1.Role and Mechanism of Lactate Metabolism/Lactylation in The Improvement of Central Nervous System Diseases by Exercise Intervention
Progress in Biochemistry and Biophysics 2025;52(6):1401-1417
Central nervous system diseases (CNSDs) refer to a range of disorders resulting from structural or functional impairments of the brain and spinal cord, including stroke, Alzheimer’s disease (AD), Parkinson’s disease, spinal cord injury (SCI), and brain tumors. As a leading cause of disability and the second leading cause of death worldwide, CNSDs involve complex pathological mechanisms that profoundly affect patients’ physical and mental health as well as their quality of life. Therefore, identifying potential therapeutic targets and developing targeted intervention strategies for the prevention and treatment of CNSDs is of great significance. Recent studies have revealed that lactate can transmit energy between cells via the “lactate shuttle” mechanism and act as an endogenous signaling molecule, exerting diverse biological functions in CNSDs. Lactylation, a novel type of post-translational modification that uses lactate and lysine residues as substrates, plays a critical role in regulating gene transcription, immune responses, and cellular metabolism under both physiological and pathological conditions. Studies have confirmed that lactate participates in the onset and progression of CNSDs through both lactate metabolism and lactylation. In AD, lactate promotes Aβ plaque formation and impairs synaptic plasticity and cognitive function. Lactylation contributes to AD pathogenesis by regulating Aβ accumulation, Tau protein phosphorylation, neuroinflammation, pyroptosis, and ferroptosis. In ischemic stroke (IS), lactate suppresses neuroinflammation and alleviates ischemic injury. Lactylation is involved in the regulation of neuroinflammation, endothelial cell apoptosis, and neuronal ferroptosis, contributing to IS progression. In SCI, lactate promotes the phenotypic transition of astrocytes from the A1 to the A2 type, thereby mitigating neural injury. Lactylation alleviates neurological dysfunction by modulating neuroinflammation, axonal regeneration, mitochondrial function, and microglial proliferation. In glioblastoma (GBM), lactate promotes M2 polarization of microglia, facilitating tumor cell growth and dissemination. Lactylation further accelerates GBM progression by enhancing tumor cell migration, proliferation, immune evasion, and drug resistance. These findings suggest that lactate may serve as a potential therapeutic target for the prevention and treatment of CNSDs. However, its precise role in CNSDs remains unclear, and the specific mechanisms by which lactate metabolism and lactylation influence disease progression warrant further investigation. Moreover, studies have confirmed that exercise, as a key non-pharmacological intervention, holds great promise in the prevention, treatment, and rehabilitation of CNSDs. Specifically, exercise can regulate lactate metabolism and lactylation, which in turn suppresses neuroinflammation, enhances synaptic plasticity, promotes neurogenesis and angiogenesis, improves mitochondrial function in the hippocampus, and facilitates the release of neuroprotective factors, ultimately contributing to the improvement of CNSDs. This review summarizes the roles of lactate metabolism and lactylation in CNSDs, as well as the potential mechanisms by which exercise regulates lactate metabolism and lactylation to improve CNSDs, providing a theoretical basis for the benefits of exercise on brain health.
2.Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi.
Ning-Ye FANG ; Wen-Cui WEI ; Jian-Jun LI ; Ping CEN ; Xian-Xiang FENG ; Dong YANG ; Kai-Ling TANG ; Shu-Jia LIANG ; Yu-Lan SHAO ; Hua-Xiang LU ; He JIANG ; Qin MENG ; Shuai-Feng LIU ; Qiu-Ying ZHU ; Huan-Huan CHEN ; Guang-Hua LAN ; Shi-Xiong YANG ; Li-Fang ZHOU ; Jing-Lin MO ; Xian-Min GE
Acta Academiae Medicinae Sinicae 2023;45(3):399-404
Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male
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Humans
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Middle Aged
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Reverse Transcriptase Inhibitors/therapeutic use*
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HIV Infections/drug therapy*
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Drug Resistance, Viral/genetics*
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China/epidemiology*
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Mutation
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HIV-1/genetics*
;
Protease Inhibitors/therapeutic use*
;
Genotype
3.Efficacy and Safety of Bushen Huoxue Formula in Patients with Discogenic Low-Back Pain: A Double-Blind, Randomized, Placebo-Controlled Trial.
Jia-Wen ZHAN ; Kai-Ming LI ; Li-Guo ZHU ; Shang-Quan WANG ; Min-Shan FENG ; Xu WEI ; Jie YU ; Bin TANG ; Xun-Lu YIN ; Tao HAN ; Ping ZHANG ; Ling-Hui LI ; Ming CHEN ; Chen-Chen SHAO
Chinese journal of integrative medicine 2022;28(11):963-970
OBJECTIVE:
To assess the efficacy and safety of Bushen Huoxue Formula (BSHXF) for the treatment of discogenic low-back pain (DLBP).
METHODS:
This was a parallel, double-blind, randomized, clinical trial performed between May 2019 and June 2020. Seventy patients were assigned by computerized random number table to the treatment group (lumbar traction and BSHXF, 35 cases) or the control group (lumbar traction and placebo, 35 cases). The patients received intervention for 3 weeks. Assessment was conducted before treatment and at week 1, 2, 3 during treatment. Primary outcome was the self-reported score of Oswestry Disability Index (ODI). Secondary outcomes included Visual Analog Scale (VAS), clinical efficacy rate by minimal clinically important difference (MCID) as well as lumbar tenderness, muscle tone and lumbar spine mobility. Adverse reactions were recorded. Follow-up was performed at 1 and 3 months after the end of treatment.
RESULTS:
In the treatment group, ODI score was significantly decreased compared with baseline (P<0.05) and the control group at 2- and 3- week treatment. Similarly, VAS score decreased compared with the baseline (P<0.05) and was lower than that in the control group at 2- and 3- week treatment (P<0.05). The clinical efficacy rate of the treatment group was higher than that of the control group after treatment [32.35% (11/34) vs. 3.13% (1/32), P<0.05). Moreover, the tenderness, and muscle tone, as well as the back extension and left flexion in lumbar spine mobility in the treatment group at 3-week treatment were significantly improved compared with the control group (P<0.05). Follow-up showed that at 1-month after treatment, the treatment group had better outcomes than the control group with regard to a total score of ODI and VAS scores, as well as clinical efficacy rate (all P<0.05). Moreover, VAS score was still significantly lower than the control group at 3-month follow-up (P<0.05). No adverse reactions were reported during the study.
CONCLUSION
BSXHF combined with lumbar traction can significantly improve the clinical symptoms including pain intensity, functionality, muscle tone, and lumbar spine mobility in DLBP patients. (Registration No. ChiCTR1900027777).
Humans
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Intervertebral Disc Degeneration/therapy*
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Low Back Pain/drug therapy*
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Lumbar Vertebrae
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Pain Measurement
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Treatment Outcome
4.Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals
Ansel Shao Pin TANG ; Kai En CHAN ; Jingxuan QUEK ; Jieling XIAO ; Phoebe TAY ; Margaret TENG ; Keng Siang LEE ; Snow Yunni LIN ; May Zin MYINT ; Benjamin TAN ; Vijay K SHARMA ; Darren Jun Hao TAN ; Wen Hui LIM ; Apichat KAEWDECH ; Daniel HUANG ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J SANYAL ; Mark MUTHIAH ; Cheng Han NG
Clinical and Molecular Hepatology 2022;28(3):483-496
Background/Aims:
Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD.
Methods:
Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD.
Results:
From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD.
Conclusions
This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.
5.Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.
Yan MA ; Dong Shan ZHU ; Ren Bo CHEN ; Nan Nan SHI ; Si Hong LIU ; Yi Pin FAN ; Gui Hui WU ; Pu Ye YANG ; Jiang Feng BAI ; Hong CHEN ; Li Ying CHEN ; Qiao FENG ; Tuan Mao GUO ; Yong HOU ; Gui Fen HU ; Xiao Mei HU ; Yun Hong HU ; Jin HUANG ; Qiu Hua HUANG ; Shao Zhen HUANG ; Liang JI ; Hai Hao JIN ; Xiao LEI ; Chun Yan LI ; Min Qing LI ; Qun Tang LI ; Xian Yong LI ; Hong De LIU ; Jin Ping LIU ; Zhang LIU ; Yu Ting MA ; Ya MAO ; Liu Fen MO ; Hui NA ; Jing Wei WANG ; Fang Li SONG ; Sheng SUN ; Dong Ting WANG ; Ming Xuan WANG ; Xiao Yan WANG ; Yin Zhen WANG ; Yu Dong WANG ; Wei WU ; Lan Ping WU ; Yan Hua XIAO ; Hai Jun XIE ; Hong Ming XU ; Shou Fang XU ; Rui Xia XUE ; Chun YANG ; Kai Jun YANG ; Sheng Li YUAN ; Gong Qi ZHANG ; Jin Bo ZHANG ; Lin Song ZHANG ; Shu Sen ZHAO ; Wan Ying ZHAO ; Kai ZHENG ; Ying Chun ZHOU ; Jun Teng ZHU ; Tian Qing ZHU ; Hua Min ZHANG ; Yan Ping WANG ; Yong Yan WANG
Biomedical and Environmental Sciences 2020;33(12):893-905
Objective:
Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.
Methods:
A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio (
Results:
Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.
Conclusion
Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult
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Aged
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COVID-19/virology*
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China/epidemiology*
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Comorbidity
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Female
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Humans
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Male
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Middle Aged
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Retrospective Studies
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Severity of Illness Index
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Treatment Outcome
6.Expert consensus on management principles of orthopedic emergency in the epidemic of coronavirus disease 2019.
Pei-Fu TANG ; Zhi-Yong HOU ; Xin-Bao WU ; Chang-Qing ZHANG ; Jun-Wen WANG ; Xin XING ; Zeng-Wu SHAO ; Ai-Xi YU ; Gang WANG ; Bin CHEN ; Ping ZHANG ; Yan-Jun HU ; Bo-Wei WANG ; Xiao-Dong GUO ; Xin TANG ; Dong-Sheng ZHOU ; Fan LIU ; Ai-Mi CHEN ; Kun ZHANG ; Kai-Nan LI ; Yan-Bin ZHU
Chinese Medical Journal 2020;133(9):1096-1098
Betacoronavirus
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Consensus
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Coronavirus Infections
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complications
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epidemiology
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prevention & control
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Epidemics
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Humans
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Minimally Invasive Surgical Procedures
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Musculoskeletal Diseases
;
complications
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therapy
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Pandemics
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prevention & control
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Pneumonia, Viral
;
complications
;
epidemiology
;
prevention & control
7.Effectiveness of snail control by immersion of molluscicides through tide diversion in marshlands: a field evaluation
Qi-Ling QIU ; Shao-Zhou CHEN ; Yin-Ping ZUO ; Kai TANG ; Guang-Lin DU ; Yi-Xin HUANG
Chinese Journal of Schistosomiasis Control 2019;31(5):535-537
Objective To compare the effectiveness of snail control between immersion of molluscicides through tide diversion and mollusciciding by spraying in marshland areas. Methods Immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion and spraying 26% suspension concentrate of metaldehyde and niclosamide alone were employed for snail control in two neighboring snail-breeding marshlands, and snails were surveyed before and after mollusciciding. The mortality of snails and the density of living snails were estimated. Results The density of living snails reduced by 72.19% and 100.00% 1 and 2 years after immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion, and 5.93% and 18.15% 1 and 2 years after spraying 26% suspension concentrate of metaldehyde and niclosamide alone. Conclusion Immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion is significantly superior to spraying 26% suspension concentrate of metaldehyde and niclosamide along for snail control, and implementation of immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion for more than 2 successive years may achieve a higher snail control efficiency.
8.Analysis of HIV infection status and factors among men who have sex with men in Guangzhou
Rong-jiao LIANG ; Cheng WANG ; Pei-zhen ZHAO ; Quan LUO ; Shao-kai TANG ; Wan-ping HE ; Yun-qing YANG ; Xing-dong YE ; Hui-lan ZHU ; Jian-qin WANG
Chinese Journal of Disease Control & Prevention 2019;23(12):1482-1486,1497
Objective To understand infection status of human immunodeficiency virus (HIV) and analyze the influencing factors among men who have sex with men (MSM) in Guangzhou. Methods Men who have sex with men (MSM) were recruited from 2014 to 2017. Face-to-face questionnaire survey was conducted to collect information of characterisitc and behaviors. Blood samples were used to detect HIV antibodie. Data were analyzed using SPSS 19.0. Results Among 2 419 MSM, 200(8.27%) participants were confirmed positive for HIV. Multivariate Logistic regression analysis showed that with Guangzhou and monthly economic income >0.5 million as reference, non-Guangzhou (OR=1.712, 95% CI: 1.176-2.492,P=0.005) and monthly economic income ≤0.5 million (OR=1.998, 95% CI: 1.409-2.833,P<0.001) were associated with HIV infection among MSM. Diagnosed syphilis (OR=2.461, 95% CI: 1.375-4.405,P=0.002) , undetected syphilis (OR=2.333, 95% CI: 1.635-3.331,P<0.001), anal sex role passive (OR=2.015, 95% CI: 1.244-3.267,P=0.004), both active and passive (OR=2.115, 95% CI: 1.374-3.251,P=0.001), non-using condoms every time during anal sex (OR=1.955, 95% CI: 1.374-2.781,P<0.001), non-fixed anal sex objects (OR=2.150, 95% CI: 1.463-3.160,P<0.001) were major risk factors for HIV infection among MSM. Conclusions The prevalance of HIV infection and high-risk sexual behavior were high among MSM in Guangzhou. It is urgent to expand the scope of HIV testing and advocate safe sexual behaviors among MSM.
9.Human tissue kallikrein-1 protects against the development of erectile dysfunction in a rat model of hyperhomocysteinemia.
Kai CUI ; Yang LUAN ; Zhe TANG ; Chuan-Chang LI ; Tao WANG ; Shao-Gang WANG ; Zhong CHEN ; Ji-Hong LIU
Asian Journal of Andrology 2019;21(5):508-515
The aim of this study was to investigate the mechanism by which a diet inducing high hyperhomocysteinemia (HHcy) leads to the deterioration of erectile function in rats and whether this is inhibited by expression of the human tissue kallikrein-1 (hKLK1) gene. We established a rat model of HHcy by feeding methionine (Met)-rich diets to male Sprague-Dawley (SD) rats. Male wild-type SD rats (WTRs) and transgenic rats harboring the hKLK1 gene (TGRs) were fed a normal diet until 10 weeks of age. Then, 30 WTRs were randomly divided into three groups as follows: the control (n = 10) group, the low-dose (4% Met, n = 10) group, and the high-dose (7% Met, n = 10) group. Another 10 age-matched TGRs were fed the high-dose diet and designated as the TGR+7% Met group. After 30 days, in all four groups, erectile function was measured and penile tissues were harvested to determine oxidative stress, endothelial cell content, and penis fibrosis. Compared with the 7% Met group, the TGR+7% Met group showed diminished HHcy-induced erectile dysfunction (ED), indicating the improvement caused by hKLK1. Regarding corpus cavernosum endothelial cells, hKLK1 preserved endothelial cell-cell junctions and endothelial cell content, and activated protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) signaling. Fibrosis assessment indicated that hKLK1 preserved normal penis structure by inhibiting apoptosis in the corpus cavernosum smooth muscle cells. Taken together, these findings showed that oxidative stress, impaired corpus cavernosum endothelial cells, and severe penis fibrosis were involved in the induction of ED by HHcy in rats, whereas hKLK1 preserved erectile function by inhibiting these pathophysiological changes.
Animals
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Apoptosis
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Diet
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Endothelial Cells
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Erectile Dysfunction/prevention & control*
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Fibrosis
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Humans
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Hyperhomocysteinemia/complications*
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Male
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Methionine
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Oxidative Stress
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Penis/pathology*
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Rats
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Rats, Sprague-Dawley
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Rats, Transgenic
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Signal Transduction/genetics*
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Tissue Kallikreins/genetics*
10.The Establishment of Porcine Scoliosis Model by the Adjustable Brace Asymmetric Tethering
Wei-Yun KONG ; Chong-Wen MAO ; Jun-Wei SHAO ; Xue-Fang TANG ; Fei WANG ; Wei XU ; Kai-Yu HOU ; Quan ZHOU
Journal of Kunming Medical University 2018;39(1):26-29
Objective To explore the feasibility of the adjustable brace asymmetric tethering in concave side for establishing a porcine scoliosis model.Methods Six minority piglets (aged 8-10-week-old, weight 8-10 kg) were selected and the adjustable brace asymmetric tethering in concave side were applied during the procedure.Roentgenography was performed before and immediately after the operation, and 1, 2 and 3 months after the procedure.Cobb angles were measured based in the plain radiograph.Results A piglet died for narcotic drug overdose and the other 5 pigs succeeded in modeling.The cobb angles were (9.0 ±1.6) ° in one month, (11.8 ±1.3) ° in two months and (21.6 ±2.4) ° in three months after the operation . Conclusion It's is an effective way to establish the porcine model of rapidly progressive structural scoliosis by the adjustable brace asymmetric tethering in concave side.It avoids the damage to the spinal elements and could be an ideal model for further study on corrective techniques.

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