Tissue-resident memory T cells （T_RM cells） are a subset of memory T cells that reside in tissues， exhibit tissue specificity， and do not recirculate. When potential hazards threaten the liver， such as pathogen invasion （bacteria， viruses， etc.） and excessive autoimmune responses， T_RM cells are essential as the first line of immune defense， playing an important role in viral hepatitis， autoimmune liver disease， metabolic dysfunction-associated fatty liver disease， liver cirrhosis， and liver transplantation. Here， we present the immunophenotypes of T_RM cells in the liver and their surface markers and transcriptional profiles， aiming to clarify the role of T_RM cells in chronic liver diseases and explore their potential function as therapeutic targets in immunotherapy.

Objective:To compare gamma pass rates for ultra-long target volumes of cervical cancer between individual measurements by moving the phantom isocenter and segmented measurements combined with merging and to assess the influence of scattering blocks on verification result during segmented measurements.Methods:A retrospective study was conducted on 24 cervical cancer patients with ultra-long target volumes (lengths: 23.5–36.0 cm) treated using helical tomotherapy. Two measurement methods were used to verify the gamma pass rates: individual measurements by moving the phantom isocenter and segmented measurements combined with merging. For the first measurement method, the patients′ treatment plans were transferred to the ArcCheck phantom. After the dose distribution was calculated and exported, the gamma pass rates measured and calculated were compared. For the segmented measurements, a 50-cm-long virtual phantom was imported, and the treatment plans of patients were then transferred to the virtual phantom. Afterward, the dose distribution of the virtual phantom was calculated and exported. Then, two dose measurements were conducted under upward and downward setup of the ArcCheck phantom. Two dose measurement files were obtained and then fused to produce a merged file. Then, the γ pass rates were calculated. Repeated measurements were conducted after scattering blocks were installed. The γ-pass rates were assessed using varying dose criteria.Results:Under various evaluation criteria, no statistically significant differences in γ pass rates were observed between the individual measurements by moving the phantom isocenter and the segmented measurement in the presence of scattering blocks ( P > 0.05). In contrast, there existed statistically significant differences in γ pass rates between the individual measurements by moving the phantom isocenter and the segmented measurement in the absence of scattering blocks according to the (global) criterion of 3%/2 mm absolute dose ( Z = -2.31, P = 0.02). Additionally, the segmented measurement in the presence of scattering blocks enhanced pass rates, with statistical significant difference under the criterion of 3%/2 mm relative dose ( Z = -2.11, P = 0.04). Conclusions:In the case where ArcCheck is used to measure the dose distribution of ultra-long target volumes in cervical cancer, it is advisable to preferentially use individual measurements by moving the phantom isocenter. When segmented measurements combined with merging are required, it is necessary to install scattering blocks during measurements. This will improve γ-pass rates during verification and ensure the accuracy of dose verification.

OBJECTIVE To compare the effect of traditional swab sampling method on etiological surveillance of in-fectious diseases for large-scale object surfaces in hospitals and validate the samples processing method based on pre-wet anti-static fabric and modified polyethylene glycol(PEG)precipitation enrichment technology so as to im-prove the capability of early warning of infectious diseases and optimize the environmental surveillance program in the hospitals.METHODS The on-site surveillance was carried out for 8 times in 3 public hospitals(Shenzhen Longgang People's Hospital,the Second People's Hospital of Longgang and Longgang Maternal and Child Health Hospital)from May 2024 to Mar.2025.Totally 23 types of respiratory tract pathogens(18 types of viruses,5 type of pathogenic bacteria)and 6 types of gastrointestinal tract pathogens were simultaneously detected by means of fluorescent quantitative polymerase chain reaction(PCR);the actual isolation rates,etiological spectrum and cycle threshold(Ct)value were compared.The acrylic plate added with standards of different loads of H1NI influ-enza viruses was used as model for laboratory evaluation.The minimum detection limit,sensitivity and repeatabili-ty were observed and compared between the methods.RESULTS The minimum detection limit of both methods was 6.0 × 104 copies/ml,however,the positive rate of nucleic acid testing of the pre-wet fabric method was 100.00％(3/3),higher than 33.33％(1/3)of the swab method;when the low viral load was 6.0× 105 copies/ml,the average concentration of viral nucleic acid of the pre-wet fabric method(X-Ct=36.59)was higher,with the re-peatability(CV=0.99％,＜3.14％)better.The results of the on-site surveillances showed that the total isolation rates of pathogens of the pre-wet fabric method ranged between 42.84％and 64.27％,higher than between 10.71％and 21.43％of the swab method,with the isolated pathogens more abundant,the Ct value lower(P＜0.05).CONCLUSION The pre-wet fabric sampling enrichment method integrated with anti-static fabric sampling and PEG enrichment technology shows higher sensitivity and stability in the etiological surveillance of large-scale object surfaces,raising the isolation rate.

Objective:To investigate the clinical value of 18F-NaF PET/CT coronary plague imaging in evaluating the long-term prognosis of patients with coronary artery disease (CAD). Methods:A retrospective cohort study was conducted among 54 patients (37 males and 17 females, aged (57.2±9.8) years) diagnosed with CAD from a multicenter study between September 2015 and October 2022. All patients underwent 18F-NaF PET/CT and coronary angiography (CAG) within 1 week, and the PET/CT imaging was performed at the First Hospital of Shanxi Medical University. Major adverse cardiovascular events (MACE) were followed up. ROC curves were established to obtain the optimal thresholds of SUV max and accumulated SUV max of all lesions of main coronary artery branches (S-SUV max) for predicting MACE. Cox proportional risk model and Kaplan-Meier method (log-rank test) were used to analyze the predictive value of PET parameters for MACE. Differences in metabolic parameters between 2 groups were compared by Mann-Whitney U test. Results:The median follow-up time of the 54 patients was 6.0(1.8, 6.6) years, and 13(24.1%) patients developed MACE, including 7 deaths, 5 myocardial infarction and 1 severe arrhythmia. S-SUV max in MACE group was significantly higher than that in the non-MACE group (2.64(2.08, 4.49) vs 1.83(0.95, 2.90); Z=-2.04, P=0.041). ROC curve showed that the optimal threshold of S-SUV max for MACE prediction was 2.05 (AUC=0.690). Multivariate Cox analysis showed that S-SUV max was a strong predictor of MACE (hazard ratio ( HR)=2.434(95% CI: 1.547-3.828), P<0.001). ROC curve showed that the optimal threshold of SUV max to predict MACE was 0.55 (AUC=0.659), and univariate Cox analysis showed that SUV max was a factor to predict MACE ( HR=10.192 (95% CI: 2.667-38.953), P=0.001). In 25 patients with incomplete revascularization (ICR), Kaplan-Meier analysis showed that the incidence of MACE in patients with positive 18F-NaF uptake (single medium stenosis (40%-70%) with SUV max≥0.55) was significantly higher than that in patients with negative 18F-NaF uptake (5/14 vs 0/11; χ2=6.07, P=0.014). Conclusions:18F-NaF PET/CT can be used as an independent predictor of MACE in patients with CAD and can quantitatively assess the long-term progression of moderate coronary artery stenosis. In the future, it is expected to be a new non-invasive way to guide the revascularization treatment decision of multi-vessel CAD.

Objective:To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. Methods:A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using " SETD1B" and " epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. Results:① The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. ② WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely, c. 5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). ③ The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. ④ A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no statistically significant difference in incidence between males and females. Conclusion:SETD1B gene variant may induced neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.

Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

Objective To investigate the prognostic value of peripheral blood neutrophil-lymphocyte ratio(NLR)and thioredoxin reductase(TrxR)in patients with ovarian cancer receiving immunotherapy.Methods A total of 109 patients with advanced ovarian cancer treated in the Tumor Hospital Affiliated to Nantong University from January 2021 to December 2021 were selected as the research objects.The levels of NLR and TrxR in peripheral blood before immunotherapy were detected,and the evaluation value of NLR and TrxR on short-term efficacy,progression-free survival(PFS)and overall survival(OS)in ovarian cancer pa-tients receiving immunotherapy was explored.Results The optimal cut-off values of TrxR and NLR were 4.97 U/mL and 2.49%,respectively.According to the optimal cut-off value of TrxR and NLR,the patients were divided into the high level of TrxR group(69 cases,≥4.97 U/mL)and the low level of TrxR group(40 cases,<4.97 U/mL),the high level of NLR group(72 cases,≥2.49%)and the low level of NLR group(37 cases,<2.49%).The objective response rate(ORR)of the high level of NLR group was lower than that of the low level NLR group(P<0.05),and the disease progression rate(DPR)was higher than that of the low NLR group(P<0.05).The high level of TrxR group had a significantly lower ORR and a significantly higher DPR than the low level of TrxR group(P<0.05).The median PFS and OS of the high level of NLR group were 15.0 months and 16.0 months,respectively.The median PFS and OS of the low level of NLR group were 19.0 months and 21.0 months,respectively.The median PFS and OS of the high level of TrxR group were 15.0 months and 17.0 months,respectively.The median PFS was 18.0 months and the median OS was 21.0 months in the low level of TrxR group.NLR and TrxR were the influencing factors of PFS and OS in pa-tients with ovarian cancer immunotherapy(P<0.05).Conclusion The levels of NLR and TrxR in peripheral blood can be used as important prognostic indicators for advanced ovarian cancer patients receiving immuno-therapy.The lower the levels of NLR and TrxR,the better the prognosis of ovarian cancer patients.

Tissue-resident memory T cells(TRM cells)are a subset of memory T cells that reside in tissues,exhibit tissue specificity,and do not recirculate.When potential hazards threaten the liver,such as pathogen invasion(bacteria,viruses,etc.)and excessive autoimmune responses,TRM cells are essential as the first line of immune defense,playing an important role in viral hepatitis,autoimmune liver disease,metabolic dysfunction-associated fatty liver disease,liver cirrhosis,and liver transplantation.Here,we present the immunophenotypes of TRM cells in the liver and their surface markers and transcriptional profiles,aiming to clarify the role of TRM cells in chronic liver diseases and explore their potential function as therapeutic targets in immunotherapy.

OBJECTIVE: To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. METHODS: A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using "SETD1B" and "epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. RESULTS: The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely c.5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+PM2_Supporting+PP2+PP3). The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no significant difference in incidence between males and females. CONCLUSION SETD1B gene variants may cause neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.
Humans ; Female ; Child ; Epilepsy/genetics* ; Language Development Disorders/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Exome Sequencing ; Male

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases