Multiple autoimmune disorders refractory to glucocorticoids after allogeneic hematopoietic stem cell transplantation: a case report and review of the literature.

We report here the case of a 50-year-old man who was first diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2019, resulting in complete remission. However, he was diagnosed in 2021 with several autoimmune disorders, including autoimmune hepatitis (AIH), Hashimoto's thyroiditis (HT), and autoimmune hemolytic anemia (AIHA). This is referred as multiple autoimmune syndrome (MAS), which is a rare occurrence after allo-HSCT, as previously noted in the literature. Despite being treated with glucocorticoids, cyclosporine A, and other medications, the patient did not fully recover. To address the glucocorticoid-refractory MAS, a four-week course of rituximab (RTX) at a weekly dose of 100mg was administered, which significantly improved the patient's condition. Thus, this case report underscores the importance of implementing alternative treatments in patients with post-transplant autoimmune diseases, who are glucocorticoid-refractory or glucocorticoid-dependent, and highlights the effectiveness of RTX as second-line therapy.

Machine learning-based longitudinal prediction for GJB2-related sensorineural hearing loss.

BACKGROUND: Recessive GJB2 variants, the most common genetic cause of hearing loss, may contribute to progressive sensorineural hearing loss (SNHL). The aim of this study is to build a realistic predictive model for GJB2-related SNHL using machine learning to enable personalized medical planning for timely intervention. METHOD: Patients with SNHL with confirmed biallelic GJB2 variants in a nationwide cohort between 2005 and 2022 were included. Different data preprocessing protocols and computational algorithms were combined to construct a prediction model. We randomly divided the dataset into training, validation, and test sets at a ratio of 72:8:20, and repeated this process ten times to obtain an average result. The performance of the models was evaluated using the mean absolute error (MAE), which refers to the discrepancy between the predicted and actual hearing thresholds. RESULTS: We enrolled 449 patients with 2184 audiograms available for deep learning analysis. SNHL progression was identified in all models and was independent of age, sex, and genotype. The average hearing progression rate was 0.61 dB HL per year. The best MAE for linear regression, multilayer perceptron, long short-term memory, and attention model were 4.42, 4.38, 4.34, and 4.76 dB HL, respectively. The long short-term memory model performed best with an average MAE of 4.34 dB HL and acceptable accuracy for up to 4 years. CONCLUSIONS: We have developed a prognostic model that uses machine learning to approximate realistic hearing progression in GJB2-related SNHL, allowing for the design of individualized medical plans, such as recommending the optimal follow-up interval for this population.

Expression pattern of ATG4C and its effect on early embryonic development of porcine oocytes.

Autophagy is essential for oocyte maturation and preimplantation embryo development. ATG4C, a member of the ATG4 family, plays a crucial role in the autophagy process. The effect of ATG4C on the early embryonic development in pig has not been studied. In this study, the expression patterns of ATG4C were explored using qRT-PCR and immunofluorescence staining. Different concentrations of serum were added to in vitro maturation (IVM) medium to investigate its effects on oocyte maturation and embryonic development. Finally, the developmental potential of parthenogenetic embryos was detected by downregulating ATG4C in MII stage oocytes under 0 % serum condition. The results revealed that ATG4C was highly expressed in porcine oocytes matured in vitro and in parthenogenetic embryos. Compared with the 10 % serum group, the cumulus cell expansion, first polar body (PB1) extrusion rate, and subsequent developmental competence of embryos were reduced in the 0 % and 5 % serum groups. The mRNA levels of LC3, ATG5, BECLIN1, TFAM, PGC1α, and PINK1 were significantly increased (P < 0.05) in the 0 % serum group. ATG4C was significantly upregulated in the embryos at the 1-cell, 2-cell, 8-cell, and 16-cell stages in the 0 % serum group (P < 0.05). Compared with the negative control group, downregulation of ATG4C significantly decreased the 4-cell, 8-cell, and blastocyst rates (P < 0.05), and the expression of genes related to autophagy, mitochondria, and zygotic genome activation (ZGA) was significantly decreased (P < 0.05). The relative fluorescence intensity of LC3 and mitochondrial content in the ATG4C siRNA group was significantly reduced (P < 0.05). Collectively, the results indicate that ATG4C is highly expressed in porcine oocytes matured in vitro and in early embryos, and inhibition of ATG4C effects embryonic developmental competence by decreasing autophagy, mitochondrial content, and ZGA under serum-free condition.

ITGB5 facilitates gastric cancer metastasis by promoting TGFBR2 endosomal recycling.

TGFBR2, a key regulator of the TGFß signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin ß5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling. Our study reveals elevated expression of ITGB5 in GC, particularly in metastatic cases, correlating with poor patient outcomes. Knockdown of ITGB5 impairs GC cell metastasis both in vitro and in vivo. Mechanistically, ITGB5 facilitates epithelial-mesenchymal transition mediated by TGFß signaling, thereby enhancing GC metastasis. Acting as a scaffold, ITGB5 interacts with TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing lysosomal degradation, thereby maintaining its surface distribution on tumor cells. Notably, TGFß signaling directly upregulates ITGB5 expression, establishing a positive feedback loop that exacerbates GC metastasis. Our findings shed light on the role of ITGB5 in promoting GC metastasis through SNX17-mediated endosomal recycling of TGFBR2, providing insights for the development of targeted cancer therapies.

Ability of Helicobacter pylori to internalize into Candida.

The following are our views regarding the "letter to the editor" (Helicobacter is preserved in yeast vacuoles! Does Koch's postulates confirm it?) by Alipour and Gaeini, and the response "letter to the editor" (Candida accommodates non-culturable Helicobacter pylori in its vacuole-Koch's postulates aren't applicable) by Siavoshi and Saniee. Alipour and Gaeini rejected the methods, results, discussion, and conclusions summarized in a review article by Siavoshi and Saniee. The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori (H. pylori) to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse, transporting potentially infectious H. pylori into the stomach of humans.

Peripheral cutaneous synucleinopathy characteristics in genetic Parkinson's disease.

Background: Cutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson's disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD. Objective: This study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies. Methods: We performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy. Results: P-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and LRRK2 and GBA mutation patients revealed prion-like activity. Conclusion: P-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.

Dearomative [2 + 1] Spiroannulation of Bromophenols with Electron-Deficient Alkenes.

A base-assisted dearomative [2 + 1] spiroannulation of p/o-bromophenols with activated olefins (methylenemalonates) to construct various cyclopropyl spirocyclohexadienone skeletons is reported. Furthermore, several other halophenols (X = Cl, I) were also tolerated in this process. Control experiments reveal a dearomative Michael addition of phenols at their halogenated positions to methylenemalonates, followed by intramolecular radical-based SRN1 dehalogenative cyclopropanation. However, according to the density functional theory (DFT) calculations, an SN2 dehalogenative cyclopropanation with the same low activation energy barrier should not be excluded. The utility of this method is showcased by gram-scale syntheses and transformations of the dearomatized products.

Paraquat disrupts KIF5A-mediated axonal mitochondrial transport in midbrain neurons and its antagonism by melatonin.

Paraquat (PQ) is a broad-spectrum herbicide used worldwide and is a hazardous chemical to human health. Cumulative evidence strengthens the association between PQ exposure and the development of Parkinson's disease (PD). However, the underlying mechanism and effective interventions against PQ-induced neurotoxicity remain unclear. In this study, C57BL/6 J mice were treated with PQ (i.p., 10 mg/kg, twice a week) and melatonin (i.g., 20 mg/kg, twice a week) for 8 weeks. Results showed that PQ-induced motor deficits and midbrain dopaminergic neuronal damage in C57BL/6 J mice were protected by melatonin pretreatment. In isolated primary midbrain neurons and SK-N-SH cells, reduction of cell viability, elevation of total ROS levels, axonal mitochondrial transport defects and mitochondrial dysfunction caused by PQ were attenuated by melatonin. After screening of expression of main motors driving axonal mitochondrial transport, data showed that PQ-decreased KIF5A expression in mice midbrain and in SK-N-SH cell was antagonized by melatonin. Using the in vitro KIF5A-overexpression model, it was found that KIF5A overexpression inhibited PQ-caused neurotoxicity and mitochondrial dysfunction in SK-N-SH cells. In addition, application of MTNR1B (MT2) receptor antagonist, 4-P-PDOT, significantly counteracted the protection of melatonin against PQ-induced neurotoxicity. Further, Kif5a-knockdown diminished melatonin-induced alleviation of motor deficits and neuronal damage against PQ in C57BL/6 J mice. The present study establishes a causal link between environmental neurotoxicants exposure and PD etiology and provides effective interventive targets in the pathogenesis of PD.

Inhibitory Effect and Potential Antagonistic Mechanism of Isolated Epiphytic Yeasts against Botrytis cinerea and Alternaria alternata in Postharvest Blueberry Fruits.

This study evaluated the biocontrol effect of isolated epiphytic yeasts (Papiliotrema terrestris, Hanseniaspora uvarum, and Rhodosporidium glutinis) against Botrytis cinerea and Alternaria alternata in blueberry fruits and its possible mechanisms. Our findings indicated that the three tested yeasts exerted a good biocontrol effect on postharvest diseases in blueberry, and that H. uvarum was the most effective. In addition, the three tested yeasts could improve the postharvest storage quality of blueberry fruits to some extent. H. uvarum demonstrated the strongest direct inhibitory effect on pathogens by suppressing spore germination, mycelial growth, and antifungal volatile organic compound (VOC) production. P. terrestris showed the highest extracellular lytic enzymes activities. It also had better adaptation to low temperature in fruit wounds at 4 °C. The biofilm formation capacity was suggested to be the main action mechanism of R. glutinis, which rapidly colonized fruit wounds at 20 °C. Several action mechanisms are employed by the superb biocontrol yeasts, while yeast strains possess distinctive characteristics and have substantially different action mechanisms.

Long-term survival outcomes and immune checkpoint inhibitor retreatment in patients with advanced cervical cancer treated with camrelizumab plus apatinib in the phase II CLAP study.

BACKGROUND: Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer (CLAP study; NCT03816553). We herein present the updated long-term results of the CLAP study and explore potential biomarkers for survival. The outcomes of patients who underwent immune checkpoint inhibitor (ICI) retreatment were also reported. METHODS: In this phase II trial, eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4-week cycles for up to two years. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. RESULTS: Between January 21 and August 1, 2019, a total of 45 patients were enrolled. Data were analyzed as of July 31, 2023, representing > 48 months since treatment initiation for all patients. Nine (20.0%) patients completed the 2-year study. The median duration of response (DOR) was 16.6 months, and 45.0% of patients achieved a DOR of ≥ 24 months. The 12-month progression-free survival (PFS) rate was 40.7% (95% confidence interval [CI], 25.2-55.6), with an 18-month PFS rate of 37.8% (95% CI, 22.7-52.8). The median overall survival (OS) was 20.3 months (95% CI, 9.3-36.9), and the 24-month OS rate was 47.8% (95% CI, 31.7-62.3). Age > 50 years, programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (versus [vs.] < 1), CPS ≥ 10 (vs. < 1), high tumor mutational burden, and PIK3CA mutations were associated with improved PFS (hazard ratio [HR] < 1) and longer OS (HR < 1). Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs. Among them, 2 (25.0%) achieved a partial response, while 5 (62.5%) had stable disease. Notably, four patients who received retreatment with ICIs survived for more than 45 months. No new safety signals were identified in the present study. CONCLUSION: Long-term survival follow-up data demonstrated that camrelizumab plus apatinib has robust, sustained, and durable efficacy in patients with advanced cervical cancer who progress after first-line platinum-based chemotherapy. No new safety signals were noted with long-term treatment.

RAG suppresses group 2 innate lymphoid cells.

Antigen specificity is the central trait distinguishing adaptive from innate immune function. Assembly of antigen-specific T cell and B cell receptors occurs through V(D)J recombination mediated by the Recombinase Activating Gene endonucleases RAG1 and RAG2 (collectively called RAG). In the absence of RAG, mature T and B cells do not develop and thus RAG is critically associated with adaptive immune function. In addition to adaptive T helper 2 (Th2) cells, group 2 innate lymphoid cells (ILC2s) contribute to type 2 immune responses by producing cytokines like Interleukin-5 (IL-5) and IL-13. Although it has been reported that RAG expression modulates the function of innate natural killer (NK) cells, whether other innate immune cells such as ILC2s are affected by RAG remains unclear. We find that in RAG-deficient mice, ILC2 populations expand and produce increased IL-5 and IL-13 at steady state and contribute to increased inflammation in atopic dermatitis (AD)-like disease. Further, we show that RAG modulates ILC2 function in a cell-intrinsic manner independent of the absence or presence of adaptive T and B lymphocytes. Lastly, employing multiomic single cell analyses of RAG1 lineage-traced cells, we identify key transcriptional and epigenomic ILC2 functional programs that are suppressed by a history of RAG expression. Collectively, our data reveal a novel role for RAG in modulating innate type 2 immunity through suppression of ILC2s.

Developing and validating prediction models for severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO) in China: a prospective observational study.

BACKGROUND: There is a lack of individualised prediction models for patients hospitalised with chronic obstructive pulmonary disease (COPD) for clinical practice. We developed and validated prediction models of severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO). METHODS: Data were obtained from the Acute Exacerbations of Chronic Obstructive Pulmonary Disease Inpatient Registry study (NCT02657525) in China. Cause-specific hazard models were used to estimate coefficients. C-statistic was used to evaluate the discrimination. Slope and intercept were used to evaluate the calibration and used for model adjustment. Models were validated internally by 10-fold cross-validation and externally using data from different regions. Risk-stratified scoring scales and nomograms were provided. The discrimination ability of the SERCO model was compared with the exacerbation history in the previous year. RESULTS: Two sets with 2196 and 1869 patients from different geographical regions were used for model development and external validation. The 12-month severe exacerbations cumulative incidence rates were 11.55% (95% CI 10.06% to 13.16%) in development cohorts and 12.30% (95% CI 10.67% to 14.05%) in validation cohorts. The COPD-specific readmission incidence rates were 11.31% (95% CI 9.83% to 12.91%) and 12.26% (95% CI 10.63% to 14.02%), respectively. Demographic characteristics, medical history, comorbidities, drug usage, Global Initiative for Chronic Obstructive Lung Disease stage and interactions were included as predictors. C-indexes for severe exacerbations were 77.3 (95% CI 70.7 to 83.9), 76.5 (95% CI 72.6 to 80.4) and 74.7 (95% CI 71.2 to 78.2) at 1, 6 and 12 months. The corresponding values for readmissions were 77.1 (95% CI 70.1 to 84.0), 76.3 (95% CI 72.3 to 80.4) and 74.5 (95% CI 71.0 to 78.0). The SERCO model was consistently discriminative and accurate with C-indexes in the derivation and internal validation groups. In external validation, the C-indexes were relatively lower at 60-70 levels. The SERCO model discriminated outcomes better than prior severe exacerbation history. The slope and intercept after adjustment showed close agreement between predicted and observed risks. However, in external validation, the models may overestimate the risk in higher-risk groups. The model-driven risk groups showed significant disparities in prognosis. CONCLUSION: The SERCO model provides individual predictions for severe exacerbation and COPD-specific readmission risk, which enables identifying high-risk patients and implementing personalised preventive intervention for patients with COPD.

Unraveling the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in aqueous host-guest complexation.

In biological systems, nucleosides play crucial roles in various physiological processes. In this study, we designed and synthesized four achiral anthracene-based tetracationic nanotubes (1-4) as artificial hosts and chiroptical sensors for nucleosides in aqueous media. Notably, different nanotubes exhibit varied chirality sensing on circular dichroism (CD)/circularly polarized luminescence (CPL) spectra through the host-guest complexation, which prompted us to explore the factors influencing their chiroptical responses. Through systematic host-guest experiments, the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in the host-guest complexation was unraveled. Firstly, the CD response originates from the anthracene rings situated at the side-wall position, resulting from the right-handed (P)- or left-handed (M)-twisted conformation of the macrocyclic structure. Secondly, the CPL signal is influenced by the presence of anthracene rings at the linking-wall position, which results from intermolecular chiral twisted stacking between these anthracene rings. Therefore, these nanotubes can serve as chiroptical sensor arrays to enhance the accuracy of nucleotide recognition through principal component analysis (PCA) analysis based on the diversified CD spectra. This study provides insights for the construction of adaptive chirality from achiral nanotubes with dynamic conformational nature and might facilitate further design of chiral functional materials for several applications.

Association of the retinol to all-trans retinoic acid pathway with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research. METHODS: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels. CONCLUSION: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes.

Ureaplasma infections: update on epidemiology, antimicrobial resistance, and pathogenesis.

Human Ureaplasma species are being increasingly recognized as opportunistic pathogens in human genitourinary tract infections, infertility, adverse pregnancy, neonatal morbidities, and other adult invasive infections. Although some general reviews have focused on the detection and clinical manifestations of Ureaplasma spp., the molecular epidemiology, antimicrobial resistance, and pathogenesis of Ureaplasma spp. have not been adequately explained. The purpose of this review is to offer valuable insights into the current understanding and future research perspectives of the molecular epidemiology, antimicrobial resistance, and pathogenesis of human Ureaplasma infections. This review summarizes the conventional culture and detection methods and the latest molecular identification technologies for Ureaplasma spp. We also reviewed the global prevalence and mechanisms of antibiotic resistance for Ureaplasma spp. Aside from regular antibiotics, novel antibiotics with outstanding in vitro antimicrobial activity against Ureaplasma spp. are described. Furthermore, we discussed the pathogenic mechanisms of Ureaplasma spp., including adhesion, proinflammatory effects, cytotoxicity, and immune escape effects, from the perspectives of pathology, related molecules, and genetics.

Prevalence of insulin resistance and its associated factors in drug-naïve patients with bipolar disorder among Han Chinese population.

BACKGROUND: Metabolic syndrome (Mets) is commonly seen in bipolar disorder (BD). As the key component and early biological index of Mets, insulin resistance (IR) among BD has received more and more attention. However, little is known about the prevalence of IR and its associated factors in drug-naïve patients with (BD), especially among Han Chinese population. METHODS: A cross-sectional study was conducted on 125 drug-naïve patients with bipolar disorder (BD) and 85 healthy controls (HC). The Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated, and IR was defined as HOMA-IR greater than the 75th percentile value for health controls (2.35). Clinical characteristics of BD were collected through semi-structural interview performed by a trained interviewer with background of psychiatric education. RESULTS: Among the measured anthropocentric variables including BMI, waist circumference, abdomen circumference, hipline, and hip-waist ratio, waist circumference was found to be the most closely related to IR (0R = 1.070, 95%CI = 1.031-1.110, P < 0.001). Male was another factor that was associated with IR (OR = 2.281, 95%CI = 1.107-4.702, P = 0.025). After adjusted for gender and waist circumference, the risk of IR was significantly higher in bipolar disorder than in healthy controls (OR = 2.66, 95%CI = 1.364-5.214, P = 0.004). No significant association was found between IR and any of the observed physical and mental comorbidities, any characteristic of illness course including age onset, number of mixed episodes, types of current state, duration of current episode, duration of illness course, rapid cycling, number of mood episodes, and subgroup of BD. Hypersomnia was the only symptomatic feature that was significantly associated with IR (OR = 0.316, 95%CI = 0.124-0.803, P = 0.016). CONCLUSIONS: Bipolar disorder increases two-to-three-fold risk of IR, both circumference and male are the risk factors of IR but hypersomnia act as a protective factor.

Utility of gadoxetate disodium-enhanced magnetic resonance imaging in evaluating liver failure risk after major hepatic resection.

Background: Post-hepatectomy liver failure (PHLF) is still a predominant cause of hepatectomy-related mortality. However, it is difficult to evaluate the remnant liver functional reserve accurately before surgery to prevent PHLF. In this study, we aimed to explore the role of gadoxetate disodium-enhanced magnetic resonance imaging (MRI) in evaluating remnant liver functional reserve. Methods: For this cross-sectional study, the sample retrospectively included 56 patients undergoing liver resections of at least three segments between June 2019 and September 2022 at The General Hospital of the Western Theater Command. Pre-surgery assessments involved liver computer tomography (CT), an indocyanine green (ICG) clearance test, the Child-Pugh scoring system, and liver function serum biochemical indicators. Each patient underwent a gadoxetate disodium-enhanced MRI before the hepatectomy, and we measured the remnant hepatocellular uptake index (rHUI) as well as the standard remnant hepatocellular uptake index (SrHUI). We examined the diagnostic utility of rHUI, SrHUI, indocyanine green retention rate of 15 minutes (ICG R15), and Albumin for PHLF. Receiver operating characteristics (ROC) analyses were used to measure the preoperative liver function parameters (namely, rHUI, SrHUI, ICG R15, and Albumin) for predicting PHLF. The areas under the curve (AUCs) were calculated and compared between different preoperative liver function parameters using the Wilson/Brown method. The Pearson or Spearman correlation coefficient was used for correlation analysis between ICG R15, Albumin, and rHUI and between ICG R15, Albumin, and SrHUI, respectively. Results: Twelve patients (21.43%) had complications of PHLF. We found significant differences in rHUI, SrHUI, ICG R15, and Albumin between the non-PHLF and PHLF groups. The pooled r between ICG R15 and rHUI was -0.591 [95% confidence interval (CI): -0.740 to -0.389, P<0.001], and between ICG R15 and SrHUI was -0.534 (95% CI: -0.703 to -0.308, P<0.001). The area under the curve (AUC) values of rHUI, SrHUI, ICG R15, and Ablumin were 0.871 (sensitivity 81.82%; specificity 91.67%), 0.878 (sensitivity 79.55%; specificity 83.33%), 0.835 (sensitivity 99.73%; specificity 66.67%), and 0.782 (sensitivity 88.64%; specificity 58.33%), respectively. Conclusions: We found that the rHUI and SrHUI calculated using the gadoxetate disodium-enhanced MRI reflected a combination of remnant hepatocyte function and liver volume, and these were useful as a quantitative assessment indicator of remnant liver functional reserve and can be a better predictor of PHLF after major hepatic resection.

Cost-effectiveness of population-based screening for chronic obstructive pulmonary disease in China: a simulation modeling study.

Background: China has the highest disease burden of chronic obstructive pulmonary disease (COPD) in the world; however, the diagnosis rate remains low. Screening for COPD in the population may improve early diagnosis and long-term health outcomes for patients with COPD. In this study, we aimed to evaluate the cost-effectiveness of population-based COPD screening policies in China. Methods: We developed a microsimulation model that simulated incidence, natural history, and clinical management of COPD over a lifetime horizon among the general population aged 35-80 years in China. We evaluated population-based screening policies with different screening methods (one-step with COPD Screening Questionnaire or two-step with additional portable spirometer test) and frequencies (one-time or every 1-10 years). We calculated the incremental cost-effectiveness ratio (ICER) of the screening policies compared with the status quo (without screening) and identified the most cost-effective screening policy. Scenario and sensitivity analyses were performed to assess the impact of key parameters and the robustness of model results. Findings: Compared with the status quo, all population-based COPD screening policies were cost-effective with estimated ICERs ranging between $8034 and $13,209 per quality-adjusted-life-year (QALY), all under the willingness-to-pay value of $38,441/QALY (three times China's gross domestic product per capita). A total of 0.39%-8.10% of COPD-related deaths and 0.58%-2.70% of COPD exacerbations were projected to be averted by COPD screening. Among all screening policies, annual two-step screening was the most cost-effective. Improving the linkage from screening to diagnosis and treatment could further increase population health benefits and the cost-effectiveness of COPD screening. Interpretation: Population-based screening for COPD could be cost-effective in China. Offering public programs for COPD screening similar to existing preventive health services for other chronic diseases could be a promising strategy to improve population health outcomes and mitigate the disease burden of COPD in China. Funding: Alexander von Humboldt Foundation, National Natural Science Foundation of China, CAMS Innovation Fund for Medical Science, Chinese Academy of Engineering project, and Horizon Europe.

Clinical characteristics, genetic alterations, and prognosis of adult T-cell leukemia/lymphoma: an 11-year multicenter retrospective study in China.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis, and there is little data available from the Chinese population. This retrospective study included 115 patients diagnosed with ATLL who were treated across five hospitals in China from June 2011 to December 2022. The median age at diagnosis was 53 years. Several genes involved in T-cell receptor-induced nuclear factor κB (TCR-NF-κB) signaling were commonly mutated, including PLCG1, CIC, PRKCB, CARD11, and IRF4. Eighty-seven patients received chemotherapy. Of these, 13 received a hematopoietic stem cell transplant (HSCT) (allogeneic-HSCT, n=9; autologous-HSCT, n=4) after chemotherapy. Following initial multiagent chemotherapy using EPOCH/CHOEP and other regimens, the overall response rates were 80.6% (complete response [CR], 44.4%) and 42.8% (CR, 14.2%), respectively. The 4-year survival rates (median survival time in days) for EPOCH/CHOEP (n=43), HSCT (n=13), and CHOP-based regimens (n=31) were 12.7% (138), 30.8% (333), and 0% (66), respectively. Lymphadenopathy, EPOCH/CHOEP, and hematopoietic stem cell transplantation were independent prognostic protective factors in patients with aggressive ATLL. Chinese patients exhibit a higher incidence of aggressive-type ATLL, sharing similar genetic alterations with Japanese patients. Etoposide-based chemotherapy (EPOCH or CHOEP) remains the preferred choice for aggressive ATLL, and upfront allogeneic HSCT should be considered in all eligible patients.