ObjectiveTo evaluate the pregnancy outcomes of assisted reproductive technology （ART） in women with a history of thyroid cancer who retained fertility intentions after completing cancer treatment. MethodsA retrospective analysis was performed on 61 patients with a history of thyroid cancer who underwent in vitro fertilization/intracytoplasmic sperm microinjection and embryo transfer （IVF/ICSI-ET）. These patients were included as the case group. A total of 122 non-cancer patients who received ART during the same period were selected as the control group using 1∶2 matching based on age and oocyte retrieval time. Baseline characteristics， outcomes of the first ART cycle， and cumulative pregnancy outcomes were compared between the two groups. ResultsThere was no significant difference in the basic data， the total amount of gonadotropin （Gn） and the days of use between the case group and the control group （P>0.05）. However， the case group had significantly fewer retrieved oocytes， mature oocytes （MII）， lower fertilization and cleavage rates， and fewer transferable and high-quality embryos， as well as fewer embryos transferred during the first cycle （P < 0.05）. However， there was no significant difference in the rate of first embryo implantation and first clinical pregnancy between the two groups （P>0.05）. In the analysis of cumulative outcomes， the two groups did not show statistically significant differences in the cumulative pregnancy rate， clinical pregnancy rate per transfer cycle， the number of oocyte retrieval cycles required per live birth， the number of embryo transfer cycles required per live birth， and the number of embryos used for each live birth （P>0.05）. However， the cumulative live birth rate was significantly lower in the case group compared to the control group （P=0.005）. ConclusionAfter treatment for thyroid cancer， when ART is used to help pregnant women， the pregnancy outcome is comparable to that of women without tumors. Individualized reproductive management and timely fertility preservation strategies are recommended to optimize reproductive outcomes in this population.

OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

The use of wastewater analysis, or wastewater-based epidemiology, to assess and monitor the situation of drug abuse is now widely used at home and abroad. However, there is currently a lack of effective evaluation methods and effective ways of comparison, supervision and standardization, which is not conducive to the analysis and comparisons of data in different countries and regions. Quality control techniques can control the laboratory's analytical errors, safeguard the consistency and comparability of identification conclusions, and promote the further improvement of the level and capacity of urban drug governance, thus playing significant roles. This paper provides an overview of sample collection, sample preservation and transportation, laboratory analysis, back-calculation of drug use and external laboratory quality control in the process of wastewater analysis, with a view to exploring more comprehensive scientific and objective methods and approaches suitable for examining and evaluating qualitative and quantitative analysis of drugs in wastewater among laboratories.

ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.

Objective To explore the mechanism of malt alcohol extract improving depression-like behavior induced by CUMS in rats by regulating gut microbiota.Methods The depression model of rats was established using an 8-weeks CUMS procedure,and the administration group was given low(59.6 mg·kg-1)and high(178.8 mg·kg-1)doses of malt alcohol extract,respectively.The depression-like behavior of rats was evaluated by classic behavioral test.The composition of intestinal microbiota of rats was analyzed by 16S rRNA sequencing.The morphological changes of colon were observed by hematoxylin and eosin(HE),the expression of ZO-1 and Occludin in colon was detected by immunofluorescence(IF),and the expression of IL-10,IL-1βand 5-HT were detected by ELISA.Results The low dose of malt alcohol extract attenuated the depressive behavior and restored the expression of 5-HT in the brain of CUMS rats.16S rRNA sequencing results showed that the diversity and relative abundance of gut microbiota changed after treatment with the low dose of malt alcohol extract.ELISA results showed that the low dose of malt alcohol extract significantly reversed the CUMS-induced reduction of IL-10 and elevation of IL-1 β.HE results showed that the low dose of malt alcohol extract significantly ameliorated CUMS-induced structural damage in colon.IF results showed increased protain expression of intestinal epithelial barrier tight junction proteins ZO-1 and Occludin by the low dose of malt alcohol extract.Conclusion The low dose of malt alcohol extract can ameliorate CUMS-induced depressive-like behavior in rats by modulating intestinal flora,restoring 5-HT expression in the brain,inhibiting inflammation,and repairing the intestinal barrier.

Objective To explore the feasibility and safety of ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer.Methods Totally 84 patients who underwent ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer were enrolled,and the technical success rate,complete ablation rate,complication rate,pain relief rate and survival time,etc.were observed.Results The median age of 84 cases was 61.5 years.Totally 86 tumors,including 44.19％(38/86)at the head/neck and 55.81％(48/86)at the body/tail of pancreas were detected,and a total of 85 ablation sessions were performed with the median ablation energy applied per tumor of 9.90(1.08,21.60)kJ and the complete ablation rate of 42.86％(36/84).The technical success rate was 100％(85/85).Thirty-nine complication events occurred in 25 cases,no ablation-related death.Among 34 patients underwent ablation mainly for pain symptoms,the pain score decreased from(6.22±1.12)points before treatment to(1.94±1.64)points after treatment(P＜0.001).During 6.8(3.3,12.9)months' follow-up,the mean survival time was(8.5±6.7)months,and all 47 patients died due to tumor progression.Conclusion Ultrasound-guided percutaneous microwave ablation was safe and feasible for unresectable pancreatic cancer.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.