P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8％)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P＜0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1％and 35.7％(P＜0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

The intelligent oxygen management system is a software designed with various algorithms to automatically titrate inhaled oxygen concentration according to specific patterns. This system can be integrated into various ventilator devices and used during assisted ventilation processes, aiming to maintain the patient's blood oxygen saturation within a target range. This paper employs a scoping review methodology, focusing on research related to intelligent oxygen management systems in neonatal intensive care units. It reviews the fundamental principles, application platforms, and clinical outcomes of these systems, providing a theoretical basis for clinical implementation.
Humans ; Intensive Care Units, Neonatal ; Infant, Newborn ; Oxygen/administration & dosage* ; Oxygen Inhalation Therapy/methods* ; Respiration, Artificial

BACKGROUND: Our understanding of the correlation between postdischarge cancer and mortality in patients with coronary artery disease (CAD) remains incomplete. The aim of this study was to investigate the relationships between postdischarge cancers and all-cause mortality and cardiovascular mortality in CAD patients. METHODS: In this retrospective cohort study, 25% of CAD patients without prior cancer history who underwent coronary artery angiography between January 1, 2011 and December 31, 2015, were randomly enrolled using SPSS 26.0. Patients were monitored for the incidence of postdischarge cancer, which was defined as cancer diagnosed after the index hospitalization, survival status and cause of death. Cox regression analysis was used to explore the association between postdischarge cancer and all-cause mortality and cardiovascular mortality in CAD patients. RESULTS: A total of 4085 patients were included in the final analysis. During a median follow-up period of 8 years, 174 patients (4.3%) developed postdischarge cancer, and 343 patients (8.4%) died. A total of 173 patients died from cardiovascular diseases. Postdischarge cancer was associated with increased all-cause mortality risk (HR = 2.653, 95% CI: 1.727-4.076, P < 0.001) and cardiovascular mortality risk (HR = 2.756, 95% CI: 1.470-5.167, P = 0.002). Postdischarge lung cancer (HR = 5.497, 95% CI: 2.922-10.343, P < 0.001) and gastrointestinal cancer (HR = 1.984, 95% CI: 1.049-3.750, P = 0.035) were associated with all-cause mortality in CAD patients. Postdischarge lung cancer was significantly associated with cardiovascular death in CAD patients (HR = 4.979, 95% CI: 2.114-11.728, P < 0.001), and cardiovascular death was not significantly correlated with gastrointestinal cancer or other types of cancer. CONCLUSIONS Postdischarge cancer was associated with all-cause mortality and cardiovascular mortality in CAD patients. Compared with other cancers, postdischarge lung cancer had a more significant effect on all-cause mortality and cardiovascular mortality in CAD patients.

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans ; Drugs, Chinese Herbal/pharmacology* ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/therapy* ; Medicine, Chinese Traditional/methods* ; Antiviral Agents/pharmacology* ; Animals

P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8％)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P＜0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1％and 35.7％(P＜0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.

Objective:Operational efficiency and influencing factors of China's basic medical insurance system from 2020 to 2021 is conducted to provide reference for improving the operational efficiency and optimizing the input-output relationship.Methods:The super-efficiency SBM model based on unexpected output and the Malmquist index are used to measure the static and dynamic efficiency of resident medical insurance in 31 provinces in China,and Tobit regression analysis is employed to analyze the influencing factors.Results:The overall operational efficiency of resident medical insurance still needs improvement.The operational efficiency of resident medical insurance in the central and western regions is lower than that in the eastern region,and the gap is significant.Different levels and regions have differentiated main constraints on the operational efficiency of resident medical insurance.In terms of dynamic efficiency,the total factor productivity of resident medical insurance operation shows an increasing trend,mainly due to technological progress.In terms of influencing factors,the degree of aging,the level of medical expenses and the level of medical insurance supervision have a significant impact on the operational efficiency.Suggestions:Efforts should be made to bridge regional disparities,promote the equitable development of medical insurance,reasonably control the level of medical expenses,strengthen the supervision of medical insurance funds,and implement active aging policies.

Objectives: To investigate whether the protective actions of ginsenoside Rb1 (Rb1) on astrocytes are mediated through the Gs-type G-protein-coupled receptor (GPCR-Gs). Methods: Primary astrocyte cultures derived from neonatal mouse brain were used. Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation (OGD/R). Cell morphology, viability, lactate dehydrogenase (LDH) leakage, apoptosis, glutamate uptake, and brain-derived neurotrophic factor (BDNF) secretion were assessed to gauge cell survival and functionality. Western blot was used to investigate the cyclic adenosine monophosphate (cAMP) and protein kinase B (Akt) signaling pathways. GPCR-Gs-specific inhibitors and molecular docking were used to identify target receptors. Results: Rb1 at concentrations ranging from 0.8 to 5 μM did not significantly affect the viability, glutamate uptake, or BDNF secretion in normal astrocytes. OGD/R reduced astrocyte viability, increasing their LDH leakage and apoptosis rate. It also decreased glutamate uptake and BDNF secretion by these cells. Rb1 had protective effects of astrocytes challenged by OGD/R, by improving viability, reducing apoptosis, and enhancing glutamate uptake and BDNF secretion. Additionally, Rb1 activated the cAMP and Akt pathways in these cells. When the GPCR-Gs inhibitor NF449 was introduced, the protective effects of Rb1 completely disappeared, and its activation of cAMP and Akt signaling pathways was significantly inhibited. Conclusion Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-Gs mediation.

Objective:To investigate the safety and short-term efficacy of yttrium-90 [ 90Y] resin microspheres transarterial radioembolization (TARE) for the treatment of initial unresectable malignant hepatic tumor. Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients with initial unresectable malignant hepatic tumor who were admitted to The First Affiliated Hospital of Army Medical University from June 2022 to June 2023 were collected. All patients were males, aged (57±4)years. Measurement data with normal distribution were represented as Mean± SD, and comparison before and after treatment within the group was conducted using the paired t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison before and after treatment within the group was conducted using the paired rank sum test. Count data were described as absolute numbers or proportions. Results:(1) Pre-treatment assessment. All 10 patients completed pre-treatment assessment, with 8 cases undergoing once of technetium 99-polymerised protein perfusion test and 2 cases under-going ≥ twice of technetium 99-polymerised protein perfusion test. The ratio of uptake of techne-tium 99-polymerised protein in tumor tissue to normal tissue, the hepatopulmonary shunting ratio and the therapeutic requirement of 90Y resin microspheres in 10 patients were 5.8±1.2, 4.8%±0.8% and (1.10±0.20)GBq, respectively. (2) Treatment strategy of 90Y resin microspheres TARE. Of the 10 patients, cases treated with whole tumor radioembolisation, radioembolisation of the main target lesion+non-target lesion radiofrequency ablation, radioembolisation of the main target lesion+non-target lesion iodine-125 particles implantation, radioembolisation of the liver lobe or liver segment were 6, 2, 1, 1, respectively. During the treatment period, one elderly case did not receive target therapy combined with immunotherapy due to intolerance, and the remaining 9 cases received target therapy combined with immunotherapy. Of the 10 patients, there were 7 cases receiving once of 90Y resin microspheres TARE, and 3 cases receiving twice of 90Y resin microspheres TARE. (3) Follow-up. All 10 patients were followed up for 4.5(range, 3.0-12.0)months. During the follow-up, none of patient had adverse event associated with 90Y resin microspheres TARE. The tumor diameter, alpha-fetoprotein (AFP), abnormal prothrombin, alanine aminotransferase (ALT), aspartate amino-transferase (AST), albumin (Alb), total bilirubin (TBiL), glutamyltransferase (GGT) of the 10 patients were 96(72,135)mm, 26(6,833)μg/L, 290(56,2 997)Au/L, (36±13)IU/L, (41+16)IU/L, (40±4)g/L, (15.3±4.1)μmol/L, (99±68)IU/L before receiving 90Y microspheres TARE. The above indicators of the 10 patients were 63(43,97)mm, 4(3,357)μg/L, 38(25, 142) Au/L, (40±16)IU/L, (51±28)IU/L, (39±4)g/L, (14.4±1.2) μmol/L, (134±93)IU/L after 90 days of receiving 90Y microspheres TARE. There were significant differences in tumor diameter and abnormal prothrombin ( Z=-2.08, -2.24, P<0.05) and there was no significant difference in AFP, ALT, AST, Alb, TBil, GGT ( Z=-1.27, t=0.63, 1.69, 1.73, 0.67, 1.30, P>0.05). During the follow-up period, 5 cases achieved clinical complete response, 4 cases achieved clinical partial remission, and 1 case experienced non-target lesion progression within 30 days after receiving 90Y resin microspheres TARE. The disease remission rate and disease control rate of the 10 patients were 9/10 and 9/10, respectively. None of patient died during follow-up period. Conclusion:90Y resin microspheres TARE for the treatment of initial unresectable malignant hepatic tumor is safe and feasible, and can achieve satisfactory short-term efficacy when combined with other treatment methods.