ObjectiveTo investigate the effect of growth hormone （GH） pretreatment on the clinical outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer （IVF/ICSI-ET） in patients with diminished ovarian reserve （DOR）. MethodsA retrospective analysis was conducted on the clinical data of 359 DOR patients undergoing IVF/ICSI-ET. Based on the use of GH pretreatment before ovarian stimulation and/or its addition during the stimulation cycle， patients were divided into three groups： the Control group （n=119）， receiving no GH pretreatment or addition； the Non-GH pretreatment group （n=115）， receiving GH （4 IU/d） only during ovarian stimulation without pretreatment； and the GH pretreatment group （n=125）， pretreated with GH （2 IU/d） for 4-6 weeks before stimulation and also receiving GH （4 IU/d） during stimulation. The basic characteristics， ovarian stimulation parameters， embryological data， and cumulative live birth rate （CLBR） were compared among the groups. Results① No significant differences were found among the three groups regarding female age， male age， duration of infertility， body mass index （BMI）， basal hormone levels， distribution of ovarian stimulation protocols， endometrial thickness， serum estradiol （E2） and luteinizing hormone （LH） levels on the day of HCG trigger， or the number of blastocysts transferred per cycle. ② The GH pretreatment group required significantly lower total gonadotropin （Gn） dosage and fewer days of stimulation than the Control and Non-GH pretreatment group（P<0.05）. Compared to the Control group， the GH pretreatment group showed significantly higher numbers of retrieved oocytes， the number of mature oocytes， 2-pronuclei （2PN） zygotes， 2PN cleaved embryos， transferable embryos， high-quality embryos， as well as higher cumulative clinical pregnancy rates and CLBR （P<0.05）. Compared to the Non-GH pretreatment group， the GH pretreatment group had significantly more transferable embryos， high-quality embryos， and a higher CLBR （P<0.05）. ③ Compared to the Control group， the Non-GH pretreatment group only had a significantly higher number of retrieved oocytes （P<0.05）， with no significant differences in the number of mature oocytes， 2PN fertilized oocytes， 2PN cleaved embryos， transferable blastocysts， high-quality blastocysts， cumulative clinical pregnancy rate， and CLBR. ConclusionFor DOR patients， GH pretreatment for 4-6 weeks prior to ovarian stimulation can improve oocyte yield， embryo quality， cumulative clinical pregnancy rate， and CLBR， thereby enhancing the clinical outcomes of IVF/ICSI-ET.

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.

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 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.

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 The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.