Objective:To understand the genetic characteristics of varicella-zoster virus（VZV）prevalent in Qinghai province，China since 2020.Methods:A total of 54 pharyngeal swab specimens were collected from sporadic suspected varicella cases in Qinghai province in 2020，2023，and 2024. Real-time fluorescence quantitative polymerase chain reaction was used for etiological screening of the specimens. Sequencing of three genes，namely ORF22，ORF38，and ORF62，and single-nucleotide polymorphism（SNP）analysis were performed on VZV nucleic acid-positive specimens.Results:All 54 suspected varicella cases were diagnosed with VZV infection，and three gene sequences were successfully obtained from 53 specimens. The results of genotype identification showed that all VZV infection case specimens obtained in this study in Qinghai province were wild strains. Among them，4 specimens in 2020 were of clade 2 type；among 14 specimens in 2023，7 were of clade 2 type and the remaining 7 were of clade 5 type；among 35 specimens in 2024，27 were of clade5 type，5 were of clade 2 type，and 3 were of clade 4 type. The SNP results showed that in 2023 and 2024，one specimen each had an A→G base mutation at position 37 990，and in 2024，3 specimens had a T→C base mutation at position 37946. Among them，the sequences containing the former mutation have been prevalent and spread in multiple regions of China，and the latter has not been reported in other regions of China.Conclusion:From 2020 to 2024 in Qinghai province，at least three genotypes of VZV，namely clade 2 type，clade 5 type，and clade 4 type，co-prevailed，and the clade 5 genotype of VZV may become the dominant prevalent strain.

Purpose To investigate the correlation between tumor budding in penile squamous cell carcinoma(SCC)and its clinicopathological features.Methods Clinical data and pathological slides from 69 cases of penile SCC were collected.Tumor budding was examined microscopically,and statistical analyses were performed to assess the relationship between tumor budding and various clinicopathological features.Results Among the 69 cases of pe-nile SCC,41 cases exhibited low-grade tumor budding and 28 cases displayed high-grade tumor budding.Tumor bud-ding was significantly correlated with tumor size,urethral invasion,invasion of the urethral corpus spongiosum,inva-sion of the penile corpus cavernosum,tumor necrosis,nerve invasion,vascular tumor thrombus,and pathological T stage(all P＜0.05).In contrast,no significant association was found between tumor budding and HPV-related versus non-HPV-related penile SCC(P＞0.05).Log-rank survival analysis indicated that patients with high-grade tumor bud-ding had a significantly lower survival rate compared to those with low-grade tumor budding(P＜0.05).Conclusion Tumor budding is a distinct pathological feature of penile SCC,and high-grade tumor budding is associated with a more aggressive biological behavior.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Objective To investigate the neurovascular coupling(NVC)status in the acute phase of patients with minor ischemic stroke(MIS)or transient ischemic attack(TIA)due to intracranial large artery moderate-to-severe stenosis or occlusion using multimodal MRI techniques and to explore its correlation with quality of life(QoL).Methods This prospective,consecutive study enrolled patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion form the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,between June 2022 and October 2023.Recruit healthy subjects with matched age,sex,and handedness form the community during the same period.Patients were divided into left-sided involvement and right-sided involvement groups based on the affected side of the responsible vessel,while the healthy subjects were set as the healthy control group.Post-hoc power analysis was performed using G*Power 3.1 software.General characteristics(age,gender,body mass index,education level)were collected and compared across all three groups.Clinical data and QoL assessment were collected and compared between the two patient groups.Collected clinical data including type of cerebrovascular events(TIA,MIS),the National Institutes of Health stroke scale(NIHSS)score at admission,the responsible vessel(internal carotid artery,middle cerebral artery)and its side location,the degree of responsibility artery stenosis(moderate-severe stenosis[50%-99%stenosis rate],occlusion[100%stenosis rate]),the intracranial collateral circulation status(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASITN/SIR]collateral circulation grading),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia,smoking history),and the laboratory test indicators at admission(glycated hemoglobin,triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,blood uric acid,blood homocysteine).QoL was assessed using the stroke impact scale(SIS),covering eight functional domains and a patient-reported overall recovery item.Multimodal MR data were acquired for all subjects.Whole-brain cerebral blood flow(CBF)images were generated using statistics parameter mapping 12(SPM 12)software,while regional homogeneity(ReHo)images were generated using DPABI software.The voxel-wise ratio of CBF to ReHo(CBF/ReHo)was calculated as the regional NVC parameter.Differences in regional NVC characteristics were compared between patient groups and the healthy control group.Correlations between NVC parameters and SIS scores within patient groups were explored.Results(1)A total of 38 patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion were included(26 males,12 females,aged 36-69 years,with mean age of[52±11]years),with 23 in the left-sided involvement group and 15 in the right-sided involvement group.Nineteen healthy subjects were included(10 males,9 females,aged 37-67 years,with mean age of[53±10]years).Post-hoc power analysis showed statistical power of 0.808 for comparing the left-sided involvement group with the healthy control group and 0.762 for comparing the right-sided involvement group with control group.(2)No statistically significant differences were found on gender,age,education level,or body mass index across the three groups(all P＞0.05).No statistically significant differences were observed on the type of cerebrovascular event,cerebrovascular risk factors,distribution of the responsible vessel,degree of stenosis in the responsible vessel,admission NIHSS score,or laboratory test results between the two patient groups(all P＞0.05).There were no statistically significant differences in the total SIS score and the scores of subscales between the two patient groups(all P＞0.05).(3)Compared with the healthy control group,the left-sided involvement group exhibited reduced CBF/ReHo values in the left superior and middle temporal gyri,supramarginal gyrus,middle and inferior frontal gyri,precentral gyrus,angular gyrus,postcentral gyrus,insula,and posterior cerebellar lobe(FDR-corrected,all P＜0.05).In the right-sided involvement group,reduced CBF/ReHo values were observed in the right supramarginal gyrus,right postcentral gyrus,inferior temporal gyrus,and insula(FDR-corrected,all P＜0.05).(4)Correlation analysis revealed that the SIS total score in the left-sided involvement group negatively correlated with CBF/ReHo values in the right inferior frontal gyrus(T=-5.91)and the right middle temporal gyrus(T=-6.65,FDR-corrected,both P＜0.05).The SIS subscale score for activities of daily living in the left-sided involvement group showed negative correlations with CBF/ReHo values in the right angular gyrus(T=-7.36),right medial superior frontal gyrus(T=-6.97),right orbitofrontal cortex(T=-8.99),and left thalamus(T=-7.51,FDR-corrected,all P＜0.05).No significant correlation was observed between the SIS total score and CBF/ReHo values in patients with right-sided involvement group.The SIS subscale for communication score in the right-sided involvement group correlated with CBF/ReHo in the left lingual gyrus(T=-12.15),left olfactory cortex(T=-7.68),and right anterior cingulate and paracingulate cortex(T=-9.46,FDR-corrected,all P＜0.05).Conclusions Patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion show abnormal NVC in the acute phase,especially those with left hemisphere involvement,who exhibit more extensive impairments.QoL in left-sided involvement patients is strongly linked to NVC in the right orbitofrontal cortex and right middle temporal gyrus.These findings require further validation in larger-scale studies.

Objective:To analyze the differences in the clinical characteristics of patients with adenomyosis of different magnetic resonance imaging (MRI) types and the differences in treatment effects after the application of dienogest.Methods:A total of 176 patients with adenomyosis who were admitted to Peking University Third Hospital from June 2017 to February 2023 were included in the study, and all of them were clearly classified by pelvic MRI and treated with dienogest. The clinical characteristics and treatment of the patients were retrospectively collected, and the patients were divided into endogenous type, exogenous type and penetrating type by MRI. The differences in clinical symptoms, imaging features and treatment effect of patients with adenomyosis of different MRI types were analyzed.Results:(1) The percentages of patients with endogenous, exogenous, and penetrating types were 40.9% (72/176), 35.2% (62/176) and 23.9% (42/176), respectively. The proportion of dysmenorrhea in patients with endogenous type (90.3%, 65/72) was significantly lower than those of exogenous type (100.0%, 62/62) and penetrating type (97.6%, 41/42; χ2=7.853, P=0.020), while there was no significant difference between exogenous type and penetrating type ( P>0.05). There were no statistically significant differences in menarche time, menstrual cycle and menstrual period among the three types of patients (all P>0.05), there was also no statistically significant difference in the proportion of menstrual abnormalities (including heavy and irregular menstrual bleeding; P>0.05). The proportions of ovarian endometrioma and deep infiltrating endometriosis in exogenous and penetrating types were significantly higher than that in endogenous type (all P<0.05). (2) The pain scores of all patients were significantly lower than those before treatment (all P<0.001), the proportion of patients with exogenous type (62.9%, 39/62) who had complete remission after treatment was higher than those of endogenous type (49.2%, 32/65) and penetrating type (46.3%, 19/41), but there was no significant difference in pain relief (i.e. the variation in the pain scores) between the three types ( P>0.05). (3) Endogenous type ( OR=0.361, 95% CI: 0.147-0.883; P=0.026), failure to apply gonadotropin-releasing hormone agonist (GnRH-a) in advance ( OR=0.208, 95% CI: 0.083-0.518; P<0.001), cystic changes ( OR=2.671, 95% CI: 1.108-6.437; P=0.029) and abnormal menstruation ( OR=3.466, 95% CI: 1.464-8.209; P=0.005) were independent risk factors for irregular bleeding after dienogest treatment. Conclusions:(1) There are obvious differences in the clinical characteristics of patients with adenomyosis of different MRI types, and patients with exogenous and penetrating types are more likely to have dysmenorrhea symptoms. (2) Dienogest could significantly alleviate the symptoms of dysmenorrhea in patients with adenomyosis. (3) Endogenous type, failure to take GnRH-a in advance and associated menstrual abnormalities are independent risk factors for irregular bleeding after dienogest treatment.

Objective:To explore the clinical characteristics and prognosis of primary renal dedifferentiated liposarcoma.Methods:A retrospective analysis was conducted on the clinical data of 10 patients diagnosed with renal dedifferentiated liposarcoma in the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2023. The cohort consisted of 8 males and 2 females, with a mean age of (59.0±6.8) years. Tumors were located in the left kidney in 8 cases and in the right kidney in 2 cases. Presentations included flank or abdominal masses in 4 patients, back pain in 3 patients, and asymptomatic in 3 patients. Imaging studies revealed solitary lesions in 9 cases and multiple lesions in 1 case. The maximum tumor diameter ranged from 95 to 178 mm, with a median of 119.5 mm. CT showed tumors within the renal parenchyma with unclear boundaries and displayed a "slow in, slow out" pattern of gradual enhancement. Clinical staging revealed T 2N 0M 0 in 3 cases, T 3N 0M 0 in 4 cases, T 4N 0M 0 in 3 cases, and T 2N 1M 0 in 1 case. Nine patients underwent radical nephrectomy, including 4 laparoscopic surgeries, 4 open surgeries, and 1 robotic-assisted with thrombectomy. One patient, presenting with multiple lymph node metastases confirmed by PET-CT, underwent a diagnostic biopsy. Postoperative pathological features, follow-up and prognosis were analyzed. Results:Pathological specimens appeared grayish-red, grayish-yellow or grayish-white cut surfaces with soft to moderate texture. Microscopically, tumor cells were ovoid or short spindle-shaped with significant atypia and cytoplasmic vacuoles, with visible pathological mitoses. Six cases showed only dedifferentiated components with tumor giant cells and multinucleated giant cells resembling pleomorphic undifferentiated sarcoma, with focal tumor necrosis. Fluorescence in situ hybridization showed MDM2 gene amplification in all cases. All cases were diagnosed as primary renal dedifferentiated liposarcoma. Pathological staging showed 4 cases as pT 2N 0M 0, 3 cases as pT 3N 0M 0, 2 cases as pT 4N 0M 0, and 1 case lacked pathological staging due to biopsy only. Five patients received postoperative adjuvant therapy, including two pT 2N 0M 0 cases who received immunotherapy and apatinib treatment respectively, with no recurrence. One pT 3N 0M 0 case received anlotinib treatment, with local recurrence after 12 months, followed by radiofrequency ablation combined with chemotherapy. Two pT 4N 0M 0 cases received ifosfamide combined with epirubicin and pirarubicin combined with lobaplatin respectively, with one case showing no progression at 11 months follow-up, and another case developing splenic metastasis 3 months post-surgery, followed by chemotherapy combined with targeted therapy, surviving for 20 months. Among the 4 cases without adjuvant therapy, two pT 2N 0M 0 cases developed multiple metastases within 1 month post-surgery and received immunotherapy combined with targeted therapy and/or chemotherapy, surviving 4-5 months.One of the two pT 3N 0M 0 cases developed local recurrence 2 months post-surgery and received chemotherapy, surviving 6 months, and another pT 3N 0M 0 case developed gluteal subcutaneous metastasis 1 month post-surgery and received immunotherapy combined with targeted therapy, surviving 8 months.One non-surgical pT 2N 1M 0 patient received chemotherapy and survived for 15 months. All patients were followed up for 4-52 months, with a median follow-up time of 11 months. At the last follow-up, 6 patients died and 4 survived. Conclusions:Primary renal dedifferentiated liposarcoma is clinically rare, with atypical symptoms and difficult preoperative diagnosis, relying on pathology for confirmation. Radical nephrectomy is the main treatment method, but surgery alone has poor prognosis with high recurrence and metastasis rates. Adjuvant therapy based on surgery may improve patient prognosis.Larger sample studies are needed for confirmation.