Personalised follow-up and management schema for patients with screen-detected pulmonary nodules: A dynamic modelling study.

BACKGROUND: Selecting the time target for follow-up testing in lung cancer screening is challenging. We aim to devise dynamic, personalized lung cancer screening schema for patients with pulmonary nodules detected through low-dose computed tomography. METHODS: We developed and validated dynamic models using data of pulmonary nodule patients (aged 55-74 years) from the National Lung Screening Trial. We predicted patient-specific risk profiles at baseline (R0) and updated the risk evaluation results in repeated screening rounds (R1 and R2). We used risk cutoffs to optimize time-dependent sensitivity at an early decision point (3 months) and time-dependent specificity at a late decision point (1 year). RESULTS: In validation, area under receiver operating characteristic curve for predicting 12-month lung cancer onset was 0.867 (95 % confidence interval: 0.827-0.894) and 0.807 (0.765-0.948) at R0 and R1-R2, respectively. The personalized schema, compared with National Comprehensive Cancer Network (NCCN) guideline and Lung-RADS, yielded lower rates of delayed diagnosis (1.7% vs. 1.7% vs. 6.9 %) and over-testing (4.9% vs. 5.6% vs. 5.6 %) at R0, and lower rates of delayed diagnosis (0.0% vs. 18.2% vs. 18.2 %) and over-testing (2.6% vs. 8.3% vs. 7.3 %) at R2. Earlier test recommendation among cancer patients was more frequent using the personalized schema (vs. NCCN: 29.8% vs. 20.9 %, p = 0.0065; vs. Lung-RADS: 33.2% vs. 22.8 %, p = 0.0025), especially for women, patients aged ≥65 years, and part-solid or non-solid nodules. CONCLUSIONS: The personalized schema is easy-to-implement and more accurate compared with rule-based protocols. The results highlight value of personalized approaches in realizing efficient nodule management.

[Determination of dimethyl oxalate and diethyl oxalate in workplace air by high performance liquid chromatography].

Objective: To establish a high performance liquid chromatography method for the simultaneous determination of dimethyl oxalate (DMO) and diethyl oxalate (DEO) in workplace air. Methods: From January 2022 to January 2023, air samples were collected by silica gel tubes, desorbed by acetonitrile, separated by C18 chromatographic column, detected by photo-array detector, and retention time was used to characterize and peak area was used to quantify at 210 nm wavelength. Results: The linear relationships of DMO and DEO were good, r>0.999. The detection limits of DMO and DEO were 0.39 and 0.52 µg/ml, respectively. The quantitative limit was 1.28 µg/ml for DMO and 1.72 µg/ml for DEO. Average desorption efficiency for DMO was 82.40%-92.72%, and DEO was 94.13%-97.69%. The intra-assay precision of DMO was 1.87%-6.18%, and DEO was 2.25%-3.31%. Inter-assay precision of DMO was 3.29%-5.73%, and DEO was 1.38%-2.94%. Average sampling efficiencies were 100% for both DMO and DEO. Breakthrough capacity of DMO was 37.61 mg (200 mg solid adsorbent), DEO was >28.11 mg (200 mg solid adsorbent). Samples should be stored at 4 ℃ for at least 7 days. Conclusion: This method is easy to operate and has strong practicability. All indicators meet the requirements of the specification, and it is suitable for the simultaneous determination of DMO and DEO in the workplace air.

[Clinical analysis of 12 cases of ovarian yolk sac tumor].

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 µg/L) were significantly higher than normal (<25 µg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

[Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study].

Objective: To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications. Methods: This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression. Results: The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion: Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Rev-erbα attenuates refractory periapical periodontitis via M1 polarization: An in vitro and in vivo study.

AIM: Rev-erbα has been reported to regulate the healing of inflammatory lesions through its effect on the immune system in a variety of inflammatory disease. Moreover, the balance of macrophages polarization plays a crucial role in immune response and inflammatory progression. However, in refractory periapical periodontitis (RAP), the role of Rev-erbα in inflammatory response and bone resorption by regulating macrophage polarization remains unclarified. The aims of the present study were to investigate the expression of Rev-erbα in experimental RAP and to explore the relationship between Rev-erbα and macrophage polarization through the application of its pharmacological agonist SR9009 into the in vivo and in vitro experiments. METHODOLOGY: Enterococcus faecalis-induced RAP models were established in SD rats. Histological staining and micro-computed tomography scanning were used to evaluate osteoclastogenesis and alveolar bone resorption. The expression of Rev-erbα and macrophage polarization were detected in the periapical tissues from rats by immunofluorescence, flow cytometry, and western blots. Furthermore, immunohistochemical staining and enzyme-linked immunosorbent assay were performed to explore the relationship between Rev-erbα and inflammatory cytokines related to macrophage polarization. RESULT: Compared to healthy periapical tissue, the expression of Rev-erbα was significantly down-regulated in macrophages from inflammatory periapical area, especially in Enterococcus faecalis-induced periapical lesions, with obvious type-1 macrophage (M1)-like dominance and the production of pro-inflammatory cytokines. In addition, Rev-erbα activation by SR9009 could induce type-2 macrophage (M2)-like polarization in periapical tissue and THP1 cell line, followed by increased secretion of anti-inflammatory cytokines IL-10 and TGF-ß. Furthermore, intracanal application of SR9009 reduced the lesion size and promoted the repair of RAP by decreasing the number of osteoclasts and enhancing the formation of mineralized tissue in periapical inflammatory lesions. CONCLUSIONS: Rev-erbα played an essential role in the pathogenesis of RAP through its effect on macrophage polarization. Targeting Rev-erbα might be a promising and prospective therapy method for the prevention and management of RAP.

[Association of lifestyle and apolipoprotein E gene with risk for cognitive frailty in elderly population in China].

Objective: To investigate the impact of lifestyle, apolipoprotein E (ApoE) gene, and their interaction on the risk for cognitive frailty in the elderly population in China. Methods: The study participants were from the Chinese Longitudinal Healthy Longevity Survey. The information about their lifestyles were collected by questionnaire survey, and a weighted lifestyle score was constructed based on ß coefficients associated with specific lifestyles to assess the combined lifestyle. ApoE genotypes were assessed by rs429358 and rs7412 single nucleotide polymorphisms. Cognitive frailty was assessed based on cognitive function and physical frailty. Cox proportional hazards regression model was used to analyze the association of lifestyle and ApoE gene with the risk for cognitive frailty and evaluate the multiplicative and additive interactions between lifestyle and ApoE gene. Results: A total of 5 676 elderly persons, with median age [M (Q1, Q3)] of 76 (68, 85) years, were included, in whom 615 had cognitive frailty. The analysis by Cox proportional hazards regression model indicated that moderate and high levels of dietary diversity could reduce the risk for cognitive frailty by 18% [hazard ratio (HR)=0.82, 95%CI: 0.68-1.00] and 28% (HR=0.72, 95%CI: 0.57-0.91), respectively; moderate and high levels of physical activity could reduce the risk by 31% (HR=0.69, 95%CI: 0.56-0.85) and 23% (HR=0.77, 95%CI: 0.64-0.93), respectively. Healthy lifestyle was associated with a 40% reduced risk for cognitive frailty (HR=0.60, 95%CI: 0.46-0.78). ApoE ε4 allele was associated with a 26% increased risk for cognitive frailty (HR=1.26, 95%CI: 1.02-1.56). No multiplicative or additive interactions were found between lifestyle and ApoE gene. Conclusions: Dietary diversity and regular physical activity have protective effects against cognitive frailty in elderly population. Healthy lifestyle can reduce the risk for cognitive frailty in elderly population regardless of ApoE ε4 allele carriage status.

Interrelationship between platelets and BUN in postmenopausal patients with coronary heart disease: findings of the NHANES from 2003 to 2016.

OBJECTIVE: During menopause, women are more likely to develop coronary heart disease (CHD) due to the significant changes in body metabolism brought on by the loss of estrogen. The purpose of this study was to investigate the independent association between platelet parameters and blood urea nitrogen (BUN) in postmenopausal patients with coronary artery disease in order to clarify the function performed by platelet parameters and BUN in thrombosis. PATIENTS AND METHODS: We took information from the NHANES between 2003 and 2016. Platelet count (PC), mean platelet volume (MPV), and PC/MPV were the independent variables, BUN was the dependent variable, and age, race, marital status, body mass index (BMI), inflammation indicators, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were the covariates. RESULTS: BUN decreased with increasing PC in postmenopausal heart disease patients after controlling for other factors. When PC/MPV was less than 30.5, there was a strong negative correlation with BUN. In addition, there was a strong positive correlation with BUN when MPV was less than 9.3 fL. CONCLUSIONS: The findings of this study will contribute to a better understanding of the mechanisms underlying thrombosis in postmenopausal women with CHD and offer fresh perspectives on how to create novel antithrombotic medications for an aging population.

[Effects of immune responses mediated by topological structures of three-dimensional bioprinted scaffolds on hair follicle cycle in mice].

Objective: To explore the effects of the immune responses mediated by topological structures of three-dimensional bioprinted scaffolds on hair follicle cycle in mice. Methods: The study was an experimental research. The alginate-gelatin composite hydrogels were printed into scaffolds using a three-dimensional bioprinter and named T45 scaffolds, T60 scaffolds, and T90 scaffolds according to the 3 topological structures of the scaffolds (the rotation angles of the printhead during printing were 45°, 60°, and 90°, respectively), and the morphology of the three scaffolds was observed after cross-linking by naked eyes. Nine 8-week-old female C57BL/6J mice were divided into T45 group, T60 group, and T90 group, according to the random number table, with three mice in each group, and the T45, T60, and T90 scaffolds were subcutaneously implanted on the back of mice, respectively. On post implantation day (PID) 7, the hair growth in the dorsal depilated area of mice was observed, the thickness of the fiber capsule around the scaffolds was observed by hematoxylin-eosin staining, and the expression levels of CD68, bone morphogenetic protein-2 (BMP-2), and tumor necrosis factor (TNF) protein in the tissue surrounding the scaffolds were observed by immunofluorescence staining. The samples of the above experiments were all 3. Results: The topological structures of the three scaffolds were all clear with high fidelity after cross-linking. On PID 7, the hair growth was obvious in the dorsal depilated area of mice in T45 group and T90 group, while hair growth was slow in the scaffold implantation area of mice in T60 group, which was significantly different from that of the unimplanted area. On PID 7, compared with (18±4) µm in T90 group, the thickness of both the fiber capsule around the scaffolds ((39±4) and (55±8) µm) of mice in T45 group and T60 group was significantly increased (P<0.05); the thickness of the fiber capsule around the scaffolds of mice in T60 group was also significantly increased compared with that in T45 group (P<0.05). On PID 7, the expression level of CD68 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05). The expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05), and the expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T45 group was significantly higher than that in T90 group (P<0.05). The expression level of TNF protein in the tissue surrounding the scaffolds of mice in T60 group was significantly lower than the levels in T45 group and T90 group (with both P values <0.05). Conclusions: Three-dimensional bioprinted scaffolds with different topological structures mediate different degrees of immune responses after being implanted in mice. A moderate immune response promotes hair growth in depilated area of mice, while an excessive immune response results inhibits the hair follicle entering into the anagen phase.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

[Associations between risk factor control and survival among cancer patients].

Objective: This study aimed to evaluate the associations between the number of cardiovascular risk factor goals achieved with all-cause mortality, atherosclerotic cardiovascular diseases (ASCVD)-related mortality, and cancer-related mortality amongst cancer patients. Methods: From 2006 to 2020, a total of 2 079 individuals with newly diagnosed cancer, free of ASCVD, were enrolled in this study from the Kailuan cohort. Patients were classified into three groups (group 1,≤1 risk factor at goal, n=407; group 2, 2 risk factors at goal, n=865; group 3,≥3 risk factors at goal, n=807) according to the control status of blood pressure, fasting blood glucose, low-density lipoprotein cholesterol and high-sensitivity C-reactive protein, using health checkup results of the latest survey after cancer diagnosis. Multivariable Cox regression analyses were performed to examine the associations between the number of risk factors at goals with all-cause mortality, ASCVD-related mortality, and cancer-related mortality. Results: The mean age at diagnosis was (60.4±10.4) years, and 71.2% were male. During a median follow-up of 2.95 (1.38, 5.12) years, 600 cases of all-cause mortality, 63 cases of ASCVD-related mortality, and 314 cases of cancer-related mortality were observed. After adjusting for age, gender, education level, smoking status, alcohol consumption, salt intake, physical activity, body mass index, triglyceride, high-density lipoprotein cholesterol, family history of cardiovascular diseases, antihypertensive drugs, hypoglycemic drugs, lipid-lowering drugs, and anti-cancer medications, compared with cancer patients achieving ≤1 risk factor goal, those achieving ≥3 risk factor goals showed significantly decreased risk of all-cause mortality, ASCVD mortality, and cancer mortality, with HR (95%CI) of 0.68 (0.54-0.86), 0.35 (0.16-0.77), and 0.60 (0.43-0.82), respectively (all P values <0.05). Significant relationships between the number of risk factor goals achieved and decreased mortality of all kinds were observed (all P values for trend<0.05). Results of the subgroup analyses suggested that the associations between the number of risk factor goals achieved and lower mortality of all kinds were more prominent among individuals who were ≥60 years, male, and those with respiratory and reproductive cancers (all P values <0.05). Conclusions: This study suggested a significant association between the number of cardiovascular risk factor goals achieved and survival in cancer patients, especially amongst those who were older, male, with respiratory cancers and reproductive cancers.

[Research advances on improving the therapeutic efficacy of mesenchymal stem cell-derived exosomes in wound repair].

How to promote high-quality wound healing is a common problem for plastic surgery and burn physicians. In recent years, numerous animal studies have demonstrated that mesenchymal stem cell-derived exosomes promote wound repair through multiple mechanisms and are promising cell-free therapeutic agents with broad prospect of application. How to enhance the therapeutic efficacy of exosomes, optimize their drug delivery strategy, and improve their biological properties are the challenges to be overcome in order to move from basic research to clinical application of exosome therapy for wound repair. This article focuses on methods to improve the wound repair potential of mesenchymal stem cell-derived exosomes, and reviews the recent research advances on improving the therapeutic efficacy of mesenchymal stem cell-derived exosomes in wound repair from three aspects, including pretreatment of parental mesenchymal stem cells, hydrogel bio-scaffold loaded with exosomes, and engineered exosomes, to provide a reference for further clinical studies.

The Role of Sarcopenia in Overactive Bladder in Adults in the United States: Retrospective Analysis of NHANES 2011-2018.

PURPOSE: To investigate the association between sarcopenia and overactive bladder (OAB) in a United States adult population from 2011 to 2018, and whether sarcopenia can predict the risk of OAB. MATERIALS AND METHODS: We analyzed data from the 2011-2018 National Health and Nutrition Examination Survey in a cross-sectional study(NHANES) of 8746 participants, of whom 1213 were diagnosed with OAB, we analyzed correlations by sex, age, race, education level, marital status, household income-to-poverty ratio, hypertension, diabetes, strenuous work activity, moderate work activity, strenuous recreational activity, moderate recreational activity, blood urea nitrogen, creatinine, and uric acid levels using restricted cubic spline plots of dose-response curves, univariate and multivariate Logistic regression. Models based on sex, age, education, household income to poverty ratio, hypertension, diabetes, sarcopenia index, and cotinine were developed and evaluated using Nomogram, calibration curves, receiver operating characteristic curves, and clinical decision curves. RESULTS: Of the 1213 OAB patients, 388 (32.0%) were male and 825 (68.0%) were female. Univariate and multivariate Logistic regression analysis showed that sarcopenia index was negatively correlated with the prevalence of OAB (OR=0.084, 95% CI, 0.056 - 0.130, P <0.001;OR=0.456, 95%CI, 0.215-0.968, P= 0.0041). Dose curve analysis of the sarcopenia index and prevalence of OAB showed that the prevalence of OAB decreased significantly with increasing sarcopenia index. Sarcopenia was positively correlated with OAB (OR=2.400, 95%CI, 2.000 - 2.800, P <0.001;OR=1.46, 95%CI, 1.096 -1.953, P = 0.010). In addition, our model shows that sarcopenia can predict the prevalence of OAB (AUC = 0.750) and has some clinical decision-making implications. CONCLUSION: Sarcopenia is positively associated with the risk of OAB in United States adults and can be used as a predictor of OAB prevalence.

Incidence and prevalence of alopecia areata in the Australian primary care setting: A retrospective analysis of electronic health record data.

BACKGROUND: Alopecia areata (AA) is a common immune-mediated non-scarring hair loss, with a worldwide incidence between 0.57% and 3.8%. The incidence and prevalence of AA in the Australian general population have not been previously reported. OBJECTIVE: To describe the incidence and prevalence of AA in Australia using primary care data. A secondary objective was to identify common demographic characteristics, comorbidities and treatment patterns among Australians living with AA. METHODS: We analysed electronic health record data captured from a national clinical practice management software over a 10-year index period between 2011 and 2020 calendar years, inclusive. The incidence of new-onset AA and the prevalence of active records with AA were estimated. Differences in incidence by sociodemographic groups, and patterns of treatment were also evaluated. RESULTS: There were 976 incident AA records. The incidence of new-onset AA in the total study cohort was 0.278 per 1000 person-years (95% CI 0.26-0.295). By age, the incidence was highest in the 19- to 34-year-old age bracket (0.503 per 1000 person-years: 95% CI 0.453-0.554). AA incidence was lower among females than males (IRR 0.763, p < 0.001, 95% CI 0.673-0.865). Among active records, 520 were prevalent AA records. AA point prevalence at 31/12/2020 was 0.13% (1.26 per 1000 persons; 95% CI 1.15-1.37). CONCLUSION: This is the first study to describe the epidemiology (incidence and point prevalence) and management of AA in the Australian primary health-care population through large-scale database analysis. Incidence and prevalence findings were consistent with earlier estimates from other regions.

Metagenomic next-generation sequencing vs. conventional detection methods for detecting the pulmonary infections.

OBJECTIVE: The absence of proper pathogen treatment in the early stages can result in missing out on treatment chances or the overuse of antibiotics, both of which are the primary factors behind fatalities caused by lung infections. In this study, we aimed to investigate the efficacy of metagenomic next-generation sequencing (mNGS) in comparison to conventional detection methods in detecting infectious pathogens. PATIENTS AND METHODS: In this retrospective study, the infection pathogens of 104 patients were examined, and 86 bronchoalveolar lavage fluid (BALF), eight pleural effusions, and ten sputum samples were collected. The conventional detection approaches and mNGS analysis were used to determine the infection pathogen profiles and their detection rates were analyzed. RESULTS: Our study showed that mNGS was more sensitive (89.42%) than the conventional detection methods (56.73%) (p < 0.001), with a 32.69% improvement in sensitivity. The efficacy of mNGS in detecting mixed infections was significantly higher than that of conventional detection methods, with a detection rate of 85.29% compared to 17.65% (p < 0.001). The study demonstrated that mNGS had a higher sensitivity than the conventional detection methods when it came to diagnosing pulmonary infections, making it a potentially useful tool for clinical diagnosis. CONCLUSIONS: Combining mNGS with other pathogenic detection techniques can be an effective way to increase the rate of detecting pulmonary infections, as well as to provide guidance for treatment adjustments. Furthermore, the timing of sample collection and antibiotic administration can influence the effectiveness of mNGS when used on BALF specimens.

[Effects of RNA M6A demethylase ALKBH5 gene deficiency on morphology and function of cerebellum in aged mice].

Objective: To investigate the effects of RNA m6A demethylase ALKBH5 gene deficiency on cerebellar morphology and function in the aged mice, and to explore the role of ALKBH5 in cerebellar degeneration. Methods: Western blot was performed to detect the protein level of ALKBH5 in the cerebellum of wild-type mice of various ages. The expression of NeuN, Calbindin-D28K, MAP2, GFAP and other proteins in the cerebella of middle-aged (12-month-old) and aged (18-month-old) wild-type mice and ALKBH5-/- mice was examined using immunohistochemistry. The balance beam test and gait analysis were performed to test the balance ability and motor coordination of the mice. Results: With aging of the mice, the expression of ALKBH5 in the cerebellum increased gradually in an age-dependent manner. In the aged mice, but not middle-aged mice, the body weight, whole brain weight and cerebellum weight of ALKBH5-/- mice decreased by 15%, 10% and 21%, respectively (P<0.05). The expression of ALKBH5 in the Purkinje cells was much higher than that in other types of neural cells. Correspondingly, ALKBH5-deficiency caused 40% reduction in the number of Purkinje cells, as well as the length and density of neuronal dendrites in the aged mice (P<0.01). In addition, the time for the aged ALKBH5-/- mice to pass the balance beam was 70% longer than that of the wild type mice of the same age, with unstable gaits (P<0.01). Conclusions: Gene deficiency of RNA m6A demethylase ALKBH5 causes cerebellar atrophy, Purkinje neuron loss and damage in the aged mice. These changes eventually affect mice's motor coordination and balance ability. These results suggest that imbalanced RNA m6A methylation may lead to neurodegenerative lesions in the cerebellum of mice.

[Constructing the Bayesian network models to explore the factors related to glomerular and tubular injury].

Objective: To construct Bayesian network (BN) models to explore the factors related to glomerular injury (GI) and tubular injury (TI). Methods: A cross-sectional study was carried out. From April to November 2019, Shanxi Provincial People's Hospital performed an opportunistic screening for chronic kidney disease in 10 counties of Shanxi Province. The general data and laboratory results of blood and urine samples were collected. Chi-square test and logistic regression were used to explore the related factors of GI and TI, which were included in the construction of BN models with max-min hill-climbing (MMHC) algorithm. Results: A total of 12 269 participants were included, there were 5 198 males and 7 071 females, with a median age of 58 (40-91) years. The prevalence of GI and TI was 12.7% (1 561/12 269) and 11.6% (1 425/12 269), respectively. The BN model consisted of 8 nodes and 10 edges for GI, and 11 nodes and 17 edges for TI, respectively. BN models showed that age and glycated hemoglobin were direct related factors for GI, while gender and fasting blood glucose were indirect related factors for GI. Age, gender, fasting blood glucose and glycosylated hemoglobin were direct related factors for TI. Additionally, the area under the receiver operating characteristic curve (AUC) was 0.761 (95%CI: 0.746-0.777) and 0.753 (95%CI: 0.736-0.769) for GI and TI BN models, respectively. Conclusions: BN models allow for identifying the complex network relationships among the factors related to GI and TI. Meanwhile, Bayesian risk reasoning can provide reference value for the clinical prevention of GI and TI.

[Association of sleep duration and risk of frailty among the elderly over 80 years old in China: a prospective cohort study].

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q1, Q3) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.

Suvemcitug as second-line treatment of advanced or metastatic solid tumors and with FOLFIRI for pretreated metastatic colorectal cancer: phase Ia/Ib open label, dose-escalation trials.

BACKGROUND: Suvemcitug (BD0801), a novel humanized rabbit monoclonal antibody against vascular endothelial growth factor, has demonstrated promising antitumor activities in preclinical studies. PATIENTS AND METHODS: The phase Ia/b trials investigated the safety and tolerability and antitumor activities of suvemcitug for pretreated advanced solid tumors and in combination with FOLFIRI (leucovorin and fluorouracil plus irinotecan) in second-line treatment of metastatic colorectal cancer using a 3 + 3 dose-escalation design. Patients received escalating doses of suvemcitug (phase Ia: 2, 4, 5, 6, and 7.5 mg/kg; phase Ib: 1, 2, 3, 4, and 5 mg/kg plus FOLFIRI). The primary endpoint was safety and tolerability in both trials. RESULTS: All patients in the phase Ia trial had at least one adverse event (AE). Dose-limiting toxicities included grade 3 hyperbilirubinemia (one patient), hypertension and proteinuria (one patient), and proteinuria (one patient). The maximum tolerated dose was 5 mg/kg. The most common grade 3 and above AEs were proteinuria (9/25, 36%) and hypertension (8/25, 32%). Forty-eight patients (85.7%) in phase Ib had grade 3 and above AEs, including neutropenia (25/56, 44.6%), reduced leucocyte count (12/56, 21.4%), proteinuria (10/56, 17.9%), and elevated blood pressure (9/56, 16.1%). Only 1 patient in the phase Ia trial showed partial response, [objective response rate 4.0%, 95% confidence interval (CI) 0.1% to 20.4%] whereas 18/53 patients in the phase Ib trial exhibited partial response (objective response rate 34.0%, 95% CI 21.5% to 48.3%). The median progression-free survival was 7.2 months (95% CI 5.1-8.7 months). CONCLUSIONS: Suvemcitug has an acceptable toxicity profile and exhibits antitumor activities in pretreated patients with advanced solid tumors or metastatic colorectal cancer.