Objective To explore the influences of long-chain noncoding RNA DHRS4-AS1 (lncRNA DHRS4-AS1) on the proliferation, invasion, migration, and apoptosis of thyroid cancer (TC) cells by regulating the microRNA-221-3p (miR-221-3p)/suppressor of cytokine signaling 3 (SOCS3) signaling axis. Methods Quantitative real-time PCR (qRT-PCR) was applied to detect the expression of lncRNA DHRS4-AS1, miR-221-3p, and SOCS3 mRNA in TC cell lines, and the optimal cell line was selected for subsequent experiments. FTC-133 cells were divided into five groups: control group, pcDNA-NC group, DHRS4-AS1 group, DHRS4-AS1 combined with agomir NC group, and DHRS4-AS1 combined with miR-221-3p-agomir group. Transfection efficiency was assessed using qRT-PCR. Dual luciferase reporter assays were applied to verify the targeting interaction between lncRNA DHRS4-AS1, SOCS3, and miR-221-3p. Western blot analysis was used to detect the expression of SOCS3 in FTC-133 cells. EdU method was used to measure cell proliferation. Flow cytometry was applied to measure the apoptosis of FTC-133 cells. Scratch experiment was applied to measure the migration of FTC-133 cells. Transwell chamber was applied to detect the invasion of FTC-133 cells. Nude mouse transplantation tumor experiment was used to observe the effect of lncRNA DHRS4-AS1 on the growth of TC transplantation tumors. Results Dual luciferase reporter assays showed a targeting relationship between lncRNA DHRS4-AS1, miR-221-3p, and SOCS3. LncRNA DHRS4-AS1 and SOCS3 were downregulated and miR-221-3p was upregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 inhibited proliferation, migration, and invasion of FTC-133 cells, while inducing apoptosis. Conversely, miR-221-3p overexpression reversed these inhibitory effects, and suppressed the apoptosis. Nude mouse transplantation experiment observed that overexpression of lncRNA DHRS4-AS1 resulted in a decrease in tumor tissue quality and volume, and a decrease in miR-221-3p expression and an increase in SOCS3 expression. Conclusion LncRNA DHRS4-AS1 is downregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 can inhibit the proliferation, invasion, and migration of TC cells and induce apoptosis by regulating the miR-221-3p/SOCS3 signaling axis.
MicroRNAs/metabolism* ; Suppressor of Cytokine Signaling 3 Protein/metabolism* ; Humans ; RNA, Long Noncoding/metabolism* ; Apoptosis/genetics* ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Thyroid Neoplasms/physiopathology* ; Animals ; Signal Transduction/genetics* ; Cell Line, Tumor ; Mice, Nude ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Mice ; Mice, Inbred BALB C

To construct a safe and effective multi-epitope vaccine against the S1 protein of chicken infectious bronchitis virus(IBV).In this study,homologous and non-homologous dominant epitopes of IBV M41,T,QX and H120 virulent strain S1 proteins were screened by various online bioprediction software,respectively,and a new peptide W with high immunogenicity was construc-ted by connecting the screened B-cell and T-cell epitopes with a linker peptide.W was ligated to the truncated sequence of the four viral strains by T2A yietding to the eukaryotic expression vector pEGFP-N1,and it was identified by PCR and double digestion,the obtained recombinant plasmid was transfected into HEK293A cells and target protein expression was measured by Western blot.The constructed plasmid was injected intramuscularly twice to detect the antibody level,cytokine level,and peripheral blood T cell subsets were detected after two immunizations.The epitope pro-tein W was successfully constructed,which was structurally stable,antigenic,and soluble;the re-combinant plasmid pEGFP-WMQtH,pEGFP-W,and pEGFP-MQtH matched the expected size;anti-IBV IgG antibody levels in pEGFP-N1 was increased greatly compared to the PBS group.cyto-kines IL-2,and γ interferon(IFN-γ)were increased greatly(P＜0.05);peripheral blood CD4+/CD8a value(P＜0.05)was increased greatly.The W epitope protein was successfully constructed,which can effectively activate the humoral immunity and cellular immunity against four infectious bronchitis viruses(IBV),laying a foundation for the development of an effective vaccine against IB.

Objective:To assess the predictive value of the percentage of Gleason pattern 4 (G4%) in prostate biopsy for adverse pathology and biochemical recurrence.Methods:We retrospectively analyzed consecutive patients who underwent radical prostatectomy in our institution between January 2019 and December 2023, and included those who were diagnosed with ISUP 2-3 cancer at biopsy. A total of 109 patients were included in this study. The average age of patients was (67.40±6.11) years, and the average BMI of patients was (25.36±2.97) kg/m 2. 49 Cases (45.0%) had a PI-RADS score of 5, and the median prostate volume was 32.60 (24.57, 45.63) ml. The median of most recent tPSA before biopsy was 9.76 (6.89, 12.95) ng/ml, the median PSAD was 0.28 (0.17, 0.44) ng/ml 2, and the median f/tPSA was 0.11 (0.08, 0.16). Clinical T 2b or higher stage was found in 84 cases (77.1%). The total biopsy core length was (22.91±5.18) cm, with a median of 24 (20, 24) biopsy cores and a median of 6 (4, 9) positive cores. Gleason score 3+ 4 was found in 52 cases (47.7%), and Gleason score 4+ 3 in 57 cases (52.3%). Cribriform was present in 30 cases (27.5%). G4% was calculated based on the proportion of Gleason grade 4 tumor relative to total tumor, tumor proportion relative to total tissue, and tissue length. Patients were divided into high-G4% (≥2.45%) and low-G4% (<2.45%) groups based on the median G4% value, with 55 and 54 cases, respectively. No significant differences were observed in baseline characteristics between the two groups ( P>0.05). The main risk factor of adverse pathology was analyzed by logistic regression, and receiver operating characteristic (ROC) curve and area under curve (AUC) were performed. Patients were further stratified by the G4% cutoff value from ROC, and Kaplan-Meier survival curves were plotted to compare biochemical recurrence free survival (BCRFS) between groups. The main risk factor affecting BCRFS was analyzed by Cox regression. Adverse pathology was defined as postoperative Gleason score ≥4+ 3 or pathological stage ≥T 3a. Results:Adverse pathology occurred in 44 (80.0%) high-G4% and 16 (29.6%) low-G4% patients ( P<0.01). Multivariate analysis identified G4% as an independent risk factor for adverse pathology ( OR=1.23, 95% CI 1.02-1.50, P=0.033). The highest ROC AUC value was seen for G4% (0.799), significantly outperforming Gleason score (0.799 vs. 0.641, P=0.003), tPSA (0.799 vs. 0.615, P=0.003), PSAD (0.799 vs. 0.679, P=0.038), positive cores (0.799 vs. 0.677, P=0.009), clinical T stage (0.799 vs. 0.607, P=0.001) and cribriform (0.799 vs. 0.639, P=0.001). The G4% cutoff value for predicting biochemical recurrence was 10.97%. The median BCRFS was significantly higher in the low G4% (<10.97%) group than that in the high G4% (≥10.97%) group (55 vs. 28 months, P=0.002). Cumulative recurrence free survival rates at 1 and 3 years were 94.6% vs. 74.1% and 78.0% vs. 47.6%, respectively. Multivariate Cox regression analysis indicates that G4% was an independent risk factor affecting BCRFS ( HR=1.11, 95% CI 1.00-1.23, P=0.041). Conclusions:For patients with ISUP 2-3 nmPCa, a higher G4% in biopsy specimens demonstrates strong predictive ability for adverse pathology and biochemical recurrence, outperforming traditional clinical indicators such as Gleason score and PSA.

Objective:To analyze the multidrug resistance and genomic characteristics of Monophasic variant of Salmonella enterica serovar Typhimurium (monophasic Salmonella enterica serovar Typhimurium) isolates from clinical patients and food sources in Henan province. Method:A total of 91 monophasic S.Typhimurium strains isolated from clinical and food sources in Henan from 2021 to 2023 were analyzed for antimicrobial sensitivity and underwent whole genome sequencing. Multilocus sequence typing(MLST), multidrug resistance genes and plasmid types were identified using the sequencing data. Phylogenetic tree based on core genome multilocus sequence typing (cgMLST) and single nucleotide polymorphism (SNP) sites was constructed to analyze the genetic evolutionary relationship by comparing with international popular strains in public databases. The Chi-square test was used to compare drug resistance rates. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Henan [82.19%(60/73) and 11/18, χ2=2.614, P=0.106]. The overall multidrug resistance (MDR) rate was 78.02%(71/91). Most strains were resistant to ampicillin, tetracycline chloramphenicol, β-lactam and sulfonamides. Resistance genes carried by the isolates varied, as well as the drug-resistant phenotypes. MLST showed that 91 strains of S.Typhimurium belonged to ST34 and carried aminoglycoside acetyltransferase gene aac(6′)-Iaa and mobile genetic elements such as plasmids IncQ1 and IncHI2/IncHI2A. The results of cgMLST typing phylogenetic trees showed that food and clinical isolates from the same region in Henan were identified as the same cgST type and clustered in the same branch, which indicated the risk for cross-infection between animal and human. The phylogenetic tree of monophasic S.Typhimurium constructed based on SNP sites showed that the majority of monophasic S.Typhimurium strains in Henan were close to the strains from other provinces in China, other strains were close to the strains from Europe and Southeast Asia, suggesting the possibility of cross regional transmission of the strains. Pork was identified as the main food source. Conclusion:The prevalent ST type of monophasic S.Typhimurium isolated from Henan was ST34, which carried multiple antibiotic resistance genes and widespread drug resistance phenotypes. Most of the monophasic S.Typhimurium isolates in Henan showed a specific phylogenetic lineage with the foreign epidemic strains, indicating the possibility of dissemination of strains between humans and food.

Objective:To comparatively observe optical coherence tomography (OCT) image features between traumatic macular hole (TMH) and idiopathic macular hole (IMH).Methods:A retrospective clinical study. A total of 174 patients (174 eyes) with macular hole (MH) diagnosed at Shantou International Eye Center from December 2008 to May 2024 were included in the study. Among them, there were 75 patients (75 eyes) with TMH and 99 patients (99 eyes) with IMH, and they were divided into the TMH group and the IMH group accordingly. All the affected eyes underwent best corrected visual acuity (BCVA) and OCT examinations. The BCVA was examined using a standard logarithmic visual acuity chart, and was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. The minimum diameter and basal diameter of the MH, as well as the average, nasal, superior, inferior, and temporal center retinal thickness (CRT) around the MH were measured by OCT. The independent-sample t test was used to compare the logMAR BCVA, hole diameter, and CRT at the hole margin between the groups. Results:There were significant differences in age ( t=-15.857) and gender ratio ( χ2=28.154) between the TMH group and the IMH group ( P<0.05), while there was no significant difference in logMAR BCVA ( t=1.962, P>0.05). The minimum diameter of the hole in the TMH group was smaller than that in the IMH group, but the basal diameter was larger, with significant differences ( t=-3.322, 2.570; P<0.05). The thickness of the neuroepithelial layer at the hole margin in the TMH group was thinner than that in the IMH group, with significant differences in the superior ( t=-2.747), inferior ( t=-2.316), and nasal ( t=-2.851) regions ( P<0.05), and no significant difference in the temporal region ( t=-1.586, P>0.05). In the TMH group, the number of eyes with macular cystoid edema (CME), posterior vitreous detachment (PVD), retinal atrophy, subretinal hemorrhage, choroidal laceration, and focal neuroepithelial detachment was 36 (48.00%, 36/75), 4 (5.33%, 4/75), 4 (5.33%, 4/75), 15 (20.00%, 15/75), 8 (10.67%, 8/75), and 19 (25.33%, 19/75) eyes, respectively. In the IMH group, the number of eyes with CME and PVD was 95 (95.96%, 95/99) and 94 (94.95%, 94/99) eyes, respectively. Conclusion:Compared with IMH, TMH has a larger basal diameter, a thinner CRT at the hole margin, a lower incidence of CME and PVD, and a higher incidence of subretinal hemorrhage, focal neuroepithelial detachment, choroidal laceration, and retinal atrophy.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

To construct a safe and effective multi-epitope vaccine against the S1 protein of chicken infectious bronchitis virus(IBV).In this study,homologous and non-homologous dominant epitopes of IBV M41,T,QX and H120 virulent strain S1 proteins were screened by various online bioprediction software,respectively,and a new peptide W with high immunogenicity was construc-ted by connecting the screened B-cell and T-cell epitopes with a linker peptide.W was ligated to the truncated sequence of the four viral strains by T2A yietding to the eukaryotic expression vector pEGFP-N1,and it was identified by PCR and double digestion,the obtained recombinant plasmid was transfected into HEK293A cells and target protein expression was measured by Western blot.The constructed plasmid was injected intramuscularly twice to detect the antibody level,cytokine level,and peripheral blood T cell subsets were detected after two immunizations.The epitope pro-tein W was successfully constructed,which was structurally stable,antigenic,and soluble;the re-combinant plasmid pEGFP-WMQtH,pEGFP-W,and pEGFP-MQtH matched the expected size;anti-IBV IgG antibody levels in pEGFP-N1 was increased greatly compared to the PBS group.cyto-kines IL-2,and γ interferon(IFN-γ)were increased greatly(P＜0.05);peripheral blood CD4+/CD8a value(P＜0.05)was increased greatly.The W epitope protein was successfully constructed,which can effectively activate the humoral immunity and cellular immunity against four infectious bronchitis viruses(IBV),laying a foundation for the development of an effective vaccine against IB.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.