Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4⁺ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4⁺ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4⁺ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4⁺ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8⁺ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α⁺ CD4⁺ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α⁺CD8⁺ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α⁺ CD8⁺ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8⁺ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.

Transient perivascular inflammation of the carotid artery(TIPIC)syndrome is a relatively rare disease,and ultrasound is the first screening method for initial diagnosis of the disease.Contrast-enhanced ultrasound(CEUS)has unique advantages in the follow-up of patients with TIPIC syndrome.This paper reports a patient with TIPIC syndrome who was treated with acute left neck pain.The inflammation was significantly re-lieved and subsided after treatment with non-steroidal anti-inflammatory drugs.The ultrasound changes of carotid artery lesions in this patient during follow-up were analyzed,and the application value of CEUS in the follow-up diagnosis of this disease was summarized,in the hope of providing clinical reference.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

OBJECTIVE: To explore prevalence, incidence and possible factors of immediate herniated discs after posterior cervical expansive open-door laminoplasty (EODL). METHODS: Totally 29 patients with cervical spinal stenosis and intervertebral disc herniation who underwent EODL from October 2020 to December 2021 were collected, including 24 males and 5 females, aged from 43 to 81 years old with an average of (61.3±9.0) years old;the courses of disease ranged from 1 to 120 months with an average of (36.4±37.0) months. Three or more intervertebral discs on C₃-C₇ were observed. The clinical efficacy was evaluated according to Japanese Orthopaedic Association (JOA) score before operation, 3 days and 1, 3, 6 and 12 months after operation, respectively. The changes of herniated disc before and after operation were measured by multipoint area method and two-dimensional distance method, and incidence and percentage of herniated disc regression were further calculated. Cervical imaging parameters such as Cobb angle (C₃-C₇), intervertebral angle, T₁ slope (T₁S), spinal canal sagittal diameter, K-line angle, dural sac sagittal diameter were measured and compared before and after operation. Pearson correlation was used to analyze correlation between cervical sagittal imaging parameters and disc herniation changes before and after operation. RESULTS: All patients obtained grade A wound healing, and 14 of them were followed up for 3(1.00, 5.25) months. There were no immediate or long-term postoperative complications. Totally 101 herniated intervertebral discs were measured, of which 79 regression numbers were obtained by area measurement. The number of intervertebral disc regressions by distance measurement was 77. There was no statistically significant difference in Cobb angle, intervertebral angle, T₁S and K-line angle of C₃-C₇ (P>0.05), however, there were statistically significant differences in sagittal diameter of spinal canal, sagittal diameter of dural sac, and JOA score before and after operation(P<0.05). The regression ratio of disc herniation ranged from 5% to 50%, and regression ratio of disc herniation was greater than 25% in 45.57%(36/79). Disc herniation in C_4,5 was positively correlated with sagittal plane diameter in C₅(r=0.423, P=0.028). There was a negative correlation between changes of C_3,4 and C_3,4 intervertebral angle (r=-0.450, P=0.041). The improvement rate of cervical JOA score immediately after operation was (59.54±15.07) %, and postoperative follow-up improved to (76.57±14.66) %. CONCLUSION Herniated disc regression immediately after EODL is a common occurrence, and EODL should be selected as far as possible under the premise of satisfying surgical indications. The regression of disc herniation is positively correlated with spinal canal sagittal diameter, and spinal canal should be enlarged as far as possible in the appropriate scope during EODL, so as to create more opportunities and conditions for disc regression and achieve better clinical results.
Humans ; Female ; Male ; Intervertebral Disc Displacement/diagnostic imaging* ; Spinal Stenosis/diagnostic imaging* ; Laminoplasty/methods* ; Middle Aged ; Aged ; Cervical Vertebrae/diagnostic imaging* ; Adult ; Aged, 80 and over ; Intervertebral Disc/surgery*

OBJECTIVE To improve the efficiency and quality of dispensed oral drug management in the inpatient pharmacy,and ensure the safety of drug use in patients.METHODS SWOT(strength,weakness,opportunity,threat)analysis method was used to analyze the internal strengths and weaknesses,as well as the external opportunities and threats in the construction of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy of our hospital,and propose improvement strategies.RESULTS&CONCLUSIONS A refined,full-process,closed-loop traceability management system for dispensed oral drugs in the inpatient pharmacies was successfully established,which is traceable in origin,trackable in destination,and accountable in responsibility.After the application of this system,the registration rate of dispensed drug information and the correctness rate of registration content both reached 100%.The proportion of overdue drug varieties in the same period of 2024 decreased by 77.78%compared to March 2020,the inventory volume decreased by 29.50%compared to the first quarter of 2020,the per-bed medication volume decreased by 32.14%compared to the first quarter of 2020;the average workload per post in the same period of 2023 increased by 49.09%compared to 2019,the dispensing accuracy rate reached 100%,and the improvement rate of quality control problem increased by 25.25%compared to 2021.This system effectively improves the safety and accuracy of dispensed oral drug management in the inpatient pharmacy.

Objective:To explore the application of viral load (VL) testing in human immunodeficiency virus (HIV) antibody screening positive but western blot (WB) negative samples, provide scientific basis for laboratory diagnosis of such populations.Methods:For the HIV antibody retest samples from the initial screening laboratory of Zaozhuang City Center for Disease Control and Prevention from 2021 to 2023, as well as samples from the voluntary counseling and testing at outpatient clinic of our unit that showed a negative WB test result, VL and CD4 + T lymphocyte counts were tested. Four weeks later, the patients were followed up and blood samples were collected by the current district (city) Center for Disease Control and Prevention, and sent to the confirmation laboratory for confirming testing. Results:Among the thirty-two patients, there were fifteen cases with target not detected (TND) by using VL. After four weeks, the follow-up results were all negative. There was one case with a VL test result of 20-5 000 copies/ml, and after four weeks, the follow-up result was positive. There were sixteen cases with a VL test result of >5 000 copies/ml. After four weeks, the follow-up results were all positive. Person correlation analysis was conducted between the log value of VL and CD4 + T lymphocyte count, and the result showed a certain degree of negative correlation ( r=-0.63, P=0.006). Conclusions:VL testing can assist in distinguishing patients with positive HIV antibody screening and negative WB results, and VL testing and WB testing should complement each other, combined with CD4 + T lymphocyte count and epidemiological history to make a diagnosis.

Background and objective The malignant tumor that has the highest global morbidity and death rate is lung cancer,which primarily affects the elderly.The therapy landscape for non-small cell lung cancer(NSCLC)has trans-formed with the introduction of immune checkpoint inhibitors(ICIs).The purpose of this study was to compare the safety and efficacy of immune monotherapy and immunotheray combined with chemotherapy in patients with advanced NSCLC aged 75 years and above.Methods This study retrospectively analyzed 111 patients with advanced NSCLC who were at least 75 years old and received treatment at the First or Fifth Medical Centers of the People's Liberation Army General Hospital from January 2018 to October 2022.These patients underwent first-line or second-line treatment,with 70 receiving immunotherapy combined with chemotherapy and 41 receiving immunotherapy alone.Propensity score matching(PSM)was used to match the baseline characteristics of the patients,including age,Eastern Cooperative Oncology Group performance status(ECOG PS)score,and the number of treatment lines.The study endpoints included objective response rate(ORR),progression-free survival(PFS),overall survival(OS),and safety assessment.Results The median OS for the immunotherapy combined with chemother-apy group was 27.87 months,and the median PFS was 11.50 months.The median OS for the immune monotherapy group was 34.93 months,and the median PFS was 17.00 months.There were no significant differences in OS(P=0.722)and PFS(P=0.474)between the two groups,but a significant difference was observed in ORR(P=0.025).After PSM matching,each group comprised 27 patients.The median OS for the immunotherapy combined with chemotherapy group was 17.70 months,the median PFS was 8.97 months.The median OS for the immune monotherapy group was 17.87 months,and the median PFS was 11.53 months.No significant differences were observed in OS(P=0.635),PFS(P=0.878)and ORR(P=0.097).In terms of safety,the overall inci-dence of adverse events(AEs)before matching was 62.86％ in the immunotherapy combined with chemotherapy group,which was higher than 41.46％ in the immune monotherapy group(P=0.029),while there was no difference in the incidence of AEs of grade 3 or above between the two groups(P=0.221).After matching,AEs occurred in 17(62.96％ )patients in the immunotherapy combined with chemotherapy group and 13(48.15％ )in the immune monotherapy group.There were no significant differences in the overall incidence of AEs(P=0.273)or the incidence of grade 3 or above(P=0.299)between the two groups.Conclusion Im-munotherapy combined with chemotherapy does not significantly improve OS or PFS in patients with NSCLC aged 75 years and above when compared to immunotherapy alone,and this conclusion was further validated by the analysis after PSM.The safety assessment suggests that before matching,the incidence of AEs of any grade in the immunotherapy combined with chemotherapy group was higher.Still,the two groups had no difference in the incidence of AEs of grade 3 or above.Following matching,the tol-erability of the treatment was similar in both groups.According to the safety assessment,the unique circumstances and course of treatment for geriatric patients with advanced NSCLC should be considered.

Objective:To investigate the effectiveness and safety of domestic upper gastrointestinal endoscopic ultrasound (EUS).Methods:A total of 160 patients undergoing EUS at Shengjing Hospital of China Medical University (Center1) and Shenzhen People's Hospital (Center 2) from March to July 2021 were randomly selected by stratified blocked randomization, and were treated with SonoScape EG-UG5T (the test group) or Fujifilm EG-580UT (the control group). The primary outcome was the ultrasound image quality excellence rate, and the comparison was verified by non-inferiority. The secondary outcomes were the endoscopic image quality excellence rate, the operational performance excellence rate, and the system stability evaluation. The safety evaluation was based on the occurrence of intraoperative and postoperative adverse events in the subjects.Results:In the intention-to-treat analysis set (ITT), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (77/77), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.8%). In the per protocol analysis set (PPS), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (75/75), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.9%). The lower limit of the confidence interval of ultrasound image quality excellence rate of both data sets was greater than the non-inferiority threshold value of -8%, which inferred that the non-inferiority hypothesis of the test machine non-inferior to the control machine was valid. The endoscopic image quality excellence rate and the operational performance excellence rate of the test group and the control group was 100.0% in both the ITT and PPS analyses, and there was no statistically significant difference between the two groups ( P=1.000). The system instability event rate was 0.0% (0/78) in the test group and 3.9% (3/77) in the control group ( P=0.120). No adverse event occurred in either group. Conclusion:The domestic upper gastrointestinal endoscopic ultrasound is standard-compliant for clinical application under normal conditions in terms of effectiveness, safety, and stability.

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome is a relatively rare disease, and ultrasound is the first screening method for initial diagnosis of the disease. Contrast-enhanced ultrasound (CEUS) has unique advantages in the follow-up of patients with TIPIC syndrome. This paper reports a patient with TIPIC syndrome who was treated with acute left neck pain. The inflammation was significantly relieved and subsided after treatment with non-steroidal anti-inflammatory drugs. The ultrasound changes of carotid artery lesions in this patient during follow-up were analyzed, and the application value of CEUS in the follow-up diagnosis of this disease was summarized, in the hope of providing clinical reference.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.