Edema， as a common pathological phenomenon， is essentially the abnormal accumulation of body fluids in the interstitial spaces of human tissues and is often a direct manifestation of various underlying diseases， such as heart failure， impaired renal filtration function， or liver metabolic disorders. In the Western medical system， strategies for treating edema primarily focus on the use of diuretics to promote the excretion of excess fluid in the body， while simultaneously addressing the underlying causes through targeted treatment. However， long-term reliance on the use of diuretics may lead to a decrease in drug sensitivity and induce side effects， including electrolyte disorders such as hypokalemia and hypercalcemia， posing a potential threat to patients' overall health. Compared with Western medicine， traditional Chinese medicine （TCM） has demonstrated well-recognized and sustained efficacy in treating edema with its unique theoretical system. Zhulingtang， as a classic and commonly used TCM formula， is widely applied as it can effectively relieve edema and related symptoms. In recent years， ongoing in-depth studies on the treatment of edema with Zhulingtang have revealed multiple mechanisms of action of Zhulingtang， including the regulation of water metabolism and the reduction of inflammatory responses， thereby providing a solid theoretical basis for clinical practice. This review summarized the research progress on the treatment of edema with Zhulingtang in recent years and analyzed the active ingredients and action pathways of Zhulingtang. Additionally， the primary mechanisms of action and efficacy were systematically analyzed， so as to provide references for the clinical application of Zhulingtang in treating various types of edema， such as cardiogenic edema， renal edema， and hepatogenic edema. This review aims to offer theoretical support and practical guidance for clinicians in deciding treatment approaches， as well as references for subsequent in-depth studies， thereby promoting further development of TCM in the treatment of edema.

Edema， as a common pathological phenomenon， is essentially the abnormal accumulation of body fluids in the interstitial spaces of human tissues and is often a direct manifestation of various underlying diseases， such as heart failure， impaired renal filtration function， or liver metabolic disorders. In the Western medical system， strategies for treating edema primarily focus on the use of diuretics to promote the excretion of excess fluid in the body， while simultaneously addressing the underlying causes through targeted treatment. However， long-term reliance on the use of diuretics may lead to a decrease in drug sensitivity and induce side effects， including electrolyte disorders such as hypokalemia and hypercalcemia， posing a potential threat to patients' overall health. Compared with Western medicine， traditional Chinese medicine （TCM） has demonstrated well-recognized and sustained efficacy in treating edema with its unique theoretical system. Zhulingtang， as a classic and commonly used TCM formula， is widely applied as it can effectively relieve edema and related symptoms. In recent years， ongoing in-depth studies on the treatment of edema with Zhulingtang have revealed multiple mechanisms of action of Zhulingtang， including the regulation of water metabolism and the reduction of inflammatory responses， thereby providing a solid theoretical basis for clinical practice. This review summarized the research progress on the treatment of edema with Zhulingtang in recent years and analyzed the active ingredients and action pathways of Zhulingtang. Additionally， the primary mechanisms of action and efficacy were systematically analyzed， so as to provide references for the clinical application of Zhulingtang in treating various types of edema， such as cardiogenic edema， renal edema， and hepatogenic edema. This review aims to offer theoretical support and practical guidance for clinicians in deciding treatment approaches， as well as references for subsequent in-depth studies， thereby promoting further development of TCM in the treatment of edema.

Total-body PET/CT, with its long axial field of view and high sensitivity detector, has shown potential for reducing the dose of radiopharmaceuticals. However, pediatric patients are significantly more sensitive to radiation and have a higher long-term cancer risk than adults, posing fundamental challenges for dose management in PET/CT examinations for these patients. In this article, the technical characteristics of total-body PET/CT and its radiation exposure status in children were systematically analyzed. The radiation exposure could be controlled by the following optimization strategies: adjusting the CT exposure parameters, optimizing the scanning mode, adding reconstruction algorithm, and reducing the injected dose of radioactive tracer. By addressing both external and internal radiation during the PET/CT scanning process, the overall radiation dose received by pediatric patients can be reduced within a certain range. In addition, this article also discusses the technical differences between “total-body” and “whole-body” concepts, and emphasizes that the future optimization of radiation dose in pediatric PET/CT should be realized by integration of personalized scanning protocols. Through reasonable management of scanning protocols and processes, low-dose and high-quality PET/CT imaging can be achieved in clinical environments, thus maximizing protection of pediatric patient health while minimizing the risks associated with ionizing radiation exposure.

Objective: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. Methods: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatinresistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich premRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. Results: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. Conclusion Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.

Objective: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. Methods: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatinresistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich premRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. Results: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. Conclusion Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.

Objective: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. Methods: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatinresistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich premRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. Results: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. Conclusion Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

ObjectiveTo compare the retest reliability and discriminant validity of dynamic postural stability indices for functional ankle instability (FAI) obtained by different algorithms based on acceleration signals at different positions of human body. MethodsFrom April to June, 2021, 21 subjects with unilateral FAI and 21 subjects with normal ankle were recruited. Three inertial sensors were attached to the waist points, knee and ankle positions. The ground reaction force (GRF) and kinematics data of the subjects in multi-direction single leg landing test were collected synchronously by 3D force plate and inertial sensors. The unbounded third order polynomial (UTOP) fitting method was used to calculate the stability time, and the root mean square was used to caculate the stability index. ResultsMost of the indicators calculated based on acceleration signal correlated with that based on GRF with low coefficient (|r| = 0.116 to 0.368, P < 0.05). The stability time and stability index based on the acceleration signals of different positions of human body showed low to high retest reliability (CMC 0.30 to 0.91). For the females, among the stability time based on acceleration signal, eleven indexes achieved average to very high discriminant validity (AUC = 0.702 to 0.942, P < 0.05); eight of the stability indexes reached general level of discriminant validity (AUC = 0.717 to 0.782, P < 0.05). No algorithms achieved good discriminant effect in male subjects. ConclusionBased on the acceleration signal of waist point in single-leg landing stability test, the stability time calculated by UTOP algorithm can evaluate the dynamic postural stability of female FAI patients with high discriminant validity and medium to high retest reliability.

Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC₅₀ = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.

Normal mammalian secondary palate development undergoes a series of processes, including palatal shelf (PS) growth, elevation, adhesion and fusion, and palatal bone formation. It has been estimated that more than 90% of isolated cleft palate is caused by defects associated with the elevation process. However, because of the rapidly completed elevation process, the entire process of elevation will never be easy to clarify. In this article, we present a novel method for three-dimensional (3D) reconstruction of thick tissue blocks from two-dimensional (2D) histological sections. We established multiplanar sections of the palate and tongue in coronal and sagittal directions, and further performed 3D reconstruction to observe the morphological interaction and connection between the two components prior to and during elevation. The method completes an imaging system for simultaneous morphological analysis of thick tissue samples using both synthetic and real data. The new method will provide a comprehensive picture of reorientation morphology and gene expression pattern during the palatal elevation process.