Analysis of High-Risk Factors and Construction of a Nomogram Predictive Model for Deep Venous Thrombosis in Pelvic and Acetabular Fracture Patients Treated Conservatively.

PURPOSE: This study aims to develop a predictive nomogram model to assist physicians in making evidence-based decisions and potentially reduce the incidence of deep venous thrombosis (DVT). METHODS: We conducted a retrospective study, including patients admitted to the hospital from January 2014 to January 2022 with a closed, single pelvic or acetabular fracture. Comprehensive data were collected for each patient, encompassing demographics, injury characteristics, comorbidities, and results from laboratory tests and lower extremity ultrasounds. Potential risk factors were identified by univariate and multivariate logistic regression analyses. The predictive model was constructed and then internally validated. Calibration accuracy was assessed using a calibration slope and the Hosmer-Lemeshow goodness-of-fit test. The discrimination of the nomogram model was evaluated using the C-statistic. RESULTS: Out of 232 individuals who underwent conservative treatment, 57 (24.6%) were classified into the DVT group and 175 (75.4%) into the non-DVT group based on lower extremity ultrasound findings. Predominantly, patients were aged between 41 and 65 in both groups. Body mass index (BMI) comparison showed that 54.29% (95/175) of the non-DVT group fell within the healthy weight range, while 45.61% (26/57) in the DVT group were overweight. Notably, the proportion of obesity in the DVT group was more than double that in the non-DVT group, indicating a higher DVT risk with increasing BMI (P=0.0215). Lower red blood cell (RBC) counts were observed in DVT patients compared to non-DVT ones (P<0.001). A similar pattern emerged for D-dimer, a marker for blood clot formation and dissolution, with significant differences noted (P=0.029). Multivariable analysis identified age, BMI, associated organ injury (AOI), American Society of Anesthesiologists score, hemoglobin (HGB), RBC, and D-dimer as candidate predictors. Significant variables included age (OR, 3.04; 95% CI, 1.76-5.26; P<0.001), BMI (OR, 1.97; 95% CI, 1.22-3.18; P=0.006), AOI (OR, 2.05; 95% CI, 1.07-3.95; P=0.031), and HGB (HR, 0.59; 95% CI, 0.39-0.88; P=0.010). The discrimination was 0.787, with a corrected c-index of 0.753. Calibration plots and the Hosmer-Lemeshow test indicated a good fit (P=0.7729). Decision curve analysis revealed a superior net clinical benefit when the predicted probability threshold ranged from 0.05 to 0.95. CONCLUSIONS: We developed a nomogram predictive model, and it could act as a practical tool in clinical workflows to assist physicians in making favorable medical decisions, which potentially reduces the incidence of DVT in those patients with pelvic and acetabular fractures treated conservatively.

[Relationship between the percentage of energy intake from macronutrients and obesity among adult residents in 15 provinces of China in 1991-2018].

OBJECTIVE: To explore the relationship between the percentage of energy intake from macronutrients and obesity in Chinese adult residents, and analyze the cut-off values of macronutrients for predicting obesity. METHODS: Data was collected in China Health and Nutrition Survey(CHNS)in 1991-2018. Adults who participated in at least two waves of the surveys and were not obese at baseline were selected as the study subjects. Obesity was defined as body mass index(BMI)≥28.0 kg/m~2. Generalized estimating equation was used to analyze the relationship between the percentage of energy intake from macronutrients and BMI and obesity, and receiver operating characteristic curve(ROC) was used to analyze the cut-off values of percentage of energy intake from macronutrients to predict obesity. RESULTS: The percentage of energy intake from protein and fat of adult residents in 15 provinces(autonomous regions and municipalities) in China showed an increasing trend(P<0.01), and the percentage of energy intake from carbohydrate showed a decreasing trend(P<0.01) between 1991 and 2018. After adjusting for covariates, the group of percentage of energy intake from fat in 20%～30%(ß=0.05, 95%CI 0.01-0.08)and ≥30%(ß=0.15, 95%CI 0.11-0.18)were positively correlated with BMI compared with the group of percentage of energy intake from fat <20%, and the risk of obesity in 20%-30% and ≥ 30% was increased by 17%(OR=1.17, 95%CI 1.04-1.31)and 6%(OR=1.06, 95%CI 1.24-1.56), respectively. Compared with the group of the percentage of energy intake from carbohydrate < 50%, the group of 50% to 65%(ß=-0.08, 95% CI-0.11--0.05) and ≥ 65%(ß=-0.17, 95%CI-0.20--0.13) was negatively correlated with BMI, and the percentage of energy intake from carbohydrate ≥ 65% reduced the risk of obesity(OR=0.71, 95%CI 0.63-0.80). CONCLUSION: Carbohydrate intake was inversely correlated with the risk of obesity, and fat intake was positively correlated with the risk of obesity. Moderate intake of carbohydrates and reduced fat intake can prevent obesity.

USP26 promotes colorectal cancer tumorigenesis by restraining PRKN-mediated mitophagy.

Deubiquitinating enzymes (DUBs) are promising targets for cancer therapy because of their pivotal roles in various physiological and pathological processes. Among these, ubiquitin-specific peptidase 26 (USP26) is a protease with crucial regulatory functions. Our study sheds light on the upregulation of USP26 in colorectal cancer (CRC), in which its increased expression correlates with an unfavorable prognosis. Herein, we evidenced the role of USP26 in promoting CRC tumorigenesis in a parkin RBR E3 ubiquitin-protein ligase (PRKN) protein-dependent manner. Our investigation revealed that USP26 directly interacted with PRKN protein, facilitating its deubiquitination, and subsequently reducing its activity. Additionally, we identified the K129 site on PRKN as a specific target for USP26-mediated deubiquitination. Our research highlights that a K-to-R mutation at the site on PRKN diminishes its potential for activation and ability to mediate mitophagy. In summary, our findings underscore the significance of USP26-mediated deubiquitination in restraining the activation of the PRKN-mediated mitophagy pathway, ultimately driving CRC tumorigenesis. This study not only elucidated the multifaceted role of USP26 in CRC but also introduced a promising avenue for therapeutic exploration through the development of small molecule inhibitors targeting USP26. This strategy holds promise as a novel therapeutic approach for CRC.

SOD1-high fibroblasts derived exosomal miR-3960 promotes cisplatin resistance in triple-negative breast cancer by suppressing BRSK2-mediated phosphorylation of PIMREG.

Platinum-based neoadjuvant therapy represented by cisplatin is widely employed in treating Triple-Negative Breast Cancer (TNBC), a particularly aggressive subtype of breast cancer. Nevertheless, the emergence of cisplatin resistance presents a formidable challenge to clinical chemotherapy efficacy. Herein, we revealed the critical role of tumor microenvironment (TME) derived exosomal miR-3960 and phosphorylation at the S16 site of PIMREG in activating NF-κB signaling pathway and promoting cisplatin resistance of TNBC. Detailed regulatory mechanisms revealed that SOD1-upregulated fibroblasts secrete miR-3960 and are then transported into TNBC cells via exosomes. Within TNBC cells, miR-3960 targets and inhibits the expression of BRSK2, an AMPK protein kinase family member. Furthermore, we emphasized that BRSK2 contributes to ubiquitination degradation of PIMREG and modulates subsequent activation of the NF-κB signaling pathway by mediating PIMREG phosphorylation at the S16 site, ultimately affects the cisplatin resistance of TNBC. In conclusion, our research demonstrated the crucial role of SOD1high fibroblast, exosomal miR-3960 and S16 site phosphorylated PIMREG in regulating the NF-κB signaling pathway and cisplatin resistance of TNBC. These findings provided significant potential as biomarkers for accurately diagnosing cisplatin-resistant TNBC patients and guiding chemotherapy strategy selection.

A phase I study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer.

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics, tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients. Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles. Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks. Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea (85.7%), vomiting (28.6%), nausea (25.0%) and decreased appetite (17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response (CR), and three achieved partial response (PR). The objective response rate (ORR) and disease control rate (DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival (PFS) was 3.98 months. Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase III trial (No. NCT05122494).

[Trends of eating out among males in China and its correlation with nutrition and health during 2000 to 2018].

OBJECTIVE: To analyze the trend of eating out among Chinese male adults and explore the association between eating out and dietary nutrition and health. METHODS: Males aged 18 and above with complete data were selected from China Health and Nutrition Survey 2000, 2004, 2006, 2009, 2011, 2015 and 2018. Eating out behavior was defined as having consumption of food prepared outside the home during the three consecutive 24-h dietary recalls period. Cochran-Armitage trend test was used to analyze the trend of prevalence of eating out and the energy contribution from eating out foods in males from 2000 to 2018. Analysis of covariance was used to compare the differences in several food and dietary nutrient intakes and nutritional indicators by eating out in 2018. RESULTS: The prevalence of eating out among Chinese male adults increased from 48.49% in 2000 to 57.51% in 2018, showing an increased trend followed by a decreased trend. Males in the 18-29 years old group, urban group, high income group, and high education level group had a higher rate of eating out(P<0.05). The energy contribution from eating out foods increased from 21.80% in 2000 to 28.77% in 2018, showing a slow upward trend. In 2018, the intake of rice, tubers and vegetables was lower in the eating out group, while intake of wheat, fruits, livestock and poultry meat, aquatic products, eggs and milk in eating out group was higher than those in the non-eating out group(P<0.05). The eating out group had a higher intake of energy, fat, protein, cholesterol, calcium, zinc, vitamin B_1 and vitamin B_2 than the non-eating out group(P<0.05). The eating out group had lower levels of systolic blood pressure, HDL-C, blood glucose and glycosylated hemoglobin than the counterparts. The levels of BMI, waist, body fat percentage, diastolic blood pressure and TG were higher in the eating out group than in the non-eating out group. CONCLUSION: From 2000 to 2011, the eating out rate of males in China showed an upward trend, and a downward trend after 2011. At the same time, the energy contribution of eating out foods is increasing. Eating out was associated with major food and nutrients intake and indicators of nutritional status in male adults.

[Changes in mild cognitive impairment and sociodemographic disparity among adults aged 55 years and above in 4 provinces of China].

OBJECTIVE: To investigate the changes in mild cognitive impairment(MCI) and sociodemographic disparity among adults aged 55 years and above in 4 provinces of China. METHODS: A total of 4687 adults aged 55 years and above from Community-based Cohort Study on Nervous System Disease who did not have Alzheimer's disease, participated in both rounds of the survey, and had complete baseline sociodemographic data and two rounds of data on cognitive function were selected. Generalized estimation equations were used to analyse the effect of sociodemographic factors on MCI. RESULTS: The detection rates of MCI in adults aged 55 years and above without Alzheimer's disease in 4 provinces of China in 2018 and 2020 were 48.56% and 42.56% respectively. MCI occurred in 30.11% of those with normal cognition(NC) at baseline, and 44.24% of those with MCI at baseline reverted to NC. The risk of MCI increased and the likelihood of MCI reversion decreased with increasing age and decreasing per capita monthly household income. In the baseline NC population, the risk of MCI in the junior high school and above group was 35% lower than that in the illiterate group(RR=0.65, 95%CI 0.53-0.80), the risk of MCI was lower in those living in rural areas(RR=0.56, 95%CI 0.49-0.65), and the risk of MCI was 1.17 times(95%CI 1.03-1.32) higher in those with a history of chronic diseases than in those without it. In the baseline MCI population, the likelihood of MCI reversion increased with education, the likelihood of MCI reversion was 1.04 times higher for workers than for non-workers(95%CI 1.00-1.08). CONCLUSION: The incidence and reversal rates of MCI were high in adults aged ≥55 years in four provinces of China. Advanced age, low education and low income level are risk factors for cognitive dysfunction.

[Epidemiological characteristics of cardio-metabolic risk factors in women aged 15-49 years in 4 provinces of China in 2018].

OBJECTIVE: To analyze the prevalence of cardio-metabolic(CM) risk in women aged 15-49 years in 4 provinces of China and the influence of socioeconomic factors on them. METHODS: A total of 2851 women aged 15-49 years from Community-based Cohort Study on Nervous System Disease in 2018 were selected. Obesity, central obesity, elevated triglyceride(TG), elevated total cholesterol(TC), decreased high-density lipoprotein cholesterol(HDL-C), elevated low-density lipoprotein cholesterol(LDL-C), elevated blood pressure, elevated blood glucose and risk factor aggregation were analyzed. χ~2 test was used for univariate analysis, multinomial Logit model was used to evaluate the relationship between socioeconomic factors and CM risk factors, and Cochran-Armitage trend test was used for trend analysis. RESULTS: The detection rate of CM risk factors in this study from high to low were central obesity(26.76%), overweight(22.41%), pre central obesity(17.47%), decreased HDL-C(15.36%), elevated TG(11.78%), borderline elevated TC(11.40%), borderline elevated TG(11.12%), elevated blood pressure(9.71%) and hypertension(9.12%). The prevalence rates of CM risk factors were different among different age groups, income groups and education levels(P<0.05). In addition to decreased HDL-C, the prevalence of other metabolic risk factors increased with age(P_(trend)<0.05). With the improvement of educational level, the prevalence rates of overweight, obesity, central obesity, central obesity, elevated TG, decreased HDL-C, elevated blood pressure, hypertension, elevated blood pressure and diabetes showed a downward trend(P_(trend)<0.05). Multinomial Logit model showed that the rick of metabolic risk factors in the age group of 40 to 49 years old was higher than that in the younger age group aged 15-29 years, and was more significant in hypertension, elevated blood pressure and elevated blood glucose, which were 8.51 times(95% CI 5.45-13.27), 3.14 times(95%CI 2.20-4.48)and 2.66(95% CI 1.52-4.66)times of the younger age group, respectively. Women with high-income level have a higher risk of borderline elevated TC, elevated TC and borderline elevated LDL-C(OR=1.85, 95% CI 1.44-2.38;OR=2.01, 95% CI 1.25-3.22;OR=2.16, 95% CI 1.61-2.90), but the lower risk of overweight and elevated blood pressure(OR=0.79, 95% CI 0.64-0.98;OR=0.69, 95% CI 0.50-0.94). The risk of obesity, hypertension and diabetes of people with college degree or above was about 50% lower than those with junior high school education or below(OR=0.52, 95% CI 0.35-0.78;OR=0.43, 95% CI 0.27-0.67; OR=0.52, 95% CI 0.28-0.96). CONCLUSION: Central obesity, overweight, pre central obesity and HDL-C decrease were prominent CM risk factors in women aged 15-49 years in four provinces of China in 2018. The detection rate of CM risk factors is higher in women of high age group or low education level.

[Application of Delphi method in the revision of dietary quality index in the elderly].

OBJECTIVE: To revise the dietary evaluation method of the elderly, and scientifically evaluate the dietary quality. METHODS: Delphi method was used to revise a diet quality evaluation method for the elderly according to expert consultation and statistical analysis. The recommended recipes in The Dietary Guidelines for Chinese Residents(2016) were selected for preliminary verification. RESULTS: Two rounds of expert consultation were conducted, 25 experts in the industry were invited. The withdraw rate of two rounds were 100% and 84%, respectively. The authoritative coefficient were 0.82 and 0.80, the degree of familiarity was 0.92, and the basis for determination were 0.73 and 0.70, respectively. The coordination coefficient W value were 0.095 and 0.098 respectively. CONCLUSION: Delphi method had some advantages in the revision of dietary index for the elderly. Dietary quality index had some practicability, but it still needs further verification and improvement.

Longitudinal Relationship between the Percentage of Energy Intake from Macronutrients and Overweight/Obesity among Chinese Adults from 1991 to 2018.

To investigate the prospective relationship between macronutrient intake and overweight/obesity, data were collected in the China Health and Nutrition Survey (CHNS) from 1991 to 2018. Adults who participated in at least two waves of the survey and were not obese at baseline were selected as the study subjects. A total of 14,531 subjects were finally included with complete data. Overweight/obesity was defined as a body mass index (BMI) ≥ 24.0 kg/m2. The generalized estimating equation (GEE) was used to analyze the relationship between the percentage of energy intake from macronutrients and BMI and overweight/obesity. The percentages of energy intake from protein and fat showed an increasing trend (p < 0.01), and the percentage of energy intake from carbohydrate showed a decreasing trend (p < 0.01) among Chinese adults between 1991 and 2018. Adjusting for covariates, the energy intake from fat was positively correlated with BMI, while the energy intake from carbohydrates was negatively correlated with BMI. The percentage of energy intake from non-high-quality protein and polyunsaturated fatty acids (PUFA) were positively correlated with overweight/obesity. In contrast, monounsaturated fatty acids (MUFA) and high-quality carbohydrates were negatively correlated with overweight/obesity. In short, fat, non-high-quality protein, saturated fatty acids (SFA), and PUFA were positively correlated with the risk of obesity, whereas higher carbohydrate, MUFA, and high-quality carbohydrate intake were associated with a lower risk of obesity. Obesity can be effectively prevented by appropriately adjusting the proportion of intake from the three major macronutrients.

Diet Mediate the Impact of Host Habitat on Gut Microbiome and Influence Clinical Indexes by Modulating Gut Microbes and Serum Metabolites.

The impact of external factors on the human gut microbiota and how gut microbes contribute to human health is an intriguing question. Here, the gut microbiome of 3,224 individuals (496 with serum metabolome) with 109 variables is studied. Multiple analyses reveal that geographic factors explain the greatest variance of the gut microbiome and the similarity of individuals' gut microbiome is negatively correlated with their geographic distance. Main food components are the most important factors that mediate the impact of host habitats on the gut microbiome. Diet and gut microbes collaboratively contribute to the variation of serum metabolites, and correlate to the increase or decrease of certain clinical indexes. Specifically, systolic blood pressure is lowered by vegetable oil through increasing the abundance of Blautia and reducing the serum level of 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1), but it is reduced by fruit intake through increasing the serum level of Blautia improved threonate. Besides, aging-related clinical indexes are also closely correlated with the variation of gut microbes and serum metabolites. In this study, the linkages of geographic locations, diet, the gut microbiome, serum metabolites, and physiological indexes in a Chinese population are characterized. It is proved again that gut microbes and their metabolites are important media for external factors to affect human health.

Association between handgrip strength and depressive symptoms in patients undergoing hemodialysis: a cross-sectional study from a single Chinese center.

BACKGROUND: The relationship between handgrip strength (HGS) and depression in patients undergoing hemodialysis (HD) was unknown. Therefore, we aimed to clarify this association in a cohort of patients. METHODS: HGS was used as a representative indicator of muscle strength and was measured with a handheld dynamometer. Depressive symptoms were assessed with the self-reported Patient Health Questionnaire-9. A multivariable logistic regression model and restricted cubic spline analysis were used to assess the relationship between HGS and depression. RESULTS: The prevalence of depression in our study was 34% in 568 Chinese patients undergoing HD. Compared with patients in the lowest tertiles of absolute and weighted HGS, patients in the highest tertiles of HGS had an approximately 59% lower [odds ratio (OR) = 0.41, 95% confidence interval (CI) = 0.24-0.68; OR = 0.41, 95%CI = (0.24-0.69)] prevalence of depressive symptoms after multivariate adjustments. Besides, the risk of depression in hemodialysis patients decreased by 33% (OR = 0.67, 95%CI = 0.53-0.85) and 32% (OR = 0.68, 95%CI = 0.54-0.85) for each standard deviation increase in absolute HGS and weighted HGS, respectively. The prevalence of depressive symptoms decreased with both increasing absolute HGS and weighted HGS after multivariate adjustments (p for trend < 0.05). Furthermore, a linear dose-response relationship was observed between absolute HGS and weighted HGS and the prevalence of depressive symptoms (pnonlinearity>0.05). CONCLUSIONS: This study suggests that lower handgrip strength, a simple and modifiable parameter, is associated with a higher prevalence of depression in Chinese patients undergoing HD. Considering that depression is often unrecognized or underdiagnosed in HD patients, lowered muscle strength should be an important indicator and incentive for medical staff to screen for depression.

A pretrain-finetune approach for improving model generalizability in outcome prediction of acute respiratory distress syndrome patients.

BACKGROUND: Early prediction of acute respiratory distress syndrome (ARDS) of critically ill patients in intensive care units (ICUs) has been intensively studied in the past years. Yet a prediction model trained on data from one hospital might not be well generalized to other hospitals. It is therefore essential to develop an accurate and generalizable ARDS prediction model adaptive to different hospital or medical centers. METHODS: We analyzed electronic medical records of 200,859 and 50,920 hospitalized patients within 24 h after being diagnosed with ARDS from the Philips eICU Institute (eICU-CRD) and the Medical Information Mart for Intensive Care (MIMIC-IV) dataset, respectively. Patients were sorted into three groups, including rapid death, long stay, and recovery, based on their condition or outcome between 24 and 72 h after ARDS diagnosis. To improve prediction performance and generalizability, a "pretrain-finetune" approach was applied, where we pretrained models on the eICU-CRD dataset and performed model finetuning using only a part (35%) of the MIMIC-IV dataset, and then tested the finetuned models on the remaining data from the MIMIC-IV dataset. Well-known machine-learning algorithms, including logistic regression, random forest, extreme gradient boosting, and multilayer perceptron neural networks, were employed to predict ARDS outcomes. Prediction performance was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS: Results show that, in general, multilayer perceptron neural networks outperformed the other models. The use of pretrain-finetune yielded improved performance in predicting ARDS outcomes achieving a micro-AUC of 0.870 for the MIMIC-IV dataset, an improvement of 0.046 over the pretrain model. CONCLUSIONS: The proposed pretrain-finetune approach can effectively improve model generalizability from one to another dataset in ARDS prediction.

Comprehensive effects of microplastics on algae-laden surface water treatment by coagulation-ultrafiltration combined process: Algae cultivation, coagulation performance and membrane fouling development.

In coastal areas, the surface water has been simultaneously exposed to the algae blooms caused by eutrophication and the microplastics (MPs) pollution originating from active human activities. As a practical alternative to address these issues in drinking water plant, coagulation-ultrafiltration combined process is still confronted with the limited understanding about the comprehensive effects of MPs on algae-laden surface water (ASW) treatment. Considering the migration of MPs in nature environment and drinking water treatment process, this study first aims to systematically investigate the influence of MPs on algae cultivation, coagulation performance and membrane fouling development. The results of algae cultivation indicate that MPs stimulated the algae activity by 58 % and then constantly suppressed the secretion of protein-like, humic-like and polysaccharide-like metabolites. The variation of particle size distribution and zeta potential confirm that MPs acted as nuclei to facilitate the development of large coagulation flocs with an increasing average size from 82.6 µm to 107.6 µm, during which the negatively charged pollutants were neutralized and removed from ASW. According to the SEM images, MPs could destroy the structure of fouling layer on 50 kDa membranes during the filtration of ASW coagulation effluent. Its synergistic effect with the enhanced coagulation performance and the suppressed EOM secretion contributed to the alleviation of membrane fouling caused by overlapped large-sized foulants. However, the interaction between the enriched organic foulants by MPs and the deposited coagulants on 300 kDa membranes facilitated the development of cake layer, leading to the deterioration of membrane permeability. This study emphasizes the importance in concerning the existence of MPs during the treatment of ASW by coagulation-ultrafiltration combined process and their exact influence in water purification efficiency.

Accurate preoperative prediction of nodal metastasis in papillary thyroid microcarcinoma: Towards optimal management of patients.

OBJECTIVE: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. METHODS: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. RESULTS: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. CONCLUSION: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.

Electrocoagulation enhanced gravity driven membrane bioreactor for advanced treatment of rural sewage.

The daily discharge of rural sewage in China occupies 30 % of the national wastewater discharge, and developing an energy-efficient, easy to operate, and decentralized rural sewage treatment technology becomes an important task. In this work, a novel rural sewage treatment technology, Electrocoagulation enhanced Gravity-Driven Membrane Bioreactor (EC-GDMBR) was exploited for the rural sewage treatment under long-term operation (160 days). Two EC-GDMBRs with various module structures of ceramic membrane (horizontal module and side module) not only displayed the desirable effluent quality, but also sustained the stable flux (8-13 LMH). The electrocoagulation, electrooxidation, biodegradation, and separation in EC-GDMBRs were able to synergistically remove the particle matter, organic (CODCr effluent <11.6 ± 1.2 mg/L) and nutrients (NH3-N effluent <0.1 mg/L, TN effluent <8.5 mg/L, TP effluent <0.05 mg/L). Besides, the high permeability of ceramic membrane and large porosity of biofilm on its surface improved the sustainability of stable flux during the long-term operation. Moreover, by analyzing bacterial abundance, Extracellular Polymeric Substances, Adenosine Tri-Phosphate and Confocal Laser Scanning Microscopy, a large number of microorganisms grew and accumulated on the carrier, as well as formed the biofilm (23.46-659.9 µm), while Nitrobacteria (1.6-4.1 %) and Nitrate (0.01-0.06 %) exited in the carrier biofilms, promoting the nitrogen removal. Compared with EC-GDMBR with side module of ceramic membrane, EC-GDMBR with horizontal module of ceramic membrane has advantages in flux behavior, organic/nutrient removal, microbial abundance/activity, abundance of nitrogen removal functional bacteria and water permeability of biofilm, because the ceramic membrane of horizontal module can promote the uniform growth of biofilm and improve the uniformity of flow penetration distribution. In general, the findings of this work verify the reliability of EC-GDMBR for the sustainable operation of wastewater treatment and improve its application value of rural sewage treatment.

Enhanced electrooxidation/electrocoagulation-ultrafiltration membrane process with S2O42- for saline algae-containing surface water treatment: Purification and membrane performance.

The surface water in coastal areas involving algae, is often affected by saline and emerging contaminants caused by saltwater intrusion, and expanding aquaculture industry. Therefore, it is necessary to conduct studies to address the issues that affect ecological safety and health of aquatic environments. This study presents the development of an enhanced electrooxidation/electrocoagulation-ultrafiltration (EO/EC-UF) membrane process using S2O42- (DTN@EO/EC-UF) for the treatment of saline water containing algae. Our results have shown that significant removal of NH3-N (95.1 %), UV254 (89.4 %) and algae (75.7 %) was achieved with the addition of S2O42- (DTN). Additionally, an optimal DTN dosage of 40 mg/L was used in the DTN@EO/EC process to enhance water purification, utilizing reactive species such as SO4·- and ·OH. After coupling with the ultrafiltration (UF) process, optimal operating conditions (DTN: 40 mg/L, current density: 4.65 mA/cm2, electrolysis: 60 s) were applied to treat the saline algae-containing surface water. The generated free chlorine, including NHCl2, accounted for approximately 22 % (0.14 mg/L). In addition, DTN significantly improved the ceramic membrane's permeability and anti-fouling characteristics, with a maximum increasing specific flux from 0.76 to 0.93, mainly attributing to the reduced the irreversible fouling resistance. Furthermore, we discovered that common membrane cleaning using acid or base enhanced the DTN@EO/EC-UF process. In conclusion, this study established an innovative DTN@EO/EC-UF process with excellent performance in terms of water purification and membrane self-cleaning. The results provided a promising alternative for treating saline algae-containing surface water.

The function of tRNA-derived small RNAs in cardiovascular diseases.

tRNA-derived small RNAs (tsRNAs) constitute a subgroup of small noncoding RNAs (ncRNAs) originating from tRNA molecules. Their rich content, evolutionary conservatism, high stability, and widespread existence makes them significant in disease research. These characteristics have positioned tsRNAs as key players in various physiological and pathological processes. tsRNA actively participates in regulating many cellular processes, such as cell death, proliferation, and metabolism. tsRNAs could be promising diagnostic markers for cardiovascular diseases (CVDs). tsRNAs have been identified in serums, suggesting their utility as early indicators for the diagnosis of CVDs. Moreover, the regulatory roles of tsRNAs in CVDs make them promising targets for therapeutic intervention. This review provides a succinct overview of the characteristics, classification, and regulatory functions of tsRNAs in the context of CVDs. By shedding light on the intricate roles of tsRNAs, this knowledge could pave the way for the development of innovative diagnostic tools and therapeutic strategies for CVDs.

Genome-wide screens identify SEL1L as an intracellular rheostat controlling collagen turnover.

Accumulating evidence has implicated impaired extracellular matrix (ECM) clearance as a key factor in fibrotic disease. Despite decades of research elucidating the effectors of ECM clearance, relatively little is understood regarding the upstream regulation of this process. Collagen is the most abundant constituent of normal and fibrotic ECM in mammalian tissues. Its catabolism occurs through extracellular proteolysis and cell-mediated uptake of collagen fragments for intracellular degradation. Given the paucity of information regarding the regulation of this latter process, here we execute unbiased genome-wide screens to understand the molecular underpinnings of cell-mediated collagen clearance. Using this approach, we discover a mechanism through which collagen biosynthesis is sensed by cells internally and directly regulates clearance of extracellular collagen. The sensing mechanism appears to be dependent on endoplasmic reticulum-resident protein SEL1L and occurs via a noncanonical function of this protein. This pathway functions as a homeostatic negative feedback loop that limits collagen accumulation in tissues. In human fibrotic lung disease, the induction of this collagen clearance pathway by collagen synthesis is impaired, thereby contributing to the pathological accumulation of collagen in lung tissue. Thus, we describe cell-autonomous, rheostatic collagen clearance as an important pathway of tissue homeostasis.

Contribution of Matrix Metalloproteinase-2 Genotypes to Taiwan Pterygium Risk.

BACKGROUND/AIM: In the literature, the studies about the role of matrix metalloproteinase-2 (MMP-2) in pterygium diagnosis are mainly based on its protein expression. The role of MMP-2 variants has never been examined. The aim of this study was to examine the association of MMP-2 genotypes with pterygium risk. MATERIALS AND METHODS: MMP-2 rs243865 and rs2285053 were genotyped in 140 pterygium cases and 280 non-pterygium controls by typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping technology. RESULTS: The genotypic frequency of MMP-2 rs243865 CC, CT and TT were 86.4%, 12.9% and 0.7% in the pterygium group and 81.1%, 17.1% and 1.8% in the non-pterygium group (p for trend=0.3389). The variant CT and TT carriers had a 0.70- and 0.38-fold pterygium risk (95%CI=0.39-1.26 and 0.04-3.25, p=0.2982 and 0.6686, respectively). As for MMP-2 rs2285053, the genotypic frequency of CC, CT and TT were 67.1%, 28.6% and 4.3% in the pterygium group, non-significantly different from those in non-pterygium group (p for trend=0.7081). The CT and TT carriers had a 0.88- and 0.71-fold pterygium risk (95%CI=0.56-1.38 and 0.27-1.88, p=0.6612 and 0.6456, respectively). The allelic analysis results showed that MMP-2 rs243865 variant T allele was not associated with pterygium risk (7.1% versus 10.4%, OR=0.67, 95%CI=0.39-1.13, p=0.1649). As for MMP-2 rs2285053, the T allele was not associated with pterygium risk either (18.6% versus 21.1%, OR=0.85, 95%CI=0.59-1.23, p=0.4136). CONCLUSION: The genotypes at MMP-2 rs243865 or rs2285053 played minor role in determining individual susceptibility for pterygium among Taiwanese.