1.Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF
Xiang-ge PENG ; Zhen-jia LIN ; Hui ZHANG ; Shi-ze LENG ; Yuan TANG ; Yu-fan ZHENG ; Zhi TAN ; Li-jun ZHOU
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(3):395-402
		                        		
		                        			
		                        			ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor (M-CSF) in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups, (n = 10 mice/group, half male and half female). The albumin control group (BSA, 0.3 μg), low dose M-CSF group (L M-CSF, 0.075 μg) and high dose M-CSF group (H M-CSF, 0.3 μg) received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration, von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold (PWT) in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin, calcitonin gene-related peptide (CGRP) and phosphorylated ERK1/2 (p-ERK) in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice, only high dose of M-CSF caused mechanical allodynia, whereas in male mice both doses produced marked allodynia. Mechanically, high-dose M-CSF induced massive aggregation of subcutaneous macrophages (marked by Iba1) in male and female mice, but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion (DRGs). Notably, CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly, the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway. 
		                        		
		                        		
		                        		
		                        	
3.Mechanism of pepsin promoting lingual tonsil hypertrophy by stimulating macrophage.
Li Jun HUANG ; Jia Jie TAN ; Ling Yi PENG ; Yuan Feng DAI ; Ze Hong LYU ; Xue Qiong HUANG ; Xiang Ping LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(10):1203-1211
		                        		
		                        			
		                        			Objective: To investigate the possible pathophysiological mechanism of laryngopharyngeal reflux (LPR) in the development of lingual tonsil hypertrophy (LTH). Methods: The lingual tonsil tissues were collected from 73 patients [48 males and 25 females, aged from 24 to 76 (52.86±12.04) years] who underwent surgery for laryngopharyngeal diseases at the Department of Otolaryngology and Head and Neck Surgery, Southern Hospital of Southern Medical University from October 2019 to December 2020, and the lingual tonsil grade (LTG), reflux symptom index (RSI) and reflux finding score (RFS) were assessed. The expression of pepsin in LTH was detected by immunohistochemistry. The coexpression of pepsin and macrophages were detected by immunohistofluorescence. In vitro, cytological experiments and pathway assays were performed on macrophages stimulated by pepsin. Pathway alterations of macrophages in pepsin-positive high-grade LTH were detected by double-fluorescence immunohistochemistry. Data were analyzed by SPSS 20.0 software. Results: There were 44 clinically significant LPRD patients with LTG 3 and 4, and the pepsin positive rate was 88.6% (39/44). While, the pepsin positive rate of LTG 1 and 2 was 48.3% (14/29). LTG was significantly positively correlated with RFS/RSI positive rate(χ2=23.01/19.62, P<0.001/0.001; r=0.54/0.51, P<0.001/0.001) and pepsin tissue staining intensity (H=21.58, P<0.001; r=0.53, P<0.001), respectively. Pepsin and macrophages were clearly colocalized in high grade LTH. In vitro, pepsin promoted macrophage proliferation (P<0.05) and production of IL-6/IL-8 (P<0.05). Pepsin significantly up-regulated the p38/JNK MAPK pathway in macrophages (P<0.05). Pepsin up-regulated the expression of IL-6 and IL-8 of macrophages by activating the p38 MAPK pathway (P<0.05), and up-regulated the expression of IL-8 by activating the JNK pathway (P<0.05). The p38/JNK MAPK pathways were highly expressed in macrophages of pepsin-positive LTH (P<0.05). Conclusions: LPR is an important pathogenic factor in LTH. Macrophages may mediate pepsin-induced inflammation and the pathogenesis of LTH.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Palatine Tonsil
		                        			;
		                        		
		                        			Pepsin A
		                        			;
		                        		
		                        			Interleukin-6
		                        			;
		                        		
		                        			Interleukin-8
		                        			;
		                        		
		                        			Hypertrophy
		                        			;
		                        		
		                        			Macrophages
		                        			;
		                        		
		                        			Laryngopharyngeal Reflux
		                        			
		                        		
		                        	
4.Comparison of vesselplasty and percutanous kyphoplasty in the treatment of Kümmell disease.
Shu-Qiang YAO ; Rui WU ; Ji-Ping ZHOU ; Yong-Jun YANG ; Yuan-Chao TAN ; Kai YANG ; Jia-Jia LI ; Ze-Wei JIANG ; Bin LIU
China Journal of Orthopaedics and Traumatology 2022;35(5):429-434
		                        		
		                        			OBJECTIVE:
		                        			To compare the efficacy between vesselplasty and percutanous kyphoplasty (PKP) in the treatment of Kümmell disease.
		                        		
		                        			METHODS:
		                        			The clinical data of patients with Kümmell disease from July 2018 to December 2019 were retrospectively analyzed. According to the different therapeutic methods, the patients were divided into vesselplasty group and PKP group. There were 20 patients in vesselplasty group, including 2 males and 18 females, aged from 54 to 83 years with an average of (67.40±7.44)years, 1 case of T10 fracture, 3 cases of T12 fracture, 9 cases of L1 fractures, 5 cases of L2 fractures and 2 cases of L3 fractures. There were 20 patients in PKP group, including 3 males and 17 females, aged from 56 to 81 with an average of(67.20±7.01) years, 2 cases of T10 fracture, 1 case of T11 fracture, 6 cases of T12 fracture, 10 cases of L1 fracture and 1 case of L3 fracture. Visual analogue scale(VAS), Cobb angle, anterior vertebral height were recorded before operation, 1 day after operation and 1 year after operation. Oswestry Disability Index(ODI) was recorded before operation, 1 month after operation and 1 year after operation. And bone cement leakage rate was compared between two groups after operation.
		                        		
		                        			RESULTS:
		                        			All the patient were followed up for more than 1 year. In vesselplasty group, VAS score was 1.20±0.41, ODI was(13.50±3.10)%, Cobb angle was(17.20±3.12)° and anterior vertebral height was(20.20±1.35) mm at 1 year after operation. In PKP group, VAS score was 1.15±0.40, ODI was (13.20±3.00)%, Cobb angle was (17.10±3.19)° and anterior vertebral height was (20.10±1.37) mm at 1 year after operation. These index was significantly better than pre-operation through intra-group comparison(P<0.05), and there was no statistically difference between the two groups(P>0.05). There were 20 cases (20 vertebrae) in vesselplasty group, of which 1 case had bone cement leakage at the upper endplate, with a leakage rate of 5%(1/20). In PKP group, there were 20 cases (20 vertebrae), 3 cases of upward endplate leakage(3/7), 1 case of downward endplate leakage(1/7), 1 case of leakage to the front of the vertebral body(1/7), 2 cases of leakage to the side of the vertebral body(2/7), with a leakage rate of 35% (7/20). The difference between two groups was statistically significant(P<0.05).
		                        		
		                        			CONCLUSION
		                        			Vesselplasty in the treatment of Kümmell disease can better reduce leakage rate of bone cement and reduce complications.
		                        		
		                        		
		                        		
		                        			Bone Cements
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fractures, Compression/surgery*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Kyphoplasty/methods*
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Osteoporotic Fractures/surgery*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Spinal Fractures/surgery*
		                        			;
		                        		
		                        			Spondylosis
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Vertebroplasty
		                        			
		                        		
		                        	
6. Regional differences of anthropometric traits in Han population
Jia-Zi WU ; Chang SUN ; Shao-Qing WEN ; Jing-Ze TAN
Acta Anatomica Sinica 2021;52(5):803-811
		                        		
		                        			
		                        			 Objective To explore the regional differences of body anthropometric traits in the Han population. Methods From 2015 to 2019, thirty-one body anthropometric traits of three Han ethnic groups were measured from Nanning (Guangxi), Zhengzhou (He'nan), and Taizhou (Jiangsu). The gender and regional difference analysis of each trait, and the correlation analysis between age and traits were carried out. Based on the principal component analysis of individual data of body phenotypic traits, the traits with significant regional difference were extracted to finely describe the physical characteristics of the Han peoplpe in the three regions. Results Most of the anthropometric traits of the three Han populations were statistically different in gender and region, and there was a positive or negative correlation between certain traits and age. The result of principal component analysis based on individual data showed that there were obvious regional differences in body anthropometric traits of the Han people. The difference between the Han Chinese in Guangxi ( south of the Yangtze River ) with He ' nan ( north of the Huaihe River ) and Jiangsu was relatively large, and difference was relatively small between He ' nan and Jiangsu Han Chinese. Meanwhile the Han Chinese in Jiangsu had its own characteristics in part of the phenotypic traits, which could be distinguished from the Han Chinese in He ' nan. Conclusion The research on the body anthropometric traits confirmed that there were significant regional differences in Han population, and suggested that the Yangtze River might be the largest geographic barrier for the population migration and genetic exchange between the north and south population. 
		                        		
		                        		
		                        		
		                        	
7.Measurement of vertebral "shell" volume after thoracolumbar fracture reductions
Ze-Li ZHONG ; Hai-Gang HU ; Xu LIN ; Lun TAN ; Chao WU ; Jun ZENG ; Jia-Yan DENG
Chinese Journal of Tissue Engineering Research 2018;22(7):1038-1043
		                        		
		                        			
		                        			BACKGROUND: Posterior screw rod system reduction and internal fixation is often used to treat thoracolumbar fractures (T11-L2). However, the "shell" phenomenon is focused on imaging findings and lacks of in-depth clinical research. OBJECTIVE: To explore the new method of "shell" volume measurement of vertebral body after thoracolumbar fractures reduction, and to evaluate the effect of different "shell" sizes on clinical treatment. METHODS: From January 2013 to December 2015, 72 patients with thoracolumbar fractures were treated in the No. 4 People's Hospital of Zigong City retrospectively. The patients with vertebral "shell" were retrospectively analyzed. Clinical and imaging data (X ray, CT and MRI) were collected. Compression degree of anterior border of the vertebral body, Cobb angle, Visual Analogue Scale score and reduction-related complication were recorded and analyzed. The volumes of vertebral "shell" and the injured vertebral body were measured by Mimics software. The volume ratio of shell/injured vertebral body was calculated. The healing of vertebral "shell" was followed up and observed. RESULTS AND CONCLUSION: (1) Among the 72 patients, there were 16 cases with a shell/injured vertebral volume ratio of < 5% (group A), 30 cases with the volume ratio of 5%-10% (group B), and 26 cases with volume ratio of > 10% (group C). (2) The "shell" healing: The "shell"nonunion rate was significantly lower in the groups A and B than in the group C (P < 0.05); and significant differences were not determined between groups A and B (P > 0.05). (3) Compression degree of the anterior border of the injured vertebral body: No significant difference was found in groups A, B and C before and right after reduction (P > 0.05). The compression was significantly higher in the groups A and B than in group C at final follow-up (P < 0.05). (4) Cobb angle was not significantly different in groups A, B and C before and right after reduction and during final follow-up (P > 0.05). (5) Visual Analogue Scale score was not significantly different between groups A and B and group C right after reduction (P > 0.05). The Visual Analogue Scale score was significantly better in the groups A and B than in the group C (P < 0.05). (6) Occurrence of complications: In the group A, one case affected incision exudate. In the group B, one case experienced incision infection and one case suffered from screw loosening. In the group C, two cases affected screw loosening, and one case experienced unilateral connecting rod fracture. No significant difference in complications was detected among groups A, B and C (P > 0.05). (7) Results indicate that the "shell"nonunion rate was high when vertebral shell/injured vertebral body volume ratio > 10%; loss of posterior vertebral height and chronic lumbago and back pain easily appeared. The measurement of the volume of vertebral "shell" plays an important role in clinical prognosis and treatment options of thoracolumbar judgment.
		                        		
		                        		
		                        		
		                        	
8.Involvement of TLR4/NLRP3 inflammasome in contrast medium-induced inflammation and injury in renal tubular epithelial cells
Yan LIN ; qiong Jia LIN ; li Chu XIE ; feng Xiao GUAN ; xian Xue TAN ; na Ze HUANG
Chinese Journal of Pathophysiology 2017;33(12):2252-2258
		                        		
		                        			
		                        			AIM: To investigate whether Toll-like receptor 4 ( TLR4 ) and Nod-like receptor protein 3 (NLRP3) inflammasome were involved in contrast medium (CM)-induced inflammation and injury in renal tubular epithe-lial cells.METHODS: Iopromide was used to injure NRK-52E cells in the study.The cell viability was measured by CCK-8 assay.The protein levels of TLR4, NLRP3, apoptosis-associated speckle-like protein (ASC), caspase-1 and cleaved caspase-3 were determined by Western blot .The releases of interleukin ( IL )-1βand IL-18 were detected by ELISA .The apoptotic rate was evaluated by Hoechst staining , and mitochondrial membrane potential ( MMP) was analyzed by JC-1 staining.siRNA was transfected into the NRK-52E cells to silence NLRP3 expression.RESULTS:CM decreased the viability of NRK-52E cells (P<0.05).CM also elevated the protein levels of cleaved caspase-3, TLR4, NLRP3, IL-1βand IL-18 (P<0.05).Silencing NLRP3 attenuated CM-induced releases of inflammatory cytokines .Moreover, treat-ment with TLR4 inhibitor TAK-242 or knockdown of NLRP3 by siRNA transfection both attenuated cell apoptosis and loss of MMP caused by CM .CONCLUSION:TLR4/NLRP3 inflammasome takes part in the pathogenesis of CM-induced acute kidney injury , and mediates CM-induced injury and inflammation in renal tubular epithelial cells .
		                        		
		                        		
		                        		
		                        	
9.A Missense Mutation in Epsilon-subunit of Acetylcholine Receptor Causing Autosomal Dominant Slow-channel Congenital Myasthenic Syndrome in a Chinese Family.
Jia-Ze TAN ; Yuan MAN ; Fei XIAO
Chinese Medical Journal 2016;129(21):2596-2602
BACKGROUNDCongenital myasthenic syndromes are a group of rare disorders that are clinically and genetically heterogeneous and caused by mutations in the genes encoding proteins of the neuromuscular junction. Here, we described a Chinese family that presented with phenotypes of classic slow-channel congenital myasthenic syndrome (SCCMS).
METHODSClinical characteristics and electrophysiological features of three patients from a Chinese family were examined, and next-generation sequencing followed by direct sequencing was carried out.
RESULTSThe patients revealed variability in clinical and electrophysiological features. However, weakness, scoliosis, and repetitive-compound muscle action potential were found in all affected members in the family. A heterozygous C>T missense mutation at nucleotide 865 in acetylcholine receptor epsilon-subunit (CHRNE) gene that causes a leucine-to-phenylalanine substitution at position 289 (L289F) was found.
CONCLUSIONSWe reported a SCCMS family of Chinese origin. In the family, classical clinical phenotype with phenotypic variability among different members was found. Genetic testing could help diagnose this rare disease.
Adult ; DNA Mutational Analysis ; Electrophysiology ; Female ; Humans ; Male ; Mutation, Missense ; genetics ; Myasthenic Syndromes, Congenital ; genetics ; physiopathology ; Receptors, Nicotinic ; genetics ; Young Adult
            
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