Characteristics of Familial Lung Cancer in Yunnan-Guizhou Plateau of China

Background: Lung cancer has inherited susceptibility and show familial aggregation, the characteristics of familial lung cancer exhibit population heterogeneity. Despite previous studies, familial lung cancer in China's Yunnan-Guizhou plateau remains understudied.Methods: Between 2015 and 2017, 1,023 lung cancer patients (residents of Yunnan-Guizhou plateau) were enrolled with no limitation on other parameters, 152 subjects had familial lung cancer. Clinicopathologic parameters were analyzed and compared, 4,754 lung cancer patients from NCI-GDC were used to represent a general population.Results: Familial lung cancer (FLC) subjects showed unique characters: early-onset; increased rate of female, adenocarcinoma, stage IV and other cancer history; unbalance in anatomic sites; all ruling out significant difference in smoking status. Unbalanced distribution of co-existing diseases or symptoms was also discovered. FLC patients were more likely to develop benign lesions (polyps, nodules, cysts) early in life, especially early-growth of multiple pulmonary nodules at higher frequency. Typical diseases with family history like diabetes and hypertension were also increased in FLC population. Compared to GDC data, our subject population was younger: the age peak of our FLC group was in 50–59; our sporadic group had an age peak around 60; while GDC patients' age peak was in 60–69. Importantly, the biggest difference happened in age 40–49: our FLC group and sporadic group had 3 times and 2 times higher ratio than GDC population, respectively. Moreover, the age peaks of our FLC males and FLC females were both in 50–59; while our sporadic females had the age peak in 50–59, much earlier than sporadic males (around 60–69); reflecting gender-specific or age-specific characters in our subject population.Conclusions: Familial lung cancer in China's Yunnan-Guizhou plateau showed unique clinicopathologic characters, differences were found in gender, age, histologic type, TNM stage and co-existing diseases or symptoms. Identification of hereditary factors which lead to increased lung cancer risk will be a challenge of both scientific and clinical significance

Adaptive Vague Preference Policy Learning for Multi-round Conversational Recommendation

Conversational recommendation systems (CRS) effectively address information asymmetry by dynamically eliciting user preferences through multi-turn interactions. Existing CRS widely assumes that users have clear preferences. Under this assumption, the agent will completely trust the user feedback and treat the accepted or rejected signals as strong indicators to filter items and reduce the candidate space, which may lead to the problem of over-filtering. However, in reality, users' preferences are often vague and volatile, with uncertainty about their desires and changing decisions during interactions. To address this issue, we introduce a novel scenario called Vague Preference Multi-round Conversational Recommendation (VPMCR), which considers users' vague and volatile preferences in CRS.VPMCR employs a soft estimation mechanism to assign a non-zero confidence score for all candidate items to be displayed, naturally avoiding the over-filtering problem. In the VPMCR setting, we introduce an solution called Adaptive Vague Preference Policy Learning (AVPPL), which consists of two main components: Uncertainty-aware Soft Estimation (USE) and Uncertainty-aware Policy Learning (UPL). USE estimates the uncertainty of users' vague feedback and captures their dynamic preferences using a choice-based preferences extraction module and a time-aware decaying strategy. UPL leverages the preference distribution estimated by USE to guide the conversation and adapt to changes in users' preferences to make recommendations or ask for attributes. Our extensive experiments demonstrate the effectiveness of our method in the VPMCR scenario, highlighting its potential for practical applications and improving the overall performance and applicability of CRS in real-world settings, particularly for users with vague or dynamic preferences

Adverse Events Associated With Anti-IL-23 Agents: Clinical Evidence and Possible Mechanisms

BackgroundAnti-interleukin (IL)-23 agents are widely used for autoimmune disease treatment; however, the safety and risks of specific symptoms have not been systematically assessed.ObjectivesThe aim of this study was to summarize the characteristics and mechanisms of occurrence of five immunological and non-immunological adverse events caused by different anti-IL-23 agents.MethodsThe Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched for eligible randomized clinical trials published from inception through May 1, 2020. Randomized clinical trials that reported at least one type of adverse event after treatment were included, regardless of sex, age, ethnicity, and diagnosis. Two investigators independently screened and extracted the characteristics of the studies, participants, drugs, and adverse event types. The Cochrane Handbook was used to assess the methodological quality of the included randomized clinical trials. Heterogeneity was assessed using the I2 statistic. Meta-regression was applied to determine the sources of heterogeneity, and subgroup analysis was used to identify the factors contributing to adverse events.ResultsForty-eight studies were included in the meta-analysis, comprising 25,624 patients treated with anti-IL-23 agents. Serious immunological or non-immunological adverse events were rare. Anti-IL-12/23-p40 agents appeared to cause adverse events more easily than anti-IL-23-p19 agents. The incidence of cancer did not appear to be related to anti-IL-23 agent treatment, and long-term medication could lead to mental diseases. The prevention of complications should be carefully monitored when administered for over approximately 40 weeks to avoid further adverse reactions, and the incidence of infection was the highest among general immunological adverse events.ConclusionsThe application of anti-IL-23 agents induced a series of immunological and non-immunological adverse events, but these agents tend to be well-tolerated with good safety profiles

Tetramethylpyrazine ameliorates acute lung injury by regulating the Rac1/LIMK1 signaling pathway

Acute lung injury (ALI) is a respiratory disorder characterized by severe inflammation of the alveoli and lung parenchyma. Tetramethylpyrazine (TMP), the main active compound in Ligusticum chuanxiong Hort (LC), can protect against lipopolysaccharide (LPS)-induced ALI. Our study aimed to investigate how TMP protects the endothelial cell barrier in pulmonary capillaries. We administered TMP intraperitoneally at different doses and found that acute lung injury in mice was improved, but not in a dose-dependent manner. TMP toxicity was tested in vitro. We observed that LPS-induced cytoskeletal remodeling was inhibited by TMP. Murine ALI was induced as follows: For the 1st hit, LPS (2 mg/kg) was injected intraperitoneally; after 16 h, for the 2nd hit, LPS (4 mg/kg) was instilled intratracheally. The mice in treatment groups had TMP or dexamethasone administered intraperitoneally 30 min prior to the 1st hit and 30 min past the 2nd hit. Mice were euthanized 24 h after the last injecting. We measured protein and mRNA levels using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase real-time PCR (RT-qPCR), respectively. The ultrastructural analysis was performed with transmission electron microscopy (TEM) and the cytoskeleton was observed by immunofluorescence. Immunohistochemistry and Western blotting were used to detect protein expression in the Rac1/LIMK1/ZO-1/occludin signal pathway. The results showed that TMP treatment decreased inflammatory cell infiltration and alleviated LPS-induced damage in lung tissue. Also, TMP significantly inhibited the Rac1/LIMK1/ZO-1/occludin signaling pathway. Our findings show that using TMP during sepsis can protect the pulmonary microvascular endothelial cell barrier and suppress inflammation. Therefore, TMP may have a promising therapeutic role in preventing acute lung injury from sepsis