Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

The study aims to investigate the impacts of prolyl oligopeptidase (POP) on the replication of foot-and-mouth disease virus (FMDV) in BHK-21 cells. Firstly, the effects of FMDV replication on POP expression in BHK-21 cells were analyzed by Western blotting and Real-time reverse transcription polymerase chain reaction (RT-qPCR). Secondly, a eukaryotic expression plasmid for POP was constructed, and the effects of POP overexpression on the replication of two different serotypes of FMDV were assessed by Western blotting, RT-qPCR, and virus titer assays. Thirdly, specific small interfering RNAs (siRNAs) targeting POP were synthesized, and their efficiency in interfering with endogenous POP expression was identified by RT-qPCR. The impacts of downregulating endogenous POP expression on FMDV replication were further evaluated by Western blotting, RT-qPCR, and virus titer assays. The results indicated that FMDV infection did not significantly affect POP expression in BHK-21 cells. Overexpression of POP dose-dependently enhanced the replication of both FMDV/O and FMDV/A serotypes. Conversely, siRNA-mediated downregulation of endogenous POP expression markedly suppressed FMDV/O replication. This study is the first to demonstrated that the role of the host POP protein in promoting FMDV replication in BHK-21 cells, thereby providing a critical theoretical foundation and potential molecular targets for developing efficient candidate cell strains for foot-and-mouth disease inactivated vaccines.
Foot-and-Mouth Disease Virus/genetics* ; Virus Replication/genetics* ; Prolyl Oligopeptidases ; Serine Endopeptidases/physiology* ; Animals ; Cell Line ; RNA, Small Interfering/genetics* ; Foot-and-Mouth Disease/virology* ; Cricetinae

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

Objective:To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories.Methods:The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory.Results:In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%).Conclusions:A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.
Humans ; Carcinoma, Renal Cell/therapy* ; Immunotherapy ; Glycolysis ; Metabolic Reprogramming ; Kidney Neoplasms/therapy* ; Tumor Microenvironment

Purpose To explore the pathological features of angioimmunoblastic T-cell lymphoma(AITL)with bone marrow involvement and to improve awareness of bone marrow infiltration in AITL.Methods The tissue morphology of 32 cases of AITL with bone marrow involvement was retrospectively analyzed.Im-munohistochemistry using the EnVision method and ten-color flow cytometry were conducted to detect AITL-related immune markers.T cell clonality was analyzed through T cell receptor(TCR)gene rearrangement.Results The predominant pat-terns of tumor cell infiltration were nodular(20/32,62.5％)and interstitial or small clusters(10/32,31.3％).The nodules showed a mixture of cellular components.In some cases,the fo-ci contained a mixture of cells with characteristic"granuloma-toid"changes.The tumor cells were mainly small to medium-sized lymphocytes with inconspicuous atypia.Some cases showed plasma cell proliferation.19 cases were subject to immunohisto-chemical staining,which revealed a low count of CD4-positive T cells,with an average of 8.4％.The positive rates of T follic-ular helper cells(TFH)markers were as follows:CD10(7/14,50.0％),BCL6(6/19,31.6％),PD-1(13/19,68.4％),and CXCL13(13/19,68.4％).In most cases,tumor cells showed co-expression of PD-1 and CXCL13,but the number of positive cells was less than 1％.Flow cytometry analysis was performed in 24 cases,among which 22 cases all consistently expressed cytoplasmic CD3(cCD3),CD5,CD4,and CD2,with varying degrees of CD10 expression.In some cases,there was a lack of expression of surface CD3(sCD3)(12/22,54.5％),while there was a lack of expression of CD7(8/22,36.4％).and no abnormal T cells were found in 2 cases.TCR gene rearrangement analysis was performed in 7 cases,with 3 cases showing TCR clonality.Conclusion AITL with bone marrow involvement exhibits a lower proportion of tumor cells and less atypia,making it prone to misdiagnosis.The presence of lymphocytic foci with mixed cellular components in the bone marrow can indicate bone marrow involvement in AITL.Flow cy-tometry detection of abnormal T cells(double positive for CD4 and CD10)strongly suggests bone marrow infiltration in AITL.A comprehensive diagnosis of bone marrow involvement in AITL re-quires consideration of bone marrow biopsy,flow cytometry,and TCR gene rearrangement analysis.

Objective:To detect the expression levels of various immune cells in peripheral blood,and to ex-plore their relationship with unexplained recurrent spontaneous abortion(URSA)and its clinical significance in di-agnosis and treatment.Methods:A total of 351 patients with URSA who visited Hebei Reproductive Health Hospi-tal between January 2020 and September 2022 were enrolled as the URSA group,while a control group compri-sing 30 healthy women who had experienced uncomplicated term delivery once and had no history of adverse pregnancy outcomes during the same period was selected.The levels of various immune cell subsets in peripheral blood during the luteal phase were measured and compared between the two groups.Receiver operating charac-teristic(ROC)curve analysis was performed to determine the optimal cutoff values of immune cell levels that could assist in URSA diagnosis and treatment,while logistic regression analysis was conducted to identify factors influ-encing URSA occurrence.Results:The number and percentage of CD3+CD8+cells in the peripheral blood of the URSA group were significantly lower compared to those in the control group(P＜0.05).Conversely,the per-centage of NK cells was significantly higher in the URSA group than in the control group(P＜0.05).Logistic re-gression analysis revealed that the increase in CD3+CD8+cell count in peripheral blood during the luteal phase was a protective factor of URSA(OR＜1,P＜0.05).ROC curve analysis determined optimal cutoff values for im-mune cell levels to assist in the diagnosing and treating URSA:702.82 cells/μl for CD3+CD8+cell count,28.39％for CD3+CD8+cell percentage,and 12.33％for NK cell percentage.After using the optimal cutoff value to convert continuous variables into binary variables,Logistic regression analysis showed that a CD3+CD8+cell count＜702.82 cells/μl and an NK cell percentage＞12.33％were independent risk factors for URSA(OR＞1,P＜0.05).Conclusions:The decrease of CD3+CD8+cells in peripheral blood during midluteal phase is closely related to the occurrence of URSA.The number of CD3+CD8+cells(702.82 cells/μl)and the percentage of NK cells(12.33％)can be used as reference values for the diagnosis and treatment of URSA.