Objective:To compare pregnancy outcomes between patients undergoing combined hysteroscopy and hysterosalpingo-contrast sonography (HyCoSy) versus hysteroscopy alone prior to intrauterine insemination, and to evaluate the safety and clinical value of the combined procedure in the diagnosis and treatment of infertility.Methods:A retrospective analysis was conducted on clinical data from 385 patients who underwent hysteroscopy at Peking University Third Hospital between October 1, 2020 and September 30, 2022, and subsequently received their first cycle of artificial insemination with donor sperm (AID) within six months. Pregnancy outcomes were compared between the group receiving combined hysteroscopy with four-dimensional HyCoSy (hysteroscopy+4D-HyCoSy group) and the group receiving hysteroscopy alone (hysteroscopy group). Multivariate logistic regression was used to analyze factors influencing pregnancy outcomes after AID.Results:Among the 385 patients included, 79 achieved clinical pregnancy. The clinical pregnancy rate (24.9%, 53/213) and live birth rate (21.1%, 45/213) in the hysteroscopy+4D-HyCoSy group were significantly higher than those in the hysteroscopy group [15.1% (26/172) and 12.8% (22/172), respectively; all P<0.05]. There was no significant difference in tubal patency between the two groups ( P>0.05); however, the time interval from tubal patency assessment to intrauterine insemination was significantly longer in the hysteroscopy group compared to the hysteroscopy+4D-HyCoSy group (median: 4.0 vs 2.0 months; P<0.001). Multivariate analysis showed that double insemination significantly increased clinical pregnancy rate compared to single insemination ( OR=2.42, 95% CI: 1.02-5.72; P=0.044). An interval exceeding 6 months between tubal patency assessment and intrauterine insemination was identified as a risk factor for reduced clinical pregnancy ( OR=0.35, 95% CI: 0.14-0.92; P=0.047). Additionally, neither the time interval from hysteroscopy to intrauterine insemination nor hysteroscopic findings and pathological diagnoses had significant effects on clinical pregnancy rates (all P>0.05). Conclusions:The combination of hysteroscopy and HyCoSy provides a safe and efficient approach for fertility assessment in infertile patients and improves clinical pregnancy rate and live birth rate in intrauterine insemination cycles. Hysteroscopy is recommended for patients with suspected endometrial or intrauterine abnormalities. If no previous tubal patency assessment has been performed or the last assessment was more than six months prior, combined hysteroscopy and HyCoSy may be considered to enhance the likelihood of clinical pregnancy.

Objective:To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values.Methods:A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed.Results:Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis.Conclusions:Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

OBJECTIVE To develop a highly sensitive and specific quantitative real-time poly-merase chain reaction(qPCR)method for detecting the VGM-R02b(a gene therapy drug for glutaric acidemia type Ⅰ)gene in cynomolgus monkeys and analyze the biological distribution of VGM-R02b.METHODS A standard curve was constructed using the VGM-R02b standard plasmid[an adeno-associ-ated virus serotype 9(AAV9)capsid]on a qPCR platform.The detection method was optimized and validated for key parameters,including the quantitative range,accuracy,precision,dilution linearity,selectivity,specificity,stability,and parallelism.The established method was used to determine the target gene of VGM-R02b in the blood,brain,stomach,heart,liver,spleen,lung,kidney,thymus,and duodenum of cynomolgus monkeys on day 29(D29)and D92 after a single,unilateral intraventricular injection of VGM-R02b.The biodistribution of VGM-R02b in cynomolgus monkeys was analyzed.RESULTS A qPCR method for quantifying the VGM-R02b target gene in cynomolgus monkeys was established and validated.The standard curve demonstrated a quantitative range of 5.00×109 to 5.00×10^1 copies·μg-1 DNA,with excellent precision,accuracy,dilution linearity,selectivity,and specificity.The target gene in tissues remained stable after being stored at room temperature for 4 h,-15 to-25℃ for 9 d,-60 to-80℃ for 90 d and after five freeze-thaw cycles.Similarly,the target gene in whole blood remained stable after being stored at room temperature for 4 h,-15 to-25℃ for 93 d,-60 to-80℃ for 93 d and after five freeze-thaw cycles.Extracted nucleic acid samples also showed stability after being stored at room temperature for 4.25 h,2-8℃ for 24.16 h,-60 to-80℃ for 109 d and after five freeze-thaw cycles.The method was also applied to evaluate the biological distribution of the target gene in cynomolgus monkeys.In the control group,the target gene was undetectable on D29 and D92 post-administration,but in the drug administration group,the target gene was distributed across the tissues,with higher concen-trations observed in the brain,liver,spleen,and spinal cord,and there were no significant differences in the target gene content across the tissues between D29 and D92.CONCLUSION The established qPCR method is robust,reliable and suitable for determination of VGM-R02b target gene in cynomolgus monkeys.

Objective To explore the correlation between serum macrophage migration inhibitory factor(MIF),25-hydroxyvitamin D[25(OH)D]and cognitive function in patients with vestibular migraine(VM).Methods A total of 200 patients with VM were selected and used as the VM group.Based on the Montreal Cognitive Assessment(MoCA)criteria,patients were divided into the cognitively normal group(128 cases)and the cognitively impaired group(72 cases).Additionally,200 healthy individuals undergoing routine health examination were selected as the control group.Serum MIF and 25(OH)D levels were measured using enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze influencing factors of cognitive impairment in VM patients.The value of serum MIF and 25(OH)D levels in diagnosing cognitive impairment in patients with VM was analyzed by using the receiver operating characteristic(ROC)curve.Results The serum MIF was higher in the VM group than that of the control group,and serum 25(OH)D was lower in the VM group(P＜0.05).The serum MIF was higher in the cognitive impairment group than that of the cognitive normal group,while the serum 25(OH)D was lower in the cognitive impairment group than that of the cognitive normal group(P＜0.05).Multivariate Logistic regression found that increased serum MIF level and decreased 25(OH)D level were independent risk factors for cognitive impairment in VM patients(P＜0.05).ROC curve analysis showed that the AUC(95%CI)of the combined diagnosis of cognitive impairment in VM patients using serum MIF and 25(OH)D levels was 0.900(0.850-0.938),which was higher than that of MIF diagnosed alone[0.797(0.735-0.851)]and 25(OH)D alone[0.817(0.756-0.868),P＜0.05].Conclusion VM patients with cognitive impairment have elevated serum MIF levels and decreased 25(OH)D levels.The combined diagnostic value of the two markers has a relatively high value for VM patients with cognitive impairment.

Objective:To compare pregnancy outcomes between patients undergoing combined hysteroscopy and hysterosalpingo-contrast sonography (HyCoSy) versus hysteroscopy alone prior to intrauterine insemination, and to evaluate the safety and clinical value of the combined procedure in the diagnosis and treatment of infertility.Methods:A retrospective analysis was conducted on clinical data from 385 patients who underwent hysteroscopy at Peking University Third Hospital between October 1, 2020 and September 30, 2022, and subsequently received their first cycle of artificial insemination with donor sperm (AID) within six months. Pregnancy outcomes were compared between the group receiving combined hysteroscopy with four-dimensional HyCoSy (hysteroscopy+4D-HyCoSy group) and the group receiving hysteroscopy alone (hysteroscopy group). Multivariate logistic regression was used to analyze factors influencing pregnancy outcomes after AID.Results:Among the 385 patients included, 79 achieved clinical pregnancy. The clinical pregnancy rate (24.9%, 53/213) and live birth rate (21.1%, 45/213) in the hysteroscopy+4D-HyCoSy group were significantly higher than those in the hysteroscopy group [15.1% (26/172) and 12.8% (22/172), respectively; all P<0.05]. There was no significant difference in tubal patency between the two groups ( P>0.05); however, the time interval from tubal patency assessment to intrauterine insemination was significantly longer in the hysteroscopy group compared to the hysteroscopy+4D-HyCoSy group (median: 4.0 vs 2.0 months; P<0.001). Multivariate analysis showed that double insemination significantly increased clinical pregnancy rate compared to single insemination ( OR=2.42, 95% CI: 1.02-5.72; P=0.044). An interval exceeding 6 months between tubal patency assessment and intrauterine insemination was identified as a risk factor for reduced clinical pregnancy ( OR=0.35, 95% CI: 0.14-0.92; P=0.047). Additionally, neither the time interval from hysteroscopy to intrauterine insemination nor hysteroscopic findings and pathological diagnoses had significant effects on clinical pregnancy rates (all P>0.05). Conclusions:The combination of hysteroscopy and HyCoSy provides a safe and efficient approach for fertility assessment in infertile patients and improves clinical pregnancy rate and live birth rate in intrauterine insemination cycles. Hysteroscopy is recommended for patients with suspected endometrial or intrauterine abnormalities. If no previous tubal patency assessment has been performed or the last assessment was more than six months prior, combined hysteroscopy and HyCoSy may be considered to enhance the likelihood of clinical pregnancy.

Objective To explore the correlation between serum macrophage migration inhibitory factor(MIF),25-hydroxyvitamin D[25(OH)D]and cognitive function in patients with vestibular migraine(VM).Methods A total of 200 patients with VM were selected and used as the VM group.Based on the Montreal Cognitive Assessment(MoCA)criteria,patients were divided into the cognitively normal group(128 cases)and the cognitively impaired group(72 cases).Additionally,200 healthy individuals undergoing routine health examination were selected as the control group.Serum MIF and 25(OH)D levels were measured using enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze influencing factors of cognitive impairment in VM patients.The value of serum MIF and 25(OH)D levels in diagnosing cognitive impairment in patients with VM was analyzed by using the receiver operating characteristic(ROC)curve.Results The serum MIF was higher in the VM group than that of the control group,and serum 25(OH)D was lower in the VM group(P＜0.05).The serum MIF was higher in the cognitive impairment group than that of the cognitive normal group,while the serum 25(OH)D was lower in the cognitive impairment group than that of the cognitive normal group(P＜0.05).Multivariate Logistic regression found that increased serum MIF level and decreased 25(OH)D level were independent risk factors for cognitive impairment in VM patients(P＜0.05).ROC curve analysis showed that the AUC(95%CI)of the combined diagnosis of cognitive impairment in VM patients using serum MIF and 25(OH)D levels was 0.900(0.850-0.938),which was higher than that of MIF diagnosed alone[0.797(0.735-0.851)]and 25(OH)D alone[0.817(0.756-0.868),P＜0.05].Conclusion VM patients with cognitive impairment have elevated serum MIF levels and decreased 25(OH)D levels.The combined diagnostic value of the two markers has a relatively high value for VM patients with cognitive impairment.

OBJECTIVE To develop a highly sensitive and specific quantitative real-time poly-merase chain reaction(qPCR)method for detecting the VGM-R02b(a gene therapy drug for glutaric acidemia type Ⅰ)gene in cynomolgus monkeys and analyze the biological distribution of VGM-R02b.METHODS A standard curve was constructed using the VGM-R02b standard plasmid[an adeno-associ-ated virus serotype 9(AAV9)capsid]on a qPCR platform.The detection method was optimized and validated for key parameters,including the quantitative range,accuracy,precision,dilution linearity,selectivity,specificity,stability,and parallelism.The established method was used to determine the target gene of VGM-R02b in the blood,brain,stomach,heart,liver,spleen,lung,kidney,thymus,and duodenum of cynomolgus monkeys on day 29(D29)and D92 after a single,unilateral intraventricular injection of VGM-R02b.The biodistribution of VGM-R02b in cynomolgus monkeys was analyzed.RESULTS A qPCR method for quantifying the VGM-R02b target gene in cynomolgus monkeys was established and validated.The standard curve demonstrated a quantitative range of 5.00×109 to 5.00×10^1 copies·μg-1 DNA,with excellent precision,accuracy,dilution linearity,selectivity,and specificity.The target gene in tissues remained stable after being stored at room temperature for 4 h,-15 to-25℃ for 9 d,-60 to-80℃ for 90 d and after five freeze-thaw cycles.Similarly,the target gene in whole blood remained stable after being stored at room temperature for 4 h,-15 to-25℃ for 93 d,-60 to-80℃ for 93 d and after five freeze-thaw cycles.Extracted nucleic acid samples also showed stability after being stored at room temperature for 4.25 h,2-8℃ for 24.16 h,-60 to-80℃ for 109 d and after five freeze-thaw cycles.The method was also applied to evaluate the biological distribution of the target gene in cynomolgus monkeys.In the control group,the target gene was undetectable on D29 and D92 post-administration,but in the drug administration group,the target gene was distributed across the tissues,with higher concen-trations observed in the brain,liver,spleen,and spinal cord,and there were no significant differences in the target gene content across the tissues between D29 and D92.CONCLUSION The established qPCR method is robust,reliable and suitable for determination of VGM-R02b target gene in cynomolgus monkeys.

Objective:To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values.Methods:A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed.Results:Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis.Conclusions:Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

Objective:To investigate the expression of programmed cell death ligand 1 (PD-L1), clinicopathologic features, immunohistochemical expression and molecular characteristics in fumarate hydratase (FH)-deficient renal cell carcinoma and to explore the potential application of immunotherapy in the patients.Methods:There were six patients with FH-deficient renal cell carcinoma treated at the First Affiliated Hospital of Fujian Medical University between January 2020 and October 2022. The clinical data, histological morphology, immunophenotype, PD-L1 expression and next-generation sequencing results were tabulated and analyzed.Results:There were 6 patients, all male, age ranged from 37 to 72 years (mean 45.7 years). Four cases were high-grade (WHO/ISUP grade3-4) with 2 or more histologic patterns, including papillary (most common), glandular, tubular, vesicular, ethmoid, nest-like, cystic and solid structures. Two cases were low-grade which showed nest-like, glandular, or tubular arrangement with eosinophilic flocculent cytoplasm and small intracellular vacuoles. Immunohistochemical analysis revealed strong expression of 2SC in all 6 cases, negative expression of FH in 5 cases, and positive expression of GATA3 in 5 cases. In high-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes in advanced tumor invasion were 180.3/mm 2 and 130.5/mm 2, respectively. PD-L1 combined positive scores (CPS) were 20, 50, 5 and 30, respectively. The Ki-67 proliferative index were 20%, 20%, 10% and 30%, respectively. In low-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes were 123.0/mm 2 and 100.5/mm 2, respectively. The PD-L1 CPS score was 1, and the Ki-67 proliferation index was 3%. High-throughput sequencing showed FH gene somatic mutation in 3 cases, FH gene germline mutation in 2 cases, and FH gene mutation was not detected in one case. Conclusion:FH-deficient renal cell carcinoma is more commonly high-grade than low grade. FH and 2SC are immunohistochemical markers used in the diagnosis of FH-deficient renal cell carcinoma, and GATA3 positivity is supportive of the diagnosis. The tumor infiltration of high-grade FH-deficient renal cell carcinoma shows an increase in CD4 and CD8 positive T-lymphocytes, and high expression of PD-L1; thus, anti-PD-L1 immunotherapy can be used as a treatment option.

OBJECTIVE: To investigate the effect of hyperbaric oxygen (HBO) on paroxysmal sympathetic hyperexcitation (PSH) after brain injury. METHODS: A multicenter retrospective study was conducted. Fifty-six patients with PSH who received HBO treatment from four hospitals in Henan Province from January 2021 to September 2023 were selected as the HBO group, and 36 patients with PSH who did not receive HBO treatment from Zhengzhou People's Hospital from May 2018 to December 2020 were selected as the control group. PSH assessment measure (PSH-AM) score [clinical feature scale (CFS) score+diagnostic likelihood tool (DLT) score] and Glasgow coma scale (GCS) were compared before and after HBO treatment, and between HBO group and control group to evaluate the effect of HBO treatment on prognosis of PSH patients. RESULTS: There were no statistically significant differences in age, gender, PSH etiology, GCS score, time from onset to occurrence of PSH, CFS score, CFS+DLT score and frequency of PSH episodes between the two groups, indicating comparability. The duration of HBO treatment ranged from 3 to 11 days for 56 patients receiving HBO treatment, and the duration of HBO treatment ranged from 3 to 5 courses. Compared with before treatment, after HBO treatment, PSH symptoms in HBO patients were significantly relieved (body temperature increase: 14.29% vs. 64.29%, heart rate increase: 25.00% vs. 98.21%, shortness of breath: 14.29% vs. 76.79%, blood pressure increase: 8.93% vs. 85.71%, sweating: 10.71% vs. 85.71%, muscle tone increased: 19.64% vs. 75.00%, all P < 0.05), CFS+DLT score decreased significantly (16.90±4.81 vs. 22.12±3.12, P < 0.01), GCS score improved (12.31±5.34 vs. 5.95±2.18, P < 0.01). After 30 days of hospitalization, compared with the control group, PSH symptoms in the HBO group were improved (body temperature increase: 14.29% vs. 19.44%, heart rate increase: 19.64% vs. 25.00%, shortness of breath: 10.71% vs. 27.78%, blood pressure increase: 7.14% vs. 22.22%, sweating: 8.93% vs. 25.00%, muscle tone increased: 19.64% vs. 38.89%, all P < 0.05 except body temperature increase), CFS+DLT score decreased (16.90±3.81 vs. 19.98±4.89, P < 0.05), GCS score increased (14.12±4.12 vs. 12.31±4.14, P < 0.01), the length of intensive care unit (ICU) stay was shortened (days: 18.01±5.67 vs. 24.93±8.33, P < 0.01). CONCLUSIONS HBO treatment can significantly relieve the symptoms of patients with PSH after brain injury and provide a new idea for the treatment of PSH patients.
Humans ; Hyperbaric Oxygenation/methods* ; Retrospective Studies ; Brain Injuries/therapy* ; Female ; Male ; Prognosis ; Glasgow Coma Scale ; Autonomic Nervous System Diseases/etiology*