Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Humans ; Parkinson Disease/diagnosis* ; Machine Learning

Objective:To comparatively study the similarities and differences between the clinical, pathological, and risk factors of advanced fibrosis in men and women with non-alcoholic fatty liver disease (NAFLD).Methods:267 patients with NAFLD diagnosed by liver biopsy were retrospectively included, and were divided into male and female groups. The difference of clinical and pathological indexes were compared between the two groups. The measurement data were in accordance with normal distribution. The comparison between the two groups was performed by independent sample t-test. The non-parametric test was used for non-normal distribution. The classification data were expressed as a percentage, and the chi-square test was used for comparison between groups. Logistic regression analysis was used to analyze the risk factors.Results:The age of onset of NAFLD was significantly lower in male than female patients ( P < 0.01). There was no statistically significant difference between the male and female groups in terms of body mass index and the prevalence of type 2 diabetes ( P > 0.05). Biochemical index: The levels of alanine aminotransferase, albumin, total bilirubin and uric acid were significantly higher in male than female patients ( P < 0.01). Liver pathology: The proportion of ballooning degeneration was significantly lower in male than female patients ( P < 0.01). There was not statistically significant difference between the two groups in the proportion of steatohepatitis score, non-alcoholic steatohepatitis (52.0% vs. 61.5%, P = 0.283) and advanced liver fibrosis (14.3% vs. 17.8%, P = 0.162). Thrombocytopenia was a common independent risk factor for advanced stage liver fibrosis ( OR = 0.984, 0.978~0.989, P < 0.01). Type 2 diabetes was only an independent risk factor for advanced stage liver fibrosis in men ( OR = 6.557, 1.667~25.782), P < 0.01). Elevated AST was only an independent risk factor for advanced stage liver fibrosis in women ( OR = 1.016, 1.003~1.028, P = 0.012). Conclusion:In NAFLD patients, there are some clinical and pathological differences between genders. Platelets are a common predictor of advanced liver fibrosis in men and women. Type 2 diabetes in men and elevated aspartate aminotransferase in women can be regarded as independent risk factors for advanced liver fibrosis.

OBJECTIVE： To analyze chemical components in active fraction of Xiaozhong zhitong lotion， to clarify the material basis of its efficacy， and to provide reference for the second development of ointment preparation. METHODS： UPLC-Q-TOF-MS was adopted to analyze the chemical components of active fraction （40％ ethanol elution site separated by D101 macroporous resin） of Xiaozhong zhitong lotion. The determination was performed on Hypersil GOLD aQ C18 column with mobile phase consisted of 0.1％ formic acid acetonitrile （A）-0.1％ formic acid water （B） （gradient elution） at the flow rate of 0.4       mL/min. The sample size was 4 μL， and the column temperature was 30 ℃. The condition of mass spectrometry was ESI detection in positive and negative scanning ion mode （ESI+/ESI－）. The scanning range was 100-2 000 Da. The collision energy was 45/－45 eV， and the energy of the extended collider was 10/15 eV. The accurate molecular weight， retention time and multi-stage fragment ion information of the compounds were collected after obtaining the chromatogram， and the chemical components were identified by comparing with the mass spectrum information of reference materials and references. RESULTS： A total of 48 compounds were identified， and 9 and 39 compounds were identified under ESI+/ESI－ ion mode， mainly including 10 phenolic acids， 8  phenylpropanoids， 9 anthraquinones， 3 flavones， 7 alkaloids， 5 tannins and 6 other categories. CONCLUSIONS： UPLC-Q-TOF- MS method is rapid， efficient and accurate for identify chemical components from active fraction of Xiaozhong zhitong lotion. Main chemical components of the active fraction are phenolic acids， phenylpropanoids， anthraquinones， alkaloids and tannins.

Objective:To study the expression and regulation of TLR2/4 in mycobacterium tuberculosis heat shock proteins 16. 3 (mycobacterium tuberculosis heat shock proteins 16. 3,MTB Hsp16. 3) effect on mouse bone marrow-derived macrophages in vitro. Methods:Bone marrow cells were isolated from tibia and femurs of BALB/c mice and incubated with GM-CSF,then detected the expression of CD11b and F4/80 with flow cytometry and observed morphology. The M0 macrophages were stimulated with MTB Hsp16. 3 for 0 h,12 h,24 h,36 h,48 h and 72 h. Real-time PCR detected the expression of TLR2/4 in intracellular at different time point. Silencing macrophages cell surface TLR2/4 molecules by siRNA technology which stimulated with MTB Hsp16. 3 for 0 h,12 h,24 h,36 h,48 h and 72 h. Real-time PCR detected the expression of TLR2/4,Ym-1,Fizz1,IL-10,TNF-α,iNOS and TGF-βin intracellular at different time point. Results:Morphology analysis showed that MTB Hsp16. 3 stimulated macrophages were round cells stretching out pseudopodia,whereas MTB Hsp16. 3 stimulated silencing TLR2/4 macrophages had elongated fibroblastoid. Real time PCR detected the expression of TLR2/4 were upregulated after MTB Hsp16. 3 stimulated M0 macrophages. MTB Hsp16. 3 stimulated silencing TLR2/4 macrophages the expression of IL-6, TNF-α, iNOS were upregulated, whereas IL-10, TGF-β, Ym-1 and Fizz1 were downregulated. Conclusion:MTB Hsp16. 3 may stimulated M0 macrophages to M2 macrophages and suppress M1 macrophages through binding with TLR2/4 receptor,which may be involved the progresss of MTB evaded macrophage phagocytosis.

Objective To investigate the role of neuroglobin ( NGB) in oxygen-glucose deprivation and reoxygenation ( OGD/R ) induced mitochondrial depolarization and reactive oxygen species ( ROS ) production in a human neuroblastoma cell line (SH-SY5Y).Methods SH-SY5Y cells were transfected with lentivirus to establish a stable cell line of NGB knockdown ( KD).After treated with OGD/R, cells were collected at different time points to analyze NGB mRNA and protein levels.Furthermore, cells were stained with JC-1 and DCFH-DA to evaluate mitochondrial depolarization and ROS production by inverted fluorescence microscope.Also, to determine the neurotoxicity , we measured the lactate dehydrogenase ( LDH) level in the cell culture medium.Results After the treatment of OGD/R, the NGB mRNA and protein started to elevate and peak at 4 h and 8 h (2.04 ±0.35 fold,1.69 ±0.18 fold).Compared with the vector group , NGB KD group had much more mitochondrial depolarization [ JC-1 red/green ( 1.10 ±0.10 ) vs (1.46 ±0.11),P<0.05] and ROS production [DCFH-DA fluorescence (36.30 ±5.32) vs (16.26 ± 2.97),P<0.05].Furthermore, NGB KD groups had a higher level of LDH release [(63.42 ±6.14)%vs (49.65 ±5.09 )%, P <0.05 ].Conclusions NGB plays an important role in the homeostasis of mitochondria.Knockdown of NGB results in increased mitochondrial depolarization , ROS production and neurotoxicity under hypoxia circumstances.