To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

Objective To evaluate the accuracy of multiparametric imaging on the dual-source CT through acceptance and commissioning testing, and to provide a reference for standardized clinical application. Methods Both the adult and pediatric dual-source CT scanning modes were used to scan the electron density phantom, and identical multiparametric image reconstruction tasks were performed, including the conventional CT images, the mixed CT images, the virtual monoenergetic images, the iodine images, the electron density images, and the effective atomic number images. Results In the adult scanning mode, the virtual monoenergetic CT numbers showed the greatest difference for the cortical bone (1722 HU at 40 keV vs. 30 HU at 80 keV), with smaller differences observed for other materials as their atomic numbers decreased. The pediatric scanning mode exhibited a similar trend, with the largest difference occurring at 40 keV (1393 HU). In the adult scanning mode, the deviations between the theoretical and measured iodine concentration values were all within 5%, whereas in the pediatric scanning mode, the largest deviation was 15% for an iodine concentration of 2.0 mg/mL. For the electron density, the largest deviation between the theoretical and measured values occurred in the LN450 lung (9.18% in the adult scanning mode and 8.96% in the pediatric scanning mode); the deviations for the LN300 lung were all below 7.2%, for aluminum below 6.3%, and for other tissues within 3%. For the effective atomic number, the deviations between the theoretical and measured values were all within 5% in both scanning modes. Conclusion To ensure the accuracy and reproducibility of the dual-source CT applications, a comprehensive acceptance testing protocol should be established to guarantee the safety and precision of the CT localization process.

BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

As the need for antibody production rises, there is an urgent need to lower the costs and enhance the efficiency of the separation process. Currently, the chromatographic media used for antibody separation and purification often focus on individual properties of antibodies, such as affinity, hydrophobicity, and charge, leading to issues like low purification efficiency or inadequate adsorption capacity. To address this, an electrostatically coupled polypeptide affinity medium (FD7-3, 5-diaminobenzoic acid n-sepharose, FD7-DA-Sepharose) was developed for rapid purification of antibodies from cell culture supernatant. This medium utilized 3, 5-diaminobenzoic acid as a spacer to attach the heptapeptide-affinity ligand (FYEILHD, FD7) to agarose microspheres. Antibodies could be adsorbed through charge interactions with the carboxyl functional group of the FD7-DA-Sepharose spacer, while FD7 enhanced electrostatic coupling and affinity adsorption through synergistic effects, significantly increasing the adsorption capacity while maintaining the affinity and specificity. The influences of pH and ionic strength on adsorption capacity were investigated with human immunoglobulin as a model protein. The static adsorption capacity (Q_m) of FD7-DA-Sepharose in the solution of pH 6.0 reached 67.73 mg/mL, representing a 52.68% increase compared with that (44.36 mg/mL) of the commercial Protein A affinity medium. Furthermore, the elution conditions for FD7-DA- Sepharose were mild (20 mmol/L PB, 0.5 mol/L NaCl, pH 6.0), in contrast to the harsh acidic elution (pH 2.7-3.6) typically associated with Protein A, which can damage antibody integrity. The FD7-DA-Sepharose medium was then employed to purify antibodies from cell culture supernatant, achieving the yield of 94.8% and the purity of 98.4%. The secondary structure of the purified antibody was determined by circular dichroism spectroscopy. The results demonstrated that FD7-DA-Sepharose enabled efficient purification of antibodies from cell culture supernatant, which provided a cost-effective solution (approximately one-third the price of commercial Protein A affinity medium) with gentle elution conditions that preserve the natural conformation of antibodies. This approach paves a novel, economical, and efficient way for the separation and purification of antibodies from cell culture supernatant.
Chromatography, Affinity/methods* ; Static Electricity ; Humans ; Sepharose/analogs & derivatives* ; Peptides/chemistry* ; Adsorption ; Antibodies/isolation & purification*

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Objective To analyze the influencing factors of clinical pregnancy and live birth rates in patients undergoing frozen-thawed embryo transfer(FET)for the first time.Methods The clinical data of 1 458 patients who underwent FET cycle-assisted pregnancy for the first time were retrospectively analyzed and divided into four groups according to clinical pregnancy and live bith outcomes.The clini-cal data were compared to analyze the factors affecting clinical pregnancy and live birth rates in FET cycles that were included in multiple logistic regression analysis.Results Of the 1458 cycles,the clinical pregnancy and live birth rates were 44.0% and 34.0%,respectively.The mean age of the clinical pregnancy and live birth groups was lower than that in non-clinical pregnancy and stillbirth groups(P<0.05).The clinical pregnancy and live birth rates of patients aged<35 years were higher than those aged≥35 years(P<0.05).The clinical preg-nancy and live birth rates of patients with≥8 mm endometrial thickness were higher than those with<8 mm endometrial thickness(P<0.05).The clinical pregnancy rate of natural cycles of endometrial preparation regimen was higher than that of HRT cycles(P<0.05).The clinical pregnancy and live birth rates of double-embryo transfers were higher than that of single-embryo transfers(P<0.05).The clinical pregnancy and live birth rates of blastocyst transfers were higher than those of cleavage stage(P<0.05).Conclusion Age,endometrial thickness,number of transplanted embryos,and embryo morphology were the independent factors influencing clinical pregnancy and live birth outcomes during FET cycle transplantation.

Objective To explore the possibility of MR Ti-mapping imaging technology to provide additional indicators for clinical quantitative evaluation of renal function in children with renal insufficiency.Methods A total of 13 children with renal insufficiency diagnosed and underwent renal function MRI examination were selected(renal insufficiency group),and 23 children with normal renal function were included as the control group.The difference of renal cortex T1 value between the control group and the renal insuffi-ciency group was compared,and the correlation between renal cortex T1 value and biochemical indexes such as serum creatinine(SCr)and cystatin C(CysC)in the renal insufficiency group was analyzed.Results There was significant difference in T1 value of renal cortex between the renal insufficiency group and the control group(P＜0.01).The correlation between T1 value of renal cortex and SCr and CysC in renal insufficiency group was higher(r=0.75,P＜0.01;r=0.68,P＜0.01).Conclusion MR T1-mapping technol-ogy can non-invasively monitor the renal function status of children with renal insufficiency,and has a suggestive value for clinical quantitative evaluation of renal function in children.

Objective:To explore the safety and feasibility of adrenal tumor resection under day surgery mode for the treatment of unilateral primary aldosteronism (UPA).Methods:The clinical data of 83 patients who underwent adrenalectomy for the treatment of UPA from January 2020 to January 2023 were retrospectively analyzed. There were 42 males (50.6%)and 41 females (49.4%), age (49.0±12.3)years old. Body mass index (25.4±3.6)kg/m 2. There were 17 patients with diabetes, 58 patients with preoperative hypertension, and the duration of hypertension was 8.2(1, 15)years. Systolic blood pressure was 151.8(137.0, 160.0)mmHg (1 mmHg=0.133 kPa), and diastolic blood pressure was 97.4(87.0, 107.0)mmHg. 20 cases had severe preoperative hypokalemia, with preoperative blood potassium levels of (2.9±0.6)mmol/L. The ratio of preoperative plasma aldosterone to renin activity was 54.1(13.0, 77.2). Tumors were located on the left side in 47 cases (56.6%)and on the right side in 36 cases (43.4%). The maximum diameter of the tumor is 1.5(1.0, 1.7)cm. Patients diagnosed with unilateral primary aldosteronism were included, and patients diagnosed with adrenal pheochromocytoma, adrenal malignancy, or severe cardiovascular disease that cannot tolerate surgery were excluded. The patient was admitted to the hospital on the same day, underwent surgery on the same day, and was evaluated after extubation within one day after surgery. The patient had no fever or lower back pain after surgery, was able to freely get out of bed, and had no obvious abnormalities in blood routine, electrolyte and other test indicators. The patient was discharged from the hospital and received continuous care outside the hospital. The patient was guided to undergo regular outpatient follow-up. Evaluate the efficacy using the Primary Aldosterone Hyperaldosteronism Surgical Outcome (PASO)criteria. Results:The patients had a mean length of hospital stay of 43.0(40.3, 44.6)hours, an operation time of 89.6(70.0, 103.0)minutes, and an operation cost of 23 820.2 (21 150.8, 24 948. 3)yuan. The postoperative free position time was 29.5(20.8, 39.7)hours, the postoperative time for fluid placement of the diet was 25.2(20.1, 27.8) hours, and 42.2(37.9, 41.9)hours of postoperative drain removal. The overall postoperative clinical remission rate was 85.5%. There were four postoperative complications, accounting for 4.8% of cases. These included two cases of interosseous vein thrombosis, one case of delayed healing, and one case of peritoneal rupture. No case of readmission was reported within 30 days.Conclusions:UPA adrenal tumour resection in ambulatory mode is safe and effective when strict inclusion and exclusion criteria are followed, adequate preoperative preparation is carried out, and expert physician assessment is provided.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane protein of the immunoglobulin superfamily, is involved in mediating cell adhesion, tissue metastasis, control of immune response, and metabolic homeostasis. Studies have shown that CEACAM1 protects the liver by promoting insulin clearance and preventing fat deposition. The down-regulation of the CEACAM1 expression level leads to a vicious cycle of insulin resistance and aggravates metabolic disorders. As CEACAM1 is critical in controlling metabolic dysfunction-associated steatotic liver disease (MASLD), stimulating its pathway or regulating its expression level might be a potential new therapeutic approach for MASLD. In this paper, therefore, we summarize the research progress of CEACAM1 in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.