.7%, 94.1%, 26.8%, and 75.0%, respectively. It might be necessary to analyze the molecular mechanisms of disease development at the genetic level to predict patients with malignant nodules more accurately in different risk strata and develop rational treatment strategies and definite management plans.

Molecular testing raises thyroid nodule fine needle aspiration diagnostic value.

Over the years, pancreatic cancer has experienced a global surge in incidence and mortality rates, largely attributed to the influence of obesity and diabetes mellitus on disease initiation and progression. In this study, we investigated the pathogenesis of pancreatic cancer in mice subjected to a high-fat diet (HFD) and observed an increase in citric acid expenditure. Notably, citrate treatment demonstrates significant efficacy in promoting tumor cell apoptosis, suppressing cell proliferation, and inhibiting tumor growth in vivo. Our investigations revealed that citrate achieved these effects by releasing secreted protein acidic and rich in cysteine (SPARC) proteins, repolarizing M2 macrophages into M1 macrophages, and facilitating tumor cell apoptosis. Overall, our research highlights the critical role of citric acid as a pivotal metabolite in the intricate relationship between obesity and pancreatic cancer. Furthermore, we uncovered the significant metabolic and immune checkpoint function of SPARC in pancreatic cancer, suggesting its potential as both a biomarker and therapeutic target in treating this patient population.

Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet.

Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study.

The integration of single-cell and bulk RNA-seq atlas reveals ERS-mediated acinar cell damage in acute pancreatitis.

Thyroid cancer is one of the most common endocrine tumors worldwide, especially among women and the metastatic mechanism of papillary thyroid carcinoma remains poorly understood.

Single-cell RNA-sequencing and spatial transcriptomic analysis reveal a distinct population of APOE cells yielding pathological lymph node metastasis in papillary thyroid cancer.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute hypoxic respiratory failure caused by diffuse lung inflammation and edema. ARDS can be precipitated by intrapulmonary factors or extrapulmonary factors, which can lead to severe hypoxemia. Patients suffering from ARDS have high mortality rates, including a 28-day mortality rate of 34.8% and an overall in-hospital mortality rate of 40.0%. The pathophysiology of ARDS is complex and involves the activation and dysregulation of multiple overlapping and interacting pathways of systemic inflammation and coagulation, including the respiratory system, circulatory system, and immune system. In general, the treatment of inflammatory injuries is a coordinated process that involves the downregulation of proinflammatory pathways and the upregulation of anti-inflammatory pathways. Given the complexity of the underlying disease, treatment needs to be tailored to the problem. Hence, we discuss the pathogenesis and treatment methods of affected organs, including 2019 coronavirus disease (COVID-19)-related pneumonia, drowning, trauma, blood transfusion, severe acute pancreatitis, and sepsis. This review is intended to provide a new perspective concerning ARDS and offer novel insight into future therapeutic interventions.

Acute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies.

The stiffness of the matrix is closely related to the progression of hepatocellular carcinoma (HCC). Although direct targeting of stromal rigidity in HCC remains a clinical challenge, cancer-associated fibroblasts (CAFs) are considered key contributors to this process. Given the heterogeneity of CAFs, this study explored the relationship between specific CAF subsets and liver cancer matrix stiffness, aiming to identify novel therapeutic targets for HCC patients.

Article	Year
Heterochiral β-Peptide Polymers Combating Multidrug-Resistant Cancers Effectively without Inducing Drug Resistance. Journal of the American Chemical Society\| PubMed ID: 35420800	2022
An Effective Strategy to Develop Potent and Selective Antifungal Agents from Cell Penetrating Peptides in Tackling Drug-Resistant Invasive Fungal Infections. Journal of medicinal chemistry\| PubMed ID: 35535860	2022
Radiation resistance of cancer cells caused by mitochondrial dysfunction depends on SIRT3-mediated mitophagy. The FEBS journal\| PubMed ID: 36871142	2023
Molecular testing raises thyroid nodule fine needle aspiration diagnostic value. Endocrine connections\| PubMed ID: 37310413	2023
Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet. The FEBS journal\| PubMed ID: 38245817	2024
The integration of single-cell and bulk RNA-seq atlas reveals ERS-mediated acinar cell damage in acute pancreatitis. Journal of translational medicine\| PubMed ID: 38605381	2024
Single-cell RNA-sequencing and spatial transcriptomic analysis reveal a distinct population of APOE cells yielding pathological lymph node metastasis in papillary thyroid cancer. Clinical and translational medicine\| PubMed ID: 39810624	2025
Acute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies. MedComm\| PubMed ID: 39866839	2025
CAFs activated by YAP1 upregulate cancer matrix stiffness to mediate hepatocellular carcinoma progression. Journal of translational medicine\| PubMed ID: 40241143	2025

Guohui Xiao

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