Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a variety of motor and non-motor symptoms. Many studies have shown that the transmembrane protein 175 (TMEM175) gene may be a potential target for the treatment of PD and other neurodegenerative disorders, but the specific pathogenic mechanism remains unclear. TMEM175 is a lysosomal protein-coding gene that encodes a lysosomal proton channel protein. This article reviews the research advances in the characterization of the TMEM175 gene and its encoded proteins, the clinical features of mutant PD, and related pathogenic mechanism. It is shown that the TMEM175 gene has an impact on the pathogenesis of PD, and patients with different mutation sites tend to have different ages of onset and clinical features. Compared with the patients without TMEM175 mutations, the patients with TMEM175 mutations tend to have an earlier age of onset, more severe motor symptoms, and more susceptibility to cognitive impairment and non-motor symptoms. This article systematically reviews the TMEM175 gene, in order to assist in the early diagnosis of PD and the discovery of new disease-modifying therapies and treatment strategies.
Parkinson Disease

OBJECTIVE To study the protective effect of phenolic acid components from Salvia deserta Schang on the oxidative stress injury of human renal tubular epithelial cells HK -2 induced by high glucose and high fat . METHODS HK-2 cells were divided into control group ，model group ，canagliflozin group （positive control group ，15 μmol/L），purified product of phenolic acids from S. deserta Schang group （10.8 μg/mL），4 monomers group （salvianic acid ，protocatechuic aldehyde ，caffeic acid，rosmarinic acid ，50 μmol/L）. In addition to the control group ，cell injury model of high glucose and high fat was established in other groups （500 μmol/L palmitic acid+ 30 mmol/L glucose for 48 h）and cultured for 48 h. The cell apoptotic rate ，the contents of malondialdehyde （MDA）and glutathione （GSH），and the activity of superoxide dismutase （SOD）were detected in each group ； the expression levels of nuclear erythroid 2-related factor 2（Nrf2），Kelch-like ECH -associated protein 1（Keap1）protein，heme oxygenase-1（HO-1）and NADH ：quinone acceptor oxidoreductase 1（NQO1）were determined in above 5 groups（except for salvianic acid ，protocatechuic aldehyde ，caffeic acid ）. RESULTS Compared with control group ，the apoptotic rate of HK -2 cells in model group was increased significantly （P＜0.01）；the content of MDA was increased significantly （P＜0.01），while the content of GSH and the activity of SOD were decreased significantly ；protein expressions of Nrf 2，NQO1 and HO -1 2018D01C169） were significantly down -regulated（P＜0.01），while the protein expression of Keap 1 was up -regulated significantly （P＜0.01）. Compared with model group ， the apoptotic rate and the content of MDA were decreased significantly in administration groups（P＜0.01）；the content of GSH in administration groups and the activity of SOD in purified product of phenolic acids group，protocatechuic aldehyde group and rosmarinic acid group were increased significantly （P＜0.01）. The protein expressions of Nrf2，HO-1 and NQO 1 in purified product of phenolic acids group as well as the protein expression of Nrf 2 in rosmarinic acid group were up -regulated significantly （P＜0.01），while the protein expression of Keap 1 was down -regulated significantly in purified product of phenolic acids group and rosmarinic acid group （P＜0.01）. CONCLUSIONS The phenolic acids components from S. deserta Schang can relieve oxidative stress injury of renal tubular epithelial cells induced by high glucose and high fat ，the mechanism of which may be associated with activating Keap 1/Nrf2 signaling pathway and inhibiting oxidative stress response .

OBJECTIVE: To assess the value of mapping allele with resolved carrier status (MaReCs) technology for the determination of balanced translocation carrier status for embryos. METHODS: Blastocysts produced by 25 reciprocal translocation carriers and 15 Robertsonian translocation carriers were detected by MaReCs. After genetic counseling, transplantable blastocysts were selected. Amniocentesis was performed to check fetal chromosomes at 16 to 20 gestational weeks, and the consistency of amniocentesis and MaReCs was determined. RESULTS: No significant difference was found in the normal rate for chromosome copy number variations (CNVs) in blastocysts between reciprocal translocation carriers and Robertsonian translocation carriers (28.6% vs. 32.0%, P> 0.05). For 12 (48%) reciprocal translocation carriers and 8 (32%) Robertsonian translocation carriers, the status of translocation carrier of embryos was successfully determined. The results of amniocentesis were consistent with that of MaReCs in all 11 pregnancies. CONCLUSION MaReCs is a reliable method to distinguish the translocation carrier status of embryos of balanced translocation carriers. It can help a certain proportion of balanced translocation carriers to select completely normal embryos while reduce transfer of embryo carrying a balanced translocation.

The activity of free radicals in follcular fluid was related to ovarian responsiveness,in vitro fertilization (IVF),and embryo transfer success rate.However,studies analyzing the relationship between the free radical scavenging capacity and embryo quality of infertile women with polycystic ovarian syndrome (PCOS) were lacking.The aim of this study was to evaluate the relationship between the free radical scavenging window of women with PCOS and their embryo quality.The free radical scavenging capacity of follicular fluid from women with PCOS was determined by a,a-diphenyl-b-picrylhydrazyl (DPPH),2,2-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) assay,superoxide radical,and reactive oxygen species (ROS) assay.In the DPPH and ROS assays,the follicular fluid from grades Ⅰ and Ⅱ embryos was significantly higher than the follicular fluid from grades Ⅲ and Ⅳ embryos.The lower control limit of DPPH radical scavenging capacity and upper control limit of ROS level were 13.2％ and 109.0 cps,respectively.The calculated lower control limit and upper control limit were further confirmed in the follicular fluid of embryos of all grades.These cut-off values of free radical scavenging activity of follicular fluid could assist embryologists in choosing the development of embryos in PCOS patients undergoing.

Objective To investigate the proliferation, immune phenotype and cytotoxicity on different cell lines of cytokine-induced killer (CIK) cells collected from healthy donors. Methods Peripheral blood mononuclear cells (PBMC) from healthy donors were induced to become CIK cells by adding cytokines including rhIL-2, rhIFN-γand CD3 McAb. The proliferation of CIK cells was tested by blood cell recording board. The CIK cells were analyzed on different time points by FACS. The cytotoxicity of CIK cells against different tumor cell lines, such as K562, BJAB, A549, MCF-7 and HepG2, was detected by MTT assays on day 13. Results CIK cells quickly proliferated from day 5, and expanded by 182-fold after 20-day culture. The immunophenotypes of CD3+, CD3+CD8+and CD3+CD56+were (97.83±1.03)%, (77.12±1.60)%and (27.58± 2.02)%. The percentages of CD3+, CD3+CD8+and CD3+CD56+increased noticeably (P＜0.01). According to the effector-tar-get ratio of 40∶1, the activity of CIK cells against tumor cells K562, BJAB, A549, MCF-7 and HepG2 were (88.89±7.22)%, (75.42±9.52)%, (63.19±5.67)%, (43.53±5.67)%and (42.63±7.69)%. The experiments showed that CIK cells possessed high-er antitumor cytotoxic activity. Conclusion CIK cells can be largely capacity cultured by adding cytokines in vitro. CIK cells were a highly efficient cytotoxic cell against tumors, and had clinical application potentials.

Objective To tested the passive targeting of nanobubbles penetrating tumor vascular endothelial cells gap.Methods Twenty female BALB/c nude mice subcutaneously bearing human ovary cancer SKOV3 were devided into two groups:group A (ultrasound imaging) and group B (frozen sections:B1 and B2).DiI labled nanobubbles and microbubbles were prepared and adjusted into the same concentrations.Group A:Microbubbles and nanobubbles of 35 μl were injected into the tail vein of every mouse respectively (1.5 h interval).Ultrasound imaging were acquired.Group B:Nanobubbles and microbubbles of 10 μl were injected into the tail vein of mice in Group B1 and Group B2 respectively.Heart perfusion by PBS or 0.9％ normal saline was carried out 1.5 h after bubbles injection to clear the free bubbles in blood circulation.And the tumor and muscle of right lower limb were immediately cut off for frozen slices (3 μm),which were stained by Hoechst 33342 to mark the nucleus.Images were obtained with a confocal microscope.Results In vivo ultrasound imaging,the time to peak and clearance time of nanobubbles were longer than those of microbubbles,whereas the intensity of enhancement was lower than microbubbles.Frozen sections showed:with the confocal laser scanning microscopy imaging,quite a number of DiI-labeled nanobubbles existed in the intercellular space of SKOV3 tumor,whereas there were few nanobubbles in skeletal muscle sections.In the control,rare DiI-labeled microbubbles were observed in tumors and skeletal muscle.Conclusions Self-made lipid nanobubbles were small enough to pass through the tumor vascular endothelial gap,namely achieve the tumor passive targeting.

Embryos with a poor morphological score at cleavage stage are usually discarded because they are considered unsuitable for transfer and cryopreservation. This study examined the in vitro blastocyst development after extended culture of these embryos and the clinical outcomes after transfer of these blastocysts in warming cycles. A total of 597 blastocysts (24.7%) were obtained from 2421 embryos with low morphological scores after extended culture. One hundred and sixty blastocysts (6.6%) with optimal morphology were vitrified. Embryo utilization rate was increased from 30.8% to 32.6%. After warming, 61 out of 92 blastocysts (66.3%) survived and were transferred in 44 cycles. The clinical pregnancy rate and the implantation rate were 40.9% (18/44) and 32.8% (20/61) respectively. Thirteen healthy babies were born, and 5 pregnancies aborted spontaneously. Our study suggested that some blastocysts derived from embryos with a poor morphological score can be successfully vitrified and give rise to live births. Selection and vitrification of viable embryos after extended culture of embryos with a poor morphological score may constitute a proposal to avoid embryo wastage.
Adult ; Cryopreservation ; methods ; Embryo Culture Techniques ; methods ; Embryo Transfer ; methods ; statistics & numerical data ; Female ; Fertilization in Vitro ; methods ; statistics & numerical data ; Humans ; Infertility ; pathology ; therapy ; Middle Aged ; Pregnancy ; Pregnancy Outcome ; Vitrification ; Young Adult

Objective To prepare targeted nanoscale lipid ultrasound contrast agent and study the targeting function in vitro.Methods After the biotinylated monoclonal antibody Herceptin was prepared,the biotinylated degree and immunological activity were determined.Then biotinylated antibody was attached to the surface of nanoscale lipid ultrasound contrast agents by avidin-biotin system to prepare the targeted nanobubbles.The targeting function was studied by observing the combination ability of the targeted nanobubbles with SKOV3 cells in vitro,non-targeted nanobubbles as controls,and observing ultrasound imaging in vitro.Results About 16 biotin molecules were coupled to each antibody in average,and the immunological activity of the biotinylated antibody didn't decrease compared with the free one(P ＞0.05).SKOV3 cells were combined firmly and surrounded regularly by red dyed targeted nanobubbles,while control groups were negative.Ultrasound imaging could be significantly enhanced by targeted nanobubble binding to SKOV3 cell slides,the other two control groups were negative.Conclusions Nanoscale ultrasound contrast agent and antibodys can be combined firmly by avidin-biotin system to produce the targeted nanobubbles,which have strong targeting function in vitro and significantly enhanced ultrasound signal.

Embryos with a poor morphological score at cleavage stage are usually discarded because they are considered unsuitable for transfer and cryopreservation. This study examined the in vitro blastocyst development after extended culture of these embryos and the clinical outcomes after transfer of these blastocysts in warming cycles. A total of 597 blastocysts (24.7%) were obtained from 2421 embryos with low morphological scores after extended culture. One hundred and sixty blastocysts (6.6%) with optimal morphology were vitrified. Embryo utilization rate was increased from 30.8% to 32.6%. After warming, 61 out of 92 blastocysts (66.3%) survived and were transferred in 44 cycles. The clinical pregnancy rate and the implantation rate were 40.9% (18/44) and 32.8% (20/61) respectively. Thirteen healthy babies were born, and 5 pregnancies aborted spontaneously. Our study suggested that some blastocysts derived from embryos with a poor morphological score can be successfully vitrified and give rise to live births. Selection and vitrification of viable embryos after extended culture of embryos with a poor morphological score may constitute a proposal to avoid embryo wastage.

Objective To explore the adverse reactions of contrast-enhanced ultrasound and treatments of the adverse reactions. Methods 6035 patients examined by contrast-enhanced ultrasound were closely observed in the process and 20 minutes after the examination. The occurrence and clinical manifestations of adverse reactions were recorded. The patients were gave symptomatic treatments. Results Two of 6035 patients experienced mild adverse reactions related with contrast-enhanced ultrasound. The incidence rate was 0. 031% (2/6035). No moderate or serious adverse reaction occurred. The two patients recovered well after symptomatic treatments. Conclusions The contrast-enhanced ultrasound has high safety and low incidence rate of adverse reaction. Patients should be under close observation in the process of contrast-enhanced ultrasound. The symptomatic treatments should be gave in time.