Objective:To assess the viability of reducing radiation dose, contrast media volume, injection flow rate and contrast medium concentration (quadruple low-dose protocol) by utilizing virtual monoenergetic images (VMI) in photon-counting detector CT (PCD-CT) for aortic CT angiography (CTA), while maintaining image quality in comparison to images obtained from energy-integrating detector CT (EID-CT).Methods:From April 2024 to June 2024, a total of 40 participants who underwent aortic CTA on PCD-CT were prospectively enrolled in the experimental group (PCD-CT group), while 40 patients with similar baseline characteristics who had previously undergone aortic CTA using EID-CT were retrospectively selected for the conventional group (EID-CT group). The EID-CT group used a tube voltage of 90 kVp, a contrast media volume of 60 ml of contrast, an injection flow rate of 3 ml/s, and a contrast concentration of 350 mgI/ml; the PCD-CT group used the QuantumPlus mode, with a tube voltage of 140 kVp, a total amount of iodine in the contrast media of 140 mgI/kg, and an injection flow rate=contrast media volume/(delay time+scan time), and a contrast media concentration of 320 mgI/ml. VMIs in PCD-CT group were reconstructed in 5-keV intervals ranging from 45 to 65 keV. The effective radiation dose and contrast injection protocols were recorded and compared between two groups. Objective image quality assessment was performed for each group. CT attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured at five anatomical locations (ascending aorta, aortic arch, descending aorta, abdominal aorta, and right common iliac artery), and image noise was recorded. Subjective image quality was independently evaluated by two readers using a 5-point Likert scale in a blinded manner. Based on data normality, the one-way ANOVA or Kruskal-Wallis test was used for image quality assessment, with Bonferroni-corrected post-hoc analysis for multiple comparisons.Results:There were no significant differences in the baseline characteristics between two groups (all P0.05). The PCD-CT group demonstrated significantly lower effective radiation dose [(3.88±0.65) mSv vs. (5.97±1.15)mSv], contrast media volume [(29.25±4.56) ml vs. 60 ml], and injection rate [(2.65±0.42) ml/s vs. 3 ml/s] than the EID-CT group, with reductions of 35%, 51%, and 12%, respectively (all P0.001). For objective image quality, except for the ascending aortic CT attenuation, the CT attenuation, SNR, and CNR of other vessels in the 55 keV PCD-CT group were comparable to those in the EID-CT group. Additionally, the difference in image noise between these two groups was not statistically significant ( P0.05). Concerning subjective image quality, at 55 keV, the PCD-CT group had similar image noise scores and vessel attenuation scores (both P0.05) and better visualization of renal artery branching ( P=0.001) compared to the EID-CT group. Conclusion:In comparison to EID-CT, the use of a 55 keV image in PCD-CT for aortic CTA has demonstrated reductions in radiation dose, contrast media volume, injection flow rate and contrast medium concentration, while maintaining image quality.

Objective:To evaluate the feasibility of head and neck vascular imaging using photon-counting detector computed tomography (PCD-CT) combined with a “quadruple lows” protocol—characterized by low contrast media volume, low iodine concentration, low injection rate, and low radiation dose—and to compare the image quality with that obtained by energy-integrating detector CT (EID-CT).Methods:A total of 105 patients with suspected cerebrovascular disease were prospectively enrolled at the First Affiliated Hospital of Zhengzhou University between April and June 2024. Patients were randomly assigned to three groups ( n=35). Group A underwent conventional head and neck CTA using EID-CT. Group B underwent PCD-CT with a protocol involving ultra-low contrast media volume, low iodine concentration, and low injection rate. Group C underwent PCD-CT with the full “quadruple low” protocol. Objective image quality parameters—including CT attenuation, image noise (standard deviation, SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR)—were measured at the ascending aorta, common carotid artery, internal carotid artery, vertebral artery, basilar artery, posterior cerebral artery, and middle cerebral artery. Two radiologists independently rated subjective image quality using a 5-point Likert scale. Differences among groups were analyzed using one-way ANOVA and the Kruskal-Wallis test. Results:Compared to Group A [contrast volume: (42.78±6.64)ml], contrast agent volume was significantly reduced in Groups B and C[ (26.26±4.45) ml and (26.54±3.83)ml, respectively], demonstrating reductions of 39% and 38% (both P<0.01). The iodine concentration was 320 mg/ml in Groups B and C, lower than 350 mg/ml in Group A (8.5%). The injection rate was also reduced in Groups B and C [(3.39±0.61) and (3.55±0.51)ml/s, respectively] compared to Group A [(4.28±0.66) ml/s], with reductions of 21% and 17% (both P<0.01). The effective dose (ED) was similar between Groups A and B [(1.40±0.15) vs. (1.40±0.19)mSv, P>0.05], while Group C demonstrated a significantly lower ED [(0.99±0.09) mSv], with a reduction of 30% compared to Group A and 29% compared to Group B (both P<0.01).In terms of objective image quality, significant differences in image noise (SD) were observed among the three groups at the vertebral artery, internal carotid artery, posterior cerebral artery, and middle cerebral artery (all P<0.05). Groups B and C showed significantly lower SD compared to Group A ( P<0.05), with no significant difference between B and C ( P>0.05). SNR was significantly higher in Groups B and C than in Group A at multiple vascular segments (all P<0.05). CNR differed only at the internal carotid artery, where Groups B and C demonstrated superior performance compared to Group A ( P<0.05).Subjective image quality scores showed no significant difference between Groups A and C ( P>0.05), while Group B had significantly higher scores than both A and C ( P<0.05). All images were deemed diagnostically acceptable. Conclusion:Compared with conventional EID-CT, PCD-CT combined with a “quadruple lows” protocol enables substantial reductions in contrast media and radiation dose while further improving image quality in head and neck CTA.

Objective:To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS).Methods:This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute′s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0.Results:From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event.Conclusion:Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.

Objective To observe the feasibility of photon-counting detector(PCD)-CT combined with"four-lows"protocol(low contrast agent concentration,low contrast dose,low contrast agent flow rate,low radiation dose)for coronary CT angiography(CCTA).Methods Totally 106 patients with suspected coronary artery disease were prospectively enrolled and randomized into energy-integrating detector(EID)-CCTA(group A,using conventional scanning protocol,n=52)or PCD-CCTA(group B,using"four-lows"scanning protocol,n=54)groups and underwent relative examinations.The radiation dose,subjective and objective evaluation results of imaging quality were compared between groups.Results The contrast agent dose and flow rate,volume CT dose index,dose length product and effective dose in group B were all lower than those in group A(all P＜0.001).The subjective scores in group B were higher than in group A(5[4,5]vs.4[4,5],Z=-2.310,P=0.021).Compared with group A,CT value,signal-to-noise ratio and contrast-to-noise ratio of aortic root and most of the main branches of coronary arteries increased in group B,while standard deviation of CT value decreased(all P＜0.05).Conclusion PCD-CT combined with"four-lows"protocol could be used for CCTA,which could improve imaging quality and reduce contrast agent usage and radiation dose.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

Parkinson's disease(PD)is the second most prevalent neurodegenerative disease and a major cause of movement disorders.Neuroinflammation plays an important role in the pathogenesis of PD.Icilin is a small molecule compound that has been reported to inhibit inflammation.Howev-er,its role in PD has not been reported.This study explored the effects of icilin on motor behavior,nerve damage,microglia activation,and neuroinflammation in MPTP-induced PD Meriones unguic-ulatus by behavioral experiments,immunohistochemistry,Western blot,and fluorescence quantifi-cation.The results showed that Icilin not only ameliorated motor dysfunction and neurological damage in MPTP-induced Meriones unguiculatus,but also inhibited microglia hyperactivation and its mediated neuroinflammation.The present study provides an evidence that icilin attenuates MPTP-induced neurodegenerative lesions in long-pawed gerbils,suggesting that it is a promising candidate for PD.

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

Utilizing network pharmacology, molecular docking, and cellular experimental validation, this study delved into the therapeutic efficacy and underlying mechanisms of matrine in combating senescence. Databases were utilized to predict targets related to the anti-senescence effects of matrine, resulting in the identification of 81 intersecting targets for matrine in the treatment of senescence. A protein-protein interaction(PPI) network was constructed, and key targets were screened based on degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on the key targets to elucidate the critical pathways involved in the anti-senescence effects of matrine. Molecular docking was conducted between matrine and key targets. A senescence model was established using human umbilical vein endothelial cells(HUVECs) induced with hydrogen peroxide(H_2O_2). Following treatment with varying concentrations of matrine(0.5, 1, and 2 mmol·L~(-1)), cell viability was assessed by using the CCK-8. SA-β-galactosidase staining was employed to observe the positive rate of senescent cells. Flow cytometry was utilized to measure the apoptosis rate. Real-time quantitative PCR(RT-PCR) was utilized to measure the mRNA expression of apoptosis-related cysteine peptidase 3(CASP3), albumin(ALB), glycogen synthase kinase 3β(GSK3B), CD44 molecule(CD44), and tumor necrosis factor-α(TNF-α). Western blot was performed to detect the protein expression of tumor protein p53(p53), cyclin-dependent kinase inhibitor 1A(p21), cyclin-dependent kinase inhibitor 2A(p16), and retinoblastoma tumor suppressor protein(pRb) in the senescence signaling pathway, p38 protein kinase(p38), c-Jun N-terminal kinase(JNK), and extracellular regulated protein kinases(ERK) in the mitogen-activated protein kinase(MAPK) pathway, and phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in the PI3K/Akt signaling pathway. The experimental results revealed that matrine significantly increased the viability of HUVECs(P<0.05), decreased the positive rate of senescent cells and the apoptosis rate(P<0.05), and reduced the mRNA expression levels of CASP3, ALB, GSK3B, CD44, and TNF-α(P<0.05). It also inhibited the protein expression of p53, p21, p16 and pRb in the senescence signaling pathway(P<0.05), upregulated the protein expression of p-PI3K/PI3K and p-Akt/Akt(P<0.05), and downregulated the protein expression of p-p38/p38, p-JNK/JNK, and p-ERK/ERK(P<0.05). Collectively, these findings suggest that matrine exerts an inhibitory effect on HUVECs senescence, and its mechanism involves the modulation of the senescence signaling pathway, MAPK pathway, and PI3K/Akt signaling pathway to suppress cell apoptosis and inflammation.
Humans ; Matrines ; Quinolizines/chemistry* ; Alkaloids/chemistry* ; Human Umbilical Vein Endothelial Cells/cytology* ; Cellular Senescence/drug effects* ; Network Pharmacology ; Molecular Docking Simulation ; Signal Transduction/drug effects* ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology*