mthl1, a potential Drosophila homologue of mammalian adhesion GPCRs, is involved in antitumor reactions to injected oncogenic cells in flies.

Injection of OCs into adult male flies induces a strong transcriptomic response in the host flies featuring in particular genes encoding bona fide G coupled proteins, among which the gene for methuselah like 1 is prominent. The injection is followed after a 3-d lag period, by the proliferation of the oncogenic cells. We hypothesized that through the product of mthl1 the host might control, at least in part, this proliferation as a defense reaction. Through a combination of genetic manipulations of the mthl1 gene (loss of function and overexpression of mthl1), we document that indeed this gene has an antiproliferative effect. Parallel injections of primary embryonic Drosophila cells or of various microbes do not exhibit this effect. We further show that mthl1 controls the expression of a large number of genes coding for chemoreceptors and genes implicated in regulation of development. Of great potential interest is our observation that the expression of the mouse gene coding for the adhesion G-protein-coupled receptor E1 (Adgre1, also known as F4/80), a potential mammalian homologue of mthl1, is significantly induced by B16-F10 melanoma cell inoculation 3 d postinjection in both the bone marrow and spleen (nests of immature and mature myeloid-derived immune cells), respectively. This observation is compatible with a role of this GPCR in the early response to injected tumor cells in mice.

Next-generation sequencing identified that RET variation associates with lymph node metastasis and the immune microenvironment in thyroid papillary carcinoma.

BACKGROUND: To date, although most thyroid carcinoma (THCA) achieves an excellent prognosis, some patients experience a rapid progression episode, even with differentiated THCA. Nodal metastasis is an unfavorable predictor. Exploring the underlying mechanism may bring a deep insight into THCA. METHODS: A total of 108 THCA from Chinese patients with next-generation sequencing (NGS) were recruited. It was used to explore the gene alteration spectrum of THCA and identify gene alterations related to nodal metastasis in papillary thyroid carcinoma (PTC). The Cancer Genome Atlas THCA cohort was further studied to elucidate the relationship between specific gene alterations and tumor microenvironment. A pathway enrichment analysis was used to explore the underlying mechanism. RESULTS: Gene alteration was frequent in THCA. BRAF, RET, POLE, ATM, and BRCA1 were the five most common altered genes. RET variation was positively related to nodal metastasis in PTC. RET variation is associated with immune cell infiltration levels, including CD8 naïve, CD4 T and CD8 T cells, etc. Moreover, Step 3 and Step 4 of the cancer immunity cycle (CIC) were activated, whereas Step 6 was suppressed in PTC with RET variation. A pathway enrichment analysis showed that RET variation was associated with several immune-related pathways. CONCLUSION: RET variation is positively related to nodal metastasis in Chinese PTC, and anti-tumor immune response may play a role in nodal metastasis triggered by RET variation.

The prevalence of imposter syndrome and associated factors in Chinese medical students and residents: A single-center pilot study.

PURPOSE: Here we aimed to define the prevalence of imposter syndrome (IS) and identify associated characteristics in Chinese medical students and residents enrolled at Peking Union Medical College Hospital (PUMCH). METHODS: This was a single-center, cross-sectional study of medical students and residents enrolled at PUMCH conducted in September and October 2022. Participants were recruited to complete a 37-question survey on demographics, a Chinese version of the Clance Imposter Phenomenon Scale (CIPS), and self-assessments of anxiety, depression, burnout, sleep quality, challenges of clinical learning, and time allocation. IS prevalence and its associated factors were analyzed. RESULTS: One hundred and forty-eight medical students and 89 residents completed the survey. IS was significant or severe in 62.8% of medical students and 57.2% of residents. Students enrolled in the eight-year program had significantly higher CIPS scores than those enrolled in the 4 + 4 program (66.4 vs. 60.7, p = .005). There were no gender differences in IS prevalence and severity. Participants with severe IS had significantly higher self-rated anxiety, depression, insomnia, and burnout than participants with mild/moderate IS. Participants significantly challenged by clinical learning had significantly higher CIPS scores. CONCLUSIONS: IS is both prevalent and severe in Chinese medical students and residents. Classroom learning, an eight-year program, and being challenged by clinical learning are potentially associated with IS.

The prognostic value of lymphatic metastatic size in head and neck squamous cell carcinoma.

BACKGROUND: Lymphatic metastatic size was proved to predict prognosis in different types of carcinomas, except in head and neck squamous cell carcinoma (HNSCC) located in hypopharynx, oropharynx and supraglottic region et al. The aim of this study is to evaluate the prognostic value of lymphatic metastatic size in HNSCC, which may guide clinical decision-making in practice. METHODS: From 2008 to 2022, 171 patients, who were diagnosed as HNSCC in our center, were included. The demographic data, clinicopathological characteristics and lymphatic metastatic size were recorded and analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTS: Among 171 patients, 107 cases were hypopharyngeal cancer, 38 cases supraglottic cancer and 26 cases oropharyngeal cancer. The median of lymphatic metastatic size was 8 mm (range 0-46). According to lymphatic metastatic size, the patients were assigned to three subgroups: Group I (0 mm), Group II ( ≤ 10 mm) and Group III (> 10 mm). Kaplan-Meier analysis with log rank test revealed that Group I and Group II had similar locoregional control rate, distant metastasis free probability, disease-free survival and overall survival (all p > 0.05), whereas Group III had significant worse prognosis. Adjusted for demographic and other clinicopathological characteristics, lymphatic metastatic size was an independent predictor of disease-free survival and overall survival in HNSCC. CONCLUSIONS: Lymphatic metastatic size was an independently prognostic factor in HNSCC, which may assist in postoperative adjuvant treatment decisions.

A risk stratification system developed to predict contralateral incidental malignant foci in early papillary thyroid carcinoma preoperatively.

BACKGROUND: In clinical practice, contralateral incidental malignant foci (CIMFs) can be found in some early (cT1N0M0) papillary thyroid carcinomas (PTCs) on postoperative pathological examination. To screen out the patients with high risk of CIMF preoperatively would help in determining the extent of thyroid surgery. METHODS: From October 2016 to February 2021, 332 patients diagnosed with early (cT1N0M0) PTC who underwent total thyroidectomy were included and randomly allocated into a training dataset (n = 233) and a test dataset (n = 99). Demographic and clinicopathological features were recorded and analyzed using logistic regression analysis. A coefficient-based nomogram was developed and validated. RESULTS: Logistic regression analyses revealed that the predictive model including BRAF V600E mutation, multifocality and margin of the contralateral nodule achieved the best diagnostic performance. The nomogram showed good discrimination, with AUCs of 0.795 (95 % CI, 0.736-0.853) for the training set and 0.726 (95 % CI, 0.609-0.843) for the test set. The calibration curve of the nomogram presented good agreement. CONCLUSION: The risk stratification system can be used to quantify the probability of CIMF and may assist in helping the patients choose total thyroidectomy or thyroid lobectomy with early (cT1N0M0) PTC.

Design and Fabrication of a Film Bulk Acoustic Wave Filter for 3.0 GHz-3.2 GHz S-Band.

Film bulk acoustic-wave resonators (FBARs) are widely utilized in the field of radio frequency (RF) filters due to their excellent performance, such as high operation frequency and high quality. In this paper, we present the design, fabrication, and characterization of an FBAR filter for the 3.0 GHz-3.2 GHz S-band. Using a scandium-doped aluminum nitride (Sc0.2Al0.8N) film, the filter is designed through a combined acoustic-electromagnetic simulation method, and the FBAR and filter are fabricated using an eight-step lithographic process. The measured FBAR presents an effective electromechanical coupling coefficient (keff2) value up to 13.3%, and the measured filter demonstrates a -3 dB bandwidth of 115 MHz (from 3.013 GHz to 3.128 GHz), a low insertion loss of -2.4 dB, and good out-of-band rejection of -30 dB. The measured 1 dB compression point of the fabricated filter is 30.5 dBm, and the first series resonator burns out first as the input power increases. This work paves the way for research on high-power RF filters in mobile communication.

Characteristics and Outcomes of Anti-interferon Gamma Antibody-Associated Adult Onset Immunodeficiency.

PURPOSE: Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome. METHODS: A systematic literature review of AIGA associated disease was conducted. Serum-positive cases with detailed clinical presentations, treatment protocols, and outcomes were included. The patients were categorized into controlled and uncontrolled groups based on their documented clinical outcome. Factors associated with disease outcome were analyzed with logistic regression models. RESULTS: A total of 195 AIGA patients were retrospectively analyzed, with 119(61.0%) having controlled disease and 76 (39.0%) having uncontrolled disease. The median time to diagnosis and disease course were 12 months and 28 months, respectively. A total of 358 pathogens have been reported with nontubercular mycobacterium (NTM) and Talaromyces marneffei as the most common pathogens. The recurrence rate was as high as 56.0%. The effective rates of antibiotics alone, antibiotics with rituximab, and antibiotics with cyclophosphamide were 40.5%, 73.5%, and 75%, respectively. In the multivariate logistic analysis, skin involvement, NTM infection, and recurrent infections remained significantly associated with disease control, with ORs of 3.25 (95% CI 1.187 ~ 8.909, P value = 0.022), 4.74 (95% CI 1.300 ~ 17.30, P value = 0.018), and 0.22 (95% CI 0.086 ~ 0.551, P value = 0.001), respectively. The patients with disease control had significant AIGA titer reduction. CONCLUSIONS: AIGA could cause severe opportunistic infections with unsatisfactory control, particularly in patients with recurrent infections. Efforts should be made to closely monitor the disease and regulate the immune system.

Association of triglyceride-glucose index trajectory and frailty in urban older residents: evidence from the 10-year follow-up in a cohort study.

BACKGROUND: Frailty is an age-related geriatric syndrome that leads to a series of clinically negative events. A better understanding of the factors associated with frailty assists in preventing its progression. The triglyceride-glucose (TyG) index, a simple alternative index of insulin resistance, has not yet been proven to be associated with frailty. The present study aimed to investigate the association between the TyG index and its trajectory with frailty from a cross-sectional, retrospective and prospective level based on an ongoing cohort. METHODS: This longitudinal study included 1,866 older residents from the "Fujian prospective aging cohort" (ChiCTR 2,000,032,949). The TyG index was calculated as ln [fasting triglyceride (mg/dL) ╳ fasting plasma glucose (mg/dL)/2] and group-based trajectory model (GBTM) was applied to identify the trajectory of TyG index. The association between different trajectory groups of TyG index with frailty risk were estimated using multinomial logistic regression analysis. RESULTS: In the cross-sectional analysis, the highest quartile of the TyG index was associated with an increased risk of frailty (TyG index Q4 vs. Q1, OR = 1.50, 95% CI 1.00-2.25, P = 0.048). Restricted cubic splines demonstrated an increasing trend for TyG index and frailty risk. During a follow-up of ten years, three distinct trajectories of the TyG index were identified: low-stable (n = 697, 38.3%), moderate-stable (n = 910, 50.0%) and high-stable (n = 214, 11.7%). Compared with those in the stable-low group of TyG index trajectory, the ORs (95% CI) of prefrailty and frailty risk were 1.79 (95% CI 1.11-2.88) and 2.17 (95% CI 1.01-3.88) for the high-stable group, respectively (P = 0.017 and P = 0.038). In the subgroup analysis, the association of the high-stable trajectory of TyG and frailty status were only observed in subjects with BMI ≥ 24 kg/m2. Prospectively, the highest quartile of the TyG index was associated with a 2.09-fold significantly increased risk of one-year ADL/IADL decline (P = 0.045). CONCLUSIONS: The present study suggests a potential role for a high and sustainable level of TyG index in the risk of frailty. The trajectories of the TyG index can help to identify older individuals at a higher risk of frailty who deserve primitive preventive and therapeutic approaches.

SHH/GLI2-TGF-ß1 feedback loop between cancer cells and tumor-associated macrophages maintains epithelial-mesenchymal transition and endoplasmic reticulum homeostasis in cholangiocarcinoma.

BACKGROUND: Tumor-associated macrophages (TAMs) play a dual role in tumors. However, the factors which drive the function of TAMs in cholangiocarcinoma remain largely undefined. METHODS: SHH signaling pathway and endoplasmic reticulum stress (ERS) indicators were detected in clinical tissues and cholangiocarcinoma cell lines. TAMs were co-cultured with cholangiocarcinoma cells under conditions of hypoxia/normoxia. Polarized TAMs were counted by flow cytometry, and TGF-ß1 levels in cell supernatants were detected by ELISA. The effects of glioma-associated oncogene GLI2 on TAMs themselves and cholangiocarcinoma cells were examined by conducting interference and overexpression assays. RESULTS: The SHH signaling pathway and ERS were both activated in tumor tissues or tumor cell lines under conditions of hypoxia. In co-culture experiments, the presence of cholangiocarcinoma cells increased the proportion of M2-polarized TAMs and the secretion of TGF-ß1 by TAMs, while knockdown of SHH expression reversed those increases. Overexpression of GLI2 in TAMS or stimulation of TAMS with Hh-Ag1.5 increased their levels of TGF-ß1 expression. Furthermore, under co-culture conditions, interference with GLI2 expression in TAMs reduced the tumor cell migration, invasion, and ER homeostasis induced by Hh-Ag1.5-pretreated TAMs. Under conditions of hypoxia, the presence of cholangiocarcinoma cells promoted the expression of GLI2 and TGF-ß1 in Tams, and in turn, TAMs inhibited the apoptosis and promoted the migration and invasion of cholangiocarcinoma cells. In vivo, an injection of cholangiocarcinoma cells plus TAMs contributed to the growth, EMT, and ER homeostasis of tumor tissue, while an injection of TAMs with GLI2 knockdown had the opposite effects. CONCLUSION: Cholangiocarcinoma cells regulated TAM polarization and TGF-ß1 secretion via a paracrine SHH signaling pathway, and in turn, TAMs promoted the growth, EMT, and ER homeostasis of cholangiocarcinoma cells via TGF-ß1.

Bifunctional Thiourea-Catalyzed Enantioselective Aza-Friedel-Crafts Reaction of 3-Aminobenzofurans with Isatin-Derived Ketimines.

A quinine-derived thiourea-promoted enantioselective aza-Friedel-Crafts reaction of 3-aminobenzofurans with isatin-derived ketimines is developed, providing a variety of 3-benzofuran-3-amino-2-oxindoles bearing a quaternary stereocenter with good to excellent yields (72-95%) and moderate to excellent enantioselectivities (48-97%). The synthetic potential of this concise and efficient protocol is revealed by gram-scale preparation and further transformation of the adduct to an optically pure spirocyclic oxindole.

Multiple rib and vertebral fractures associated with Bordetella pertussis infection: a case report.

BACKGROUND: Pertussis is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis, characterized by paroxysms of severe coughing, and predominantly affects children. We report the first case of multiple fractures in the ribs, lumbar spine, and sacrum associated with severe coughing caused by Bordetella pertussis infection in an adult. CASE PRESENTATION: A 49-year-old female presented with acute-onset chest wall pain for 3 weeks. Imaging results revealed multiple fractures in the ribs and vertebrae, as well as bilateral pleural effusion, pericardial effusion, right pneumothorax, and enlargement of the left parapharyngeal and subclavian lymph nodes. The patient's bone density scan, autoimmune antibodies, bone marrow biopsy, and sacral bone biopsy all came back normal. Imaging test results found no evidence of solid tumors or active TB infection. The patient later recalled having violent coughing prior to the onset of chest pain and several family members having similar symptoms. Her blood sample was sent to the CDC, revealing Bordetella pertussis toxin (PT) IgG titer of 110.68 IU/mL. The patient was diagnosed with pertussis and multiple stress fractures from violent coughing. Symptomatic treatments were administered, and the patient's symptoms improved. The patient was followed up 8 weeks later, she reported no more coughing or chest pain. CONCLUSIONS: Pertussis is not just a pediatric disease, but diagnosis in adults is challenging as patients may present with a myriad of confusing symptoms, such as multiple stress fractures due to violent coughing. Medical and epidemiological histories are key to reaching the correct diagnosis, which is essential for appropriate treatments to avoid further complications. Adult immunization should be suggested both for the protection of the adult population and to prevent transmission to children.

Effects of mushroom-tobacco rotation on microbial community structure in continuous cropping tobacco soil.

AIMS: Rotation is an effective strategy for controlling crop diseases and improving plant health. However, the effect of a mushroom-tobacco rotation on the composition and structure of microbial communities in continuous cropping soil is unclear. METHODS AND RESULTS: This study analysed the structure and function of soil bacterial and fungal communities using Illumina MiSeq high-throughput 16S rRNA gene sequencing. The results showed that the physicochemical properties (organic matter, available nitrogen, available phosphorus, and available potassium) and enzymatic activity (phosphatase, catalase, urease and invertase activity) in the rotation treatments (Y1, M1, Y2 and M2) were significantly higher than those in the control (continuous cropping) treatment (CK) and reached peak values in the M2 treatment. PCA showed that the soil microbial community structure in each rotation treatment was different from that in the control. The dominant bacterial phyla of the different soil treatments were Proteobacteria and Actinobacteriota, and the dominant fungal phyla of the different soil treatments were Ascomycota and Basidiomycota. The M2 rotation significantly reduced the relative abundance of harmful fungi (Penicillium and Gibberella) compared to the other treatments. RDA showed that the most abundant bacterial taxa were negatively correlated with pH and positively correlated with physicochemical properties. However, the most abundant fungal taxa were positively correlated with pH and negatively correlated with physicochemical properties. CONCLUSIONS: The mushroom-tobacco rotation can effectively maintain the ecological balance of the substrate microbial environment, and provide a more effective way to prevent the continuous cropping of tobacco.

Gasless endoscopic thyroidectomy via the anterior chest approach: the experience with 1500 cases.

BACKGROUND: Conventional thyroidectomy leaves an eye-catching scar in the anterior neck region. Endoscopic thyroidectomy may achieve a better esthetic effect and improve quality of life postoperatively. The aim of this study was to undertake a complete review of a large cohort of the patients undergoing gasless endoscopic thyroidectomy (GET) via anterior chest approach (ACA) with a long-term follow-up period, and evaluate the results and limits of this procedure. METHODS: Between 2003 and 2022, 1413 patients undergoing GET via ACA in our department were included. The demographic, clinicopathological characteristics, oncologic and esthetic outcomes were summarized and analyzed. RESULTS: The indication for surgery was papillary thyroid carcinoma in 686 (48.5%) patients and benign thyroid diseases in 727 (51.5%) patients. Among them, 802 (56.8%) patients took hemithyroidectomy, and 611 (43.2%) patients did sub-total/total thyroidectomy. Meanwhile, 598 (42.3%) ones had central neck dissection, while 88 (6.2%) lateral neck dissection. The most common complication was transient hypoparathyroidism with an incidence of 2.9%. During the follow-up period of 2 to 232 months, three patients were confirmed locoregional recurrence. Most of the patients were satisfied with the cosmetic results. CONCLUSION: Gasless endoscopic thyroidectomy via anterior chest approach is a safe and feasible procedure, which could achieve excellent oncologic and esthetic outcomes.

Clinical nutrition service capacity of 445 secondary or above hospitals in Sichuan, China: the 2021 annual survey.

BACKGROUND AND OBJECTIVES: To investigate the capacity of clinical nutrition services in secondary and tertiary hospitals in the Sichuan Province, China. METHODS AND STUDY DESIGN: Convenience sampling was used. E-questionnaires were distributed to all eligible medical institutions in Sichuan through the official network of provincial and municipal clinical nutrition quality control centers. The data obtained were sorted in Microsoft Excel and analyzed by SPSS. RESULTS: A total of 519 questionnaires were returned, of which 455 were valid. Only 228 hospitals were accessible to clinical nutrition services, of which 127 hospitals had independently set up clinical nutrition departments (CNDs). The ratio of clinical nutritionists to beds was 1:214. During the last decade, the rate of constructing new CNDs was maintained at approximately 5 units/year. A total of 72.4% of hospitals managed their clinical nutrition units as part of their medical technology departments. The specialist number ratio of senior, associate, intermediate and junior is approximately 1:4:8:10. There were 5 common charges for clinical nutrition. CONCLUSIONS: The sample representation was limited, and the capacity of clinical nutrition services may have been overestimated. Secondary and tertiary hospitals in Sichuan are currently in the second high tide of department establishment, with a positive trend of departmental affiliation standardization and a basic formation of a talent echelon.

Systematically analyzed molecular characteristics of lung adenocarcinoma using metabolism-related genes classification.

High heterogeneity of lung adenocarcinoma (LUAD) is a major clinical challenge. This study aims to characterize the molecular features of LUAD through classification based on metabolism-related genes. A total of 500 LUAD samples from The Cancer Genome Atlas (TCGA) and 612 from Gene Expression Omnibus (GEO) were integrated with 2,753 metabolism-related genes to determine the molecular classification. Systematic bioinformatics analysis was used to conduct correlation analysis between metabolism-related classification and molecular characteristics of LUAD. LUAD patients were divided into three molecular clusters (C1-C3). Survival analysis revealed that C1 and C2 showed good and poor prognoses, respectively. Associational analysis of classification and molecular characteristics revealed that C1 was associated with low pathological stage, metabolic pathways, high metabolic process, active immune process and checkpoint, sensitive drug response, as well as a low genetic mutation. Nevertheless, C2 was associated with high pathological stage, carcinogenic pathways, low metabolic process, inactive immune signatures, resistant drug response, and frequent genetic mutation. Eventually, a classifier with 60 metabolic genes was constructed, confirming the robustness of molecular classification on LUAD. Our findings promote the understanding of LUAD molecular characteristics, and the research data may be used for providing information be helpful for clinical diagnosis and treatment.

The relationship between alarm fatigue and burnout among critical care nurses: A cross-sectional study.

BACKGROUND: Alarm fatigue has significant negative impacts on nurses and patient safety. However, the relationship between alarm fatigue and burnout is still unclear. AIMS: This study aimed to explore the relationship between alarm fatigue and burnout among critical care nurses. STUDY DESIGN: A descriptive-analytical cross-sectional study design was used. Data were collected from five hospitals in mainland China between January 2022 and March 2022. A general information questionnaire, the Chinese version of the Intensive Care Unit Nurse Alarm Fatigue Questionnaire, and the Chinese version of the Maslach Burnout Inventory were used. RESULTS: A total of 236 critical care nurses were enrolled in this study. The mean score of alarm fatigue among critical care nurses was 21.11 ± 6.83. The results showed that critical care nurses experienced moderate alarm fatigue levels, and most nurses had moderate to high levels of burnout. The multiple linear regression analyses showed that alarm fatigue was independently associated with emotional exhaustion, depersonalization dimensions, and reduced personal accomplishment dimension. CONCLUSIONS: Alarm fatigue was associated with burnout among critical care nurses. Reducing critical care nurses' alarm fatigue may help to alleviate burnout. RELEVANCE TO CLINICAL PRACTICE: Managers should provide comprehensive training for nurses and promote the application of artificial intelligence technology in alarm management to reduce alarm fatigue and improve burnout among critical care nurses.

Color doppler ultrasound analysis of pathological myopia induced changes in retrobulbar blood flow and its relationship with characteristic changes in myopia.

Objective: To analyze changes in retrobulbar blood flow in patients with pathological myopia using color doppler ultrasound (CDU), and to explore the relationship of these changes with the characteristic changes resulting from myopia. Methods: One hundred and twenty patients who met the selection criteria in the ophthalmology department of He Eye Specialist Hospital from May 2020 to May 2022 were included in this study. Patients with normal vision (n=40) were considered Group-A, patients with low and moderate myopia (n=40) were considered Group-B, and patients with pathological myopia (n=40) were considered Group-C. All three groups underwent ultrasonography. The peak systolic blood flow velocity (PSV), end-diastolic blood flow velocity (EDV), and resistance index (RI) of the ophthalmic artery, central retinal artery, and posterior ciliary artery were recorded and compared, and the characteristics of these parameters and myopia severity were analyzed. Results: Pathological myopia resulted in significantly lower PSV and EDV of the ophthalmic artery, central retinal artery and posterior ciliary artery and higher RI values than patients with normal vision and low/moderate myopia (P<0.05). Pearson correlation analysis showed that retrobulbar blood flow changes were significantly correlated with age, eye axis, best corrected visual acuity, and retinal choroidal atrophy. Conclusion: CDU can objectively evaluate the retrobulbar blood flow changes in pathological myopia, and such blood flow changes are significantly correlated with the characteristic changes of myopia.

Polymorphisms of acetaldehyde dehydrogenase 2 and alcohol dehydrogenase 1B on the malignant transformation of vocal cord leukoplakia: A Chinese cohort.

Severe dysplasia of vocal cord leukoplakia (VCL) is more likely to occur in laryngeal carcinoma. Alcohol dehydrogenase and acetaldehyde dehydrogenase are both important enzymes in alcohol metabolism. This study aimed to investigate the incidence rate of malignant transformation in patients with VCL and the role of drinking habits and ALDH2 and ADH1B genetic polymorphisms in the malignant transformation of VCL. From January 2007 to January 2017, 136 cases of VCL were included in this retrospective analysis. Information on medical history, alcohol and tobacco consumption habits, ALDH2 and ADH1B genotypes, gastroesophageal reflux, and clinical pathological characteristics of VCL was collected. As a result, patients had a median follow-up of 9.6 years (interquartile range: 7.5-12.5 years). Twenty-three of 136 VCL patients finally developed laryngeal carcinoma, resulting in a cumulative malignant transformation rate of 16.9%. Cox regression analysis demonstrated that the independent risk factors for the malignant transformation of VCL included age over 60 years (hazard ratio [HR]: 13.872, p < 0.001), ALDH2 *2 allele status (HR: 9.694, p < 0.001), alcohol (HR: 10.011, p < 0.001) and tobacco (HR: 8.869, p < 0.001) exposure after operation, and drinking frequency (HR: 2.178, p = 0.016). Therefore, among patients over 60 years old, an ALDH2-inactivating mutation and excessive ethanol and tobacco consumption are potential contributors to the malignant transformation of VCL.

The identification and prediction of frailty based on Bayesian network analysis in a community-dwelling older population.

BACKGROUND: We have witnessed frailty, which characterized by a decline in physiological reserves, become a major public health issue in older adults. Understanding the influential factors associated with frailty may help prevent or if possible reverse frailty. The present study aimed to investigate factors associated with frailty status and frailty transition in a community-dwelling older population. METHODS: A prospective cohort study on community-dwelling subjects aged ≥ 60 years was conducted, which was registered beforehand (ChiCTR 2,000,032,949). Participants who had completed two visits during 2020-2021 were included. Frailty status was evaluated using the Fried frailty phenotype. The least absolute shrinkage and selection operator (LASSO) regression was applied for variable selection. Bayesian network analysis with the max-min hill-climbing (MMHC) algorithm was used to identify factors related to frailty status and frailty transition. RESULTS: Of 1,981 subjects at baseline, 1,040 (52.5%) and 165 (8.33%) were classified as prefrailty and frailty. After one year, improved, stable, and worsening frailty status was observed in 460 (35.6%), 526 (40.7%), and 306 (23.7%) subjects, respectively. Based on the variables screened by LASSO regression, the Bayesian network structure suggested that age, nutritional status, instrumental activities of daily living (IADL), balance capacity, and social support were directly related to frailty status. The probability of developing frailty is 14.4% in an individual aged ≥ 71 years, which increases to 20.2% and 53.2% if the individual has balance impairment alone, or combined with IADL disability and malnutrition. At a longitudinal level, ADL/IADL decline was a direct predictor of worsening in frailty state, which further increased the risk of hospitalization. Low high-density lipoprotein cholesterol (HDL-C) and diastolic blood pressure (DBP) levels were related to malnutrition, and further had impacts on ADL/IADL decline, and ultimately led to the worsening of the frailty state. Knowing the status of any one or more of these factors can be used to infer the risk of frailty based on conditional probabilities. CONCLUSION: Older age, malnutrition, IADL disability, and balance impairment are important factors for identifying frailty. Malnutrition and ADL/IADL decline further predict worsening of the frailty state.

Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: The addition of camrelizumab to gemcitabine and cisplatin showed promising activity as first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma in a phase 1 trial. We therefore compared camrelizumab plus gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin in a randomised phase 3 trial. METHODS: In this randomised, double-blind, phase 3 trial done at 28 hospitals in China, patients were eligible if they were aged 18-75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and had previously untreated recurrent or metastatic nasopharyngeal carcinoma. Patients were randomly assigned (1:1; using an interactive web-response system with a block size of four) to receive either camrelizumab (200 mg on day 1) or matching placebo intravenously, plus gemcitabine and cisplatin (gemcitabine 1000 mg/m2 on days 1 and 8; cisplatin 80 mg/m2 on day 1) intravenously every 3 weeks for four to six cycles, followed by maintenance therapy with camrelizumab or placebo, until radiographic progression, unacceptable toxicity, start of new anticancer treatment, investigator decision, or withdrawal of consent. Stratification factors used in randomisation were liver metastases, previous radical concurrent chemoradiotherapy, and ECOG performance status. The allocation sequence was generated by an independent randomisation group. The primary endpoint was progression-free survival per independent review committee. The significance threshold for independent review committee-assessed progression-free survival was p=0·0086 (one-sided) at the interim analysis. Efficacy and safety analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03707509, and is closed for enrolment but is ongoing. FINDINGS: Between Nov 13, 2018, and Nov 29, 2019, 343 patients were screened and 263 were eligible and were randomly assigned to the camrelizumab group (n=134) or placebo group (n=129). At the prespecified interim analysis (June 15, 2020), independent review committee-assessed progression-free survival was significantly longer in the camrelizumab group (median 9·7 months [95% CI 8·3-11·4]) than in the placebo group (median 6·9 months [5·9-7·3]; hazard ratio 0·54 [95% CI 0·39-0·76]; one-sided p=0·0002). As of Dec 31, 2020, the most common grade 3 or worse adverse events of any cause were decreased white blood cell count (89 [66%] of 134 patients in the camrelizumab group vs 90 [70%] of 129 patients in the placebo group), decreased neutrophil count (86 [64%] vs 85 [66%]), anaemia (53 [40%] vs 57 [44%]), and decreased platelet count (53 [40%] vs 52 [40%]). Serious adverse events were reported in 59 (44%) of 134 patients in the camrelizumab group and 48 (37%) of 129 patients in the placebo group. Treatment-related deaths occurred in five (4%) patients in the camrelizumab group (two unknown cause of death, one multiple organ dysfunction syndrome, one pharyngeal haemorrhage, and one arrhythmia) and one (<1%) patient in the placebo group (unknown cause of death). INTERPRETATION: Our findings suggest that camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. Longer follow-up is needed to confirm this conclusion. FUNDING: Jiangsu Hengrui Pharmaceuticals (formerly Jiangsu Hengrui Medicine). TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.