Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective To investigate the effect of butorphanol on the malignant biological behavior of glioma cells by regulating the sonic hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) signaling pathway. Methods Glioma LN229 cells were divided into control group, low-dose butorphanol group, medium-dose butorphanol group, high-dose butorphanol group, high-dose butorphanol+pcDNA3.1 group and high-dose butorphanol+pc-SHH group. MTT and Edu assays were used to detect cell proliferation; flow cytometry was used to detect cell apoptosis rate; Transwell chamber assay was used to detect cell migration and invasion; real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect SHH mRNA and GLI1 mRNA expression levels; Western blot was used to detect the protein expression levels of Ki-67, matrix metalloproteinase-2 (MMP-2), cleaved caspase-3, SHH and GLI1. Results Butorphanol could reduce the viability and proliferation rate of LN229 cells, and decreased the number of cell migration and invasion (P < 0.05). Butorphanol could reduce the expression levels of SHH mRNA, GLI1 mRNA and the protein expression of Ki-67, MMP-2, SHH as well as GLI1 in LN229 cells, promote cell apoptosis and increase the protein expression of cleaved caspase-3 (P < 0.05). Overexpression of SHH could partially reverse the inhibitory effect of butorphanol on LN229 cells (P < 0.05). Conclusion Butorphanol can inhibit the malignant biological behavior of glioma cells, and its mechanism may be related to the inhibition of the SHH/GLI1 signaling pathway.

Objective To investigate the relationships of serum levels of human fractalkine (CX3CL1) and chitinase-3-like protein 1 (YKL-40) with early cognitive impairment in elderly patients with Alzheimer's disease (AD). Methods A total of 110 AD patients in the Second Affiliated Hospital of Xinxiang Medical University from February 2021 to December 2023 were selected as AD group, and 50 healthy individuals with physical examination during the same period were selected as control group. Clinical materials and serum levels of CX3CL1 and YKL-40 were compared between the two groups, and multivariate Logistic regression models were used to analyze the influencing factors of cognitive impairment in AD patients. Based on the Mini-Mental State Examination (MMSE) score, the 110 AD patients were divided into mild cognitive impairment group (n=47), moderate cognitive impairment group (n=36), and severe cognitive impairment group (n=27). Spearman correlation analysis was performed to explore the relationships of serum CX3CL1 and YKL-40 with MMSE score, Addenbrooke's Cognitive Examination-Ⅲ (ACE-Ⅲ) score, and Montreal Cognitive Assessment (MoCA) score. Results The AD group had higher proportions of patients aged over 80 years, with an education level of primary school or below, smoking history, alcohol consumption history, diabetes mellitus, hypertension, AD family history, and living alone as well as higher serum levels of CX3CL1 and YKL-40 compared to the control group; conversely, the AD group had a lower proportion of patients engaging in no physical exercise/labor, and lower MMSE, ACE-Ⅲ, and MoCA scores, with significant between-group differences (P < 0.05). Advanced age, diabetes mellitus, and high serum levels of CX3CL1 and YKL-40 were independent risk factors for cognitive impairment in AD patients (P < 0.05), while an education level of college or above was a protective factor (P < 0.05). Compared with the mild cognitive impairment group, the moderate and severe cognitive impairment groups had higher serum levels of CX3CL1 and YKL-40, and the severe cognitive impairment group had higher serum levels of CX3CL1 and YKL-40 than the moderate group, with significant between-group differences (P < 0.05). Spearman correlation analysis revealed that serum CX3CL1 and YKL-40 were negatively correlated with MMSE, ACE-Ⅲ, and MoCA scores (P < 0.05). Conclusion Serum CX3CL1 and YKL-40 are highly expressed in elderly AD patients, and are closely related to early cognitive impairment in elderly AD patients.

Viruses are powerful tools for the study of modern neurosciences. Most of the research on the connection and function of neurons were done by using recombinant viruses, among which neurotropic herpesvirus is one of the most important tools. With the continuous development of genetic engineering and molecular biology techniques, several recombinant neurophilic herpesviruses have been engineered into different viral tools for neuroscience research. This review describes and discusses several common and widely used neurophilic herpesviruses as nerve conduction tracers, viral vectors for neurological diseases, and lytic viruses for neuro-oncology applications, which provides a reference for further exploring the function of neurophilic herpesviruses.
Herpesviridae/genetics* ; Neurosciences ; Genetic Vectors/genetics* ; Genetic Engineering ; Neurons

ObjectiveTo explore the effect of hip neuromuscular training on reducing the risk of anterior cruciate ligament (ACL) injury in female soccer players. MethodsFrom March to May, 2022, 39 female soccer players from Xi'an Physical Education University were randomly divided into control group (n = 19) and experimental group (n = 20). On the basis of daily training, the control group received sham intervention, and the experimental group received hip neuromuscular training, for six weeks. Before and after training, they were measured dynamic knee valgus (DKV) angle and assessed with Landing Error Score System (LESS); while they were also measured the maximal voluntary isometric contraction (MVIC) and root mean square (RMS) of electromyography as single leg landing of gluteus medius and gluteus maximus. ResultsAll the indexes varied little after training in the control group (|t| < 1.178, P > 0.05), while the indexes improved in the experimental group (|t| > 2.288, P < 0.05), except sagittal score of LESS; and all the indexes improved more in the experimental group than in the control group (|t| > 2.609, P < 0.05), except sagittal score of LESS and MVIC of gluteus maximus. ConclusionHip neuromuscular training can reduce the risk of ACL injury in female soccer players.

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.
Breast Neoplasms/enzymology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Humans ; MCF-7 Cells ; N-Terminal Acetyltransferases/metabolism* ; Organoplatinum Compounds/pharmacology* ; Oxaliplatin/pharmacology* ; X-ray Repair Cross Complementing Protein 1

Objective : To study the relationship between lncRNA SIL and proliferation and migration of alveolar epithelial cell during pulmonary fibrosis. Methods : The expression level of lncRNA SIL in A549 cells induced by transforming growth factor(TGF⁃ β1) was detected by RNA fish. The eukaryotic expression vector of lncRNA SIL was built and transfected into A549 cells , the proliferation and migration of the cells after overexpressing lncRNA SIL were studied by RT⁃PCR , MTT , Western blot , cell damage repair experiments and immunofluorescence. Result: The migration and proliferation of A549 cells were significantly reduced compared with the control group after transfected by lncRNA SIL. When lncRNA SIL was overexpressed in A549 cells , cell proliferation , migration and expression of proliferation - related proteins PCNA and Ki67 were decreased compared with the control group. Analysis of the expression of cellular marker proteins showed that , the expression levels of interstitial cell marker proteins α ⁃SMA and Collagen⁃1 were significantly reduced , while the expression level of alveolar epithelial marker protein E. cad significantly increased. Conclusion LncRNA SIL can inhibit the proliferation and migration of A549 cells , and also can inhibit EMT induced by TGF⁃ β1 .

OBJECTIVE: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer. METHODS: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning. RESULTS: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein. CONCLUSION The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
Asian Continental Ancestry Group ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; Exome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Phenotype

Objective: To investigate the effect of erythropoietin (EPO) on the expression of aquaporin 2-3 after the release of unilateral ureter obstruction in young rats. Methods: Twenty-four SD rats were randomly divided into 3 groups(CUUO-R group, CUUO-R+ EPO group and sham group, with 8 rats in each group). The CUUO-R model was built through unilateral ureteral ligation, after 48 h the obstruction was released.EPO was given to the CUUO-R+ EPO group at the time point of removing obstruction, and then repeated every other day for 1 week, and the same volume of saline was simultaneously given to the CUUO-R rats.The rats in sham group experienced the laparotomy and free dissection of left ureter but not ligation.The kidneys were harvested 7 d after the release of CUUO.The methods of Western blot and immunohistochemistry were used to examine the effects of erythropoietin on the expression of AQP2 and AQP3. Results: The osmotic pressure of CUUO-R+ EPO group was higher than those of CUUO-R group, but lower than that of sham group(P=0.007). The concentration of creatinine and urea in the CUUO-R group[(58.001±2.416) μmol/L and (9.025±1.158) mmol/L]were higher than those of CUUO-R+ EPO group [(57.072±2.286) μmol/L and (1.479±0.043) mmol/L] and sham group [(54.820±1.536) μmol/L and (6.929±0.604) mmol/L]. The differences of the concentration of creatinine and urea between CUUO-R group and sham group were statistically significant(P<0.05). There was no significant difference between CUUO-R+ EPO group and Sham group(P>0.05). The immunohistochemistry showed that the expressions of AQP2 and AQP3 in co-llecting duct in CUUO-R group were significantly weaker than those of in sham group, and the expression of those in CUUO-R+ EPO group were slightly weaker than sham group.These results were further confirmed by Western blot, as the relative quantity of AQP2 and AQP3 were also the lowest in CUUO-R group(AQP2 in 3 groups were 0.974±0.109, 1.923±0.097 and 2.002±0.044, F=392.4, P=0.000; AQP3 in 3 groups were 0.941±0.048, 1.497±0.043 and 1.863±0.043, F=735.8, P=0.000). Conclusions EPO treatment is beneficial for the recovery expre-ssion of AQP2 and AQP3 as well as renal function at the early period after the release of ureteral obstruction in young rats.

Objective: To explore the association between dust exposure and the incidence of hypertension in male coal miners. Methods: Using the method of retrospective cohort study,a hypertension cohort of colliery in Henan Province was established in January 2006. From 2006 to 2017,all the male coal miners in a colliery who were exposed to dust were selected into the exposure group including tunneling, mining,auxiliary and combining workers, and workers from administrative logistics departments who were not exposed to dust were selected into the control group. The eligible participants should satisfy following conditions: working more than one year, with clear and complete record of occupation change, and with complete archives and reliable diagnosis of occupational health surveillance. The exclusion criteria of participants were with hypertension at the baseline of study or with heart,liver,kidney diseases and malignant tumors. A total of 12 647 participants were enrolled in this study (11 663 in the exposure group and 984 in the control group). The follow-up period was from January 2006 to December 2017,with a total follow-up of 89 259.75 person-years. Questionnaires and physical measurements were used to collect general demographic characteristics, occupational exposure history and occupational health surveillance data of all participants. The Cox proportional hazards regression model was used to estimate the association between the dust exposure and the incidence of hypertension. Results: During the follow-up period, 2 549 new-onset hypertension patients were identified with an incidence density of hypertension about 2 855.71 per 100 000 person-years. The incidence density of hypertension was 2 967.58 per 100 000 person-years in the exposure group, and 1 643.85 per 100 000 person-years in the control group. The results of multivariate Cox proportional hazards regression model showed that after the adjustment of marriage, age, smoking, alcohol drinking and body mass index,the risk of hypertension was higher in the exposure group compared with the control group (HR=1.692, 95%CI: 1.410-2.032). Further analysis showed that compared with workers from administrative logistics departments,the risk of hypertension in tunneling,mining and auxiliary working was 1.629(1.345-1.973),1.677(1.374-2.046) and 1.782(1.475-2.151),respectively. Conclusion Dust exposure may increase the risk of hypertension in male coal miners.