Purpose To explore the role of translesion synthesis-related gene NmrA like redox sensor 1(NMRAL1)in the development of papillary thyroid carcinoma(PTC).Methods Bioinformatics analysis was em-ployed to investigate the expression of the NMRAL1 gene across various cancer types and its correlation with prognosis.Immunohistochemistry was utilized to analyze the expression pattern of NMRAL1 in PTC and conduct clinicopathological correlation analysis.Additionally,stable cell lines overexpressing NMRAL1 were established in TPC-1 cells.The effects of NMRAL1 overexpression on cell proliferation,migration,and invasion of TPC-1 and Nthy-ori 3-1 cells were assessed using CCK-8 assay,clonogenic assay,Transwell assay,and scratch assay,respectively.Furthermore,RT-qPCR experiments were conducted to investigate the regulatory effect of NMRAL1 on the expression of genes associated with translesion DNA synthesis.Results Bioinformatics analysis revealed that NMRAL1 was highly expressed in all 26 types of tumors compared to normal tissues in the TCGA x GTEx dataset.Patients with high expression of NMRAL1 in thyroid cancer had significantly lower survival rates than those with low expression(P＜0.05).In the immunohisto-chemical validation of 30 PTC samples,NMRAL1 had a positive rate of 73.33％,in PTC tissues,while it was not ex-pressed in adjacent normal thyroid tissues.The staining intensity scores of NMRAL1 in PTC and adjacent tissues exhib-it significant differences(P＜0.000 1).High expression of NMRAL1 was associated with the size of the tumor(P=0.027 4)and lymph node metastasis(P=0.044 1).In vitro functional experiments revealed a significant enhance-ment in both cell proliferation and migration/invasion capacities upon overexpression of NMRAL1(P＜0.05).Moreo-ver,mRNA and protein expression levels of translesion synthesis-related genes were upregulated(P＜0.001).Con-clusion NMRAL1 promotes proliferation and migration of thyroid carcinoma cells,suggesting that this function may be achieved by enhancing DNA damage repair capacity,thereby improving the survival of damaged cells.

Objective:To compare the clinical efficacy and safety of minocycline in the treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia (MRMP) in children of different age groups. Methods:The clinical data of MRMP cases treated with minocycline hydrochloride capsules in the Department of Infectious Diseases of Shanghai Children′s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from June 2023 to June 2024 were collected through the hospital′s electronic medical record system. This study used a retrospective cohort study. According to the age of onset, they were divided into two groups: children <8 year-old-group and those ≥8 year-old-group. The indicators including the duration of temperature after medication, the recovery time of serum amyloid A (SAA) and C-reactive protein (CRP) were compared between the two groups. The adverse reactions during hospitalization and follow-up of six months after discharge were analyed. Non-parametric rank sum test was used for statistical comparison.Results:A total of 274 MRMP cases were included, including 151 in the <8-year-old group and 123 in the ≥8-year-old group. After minocycline hydrochloride capsule treatment, the duration of fever in the ≥8-year-old group was 1.5(1.0, 2.0) d, which was shorter than 2.0(1.0, 2.0) d in the <8-year-old group. The difference was statistically significant ( Z=-2.02, P=0.044). The recovery time for SAA (3.0(2.0, 6.0) d vs 5.0(3.0, 6.0) d) and CRP (3.0(2.0, 5.0) d vs 4.0(3.0, 6.0) d) in the <8-year-old group were both shorter than those in the ≥ 8-year-old group, and the differences were both statistically significant ( Z=-2.62, P=0.009 and Z=-3.10, P=0.002, respectively). During hospitalization, there were two cases of nausea, four cases of vomiting, one case of abdominal pain, with no rash, dizziness and tetracycline teeth in the <8-year-old group, and the incidence of adverse reactions was 4.6%(7/151). In the ≥8-year-old group, there were one case of nausea, one case of vomiting, one case of rash, one case of dizziness, with no abdominal pain and tetracycline teeth, and the incidence of adverse reactions was 3.3%(4/123). There were 253 cases of follow-up, of which 148 cases (58.5%) did not re-examine because of the normal blood routine at the last time during hospitalization, 105 cases (41.5%) re-examined blood routine, and the results were all normal. Twenty-five cases were normal in liver and kidney functions. Some children under six years old who did not change permanent teeth failed to clarify the impact of minocycline on teeth due to the short follow-up time. The total effective rate of minocycline in the two groups was consistent, both was 100.00%. Conclusions:Minocycline has a good clinical efficacy for MRMP. The total effective rate of clinical treatment for MRMP in children <8 years old and ≥8 years is consistent, with fewer adverse reactions and good safety. The impact on the teeth of children under six years old who have not replaced their deciduous teeth with permanent teeth requires further observation.

[Purpose]To analyze the incidence and mortality of oral and pharyngeal cancer in can-cer registration areas of Hunan Province in 2021 and the trend changes from 2012 to 2021.[Methods]Data on oral and pharyngeal cancer incidence and mortality from 2012 to 2021 were collected from 78 quality-controlled cancer registries in Hunan Province,with population data sourced from household registration statistics provided by public security authorities.Indicators such as crude incidence and mortality rates,age-standardized incidence and mortality rates by Chinese standard population(ASIRC/ASMRC),and world standard population(ASIRW,ASMRW)in 2021 were calculated.The Chinese standard population(2000 national census)and Segi's world standard population were used for standardization.Joinpoint Regression Program 4.9.0.0 software was used to fit a Log-linear regression model,and the average annual percentage change(AAPC)of ASIRC/ASMRC of oral and pharyngeal cancer from 2012 to 2021 was calculated to analyze the changing trends.[Results]In 2021,the crude incidence rate of oral and pharyngeal cancer in cancer registration areas of Hunan Province was 9.28/105(15.14/105 for males and 3.07/105 for fe-males),with an ASIRC of 6.10/105;the crude mortality rate was 3.75/105(6.19/105 for males and 1.16/105 for females),with an ASMRC of 2.16/105.Both the incidence and mortality rates in male were significantly higher than those in female.Age distribution analysis showed that the incidence rate of oral and pharyngeal cancer increased with age after 30 years old,peaking in the age group of 60～64 years old(22.29/105);the mortality rate continued to rise after 35 years old,reaching the peak in the population aged ≥85 years old(14.52/105).Trend analysis from 2012 to 2021 indicated that the crude incidence rate and ASIRC of oral and pharyngeal cancer increased from 3.50/105 and 2.63/105 in 2012 to 9.28/105 and 6.10/105 in 2021,with AAPC of 12.33％and 10.80％,re-spectively;the crude mortality rate and ASMRC also showed upward trends(AAPC of 9.87％and 7.21％,respectively);all trend changes were statistically significant(all P＜0.05).Sex stratification revealed that the AAPC of ASIRC and ASMRC of oral and pharyngeal cancer in male were higher than those in female(AAPC of ASIRC:12.65％for males vs 4.28％for females;AAPC of ASMRC:8.79％for males vs 4.13％for females).Age-specific trend analysis found that the ASIRC of oral and pharyngeal cancer in the population aged ≤ 44 years old showed an upward trend(AAPC=11.73％,P＜0.001),with the AAPC of male in this group reaching 14.57％;the AAPC of ASIRC for the age groups of 45～64 years old and ≥65 years old were 11.03％and 9.74％,respectively,and the AAPC of ASMRC for these two groups were 10.05％and 8.19％,respectively,with all trend changes being statistically significant(all P＜0.05);there was no statistically significant change in the ASMRC of the population aged ≤44 years old(AAPC=5.66％,P=0.087).[Conclusion]The incidence and mortality rates of oral and pharyngeal cancer in cancer registration areas of Hunan Province remain high and show an upward trend,with a tendency of younger onset.Males and middle-aged and elderly populations are the key focuses of prevention and control.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

Purpose To explore the role of translesion synthesis-related gene NmrA like redox sensor 1(NMRAL1)in the development of papillary thyroid carcinoma(PTC).Methods Bioinformatics analysis was em-ployed to investigate the expression of the NMRAL1 gene across various cancer types and its correlation with prognosis.Immunohistochemistry was utilized to analyze the expression pattern of NMRAL1 in PTC and conduct clinicopathological correlation analysis.Additionally,stable cell lines overexpressing NMRAL1 were established in TPC-1 cells.The effects of NMRAL1 overexpression on cell proliferation,migration,and invasion of TPC-1 and Nthy-ori 3-1 cells were assessed using CCK-8 assay,clonogenic assay,Transwell assay,and scratch assay,respectively.Furthermore,RT-qPCR experiments were conducted to investigate the regulatory effect of NMRAL1 on the expression of genes associated with translesion DNA synthesis.Results Bioinformatics analysis revealed that NMRAL1 was highly expressed in all 26 types of tumors compared to normal tissues in the TCGA x GTEx dataset.Patients with high expression of NMRAL1 in thyroid cancer had significantly lower survival rates than those with low expression(P＜0.05).In the immunohisto-chemical validation of 30 PTC samples,NMRAL1 had a positive rate of 73.33％,in PTC tissues,while it was not ex-pressed in adjacent normal thyroid tissues.The staining intensity scores of NMRAL1 in PTC and adjacent tissues exhib-it significant differences(P＜0.000 1).High expression of NMRAL1 was associated with the size of the tumor(P=0.027 4)and lymph node metastasis(P=0.044 1).In vitro functional experiments revealed a significant enhance-ment in both cell proliferation and migration/invasion capacities upon overexpression of NMRAL1(P＜0.05).Moreo-ver,mRNA and protein expression levels of translesion synthesis-related genes were upregulated(P＜0.001).Con-clusion NMRAL1 promotes proliferation and migration of thyroid carcinoma cells,suggesting that this function may be achieved by enhancing DNA damage repair capacity,thereby improving the survival of damaged cells.

[Purpose]To analyze the incidence and mortality of oral and pharyngeal cancer in can-cer registration areas of Hunan Province in 2021 and the trend changes from 2012 to 2021.[Methods]Data on oral and pharyngeal cancer incidence and mortality from 2012 to 2021 were collected from 78 quality-controlled cancer registries in Hunan Province,with population data sourced from household registration statistics provided by public security authorities.Indicators such as crude incidence and mortality rates,age-standardized incidence and mortality rates by Chinese standard population(ASIRC/ASMRC),and world standard population(ASIRW,ASMRW)in 2021 were calculated.The Chinese standard population(2000 national census)and Segi's world standard population were used for standardization.Joinpoint Regression Program 4.9.0.0 software was used to fit a Log-linear regression model,and the average annual percentage change(AAPC)of ASIRC/ASMRC of oral and pharyngeal cancer from 2012 to 2021 was calculated to analyze the changing trends.[Results]In 2021,the crude incidence rate of oral and pharyngeal cancer in cancer registration areas of Hunan Province was 9.28/105(15.14/105 for males and 3.07/105 for fe-males),with an ASIRC of 6.10/105;the crude mortality rate was 3.75/105(6.19/105 for males and 1.16/105 for females),with an ASMRC of 2.16/105.Both the incidence and mortality rates in male were significantly higher than those in female.Age distribution analysis showed that the incidence rate of oral and pharyngeal cancer increased with age after 30 years old,peaking in the age group of 60～64 years old(22.29/105);the mortality rate continued to rise after 35 years old,reaching the peak in the population aged ≥85 years old(14.52/105).Trend analysis from 2012 to 2021 indicated that the crude incidence rate and ASIRC of oral and pharyngeal cancer increased from 3.50/105 and 2.63/105 in 2012 to 9.28/105 and 6.10/105 in 2021,with AAPC of 12.33％and 10.80％,re-spectively;the crude mortality rate and ASMRC also showed upward trends(AAPC of 9.87％and 7.21％,respectively);all trend changes were statistically significant(all P＜0.05).Sex stratification revealed that the AAPC of ASIRC and ASMRC of oral and pharyngeal cancer in male were higher than those in female(AAPC of ASIRC:12.65％for males vs 4.28％for females;AAPC of ASMRC:8.79％for males vs 4.13％for females).Age-specific trend analysis found that the ASIRC of oral and pharyngeal cancer in the population aged ≤ 44 years old showed an upward trend(AAPC=11.73％,P＜0.001),with the AAPC of male in this group reaching 14.57％;the AAPC of ASIRC for the age groups of 45～64 years old and ≥65 years old were 11.03％and 9.74％,respectively,and the AAPC of ASMRC for these two groups were 10.05％and 8.19％,respectively,with all trend changes being statistically significant(all P＜0.05);there was no statistically significant change in the ASMRC of the population aged ≤44 years old(AAPC=5.66％,P=0.087).[Conclusion]The incidence and mortality rates of oral and pharyngeal cancer in cancer registration areas of Hunan Province remain high and show an upward trend,with a tendency of younger onset.Males and middle-aged and elderly populations are the key focuses of prevention and control.

Objective:To compare the clinical efficacy and safety of minocycline in the treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia (MRMP) in children of different age groups. Methods:The clinical data of MRMP cases treated with minocycline hydrochloride capsules in the Department of Infectious Diseases of Shanghai Children′s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from June 2023 to June 2024 were collected through the hospital′s electronic medical record system. This study used a retrospective cohort study. According to the age of onset, they were divided into two groups: children <8 year-old-group and those ≥8 year-old-group. The indicators including the duration of temperature after medication, the recovery time of serum amyloid A (SAA) and C-reactive protein (CRP) were compared between the two groups. The adverse reactions during hospitalization and follow-up of six months after discharge were analyed. Non-parametric rank sum test was used for statistical comparison.Results:A total of 274 MRMP cases were included, including 151 in the <8-year-old group and 123 in the ≥8-year-old group. After minocycline hydrochloride capsule treatment, the duration of fever in the ≥8-year-old group was 1.5(1.0, 2.0) d, which was shorter than 2.0(1.0, 2.0) d in the <8-year-old group. The difference was statistically significant ( Z=-2.02, P=0.044). The recovery time for SAA (3.0(2.0, 6.0) d vs 5.0(3.0, 6.0) d) and CRP (3.0(2.0, 5.0) d vs 4.0(3.0, 6.0) d) in the <8-year-old group were both shorter than those in the ≥ 8-year-old group, and the differences were both statistically significant ( Z=-2.62, P=0.009 and Z=-3.10, P=0.002, respectively). During hospitalization, there were two cases of nausea, four cases of vomiting, one case of abdominal pain, with no rash, dizziness and tetracycline teeth in the <8-year-old group, and the incidence of adverse reactions was 4.6%(7/151). In the ≥8-year-old group, there were one case of nausea, one case of vomiting, one case of rash, one case of dizziness, with no abdominal pain and tetracycline teeth, and the incidence of adverse reactions was 3.3%(4/123). There were 253 cases of follow-up, of which 148 cases (58.5%) did not re-examine because of the normal blood routine at the last time during hospitalization, 105 cases (41.5%) re-examined blood routine, and the results were all normal. Twenty-five cases were normal in liver and kidney functions. Some children under six years old who did not change permanent teeth failed to clarify the impact of minocycline on teeth due to the short follow-up time. The total effective rate of minocycline in the two groups was consistent, both was 100.00%. Conclusions:Minocycline has a good clinical efficacy for MRMP. The total effective rate of clinical treatment for MRMP in children <8 years old and ≥8 years is consistent, with fewer adverse reactions and good safety. The impact on the teeth of children under six years old who have not replaced their deciduous teeth with permanent teeth requires further observation.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

Purpose Focusing on the characteristics of for-malin fixed paraffin embedded(FFPE)samples,explored nano-magnetic bead nucleic acid extraction solutions with higher qual-ity/yield and continued to improve molecular pathology technolo-gy.Methods Alternative magnetic beads were synthesised in four major categories and 15 sub-categories and we screened to obtain high-quality/yield magnetic beads centred on FFPE samples.Simulated conventional tissues,simulated coarse needle punctures(liver),and simulated fiberoptic bronchoscopy sam-ples(lungs)were sectioned with the same number of serial slices in tubes.The nucleic acids of slices were extracted using the best magnetic beads screened in this study and common com-mercially available kits,and then perform comparison and purifi-cation quality parameters such as total amount and fragment size.The downstream applications of nucleic acids were validated by PCR and Sanger sequencing.Results Screening all homemade nanomagnetic beads centered on the DNA of FFPE samples,the total recoveries of the best performance nanomagnetic beads were obtained to be 58.5％±1.58％,and the total recoveries of five commercially available commercial magnetic beads and three do-mestic kit magnetic beads ranged from 18.68％to 40.71％.The total amount of DNA(ng)extracted from the same amount of tis-sue(serial slices),the nucleic acid yield of this study in simu-lated conventional tissues,simulated coarse needle punctures,and simulated fiberoptic bronchoscopy samples were increased by 39.49％-181.72％compared with those of the commercially a-vailable kits(P＜0.05).The total amount of extracted nucleic acid from simulated fiberoptic bronchoscopy tissue sections can be more than 100 ng for 1 slice(4 μm)and more than 400 ng for 5 slices.Conclusion The DNA purification nanomagnetic beads screened with DNA from FFPE samples have a significant enhancement comparing to the existing commercial bead proto-cols,and provide space for quality assurance,automated testing,and program expansion for clinical molecular pathology testing.