[Epidemiological investigation of iron deficiency among preschool children in 10 provinces, autonomous regions, or municipalities in China].

Objective: To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China. Methods: A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test. Results: A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) µg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region (χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference (χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) (χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant (χ2=0.51, P=0.476). Conclusions: There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Cardiac MRI feature-tracking-derived torsion mechanics in systolic and diastolic dysfunction in systemic light-chain cardiac amyloidosis.

AIM: To describe the myocardial torsion mechanics in cardiac amyloidosis (CA), and evaluate the correlations between left ventricle (LV) torsion mechanics and conventional parameters using cardiac magnetic resonance imaging feature tracking (CMR-FT). MATERIALS AND METHODS: One hundred and thirty-nine patients with light-chain CA (AL-CA) were divided into three groups: group 1 with preserved systolic function (LV ejection fraction [LVEF] ≥50%, n=55), group 2 with mildly reduced systolic function (40% ≤ LVEF <50%, n=51), and group 3 with reduced systolic function (LVEF <40%, n=33), and compared with age- and gender-matched healthy controls (n=26). All patients underwent cine imaging and late gadolinium-enhancement (LGE). Cine images were analysed offline using CMR-FT to estimate torsion parameters. RESULTS: Global torsion, base-mid torsion, and peak diastolic torsion rate (diasTR) were significantly impaired in patients with preserved systolic function (p<0.05 for all), whereas mid-apex torsion and peak systolic torsion rate (sysTR) were preserved (p>0.05 for both) compared with healthy controls. In patients with mildly reduced systolic function, global torsion and base-mid torsion were lower compared to those with preserved systolic function (p<0.05 for both), while mid-apex torsion, sysTR, and diasTR were preserved (p>0.05 for all). In patients with reduced systolic function, only sysTR was significantly worse compared with mildly reduced systolic function (p<0.05). At multivariable analysis, right ventricle (RV) end-systolic volume RVESV index and NYHA class were independently related to global torsion, whereas LVEF was independently related to sysTR. RV ejection fraction (RVEF) was independently related to diasTR. LV global torsion performed well (AUC 0.71; 95% confidence interval [CI]: 0.61, 0.77) in discriminating transmural from non-transmural LGE in AL-CA patients. CONCLUSION: LV torsion mechanics derived by CMR-FT could help to monitor LV systolic and diastolic function in AL-CA patients and function as a new imaging marker for LV dysfunction and LGE transmurality.

Predictive effect of net water uptake on futile recanalisation in patients with acute large-vessel occlusion stroke.

AIM: To determine whether net water uptake (NWU) based on automated software evaluation could predict futile recanalisation in patients with acute anterior circulation large-vessel occlusion (LVO). MATERIALS AND METHODS: Patients with acute anterior circulation LVO undergoing mechanical thrombectomy in Jinling Hospital were evaluated retrospectively. NWU and other baseline data were evaluated by performing univariate and multivariate analyses. The primary endpoint was 90-day modified Rankin scale score ≥3. A nomogram to predict poor clinical outcomes was developed based on multivariate logistic regression analysis. RESULTS: Overall, 135 patients who underwent thrombectomy with a TICI grade ≥2b were enrolled. In multivariate logistic regression analysis, the following factors were identified as independent predictors of futile recanalisation: age (odds ratio [OR]: 1.055, 95 % confidence interval [CI]: 1.004-1.110, p=0.035), female (OR: 0.289, 95 % CI: 0.098-0.850, p=0.024), hypertension (OR: 3.182, 95 % CI: 1.160-8.728, p=0.025), high blood glucose level (OR: 1.36, 95 % CI: 1.087-1.701, p=0.007), admission National Institutes of Health Stroke Scale score (OR: 1.082, 95 % CI: 1.003-1.168, p=0.043), and NWU (OR: 1.312, 95 % CI: 1.038-1.659, p=0.023). CONCLUSIONS: NWU based on Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) could be used to predict the occurrence of futile recanalisation in patients with acute anterior circulation LVO ischaemic stroke.

[The association between body mass index and in-hospital major adverse cardiovascular and cerebral events in patients with acute coronary syndrome].

Objective: To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS). Methods: This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), overweight (BMI between 25.0 and 29.9 kg/m2), and obese (BMI≥30.0 kg/m2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results: A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively (P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group (OR=1.30, 95%CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion: ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

Causal relationship between cigarette smoking behaviors and the risk of hernias: a Mendelian randomization study.

PURPOSE: As the global population continues to age, there is a noticeable yearly rise in the incidence of hernias. Simultaneously, smoking, a widespread addictive behavior and a significant contributor to mortality, has evolved into a pervasive public health concern. Existing literature has already established a connection between smoking and an increased risk of postoperative recurrence and postoperative infections following hernia surgery. However, there remains a dearth of research exploring the association between smoking and hernia morbidity. In this study, our objective is to systematically evaluate the causal relationship between cigarette smoking behaviors and hernia morbidity using a Mendelian randomization (MR) approach. METHODS: Hernia-related data were sourced from the FinnGen Biobank database, while cigarette smoking behavior data were gathered from the GWAS and Sequencing Consortium of Alcohol and Nicotine Use. To assess the causal relationship, we employed five methods: the weighted median, the weighted mode the inverse variance weighted (IVW), MR-Egger, and the simple mode. Sensitivity analysis was conducted, incorporating Cochran's Q test, the MR-Egger intercept test, leave-one-out analysis, and funnel plot. The presentation of the causal relationship is expressed as an odds ratio (OR) along with their corresponding 95% confidence intervals (CI). RESULTS: Employing the IVW method as the reference standard, we found that smoking intensity is associated with an increased risk of diaphragmatic hernia (OR = 1.21, 95% CI 1.00-1.46, P = 0.047). These consistent findings were further corroborated by the weighted median and weighted mode methods (OR = 1.26, 95% CI 1.03-1.54, P = 0.026; OR = 1.25, 95% CI 1.02-1.52, P = 0.045). Conversely, when applying the IVW method, we identified no statistically significant causal relationship between smoking age, smoking initiation status, smoking cessation status, and the incidence of hernia. CONCLUSIONS: Our MR study has uncovered genetic evidence linking smoking intensity and the occurrence of diaphragmatic hernia. The risk of developing diaphragmatic hernia rises in tandem with the intensity of smoking. This emphasizes the crucial role of regularly advising patients to cease smoking in clinical settings.

Particulated autologous cartilage transplantation for the treatment of osteochondral lesion of the talus: can the lesion cartilage be recycled?

Aims: Osteochondral lesions of the talus (OLT) are a common cause of disability and chronic ankle pain. Many operative treatment strategies have been introduced; however, they have their own disadvantages. Recently lesion repair using autologous cartilage chip has emerged therefore we investigated the efficacy of particulated autologous cartilage transplantation (PACT) in OLT. Methods: We retrospectively analyzed 32 consecutive symptomatic patients with OLT who underwent PACT with minimum one-year follow-up. Standard preoperative radiography and MRI were performed for all patients. Follow-up second-look arthroscopy or MRI was performed with patient consent approximately one-year postoperatively. Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) score and International Cartilage Repair Society (ICRS) grades were used to evaluate the quality of the regenerated cartilage. Clinical outcomes were assessed using the pain visual analogue scale (VAS), Foot Function Index (FFI), and Foot Ankle Outcome Scale (FAOS). Results: All patients had ICRS grade IV cartilage lesions, except for one (ICRS grade III). The paired MOCART scores significantly improved from 42.5 (SD 1.53) to 63.5 (SD 22.60) (p = 0.025) in ten patients. Seven patients agreed to undergo second-look arthroscopy; 5 patients had grade I (normal) ICRS scores and two patients had grade II (nearly normal) ICRS scores. VAS, FFI, and all subscales of FAOS were significantly improved postoperatively (p ≤ 0.003). Conclusion: PACT significantly improved the clinical, radiological, and morphological outcomes of OLT. We consider this to be a safe and effective surgical method based on the short-term clinical results of this study.

Cyanine Dye Conjugation Enhances Crizotinib Localization to Intracranial Tumors, Attenuating NF-κB-Inducing Kinase Activity and Glioma Progression.

Glioblastoma (GBM) is a highly aggressive form of brain cancer with a poor prognosis and limited treatment options. The ALK and c-MET inhibitor Crizotinib has demonstrated preclinical therapeutic potential for newly diagnosed GBM, although its efficacy is limited by poor penetration of the blood brain barrier. Here, we identify Crizotinib as a novel inhibitor of nuclear factor-κB (NF-κB)-inducing kinase, which is a key regulator of GBM growth and proliferation. We further show that the conjugation of Crizotinib to a heptamethine cyanine dye, or a near-infrared dye (IR-Crizotinib), attenuated glioma cell proliferation and survival in vitro to a greater extent than unconjugated Crizotinib. Moreover, we observed increased IR-Crizotinib localization to orthotopic mouse xenograft GBM tumors, which resulted in impaired tumor growth in vivo. Overall, IR-Crizotinib exhibited improved intracranial chemotherapeutic delivery and tumor localization with concurrent inhibition of NIK and noncanonical NF-κB signaling, thereby reducing glioma growth in vitro, as well as in vivo, and increasing survival in a preclinical rodent model.

ACL Mucoid Degeneration-Anterior and Posterior Arthroscopic Decompression for Combined Knee Flexion-Extension Deficit.

Mucoid degeneration of the ACL (MDACL, ACL ganglion cysts) is a disease involving ACL thickening due to accumulation of mucoid substance and fiber degeneration with possible formation of "ganglions". Clinically, it leads to anteroposterior impingement and painful limitation of knee range of motion due to impingement of the anterior portion of the thickened ACL with the intercondylar notch during knee extension and the thickened posterior part of the ligament with posterior structures of the knee in flexion. Different treatment methods have been described, including total or partial resection of the ACL degenerative fibers. However, these techniques do not allow for ACL preservation and are associated with a risk of postoperative instability. Also, most procedures treat anterior impingement only. Therefore, the aim of this technical note is to present an arthroscopic technique allowing for minimally invasive anteroposterior ACL decompression. The technique is focused on evacuation of the interfibrous mucoid substance, ganglions, and bony decompression, as well as maintenance of ligament integrity. Its greatest advantage is that it is safe and ACL-preserving yet allows for comprehensive treatment of all intra- and extra-ligamentous possible reasons of MDACL origin and promoting good healing conditions.

Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells.

The prognosis of high-grade gliomas, such as glioblastoma multiforme (GBM), is extremely poor due to the highly invasive nature of these aggressive cancers. Previous work has demonstrated that TNF-weak like factor (TWEAK) induction of the noncanonical NF-κB pathway promotes the invasiveness of GBM cells in an NF-κB-inducing kinase (NIK)-dependent manner. While NIK activity is predominantly regulated at the posttranslational level, we show here that NIK (MAP3K14) is upregulated at the transcriptional level in invading cell populations, with the highest NIK expression observed in the most invasive cells. GBM cells with high induction of NIK gene expression demonstrate characteristics of collective invasion, facilitating invasion of neighboring cells. Furthermore, we demonstrate that the E2F transcription factors E2F4 and E2F5 directly regulate NIK transcription and are required to promote GBM cell invasion in response to TWEAK. Overall, our findings demonstrate that transcriptional induction of NIK facilitates collective cell migration and invasion, thereby promoting GBM pathogenesis.

[Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study].

Objective: To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD). Methods: A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results: A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion: The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

Imaging Biomarkers to Predict Outcomes in Patients With Large B-Cell Lymphoma With a Day 28 Partial Response by 18F-FDG PET/CT Imaging Following CAR-T Therapy.

BACKGROUND: CD19 directed CAR-T therapy for Large B-cell lymphoma (LBCL) has shown great therapeutic response in patients with relapsed/refractory disease with response rates of 60-80%. However, in patients with a partial response (PR) on initial day 28 post CAR-T therapy imaging, clinical uncertainty remains as half of these patients will ultimately have relapsed disease.   PATIENTS: In 24 patients receiving CD19 directed CAR-T therapy for relapsed/refractory LBCL achieving a PR on day 28, we utilize imaging biomarkers by 18F-FDG PET/CT imaging at pre CAR-T therapy baseline and day 28 to determine factors that may predict best overall response (B-OR), progression free survival (PFS), and overall survival (OS).   METHODS: Out of 75 patients receiving CAR-T therapy at a single institution, we retrospectively identified and reviewed 25 (33%) as achieving a PR on day 28. PR was defined using the 2014 Lugano classification system. All patients received standard of care CD19 directed CAR-T therapy with axicabtagene ciloleucel. Two independent nuclear medicine physicians measured baseline (pre-CAR-T therapy) and day 28 PET/CT SUVmax, SUVmean and TMV (cm3) of each lesion (node, organ or marrow uptake, if any) using ROVER software. All statistical tests were two-sided and conducted at the 0.05 level of significance. R version 1.3.1099 (R-studio) was used for statistical modeling.   CONCLUSION: We demonstrate that a higher day 28 SUVmax was significantly higher in those with a B-OR of PR and in our modeling, a lower day 28 SUVmax may predict favorable PFS and OS. Additionally, lower TMV, both at baseline and day 28, may also be predictive of longer PFS and OS, while lower TLG at baseline, but not day 28 is significantly associated with a B-OR of CR. While further study is warranted, these imaging biomarkers may allow for early identification of those with a day 28 PR at highest risk for relapse leading to early intervention to improve long term outcomes.

[Forecasting the burden of disease from diabetes under the scenarios of specific risk factors control in China in 2030].

Objective: To forecast mortality, age-standardized mortality, and probability of premature mortality from diabetes, and to simulate the impact of controlling risk factors by 2030 in China. Methods: We simulated the burden of disease from diabetes in six scenarios according to the development goals of risk factors control by the WHO and Chinese government. Based on the theory of comparative risk assessment and the estimates of the burden of disease for China from the Global Burden of Disease Study 2015, we used the proportional change model to project the number of deaths, age-standardized mortality, and probability of premature mortality from diabetes under different scenarios of risk factors control in 2030. Results: If the trends in exposures to risk factors from 1990 to 2015 continued. Mortality, age-standardized mortality, and probability of premature mortality from diabetes would increase to 32.57/100 000, 17.32/100 000, and 0.84% by 2030, respectively. During that time, mortality, age-standardized mortality and probability of premature mortality for males would all be higher than for females. If the goals of controlling risk factors were all achieved, the number of deaths from diabetes in 2030 would decrease by 62.10% compared to the predicted numbers based on the historical trends in exposure to risk factors, and the probability of premature mortality would drop to 0.29%. If only the exposure to a single risk factor were achieved by 2030, high fasting plasma glucose control would have the greatest impact on diabetes, resulting in a 56.00% reduction in deaths compared to the predicted numbers based on the historical trends, followed by high BMI (4.92%), smoking (0.65%), and low physical activity (0.53%). Conclusions: Risk factors control plays an important role in reducing the number of deaths, age-standardized mortality rate, and probability of premature mortality from diabetes. We suggest taking comprehensive measures to control relevant risk factors for certain populations and regions, to achieve the goal of reducing the burden of disease from diabetes as expected.

[Potential short-term effects of tobacco control scheme under various application scenarios of tobacco control measures across the globe: a Meta-analysis].

Objective: based on summarizing the simulation and prediction of tobacco control measures across the globe and sorting out the various scenarios of tobacco control measures, the potential short-term effects of seven tobacco control measures in different scenarios were systematically analyzed. Methods: Until April 2022, PubMed, Embase, EconLit, PsychINFO, and CINAHL databases were used to retrieve literature about tobacco control measures simulation and prediction models across the globe. Inclusion and exclusion criteria were strictly followed. Meta-analysis for the potential short-term effects of seven tobacco control measures in different scenarios was performed using the R software. Results: A total of 22 papers covering 16 countries were selected. Five studies were conducted in the United States, three in Mexico, and two in Italy. There were all papers with the measures to tax increases, smoke-free air laws, and mass media campaigns, 21 papers with youth access restrictions, 20 with marketing restrictions, and 19 with cessation treatment programs and health warnings. The tax increases had diverse influences on the price elasticity of different age groups. The price elasticity in the age group 15-17 years was the highest, which was 0.044 (95%CI: 0.038-0.051). The potential short-term effects of smoke-free air laws in workplaces were higher than in restaurants and other indoor public places. The effects of youth access restrictions were greater in the age group <16 years than in the age group 16-17. The stronger the implementation of other measures, the greater the potential short-term effects. A comparison of seven tobacco control measures showed that the cessation treatment programs increase in cessation rate was the highest, 0.404 (95%CI: 0.357-0.456). The reduction in smoking rate and reduction in initiation rate of youth access restrictions strongly enforced and publicized was the highest in the age group <16 years, 0.292 (95%CI: 0.269-0.315), and 0.292 (95%CI: 0.270-0.316). Conclusions: The potential short-term effects of seven tobacco control measures in different scenarios were evaluated more accurately and objectively through Meta-analysis. In the short term, cessation treatment programs will substantially increase smoking cessation rates, and strong youth access enforcement will sharply reduce smoking and initiation rates among adolescents under 16. These results also offer strong data-related support for the simulation and prediction of tobacco control measures in China and other countries.

Nanoscale thermodynamics needs the concept of a disjoining chemical potential.

Disjoining pressure was discovered by Derjaguin in 1930's, which describes the difference between the pressure of a strongly confined fluid and the corresponding one in a bulk phase. It has been revealed recently that the disjoining pressure is at the origin of distinct differential and integral surface tensions for strongly confined fluids. Here we show how the twin concept, disjoining chemical potential, arises in a reminiscent way although it comes out eighty years later. This twin concept advances our understanding of nanoscale thermodynamics. Ensemble-dependence (or environment-dependence) is one hallmark of thermodynamics of small systems. We show that integral surface tension is ensemble-dependent while differential surface tension is not. Moreover, two generalized Gibbs-Duhem equations involving integral surface tensions are derived, as well as two additional adsorption equations relating surface tensions to adsorption-induced strains. All the results obtained in this work further evidence that an approach alternative of Hill's nanothermodynamics is possible, by extending Gibbs surface thermodynamics instead of resorting to Hill's replica trick. Moreover, we find a compression-expansion hysteresis without any underlying phase transition.

[Analysis of the core knowledge level of chronic diseases in Chinese adults and related factors].

Objective: To understand the core knowledge level and influencing factors of chronic disease prevention and control in Adults in China, and to provide a scientific basis for formulating chronic disease prevention and control measures. Methods: In this study, cross-sectional survey and quota sampling were used to recruit 173 819 permanent residents aged 18 and above from 302 counties of adult chronic diseases and nutrition surveillance in China to conduct an online questionnaire survey, including basic information and core knowledge of chronic diseases. The scores of the core knowledge of chronic disease prevention and control were described by median and interquartile range, the Wilcoxon rank sum test or the Kruskal Wallis test was used for the inter-group comparison, and the correlation factors of the total score were analyzed by the multilinear regression model. Results: A total of 172 808 participants were surveyed in 302 counties and districts, of which 42.60%(73 623) were male and 57.40%(99 185) were female; The proportion of respondents aged 18-44, 45-59, and 60 years old and above was 54.74% (94 594), 30.91% (53 423) and 14.35% (24 791), respectively. The total score of the core knowledge of chronic prevention and control in the total population was 66(13), and the scores of different characteristic groups were different, and the differences were statistically significant: the eastern region had the highest score at 67(11) (H=840.66, P<0.01), the urban 66(12) was higher than the rural 65(14) (Z=-31.35, P<0.01), and the male 66(14) was lower than female 66(12) (Z=-11.66, P<0.01), 18-24 years old 64(13) was lower than other age groups(H=115.80, P<0.01), and undergraduate degree and above had the highest score compared to other academic qualifications, with 68(9) points(H=2 547.25, P<0.01). Multivariate analysis showed that eastern (t=27.42, P<0.01), central (t=17.33, P<0.01), urban (t=5.69, P<0.01), female (t=17.81, P<0.01), high age (t=46.04, P<0.01) and high education (t=57.77, P<0.01) had higher scores of core knowledge of chronic disease prevention and control than other groups, the scores of core knowledge of chronic disease prevention and control of professional and technical personnel (t=8.63, P<0.01), state enterprises and institutions (t=38.67, P<0.01), agriculture, forestry, animal husbandry, fishery and water conservancy production (t=5.30, P<0.01), production, transportation and commercial personnel (t=24.87, P<0.01), and other workers (t=8.89, P<0.01) were higher than those of non-employed people. Conclusion: There are differences in the total scores of the core knowledge of chronic disease prevention and control in different characteristics of people in China, and in the future, health education on the prevention and treatment of chronic diseases should be strengthened for specific groups to improve the knowledge level of residents.

[Teriparatide regulates osteoblast differentiation in high-glucose microenvironment through the cAMP/PKA/CREB signaling pathway].

OBJECTIVE: To investigate the effect of teriparatide on the differentiation of MC3T3-E1 cells in high-glucose microenvironment and explore the possible mechanism. METHODS: MC3T3-E1 cells cultured in normal glucose or high-glucose (25 mmol/L) medium were treated with 10 nmol/L teriparatide with or without co-treatment with H-89 (a PKA inhibitor). CCK-8 assay was used to detect the changes in cell proliferation, and cAMP content in the cells was determined with ELISA. Alkaline phosphatase (ALP) activity and mineralized nodules in the cells were detected using ALP kit and Alizarin red staining, respectively. The changes in cell morphology were detected by cytoskeleton staining. Real-time PCR was used to detect the mRNA expressions of PKA, CREB, RUNX2 and Osx in the treated cells. RESULTS: The treatments did not result in significant changes in proliferation of MC3T3-E1 cells (P > 0.05). Compared with the cells in routine culture, the cells treated with teriparatide showed significantly increased cAMP levels (P < 0.05) with enhanced ALP activity and increased area of mineralized nodules (P < 0.05). Teriparatide treatment also resulted in more distinct visualization of the cytoskeleton in the cells and obviously up-regulated the mRNA expressions of PKA, CREB, RUNX2 and Osx (P < 0.05). The opposite changes were observed in cells cultured in high glucose. In cells exposed to high glucose, treatment with teriparatide significantly increased cAMP levels (P < 0.05), ALP activity and the area of mineralized nodules (P < 0.05) and enhanced the clarity of the cytoskeleton and mRNA expressions of PKA, CREB, RUNX2 and Osx; the effects of teriparatide was strongly antagonized by co-treatment with H-89 (P < 0.05). CONCLUSION: Teriparatide can promote osteoblast differentiation of MC3T3-E1 cells in high-glucose microenvironment possibly by activating the cAMP/PKA/CREB signaling pathway.

NF-κB-inducing kinase maintains mitochondrial efficiency and systemic metabolic homeostasis.

NF-κB-inducing kinase (NIK) is an essential upstream inducer of noncanonical NF-κB signaling and a critical regulator of immunity and inflammation. Our recent work has demonstrated that NIK regulates mitochondrial respiration and adaptive metabolic responses in cancer and innate immune cells. However, it is not clear whether NIK also has roles in regulating systemic metabolism. In this study, we demonstrate that NIK has local and systemic effects on developmental and metabolic processes. Our findings show that NIK-deficient mice exhibit reduced adiposity, as well as elevated energy expenditure both basally, and under the stress of a high-fat diet. Moreover, we identify NF-κB-independent and -dependent functions for NIK in white adipose tissue metabolism and development. Specifically, we found that in an NF-κB-independent manner NIK is required for maintaining mitochondrial fitness, as NIK-deficient adipocytes have impaired mitochondrial membrane potential and spare respiratory capacity. In addition to mitochondrial exhaustion, NIK-deficient adipocytes and ex vivo adipose tissue exhibit a compensatory upregulation of glycolysis to meet bioenergetic demands. Finally, while NIK regulation of mitochondrial metabolism in preadipocytes is NF-κB-independent, we demonstrate that NIK has a complementary role in adipocyte differentiation that requires activation of RelB and the noncanonical NF-κB pathway. Collectively, these data demonstrate that NIK has critical roles in local and systemic development and metabolism. Our findings establish NIK as an important regulator of organelle, cell, and systemic metabolic homeostasis, suggesting that metabolic dysfunction may be an important and unappreciated component of immune disorders and inflammatory diseases arising from NIK deficiency.

[Analysis on the allocation of human resources for chronic disease prevention and control in 664 district/county-level centers for disease control and prevention in China in 2020].

Objective: To analyze the allocation of human resources for chronic disease prevention and control of district/county-level centers for disease control and prevention(CDC) in China in 2020. Methods: Survey subjects were from National Chronic Noncommunicable Disease and Risk Factor Surveillance Sites and National Demonstration Areas for Chronic Noncommunicable Disease Prevention and Control (demonstration areas). A survey examining the allocation of human resources for chronic disease prevention and control at district/county-level CDC was conducted in December 2021 through the National Demonstration Areas Management Information System. The number and rate of allocation of human resources for chronic disease prevention and control in district/county-level CDC were analyzed and the Wilcoxon rank sum test was used to compare the difference between demonstration and non-demonstration areas and between urban and rural areas. The Kruskal-Wallis H test was used to compare the difference in east, central and west regions. The Gini coefficient and Theil index were used to evaluate the balance of human resource for chronic disease prevention and control. Results: A total of 678 districts/counties were investigated, and 664 districts/counties responded effectively, with an effective response rate of 97.9%. The establishment rate of district/county-level CDC was 98.34% (653/664), and the establishment rate of chronic disease prevention and control departments of district/county-level CDC was 96.02% (627/653). In 627 district/county-level CDC with departments for chronic disease prevention and control, the median number of full-time technical personnel for chronic disease prevention and control was 4, the median number of full-time technical personnel in demonstration areas (4 persons) was higher than in non-demonstration areas (3 persons), highest in the east region (5 persons) than in the middle region (4 persons) and the west region (4 persons), higher in urban areas (4 persons) than in rural areas (4 persons) (all P values<0.05). The allocation rate was 0.71 people/100 000, which was higher in demonstration areas (0.73 people/100 000) than in non-demonstration areas (0.67 people/100 000), highest in the west region (0.82 people/100 000) than in the middle region (0.71 people/100 000) and east region (0.67 people/100 000), higher in rural areas (0.77 people/100 000) than in urban areas (0.68 people/100 000) (all P values<0.05). The Gini coefficient for the allocation by population size was 0.352 9. The total Theil index for demonstration and non-demonstration areas, different regions, and urban-rural areas were 0.067 8, 0.076 3, and 0.000 2, with the intra-group contribution of 97.35%, 99.52%, and 98.80%, respectively. Conclusion: In 2020, the allocation of human resources for chronic disease prevention and control in district/county-level CDC is relatively balanced. The variation in the allocation of human resources for chronic disease prevention and control exist between demonstration and non-demonstration areas, urban and rural areas, and across regions.

Safety and Effectiveness of SB2 (Infliximab Biosimilar) in Adult Patients with Immune-Mediated Inflammatory Diseases: A Post-Marketing Surveillance in Korea.

INTRODUCTION: SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. METHODS: This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. RESULTS: In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks. CONCLUSION: This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.