Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Light Conversion by Electrochemiluminescence at Semiconductor Surfaces.

ConspectusElectrochemiluminescence (ECL) is the electrochemical generation of light. It involves an interfacial charge transfer that produces the excited state of a luminophore at the electrode surface. ECL is a powerful readout method that is widely employed for immunoassays and clinical diagnostics and is progressively evolving into a microscopy technique. On the other hand, photoelectrochemistry at illuminated semiconductors is a field of research that deals with the transfer of photogenerated charge carriers at the solid-liquid interface. This concept offers several advantages such as a considerable lowering of the onset potential required for triggering an electrochemical reaction as well as light addressable chemistry, via the spatial confinement of redox reactions at locally illuminated semiconductor electrodes. The combination of ECL with photoelectrochemistry at illuminated semiconductors is termed photoinduced ECL (PECL). It deals with the triggering of an ECL reaction through the transfer of photogenerated minority charge carriers at the illuminated solid/liquid interface. PECL results in the conversion of incident photons (λexc), that are absorbed by the semiconductor photoelectrode to emitted photons (λPECL), produced by the ECL reaction. Although demonstrated in the 1970s by Bard et al. in ultradry organic solvents, PECL remained unexplored until the last five years. Nowadays, as a result of the considerable progress achieved in semiconductor photoelectrodes and ECL systems, a large variety of PECL systems can be designed by combining photoelectrode materials with ECL luminophores, making it a versatile tool for light conversion in aqueous media.In this Account, we introduce the fundamentals of ECL and photoelectrochemistry at illuminated semiconductors and review the recent developments in PECL. We discuss the two main PECL light conversion schemes: downconversion (where λexc < λPECL) and upconversion (where λexc > λPECL). Besides, PECL can be used to simplify considerably the common electrochemical setups employed for ECL. Indeed, by engineering the photoelectrode material and carefully considering the reactivity involved for ECL and its counter-reaction, PECL enables the ultimate concept of all-optical ECL (AO-ECL), i.e., ECL generation at an illuminated monolithic device immersed into the electrolyte solution. As discussed in this Account, AO-ECL is an important breakthrough that allows the simplest ECL experimental configuration ever reported, eliminating constraints such as an electrical power supply, wires, electrodes, connections, and specific electrochemical knowledge. As shown at the end of this Account, due to the robustness of recently manufactured PECL systems, several applications can already be envisioned for microscopy, elucidation of solar conversion mechanisms, near-infrared imaging, and bioanalysis.

Subcutaneous versus intravenous nivolumab for renal cell carcinoma.

BACKGROUND: The evolving oncology treatment paradigm has created an unmet need for administration options that improve patient experiences and healthcare efficiencies. PATIENTS AND METHODS: CheckMate 67T (NCT04810078) was a phase 3, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20,000 units) or intravenous nivolumab (3 mg/kg every 2 weeks). Primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis (time-averaged serum concentration over the first 28 days [Cavgd28], and minimum steady-state serum concentration [Cminss]; noninferiority threshold: lower boundary of 90% confidence interval (CI) of the geometric mean ratios [GMR] ≥0.8). Objective response rate (ORR) was a key secondary endpoint powered for noninferiority (noninferiority threshold: lower boundary of 95% CI of relative risk of ORR [subcutaneous versus intravenous nivolumab] ≥0.60). RESULTS: Overall, 495 patients were randomized. Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of Cavgd28 and Cminss was 2.098 (90% CI, 2.001-2.200) and 1.774 (90% CI, 1.633-1.927), respectively. After 8 months minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI, 19.0-30.0) versus 18.2% with intravenous nivolumab (95% CI, 13.6-23.6; relative risk: 1.33 [95% CI, 0.94-1.87]). Coprimary endpoints and ORR met noninferiority thresholds. Additional efficacy and safety measures were similar. CONCLUSION: Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. No new safety signals were observed.

Non-Abelian Braiding of Topological Edge Bands.

Braiding is a geometric concept that manifests itself in a variety of scientific contexts from biology to physics, and has been employed to classify bulk band topology in topological materials. Topological edge states can also form braiding structures, as demonstrated recently in a type of topological insulators known as Möbius insulators, whose topological edge states form two braided bands exhibiting a Möbius twist. While the formation of Möbius twist is inspiring, it belongs to the simple Abelian braid group B_{2}. The most fascinating features about topological braids rely on the non-Abelianness in the higher-order braid group B_{N} (N≥3), which necessitates multiple edge bands, but so far it has not been discussed. Here, based on the gauge enriched symmetry, we develop a scheme to realize non-Abelian braiding of multiple topological edge bands. We propose tight-binding models of topological insulators that are able to generate topological edge states forming non-Abelian braiding structures. Experimental demonstrations are conducted in two acoustic crystals, which carry three and four braided acoustic edge bands, respectively. The observed braiding structure can correspond to the topological winding in the complex eigenvalue space of projective translation operator, akin to the previously established point-gap winding topology in the bulk of the Hatano-Nelson model. Our Letter also constitutes the realization of non-Abelian braiding topology on an actual crystal platform, but not based on the "virtual" synthetic dimensions.

Emergent Spin-Gapped Magnetization Plateaus in a Spin-1/2 Perfect Kagome Antiferromagnet.

The two-dimensional spin-1/2 kagome Heisenberg antiferromagnet is believed to host quantum spin liquid (QSL) states with no magnetic order, but its ground state remains largely elusive. An important outstanding question concerns the presence or absence of the 1/9 magnetization plateau, where exotic quantum states, including topological ones, are expected to emerge. Here we report the magnetization of a recently discovered kagome QSL candidate YCu_{3}(OH)_{6.5}Br_{2.5} up to 57 T. Above 50 T, a clear magnetization plateau at 1/3 of the saturation moment of Cu^{2+} ions is observed, supporting that this material provides an ideal platform for the kagome Heisenberg antiferromagnet. Remarkably, we found another magnetization plateau around 20 T, which is attributed to the 1/9 plateau. The temperature dependence of this plateau reveals the presence of the spin gap. The observation of 1/9 and 1/3 plateaus highlights the emergence of novel states in quantum spin systems.

Local Excitation of Kagome Spin Ice Magnetism Seen by Scanning Tunneling Microscopy.

The kagome spin ice can host frustrated magnetic excitations by flipping its local spin. Under an inelastic tunneling condition, the tip in a scanning tunneling microscope can flip the local spin, and we apply this technique to kagome metal HoAgGe with a long-range ordered spin ice ground state. Away from defects, we discover a pair of pronounced dips in the local tunneling spectrum at symmetrical bias voltages with negative intensity values, serving as a striking inelastic tunneling signal. This signal disappears above the spin ice formation temperature and has a dependence on the magnetic fields, demonstrating its intimate relation with the spin ice magnetism. We provide a two-level spin-flip model to explain the tunneling dips considering the spin ice magnetism under spin-orbit coupling. Our results uncover a local emergent excitation of spin ice magnetism in a kagome metal, suggesting that local electrical field induced spin flip climbs over a barrier caused by spin-orbital locking.

Unveiling the temperature-dependent thermoelectric properties of the undoped and Na-doped monolayer SnSe allotropes: a comparative study.

Motivated by the excellent thermoelectric (TE) performance of bulk SnSe, extensive attention has been drawn to the TE properties of the monolayer SnSe. To uncover the fundamental mechanism of manipulating the TE performance of the SnSe monolayer, we perform a systematic study on the TE properties of five monolayer SnSe allotropes such asα-,ß-,γ-,δ-, andε-SnSe based on the density functional theory and the non-equilibrium Green's functions. By comparing the TE properties of the Na-doped SnSe allotropes with the undoped ones, the influences of the Na doping and the temperature on the TE properties are deeply investigated. It is shown that the figure of meritZTwill increase as the temperature increases, which is the same for almost all the Na-doped and undoped cases. The Na doping can enhance or suppress theZTin different SnSe allotropes at different temperatures, implying the presence of the anomalous suppression of theZT. The Na doping inducedZTsuppression may be caused basically by the sharp decrease of the power factor and the weak decrease of the electronic thermal conductance, rather than by the decrease of the phononic thermal conductance. We hope this work will be able to enrich the understanding of the manipulation of TE properties by means of dimensions, structurization, doping, and temperature.

Pretreatment synthetic MRI features for triple-negative breast cancer.

AIM: To evaluate the quantitative parameters derived from synthetic magnetic resonance imaging (SyMRI) for predicting triple-negative breast cancer (TNBC). MATERIALS AND METHODS: This prospective study enrolled participants with invasive ductal breast carcinoma (IDBC) and separated them into a TNBC group and a Non-TNBC group. Preoperative breast MRI included both the SyMRI and conventional MRI sequences. The quantitative parameters derived from the SyMRI included T1 and T2 relaxation times, proton density (PD), and their standard deviations (SD). Clinicopathological characteristics, conventional MRI findings, and quantitative synthetic parameters were assessed for all participants. Multivariable logistic regression analysis was performed to determine the potential independent imaging predictors for TNBC preoperatively. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of these parameters. RESULTS: A total of 231 participants with histopathological proven IDBC were included in this study (n=46 in the TNBC group and n=185 in the Non-TNBC group). The TNBC group had significantly larger tumour size (p=0.011) and more frequent intratumoural cystic or necrotic lesions (p<0.001) as compared to the Non-TNBC group. The univariate analysis showed that the TNBC tumours had significantly higher T1 (p=0.006) and T2 (p<0.001) values than Non-TNBC tumours. Subsequent multivariable analysis indicated that T2 values and the presence of cystic or necrotic lesions were the independent predictors for TNBC. CONCLUSION: The T2 from synthetic imaging and the presence of cystic degeneration or necrosis within the breast cancer may serve as potential imaging biomarkers for preoperative differentiation of TNBC from Non-TNBC.

Clinical characteristics, outcomes and risk factors for mortality in hospitalized diabetes and chronic kidney disease patients after COVID-19 infection following widespread vaccination.

BACKGROUND: COVID-19 poses a significant threat to patients with comorbidities, such as diabetes and chronic kidney disease (CKD). China experienced a nationwide COVID-19 endemic from December 2022 to January 2023, which is the first occurrence of such an outbreak following China's widespread administration of COVID-19 vaccinations. METHODS: A total of 338 patients with diabetes and CKD combined with COVID-19 infection between December 7, 2022 and January 31, 2023 were included in this study. The end follow-up date was February 10, 2023. Univariate analysis and multivariate Cox analysis were used to analyze risk factors for death. RESULTS: During the 50-day median follow-up period, 90 patients in the study cohort died, for a mortality rate of 26.63%. The median age of the study cohort was 74 years, with a male predominance of 74%. During hospitalization, 21% of patients had incident AKI, 17% of patients experienced stroke, and 40% of patients experienced respiratory failure. Cox proportional hazard regression showed that older age, a diagnosis of severe or critically severe COVID-19 infection, incident AKI and respiratory failure, higher level of average values of fasting glucose during hospitalization, UA, and total bilirubin were independent risk factors for death in our multivariate model. CONCLUSIONS: These findings highlight the critical importance of identifying and managing comorbid risk factors for COVID-19, especially among the elderly, in order to optimize clinical outcomes, even after COVID-19 vaccination.

Acromegaly presented with acne vulgaris: a retrospective study with 123 cases.

BACKGROUND: Acne vulgaris is a prevalent skin condition. We have found that some acromegaly patients have acne. However, no study has examined the relationship between acromegaly and acne. OBJECTIVE: To explore prevalence and correlation of adult acne in patients with acromegaly. METHODS: For this cross-sectional study, we collected questionnaires, clinical information, and laboratory test results of acromegaly patients from January 2022 to December 2022 at Huashan Hospital. Of the 133 questionnaires returned, 123 had valid responses. RESULTS: Of the 123 patients with acromegaly enrolled in this study, 54.5% had adult acne. No statistically significant difference was found in prevalence between male and female patients. 61.2% of adult acne patients reported late-onset acne. Late-onset acne patients first developed acne years before acromegaly diagnosis (mean of 5.6 years for male and 4.5 years for female patients). Some acne patients have received traditional anti-acne treatment. Moreover, 31% of the patients reported no improvement, and only 3.5% of patients claimed complete resolution of acne after treatment. Before acromegaly treatment, the prevalence of adult acne was 51.2%, with mild acne accounting for 73.0%, moderate acne accounting for 23.8%, and severe acne accounting for 3.2%. After acromegaly treatment, the prevalence of adult acne was significantly decreased to 37.4% (P = 0.007). An overall decrease in acne severity was noted, with 93.5%, 6.5%, and 0% having mild, moderate, and severe acne, respectively. A total of 83.6% of the patients had self-assessed acne remission, and 33.3% of the patients reported complete acne resolution. However, 9.0% of patients reported that their condition had worsened after acromegaly treatment. After treatment, GH, IGF-1, IGF-1 index, insulin levels, and HOMA-IR decreased significantly in all patients with acromegaly (P < 0.05). Acne remission correlated positively with IGF-1 levels, but not with GH levels. The relationship between acromegaly and acne remains to be elucidated. CONCLUSIONS: Our findings provide preliminary evidence of the high prevalence of adult acne in acromegaly patients, and a high rate of late-onset acne as well. Traditional anti-acne treatments are less effective. Acne could be considerably relieved by treating acromegaly. Acne remission positively correlated with IGF-1 decline as well, which revealed the correlation between acne and IGF-1.

Orychophragmus violaceus and/or chicory forage affects performance, egg quality, sensory evaluation and antioxidative properties in native laying hens.

Orychophragmus violaceus (OV) and chicory (Cichorium intybus L., CC) can be used as fresh or dry forage for animals. To determine whether OV and/or CC have beneficial effects on performance and egg quality, a total of 1212 28-wk-old Beijing You Chicken (BYC) laying hens with similar performance were randomly allocated to 4 groups with 3 replicate pens per group, and 101 birds per pen. The birds were fed a basal diet (control), the basal diet + OV (3.507 kg/d/pen), the basal diet + CC (2.525 kg/d/pen), and the basal diet + OV + CC (OVC, 1.7535 kg/d/pen OV + 1.2625 kg/d/pen CC) for 3 wks after one wk of adaptation. The results showed that egg-laying rate was not affected by OV, CC and OVC (p > 0.05), but weekly average egg mass was significantly increased by OV and CC (p < 0.05). The feed egg ratio in the CC group (2.82) was significantly lower than that in the other three groups (p < 0.05). The eggshell thickness (EST), albumen height (AH) and Haugh unit (HU) were decreased by OV and CC (p < 0.05); while yolk color (YC) was increased in the CC and OVC groups (p < 0.05). Egg grade was decreased by OV (p < 0.05). Sensory evaluation showed that there was a trend for increased YC in OV, CC and OVC (p = 0.089). Serum total protein was significantly lower in OV group than those in the control and CC group (p < 0.05); serum albumin content was significantly decreased in OV, CC and OVC groups (p = 0.006). Serum glutathione peroxidase activity in CC and OVC groups was significantly higher than that in the control group (p < 0.05). In conclusion, the present study suggests that CC had a better effect on the performance of the native laying hens than OV. The OV and CC affected egg quality, while YC was increased in CC and OVC groups. The OVC improved YC and serum antioxidative properties of native laying hens without affecting the performance.

Longitudinal characterization of serum metabolome and lipidome reveals that the ceramide profile is associated with metabolic health in early postpartum cows experiencing different lipolysis.

Reduced feed intake in early lactation prompts increased fat mobilization to meet dairy cow energy needs for milk production. The increased lipolysis in cows presents significant health risks with unclear mechanisms. The objectives of our study were to compare the longitudinal profiles of metabolites and lipids of serum from high- and low-lipolysis cows. Forty multiparous Holstein dairy cows were enrolled in the retrospective study. Serum samples were collected on d 7 before expected calving, as well as on d 5, 7, 14, and 21 postpartum. Dairy cows were grouped according to mean serum nonesterified fatty acids on d 5 and 7 after parturition as low (<0.600 mmol/L; n = 8; LFM) and high (>0.750 mmol/L; n = 8; HFM), indicating fat mobilization during early lactation. Lactational performance and serum metabolic parameters related to glucose and lipid metabolism, liver functions, oxidative status, and inflammatory responses were determined. Serum samples were subjected to liquid chromatography-MS-based metabolomics and lipidomics. Despite differences in postpartum BW change, there were no observed variations in milk yield and composition between the 2 groups. Serum ß-hydroxybutyric acid, glucose, leptin, aspartate aminotransferase, IL-6, and tumor necrosis factor alpha were greater in cows with HFM than in cows with LFM. Serum adiponectin, revised quantitative insulin sensitivity check index, and albumin were lower in cows with HFM than in cows with LFM. Intensified fat mobilization in the HFM cows came along with reduced estimated insulin sensitivity, impaired liver functions, and increased oxidative stress and inflammatory responses. Differences in metabolic patterns were observed across the transition period when comparing serum blood matrixes (e.g., in different amino acids, acylcarnitines, and sphingolipids). The serum metabolome of the HFM cows was characterized by higher concentrations of glycine, acylcarnitines, carnosine, Cer(d20:0/18:0), Cer(d18:1/16:0), and Cer(t18:0/24:0) compared with LFM cows. The differential serum metabolites and lipids at different sampling times during the peripartum period were enriched in the sphingolipid metabolism. Differences in serum metabolic status parameters suggest that cows adopt varied metabolic adaptation strategies to cope with energy deficits postpartum. Our investigation found a comprehensive remodeling of the serum metabolic profiles in transition dairy cattle, highlighting the significance of alterations in sphingolipid species, as they play a crucial role in insulin resistance and metabolic disorders.

Rectal microbiomes and serum metabolomics reveal the improved effect of Artemisia ordosica crude polysaccharides on the lactation performance, antioxidant status, and immune responses of lactating donkeys.

This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant status, and immune status of lactating donkeys and analyzing rectal microbiomes and serum metabolomes. Fourteen lactating Dezhou donkeys with similar age (6.16 ± 0.67 yr of BW ± SD), weight (250.06 ± 25.18 kg), DIM (39.11 ± 7.42 d), and average parity of 3 were randomly allocated into 2 treatments: a control group (CON, basal diet) and an AOCP group (AOCP, basal diet with 1.0 g/kg DM AOCP). Ten weeks were allotted for the experiment, 2 wk for adaptation, and 8 wk for collecting data and samples. The results showed that supplementation of donkey diets with AOCP increased lactation performance, including DMI, milking yield, estimated milk yield, solids-corrected milk, ECM, milk fat yield, milk protein yield, milk lactose yield, milk TS yield, and milk SNF yield. The digestibility of DM, CP, ADF, and NDF was increased in the AOCP group compared with the CON group. The AOCP group increased the concentrations of IgA, IgG, and IgM, the activities of the superoxide dismutase, catalase, and total antioxidant capacity in the serum. Artemisia ordosica crude polysaccharides decreased the concentrations of tumor necrosis factor-α, nitric oxide, reactive oxygen species, and malondialdehyde in the serum. Compared with the CON group, AOCP increased propionate, butyrate, isovalerate, and total VFA concentrations in rectal feces (P < 0.05). The addition of AOCP to increased diversity (Shannon index) and altered structure of the rectal microflora. As a result of AOCP supplementation, there has been a significant improvement in the colonization of beneficial bacteria, including Lactobacillus, Unclassified_f_Prevotellacea, Ruminococcus, and Fibrobacter genera. In contrast, a decrease in the colonization of the Clostridium_sensu_stricto_1 bacterial genus and other pathogenic bacteria was observed. Meanwhile, metabolomics analysis found that AOCP supplementation upregulated metabolites l-tyrosine content while downregulating 9(S)-HODE, choline, sucrose, lysophosphatidylcholine (LysoPC) (18:0), LysoPC (18:1(9Z)), and LysoPC (20:2(11Z,14Z)) concentrations. These altered metabolites were involved in the PPAR signaling pathway, prolactin signaling pathway, glycerophospholipid metabolism, carbohydrate digestion and absorption, and tyrosine metabolism pathways, which were mainly related to antioxidant capacity, immune responses, and protein metabolism in the lactating donkeys. As a consequence of feeding AOCP diets, beneficial bacteria were abundant, and antioxidant and protein metabolism-related pathways were enriched, which may enhance lactation performance in donkeys. Therefore, supplementing AOCP diets is a desirable dietary strategy to improve donkey health and lactation performance.

Global trends in deaths and disability-adjusted life years of diabetes attributable to second-hand smoke and the association with smoke-free policies.

OBJECTIVES: The diabetic burden attributable to second-hand smoke (SHS) is a global public health challenge. We sought to explore the diabetic burden attributable to SHS by age, sex, and socioeconomic status during 1990-2019 and to evaluate the health benefit of smoke-free policies on this burden. STUDY DESIGN: Cross-sectional study. METHODS: The diabetic burden attributable to SHS was extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 dataset. Country-level smoke-free policies were obtained from the World Health Organization Global Health Observatory. The deaths or disability-adjusted life years (DALYs) were quantified, and the average annual percentage changes were calculated. Hierarchical linear mixed models were applied to evaluate the health effects. RESULTS: From 1990 to 2019, the absolute number of global deaths and DALYs of diabetes attributable to SHS has doubled, and the age-standardised rate has significantly increased. The disease burden was higher in females than in males and increased with increasing age. The SHS-related diabetic burden varied across regions and countries. Age-standardised death or DALY rates first increased and then decreased with increased Socio-demographic Index (SDI), peaking in the 0.60-0.70 range. In low to low-middle, and middle to high-middle SDI countries, SHS-related diabetic deaths and DALYs were significantly lower in countries with more than 3 smoke-free public places than in countries with 0-2 smoke-free public places. CONCLUSIONS: More attention should be paid to females and the elderly, who bear a heavy SHS-related diabetic burden. Banning smoking in public places was associated with reduced burden of SHS-attributable diabetes, especially in low to middle social development countries.

Estimation and projection of the burden of hearing loss in China: findings from the Global Burden of Disease Study 2019.

OBJECTIVES: The comprehensive description of hearing loss in China and the shifting pattern remain unclear. We conducted the study to estimate the burden of hearing loss in China and project the trends from 2020 to 2034. STUDY DESIGN AND METHOD: Data on the disease burden of hearing loss were extracted from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPCs) were calculated to quantify the trends of the age-standardized rates. Projections of hearing loss burden were made until 2034 using Bayesian age-period-cohort analysis. RESULTS: In China, prevalent cases of hearing loss increased from 224.4 million in 1990 to 426.5 million in 2019, representing an increase of 90.1 %. The age-standardized prevalence rate of hearing loss ranged from 22,592.8/100,000 in 1990-22,612.4/100,000 in 2019, with an EAPC of 0.003 %, representing a stable trend. Of the category of hearing loss, mild hearing loss accounted for the highest proportion, with 331.4 million people. More than 95 million people had moderate-to-complete hearing loss. Moreover, hearing loss was mostly attributable to age-related and other factors for adults and otitis media for children younger than 10 years. Based on the projection results, there will be 561 million people (40.1 % of the total population) have hearing loss by 2034. CONCLUSIONS: The prevalent cases of hearing loss in China substantially increased over the last 30 years. Over two in five Chinese people will have hearing loss by 2034, thus suggesting more solutions should be established to reduce the burden of hearing loss.

The impacts of exposure to risk factors during youth on the increasing global trend of early-onset pancreatic cancer.

OBJECTIVES: An increasing trend of pancreatic cancer in young adults has emerged in some countries. This study aimed to investigate global trends of pancreatic cancer in young adults and explore the impact of exposure to risk factors on pancreatic cancer incidence during youth. METHODS: Global and national data on pancreatic cancer incidence, disability-adjusted life-years, attributive mortality, and summary exposure values of risk factors were retrieved from the Global Burden of Disease 2019. The average annual percent change (AAPC) of incidence and mortality was calculated. Additionally, generalized additive models were applied to explore the non-linear associations between the levels and changes in the Human Development Index and AAPC. RESULTS: Global pancreatic cancer incidence increased during various periods from 1990 to 2019, particularly in adults aged <45 years from 2010 to 2019, at an average annual increase rate of 0.7% (95% confidence interval: 0.4-1.0%). The AAPC of early-onset pancreatic cancer incidence from 2010 to 2019 was negatively correlated with Human Development Index levels in both 2010 and 2019 but positively correlated with Human Development Index acceleration. Significant increases in early-onset pancreatic cancer incidence were observed over this period in 32 of 88 countries, primarily in South America, North America, Oceania, and Africa. Early-onset pancreatic cancer mortality attributed to high body mass index and fasting plasma glucose increased, while that attributed to tobacco use declined. CONCLUSIONS: An increasing trend has emerged in the global incidence and burden of early-onset pancreatic cancer over the last few decades. This rise may partly be attributed to global epidemics of high body mass index and fasting plasma glucose.

Short-term effects of air pollutants and meteorological factors on outpatients with allergic airway disease in Ningbo, China, 2015-2021.

OBJECTIVES: The allergic airway disease, such as allergic rhinitis, chronic rhinosinusitis, asthma, is a general term of a range of inflammatory disorders affecting the upper and lower airways and lung parenchyma. This study aimed to investigate the short-term effects of air pollutants and meteorological factors on AAD-related daily outpatient visits. STUDY DESIGN: An ecological study. METHODS: Data on outpatient visits due to AAD (n = 4,554,404) were collected from the platform of the Ningbo Health Information from January 1, 2015 to December 31, 2021. A Quasi-Poisson generalized additive regression model was established to analyze the lag effects of air pollution on daily outpatient visits for AAD. Restricted cubic spline functions were used to explore the potential non-linear relationships between air pollutants and meteorological and daily outpatient visits for AAD. RESULTS: PM2.5, PM10, SO2, NO2, or CO were associated with daily outpatient visits for AAD, and there was a significant increasing trend in the cumulative lag effects. SO2 had the largest effect at Lag07, with a 25.3% (95% CI: 21.6%-29.0%) increase in AAD for every 10 µg/m3 increase in exposure concentration. Subgroup analysis showed that the 0-18 years old age group had the strongest effects, especially for AR, and all effects were stronger in the cold season. CONCLUSIONS: Given that patients aged 0-18 are more susceptible to environmental changes, protective measures specifically for children should be taken during dry and cold weather conditions with poor air quality.

A retrospective cohort study of intra-corporeal versus extra-corporeal anastomosis for right hemicolectomy with cost-effectiveness analysis.

BACKGROUND: We aimed to compare outcomes and cost effectiveness of extra-corporeal anastomosis (ECA) versus intra-corporeal anastomosis (ICA) for laparoscopic right hemicolectomy using the National Surgical Quality Improvement Programme data. METHODS: Patients who underwent elective laparoscopic right hemicolectomy for colon cancer from January 2018 to December 2022 were identified. Non-cancer diagnoses, emergency procedures or synchronous resection of other organs were excluded. Surgical characteristics, peri-operative outcomes, long-term survival and hospitalisation costs were compared. Incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness. RESULTS: A total of 223 patients (175 ECA, 48 ICA) were included in the analysis. Both cohorts exhibited comparable baseline patient, comorbidity, and tumour characteristics. Distribution of pathological TMN stage, tumour largest dimension, total lymph node harvest and resection margin lengths were statistically similar. ICA was associated with a longer median operative duration compared with ECA (255 min vs. 220 min, P < 0.001). There was a quicker time to gastrointestinal recovery, with a shorter median hospital stay in the ICA group (4.0 versus 5.0 days, P = 0.001). Overall complication rates were comparable. ICA was associated with a higher surgical procedure cost (£6301.57 versus £4998.52, P < 0.001), but lower costs for ward accommodation (£1679.05 versus £2420.15, P = 0.001) and treatment (£3774.55 versus £4895.14, P = 0.009), with a 4.5% reduced overall cost compared with ECA. The ICER of -£3323.58 showed ICA to be more cost effective than ECA, across a range of willingness-to-pay thresholds. CONCLUSION: ICA in laparoscopic right hemicolectomy is associated with quicker post-operative recovery and may be more cost effective compared with ECA, despite increased operative costs.

[Application of cardiac magnetic resonance imaging in subclinical systemic sclerosis primary heart involvement].

Objectives: Primary cardiac involvement (SSc-PHI) in systemic sclerosis is an important prognostic factor. We aimed to characterize and identify subclinical SSc-PHI using cardiovascular MRI to determine whether disease severity and serum biomarkers are associated with subclinical SSc-PHI. Methods: A total of 26 patients with SSc who had no history of cardiovascular disease or pulmonary hypertension underwent 3 T-enhanced cardiovascular MRI. Measurements included native T1, extracellular volume, advanced gadolinium enhancement, T2 mapping, and left ventricular volume function. Troponin T and N telencephalic natriuretic peptide precursors were also determined. Results: LGE was observed in 13 of 26 patients (50.0%), suggesting focal fibrosis, and T2 mapping was significantly higher in the dcSSc group than in the lcSSc group (P=0.009). Left ventricular volume and function were within the normal range in all patients, but final systolic left ventricular volume was significantly higher in dcSSc than in lcSSc (P=0.021). The modified Rodnan skin score (mRSS) was significantly higher in patients with LGE focal fibrosis (P=0.019). Logistic regression analysis confirmed the association between mRSS and LGE (OR=1.224, P=0.037). In multivariate analysis, T2 mapping was negatively correlated with disease course, and was correlated with dcSSc and fingertip ulcer (R2=0.711, P=0.018, P=0.013, P=0.030). Troponin T was correlated with T2 mapping (r=0.555, P=0.049). Conclusions: Subclinical SSc-PHI is characterized by diffuse and focal myocardial fibrosis, but preserves myocardial systolic function. Subclinical SSC-Phi is associated with TNT, SSc disease severity, and complex peripheral vascular disease. These data provide information for identifying individuals at risk of SSc-PHI.

[Analyses of the risk factors for the progression of primary antiphospholipid syndrome to systemic lupus erythematosus].

Objectives: Analyze the clinical characteristics of patients with primary antiphospholipid syndrome (PAPS) progressing to systemic lupus erythematosus (SLE).Explore the risk factors for the progression from PAPS to SLE. Methods: The clinical data of 262 patients with PAPS enrolled in Peking Union Medical College Hospital from February 2005 to September 2021 were evaluated. Assessments included demographic data, clinical manifestations, laboratory tests (serum levels of complement, anti-nuclear antibodies, anti-double-stranded DNA antibodies), treatment, and outcomes. Kaplan-Meier analysis was used to calculate the prevalence of SLE in patients with PAPS. Univariate Cox regression analysis was employed to identify the risk factors for PAPS progressing to SLE. Results: Among 262 patients with PAPS, 249 had PAPS (PAPS group) and 13 progressed to SLE (5.0%) (PAPS-SLE group). Univariate Cox regression analysis indicated that cardiac valve disease (HR=6.360), positive anti-double-stranded DNA antibodies (HR=7.203), low level of complement C3 (HR=25.715), and low level of complement C4 (HR=10.466) were risk factors for the progression of PAPS to SLE, whereas arterial thrombotic events (HR=0.109) were protective factors (P<0.05 for all). Kaplan-Meier analysis showed that the prevalence of SLE in patients suffering from PAPS with a disease course>10 years was 9%-15%. Hydroxychloroquine treatment had no effect on the occurrence of SLE in patients with PAPS (HR=0.753, 95%CI 0.231-2.450, P=0.638). Patients with≥2 risk factors had a significantly higher prevalence of SLE compared with those with no or one risk factor (13-year cumulative prevalence of SLE 48.7% vs. 0 vs. 6.2%, P<0.001 for both). Conclusions: PAPS may progress to SLE in some patients. Early onset, cardiac-valve disease, positive anti-dsDNA antibody, and low levels of complement are risk factors for the progression of PAPS to SLE (especially in patients with≥2 risk factors). Whether application of hydroxychloroquine can delay this transition has yet to be demonstrated.