[Epidemiological characteristics of local visceral leishmaniasis in Beijing Municipality from 2021 to 2023].

OBJECTIVE: To investigate the epidemiological characteristics of local visceral leishmaniasis in Beijing Municipality from 2021 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy. METHODS: Epidemiological data of visceral leishmaniasis cases reported in Beijing Municipality from 2021 to 2023 were collected from the National Health Informatization Disease Prevention and Control Information System, and the epidemiological characteristics of local visceral leishmaniasis cases were analyzed using a descriptive epidemiological method. In November 2021 and 2023, 50 to 100 permanent residents were voluntarily selected within a 100 meter radius of sites where patients lived or acquired Leishmania infections, and venous blood was sampled for anti-Leishmania antibody testing. Venous blood was sampled from dogs for anti-Leishmania antibody testing in natural villages where patients lived or acquired Leishmania infections, or in districts where Leishmania infected dogs were reported. In addition, sandflies were captured with CO2 mosquito traps and fine mesh nets in natural villages where patients lived or acquired Leishmania infections from May to September, 2021 and 2023, for sandfly species identification. RESULTS: A total of 4 local visceral leishmaniasis cases were reported in Beijing Municipality from 2021 to 2023, with ages of 2 to 77 years, and acquiring Leishmania infections in Mentougou District (2 cases), Changping District (1 case), and Yanqing District (1 case). The anti-Leishmania antibody testing was all negative in 73 human blood samples and the sero-prevalence of anti-Leishmania antibody was 25.00% in 36 venous blood samples from domestic dogs in 2021, with a total of 4 520 Phlebotomus chinensis captured. The sero-prevalence of anti-Leishmania antibody was 0.51% in 198 human blood samples and 13.58% in 243 venous blood samples from domestic dogs in 2023, with 16.10%, 25.00%, 17.78% and 3.13% sero-prevalence in dogs sampled from Mentougou District, Changping District, Yanqing District and Haidian District, respectively (P = 0.011), while a total of 1 712 Ph. chinensis were captured, including 1 421 female sandflies (86.54%). CONCLUSIONS: The prevalence of local visceral leishmaniasis was low in Beijing Municipality from 2021 to 2023; however, there is a risk of further spread in the epidemic foci. Intensified visceral leishmaniasis surveillance and control is recommended.

[Progress in cohort study of children and adolescents health].

Cohort study of children and adolescents health is an ideal method to explore health-related problems from childhood to adulthood, to which more attention has been paid. This paper summarizes the progress in cohort study of children and adolescents health conducted both at home and abroad by introducing the study design, main contents. Emphasizing the international exchange and cohort integration, continuously expanding cohort research field, and using multi-source data for high-quality follow-up have become the trend of cohort study of children and adolescents health.

[Epidemiological characteristics of human respiratory syncytial virus in influenza-like illness in Shenzhen City from 2019 to 2023].

Objective: To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among cases presenting with influenza-like illness (ILI) in Shenzhen City from 2019 to 2023. Methods: Respiratory specimens were collected from two national sentinel hospitals in Shenzhen from March 2019 to December 2023, specifically targeting cases of ILI. The real-time PCR method was used for the detection and genotyping of HRSV. Basic demographic information was collected and used for the epidemiological analysis. Results: A total of 9 278 respiratory specimens of influenza-like cases were collected and detected, with a total positive rate of 4.77% (443/9 278) for HRSV. In 2021 (8.48%, 167/1 970), the positive rate of HRSV was significantly higher than in 2019 (3.35%, 52/1 552), 2022 (1.80%, 39/2 169), and 2023 (4.49%, 133/2 960), and the difference was statistically significant (χ2=102.395, P<0.001). The prevalence of HRSV was mainly in summer and early autumn (September), and there was an abnormal increase in the positive rate of HRSV in winter 2022. The highest positive rate of HRSV was in children under five years old (9.84%, 330/335). The typing results showed that in 2022, the prevalence of HRSV-A was predominant (71.79%, 28/39), and in 2023, HRSV-A and HRSV-B subtypes coexisted. Conclusions: The prevalence of HRSV in Shenzhen from 2019 to 2023 has obvious seasonality, mainly in summer and early autumn. Children under five years old are the main population of HRSV infections.

[Construction and application of a risk index of Echinococcus infection based on the classification of echinococcosis lesions].

OBJECTIVE: To investigate the feasibility of constructing the risk index of Echinococcus infection based on the classification of echinococcosis lesions, so as to provide insights into the management of echinococcosis. METHODS: The imaging data of echinococcosis cases were collected from epidemiological surveys of echinococcosis in China from 2012 to 2016, and the detection of incident echinococcosis cases was captured from the annual echinococcosis prevention and control reports across provinces (autonomous regions) and Xinjiang Production and Construction Corps in China from 2017 to 2022. After echinococcosis lesions were classified, a risk index of Echinococcus infection was constructed based on the principle of discrete distribution marginal probability and multi-group classification data tests. The correlation between the risk index of Echinococcus infection and the detection of incident echinococcosis cases was evaluated in the provinces (autonomous regions and corps) from 2017 to 2022, and the correlations between the short and medium-term risk indices and between the medium and long-term risk indices of Echinococcus infection were examined using a univariate linear regression model. RESULTS: A total of 4 014 echinococcosis cases in China from 2012 to 2016 were included in this study. The short-, medium- and long-term risk indices of E. granulosus infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 4.12 to 708.65, all P values < 0.05), with high short- (0.058), medium- (0.137) and long-term risk indices (0.104) in Tibet Autonomous Region, and the short-, medium- and long-term risk indices of E. multilocularis infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 6.74 to 122.60, all P values < 0.05), with a high short-term risk index in Sichuan Province (0.016) and high medium- (0.009) and long-term risk indices in Qinghai Province (0.018). There were no significant correlations between the risk index of E. granulosus infection and the detection of incident cystic echinococcosis cases during the study period (t = -0.518 to 2.265, all P values > 0.05), and strong correlations were found between the risk indices of E. multilocularis infection and the detection of incident alveolar echinococcosis cases (including mixed type) in 2018, 2020, 2021, 2022, during the period from 2017 through 2020, from 2017 through 2021, from 2017 through 2022 (all r values > 0.7, t = 2.521 to 3.692, all P values < 0.05). Linear regression models were established between the risk index of E. multilocular infection and the detection of alveolar echinococcosis cases (including mixed type), and the models were all statistically significant (b = 0.214 to 2.168, t = 2.458 to 3.692, F = 6.044 to 13.629, all P values < 0.05). The regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. granulosus infection were 2.339 and 0.765, and the regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. multilocular infection were 0.280 and 1.842, with statistical significance seen in both the regression coefficients and regression models (t = 16.479 to 197.304, F = 271.570 to 38 928.860, all P values < 0.05). CONCLUSIONS: The risk index of Echinococcus infection has been successfully established based on the classification of echinococcosis lesions, which may provide insights into the prevention and control, prediction, diagnosis and treatment, and classified management of echinococcosis.

Endoscopic dacryocystorhinostomy with and without bicanalicular silicone tube in patients with a small lacrimal sac: a comparative study.

BACKGROUND: To establish whether bicanalicular silicone tube intubation is required during endoscopic dacryocystorhinostomy (En-DCR) for treating chronic dacryocystitis with a small lacrimal sac. METHODS: In total, this study enrolled 264 patients diagnosed with unilateral chronic dacryocystitis with small lacrimal sacs via computed tomography-dacryocystography that underwent En-DCR from March 2016-September 2020. Patients were randomized into two treatment groups, with those in group A undergoing tubes intubation and those in group B not undergoing this procedure. The tubes were removed 3 months post-operation in group A. Surgical outcomes and related complication rates were then compared. RESULTS: This study included 242 patients, including124 and 118 in groups A and B, respectively. At the three-month follow-up time point, 12.90% of patients in group A exhibited ostial granulation tissue, with this frequency with no differences observed in group B (11.86%). At 6 months post-surgery, 80.65% of patients in group A and 72.88% of patients in group B exhibited successful surgical outcomes, with no significant differences between groups. At 9 months postoperatively, the overall effective success rate was 60.74%, and the success rate was significantlyhigher in group A relative to group B (group A: 75.81%; group B: 44.92%). There were no failed patient outcomes observed as of the 12-month follow-up time point. CONCLUSIONS: While En-DCR-based treatment of chronic dacryocystitis in those with smalllacrimal sacs did not yield satisfactory outcomes with respect to the overall effective success rate, these results suggest that intraoperative intubation may improve success rates in long-term follow-up.

[High expression of fragile X mental retardation protein inhibits ferroptosis of colorectal tumor cells by activating the RAS/MAPK signaling pathway].

OBJECTIVE: To investigate the mechanism by which fragile X mental retardation protein (FMRP) regulates ferroptosis evasion in colorectal cancer (CRC) cells. METHODS: We examined FMRP expression levels in CRC cell lines using RT-qPCR and Western blotting and analyzed the biological functions and signaling pathways involved in FMRP-mediated regulation of CRC progression using the TCGA database. A lentiviral FMRP overexpression vector (Lv-FMRP) and 3 knockdown vectors (siFMRP-1, siFMRP-2, and siFMRP-3) were constructed, and their effects on proliferation of HCT116 cells were examined using CCK8 assay and plate clone formation assay; the changes in cell ferroptosis level was determined using MDA/ROS/GSH/Fe2+ kits, mitochondrial membrane potential changes were detected using JC-1 fluorescence staining, and the expressions of proteins associated with ferroptosis and the RAS/MAPK signaling pathway were detected using Western blotting. The subcutaneous tumorigenic potential of the transfected cells was evaluated in nude mice. RESULTS: Compared with normal colonic mucosal epithelial NCM460 cells, the CRC cell lines had significantly higher FMRP expression level. Bioinformatics analysis suggested the involvement of FMRP in regulation of reactive oxygen, oxidative stress-induced cell death, mitochondrial respiration, and glutathione metabolism pathways. In the cell experiments, FMRP knockdown significantly inhibited proliferation of HCT116 cells, lowered cellular GSH content, increased MDA and ROS levels, Fe2+ fluorescence intensity, and mitochondrial membrane potential, and decreased SLC7A11/GPX4 protein expressions and the phosphorylation levels of ERK, MEK, MAPK, and RAS proteins; FMRP overexpression resulted in the opposite changes in the cells. In the tumor-bearing nude mice, HCT116 cells with FMRP knockdown showed attenuated tumorigenic potential with lowered xenograft growth rate and reduced SLC7A11 expression in the xenograft. CONCLUSION: The high expression of FMRP inhibits ferroptosis in CRC cells and promotes progression of CRC by activating the RAS/MAPK signaling pathway.

[Exploratory analysis of gut microbiota differences in patients with bronchial asthma of different inflammatory types].

Objective: To observe the characteristics and differences of gut microbiota in asthma patients with different inflammatory types through metagenomic analysis. Methods: Adults aged ≥18 years who visited the Respiratory Clinic of Peking University Third Hospital from August 1, 2021 to August 31, 2022 and were primarily diagnosed with asthma were selected as the study subjects. Finally, 29 patients with stable asthma were included. Fresh fecal samples were collected and the fecal DNA was extracted for high-throughput 16sRNA sequencing of gut microbiota. The diversity and community structure of gut microbiota in different groups of asthma patients were compared, and the species differences were analyzed through random forest and LEfSe analysis. Results: There were sex-based differences in asthma patients with different types of inflammation, and the proportion of female patients was higher in neutrophilic asthma patients (χ2=4.14, P=0.042). There was no significant intergroup difference in the alpha diversity of gut microbiota among asthma patients with different inflammatory types, but there were significant differences in the microbiome. Patients with neutrophilic asthma had higher relative abundance of Bacillales (P=0.029) and Oscillospiraceae (P=0.015). In species LEfSe analysis, patients with eosinophilic asthma had a higher relative abundance of fungi. Conclusion: There are intergroup differences in the gut microbiota of asthma patients with different inflammation types, and fungi are biomarkers that distinguish the differences in gut microbiota between patients with eosinophilic asthma and neutrophilic asthma.

Interplay of metabolic dysfunction-associated fatty liver disease and papillary thyroid carcinoma: insights from a Chinese cohort.

PURPOSE: Thyroid cancer is one of a set of extrahepatic cancers that closely linked to metabolic dysfunction-associated fatty liver disease (MAFLD). However, the connection between MAFLD and the characteristics of papillary thyroid cancer (PTC) remains unexplored. METHODS: Between Jan 2020 and Oct 2022, surgical cases of PTC patients were examined at the first Affiliated Hospital of Wenzhou Medical University. Clinical data extracted from the electronic medical system underwent a rigorous comparison between two groups, classified based on MAFLD criteria, using logistic regression analysis. RESULTS: In this study of 4,410 PTC patients, 18.3% had MAFLD. MAFLD emerged as a distinct risk factor for lymph node metastasis (OR = 1.230, 95% CI 1.018-1.487) in this cohort, especially in females (OR = 1.321, 95% CI 1.026-1.702) and those with BMI ≥ 23 kg/m2 (OR = 1.232, 95% CI 1.004-1.511). The presence of MAFLD was found to significantly elevate the risk of BRAF V600E mutation in both subgroups characterized by FIB-4 score ≥ 1.3 (OR = 1.968, 95% CI 1.107-3.496) and BMI < 23 kg/m2 (OR = 2.584, 95% CI 1.012-6.601). Moreover, among the subset of individuals without non-alcoholic fatty liver disease (NAFLD), it was noted that MAFLD considerably increased the likelihood of tumor multifocality (OR = 1.697, 95% CI 1.111-2.592). Nevertheless, MAFLD did not exhibit any correlation with increased tumor size, extra-thyroidal extension (ETE), or later TNM stage in PTC. CONCLUSION: In this cross-sectional study, we discovered a significant association between MAFLD and increased occurrences of lymph node metastasis. Furthermore, MAFLD was linked to a higher chance of BRAF V600E mutation and the presence of multiple tumors in certain subgroups.

[Changes of hemodynamic parameters in normal pregnant women and their relationship with maternal basic characteristics].

Objective: To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics. Methods: A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline. Results: (1) CO (r=0.155, P<0.001), TFC (r=0.338, P<0.001), MAP (r=0.204, P<0.001), and HR (r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation (r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age (r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR (P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy (P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions: The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

[Investigation of the population diversity of intermediate host snails and crabs of Paragonimus along Jiulong River, Zhangjiang River and Dongxi River basins in southern Fujian Province].

OBJECTIVE: To investigate the population distribution of intermediate host snails and crabs of Paragonimus along the Jiulongjiang River, Zhangjiang River, and Dongxi River basins in Bopingling Mountain, southern Fujian Province, so as to provide baseline data for researches on parasitic disease prevention and control and enlargement of samples in the parasitic resource bank. METHODS: A total of 23 villages in 8 counties (districts) along the Jiulong River, Zhangjiang River, and Dongxi River basins in Zhangzhou City, Fujian Province were selected as survey sites during the period from November 2020 through March 2023, and snail and freshwater crabs were sampled from 1 to 3 streams and ditches neighboring residential areas in each village. Morphological identification of snails was performed according to the external morphological characteristics of collected snail shells, and the unidentified snail species sampled from the natural foci of paragonimiasis in Yunxiao County were subjected to se-quence analysis of the mitochondrial cytochrome oxidase 1 (CO1) gene. The crab species was identified by observing the morphological characteristics of the terminal segment of the first pleopod of male crabs, and Paragonimus cercariae and metacercariae were detected in collected snails. RESULTS: The shells of the unidentified snails sampled from the natural foci of paragonimiasis in Yunxiao County were approximately 50 mm in height and 18 mm in width, thick and solid, long tower cone-shaped, and had 8 to 10 whorls. CO1 gene sequence analysis identified the snail species as Sulcospira hainanensis. A total of 6 freshwater snail species belonging to 5 genera within 3 families, identified 23 survey sites, including Semisulcospira libertina, Paludomus zhangchouensis and S. hainanensis that belonged to the Family Pleurceridae, Tricula fujianensis and T. huaanensis that belonged to the subfamily Triculinae, Family Pomatiopsidae, and Melanoides tuberculata (Family Thiaridae), and 11 species of freshwater crabs belonging to 5 genera within 2 families were identified, including Sinopotamon genus of S. jianglense, S. pinheense, and S. zhangzhouense, Huananpotamon genus of H. planopodum and H. zhangzhouense, Nanhaipotamon genus of N. huaanense and N. longhaiense, and Minpotamon genus of M. nasicum and M. auritum that belonged to the Family Potamidae, and Somanniathelphusa genus of S. huaanensis and S. zhangpuensis (Family Parathelphusidae). In addition, the prevalence of P. westermani cercariae infections was 0.08% (2/2 317) in P. zhangchouensis from Danyan Village in Changtai District and 0.09% (1/1 039) in S. hainanensis from Jinkeng Village in Yunxiao County, and the prevalence of P. westermani metacercariae infections was 25.81% (8/31) in S. jianglense from Danyan Village in Changtai District, and 26.31% (5/19) in S. zhangzhouense from Jinkeng Village in Yunxiao County, respectively. CONCLUSIONS: There is a population diversity in the intermediate host snails and crabs along the Jiulongjiang River, Zhangjiang River, and Dongxi River basins in Bopingling Mountain, southern Fujian Province, and P. zhangzhouensis and S. hainanensis are, for the first time, confirmed as the first intermediate hosts of P. westermani.

The factors influencing the occurrence of post-ischemic stroke depression and its relationship with the burden score of cerebral small vessel disease.

OBJECTIVE: This study explored the determinants of post-stroke depression (PSD) in ischemic stroke (AIS) patients and its association with the burden score of cerebral small vessel disease (CSVD). PATIENTS AND METHODS: We analyzed 374 AIS patients treated between January 2020 and January 2022. Patients were categorized into 90 with PSD and 284 without PSD, enabling an investigation into PSD risk factors and the CSVD-PSD relationship. RESULTS: There was no significant difference in health factors between PSD and non-PSD patients (p>0.05). However, significant disparities were noted in age, gender, initial Barthel Index (BI), Mini-Mental State Examination (MMSE) score, plasma fibrinogen, homocysteine, red cell distribution width, National Institutes of Health Stroke Scale (NIHSS) score, and CSVD burden score (p<0.05). Regression analysis indicated that these variables were pivotal PSD predictors (OR>1, p<0.05). Surprisingly, a positive correlation with PSD occurrence was found for age, NIHSS score, plasma fibrinogen, homocysteine levels, red cell distribution width, CSVD burden score (r=0.565, 0.615, 0.482, 0.514, 0.572, 0.608, respectively; p<0.05). Meanwhile, the MMSE score and BI index were inversely related to PSD onset (r=-0.604, -0.590; p<0.05). The ROC curve analysis of the combination model based on MMSE, NIHSS and CSVD score revealed an AUC of 0.926 and Youden's index of 0.744. CONCLUSIONS: Age, MMSE score, BI index, NIHSS score, plasma fibrinogen concentration, homocysteine level, red blood cell distribution width, and CSVD burden score are all major influencing factors in the occurrence of PSD. The combination model based on MMSE, NIHSS, and CSVD scores presented a valuable approach to predicting PSD.

[Application of computational fluid dynamics in the evaluation of left ventricular function in cardiomyopathies and coronary disease].

Computational fluid dynamics (CFD) is an emerging technology applied in the field of cardiovascular medicine, which can obtain hemodynamic data by simulating the blood flow in the patient's heart for cardiac function assessment and disease diagnosis. Left ventricular function plays a key role in the occurrence and development of cardiomyopathies and coronary disease. CFD can reconstruct the left ventricular anatomic structures of patients to clarify pathophysiologic mechanisms and analyze hemodynamic parameters to evaluate left ventricular function, verify surgical efficacy, and guide surgical strategy, which has a positive effect on achieving early diagnosis and reducing mortality from cardiomyopathies and coronary disease. At present, there are still technical limitations in the large-scale clinical application of CFD, and various solutions are being developed and tested, and further improvement and refinement are needed.

[A digital droplet PCR detection technique based on filter faster R-CNN].

OBJECTIVE: To propose a method for mitigate the impact of anomaly points (such as dust, bubbles, scratches on the chip surface, and minor indentations) in images on the results of digital droplet PCR (ddPCR) detection to achieve high-throughput, stable, and accurate detection. METHODS: We propose a Filter Faster R-CNN ddPCR detection model, which employs Faster R-CNN to generate droplet prediction boxes followed by removing the anomalies within the positive droplet prediction boxes using an outlier filtering module (Filter). Using a plasmid carrying a norovirus fragment as the template, we established a ddPCR dataset for model training (2462 instances, 78.56%) and testing (672 instances, 21.44%). Ablation experiments were performed to test the effectiveness of 3 filtering branches of the Filter for anomaly removal on the validation dataset. Comparative experiments with other ddPCR droplet detection models and absolute quantification experiments of ddPCR were conducted to assess the performance of the Filter Faster R-CNN model. RESULTS: In low-dust and dusty environments, the Filter Faster R-CNN model achieved detection accuracies of 98.23% and 88.35% for positive droplets, respectively, with composite F1 scores reaching 99.15% and 99.14%, obviously superior to the other models. The introduction of the filtering module significantly enhanced the positive accuracy of the model in dusty environments. In the absolute quantification experiments, a regression line was plotted using the results from commercial flow cytometry equipment as the standard concentration. The results show a regression line slope of 1.0005, an intercept of -0.025, and a determination coefficient of 0.9997, indicating high consistency between the two results. CONCLUSION: The ddPCR detection technique using the Filter Faster R-CNN model provides a robust detection method for ddPCR under various environmental conditions.

The ability of a portable near infrared instrument to evaluate the shelf-life of fresh and thawed goat muscles.

The objective of this study was to evaluate the use of a portable near infrared (NIR) instrument to monitor the shelf-life of four goat muscles [longissimus thoracis et lumborum (LTL), semimembranosus (SM), semitendinosus (ST) and biceps femoris (BF)] stored for up to 8 days (4 °C). The NIR spectra of the muscle samples were collected at day 0, and after 1, 4 and 8 days of storage using a MicroNIR instrument (900-1600 nm). The coefficient of determination in cross-validation (R2) and the standard error in cross validation (SECV) obtained for the prediction of days of storage ranged between 0.76 and 0.86, where the SECV ranged from 0.32 to 0.41. The best statistics in cross-validation were obtained for the prediction of days of storage in the BF samples, followed by the ST and LTL muscles. Differences in the PLS loadings for the cross-validation models were observed due to the interactions between the different muscle samples and days of storage. Overall, these results showed the potential of NIR spectroscopy to identify the time of storage in four different goat muscles. Similar data and techniques could be used to predict the remaining shelf life of meat derived from different species under storage. This information can then be used as a tool to predict and guarantee the safety of meat samples to the consumer along the meat supply and value chains.

Imaging the Meissner effect in hydride superconductors using quantum sensors.

By directly altering microscopic interactions, pressure provides a powerful tuning knob for the exploration of condensed phases and geophysical phenomena1. The megabar regime represents an interesting frontier, in which recent discoveries include high-temperature superconductors, as well as structural and valence phase transitions2-6. However, at such high pressures, many conventional measurement techniques fail. Here we demonstrate the ability to perform local magnetometry inside a diamond anvil cell with sub-micron spatial resolution at megabar pressures. Our approach uses a shallow layer of nitrogen-vacancy colour centres implanted directly within the anvil7-9; crucially, we choose a crystal cut compatible with the intrinsic symmetries of the nitrogen-vacancy centre to enable functionality at megabar pressures. We apply our technique to characterize a recently discovered hydride superconductor, CeH9 (ref. 10). By performing simultaneous magnetometry and electrical transport measurements, we observe the dual signatures of superconductivity: diamagnetism characteristic of the Meissner effect and a sharp drop of the resistance to near zero. By locally mapping both the diamagnetic response and flux trapping, we directly image the geometry of superconducting regions, showing marked inhomogeneities at the micron scale. Our work brings quantum sensing to the megabar frontier and enables the closed-loop optimization of superhydride materials synthesis.

Long-term efficacy and safety of baricitinib in patients with severe alopecia areata: 104-week results from BRAVE-AA1 and BRAVE-AA2.

BACKGROUND: Efficacy of the Janus kinase (JAK) inhibitor baricitinib for severe alopecia areata (AA) continuously increased over 52 weeks in two Phase 3 trials. There are limited long-term data on JAK inhibitors in AA. OBJECTIVES: To evaluate efficacy and safety of baricitinib for severe AA through 104 weeks of continuous therapy. METHODS: Integrated data from the BRAVE-AA1 and BRAVE-AA2 Phase 3 trials included adults with Severity of Alopecia Tool (SALT) scores ≥50 (≥50% scalp hair loss) randomized to and continuously treated with 2-mg or 4-mg baricitinib through Week 104. Patients who qualified to remain on continuous treatment included subjects who achieved SALT score ≤20 at Week 52 (Week-52 responders; 2-mg: N = 65; 4-mg: N = 129) and baricitinib 4-mg-treated patients who had SALT score >20 at Week 52 but achieved SALT score ≤20 at prior visit(s) and/or had significant improvement in eyebrow or eyelash hair growth relative to baseline by Week 52 (Week-52 mixed responders; N = 110). Week-104 outcomes included the proportion of patients achieving SALT score ≤20 (≤20% scalp hair loss). Data were censored after treatment discontinuation. RESULTS: Among baricitinib 4-mg-treated and baricitinib 2-mg-treated Week-52 responders, 90.7% and 89.2%, respectively, maintained SALT score ≤20 at Week 104. Among Week-52 mixed responders, 39.1% reached SALT score ≤20 by Week 104. Continued improvement in eyebrow and eyelash regrowth was observed across groups. The most frequent treatment-emergent adverse events were COVID-19, upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection and creatine phosphokinase increase. CONCLUSIONS: Baricitinib demonstrated a high level of maintenance of efficacy over 104 weeks in patients with severe AA. Efficacy increased in Week-52 mixed responders, illustrating that long-term treatment is necessary to observe maximum benefit in some patients. No new safety signals were observed.

[Clinicopathological and genetic characteristics of congenital cystic adenomatoid malformation of lung and its associated lung cancer in adults].

Objective: To investigate the clinicopathological features and genetic characteristics of congenital cystic adenomatoid malformation (CCAM) of lung and CCAM associated lung cancer in adults. Methods: A total of 13 cases of CCAM of lung in adults, diagnosed from June 2015 to May 2023, were collected from the Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, China. Their histopathological features were correlated with probable development into lung cancer. Next-generation sequencing was performed on the benign and malignant areas of all cases. Results: The pathological classification of all cases were of CCAM of lung type 1. There were 4 male and 9 female cases, age ranged from 18 to 65 years, with a mean age of 41 years. Six cases were accompanied by lung cancer, all of them were mucinous adenocarcinoma. Next-generation sequencing showed no gene mutation in 2 of the 13 cases; KRAS mutations in exon 2 were detected in 7 cases, in which there were 6 cases complicated with lung mucinous adenocarcinoma and no matter in the malignant or benign regions, the same case exhibited the same mutation sites in KRAS gene. Conclusions: CCAM of the lung is a congenital disease, and in adults, type 1 is most commonly found in the pathological classification, and it is often accompanied by cancer. Gene mutations are frequently detected in CCAM of the lung, KRAS being the most recurrent mutation which may play an important role in the carcinogenesis.