Parkinson disease is a neurodegenerative disorder with motor and cognitive impairments as the main clinical symptoms. The disease is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of Lewy bodies， which are eosinophilic inclusions composed of α-synuclein， in the remaining dopaminergic neurons. The disease predominantly affects middle-aged and elderly individuals. Oxidative stress caused by mitochondrial dysfunction can lead to the loss of dopaminergic neurons， so mitochondrial dysfunction is considered as the main cause of Parkinson disease. Mitochondrial biogenesis has an important effect on the function of mitochondria. Therefore， abnormality of the regulation system of mitochondrial biogenesis is closely related to the occurrence and development of Parkinson disease. This review focuses on the regulatory mechanism of mitochondrial biogenesis control system and aims to provide promising therapeutic targets for Parkinson disease.
Parkinson Disease

Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome(PCOS).The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.Methods A customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used.The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice(8 mice per group)to establish the control group and letrozole-induced PCOS model group.Both groups were treated with a high-fat diet starting the day after administration.The modeling period lasted for 5 weeks,during which body weight and 24-hour food intake were monitored in each group every week.When samples were collected,liver weight was recorded.Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin(HE)staining,while hepatic lipid deposition was observed by Oil Red O staining.The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining,and hepatic fibrosis levels were observed by Masson's trichrome staining.Transcriptomic sequencing was performed to analyze differentially expressed genes(DEGs)in liver tissues between the control and model groups,followed by enrichment analysis of significant DEGs.Quantitative real-time fluorescent quantitative PCR(qPCR)was subsequently used to validate the expression of significant DEGs in liver tissues of both groups.Results Compared with the control group,the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight(P＜0.001),prominent polycystic ovarian morphology,and significantly decreased liver-to-body weight ratio(P＜0.05).However,no significant changes were observed in absolute liver weight(P＞0.05),hepatic histomorphology,or lipid deposition.Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice,which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis,steroid hormone metabolism,and inflammatory responses.qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver(P＜0.01),while mRNA expression of IL4,CCL2 and COL1A1 was downregulated(P＜0.05)in the model group compared with the control group.However,Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.Conclusion Subcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS.The model mice exhibited significant changes in hepatic gene expression.Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.

Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome(PCOS).The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.Methods A customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used.The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice(8 mice per group)to establish the control group and letrozole-induced PCOS model group.Both groups were treated with a high-fat diet starting the day after administration.The modeling period lasted for 5 weeks,during which body weight and 24-hour food intake were monitored in each group every week.When samples were collected,liver weight was recorded.Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin(HE)staining,while hepatic lipid deposition was observed by Oil Red O staining.The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining,and hepatic fibrosis levels were observed by Masson's trichrome staining.Transcriptomic sequencing was performed to analyze differentially expressed genes(DEGs)in liver tissues between the control and model groups,followed by enrichment analysis of significant DEGs.Quantitative real-time fluorescent quantitative PCR(qPCR)was subsequently used to validate the expression of significant DEGs in liver tissues of both groups.Results Compared with the control group,the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight(P＜0.001),prominent polycystic ovarian morphology,and significantly decreased liver-to-body weight ratio(P＜0.05).However,no significant changes were observed in absolute liver weight(P＞0.05),hepatic histomorphology,or lipid deposition.Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice,which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis,steroid hormone metabolism,and inflammatory responses.qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver(P＜0.01),while mRNA expression of IL4,CCL2 and COL1A1 was downregulated(P＜0.05)in the model group compared with the control group.However,Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.Conclusion Subcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS.The model mice exhibited significant changes in hepatic gene expression.Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.

Objective The radiotherapy resistance is one of important causes for nasopharyngeal carcinoma(NPC) treatment failure.Junctional adhesion molecule A(JAMA)is closely correlated with the tumor poor prognosis.Thus this experiment is to in vestigate the relationship between JAMA expression and the radiosensitivity of NPC.Methods To overexpress or interfere the JAMA expression in CNE2 and HONE1 cell lines.Then different doses of X-ray were adopted to conduct irradiation.The cell clone formation capacity and cellular apoptosis change were detected after 24 h.The role of JAMA in the NPC radiotherapy was understand.The related signal pathway protein in cell lines with different JAMA expression was detected by Western blot.Results The cell lines with low JAMA expression were more sensitive to radiotherapy:After low JAMA expression,the D0 value in the CNE2 cell line was decreased from 3.26 ±0.78 to 1.92 ± 0.23;the Dq value was decreased from 46.51 ± 4.27 to 32.12 ± 3.19.The radio therapy induced apoptosis was significantly increased in the cell lines with low JAMA expression,after low JAMA expressing,thcellular apoptosis was elevated from 6.9 ％ ± 0.9 ％ to 13.7 ％ ± 1.3 ％;the HONE1 cellular apoptosis was elevated from 6.5 ％ + 1.1 ％ to 12.3 ％ ± 1.7％;JAMA overexpression cell lines were significantly decreased.The preliminary mechanism research results showed that JAMA played the effect via Akt signal pathway.Conclusion This research results verifiy that JAMA expression level is closely correlated with the radiosensitivity of NPC cell line:JAMA can increase the radiotherapy resistance of NPC cell lines,which provides a new feasible research direction for NPC enhancing radiosensitivity.

Objective To identify the role of miR-124 in regulating the radiosensitivity and the epithelial-mesenchymal transition (EMT) of nasopharyngeal carcinoma (NPC). Methods Transient transfection of cells with miR-124 mimic or inhibitor was performed and wound-healing assay was used to investigate the role of miR-124 in the EMT of NPC. The apoptosis affected by miR-124 was also measured after irradiation , followed by investigating the cell proliferation by EdU assay. Finally , proteins of Akt and ERK associated with EMT and radiosensitivity, were measured by western blot. Results The migration index from NPC cell line indicated that miR-124 repressed the EMT. The results from caspase-3 activity assay showed that caspase-3 activity after irradiation significantly increased in miR-124 mimic group compared with the control group (P < 0.01). It was also confirmed that irradiation led to a higher percentage of apoptosis in miR-124 group compared with the control group in NPC cells. Cell proliferation after irradiation was significantly decreased in MiR-124 group as compared with control group . MiR-124 inhibited the protein expression of p-Akt . Conclusion MiR-124 may repress the EMT and decrease radio-resistance of NPC via p-Akt signaling pathway , which may provide a new insight into radio-resistance in NPC.

Objective To investigate the clinical features,diagnosis and treatment experience of idiopathic calcinosis of the scrotum(ICS).Methods We report 5 cases with a 4-month to 20-year history of ICS.The related literatures were reviewed.Results The multiple scrotum masses in these patients were increased slowly in size and number.The levels of blood calcium and phosphorus were normal.Histopathologically,nodules were composed of basophilic calcified material and located in the dermis.There was no epithelial lining around the calcified nodules.Conclusion ICS is a rare localized benign disease.The diagnosis of the tumor relies largely on the histopathology.Surgical excision is the best choice for treatment.

This study investigated the changes of CD4(+) CD25(+) regulatory T cells (Tregs) in peripheral blood of patients with hepatocellular carcinoma before and after transcatheter arterial chemoembolization (TACE). The proportion of CD4(+) CD25(+) Tregs among CD4(+) T lymphocytes in peripheral blood of 33 patients with hepatocellular carcinoma was determined by flow cytometry before, 1 week and 1 month after TACE. And 25 healthy volunteers served as control. One month after TACE, the patients were divided into two groups: 22 in group A, who were in stable condition or getting better; and 10 in group B, who were deteriorating. One patient died and was excluded. The results showed that the percentage of CD4(+)CD25(+) Tregs among CD4(+) T lymphocytes did not significantly change in the 33 patients 1 week after TACE as compared with that before TACE, however, the difference was significant (P<0.01) between the patients with hepatocellular carcinoma and the healthy subjects. The percentage of CD4(+) CD25(+) Tregs among CD4(+) T lymphocytes in group A 1 month after TACE was decreased significantly in comparison with that before and 1 week after TACE (P<0.01), whereas, that in group B was increased significantly 1 month after TACE (P<0.01). It was concluded that patients with hepatocellular carcinoma had a higher proportion of CD4(+)CD25(+) Tregs in peripheral blood. TACE did not significantly affect the level of CD4(+) CD25(+) Tregs within short time (such as 1 week). The proportion of CD4(+)CD25(+) Tregs in peripheral blood 1 month after TACE was related to the prognosis of hepatocellular carcinoma.
Antineoplastic Agents/administration & dosage ; Carcinoma, Hepatocellular/*immunology ; Carcinoma, Hepatocellular/therapy ; Chemoembolization, Therapeutic/*methods ; Liver Neoplasms/*immunology ; Liver Neoplasms/*therapy ; T-Lymphocytes, Regulatory/*immunology

This study investigated the changes of CD4+CD25+ regulatory T cells (Tregs) in peripheral blood of patients with hepatocellular carcinoma before and after transcatheter arterial chemoembolization (TACE). The proportion of CD4+CD25+ Tregs among CD4+ T lymphocytes in peripheral blood of 33 patients with hepatocellular carcinoma was determined by flow cytometry before, 1 week and 1 month after TACE. And 25 healthy volunteers served as control. One month after TACE, the patients were divided into two groups: 22 in group A, who were in stable condition or getting better;and 10 in group B, who were deteriorating. One patient died and was excluded. The results showed that the percentage of CD4+CD25+ Tregs among CD4+ T lymphocytes did not significantly change in the 33 patients 1 week after TACE as compared with that before TACE, however, the difference was significant (P<0.01) between the patients with hepatocellular carcinoma and the healthy subjects. The percentage of CD4+ CD25+ Tregs among CD4+ T lymphocytes in group A 1 month after TACE was decreased significantly in comparison with that before and I week after TACE (P<0.01), whereas,that in group B was increased significantly 1 month after TACE (P<0.01). It was concluded that patients with hepatocellular carcinoma had a higher proportion of CD4~CD25+ Tregs in peripheral blood. TACE did not significantly affect the level of CD4+ CD25+ Tregs within short time (such as 1 week). The proportion of CD4+CD25+ Tregs in peripheral blood 1 month after TACE was related to the prognosis of hepatocellular carcinoma.