Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Objective: To assess the impact of long-term antiretroviral therapy (ART) on human immunodeficiency virus (HIV) blood screening outcomes in post-exposure prophylaxis (PEP) failure cases through a longitudinal analysis of blood screening results over a 7-year period in a patient with HIV PEP failure. Methods: This study conducted 13 follow-up assessments for a high-risk individual who initiated ART shortly after exposure. The effectiveness of various blood screening methods, including immunological assays and nucleic acid testing (NAT), was analyzed. Blood samples were also tested with HIV RNA quantification testing, Western blot (WB) confirmation testing, chemiluminescence immunoassay (CLIA), and HIV rapid tests utilizing gold and selenium labels. A comprehensive analysis was performed to evaluate the changes in diagnostic capabilities of different testing methods for HIV biomarkers over an extended period following PEP failure. Results: The patient had two high-risk exposures: one day before ART initiation (BA1) and seven days preceding treatment (BA7). On the first day after the ART treatment (AA1), the HIV RNA concentration (viral load) was 9.07×10 copies/mL; by day five (AA5), the viral load decreased to 1.04×10 copies/mL. At day eleven (AA11), NAT and ELISA tests were both positive, with the WB result remaining indeterminate (gp160+). At day 48 (AA48), the S/CO value of the fourth generation ELISA reagent was 1.07, while results from a 6-sample pool and quantitative NAT were negative. However, a single sample NAT returned a positive result and WB tests indicated positivity for p17, p24, and gp160. At AA74, the quantitative NAT rebounded to 2.83×10 copies/mL, with positive NAT results for single and 6-sample pool NAT tests. The S/CO values of the imported and domestic ELISA reagents were 3.39 and 23.44, respectively. At AA201, 6-sample pool and quantitative NAT were negative again, while single sample NAT remained positive. From AA319 to AA2221, all NAT results have remained consistently below the minimum detection limit. At AA2221, S/CO values of the imported and domestic ELISA reagents were 3.47 and 23.44, respectively. Conclusion: The findings indicate that patients experiencing PEP failure after high-risk HIV exposure are at a higher risk of being missed by mixed-sample NAT pools and individual serological tests. Nonetheless, anti-HIV antibody levels are sustained at elevated values for an extended duration, underscoring antibody testing as an effective measure for blood screening.

Biliary tract cancer (BTC) represents a group of highly malignant solid tumors with a five-year survival rate of only 10%. For patients with unresectable BTC, gemcitabine combined with cisplatin has been the conventional first-line treatment regimen. With the remarkable efficacy of immunotherapy and targeted therapy observed in other solid tumors, numerous studies have investigated their potential in unresectable BTC. This article provides an overview of the current status of targeted and immunotherapeutic approaches for unresectable BTC, with a focus on research advancements in immune checkpoint inhibitor (ICI) and targeted agents against fibroblast growth factor receptor(FGFR), isocitrate dehydrogenase(IDH), and human epidermal growth factor receptor 2(HER2), as well as future trends in immunotherapy and targeted therapy, aiming to contribute to the development of more effective treatment strategies.

Objective To explore the correlation between central venous oxygen saturation(ScvO2)-re-lated indexes at different time points and the occurrence of low cardiac output syndrome(LCOS)after con-genital heart disease(CHD)correction surgery.Methods A total of 73 children who underwent CHD correc-tion surgery in this hospital from July 1st,2021 to July 1st,2024 were selected as the research subjects.The clinical data,preoperative conditions,and postoperative conditions of the children were collected.The ScvO2 and arterial lactate(Lac)levels of the children at different time points(the 1st,6th,12th,and 24th hours after surgery)were monitored,and the ScvO2/Lac at different time points and the change rate of ScvO2 in different time periods were calculated.The correlation between ScvO2-related indexes and LCOS after CHD correction surgery was analyzed.Results ScvO2 at the 6th hour after surgery,ScvO2 at the 12th hour after surgery,Sc-vO2/Lac at the 12th hour after surgery,the change rate of ScvO2 from the 1st to the 24th hour after surgery,the change rate of ScvO2 from the 6th to the 12th hour after surgery,and the change rate of ScvO2 from the 12th to the 24th hour after surgery were independent influencing factors of LCOS occurrence after CHD cor-rection surgery(P＜0.05).There was a negative correlation between ScvO2 at the 12th hour after surgery,ScvO2/Lac and LCOS occurrence after CHD correction surgery(r=-0.543,-0.523,P＜0.05).The area under the curve(AUC)of ScvO2 at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.938(95％CI:0.865-1.000);the AUC of ScvO2/Lac at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.922(95％CI:0.851-0.994).Conclusion ScvO2 and ScvO2/Lac at the 12th hour after surgery have good predictive potential for LCOS occurrence af-ter CHD correction surgery.

Background Bacteria are the most diverse and widely sourced microorganisms in the indoor air of subway stations, where pathogenic bacteria can spread through the air, leading to increased health risks. Objective To understand the status and distribution characteristics of indoor air bacterial pollution in subway stations and compartments in a city of Central South China, and to provide a scientific basis for formulating intervention measures to address indoor air bacteria pollution in subways. Methods Three subway stations and the compartments of trains parking there in a city in Central South China were selected according to passenger flow for synchronous air sampling and monitoring. Temperature, humidity, wind speed, carbon dioxide (CO₂), fine particulate matter (PM_2.5), and inhalable particulate matter (PM₁₀) were measured by direct reading method. In accordance with the requirements of Examination methods for public places-Part 3: Airborne microorganisms (GB/T 18204.3-2013), air samples were collected at a flow rate of 28.3 L·min⁻¹, and total bacterial count was estimated. Bacterial microbial species were identified with a mass spectrometer and pathogenic bacteria were distinguished from non-pathogenic bacteria according to the Catalogue of pathogenic microorganisms transmitted to human beings issued by National Health Commission. Kruskal-Wallis H test was used to compare the subway hygiene indicators in different regions and time periods, and Bonferroni test was used for pairwise comparison. Spearman correlation test was used to evaluate the correlation between CO₂ concentration and total bacterial count. Results The pass rates were 100.0% for airborne total bacteria count, PM_2.5, and PM₁₀ in the subway stations and train compartments, 94.4% for temperature and wind speed, 98.6% for CO₂, but 0% for humidity. The overall median (P₂₅, P₇₅) total bacteria count was 177 (138,262) CFU·m⁻³. Specifically, the total bacteria count was higher in station halls than in platforms, and higher during morning peak hours than during evening peak hours (P<0.05). A total of 874 strains and 82 species were identified by automatic microbial mass spectrometry. The results of identification were all over 9 points, and the predominant bacteria in the air were Micrococcus luteus (52.2%) and Staphylococcus hominis (9.8%). Three pathogens, Acinetobacter baumannii (0.3%), Corynebacterium striatum (0.1%), and Staphylococcus epidermidis bacilli (2.2%) were detected in 23 samples (2.6%), and the associated locations were mainly distributed in train compartments during evening rush hours. Conclusion The total bacteria count in indoor air varies by monitoring sites of subway stations and time periods, and there is a risk of opportunistic bacterial infection. Attention should be paid to cleaning and disinfection during peak passenger flow hours in all areas.

Objective To explore the viral pathogen spectrum characteristics of acute intestinal infection in Hanzhong from 2019 to 2022. Methods Fecal samples from patients with acute intestinal infection in the outpatient clinic of 3201 Hospital from January 2019 to December 2022 were collected. Common enteroviruses such as enterovirus 71 (EV-A71), coxsackievirus 16 (CV-A16), CV-A10, CV-A6, CV-A2, CV-A4, and CV-B3 were detected and analyzed by real-time fluorescence quantitative PCR. Results A total of 5 194 fecal samples were collected, and the positive rate of nucleic acid detection was 23.95%. In terms of the enteroviruses, the highest detection rate was 9.82% for EV-A71, followed by 4.58% for CV-A16 and 3.37% for CV-A6. The positive detection rate of common enteroviruses showed statistical difference among different age groups (P<0.05), with the highest detection rate of 41.49% in 0-4 years old group. There was no significant difference in the positive virus detection rate between different genders (P>0.05). EV-A71 infection showed no seasonal characteristics, whereas the detection of CV-A16 and CV-A6 infections was concentrated in summer and autumn. There were 106 cases of mixed infection, and the prevalence rate was 2.04%, with EV-A71 and CV-A6 mixed infections accounting for the majority of cases. Conclusion The main pathogens of acute intestinal infections in the Hanzhong area from 2019 to 2022 are EV-A71, CV-A16, and CV-A6. It is necessary to strengthen the monitoring of acute intestinal infections in children aged 4 years and below.

Objective To investigate the relationship between the expression levels of thyroid transcription factor-1(TTF-1)and Galectin-3 in differentiated thyroid carcinoma(DTC)tissues and clinical manifestations and prognosis of patients.Methods A total of 76 DTC patients admitted to the hospital from January 1,2017 to May 30,2020 were selected as the study objects.Cancer tissue specimens obtained during surgery were in-cluded in the DTC group(n=76),and corresponding paracancer tissue specimens were included in the para-cancer group(n=76).The expressions of TTF-1 and Galectin-3 in DTC group and paracancer group were de-tected by immunohistochemistry,and the relationship between the expression levels of TTF-1 and Galectin-3 and the clinicopathological characteristics of DTC patients was analyzed.Multivariate Cox regression analysis was used to investigate the prognostic factors of DTC patients.Results The positive expression rates of TTF-1 and Galectin-3 in DTC group were higher than those in paracancer group,and the difference was statistically significant(P＜0.05).The TTF-1 positive expression rate and Galectin-3 positive expression rate in DTC pa-tients with TNM stage Ⅲ to Ⅳ,low differentiation,tissue type of papillary thyroid carcinoma and lymph node metastasis were higher than those in DTC patients with TNM stage Ⅰ to Ⅱ,medium/high differentiation,tis-sue type of thyroid follicular carcinoma and no lymph node metastasis.The difference was statistically signifi-cant(P＜0.05).The 3-year overall survival rate of TTF-1 negative and Galectin-3 negative DTC patients was higher than that of TTF-1 positive and Galectin-3 positive DTC patients,and the difference was statistically significant(P＜0.05).Multivariate Cox regression analysis showed that lymph node metastasis,positive TTF-1 and positive Galectin-3 were prognostic factors in DTC patients(P＜0.05).Conclusion TTF-1 and Galectin-3 are related to TNM stage,differentiation degree,tissue type,lymph node metastasis and 3-year sur-vival rate of DTC patients,and have important reference value for the diagnosis and prognosis evaluation of DTC patients.

Pharmaceutical excipients, as an indispensable part of drug preparation, play crucial roles as drug carriers, improving drug release, ensuring drug stability, and enhancing patient compliance. Traditional Chinese Medicine (TCM) boasts a rich developmental history. With the modernization of technology, the deep integration of pharmacy, chemistry, and materials science has provided broader opportunities for innovative research in TCM. Simultaneously, the demand for high-quality excipients has become increasingly critical.This paper aims to review current research and applications of excipients in TCM preparations, including pre-mixed and co-processed excipients, modified excipients, and the unification of drugs and excipients, such as flavoring agents, fillers, penetration enhancers, and delivery systems. A meticulous synthesis and analysis of existing research aims to provide a reference for selecting excipients in TCM preparations, stimulate innovation in excipient development for TCM, and advocate for the development of personalized excipients.

Objective:To investigate the effects of astragaloside IV (AS-IV) on acute myocardial injury in rats with high-level spinal cord injury (SCI).Methods:Twenty-four healthy male SD rats, aged 8-10 weeks with a body weight of 250-300 g, were randomly divided into 4 groups using a random number table method: sham operation group, high-level SCI group (SCI group), high-level SCI+AS-IV group (SCI+AS-IV group) and high-level SCI+AS-IV+silent information regulator 1 (SIRT1) inhibitor EX527 group (SCI+AS-IV+EX527 group), with 6 rats in each group. The SCI model was established using the modified Allen method and the sham operation group underwent the spinal cord exposure only. In the SCI+AS-IV group, 40 mg/kg of AS-IV was injected intraperitoneally immediately after injury. SCI+AS-IV+EX527 group received an intraperitoneal injection of 5 mg/kg EX527 at one hour before injury and another injection of 40 mg/kg AS-IV in the same way immediately after injury. The sham operation group and the SCI group received an equal volume of saline via intraperitoneal injection. Immediately after awakening from injury, the hind limb motor function of the rats in each group was observed, recorded and then evaluated using the BBB method. At 24 hours after injury, the ultrastructure of the cardiomyocytes was examined under a transmission electron microscope; the levels of serum cardiac troponin I (cTnI), myocardial tissue inflammatory factors interleukin (IL)-18 and IL-1β were quantified by the ELISA method; the level of reactive oxygen species (ROS) of the myocardial tissue was assessed utilizing the dihydroethidium (DHE) assay; biochemical analyses were employed to determine the superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentrations; mRNA and protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin D (GSDMD), SIRT1 and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) were examined using RT-PCR and Western blot; cardiomyocyte pyroptosis rate was evaluated by caspase-1 and TUNEL double-labeled fluorescence staining.Results:Immediately after awakening from injury, the sham operation group exhibited normal hind limb activity, with BBB scores of 21(21, 21)points, while the remaining groups displayed flaccid paralysis in both hind limbs, accompanied by the cessation of spontaneous excretion, with BBB scores of 0(0, 0)points. At 24 hours after injury, transmission electron microscopy did not reveal any significant abnormalities in the ultrastructure of the myocardiomyocytes in the sham operation group, while changes of varying degrees were observed in the SCI group. The ELISA results indicated that at 24 hours after injury, the serum cTnI level in the SCI group was (1 435.3±148.1)pg/ml, higher than (619.6±95.4)pg/ml in the sham operation group ( P<0.01); the cTnI level was (1 154.0±80.0)pg/ml in the SCI+AS-IV group, lower than that in the SCI group ( P<0.01); the cTnI level was (1 321.8±50.2)pg/ml in the SCI+AS-IV+EX527 group, higher than that in the SCI+AS-IV group ( P<0.05). The levels of IL-18 and IL-1β in the myocardial tissue in the SCI group were (493.0±145.0)pg/ml and (936.7±93.2)pg/ml, higher than (131.1±62.5)pg/ml and (281.7±83.6)pg/ml in the sham operation group ( P<0.01); the levels of IL-18 and IL-1β in the SCI+AS-IV group were (182.4±45.6)pg/ml and (573.4±99.5)pg/ml, lower than those in the SCI group ( P<0.01); the levels of IL-18 and IL-1β in the SCI+AS-IV+EX527 group were (337.4±72.0)pg/ml and (742.6±82.7)pg/ml, higher than those in the SCI+AS-IV group ( P<0.05), yet lower than those in the SCI group ( P<0.01). At 24 hours after injury, DHE and biochemical assays showed that the levels of ROS and MDA in the myocardial tissue in the SCI group were (65±6)% and (1.97±0.27)nmol/mg, higher than (19±10)% and (1.03±0.16)nmol/mg in the sham operation group ( P<0.01); the ROS and MDA levels in the SCI+AS-IV group were (37±10)% and (1.39±0.11)nmol/mg, lower than those in the SCI group ( P<0.01); the ROS and MDA levels in the SCI+AS-IV+EX527 group were (52±7)% and (1.70±0.14)nmol/mg, higher than those in the SCI+AS-IV group ( P<0.05). The SOD level in the myocardial tissue of the SCI group was (658.48±77.56)U/mg, lower than (1 059.55±71.91)U/mg in the sham operation group ( P<0.01); the SOD level in the SCI+AS-IV group was (901.74±32.30)U/mg, higher than that in the SCI group ( P<0.01); the SOD level in the myocardial tissue in the SCI+AS-IV+EX527 group was (799.86±26.70)U/mg, lower than that in the SCI+AS-IV group ( P<0.05). At 24 hours after injury, RT-PCR showed that the mRNA expression levels of NLRP3, caspase-1 and GSDMD in the myocardial tissue of the SCI group were 2.07±0.25, 2.46±0.28 and 1.82±0.12 respectively, which were higher than 1.10±0.13, 0.95±0.17 and 1.03±0.08 in the sham operation group ( P<0.01); the mRNA expression levels of NLRP3, caspase-1 and GSDMD in the SCI+AS-IV group were 1.47±0.24, 1.51±0.16 and 1.42±0.13 respectively, which were lower than those in the SCI group ( P<0.01); the mRNA expression levels of NLRP3, caspase-1 and GSDMD in the SCI+AS-IV+EX527 group were 1.93±0.28, 1.97±0.31 and 1.65±0.16 respectively, which were higher than those in the SCI+AS-IV group, yet lower than those in the SCI group ( P<0.05). The mRNA expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI group were 0.41±0.09 and 0.56±0.07, lower than 1.20±0.14 and 1.29±0.20 in the sham operation group ( P<0.01); the mRNA expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI+AS-IV group were 0.78±0.08 and 1.01±0.19, higher than those of the SCI group ( P<0.01); the mRNA expression levels of SIRT1 and PGC-1α in the myocardial tissue of the SCI+AS-IV+EX527 group were 0.53±0.12 and 0.72±0.22, lower than those of the SCI+AS-IV group ( P<0.05). At 24 hours after injury, the western blot analysis showed that the protein expression levels of NLRP3, caspase-1 and GSDMD in the myocardial tissue in the SCI group were 1.00±0.20, 0.60±0.19 and 0.77±0.15 respectively, which were higher than 0.27±0.09, 0.18±0.10 and 0.28±0.08 in the sham operation group ( P<0.01); the protein expression levels of NLRP3, caspase-1 and GSDMD in the SCI+AS-IV group were 0.59±0.10, 0.25±0.11 and 0.33±0.11 respectively, lower than those in the SCI group ( P<0.01); the protein expression levels of NLRP3, caspase-1 and GSDMD in the myocardial tissue in the SCI+AS-IV+EX527 group were 0.85±0.15, 0.54±0.12 and 0.55±0.13 respectively, higher than those in the SCI+AS-IV group ( P<0.05). The protein expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI group were 0.44±0.16 and 0.28±0.10, lower than 0.93±0.22 and 0.75±0.16 in the sham operation group ( P<0.01); the protein expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI+AS-IV group were 0.78±0.19 and 0.55±0.12, higher than those in the SCI group ( P<0.01); the protein expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI+AS-IV+EX527 group were 0.46±0.16 and 0.35±0.07, lower than those in the SCI+AS-IV group ( P<0.05). At 24 hours after injury, caspase-1 and TUNEL double-labeled fluorescence staining showed that the cardiomyocyte pyroptosis rate in the SCI group was (34.5±6.7)%, higher than (5.3±2.9)% in the sham operation group ( P<0.01); the cardiomyocyte pyroptosis rate in the SCI+AS-IV group was (13.4±3.0)%, lower than that in the SCI group ( P<0.01); the cardiomyocyte pyroptosis rate in the SCI+AS-IV+EX527 group was (22.5±5.9)%, higher than that in the SCI+AS-IV group ( P<0.01), yet lower than that in the SCI group ( P<0.01). Conclusions:AS-IV can significantly reduce acute myocardial injury in rats with high-level SCI. Its mechanism may involve activating the myocardial SIRT1/PGC-1α signaling pathway, protecting the mitochondria, enhancing the ability to resist oxidative stress, and effectively inhibiting the NLRP3 inflammasome-mediated pyroptosis pathway.

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensi-tivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen"green"natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression.Considering the high GST levels in HCC patients,this compound demon-strated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.