1.Prospects for histone deacetylase inhibitors as antidepressants
Kai-yun YAO ; Hong-wan DING ; Lin-yu CAO ; Yin-ge GAO ; Jian-jun ZHANG ; Gui-bin WANG
Acta Pharmaceutica Sinica 2021;56(1):29-36
Depression is a serious mental illness with a high incidence. At present, we do not fully understand the specific pathological mechanisms of depression, and the efficacy of drug treatments is very limited. Recent studies have shown that epigenetic changes that occur in specific brain regions may be a key mechanism by which environmental factors to interact with individuals to influence the risk of depression. Therefore, drugs that target epigenetic regulation may become a new direction for the development of antidepressants. Histone deacetylase inhibitors (HDACi) are a class of compounds that inhibit histone deacetylase activity, which has been reported to be associated with depression; this article addresses the use of HDACi in preclinical studies, and their potential therapeutic role and limitations of use in depression.
2.Influential factors for methylphenidate treatment compliance in children with attention deficit hyperactivity disorder.
Kai-Jing DING ; Yun-Fen LIU ; Chuan-Yuan KANG ; Rui-Xiang LIU ; Xue-Rong LI ; Shuai WAN
Chinese Journal of Contemporary Pediatrics 2013;15(5):343-347
OBJECTIVETo investigate influential factors for the tendency to medicate and medication compliance in children with attention deficit hyperactivity disorder (ADHD).
METHODSA total of 188 children aged from 5 to 16 years, who were initially diagnosed with ADHD according to DSM-IV criteria, were included in the study. They underwent symptom assessment and cognitive function test. The compliance of methylphenidate treatment was evaluated.
RESULTSPatients with better emotional state, and fewer oppositional and hyperactive behaviors and those who had a family history of psychiatric diseases and who obtained lower scores in the number cancellation test (NCT), were more prone to medication and/or exhibited better medication compliance. Logistic regression analysis showed that fewer oppositional and hyperactive behaviors and lower NCT scores were the predictive factors for a higher tendency to medicate, and a better emotional state was the predictive factor for better medication compliance. Patients of predominantly inattentive type were more prone to medication and showed better medication compliance, as compared with those of combined type. Gender, age and symptom severity were not associated with the tendency to medicate and/or medication compliance.
CONCLUSIONSThere is a need to enhance medication compliance in children with ADHD who have hyperactive, impulsive and oppositional behaviors, and to improve their long-term social functions.
Adolescent ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; psychology ; Central Nervous System Stimulants ; therapeutic use ; Child ; Child, Preschool ; Emotions ; Female ; Humans ; Logistic Models ; Male ; Medication Adherence ; Methylphenidate ; therapeutic use
3.Morphological and functional alterations of ear in lysosomal neuraminidase gene deficient mouse.
Yun-kai GUO ; Ding-hua XIE ; Xin-ming YANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2005;40(11):824-829
OBJECTIVETo observe the alterations of the auditory function and morphology of the ear in the mouse sialidosis models which has been generated by targeted deletion of lysosomal neuraminidase gene (Neul) and closely resembled the phenotypes in corresponding human conditions, and to explore pathophysiological mechanisms of hearing impairment.
METHODSNeul homozygous (Neul -/-) mice at 3 weeks, 2 and 4 months of age, and their wildtype littermates (Neu1 +/+) were examined for auditory thresholds through auditory brainstem responses (ABR) to click, 8, 16, and 32 kHz stimuli. Morphological analyses in ears were performed by series temporal bone section and light microscopy.
RESULTSNeul -/- mice at 3 weeks of age showed an elevated ABR threshold, 50-55 dB above those of Neul +/+ mice. Up to 2 and 4 months of age, their thresholds were further elevated for 60-68 dB. There were distinct pathological changes of middle and inner ear of 3 weeks of age in Neul -/- mice, especially at 2-4 months of age there were significant cerumen occlusion in the external auditory canal and severe otitis media. Vacuolation associated with lysosomal storage was observed within ossicles and cochlear bone cells, stria vascularis cells, spiral ganglion neurons and macrophages, spiral limbus, spiral prominence, Reissner's membrane cells, and the mesothelial cells of the perilymphatic scala and basilar membrane, but not within the organ of Corti. Vestibular ganglion neurons, hair cells and supporting cells in cristae and maculae also showed vacuolation.
CONCLUSIONSThe deficiency of lysosomal neuraminidase may result in a serious hearing loss and morphological alterations of ear. The external auditory canal obstruction, otitis media and ossicle changes may cause conductive hearing loss, and the defects in lysosomal storage of neurons, stria vascularis, spiral limbus, Reissner's membrane and basilar membrane cells may contribute to sensorineural deafness.
Animals ; Ear, Middle ; anatomy & histology ; pathology ; Evoked Potentials, Auditory, Brain Stem ; Hearing Loss ; pathology ; physiopathology ; Mice ; Mice, Knockout ; Mucolipidoses ; pathology ; physiopathology ; Neuraminidase ; genetics ; Otitis Media ; pathology
4.Effect of electroacupuncture and acupoint injection on expression of plasma proinflammatory cytokines and motilin for patients with early postoperative inflammatory intestinal obstruction.
Li-Ping SHEN ; Chun-Hua LEI ; Kai-Yun DING
Chinese Acupuncture & Moxibustion 2011;31(9):795-798
OBJECTIVETo verify the efficacy of electroacupuncture (EA) and acupoint injection on early postoperative intestinal obstruction and explore its mechanism.
METHODSOne hundred and sixteen cases were divided randomly into two groups. In control group (56 cases), the conventional western medicine was applied, including gastrointestinal decompression, parenteral nutrition (PN), anti-inflammation and supporting therapy. In observation group (60 cases), on the basis of the treatment as control group, EA and acupoint injection with Neostigmine were supplemented. Zusanli (ST 36), Shangjuxu (ST 37)/Xiajuxu (ST 39) and Dachangshu (BL 25) were selected as main points. Before treatment and after 3 days treatment, the levels of plasma interleukint (IL-6), tumor necrosis factor-alpha (TNF-alpha) and motilin (MOT) were determined.
RESULTSIn observation group, the mean recovery time of bowel sound and the mean frequency of passing gas were less than those in control group (both P < 0.01). After treatment, in either group, the levels of IL-6 and TNF-alpha were down-regulated as compared with those before treatment (all P < 0.01). After treatment, in observation group, IL-6 level was (15.2 +/- 4.1) pg/mL and TNF-alpha level was (18.3 +/- 6.5) pg/mL. They were (35.5 +/- 7.2) pg/mL and (52.7 +/- 12.3) pg/mL respectively in control group, indicating significant difference in statistics between two groups (both P < 0.01). In either group, MOT level increased after treatment as compared with that before treatment (both P < 0 01). After treatment, in observation group, the increase of MOT level was superior to that in control group [(190.7 +/- 48. 5 ) pg/mL vs (114.6 +/- 36.9) pg/mL, P < 0.01].
CONCLUSIONElectroacupuncture and acupoint injection are significantly effective in the treatment of early postoperative intestinal obstruction. This therapy may inhibit the release of inflammatory factors to reduce intestinal wall edema and it may promote MOT secretion to increase intestinal peristalsis. As a result, the recovery of gastrointestinal function is promoted.
Acupuncture Points ; Adult ; Aged ; Cytokines ; blood ; Electroacupuncture ; Female ; Humans ; Inflammation ; therapy ; Injections ; Intestinal Obstruction ; therapy ; Male ; Middle Aged ; Motilin ; blood ; Postoperative Complications ; therapy
5.Clinical observation on electroacupuncture combined with acupoint injection for treatment of early postoperative inflammatory intestinal obstruction.
Li-ping SHEN ; Juan GUAN ; Kai-yun DING
Chinese Acupuncture & Moxibustion 2010;30(1):27-30
OBJECTIVETo search for a better therapy for early postoperative inflammatory small bowel obstruction (EPISBO).
METHODSTwo hundred and forty cases were divided into four groups according to admitting order, 60 cases in each group. Routine treatments in western medicine were used in group A including gastrointestinal decompression, parenteral nutrition, anti-infection, supportive therapy and so on. Group B was treated with electroacupuncture in Zusanli (ST 36), Shangjuxu (ST 37) etc. in addition to those given in group A. Group C was treated with acupoint injection with Neostigmine in Dachangshu (BL 25), Zusanli (ST 36) etc. in addition to the treatment used in group A. Group D was treated with all of the treatments used in group A, B and C.
RESULTSThe total effective rate was 93. 3% in group A, 96. 7% in group B, 100.0% in group C and group D. There was no significant difference among the four groups (P>0. 05). The average recovery time of bowel sound was (11. 512. 9) days in group A, (9. 3 +/- 2.5) days in group B, (5.6 +/- 3.5) days in group C and (2. 2 +/- 1.7) days in group D. The average anal exsufflation time was (12. 5 +/- 3. 1) days in group A, (10. 7 +/- 3.6) days in group B, (7. 2 +/- 3. 1) days in group C and (2. 5 +/- 1. 5) days in group D. Group D was superior to those of other three groups obviously, and there were significant differences between them (all P<0. 01).
CONCLUSIONElectroacupuncture combined with acupoint injection has a satisfied therapeutic effect for treatment of EPISBO.
Acupuncture Points ; Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Electroacupuncture ; Female ; Humans ; Injections ; Intestinal Obstruction ; immunology ; surgery ; Male ; Middle Aged ; Neostigmine ; administration & dosage ; Postoperative Complications ; drug therapy ; immunology ; therapy ; Treatment Outcome
6.Orientation of three lysosomal enzymes in the mouse inner ear and hearing loss in enzyme gene deficiency.
Yun-kai GUO ; Ding-hua XIE ; Xin-ming YANG
Journal of Central South University(Medical Sciences) 2006;31(1):79-84
OBJECTIVE:
To determine the distribution and influence of lysosomal neuraminidase (Neul), protective protein/cathepsin A (PPCA) and beta-galactosidase (beta-gal) in the inner ear of the mouse, and to observe their auditory alterations in enzyme deficiency.
METHODS:
Six wild type (2 months postnatal) (Neu1+/+, PPCA+/+ and beta-gal+/+) mice were used, and Neu1, PPCA and beta-gal homozygous (Neu1-/-, PPCA-/- and beta-gal-/-) mice at the same age used as control in this experiment. The auditory thresholds were examined through the auditory brainstem responses (ABR) to click, which tone pips were 8, 16, and 32 kHz. The mice were intracardically perfused with 4% paraformaldehyde. The bulla were further fixed in 4% paraformaldehyde, processed and sectioned with paraffin embedded method. Immunohistochemistry was used to determine the cellular localizations of Neu1, PP-CA, and beta gal in the inner ear.
RESULTS:
There was a similar distributive pattern of Neu1, PPCA and betagal in the inner ear. Neu1 intense staining was observed in the cochlear spiral ganglion cells, spiral limbus, spiral ligament, vestibular ganglion cells, cristae, maculae hair cells, and weak staining in inner hair cells, outer hair cells, supplying cells of the organ of Corti and stria vascularis. The intense staining of PPCA and beta-gal were observed in the spiral ganglion and vestibular ganglion cells, and weak staining in the spiral limbus, spiral ligament, stria vascularis and organ of Corti. The inner ear exhibited no staining when Neul, PPCA and beta-gal were deficient, respectively. A positive staining of PPCA and beta-gal was presented in Neu1-/- mice, and as well as Neu1 and PPCA in beta-gal-/- mice. However, the staining of Neu1 was not presented, and only very weak staining of beta-gal in PPCA-/- mice. The auditory thresholds of Neul, PPCA, and beta-gal mice were elevated for 60-69 dB, 40-48 dB, and 7-10 dB above those of wildtype littermates, respectively.
CONCLUSION
Neu1 PPCA and beta-gal are distributed in the inner ear of mouse, and the three enzymes also form a lysosomal multi-enzyme complex in the inner ear. The respective enzyme deficiencies can induce the hearing the loss of different levels.
Animals
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Auditory Threshold
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Cathepsin A
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genetics
;
metabolism
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Ear, Inner
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enzymology
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Evoked Potentials, Auditory, Brain Stem
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physiology
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Hearing Loss, Sensorineural
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enzymology
;
genetics
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Lysosomes
;
enzymology
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Mice
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Mice, Knockout
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Neuraminidase
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genetics
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metabolism
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beta-Galactosidase
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genetics
;
metabolism
7.Identification of a novel mutation of F (13) A gene in a pedigree with factor XIII deficiency.
Wei-Yun JIAO ; Jing-Sheng WU ; Qiu-Lan DING ; Xue-Feng WANG ; Xiu-Cai XU ; Kai-Yang DING ; Xin LIU
Chinese Journal of Hematology 2007;28(9):598-601
OBJECTIVETo explore F (13) A gene mutation in a pedigree with hereditary coagulation factor XIII (FXIII) deficiency.
METHODSThe FXIII deficiency was diagnosed by clot solubility test and other standard laboratory clotting tests. All exons, exon-intron boundary sequences of F(13) A gene were amplified by PCR and the products were sequenced directly. Any mutation identified by direct sequencing was confirmed by reverse sequencing. The mutation identified in the proband was screened in the family members.
RESULTSThe assays of PT, Qiulan, fibrinogen leveling, platelet counts, bleeding time were normal and the clot solubility test was positive in the proband. The homozygous deletion of 33 nucleotides (127067de133) in exon 10 of F(13) A gene which resulted in deletion of 11 amino acids in FXIIII A protein with 720aa residues was identified in the proband. Family studies showed that the mutation was inherited from the parents both of whom carried the heterozygous deletion mutation.
CONCLUSIONThe homozygous 127067de133 mutation of F(13) A gene is responsible for the disorder of the pedigree.
Adolescent ; Factor XIII ; genetics ; Factor XIII Deficiency ; genetics ; Heterozygote ; Homozygote ; Humans ; Male ; Pedigree ; Sequence Deletion
8.Analytical surveys for epidemiological prevalence of fluorosis of brick-tea type in Sichuan Province in 2006
Xiao-jing, YANG ; Jia-yun, DENG ; Ding-you, ZHOU ; Jing, CHEN ; Dai-hua, LIANG ; Zai-yue, WANG ; Zhi-lin, HU ; Kai-hua, CHEN ; Yan-feng, QI ; Ding-chao, YANF ; Xiao-ming, YANG
Chinese Journal of Endemiology 2008;27(2):170-173
Objective To find out the status of brick-tea type fluorosis in the epidemic areas.Methods Based on "Scheme for Epidemiological Brick-tea Type Fluorosis in Sichuan Province",ten counties were selected in Sichuan brick-tea areas and ten towns were selected in every county,then the epidemicologic survey was performed in children of 8~12 year-old and adults aged above 20 years old.Results 5044 children and 4053 adults were selected from brick-tea areas.The rates of dental fluorosis in children and adults were 55.69%(2809/5044)and 60.41%(4053/6709)respectively.The dental fluorosis was mainly of mild damage.The skeletal fluorosis found in X-ray film was 44.64%(167/1241)and in clinical examination,38.94%(3883/9973).The levels of urine fluoride in children and adults were 1.88 and 2.78 mg/L.The level of urine fluoride was not differenet among children of different age,but in adults it was higher in the elder than the younger.The level of fluoride in urine was related to the severeness of skeletal fluorosis(r=0.74).The detective rates of skeletal fluorosis in agricuIture,pasturing,and agriculture-pasturing areaswere 31.70%(1369/4318),50.04%(1228/2454),and 40.17%(1286/3201),respectively.The X-ray detecting rates of skeletal fluorosis in men and wonlen were 49.57%(229/462)and 41.72%(325/779) respectively(χ2=11.72,P<0.05).Conclusion The prevalence of brick-tea type fluorosis is very serious in the regions studied.
9.Clinical observation of sensorineural hearing loss in patients suffering from nasopharyngeal carcinoma after radiotherapy.
Yun-kai GUO ; Xin-ming YANG ; Ding-hua XIE ; Qing-lai TANG ; Yong-de LU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2005;40(11):805-809
OBJECTIVETo study the extent and incidence of sensorineural hearing loss (SNHL) after radiotherapy (RT).
METHODSTwenty-eight patients with diagnosed nasopharyngeal carcinoma (NPC) were selected. The pure-tone audiography, auditory brain stem evoked response (ABR), impedance audiometry and evoked otoacoustic emissions (EOAE) recordings were performed before RT, 1 month, 1, 2 and 5 years after RT.
RESULTSAt 1 month after RT, there were 7.1 and 25.7 dB increased mean bone conduction (BC) thresholds at speech (0.5 - 4.0 kHz) and at high frequency (8.0 kHz), and their BC thresholds were statistically significant increase than those before RT, respectively (P < 0.001). At 1 year after RT, there were 17.6 and 28.1 dB increased respectively, and their thresholds were statistically significant increase than those at pre-irradiation (P < 0.001). There were also significant increases in thresholds than those at 1 month of post-irradiation (P <0.001 or P < 0.05). At 2 years after RT, 21 and 27.4 dB were increased at respective those two frequencies, and there was a statistically difference only at speech frequencies when compared with those at 1 year after RT (P < 0.05). At 5 years after RT, 26.7 and 35.8 dB were increased at these two frequencies, and there were significant increases in threshold than those before, 1 month, 1 and 2 years after RT, respectively (P < 0.001). From 1 month to 5 years after RT, 37. 5% to 94. 7% of ears had a BC hearing threshold of at least 15 dB losses at speech frequency, whereas the percentage at high frequency was 85.4 to 97.4%. Up to 63.2% and 73.7% of ears had 30 dB SNHL at least at speech and high frequency, respectively. Furthermore, the degree of mean threshold loss was greater at high frequency than at speech frequency. The mean value of wave I, III and V latency, and I -V interpeak latency intervals of ABR had no significant difference between at 1 month after RT and before RT (P > 0.05). The wave I , III and V latency, and I - V interpeak latency intervals at 1 year and 2 years were significantly prolonged when compared with those before and 1 month after RT (P < 0.05), but there were no significant difference between 1 year and 2 years after RT (P > 0.05). The wave I, III and V latency, and I -V interpeak latency intervals at 5 years after RT were also significantly longer than those before RT (P < 0.001). There were significant difference in wave I , III and V latency (P < 0.05), and no significant difference in wave I - V interpeak latency intervals (P > 0. 05) between 5 years after RT and 1 year or 2 years after RT. Seven of 10 ears at 1 year after RT and 4 of 7 ears at 5 years after RT had normal EOAE, but they all had abnormal ABR response.
CONCLUSIONSSNHL in NPC patients start soon after completion of RT, especially more commonly in high frequency. The incidence and the extent of hearing loss are increased with time of follow-up. The hearing impairment could occur in the cochlea and/or the retrocochlear auditory pathway, which show that the sensitivity of radiation damage may be different in different patient and anatomic site of auditory system.
Adult ; Audiometry ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Loss, Sensorineural ; etiology ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Otoacoustic Emissions, Spontaneous ; Radiotherapy ; adverse effects
10.Optimum selection of acupuncture treatment programs of cerebral infarction and its effects on insulin resistance.
Ding-jian HUANG ; Biao LIU ; Shang-jie CHEN ; Kai-bin ZHOU ; Wen CHEN ; Wei-hua DOU ; Lin ZHOU-JIE ; Yun-zhu LIU ; Ben-hua LUO
Chinese Acupuncture & Moxibustion 2005;25(2):79-81
OBJECTIVETo study the optimum acupuncture treatment program and the mechanism for treatment of cerebral infarction.
METHODSSixty-three cases were randomly divided into 9 groups. The four factors, times of manipulation, the retaining time of the needle, acupuncture instrument and acupoints,and their corresponding three levels were adopted respectively in treatment of each group. Then nerve function defect score and insulin resistance were observed before and after treatment.
RESULTSThe acupoints, the times of manipulation and the retaining time of the needle have significant effects on nerve function defect and insulin resistance (P < 0.01 or P < 0.05), and the acupuncture instrument has a significant effect on insulin resistance (P < 0.01). The choice of acupoints was the most important factor for acupuncture treatment of cerebral infarction.
CONCLUSIONAcupuncture for regulating The Governor Vessel with twice manipulations and retaining the needle for 60 min is optimum treatment program for cerebral infarction. The good regulating effect of acupuncture on insulin resistance is one of the mechanisms of achieving the therapeutic results.
Acupuncture Points ; Acupuncture Therapy ; Cerebral Infarction ; Humans ; Insulin Resistance ; Needles