Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.

Nitrofurantoin(NFT)is a nitrofuran antibiotic commonly used as a veterinary drug to treat bacterial infections in animals.However,due to the low solubility and bioaccumulation properties,NFT is prone to leave excessive residues in animal-derived foods and water systems,posing serious threats to human health and ecosystems.Therefore,there is an urgent need to develop an efficient and rapid detection method for NFT.In this work,nitrogen-doped carbon nanomaterials with unique bowl-like structures(N-CNBs)were synthesized via a hydrothermal-carbonization method.The morphology,surface structure,and specific surface area of N-CNBs were characterized using transmission electron microscopy(TEM),scanning electron microscopy(SEM),and X-ray photoelectron spectroscopy(XPS).The N-CNB modified glassy carbon electrode(N-CNB/GCE)was prepared,and the electrochemical test revealed that the N-CNB/GCE exhibited higher conductivity and larger electrochemical active surface area compared to bare GCE and nitrogen-doped hollow carbon nanosphere-modified electrode(N-HCNS/GCE).Additionally,the N-CNB/GCE demonstrated superior electrocatalytic activity toward NFT.An NFT electrochemical sensor was constructed based on N-CNB/GCE.The detection conditions of the sensor were optimized,and differential pulse voltammetry(DPV)was employed for NFT detection under optimal experimental conditions.The established NFT electrochemical sensor had a wide linear range of 0.4-500 μmol/L,a low detection limit(S/N=3)of 0.015 μmol/L and high selectivity,with excellent stability and reproducibility.The practical feasibility of this sensor was confirmed by analysis of NFT in milk and tap water samples,with spiked recoveries ranging from 94.2%to 108.9%.

Aim To explore the mechanism of the effect of siRNA-mediated MAGE-3 silencing on intesti-nal flora,gastric mucosal PTEN expression and liver metastasis in rats with gastric cancer based on MAPK/ERK signaling pathway.Methods Thirty rats were randomly divided into the normal(CO)group,model(MO)group,and MAGE-3 silenced(SM)group,with 10 rats in each group.The model of MO group and SM group was established by MNNG gavage meth-od.After successful modeling,the SM group was intri-toneally injected with 20 μg·kg-1 shRNA MAGE-3 lentiviral vector.The number of intestinal flora in rats was detected by selective medium of intestinal flora,the expression of PTEN in gastric mucosa was detected by immunohistochemistry,liver metastasis was detected by HE staining,and the protein expression of MAPK/ERK signaling pathway was detected by Western blot.The regulatory effect of siRNA-mediated MAGE-3 si-lencing on MAPK/ERK signaling pathway was verified in vitro.Results Compared with CO group,the con-tents of Enterococcus and Escherichia coli,the protein expressions of P-MEK1,P-ERK1 and P-ELK1 in MO group increased(P＜0.05),while the contents of Lactobacillus and Bifidobacterium and the expression of PTEN decreased(P＜0.05).In SM group,the con-tents ofEnterococcus,Escherichiacoli,P-MEK1,P-ERK1 and P-ELK1 protein expressions decreased(P＜0.05),while the contents of Lactobacillus,Bifidobac-terium and PTEN expression increased(P＜0.05).Compared with group CO,the protein expressions of P-MEK1,p-ERK1 and P-ELK1 in group MO were not significantly different(P＞0.05),while the protein expressions of P-MEK1,p-ERK1 and P-ELK1 in group SM were reduced compared with group MO(P＜0.05).Conclusions siRNA-mediated MAGE-3 si-lencing can significantly improve intestinal flora,pro-mote the expression of PTEN in gastric mucosa,and inhibit liver metastasis in rats with gastric cancer.The mechanism may be related to the inhibition of MAPK/ERK signaling pathway.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

This study investigated the mechanism by which Jianpi Bushen Yiqi Decoction promotes acetylcholine receptor(AChR) clustering in myasthenia gravis through the Agrin/low-density lipoprotein receptor-related protein 4(LRP4)/muscle-specific receptor tyrosine kinases(MuSK) signaling pathway. A total of 114 female C57BL/6J mice were divided into the normal group, modeling group, and solvent control group. The normal group and the solvent control group were immunized with phosphate-buffered saline(PBS), while the modeling group was established as an experimental autoimmune myasthenia gravis(EAMG) model using the murine-derived AChR-α subunit R97-116 peptide fragment. After successful modeling, the mice were randomly assigned to the model group, the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups, and the prednisone group. After four weeks of continuous treatment, muscle strength was assessed using Lennon scores and grip strength tests. Immunofluorescence staining was conducted on differentiated C2C12 myotubes incubated with a drug-containing serum to observe the number of AChR clusters. The integrity of AChR on myofilaments in mouse gastrocnemius muscles was further assessed by immunofluorescence staining. Hematoxylin-Eosin(HE)staining was applied to examine pathological changes in the gastrocnemius muscles of EAMG mice treated with Jianpi Bushen Yiqi Decoction. Western blot was utilized to detect the expression of key proteins in the Agrin/LRP4/MuSK signaling pathway in both C2C12 myotubes and mouse gastrocnemius muscles. The results demonstrated that compared to the model group, the prednisone group exhibited a significant decrease in the body weights of mice, whereas no significant differences in the body weights of mice were observed among the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups. All treatment groups showed significantly improved grip strength and Lennon scores. Additionally, the formula promoted AChR clustering on myotubes and enhanced AChR integrity in gastrocnemius myofilaments and reduced inflammatory infiltration between muscle tissue and fibrous hyperplasia. Furthermore, Jianpi Bushen Yiqi Decoction upregulated the protein expression of AChRα1, Agrin, and p-MuSK in C2C12 myotubes and increased the protein expression of AChRα1, Agrin, MuSK, p-MuSK, LRP4, and docking protein 7(Dok-7)in gastrocnemius tissue. In conclusion, Jianpi Bushen Yiqi Decoction may promote AChR clustering by targeting key proteins in the Agrin/LRP4/MuSK signaling pathway, thereby improving neuromuscular junction function and enhancing muscle strength.
Animals ; Agrin/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Receptors, Cholinergic/genetics* ; Female ; Mice, Inbred C57BL ; Receptor Protein-Tyrosine Kinases/genetics* ; Neuromuscular Junction/metabolism* ; Myasthenia Gravis, Autoimmune, Experimental/physiopathology* ; Humans ; LDL-Receptor Related Proteins

OBJECTIVES: To investigate the application value of targeted next-generation sequencing (tNGS) in the etiological diagnosis of moderate to severe respiratory distress syndrome (RDS) in neonates. METHODS: A prospective randomized controlled trial was conducted, enrolling 81 term and late-preterm neonates with moderate to severe RDS admitted to Fujian Children's Hospital between December 2023 and December 2024. Patients were randomly assigned to the conventional microbiological test (CMT) group (n=42) or the tNGS group (n=39). For routine pathogen detection, bronchoalveolar lavage fluid was obtained via bronchoscopy, and lower respiratory tract specimens were collected via the endotracheal tube; all specimens underwent culture, and some specimens additionally underwent polymerase chain reaction or antigen testing. In the tNGS group, tNGS was performed in addition to routine pathogen detection on the same specimen types. The detection rate of pathogens, the detection rate of co-infections, and the duration of antibiotic use were compared between the two groups. RESULTS: The pathogen detection rate in the tNGS group (18/39, 46%) was significantly higher than that in the CMT group (8/42, 19%) (P=0.009). The co-infection detection rate was 13% (5/39) in the tNGS group, while no co-infections were identified in the CMT group (P=0.024). Regarding treatment, the duration of antibiotic use in the tNGS group was shorter than that in the CMT group [(12±4) days vs (15±5) days, P=0.003]. CONCLUSIONS tNGS significantly improves the pathogen detection rate in neonates with moderate to severe RDS and offers advantages in the rapid identification of co-infections and reduction of antibiotic treatment duration, suggesting it has clinical utility and potential for wider adoption.
Humans ; Prospective Studies ; Infant, Newborn ; Female ; Respiratory Distress Syndrome, Newborn/etiology* ; Male ; High-Throughput Nucleotide Sequencing/methods*

This paper aimed to systematically evaluate the effects of hypoxic training at different fraction of inspired oxygen (FiO₂) on body composition, glucose metabolism, and lipid metabolism in obese individuals, and to determine the optimal oxygen concentration range to provide scientific evidence for personalized and precise hypoxic exercise prescriptions. A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, Embase, and CNKI databases for randomized controlled trials and pre-post intervention studies published up to March 31, 2025, involving hypoxic training interventions in obese populations. Meta-analysis was performed using RevMan 5.4 software to assess the effects of different fraction of inspired oxygen (FiO₂≤14% vs. FiO₂>14%) on BMI, body fat percentage, waist circumference, fasting blood glucose, insulin, HOMA-IR, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with subgroup analyses based on oxygen concentration. A total of 22 studies involving 292 participants were included. Meta-analysis showed that hypoxic training significantly reduced BMI (mean difference (MD)=-2.29,95%CI: -3.42 to -1.17, P<0.000 1), body fat percentage (MD=-2.32, 95%CI: -3.16 to -1.47, P<0.001), waist circumference (MD=-3.79, 95%CI: -6.73 to -0.85, P=0.01), fasting blood glucose (MD=-3.58, 95%CI: -6.23 to -0.93, P=0.008), insulin (MD=-1.60, 95%CI: -2.98 to -0.22, P=0.02), TG (MD=-0.18, 95%CI: -0.25 to -0.12, P<0.001), and LDL-C (MD=-0.25, 95%CI: -0.39 to -0.11, P=0.000 3). Greater improvements were observed under moderate hypoxic conditions with FiO₂>14%. Changes in HOMA-IR (MD=-0.74, 95%CI: -1.52 to 0.04,P=0.06) and HDL-C (MD=-0.09, 95%CI: -0.21 to 0.02, P=0.11) were not statistically significant. Hypoxic training can significantly improve body composition, glucose metabolism, and lipid metabolism indicators in obese individuals, with greater benefits observed under moderate hypoxia (FiO>14%). As a key parameter in hypoxic exercise interventions, the precise setting of oxygen concentration is crucial for optimizing intervention outcomes.

Objective To observe the difference of bone micro-structure in different regions of proximal femur,micro-CT scanning was performed on 30 proximal femur specimens to explain the mechanism of proximal femur fracture and to provide anatomical basis for prosthesis design.Methods Totally 30 intact proximal femur specimens were obtained from 60-80 year-old cadavers.Micro-CT scanning was used to measure the trabecular thickness(Tb.Th),trabecular number(Tb.N),trabecular space(Tb.Sp),connectivity(Conn)and bone mineral density(BMD)and other parameters in 7 regions of proximal femur,including proximal pressure trabecular(PPT),distal pressure trabecular(DPT),femoral head-neck junction(FHNJ),head and neck of femoral neck(HNFN),the base of femoral neck(BPFN),intertrochanteric line(IL)and greater trochanter(GT).Results The bone mineral density of IL and GT were higher than those of BPFN,FHNJ,DPT and PPT.The trabecular thickness of GT was the largest,followed by IL,BPFN and HNFN,and the smallest was FHNJ,DPT and PPT.The trabecular space of IL was larger than that of GT,and the data of both were larger than those of other parts,among which DPT and PPT were the smallest.The trabecular number of IL and GT were the smallest,BPFN,HNFN and FHNJ were larger,and DPT was the largest.The volume fraction of IL was the smallest,BPFN and HNFN were larger,DPT and PPT were the largest.Conclusion The bone density,trabecular thickness,bone volume,and total volume of GT and IL in the proximal femur of elderly patients are all relatively large,so the reason for the high incidence of fractures is not due to weak internal bone microstructure;The bone density,trabecular thickness,and trabecular gap at the proximal and distal ends of the vertical trabecular bone are relatively small.If it is necessary to perform core decompression for prosthesis filling at this location,the design should be conducive to the mechanical conduction of the prosthesis and the regeneration of surrounding bone tissue.

With the rapid development of mobile internet technology, mobile health application (mHealth APP) are increasingly widely used in the field of health management and have been proven to play an important role in the management of chronic diseases. Solid organ transplant recipients face complex health management needs after surgery, including postoperative follow-up, medication management, prevention and treatment of complications and comorbidities, and lifestyle adjustment. mHealth APP can provide solid organ transplant recipients with convenient self-management tools. Although some progress has been made in this field, there are still many challenges, such as insufficient user experience, technological dependence, and data security risks. Therefore, this article discusses the development process, main functions and current application status of mHealth APP, and analyzes its advantages in improving the self-management ability of solid organ transplant recipients, promoting doctor-patient communication and reducing the incidence of complications. At the same time, based on the practical experience of author’s team in developing the “TransMate” mHealth APP, we propose the directions that mHealth APPs should focus on in the future, in order to provide more effective support and services for the health management of solid organ transplant recipients.

Immune checkpoint blockade therapy has demonstrated remarkable efficacy in treating various malignancies; however, its clinical application remains challenged by low response rates and immune-related adverse events. Immunoglobulin superfamily member 11 (IGSF11), an inhibitory immune checkpoint molecule, serves as a specific ligand for the V-domain immunoglobulin suppressor of T cell activation (VISTA). Through the IGSF11/VISTA axis, it suppresses T cell function and represents a promising novel target for cancer immunotherapy. IGSF11 is widely expressed across multiple tumor types, though its regulatory mechanisms vary depending on the malignancy. Studies have confirmed that blocking the IGSF11-VISTA interaction or specifically inhibiting IGSF11 exerts antitumor effects. While IGSF11 is closely associated with patient prognosis, its prognostic significance differs among cancer types. This review systematically summarizes the structural characteristics of IGSF11, its regulatory mechanisms, interaction with VISTA, and functional role within the tumor microenvironment.
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Humans ; Immunotherapy ; Neoplasms/metabolism* ; B7 Antigens/chemistry* ; Animals ; Molecular Targeted Therapy ; Tumor Microenvironment