Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation,and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice.Methods Forty-eight male C57/BL6 mice were randomly assigned to four groups:the control group,the low-dose group,the medium-dose group,and the high-dose group.The low-dose,medium-dose,and high-dose groups received 62.5 mg/mL,125 mg/mL,and 250 mg/mL neodymium oxide,respectively,via non-exposed tracheal instillation.The control group received an equivalent volume of saline using the same administration method.After 35 days,the mice were euthanized,and brain tissues were collected.RT-PCR was used to assess the mRNA expression changes of Claudin-5 and Occludin.Western blot analysis was performed to evaluate the expression changes of Claudin-5 and Occludin tight junction proteins,as well as the expression changes of MMP-2 and MMP-9 in the brain tissues.Additionally,the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined.Changes in oxidative stress markers,including MDA,T-AOC,and NO,were measured using a kit method.Results The mRNA expression of Claudin-5 was significantly reduced in the middle-dose and high-dose groups compared to the control group(P<0.05).Similarly,the mRNA expression of Occludin was significantly lower in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).Additionally,the protein expression of Claudin-5,MMP-2,and Occludin was significantly decreased in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).The protein expression of MMP-9 and RhoA was also signifi-cantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05).Furthermore,the protein expression of ROCK2 and p-cofilin in the high-dose group was significantly lower than that in the control group(P<0.05).The content of MDA and T-AOC was significantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05),and the content of NO in the high-dose group was significantly lower than that in the control group(P<0.05).Conclusion Exposure to neodymium oxide results in increased permeability of the blood-brain barrier in mice,leading to oxidative stress,inflammatory responses,and activation of the RhoA/ROCK2 signaling pathway.

Purpose To explore the clinical manifestations,imaging features,and histopathological characteristics of intravascular large B-cell lymphoma(IVL-BCL)involving the central nervous system(CNS).Methods Clinical and imaging data from 5 cases of IVL-BCL were collected.Immunohistochemical staining and FISH were performed to analyze their clinicopathological characteristics,with a comprehensive review of relevant literatures.Results All 5 pa-tients were elderly,with a male-to-female ratio of 4∶1,and an age of onset ranging from 53 to 67 years.The disease course varied from 4 months to 2 years.All patients had varying degrees of neurological damage symptoms.In this study,4 patients experienced varying degrees of weakness in the lower limbs.MRI findings were nonspecific,but all 5 patients showed evidence of cerebrovascular lesions.Histologically,the lesions were characterized by aggregates of lymphoid tumor cells within the lumens of small cerebral vessels,which could obstruct the lumens and cause ischemic and hypoxic changes.Tumor cells did not involve the extravascular brain parenchyma.Immunohistochemically,tumor cells widely expressed mature B-cell markers(CD19,CD20,CD79a,PAX5)with a high Ki67 proliferation index.All 5 patients received systemic chemotherapy after diagnosis,1 patient died,2 patients achieved clinical and physical symptom relief and were still under follow-up.2 patients were undergoing systemic examination before chemotherapy.Conclusion Intravascular large B-cell lymphoma involving the central nervous system is rare,and both clinical mani-festations and imaging examinations lack specific indicators.Preoperative diagnosis is very difficult and can only rely on diagnostic brain biopsy or pathological diagnosis after craniotomy.

Purpose To explore the clinical manifestations,imaging features,and histopathological characteristics of intravascular large B-cell lymphoma(IVL-BCL)involving the central nervous system(CNS).Methods Clinical and imaging data from 5 cases of IVL-BCL were collected.Immunohistochemical staining and FISH were performed to analyze their clinicopathological characteristics,with a comprehensive review of relevant literatures.Results All 5 pa-tients were elderly,with a male-to-female ratio of 4∶1,and an age of onset ranging from 53 to 67 years.The disease course varied from 4 months to 2 years.All patients had varying degrees of neurological damage symptoms.In this study,4 patients experienced varying degrees of weakness in the lower limbs.MRI findings were nonspecific,but all 5 patients showed evidence of cerebrovascular lesions.Histologically,the lesions were characterized by aggregates of lymphoid tumor cells within the lumens of small cerebral vessels,which could obstruct the lumens and cause ischemic and hypoxic changes.Tumor cells did not involve the extravascular brain parenchyma.Immunohistochemically,tumor cells widely expressed mature B-cell markers(CD19,CD20,CD79a,PAX5)with a high Ki67 proliferation index.All 5 patients received systemic chemotherapy after diagnosis,1 patient died,2 patients achieved clinical and physical symptom relief and were still under follow-up.2 patients were undergoing systemic examination before chemotherapy.Conclusion Intravascular large B-cell lymphoma involving the central nervous system is rare,and both clinical mani-festations and imaging examinations lack specific indicators.Preoperative diagnosis is very difficult and can only rely on diagnostic brain biopsy or pathological diagnosis after craniotomy.

Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation,and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice.Methods Forty-eight male C57/BL6 mice were randomly assigned to four groups:the control group,the low-dose group,the medium-dose group,and the high-dose group.The low-dose,medium-dose,and high-dose groups received 62.5 mg/mL,125 mg/mL,and 250 mg/mL neodymium oxide,respectively,via non-exposed tracheal instillation.The control group received an equivalent volume of saline using the same administration method.After 35 days,the mice were euthanized,and brain tissues were collected.RT-PCR was used to assess the mRNA expression changes of Claudin-5 and Occludin.Western blot analysis was performed to evaluate the expression changes of Claudin-5 and Occludin tight junction proteins,as well as the expression changes of MMP-2 and MMP-9 in the brain tissues.Additionally,the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined.Changes in oxidative stress markers,including MDA,T-AOC,and NO,were measured using a kit method.Results The mRNA expression of Claudin-5 was significantly reduced in the middle-dose and high-dose groups compared to the control group(P<0.05).Similarly,the mRNA expression of Occludin was significantly lower in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).Additionally,the protein expression of Claudin-5,MMP-2,and Occludin was significantly decreased in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).The protein expression of MMP-9 and RhoA was also signifi-cantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05).Furthermore,the protein expression of ROCK2 and p-cofilin in the high-dose group was significantly lower than that in the control group(P<0.05).The content of MDA and T-AOC was significantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05),and the content of NO in the high-dose group was significantly lower than that in the control group(P<0.05).Conclusion Exposure to neodymium oxide results in increased permeability of the blood-brain barrier in mice,leading to oxidative stress,inflammatory responses,and activation of the RhoA/ROCK2 signaling pathway.

To investigate the clinical and pathological characteristics of duodenal-type follicular lymphoma (D-FL), and to deepen the understanding of Duodenal-type follicular lymphoma. The clinical symptoms, endoscopic features, pathologic features, immunophenotype, molecular pathological features and treatment follow-up of 18 D-FL patients diagnosed in Department of Pathology, Beijing Tiantan Hospital affiliated to Capital Medical University between January 2020 and July 2023 were summarized. A total of 18 patients with D-FL were included, including 10 males and 8 females. The median age was 49 (32-69) years respectively. Most of the patients were found during gastroenteroscopy or presented with the common gastrointestinal symptoms of stomach pain, acid reflux, vomiting and diarrhea. Most endoscopic findings were multiple small gray and white polyposis. In the pathological morphology, the mucous layer and submucous layer showed lymphoid follicular structures with full and strained follicles. The immunophenotype showed that the tumor cells strongly expressed CD20 and BCL2 and had low proliferation activity. Immunoglobulin clonal analysis of 1 case showed IgK monoclonal rearrangement (1/1). FISH showed 1 case of BCL2 gene rearrangement (1/3). All patients did not receive targeted chemotherapy and adopted a wait-and-see strategy. Median follow-up was 12 (2-34) months. This study shows that D-FL is an indolent lymphoma, which tends to occur in the duodenum and has a good prognosis.

Objective To investigate the effect and mechanism of sodium ferulate in the treatment of Ménière disease(MD)model mice.Methods BALB/c mice were selected,and an MD model was constructed using posterior fossa epidural approach combined with intraperitoneal injection of aldosterone.Sixty model mice were randomly grouped into the model group,the low dose sodium ferulate group,the medium dose sodium ferulate group,the high dose sodium ferulate group and the dexamethasone group,with 12 mice in each group.Another 12 BALB/c mice were selected as the sham operation group.After grouping and tympanic administration,auditory evoked brainstem response(ABR)was applied to detect the hearing level of mice in each group.HE staining and magnetic resonance imaging(MRI)were applied to observe the morphology of cochlea and membranous labyrinth hydrops of mice in each group.Enzyme-linked immunosorbent assay was applied to detect serum levels of lipoprotein a[Lp(a)],pro-inflammatory factor interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in each group.Immunohistochemical staining and Western blot assay were applied to detect the expression of Lp(a)in each group.Results Compared with the sham operation group,the ABR threshold,the score of membranous labyrinth hydrops,the proportion of middle stage area,serum levels of Lp(a),IL-6 and TNF-α,the IOD value of Lp(a)positive expression and the expression of Lp(a)protein in the cochlea of mice were significantly increased in the model group(P＜0.05).Compared with the model group,the ABR threshold,the score of membranous labyrinth hydrops,the proportion of middle stage area,levels of serum Lp(a),IL-6 and TNF-α,the IOD value of Lp(a)positive expression and the expression of Lp(a)protein in the cochlea of mice were significantly decreased in the low,medium and high dose sodium ferulate groups and the dexamethasone group(P＜0.05),and the effect of high dose sodium ferulate was more obvious.Conclusion Sodium ferulate can down regulate the expression of Lp(a)protein,reduce the production of proinflammatory factors,inhibit the inflammatory reaction,thereby alleviating the symptoms of membranous labyrinth hydrops in MD mice,and improving their auditory function.

Objective To explore the effects of low centrifugal force on sperm morphology analysis of normal and non-liquefied semen samples.Methods A total of 169 patients who underwent semen routine examination and sperm morphology analysis at the Reproduc-tive Center of the 904th Hospital of the Joint Logistics Support Force of PLA from January 2021 to December 2021 were collected as the study subjects.Among them,126 were the patients with normal semen routine parameters,and 43 with non-liquefied semen.The mor-phological analysis results of 126 normal semen samples treated by the direct smear method and centrifugation methods under two differ-ent of low centrifugal force were compared.The results of morphological analysis for the 43 non-liquefied semen samples treated by the direct smear method after promoting liquefaction and centrifugation were compared.Results The percentage of normal morphological sperm[(9.39±0.50)％]obtained by centrifugation of 340xg centrifugal force for 10 min was significantly lower than that[(11.08± 0.41)％]obtained by the direct smear method,and the abnormal rate of sperm in the middle segment[(62.05±1.44)％]obtained by centrifugation of 340xg centrifugal force was significantly higher than that[(57.17±0.82)％]obtained by the direct smear method.The percentage of normal morphological sperm[(9.41±0.57)％]obtained by centrifugation at 151×g centrifugal force was significantly lower than that obtained by the direct smear method,and the abnormal rate of sperm in the middle segment[(60.95±1.17)％]ob-tained by centrifugation at 151×g centrifugal force was significantly higher than that obtained by the direct smear method.For non-lique-fied semen samples,the percentage of normal morphological sperm obtained by centrifugation at 340xg centrifugal force for 10 min was[(9.61±0.60)％],while that obtained by the direct smear method after promoting liquefaction was[(11.10±0.73)％].The difference was not statistically significant between the two methods.The abnormal rate of sperm in the middle segment[(60.21±1.51)％]ob-tained by the centrifugation method was also not significantly different from that[(57.36±1.34)％]obtained by the direct smear meth-od after promoting liquefaction.Conclusion Both kinds of low centrifugal force affected the sperm morphology.However,the low cen-trifugal force has no significant effect on the non-liquefied semen.In the clinical application of sperm morphology analysis,the nature of male semen should be referred to determine whether the centrifugation is need or not and the magnitude of centrifugal force.

OBJECTIVE: To analyze the molecular genetics of a Chinese pedigree with congenital hand foot cleft. METHODS: Single nucleotide polymorphism microarray (SNP array) was used to analyze the whole genome copy number variation. RESULTS: SNP array analysis showed that there was a 433 kb repeat in 10q24.31-10q24.32 region, which contained LBX1, BTRC, POLL, OPCD and FBXW4 genes. CONCLUSION Microduplication of chromosome 10q24.31-10q24.32 may be the cause of congenital hand foot cleft in this pedigree.
China ; DNA Copy Number Variations/genetics* ; Foot Deformities, Congenital/genetics* ; Hand Deformities, Congenital/genetics* ; Humans ; Pedigree

Objective:To investigate the association of single nucleotide polymorphism at the estrogen receptor 1(ESR1) gene rs1801132 with the risk of brick-tea type skeletal fluorosis.Methods:The typical brick-tea type fluorosis areas in Qinghai, Xinjiang, and Inner Mongolia were selected as the survey sites for a cross-sectional study. An epidemiological questionnaire was conducted by the staffs on the sites for participants older than 16 years, and physical examination and X-ray diagnosis were performed. Brick tea, blood, and urine samples were collected at the same time. The diagnosis of skeletal fluorosis through X-ray was based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS/T 192-2008); The determination of tea's fluoride and urinary fluoride was performed by fluoride ion-selective electrode method; gene sequencing analysis of rs1801132 locus of ESR1 gene was done by Sequenom MassARRAY flight mass spectrometry system.Results:A total of 994 patients were included in this study. The total prevalence of skeletal fluorosis was 23.9% (238/994). The prevalence of skeletal fluorosis in Tibetans(39.9%, 123/308) was higher than those of Mongolian and Han nationality [22.2% (58/261), 13.4% (57/425), χ 2=20.435, 67.811, P < 0.05]. Based on binary logistic analysis, the daily tea fluoride intake ≤ 3.5 mg, urinary fluoride content ≤1.6 mg/L, and age ≤45 years were used as the reference groups, and then, when the daily tea fluoride intake > 7.0 mg ( OR=2.865, 95% CI: 1.923-4.268), urinary fluoride content > 1.6-3.2 mg/L ( OR=2.368, 95% CI: 1.686-3.326) and > 3.2 mg/L ( OR=3.559, 95% CI: 2.401-5.276), the age > 45-65 years old ( OR=2.361, 95% CI: 1.603-3.477) and > 65 years old ( OR=4.556, 95% CI: 2.845-7.296), the risk of fluorosis was higher than that of the reference group, respectively. When the daily tea fluoride intake was > 3.5-7.0 mg and the level of urinary fluoride was > 1.6-3.2 mg/L, G allele had a protective effect on skeletal fluorosis in Mongolian population (adjusted OR=0.207, 95% CI: 0.044-0.974); when the daily tea fluoride intake was > 3.5-7.0 mg, gender was male group, G allele had a protective effect on skeletal fluorosis in Han population (adjusted OR=0.315, 95% CI: 0.112-0.887). Conclusion:The single nucleotide polymorphism of the rs1801132 locus at the ESR1 gene may be associated with the risk of susceptibility to brick-tea type skeletal fluorosis in Mongolian and Han nationality.

Objective:To study and establish a high-throughput and rapid detection method for fluorine ion content in water based on 96-well plate and microplate reader, and to evaluate its performance.Methods:According to the principle of blue ternary complex formed by reaction of fluorine ion with fluorine reagent and lanthanum nitrate, the absorbance of the complex at the wavelength of 650 nm was proportional to the concentration of fluoride ion, and the content of fluoride ion in water samples was quantitatively determined by microplate reader. The accuracy, precision and detection limit of the method were evaluated by the standard recovery rate method and the reference material method.Results:The linear correlation coefficient of the standard curve of this method was > 0.999; the standard recovery rates of different concentrations were 99.00% - 103.33% in the accuracy experiment of this method, and the average recovery rate was 101.08%. In the standard material method, the measured values are all within the calibration range of the standard solution. The relative standard deviation of water samples with different concentrations was ≤10% in the precision experiment and the detection limit was 0.06 mg/L.Conclusion:The method has good accuracy and precision, low detection limit and small sample consumption, and this method can greatly improve the detection efficiency.