Pulmonary lymphangioleiomyomatosis is a rare disease characterized by the abnormal proliferation of pulmonary lymphatic smooth muscle cells. It is common in women and often accompanied by recurrent pneumothorax, chylothorax and progressive dyspnea, imaging characterized by diffuse cystic lesions in both lungs. Pulmonary lymphangioleiomyomatosis progresses aggressively and has a very poor prognosis, with a lack of effective medical treatment options in the advanced stages. Lung transplantation is a safe and effective method for the treatment of advanced pulmonary lymphangioleiomyomatosis, which may significantly improve the survival rate and quality of life of patients. The median survival period after surgery can reach 12 years. This article reviews the pathogenesis, diagnosis, treatment of pulmonary lymphangioleiomyomatosis, and the current status and existing problems of lung transplantation in pulmonary lymphangioleiomyomatosis, aiming to provide a reference for the clinical treatment and subsequent research of pulmonary lymphangioleiomyomatosis.

This article investigates the collaborative management of metabolic dysfunction-associated fatty liver disease （MAFLD） and chronic kidney disease （CKD）. As major public health issues worldwide， MAFLD and CKD are closely related in terms of epidemiology， pathogenesis， and management strategies， and however， there are still many challenges in the multidisciplinary collaborative management of the two diseases. This article systematically elaborates on the epidemiology of MAFLD and CKD， summarizes their common risk factors such as metabolic disorder， genetic susceptibility， and active metabolites， and reviews the mutual screening strategies and combined management models based on noninvasive imaging， serum markers， FIB-4 score， and liver stiffness measurement. In addition， this article summarizes the advances in the application of lifestyle intervention and new drugs （such as GLP-1 receptor agonists and SGLT-2 inhibitors） and emphasizes the importance of multidisciplinary collaboration in improving the prognosis of patients. Due to the close association between MAFLD and CKD， their joint management is crucial， and therefore， it is necessary to establish a multidisciplinary collaboration mechanism and implement the measures of precise screening， comprehensive treatment， and long-term monitoring， so as to improve the prognosis of patients and reduce the risk of complications. Finally， this article proposes that in the future， more effective combined treatment regimens should be explored to expand the clinical options for the co-management of the liver and the kidney.

Objective To compare the differences in intraoperative radiation exposure between leadless and transvenous pacemaker implantation. Methods Cumulative dose (CD), dose area product (DAP), and fluoroscopy time during procedure were recorded and analyzed in 21 patients with leadless pacemaker implantation (Micra group), 55 patients with transvenous single-chamber pacemaker implantation (VVI group), and 216 patients with transvenous dual-chamber pacemaker implantation (DDD group). Results The fluoroscopy times of the Micra group, VVI group, and DDD group were 5.0 ± 1.9, 4.8 ± 1.4, and 7.6 ± 1.9 min, respectively (P < 0.001). Their CD values were 203.5 ± 76.1, 147.0 ± 41.0, and 249.6 ± 58.2 mGy, respectively (P < 0.001). Their DAP values were 18.6 ± 7.1, 13.4 ± 3.9, and 22.6 ± 5.6 Gy·cm², respectively (P < 0.001). Compared with the VVI group, the Micra group had similar fluoroscopy time (P=0.813) but higher CD (P=0.010) and DAP values (P = 0.012). Compared with the DDD group, the Micra group had reduced fluoroscopy time (P < 0.001), CD value (P = 0.033), and DAP value (P = 0.047). Conclusion Leadless pacemaker implantation is associated with increased radiation exposure compared to transvenous single-chamber pacemaker implantation. However, it offers a significant advantage in reducing radiation exposure for both medical staff and patients compared to transvenous dual-chamber pacemaker implantation.

Proteolysis-targeting chimeras (PROTACs) represent a promising class of drugs that can target disease-causing proteins more effectively than traditional small molecule inhibitors can, potentially revolutionizing drug discovery and treatment strategies. However, the links between in vitro and in vivo data are poorly understood, hindering a comprehensive understanding of the absorption, distribution, metabolism, and excretion (ADME) of PROTACs. In this work, ¹⁴C-labeled vepdegestrant (ARV-471), which is currently in phase III clinical trials for breast cancer, was synthesized as a model PROTAC to characterize its preclinical ADME properties and simulate its clinical pharmacokinetics (PK) by establishing a physiologically based pharmacokinetics (PBPK) model. For in vitro-in vivo extrapolation (IVIVE), hepatocyte clearance correlated more closely with in vivo rat PK data than liver microsomal clearance did. PBPK models, which were initially developed and validated in rats, accurately simulate ARV-471's PK across fed and fasted states, with parameters within 1.75-fold of the observed values. Human models, informed by in vitro ADME data, closely mirrored postoral dose plasma profiles at 30 mg. Furthermore, no human-specific metabolites were identified in vitro and the metabolic profile of rats could overlap that of humans. This work presents a roadmap for developing future PROTAC medications by elucidating the correlation between in vitro and in vivo characteristics.

Objective To investigate T cell subtypes and their functions in liver immune microenvironments among patients with alveolar echinococcosis (AE) using single-cell RNA sequencing (scRNA-seq). Methods Four AE patients that were admitted to Qinghai Provincial People’s Hospital in 2023 for hepatic surgery for the first time were enrolled, and liver specimens were sampled 1 cm (peri-lesion, PL group) and > 5 cm from AE lesions (distal lesion, DL group) among each patient. Finally, a total of eight liver specimens were sampled from four AE patients for scRNA-seq analysis. Genome and transcriptome data of liver specimens were processed using the software Cell Ranger and R package. Differentially expressed genes (DEGs) and their biological functions were analyzed using gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the primary intercellular communication patterns and interaction mechanisms were identified among T cell subtypes in liver specimens using the CellChat package. In addition, the developmental stages of T cells were subjected to trajectory analysis with the monocle package to investigate the expression of genes associated with cell growth and tumor transformation, and to predict the developmental trajectories of T cells. Results All four AE patients were female, with a mean age of (25.00 ± 9.06) years, and there were three cases from Jiuzhi County, Golog Tibetan Autonomous Prefecture and one case from Chengduo County, Yushu Tibetan Autonomous Prefecture, Qinghai Province. The viability of single-cell samples from eight liver specimens was 90.41% to 96.33%, and a total of 81 763 cells were analyzed, with 19 cell types annotated. Of these cell types, 13 were immune cells (87.60%), and T cells (33.13%), neutrophils (15.40%), and natural killer cells (11.92%) were the three most common cell types. Re-clustering of 27 752 T cells and proliferative T cells identified 10 distinct T cell subtypes, with CD8⁺ cytotoxic T cells (23.43%), CD8⁺ naive T cells (12.80%), and CD4⁺ effector memory T cells (17.73%) as dominant cell types. The proportions of T helper 2 (Th2) cells (5.19% vs. 3.63%; χ² = 38.35, P < 0.01) and CD4⁺ effector memory T cells (21.59% vs. 13.67%; χ² = 244.70, P < 0.01) were significantly higher in liver specimens in the PL group than in the DL group, and the proportion of CD4⁺ helper T cells was significantly lower in the PL group than in the DL group (7.50% vs. 14.75%; χ² = 330.52, P < 0.01). KEGG pathway analysis revealed that Th2 cells were significantly enriched in cell apoptosis and multiple cancer-associated pathways, and CD4⁺ effector memory T cells were significantly enriched in the regulation of cytokines and chronic inflammation, while CD4⁺ helper T cells were significantly enriched in immune responses regulation. Trajectory analysis of T cells showed that CD4⁺ helper T cells were at an earlier developmental stage relative to Th2 cells and CD4⁺ effector memory T cells, and the expression of inhibitor of DNA binding 3 (ID3), thioredoxin interacting protein (TXNIP), Bcl2-associated athanogene 3 (BAG3) and heat shock protein family B (small) member 1 (HSPB1) genes appeared a tendency towards a decline over time. Conclusions CD4⁺ effector memory T cells and CD8⁺ cytotoxic T cells are primary interacting cells in the liver specimens of AE patients. Reduced expression of Th2 cells and CD4⁺ helper T cells contributes to an inhibitory immune microenvironment, which promotes immune evasion by Echinococcus multilocularis, and Th2 cells are significantly enriched in multiple cancer-associated pathways, which may be linked to the invasive growth of E. multilocularis.

In 2020， an international expert panel proposed to replace nonalcoholic fatty liver disease with metabolic associated fatty liver disease （MAFLD）. Recent studies have shown that there is a higher risk of chronic kidney disease （CKD） in the MAFLD population and that MAFLD is an independent risk factor for CKD. However， up to now， there are still no guidelines on the prevention and treatment of MAFLD-related CKD. Based on the Delphi method， the authors led a multidisciplinary team of 50 authoritative experts from 26 countries to reach a consensus on some open-ended research issues about the association between MAFLD and CKD， which can help to clarify the important clinical association between MAFLD and the risk of CKD and improve the understanding of the epidemiology， pathogenesis， management， and treatment of MAFLD and CKD， so as to establish a framework for the early prevention and management of these two common and interrelated diseases.

Purpose To explore the value of dual-layer spectral detector CT(DLSCT)in evaluating preoperative tumor staging in rectal adenocarcinoma(RA).Materials and Methods A total of 78 patients with pathologically confirmed RA in Guangdong Provincial Hospital of Chinese Medicine from May 2021 to March 2022 were involved in this retrospective study.All the patients underwent plain and dual-phase contrast-enhanced scans by DLSCT within one week before surgery.Taking pathological results as the golden standard,the accuracy rates of tumor staging were calculated and compared between the multiple-parameter maps derived from DLSCT and 120 kVp polyenergetic image.The effective atomic number(Z-eff)from plain scan,iodine concentration(IC)from arterial phase(AP)and venous phase(VP)were measured.The normalized iodine concentration(NIC)in AP and VP were calculated.The differences of Z-eff,NICAP and NICVP were compared among the pT1-2,pT3 and pT4 groups.The correlation between the pT stages and above values was assessed and the diagnostic efficiencies were analyzed.Results The overall accuracy rate(88.46%vs.67.95%;χ2=9.628,P=0.002),the pT1-2 staging accuracy rate(80.00%vs.40.00%;χ2=6.667,P=0.01),and the pT3 staging accuracy rate(88.10%vs.69.05%;χ2=4.525,P=0.033)of multiple-parameter maps derived from DLSCT were significantly higher than those of 120 kVp polyenergetic image,respectively.The Z-eff,NICAP and NICVP were significantly different among pT stage groups(F=6.456,11.029,12.698,all P<0.05)and exhibited a positive correlation with pT stages(r=0.371,0.367,0.363,all P<0.01).The areas under the curve of Z-eff,NICAP and NICVP to assess pT3-4 staging RA were 0.77,0.71 and 0.74,respectively.Conclusion The multiple-parameter maps derived from DLSCT can significantly improve the diagnostic accuracy of preoperative tumor staging of RA.Z-eff from plain scan and NIC from dual-phase helps differentiate pT1-2 from pT3-4 staging RA.

The limitations of antifungal drugs and severe drug resistance make the treatment of invasive fungal infections (IFIs) a great challenge. Itraconazole (ITZ), as a clinical first-line drug, has a wide range of antifungal activity, but it is still limited by adverse reactions such as liver and kidney toxicity, headache and abdominal pain due to its poor water solubility and easy to cause drug accumulation by injection. In this study, the amphiphilic polymer gallic acid-chitosan-cinnamaldehyde (GA-CS-CN) was prepared by amide reaction and Schiff-base reaction. The drug-loaded nanoparticles (GA-CS-CN/ITZ) were prepared by ultrasonic method. The properties of nanoparticles formulations and its in vitro antifungal activity were investigated in the study. Studies have shown that GA-CS-CN/ITZ is spherical, homogeneous and stable, and has good biological safety. The average particle size was 239.57 ± 31.37 nm, ITZ encapsulation efficiency was (93.41 ± 1.12)%, and the cumulative drug release was (62.25 ± 1.88)% at 48 h in vitro. The antifungal activity results of Candida albicans ATCC 10231 (C. albicans) showed that it had the optimal antifungal effect and could significantly enhance the antifungal activity of free drugs. GA-CS-CN/ITZ prepared in this study has excellent biological safety and anti-C. albicans performance, which provides a new choice for the treatment of C. albicans infection and has good application potential in the treatment of this fungal infection.

ObjectiveTo observe the clinical effect of hand controlled rhythm music therapy on unilateral spatial neglect for stroke patients. MethodsFrom September, 2020 to September, 2022, 52 patients with unilateral spatial neglect after stroke in Wuxi Central Rehabilitation Hospital were randomly divided into control group (n = 26) and observation group (n = 26). Both groups accepted routine rehabilitation, and the observation group accepted hand controlled rhythm music therapy in addition, for eight weeks. Before and after treatment, the patients were assessed with Chinese Behavioral Inattention Test-Hong Kong version (CBIT-HK) routine tests (line crossing, letter cancellation, star cancellation, line bisection, figure and shape copying, and representational drawing) and modified Barthel Index (MBI). ResultsAfter treatment, six scores of CBIT-HK routine tests and the scores of MBI increased in both groups (|t| > 3.077, P < 0.05), and they were higher in the observation group than in the control group (|t| > 2.639, P < 0.05). ConclusionHand controlled rhythm music therapy could effectively alleviate the symptoms of unilateral spatial neglect after stroke, and improve the activities of daily living.

Yeast autolysis affects the flavor and quality of beer. The regulation of yeast autolysis is a need for industrial beer production. Previous studies on brewer's yeast autolysis showed that the citric acid cycle-related genes had a great influence on yeast autolysis. To explore the contribution of isocitrate dehydrogenase genes in autolysis, the IDP1 and IDP2 genes were destroyed or overexpressed in typical lager yeast Pilsner. The destruction of IDP1 gene improved the anti-autolytic ability of yeast, and the anti-autolytic index after 96 h autolysis was 8.40, 1.5 times higher than that of the original strain. The destruction of IDP1 gene increased the supply of nicotinamide adenine dinucleotide phosphate (NADPH) and the NADPH/NADP⁺ ratio was 1.94. After fermentation, intracellular ATP level was 1.8 times higher than that of the original strain, while reactive oxygen species (ROS) was reduced by 10%. The destruction of IDP2 gene resulted in rapid autolysis and a decrease in the supply of NADPH. Anti-autolytic index after 96 h autolysis was 4.03 and the NADPH/NADP⁺ ratio was 0.89. After fermentation, intracellular ATP level was reduced by 8% compared with original strain, ROS was 1.3 times higher than that of the original strain. The results may help understand the regulation mechanism of citric acid cycle-related genes on yeast autolysis and provide a basis for the selection of excellent yeast with controllable anti-autolytic performance.
Humans ; Isocitrate Dehydrogenase/genetics* ; NADP ; Reactive Oxygen Species ; Autolysis ; Adenosine Triphosphate