Individualized, dynamic, and full-course vancomycin dosing prediction: a study on the customized dose model.

Purpose: The single-point trough-based therapeutic drug monitoring (TDM) and Bayesian forecasting approaches are still limited in individualized and dynamic vancomycin delivery. Until recently, there has not yet been enough focus on the direct integration of pharmacokinetic/pharmacodynamic (PK/PD) and TDM to construct a customized dose model (CDM) for vancomycin to achieve individualized, dynamic, and full-course dose prediction from empirical to follow-up treatment. This study sought to establish CDM for vancomycin, test its performance and superiority in clinical efficacy prediction, formulate a CDM-driven full-course dosage prediction strategy to overcome the above challenge, and predict the empirical vancomycin dosages for six Staphylococci populations and four strains in patients with various creatinine clearance rates (CLcr). Methods: The PK/PD and concentration models derived from our earlier research were used to establish CDM. The receiver operating characteristic (ROC) curve, with the area under ROC curve (AUCR) as the primary endpoint, for 21 retrospective cases was applied to test the performance and superiority of CDM in clinical efficacy prediction by comparison to the current frequently-used dose model (FDM). A model with an AUCR of at least 0.8 was considered acceptable. Based on the availability of TDM, the strategy of CDM-driven individualized, dynamic, and full-course dose prediction for vancomycin therapy was formulated. Based on the CDM, Monte Carlo simulation was used to predict the empirical vancomycin dosages for the target populations and bacteria. Results: Four CDMs and the strategy of CDM-driven individualized, dynamic, and full-course dose prediction for vancomycin therapy from empirical to follow-up treatment were constructed. Compared with FDM, CDM showed a greater AUCR value (0.807 vs. 0.688) in clinical efficacy prediction. The empirical vancomycin dosages for six Staphylococci populations and four strains in patients with various CLcr were predicted. Conclusion: CDM is a competitive individualized dose model. It compensates for the drawbacks of the existing TDM technology and Bayesian forecasting and offers a straightforward and useful supplemental approach for individualized and dynamic vancomycin delivery. Through mathematical modeling of the vancomycin dosage, this study achieved the goal of predicting doses individually, dynamically, and throughout, thus promoting "mathematical knowledge transfer and application" and also providing reference for quantitative and personalized research on similar drugs.

Association between weekend catch-up sleep and depressive symptoms in American adults: Finding from NHANES 2017-2020.

BACKGROUND: The effect of weekend catch-up sleep (WCS) on depressive symptoms is inconsistent among different populations, with limited evidence in Americans. Therefore, we aimed to investigate the association between WCS and depressive symptoms in American adults. METHODS: We recruited 7719 participants from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Information on sleep duration and depressive symptoms were assessed by several self-reported questions and Patient Health Questionnaire-9 (PHQ-9), respectively. Then, WCS duration was calculated as weekend sleep duration minus weekday sleep duration, and WCS was further defined as WCS duration >0 h. Survey designed regression analyses were used to assess the association of WCS and depressive symptoms. RESULTS: In fully adjusted multivariate logistic regression models, the odds ratio (95 % confidence interval) for depressive symptoms and the ß (95 % confidence interval) for PHQ-9 score in response to WCS were 0.746 (0.462, 1.204; P = 0.218) and -0.429 (-0.900, 0.042; P = 0.073), respectively. Besides, the smooth relationship presented L-shaped, and only WCS duration of 0-2 h was statistically significantly associated with depressive symptoms or PHQ-9 score. Subgroup analyses showed that the negative associations were stronger among men, adults younger than 65 years, and those with short weekday sleep duration (P for interaction <0.05). LIMITATIONS: The cross-sectional design limits the capability for causal relationship between WCS and depressive symptoms. CONCLUSIONS: This study suggests that moderate WCS is associated with reduced odds of depressive symptoms, which provides additional epidemiological evidence for the effects of sleep on depressive symptoms.

Transcriptome and Proteome Association Analysis to Screen Candidate Genes Related to Salt Tolerance in Reaumuria soongorica Leaves under Salt Stress.

This work aims at studying the molecular mechanisms underlying the response of Reaumuria soongorica to salt stress. We used RNA sequencing (RNA-Seq) and Tandem Mass Tag (TMT) techniques to identify differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in R. soongorica leaves treated with 0, 200, and 500 mM NaCl for 72 h. The results indicated that compared with the 0 mM NaCl treatment group, 2391 and 6400 DEGs were identified in the 200 and 500 mM NaCl treatment groups, respectively, while 47 and 177 DEPs were also identified. Transcriptome and proteome association analysis was further performed on R. soongorica leaves in the 0/500 mM NaCl treatment group, and 32 genes with consistent mRNA and protein expression trends were identified. SYP71, CS, PCC13-62, PASN, ZIFL1, CHS2, and other differential genes are involved in photosynthesis, vesicle transport, auxin transport, and other functions of plants, and might play a key role in the salt tolerance of R. soongorica. In this study, transcriptome and proteome association techniques were used to screen candidate genes associated with salt tolerance in R. soongorica, which provides an important theoretical basis for understanding the molecular mechanism of salt tolerance in R. soongorica and breeding high-quality germplasm resources.

Projection of Premature Cancer Mortality in Hunan, China, Through 2030: Modeling Study.

BACKGROUND: The United Nations Sustainable Development Goals for 2030 include reducing premature mortality from noncommunicable diseases by one-third. Although previous modeling studies have predicted premature mortality from noncommunicable diseases, the predictions for cancer and its subcategories are less well understood in China. OBJECTIVE: The aim of this study was to project premature cancer mortality of 10 leading cancers in Hunan Province, China, based on various scenarios of risk factor control so as to establish the priority for future interventions. METHODS: We used data collected between 2009 and 2017 from the Hunan cancer registry annual report as empirical data for projections. The population-attributable fraction was used to disaggregate cancer deaths into parts attributable and unattributable to 10 risk factors: smoking, alcohol use, high BMI, diabetes, physical inactivity, low vegetable and fruit intake, high red meat intake, high salt intake, and high ambient fine particulate matter (PM2.5) levels. The unattributable deaths and the risk factors in the baseline scenario were projected using the proportional change model, assuming constant annual change rates through 2030. The comparative risk assessment theory was used in simulated scenarios to reflect how premature mortality would be affected if the targets for risk factor control were achieved by 2030. RESULTS: The cancer burden in Hunan significantly increased during 2009-2017. If current trends for each risk factor continued to 2030, the total premature deaths from cancers in 2030 would increase to 97,787 in Hunan Province, and the premature mortality (9.74%) would be 44.47% higher than that in 2013 (6.74%). In the combined scenario where all risk factor control targets were achieved, 14.41% of premature cancer mortality among those aged 30-70 years would be avoided compared with the business-as-usual scenario in 2030. Reductions in the prevalence of diabetes, high BMI, ambient PM2.5 levels, and insufficient fruit intake played relatively important roles in decreasing cancer premature mortality. However, the one-third reduction goal would not be achieved for most cancers except gastric cancer. CONCLUSIONS: Existing targets on cancer-related risk factors may have important roles in cancer prevention and control. However, they are not sufficient to achieve the one-third reduction goal in premature cancer mortality in Hunan Province. More aggressive risk control targets should be adopted based on local conditions.

One-off low-dose CT screening of positive nodules in lung cancer: A prospective community-based cohort study.

BACKGROUND: To improve the early stage diagnosis and reduce the lung cancer (LC) mortality for positive nodule (PN) population, data on effectiveness of PN detection using one-off low-dose spiral computed tomography (LDCT) screening are needed to improve the PN management protocol. We evaluate the effectiveness of PN detection and developed a nomogram to predict LC risk for PNs. METHODS: A prospective, community-based cohort study was conducted. We recruited 292,531 eligible candidates during 2012-2018. Individuals at high risk of LC based on risk assessment underwent LDCT screening and were divided into PN and non-PN groups. The effectiveness of PN detection was evaluated in LC incidence, mortality, and all-cause mortality. We performed subgroup analysis of characteristic variables for the association between PN and LC risk. A competing risk model was used to develop the nomogram. RESULTS: Participants (n = 14901) underwent LDCT screening; PNs were detected in 1193 cases (8·0%). After a median follow-up of 6·1 years, 193 were diagnosed with LC (1·3%). Of these, 94 were in the PN group (8·0%). LC incidence, mortality, and all-cause mortality were significantly higher in the PN group (adjusted hazard ratios: 10.60 (7.91-14.20), 7.97 (5.20-12.20), and 1.94 (1.51-2.50), respectively). Additionally, various PN characteristics were associated with an increased probability of developing LC. The C-index value of the nomogram for predicting LC risk of PN individuals was 0·847. CONCLUSIONS: The protocol of PNs management for improvement could focus on specific characteristic population and high-risk PN individuals by nomogram assessment.

Comparison of Colonoscopy, Fecal Immunochemical Test, and Risk-Adapted Approach in a Colorectal Cancer Screening Trial (TARGET-C).

BACKGROUND & AIMS: The screening yield and related cost of a risk-adapted screening approach compared with established screening strategies in population-based colorectal cancer (CRC) screening are not clear. METHODS: We randomly allocated 19,373 participants into 1 of the 3 screening arms in a 1:2:2 ratio: (1) one-time colonoscopy (n = 3883); (2) annual fecal immunochemical test (FIT) (n = 7793); (3) annual risk-adapted screening (n = 7697), in which, based on the risk-stratification score, high-risk participants were referred for colonoscopy and low-risk ones were referred for FIT. Three consecutive screening rounds were conducted for both the FIT and the risk-adapted screening arms. Follow-up to trace the health outcome for all the participants was conducted over the 3-year study period. The detection rate of advanced colorectal neoplasia (CRC and advanced precancerous lesions) was the main outcome. The trial was registered in the Chinese Clinical Trial Registry (number: ChiCTR1800015506). RESULTS: In the colonoscopy, FIT, and risk-adapted screening arms over 3 screening rounds, the participation rates were 42.4%, 99.3%, and 89.2%, respectively; the detection rates for advanced neoplasm (intention-to-treat analysis) were 2.76%, 2.17%, and 2.35%, respectively, with an odds ratio (OR)colonoscopy vs FIT of 1.27 (95% confidence interval [CI]: 0.99-1.63; P = .056), an ORcolonoscopy vsrisk-adapted screening of 1.17 (95% CI, 0.91-1.49; P = .218), and an ORrisk-adapted screeningvs FIT of 1.09 (95% CI, 0.88-1.35; P = .438); the numbers of colonoscopies needed to detect 1 advanced neoplasm were 15.4, 7.8, and 10.2, respectively; the costs for detecting 1 advanced neoplasm from a government perspective using package payment format were 6928 Chinese Yuan (CNY) ($1004), 5821 CNY ($844), and 6694 CNY ($970), respectively. CONCLUSIONS: The risk-adapted approach is a feasible and cost-favorable strategy for population-based CRC screening and therefore could complement the well-established one-time colonoscopy and annual repeated FIT screening strategies. (Chinese Clinical Trial Registry; ChiCTR1800015506).

The new 'coN' staging system combining lymph node metastasis and tumour deposit provides a more accurate prognosis for TNM stage III colon cancer.

OBJECTIVE: Despite controversy over its origin and definition, the significance of tumour deposit (TD) has been underestimated in the tumour node metastasis (TNM) staging system for colon cancer, especially in stage III patients. We aimed to further confirm the prognostic value of TD in stage III colon cancer and to establish a more accurate 'coN' staging system combining TD and lymph node metastasis (LNM). METHODS: Information on stage III colon cancer patients with a definite TD status was retrospectively collected from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2017. The effect of TD on prognosis was estimated using Cox regression analysis. Maximally selected rank statistics were used to select the optimal cut-off value of TD counts. The predictive power of conventional N staging and the new coN staging was evaluated and compared by Akaike's information criterion (AIC), Harrell's concordance index (C-index) and time-dependent receiver operating characteristic (ROC) curves. Clinicopathological data of stage III colon cancer patients in the Xiangya database from 2014 to 2018 were collected to validate the coN staging system. RESULTS: A total of 39,185 patients with stage III colon cancer were included in our study: 38,446 in the SEER cohort and 739 in the Xiangya cohort. The incidence of TD in stage III colon cancer was approximately 30% (26% in SEER and 30% in the Xiangya database). TD was significantly associated with poorer overall survival (OS) (HR = 1.37, 95% CI 1.31-1.44, p < 0.001 in SEER). The optimal cut-off value of TD counts was 4, and the patients were classified into the TD0 (count = 0), TD1 (count = 1-3) and TD2 (count ≥ 4) groups accordingly. The estimated 5-year OS was significantly different among the three groups (69.4%, 95% CI 68.8%-70.0% in TD0; 60.5%, 95% CI 58.9%-62.2% in TD1 and 42.6%, 95% CI 39.2%-46.4% in TD2, respectively, p < 0.001). The coN system integrating LNM and TD was established, and patients with stage III colon cancer were reclassified into five subgroups (coN1a, coN1b, coN2a, coN2b and coN2c). Compared with conventional N staging, the coN staging Cox model had a smaller AIC (197097.581 vs. 197358.006) and a larger C-index (0.611 vs. 0.601). The AUCs of coN staging at 3, 5 and 7 years were also greater than those of conventional N staging (0.6305, 0.6326, 0.6314 vs. 0.6186, 0.6197, 0.6160). Concomitant with the SEER cohort results, the coN staging Cox model of the Xiangya cohort also had a smaller AIC (2883.856 vs. 2906.741) and a larger C-index (0.669 vs. 0.633). Greater AUCs at 3, 5 and 7 years for coN staging were also observed in the Xiangya cohort (0.6983, 0.6774, 0.6502 vs. 0.6512, 0.6368, 0.6199). CONCLUSIONS: Not only the presence but also the number of TDs is associated with poor prognosis in stage III colon cancer. A combined N staging system integrating LNM and TD provides more accurate prognostic prediction than the latest AJCC N staging in stage III colon cancer.

Development and validation of tumor-size-stratified prognostic nomograms for patients with uterine sarcoma: A SEER database analysis.

BACKGROUND: Tumor-size-stratified analysis on the prognosis of uterine sarcoma is insufficient. This study aimed to establish the tumor-size-stratified nomograms to predict the 3- and 5-year overall survival (OS) of patients with uterine sarcoma. METHODS: The data analyzed in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. We collected data from patients with uterine sarcoma diagnosed between 2004 and 2015. According to the median tumor size of 7.8 cm, the enrolled patients were divided into two tumor size (TS) groups: TS <7.8 cm and TS ≥7.8 cm. Patients in each group were randomly divided into the training and validation cohorts with a ratio of 7:3. Chi-square test was used to compare differences between categorical variables. Multivariate Cox regression models were used to identify significant predictors. We calculated the concordance index (C-index) and the area under the receiver operating characteristics curve (AUC) to validate the nomograms. RESULTS: Compared with TS <7.8 cm group, TS ≥7.8 cm group had more patients of 45-64 years group, higher black race prevalence, higher proportion of myometrium tumor, higher stage, and higher grade; In the TS <7.8 cm training cohort, six variables (age, race, marital status, tumor primary site, stage, and grade) were identified as significantly associated with OS in multivariate analysis. However in the TS ≥7.8 cm training cohort, only four variables (surgery on primary site, tumor size, stage, and grade) were significantly identified; The C-index of two nomograms were 0.80 and 0.73 in training cohorts, respectively, and the AUC values for 3- and 5-year OS predictions in training cohorts were all above 0.80. Similar results were observed in validation cohorts. CONCLUSIONS: This study found that the significant prognostic factors were different between two tumor size groups of uterine sarcoma patients. The tumor-size-stratified nomograms, which we constructed and validated, might be useful to predict the probability of survival for patients with uterine sarcoma.

Association between dietary inflammatory index and oral cancer risk: A systematic review and dose-response meta-analysis.

Background: Dietary inflammatory index (DII) has been suggested to be associated with oral cancer risk. However, a quantitative comprehensive assessment of the dose-response relationship has not been reported. We performed a meta-analysis to clarify the risk of oral cancer with DII. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to 1 March 2022. Fixed- or random-effects models were utilized to estimate the pooled odds ratio (OR) of oral cancer with DII, as appropriate. Restricted cubic splines were used to model the dose-response relationship. Results: We included five case-control studies involving 1,278 cases and 5,137 controls in the meta-analysis. Risk of oral cancer was increased by 135% with the highest versus lowest DII level [OR: 2.35, 95% confidence interval (CI): 1.88-2.94], and 79% with higher versus lower DII level (OR: 1.79, 95% CI: 1.49-2.15). We found no evidence of a nonlinear dose-response association of DII with oral cancer (pnon-linearity = 0.752), and the risk was increased by 17% (OR: 1.17, 95% CI: 1.05-1.30) with 1 unit increment in DII score. Conclusion: This meta-analysis suggested that a higher DII score was associated with increased risk of oral cancer. Therefore, reducing pro-inflammatory components and promoting anti-inflammatory components of diet may be effective in the prevention of oral cancer.

Uptake of lung cancer screening with low-dose computed tomography in China: A multi-centre population-based study.

Background: Optimal uptake rates of low-dose computed tomography (LDCT) scans are essential for lung cancer screening (LCS) to confer mortality benefits. We aimed to outline the process model of the LCS programme in China, identify the high-risk individuals with low uptake based on a prospective multi-centre population-based cohort, and further explore associated structural characteristics. Methods: A total of 221,955 individuals at high-risk for lung cancer from the National Lung Cancer Screening cohort were included. The logistic regression model was performed to identify the individual characteristics associated with the uptake of LCS, defined as whether the high-risk individual undertook LDCT scans in designated hospitals within six months following the initial risk assessment. The linear regression model was adopted to explore the structural characteristics associated with the uptake rates in 186 communities. Findings: The overall uptake rate was 33·0%. The uptake rate was negatively correlated with the incidence of advanced-stage lung cancer (Pearson's coefficient -0·88, p-value 0·0007). Multivariable regression models found that lower uptake rates were associated with males (OR 0·88, 95%CI 0·85-0·91), current smokers (OR 0·93, 95%CI 0·90-0·96), individuals with depressive symptoms (OR 0·92, 95%CI 0·90-0·94), and the structural characteristics, including longer structural delays in initiating LDCT scans (30-90 days vs. ≤14 days: ß -7·17, 95%CI -12·76∼ -1·57; >90 days vs. ≤14 days: ß -13·69, 95%CI -24·61∼ -2·76), no media-assisted publicity (ß -6·43, 95%CI -11·26∼ -1·60), and no navigation assistance (ß -5·48, 95%CI -10·52∼ -0·44). Interpretation: Multifaceted interventions are recommended, which focus on poor-uptake individuals and integrate the 'assessment-to-timely-screening' approach to minimise structural delays, media publicity, and a navigation assistance along the centralised screening pathway. Funding: Ministry of Finance and National Health Commission of the People's Republic of China.

Associations of depressive symptoms and chronic diseases with activities of daily living among middle-aged and older population in China: A population-based cohort study.

Background: Activities of daily living (ADL) disability is a concern in the aging population and can lead to increased health service demands and lower quality of life. The aim of this longitudinal study was to assess the associations of chronic conditions and depressive symptoms with ADL disability. Methods: This prospective cohort study used two waves of data (2011 and 2015) from the China Health and Retirement Longitudinal Study (CHARLS). A total of 10,864 participants aged 45 and older were included for analysis. Chronic diseases were assessed by self-report and depressive symptoms were assessed using the validated 10-item of Center for Epidemiologic Studies Depression Scale at baseline. Incidents of ADL disability during follow-up were assessed using the Katz ADL scales. Results: After 4 years of follow-up, there were 704 participants incidents of ADL disability. The incident rate was 17.22 per 1,000 person-years. Having at least one chronic disease was independently associated with a 39% increased risk of incident ADL disability (adjusted HR, 1.39; 95%CI: 1.16, 1.67). The presence of depression symptoms was independently associated with a 54% increased risk of incident ADL disability (adjusted HR, 1.54; 95%CI: 1.30, 1.82). However, there was no significant additive interaction effect between chronic diseases and depressive symptoms on ADL disability. Conclusion: Chronic diseases and depressive symptoms are associated with an increased risk of ADL disability in middle-aged and older Chinese adults. Improving chronic diseases and depressive symptoms can prevent ADL disability.

Cervical cancer prognosis and related risk factors for patients with cervical cancer: a long-term retrospective cohort study.

This study aims to explore the recurrence rate and overall survival for patients with cervical cancer after the first treatment and the related risk factors. A retrospective cohort study was conducted on cervical cancer patients enrolled in a cancer specialist hospital in Hunan Province, China from January 1992 to December 2005 and followed up until December 2010. Kaplan-Meier survival analysis was used to estimate the cumulative recurrence rate, and Cox proportional hazards model was utilized to identify risk factors associated with prognosis. A total of 4358 patients were enrolled with a median follow-up of 7.4 years (range 5-19 years), and 372 (8.5%) patients had cancer recurrence. The cumulative recurrence rate showed a rapid increase from 3.8% in the first year after discharge to 8.0% in the fifth year, and the recurrence rate remained relatively stable afterward reaching 9.7% and 10.8% in the 10th and the 15th year, respectively. The median time to recurrence was 15.5 months with an IQR of 5.5-40.0 months. The Cox regression showed that miscarriage, clinical stage, and treatment received were significantly associated with cervical cancer recurrence after adjustment for confounders. Patients with recurrence showed a significantly higher risk for mortality than those without recurrence (HR 2.79, 95% CI 2.42-3.22). This study depicted the long-term recurrence rate and survival after recurrence for patients with cervical cancer after the first treatment, and reported time to recurrence and risk factors related to recurrence. These findings may provide important evidence for designing targeted interventions for the treatment of cervical cancer.

One-off low-dose CT for lung cancer screening in China: a multicentre, population-based, prospective cohort study.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. Data on the effectiveness of one-off low-dose CT (LDCT) in reducing lung cancer mortality and all-cause mortality are needed to inform screening programmes in countries with limited medical resources. We aimed to evaluate the effectiveness of one-off LDCT screening in the early detection of lung cancer in China. METHODS: A multicentre, population-based, prospective cohort study was done in 12 cities of eight provinces across China, recruiting individuals aged 40-74 years who were asymptomatic for lung cancer with no lung cancer history. Participants were classified as at high risk or low risk of lung cancer using a sex-specific risk score that incorporated cigarette smoking, level of physical activity, occupational exposures, history of chronic respiratory diseases, family history of lung cancer, diet, and passive smoking (women only). Participants at high risk were invited for a one-off LDCT scan and were classified into screened and non-screened groups on the basis of whether or not they had the scan. Lung cancer incidence density, lung cancer mortality, and all-cause mortality were calculated for the screened and non-screened groups. The effectiveness of a one-off LDCT scan was evaluated by a comparison of the screened and non-screened groups in terms of lung cancer mortality and all-cause mortality in the period from cohort entry until administrative censoring (June 20, 2020). Inverse probability weighting was adopted to account for potential imbalanced factors between the two groups and Cox proportional hazards model was used to estimate the weighted associations between mortality and one-off LDCT scans. FINDINGS: Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 individuals were assessed for eligibility. 1 016 740 participants were enrolled in the study, of whom 3581 had a lung cancer diagnosis after a median follow-up of 3·6 years (IQR 2·8-5·1). Among the 223 302 participants at high risk, 79 581 (35·6%) had an LDCT scan (screened group) and 143 721 (64·4%) did not (non-screened group). After inverse probability weighting, lung cancer incidence density was 47·0% higher (hazard ratio 1·47 [95% CI 1·27-1·70]; p<0·0001), lung cancer mortality was 31·0% lower (0·69 [95% CI 0·53-0·92]; p=0·010) and all-cause mortality was 32·0% lower (0·68 [0·57-0·82]; p<0·0001) for participants in the screened group compared with those in the non-screened group. INTERPRETATION: One-off LDCT screening was associated with significantly lower lung cancer mortality and all-cause mortality in a large population in China. Our results point to the promise of one-off LDCT screening in countries with limited medical resources. Further studies are needed to explore interactions by subgroup-including sex, age, smoking status, and economic status-to develop population-specific screening strategies. FUNDING: Ministry of Finance and National Health Commission of the People's Republic of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Physiological response and proteomics analysis of Reaumuria soongorica under salt stress.

Soil salinity can severely restrict plant growth. Yet Reaumuria soongorica can tolerate salinity well. However, large-scale proteomic studies of this plant's response to salinity have yet to reported. Here, R. soongorica seedlings (4 months old) were used in an experiment where NaCl solutions simulated levels of soil salinity stress. The fresh weight, root/shoot ratio, leaf relative conductivity, proline content, and total leaf area of R. soongorica under CK (0 mM NaCl), low (200 mM NaCl), and high (500 mM NaCl) salt stress were determined. The results showed that the proline content of leaves was positively correlated with salt concentration. With greater salinity, the plant fresh weight, root/shoot ratio, and total leaf area increased initially but then decreased, and vice-versa for the relative electrical conductivity of leaves. Using iTRAQ proteomic sequencing, 47 177 136 differentially expressed proteins (DEPs) were identified in low-salt versus CK, high-salt versus control, and high-salt versus low-salt comparisons, respectively. A total of 72 DEPs were further screened from the comparison groupings, of which 34 DEPs increased and 38 DEPs decreased in abundance. These DEPs are mainly involved in translation, ribosomal structure, and biogenesis. Finally, 21 key DEPs (SCORE value ≥ 60 points) were identified as potential targets for salt tolerance of R. soongolica. By comparing the protein structure of treated versus CK leaves under salt stress, we revealed the key candidate genes underpinning R. soongolica's salt tolerance ability. This works provides fresh insight into its physiological adaptation strategy and molecular regulatory network, and a molecular basis for enhancing its breeding, under salt stress conditions.

Effect of salt stress on the photosynthetic characteristics and endogenous hormones, and: A comprehensive evaluation of salt tolerance in Reaumuria soongorica seedlings.

Salinity is a major limiting factor in desert ecosystems, where Reaumuria soongarica is a dominant species. It is crucial to study the growth and physiological response mechanisms of R. soongorica under salt stress for the protection and restoration of the desert ecosystems. However, the effects of salt concentration and stress duration on endogenous hormonal content and photosynthetic efficiency and salt injury index of R. soongorica leaves have not been reported. Currently, there is no systematic evaluation system to determine physiological adaptation strategies of R. soongorica seedlings in response to salt stress. In this study, simulation experiments were performed with NaCl solution mixed with soil. Enzyme-linked immunosorbent assay and LI-6800 portable photosynthesis analyzer were used to measure indole acetic acid (IAA), corn nucleoside hormone (ZR), abscisic acid (ABA), and photosynthesis-related parameters in leaves of R. soongorica seedlings at 0 (24-48 h after salt treatment), 3, 6, and 9 days. At the same time, growth indicators (salt injury index, root-to-shoot ratio), reactive oxygen species content, superoxide dismutase enzyme (SOD) activity, osmolyte content, membrane peroxidation, and leaf pigment content were measured at different salt concentrations and treatment times. Finally, principal component analysis and membership function method were used to comprehensively evaluate the salt tolerance of seedlings. The results showed that treatment with 200 mM NaCl for 3 days significantly increased SOD activity, the content of osmotic adjustment substances (proline, soluble protein), endogenous hormone content (ABA, ZR), root-to-shoot ratio, and Chla/Chlb values but decreased malondialdehyde content (MDA) in the leaves of R. soongorica seedlings. Leaf water content (LRWC), net photosynthetic rate (Pn), transpiration rate (Tr), water use efficiency (WUE), and IAA content in R. soongorica seedlings were lower than those in the control, when exposed to 400 and 500 mM NaCl solutions. Finally, the principal component analysis revealed endogenous hormone content and antioxidant enzyme activity to be useful for the comprehensive evaluation of salt tolerance in R. soongorica seedlings. The R. soongorica seedlings showed the strongest salt tolerance when exposed to 200 mM NaCl for 3 days. This study provides a theoretical foundation for gene mining and breeding of salt-tolerant species in the future.

Influencing factors and risk prediction model for cervical cancer recurrence. / å®«é¢ˆç™Œå¤å‘çš„å½±å“å› ç´ åŠé£Žé™©é¢„æµ‹æ¨¡åž‹.

OBJECTIVES: Cervical cancer is the most common malignant tumor in the female reproductive system worldwide. The recurrence rate for the treated cervical cancer patients is high, which seriously threatens women's lives and health. At present, the risk prediction study of cervical cancer has not been reported. Based on the influencing factors of cervical cancer recurrence, we aim to establish a risk prediction model of cervical cancer recurrence to provide a scientific basis for the prevention and treatment of cervical cancer recurrence. METHODS: A total of 4 358 cervical cancer patients admitted to the Hunan Cancer Hospital from January 1992 to December 2005 were selected as research subjects, and the recurrence of cervical cancer patients after treatment was followed up. Univariate analysis was used to analyze the possible influencing factors. Variables that were significant in univariate analysis or those that were not significant in univariate analysis but may be considered significant were included in multivariate Cox regression analysis to establish a cervical cancer recurrence risk prediction model. Line graphs was used to show the model and it was evaluated by using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis. RESULTS: Univariate analysis showed that the recurrence rates of cervical cancer patients with different age, age of menarche, parity, miscarriage, clinical stage, and treatment method were significantly different (all P<0.05). Multivariate Cox regression analysis showed that RR=-0.489×(age≥55 years old)+0.481×(age at menarche >15 years old)+0.459×(number of miscarriages≥3)+0.416×(clinical stage II)+0.613×(clinical stage III/IV)+0.366×(the treatment method was surgery + chemotherapy) + 0.015×(the treatment method was chemotherapy alone). The area under the ROC curve (AUC) of the Cox risk prediction model for cervical cancer recurrence constructed was 0.736 (95% CI 0.684 to 0.789), the best prediction threshold was 0.857, the sensitivity was 0.576, and the specificity was 0.810. The accuracy of the Cox risk model constructed by this model was good. From the clinical decision curve, the net benefit value was high and the validity was good. CONCLUSIONS: Patient age, age at menarche, miscarriages, clinical stages, and treatment methods are independent factors affecting cervical cancer recurrence. The Cox proportional hazards prediction model for cervical cancer recurrence constructed in this study can be better used for predicting the risk of cervical cancer recurrence.

Menstrual factors, reproductive history, and risk of lung cancer: a multi-center population-based cohort study in Chinese females.

BACKGROUND: Female menstrual and reproductive factors, as remarkable indicators of hormone effect, were hypothesized to be associated with lung cancer risk, whereas the existed epidemiological evidence was inconsistent. Our study aims to investigate the association between menstrual and reproductive factors and lung cancer risk based on the Chinese Lung Cancer Screening Program. METHODS: This study was based on a large-scale multi-center population cohort across China recruiting individuals aged 40-74 years old between 2013-2018. Cox regression model was applied to estimate the HRs and 95% CIs. Restricted cubic spline (RCS) analysis was used to estimate dose-response relationships and test for nonlinear associations. RESULTS: Among 553,434 female participants, 1,529 incident lung cancer cases were identified with a median follow-up of 3.61 years. With adjustment for multiple covariates and all significant hormonal factors, elevated lung cancer risk was associated with later age (15, or ≥16 years) at menarche (HR =1.27, 95% CI: 1.04-1.56; HR =1.45, 95% CI: 1.19-1.76), later age (25-29, or ≥30 years) at first live birth (HR =1.27, 95% CI: 1.13-1.43; HR =1.23, 95% CI: 1.00-1.51), and benign breast disease history (HR =1.25, 95% CI: 1.10-1.41). For postmenopausal females specifically, surgical menopause (HR =1.62; 95% CI: 1.29-2.05) and other surgeries on the reproductive system (HR =1.19; 95% CI: 1.01-1.40) both appeared to be predictive of elevated lung cancer risk. Concerning age at menopause, a nonlinear association was observed (P-nonlinear =0.0126). Increased lung cancer risk was observed among females with age at menopause especially above 50. Although we observed no significant associations between longer time (≥13 months) of breastfeeding and lung cancer risk among all participants (HR =0.86; 95% CI: 0.71-1.04), significant decreased adenocarcinoma risk (HR =0.65; 95% CI: 0.53-0.81) was noted among nonsmoking females. CONCLUSIONS: Our findings add some support for the role of menstrual and reproductive factors in lung carcinogenesis. However, these relationships were complex, and required further investigations addressing the biological mechanisms.

Development and external validation of a nomogram to predict the risk of Upper gastrointestinal precancerous lesions in a non-high-incidence area.

BACKGROUND: Upper gastrointestinal precancerous lesions (UGPL) is the major preventable disease in non-high-incidence area. A prognostic nomogram was constructed to predict and identity susceptible population of UGPL before endoscope screening. METHODS: We recruited 300 ,016 eligible participants for upper gastrointestinal cancer (UGC) screening aged 40-74 years from two cities in Hunan province from 2012 to 2019. Individuals at high risk of UGC on basis of questionnaire estimation underwent endoscopic screening. Participants in two cities accepting endoscopy were used as training and external validation cohorts, respectively. A nomogram was developed based on independent prognostic factors of UGPL determined in multivariable logistic regression analysis. RESULTS: Of 35, 621 with high risk for UGC, 10, 364 subjects undertook endoscopy (participation rate of 29.1%). The detection rate for UGPL was 4.55%. The nomogram showed that age, gender, mental trama, picked food, and atrophic gastritis history in a descending order were significant contributors to UGPL risk. The C-index value of internal and external validation of the model is 0.612 and 0.670, respectively. The calibration data for UGPL showed optimal agreement between the nomogram prediction and actual observation. Furthermore, high-risk and low-risk group divided based on score from the nomogram predicted a significantly distinct detection rate. CONCLUSION: The nomogram provides screening workers a simple and accurate tool for identifying individuals at a higher risk of UGPL as primary screening before endoscopy among Chinese population in non-high-risk areas, thus reducing the incidence of UGC by improving the UGPL detection.

LINC00657 promotes colorectal cancer stem-like cell invasion by functioning as a miR-203a sponge.

Recently, the role of long non-coding RNAs (lncRNAs) in regulating multiple cancer types has attracted increasing interest because of their involvement in cell metastasis in different cancer types. Previous studies indicated that LINC00657 may work as an oncogene in gastric and colon cancer. However, the functional role and mechanistic action of LINC00657 on colorectal cancer (CRC) remains unknown. Therefore, in this study, the role of LINC00657 in CRC was evaluated. Our results showed that LINC00657 was enriched in CRC stem-like cells (CSCs) and significantly promoted CSCs invasion ability. LINC00657 expression resulted frequently up-regulated in CRC patient tissue, and high expression of LINC00657 was correlated with an advanced clinical stage, lymph node metastasis, distant metastasis and poor overall survival of CRC patients. Furthermore, LINC00657 worked as a competing endogenous RNA (ceRNA) for miR-203a, antagonizing its function as a tumor suppressor and leading to the de-repression of CSCs invasion. Collectively, our observations revealed that LINC00657 is involved in CRC invasion by acting as a competing endogenous RNA. Thus, LINC00657 may serve as a potential prognostic factor and/or therapeutic target for CRC.