1.The Role of α7nAChR in Alzheimer’s Disease
Dao-Bo DING ; Wen-Jun MU ; Xin LI ; Huan CHEN ; Hong-Wei HOU ; Qing-Yuan HU
Progress in Biochemistry and Biophysics 2024;51(11):2897-2904
As the global population continues to age, the incidence of Alzheimer’s disease (AD), one of the most common neurodegenerative diseases, continues to rise significantly. As the disease progresses, the patient’s daily living abilities gradually decline, potentially leading to a complete loss of self-care abilities. According to estimates by the Alzheimer’s Association and the World Health Organization, AD accounts for 60%-70% of all other dementia cases, affecting over 55 million people worldwide. The case number is estimated to double by 2050. Despite extensive research, the precise etiology and pathogenesis of AD remain elusive. Researchers have a profound understanding of the disease’s pathological hallmarks, which include amyloid plaques and neurofibrillary tangles resulting from the abnormal phosphorylation of Tau protein. However, the exact causes and mechanisms of the disease are still not fully understood, leaving a vital gap in our knowledge and understanding of this debilitating disease. A crucial player that has recently emerged in the field of AD research is the α7 nicotinic acetylcholine receptor (α7nAChR). α7nAChR is composed of five identical α7 subunits that form a homopentamer. This receptor is a significant subtype of acetylcholine receptor in the central nervous system and is widely distributed in various regions of the brain. It is particularly prevalent in the hippocampus and cortical areas, which are regions associated with learning and memory. α7nAChR plays a pivotal role in several neurological processes, including neurotransmitter release, neuronal plasticity, cell signal transduction, and inflammatory response, suggesting its potential involvement in numerous neurodegenerative diseases, including AD. In recent years, the role of α7nAChR in AD has been the focus of extensive research. Emerging evidence suggests that α7nAChR is involved in several critical steps in the disease progression of AD. These include involvement in the metabolism of amyloid β-protein (Aβ), the phosphorylation of Tau protein, neuroinflammatory response, and oxidative stress. Each of these processes contributes to the development and progression of AD, and the involvement of α7nAChR in these processes suggests that it may play a crucial role in the disease’s pathogenesis. The potential significance of α7nAChR in AD is further reinforced by the observation that alterations in its function or expression can have significant effects on cognitive abilities. These findings suggest that α7nAChR could be a promising target for therapeutic intervention in AD. At present, the results of drug clinical studies targeting α7nAChR show that these compounds have improvement and therapeutic effects in AD patients, but they have not reached the degree of being widely used in clinical practice, and their drug development still faces many challenges. Therefore, more research is needed to fully understand its role and to develop effective treatments based on this understanding. This review aims to summarize the current understanding of the association between α7nAChR and AD pathogenesis. We provide an overview of the latest research developments and insights, and highlight potential avenues for future research. As we deepen our understanding of the role of α7nAChR in AD, it is hoped that this will pave the way for the development of novel therapeutic strategies for this devastating disease. By targeting α7nAChR, we may be able to develop more effective treatments for AD, ultimately improving the quality of life for patients and their families.
2.Relationship between the gross motor function classification system and hip and lumbar spine development in children with spastic cerebral palsy.
Gang LIU ; Li LIU ; Lin XU ; Chao MA ; Bo-Wen DENG ; Sheng-Yuan JIANG ; Rui-Qin YU ; Yi ZHAO ; Xiao-Hong MU
China Journal of Orthopaedics and Traumatology 2023;36(1):79-85
OBJECTIVE:
To investigate the relationship among the gross motor function classification system (GMFCS)and the development of hip joint and lumbar spine in children with spastic cerebral palsy.
METHODS:
The clinical data of 125 children with spastic cerebral palsy admitted from January 2018 to July 2021 were retrospectively analyzed. There were 85 males and 40 females, aged from 4 to 12 years old with an average of (8.4±2.9) years. According to GMFCS, the patients were divided into gradeⅠ, Ⅱ, Ⅲ and Ⅳ groups. There were 27 cases in gradeⅠgroup, 40 cases in gradeⅡgroup, 35 cases in grade Ⅲ group and 23 cases in grade Ⅳ group. The migration percentage(MP), central edge angle(CE), neck-shaft angle(NSA), acetabular index(AI) were measured by the radiograph of pelvis, abnormal parameters were selected to evaluate the relationship between different GMFCS grades and hip joint development. Lumbar sagittal Cobb angle, lumbar sacral angle, lumbar lordosis index and apical distance were measured by lateral lumbar radiographs to evaluate the relationship between different GMFCS grades and lumbar spine development.
RESULTS:
①Among the 125 spastic cerebral palsy children, there were 119 cases of pelvic radiographs that met the measurement standards. In the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, MP was (22.72±3.88), (26.53±4.36), (33.84±4.99), and (49.54±7.87)%, CE was(30.10±6.99) °, ( 22.92±4.19) °, ( 17.91±5.50) °, and (-0.70±17.33)°, AI was (16.41±2.77) °, (20.46±4.63) °, (23.76±5.10) °, and ( 29.15±7.35)°, respectively, there were significant differences between the two comparisons (P<0.05). And the higher GMFCS grade, the greater MP and AI, and the smaller CE.The NSA was(142.74±10.03) °, (148.66±9.09) °, (151.66±10.52) °, and (153.70±8.05)° in four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, respectively. The differences between the two comparisons of the GMFCS gradeⅠgroup and the other three groups were statistically significant (P<0.05). NSA of GMFCSⅠgroup was significantly lower than that of the others, there was no significant difference among other groups(P>0.05). ② Among the 125 spastic cerebral palsy children, there were 88 cases of lumbar spine radiographs that met the measurement standards. ③The lumbar sagittal Cobb angle was(32.62±11.10) °, (29.86±9.90) °, (31.70±11.84) °, and (39.69±6.80)° in the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, respectively;GMFSS of grade Ⅳ group was significantly higher than that of other three groups, there was significant difference between the two comparisons (P<0.05);there were no significant differences between other groups (P>0.05). In the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, the lumbosacral angle was (31.02±9.91) °, ( 26.57±9.41) °, (28.08±8.56) °, and ( 27.31±11.50)°, the lumbar lordosis index was (4.14±12.89), (8.83±13.53), (13.00±11.78), and (10.76±9.97) mm, the arch apex distance was (9.50±6.80), (6.68±3.20), (7.16±4.94), and (6.62±4.13) mm, respectively, there were no significant differences between the two comparisons(P>0.05).
CONCLUSION
①In children with GMFCS gradeⅠ-Ⅳ, the higher the GMFCS grade, the worse the hip develops. ② Children with GMFCS grade Ⅲ-Ⅳ may be at greater risk for lumbar kyphosis.
Male
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Female
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Humans
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Child
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Child, Preschool
;
Lordosis
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Retrospective Studies
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Cerebral Palsy
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Hip Dislocation
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Lumbar Vertebrae/diagnostic imaging*
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Muscle Spasticity
4.Debridement, Antibiotics and Implant Retention for the Treatment of Periprosthetic Joint Infection After Arthroplasty: A Narrative Review
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(2):181-187
Periprosthetic joint infection (PJI) following joint arthroplasty is devastating and technique-demanding. At present, the surgical treatment for PJI includes debridement, antibiotics, and implant retention (DAIR), single- or two-stage revision, arthrodesis, and amputation. DAIR is appealing to both surgeons and patients as it can avoid unnecessary implants removal, making it less time-consuming and less invasive. In this article, we review the current knowledge in surgical timing, intraoperative details and antibiotics strategy of DAIR.
5. Screening and functional study of key miRNAs in circulating exosomes of hypertension
Bo-Tao ZHANG ; Wen YUAN ; Xiao-Yan LIU ; Jiii-Chang ZHONG ; Mu-Lei CHEN ; Hong-Shi WANG ; Hua-Guang WANG ; Hong-Jie CHI
Chinese Pharmacological Bulletin 2022;38(4):544-551
Aim To clarify the effect of circulating exosomes on hypertension, screen out miRNAs which plays a key role, and explore its function.Methods The plasma exosomes of spontaneously hypertensive rats were extracted and injected into Sprague Dawley rats.The blood pressure changes of rats were detected.Plasma exosomes and exosomal RNA of hypertensive patients and SHR were extracted.Real time PCR was used to verify the expression changes of the selected 8 miRNAs; Western blot was used to detect the expression changes of LKB1 and PTEN protein levels in human umbilical vein endothelial cells transfected with miR-17-5p mimics.Results The plasma exosomes of SHRs significantly increased the blood pressure of SD rats(P<0.05).The expression of miR-17-5p and miR-218-5p in the plasma exosomes of hypertensive patients and SHRs both significantly increased.miR-17-5p inhibitors significantly attenuated the effect of SHR-exos on raising blood pressure.miR-17-5p mimics down-regulated the expression of LKB1 and PTEN in HUVECs cultured in vitro.Conclusions The plasma exosomes of SHR can significantly increase blood pressure of Sprague Dawley rats.miR-17-5p may be the key miRNA.exo-miR-17-5p may promote the occurrence and development of hypertension by regulating the LKB1/PTEN signal.
6.Application of failure mode and effect analysis in low-energy X-ray radiotherapy
Yining YANG ; Song WANG ; Qingfeng LIU ; Xinyuan GONG ; Mu LI ; Nana LI ; Bo JIANG ; Yuna PENG ; Ping SHEN ; Yu ZHU ; Guangjie YUAN ; Wen SHEN
Chinese Journal of Radiation Oncology 2021;30(3):266-271
Objective:To explore the application of failure mode and effects analysis (FMEA) in low-energy X-ray intraoperative radiotherapy (IORT), analyze its potential risks in IORT, and preliminarily explore the feasibility of FMEA in optimizing IORT management and reducing the occurrence of potential risks.Methods:An FMEA working group was established by the IORT team (1 radiologist, 1 radiology physicist, 2 surgeons, and 2 nurses) to apply the FMEA methodology to conduct a systematic risk assessment. The process modules were established, the potential failure modes and causes for each module were analyzed, the severity (SR), frequency of occurrence (OR) and likelihood of detection (DR) of failure modes were scored and the risk priority number (RPN) was calculated: RPN= SR × OR × DR. The possible errors and potential clinical impact of each part of the radiotherapy process were prospectively analyzed and understood, the causes and current measures were analyzed for each failure mode and preventive measures were proposed and risk management measures were taken accordingly.Results:The IORT process was divided into 8 modules with 14 failure modes. The highest OR value was unsatisfactory target area confirmation (7 points), the highest SR value was equipment failure to discharge the beam (10 points), the highest DR value was wrong key entry after dose calculation (7 points), the highest RPN values were unsatisfactory target area confirmation (210 points) and ineffective protection of endangered organs (180 points). Weaknesses were corrected according to priorities, workflows were optimized and more effective management methods were developed.Conclusion:FMEA is an effective method of IORT management and contributes to reducing the occurrence of potential risks.
7.Role of JAK2/STAT3 signaling pathway in microglia activation after hypoxic-ischemic brain damage.
Jie ZENG ; Ya-Lin ZHAO ; Bo-Wen DENG ; Xiao-Ye LI ; Jie XU ; Le WANG ; Xiao-Hong MU
China Journal of Orthopaedics and Traumatology 2020;33(2):190-194
Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal death and neurodevelopmental disorders in infants. Part of patients have different degrees of neurological sequelae, such as cerebral palsy, cognitive and motor function development disorders. Hypoxia-ischemia may activate JAK2/STAT3 signaling pathway, which leads to the microglia activation and neuroinflammation. Down-Regulating JAK2/STAT3 signaling pathway can inhibit microglia activation and regulate the inflammatory injury of nervous system. At present, the treatment of hypoxic ischemic encephalopathy is limited, so the study of regulatory mechanism about microglia activation has important value for the treatment of hypoxic-ischemic encephalopathy. This paper summarizes the role of JAK2/STAT3 signaling pathway in microglia activation and analyzes the relationship between them, in order to provide new ideas and strategies for treatment on hypoxic-ischemic encephalopathy.
8.Clinical observation of selective posterior rhizotomy for improving spasticity and gross movement in patients with cerebral palsy.
Jie XU ; Lin XU ; Jie ZENG ; Xing-Kui YANG ; Zhao-Hui LI ; Gao-Kai SHAO ; Xiao-Ye LI ; Bo-Wen DENG ; Xiao-Hong MU
China Journal of Orthopaedics and Traumatology 2019;32(9):815-819
OBJECTIVE:
To explore the effect of selective lumbosacral posterior rhizotomy(SPR) on lower limb spasticity and gross motor function in patients with cerebral palsy.
METHODS:
From January 2018 to October 2018, 47 patients with cerebral palsy were treated with rehabilitation alone and SPR combined with rehabilitation. According to whether SPR was performed, the patients were divided into group A and group B. Group A was treated with rehabilitation combined with SPR at lumbosacral level, and group B was treated with rehabilitation alone. There were 23 cases in group A, including 15 males and 8 females, with an average age of (7.30±3.25) years old; 24 cases in group B, 13 males and 11 females, with an average age of (7.00±3.09) years old. Forty-seven patients were assessed with modified Ashworth(MAS) and Gross Motor Function Scale(GMFM-88 items) before and after treatment. The changes of MAS and GMFM-88 scores before and after treatment were compared to evaluate the degree of spasm and the improvement of gross motor function in the two groups.
RESULTS:
All 47 patients were followed up. At 6 months after treatment, the MAS classification of the two groups was significantly improved(<0.05), and the improvement of group A was more obvious than that of group B(<0.05). Six months after treatment, the D, E and total scores of GMFM-88 between two groups were significantly improved compared with those before operation(<0.05). The improvement of D and total scores in group A was more obvious than that in group B. There was no significant difference in the improvement of area E between two groups.
CONCLUSIONS
Selective posterior rhizotomy combined with rehabilitation can significantly improve the spastic state and gross motor function of lower limbs in children with cerebral palsy, and can effectively promote the reconstruction and recovery of motor function of lower limbs in children with cerebral palsy.
Cerebral Palsy
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surgery
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Child
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Child, Preschool
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Female
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Humans
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Lower Extremity
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Male
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Movement
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Muscle Spasticity
;
Rhizotomy
9.Effects of two screening models for eye diseases in premature infants
Hai-Bo LIN ; Wen-Lin LI ; Xiao ZHUO ; Ai-Qun HE ; Mu-Dan CHEN
International Eye Science 2018;18(3):596-598
·AIM:To investigate and compare the application of two screening models in the detection of retinopathy of prematurity (ROP). ·METHODS: The clinical data of 600 premature infants (1200 eyes) who underwent screening of eye diseases in the Department of Ophthalmology during the period from January 2016 to January 2017 were analyzed retrospectively. The fundus lesions were examined with binocular indirect ophthalmoscope (BIO) and the third generation of wide-angle digital retinal imaging system (RetCam Ⅲ). The examination results and adverse events during operation were statistically analyzed. ·RESULTS:In 1200 eyes of 600 patients,the probabilities of ROP detected by BIO and RetCam Ⅲ were 10.92% and 10.75%, respectively (P>0.05). With BIO as the golden standard, the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of RetCam Ⅲ in examining ROP were 98.67%, 93.13%, 99.35%, 94.57% and 99.16%, respectively. There was no significant difference in the stage of ROP detected by BIO or RetCam Ⅲ (P>0.05). The probabilities of non-ROP lesions examined by BIO and RetCam Ⅲ were 4.83% and 4.58%, respectively (P>0.05). With BIO as the golden standard, the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of RetCam Ⅲ in examining fundus non-ROP diseases were 99.67%, 94.83%, 99.91%, 98.21% and 99.74%, respectively. During the screening of BIO and RetCam Ⅲ,there were 17 cases (2.83%) and 7 cases(1.17%) with adverse events, respectively (P<0.05).·CONCLUSION: The examination results of RetCam Ⅲ are basically the same as those of BIO for ROP and non-ROP diseases. However,RetCam Ⅲ has more advantages in reducing adverse events during operation.
10.Association of Ureaplasma urealyticum with the types of antisperm antibody in infertile men.
Zhen-Cheng ZHANG ; Mu-Tian HAN ; Wen-Jun WU ; Gai-Gai WANG ; Dong-Hong LIU ; Hong-Bo CHENG ; Jia-Xiong WANG ; Li-Yan SHEN ; Yi-Chao SHI
National Journal of Andrology 2018;24(2):147-151
Objective:
To investigate the prevalence of Ureaplasma urealyticum (UU) infection in infertile men, its influence on routine semen parameters and the distribution of antisperm antibody (AsAb) and its types in infertile patients with UU infection.
METHODS:
We detected the positive rate of UU infection, semen parameters, and the distribution of AsAb and its types in 662 infertile men and 25 normal fertile male controls followed by comparison of the obtained data between the two groups of subjects.
RESULTS:
The positive rate of UU infection was significantly higher in the infertile men than in the normal controls (52.87% [350/662] vs 16.00% [4/25], χ2 = 11.68, P <0.05). The semen volume, sperm count, sperm concentration and percentage of progressively motile sperm were remarkably lower in the UU-positive infertile males than in the control group (P <0.05). No statistically significant difference was observed between the UU-positive and UU-negative groups in the positive rates of total AsAb (43.4% vs 36.5%, χ2 = 3.25, P >0.05) and AsAb IgA, IgM and IgG in the seminal plasma, or in the percentages of serum AsAb IgM (16.9% vs 20.5%, χ2 = 1.22, P >0.05) and IgG (32.7% vs 28.9%, χ2 = 0.99, P >0.05) except in that of serum AsAb IgA (23.6% vs 17.0%, χ2 = 4.03, P <0.05).
CONCLUSIONS
The UU infection rate is high in infertile males, which decreases the semen volume, total sperm count, motile sperm concentration and percentage of progressively motile sperm and increases the positive rate of serum AsAb IgA.
Antibodies, Bacterial
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analysis
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Humans
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Infertility, Male
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immunology
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microbiology
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Male
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Semen
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Sperm Count
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Spermatozoa
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immunology
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Ureaplasma Infections
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diagnosis
;
immunology
;
Ureaplasma urealyticum
;
immunology

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