1.Tiaoshen Guben holistic therapy of acupuncture and moxibustion for 24 cases of comorbidity of depression and insomnia.
Zhongxian LI ; Pan ZHANG ; Qiaoyu JI ; Min PENG ; Zitong JIAO ; Yifu ZHOU ; Junquan LIANG ; Luda YAN ; Wenbin FU ; Peng ZHOU
Chinese Acupuncture & Moxibustion 2025;45(11):1559-1564
OBJECTIVE:
To observe the clinical effect of Tiaoshen Guben holistic therapy of acupuncture and moxibustion (holistic treatment with acupuncture and moxibustion by adjusting the mind and consolidating the root) on comorbidity of depression and insomnia.
METHODS:
Twenty-four patients with comorbidity of depression and insomnia were included and treated with Tiaoshen Guben holistic therapy of acupuncture and moxibustion. Acupuncture was applied to Baihui (GV20), Guanyuan (CV4), bilateral Neiguan (PC6), etc. The refined moxibustion therapy was delivered at Zhongwan (CV12), Qihai (CV6), bilateral Yongquan (KI1), etc. Subcutaneous embedding therapy with thumb-tack needle was adopted at bilateral Xinshu (BL15), bilateral Pishu (BL20), etc. The intervention was operated once every other day, 3 treatments a week, and for 6 consecutive weeks. Before and after treatment completion, and in 1 month after treatment, Pittsburgh sleep quality index (PSQI) and Hamilton's depression scale (HAMD-17) were adopted to assess sleep quality and depression symptoms in the patients, respectively. Before and after treatment completion, using functional magnetic resonance imaging (fMRI), the functional connectivity (FC) of locus coeruleus (LC) in brain regions was evaluated; and the levels of serum norepinephrine (NE), cortisol (CORT), adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) were detected.
RESULTS:
Compared with the scores before treatment, PSQI and HAMD-17 scores after treatment completion and in 1 month after treatment were reduced (P<0.01); and strengthened FC was revealed between the right LC and the pars opercularis of the left inferior frontal gyrus, as well as the lateral occipital lobe region. After treatment completion, serum NE was elevated (P<0.01), the levels of CORT, ACTH and CRH were reduced (P<0.01). Before and after treatment completion, the difference in FC between the right LC and the pars opercularis of the left inferior frontal gyrus was negatively correlated with the differences in PSQI score (r = -0.484, P = 0.016) and HAMD-17 score (r = -0.233, P = 0.027).
CONCLUSION
Tiaoshen Guben holistic therapy of acupuncture and moxibustion can effectively alleviate depression symptoms and improve sleep quality in the patients with comorbidity of depression and insomnia, which is obtained probably through reducing the levels of serum CORT, ACTH and CRH, increasing serum NE, strengthening the FC of the right LC with the pars opercularis of the left inferior frontal gyrus and the lateral occipital lobe region.
Humans
;
Moxibustion
;
Sleep Initiation and Maintenance Disorders/therapy*
;
Male
;
Female
;
Middle Aged
;
Adult
;
Acupuncture Therapy
;
Depression/complications*
;
Aged
;
Young Adult
;
Acupuncture Points
;
Comorbidity
2.Research progress on the effect of α7 nicotinic acetylcholine receptor on perioperative neurocognitive function
Shang-Kun SI ; Ying-Xue XU ; Wei-Liang ZHANG ; Jia-Fu JI ; Dong-Bin ZHANG
Medical Journal of Chinese People's Liberation Army 2024;49(3):343-348
α7 nicotinic acetylcholine receptor(α7nAChR)is widely expressed in the central nervous system and immune system,and plays a neuro-immunoregulatory role.On the one hand,α7nAChR is involved in the transmission of neurotransmitters,the conduction of excitatory signals and the maintenance of synaptic plasticity,which is of great significance for maintaining the normal and stable neurocognitive function.On the other hand,as an important part of the cholinergic anti-inflammatory pathway,α7nAChR is involved in the regulation of physiological and pathological processes such as inflammatory response,oxidative stress,apoptosis and autophagy in the central system,and plays an immunomodulatory and neuroprotective role,thus being potential target for improving perioperative neurocognitive function.This article reviews the biological characteristics of α7nAChR and its effect on perioperative neurocognitive function,in order to provide ideas and methods for clinical improvement of perioperative neurocognitive function in surgical patients.
3.Clinical effect of ultra-early endovascular treatment of ruptured tiny intracranial aneurysms
Ying SONG ; Jian LIU ; Fangyuan JI ; Liang ZHANG ; Hui FU
Journal of Clinical Surgery 2024;32(10):1091-1094
Objective To evaluate the clinical effect of ultra-early endovascular treatment of ruptured tiny intracranial aneurysms(RTIAs).Methods A total of 35 patients with RTIAs who were treated with endovascular embolization within 24 hours after subarachnoid hemorrhage in our department from May 2017 to November 2022 were retrospectively analyzed.The basic clinical information,endovascular treatment results,clinical and imaging follow-up results were analyzed.Results The mean aneurysms maximum diameter is was(2.5±0.4)mm.Of these 35 patients with RTIAs,23 patients(65.7%)were treated with simple coil embolization,12 patients(34.3%)with stent assisted coiling.Immediate angiographic results showed that Raymond grade Ⅰ in 20 patients(57.1%),Ⅱ in 13(37.2%),Ⅲ in 2(5.7%).Perioperative complications occurred in 4 patients(11.4%),including Intraoperative aneurysm rupture in 2(5.7%),intra-stent thrombosis in 2(5.7%),massive cerebral infarction followed by decompressive craniectomy in 1,postoperative death in 1.Angiographic follow-up was performed in 24 patients(68.6%),recurrence in 1 patient receiving retreatment.Clinical follow-up were performed in 33 patients,The mRS of 0-2 were in 31 patients(93.9%).Conclusion Ultra-early endovascular treatment of RTIAs is effective and relatively safe,with favorable angiographic results and clinical outcomes at follow up.Intraoperative aneurysm rupture and thrombosis are the major perioperative complications.
4.The factors affecting pathological complete response of triple negative breast cancer patients after neoadjuvant chemotherapy and the construction of related model
Liu YANG ; Fu-Qing JI ; Ming-Kun ZHANG ; Zhe WANG ; Ju-Liang ZHANG
Medical Journal of Chinese People's Liberation Army 2024;49(8):855-860
Objective To analyze the factors affecting pathological complete response(pCR)of triple-negative breast cancer(TNBC)patients after neoadjuvant chemotherapy,and construct a nomogram to forecast the pCR rate.Methods The clinical and pathological data of 348 TNBC patients who received neoadjuvant chemotherapy in the Air Force Medical University-Affiliated Xijing Hospital from May 2018 to May 2021 were collected and set as modeling set.The clinical and pathological data of 69 TNBC patients who received neoadjuvant chemotherapy in the Xi'an No.3 Hospital from May 2018 to May 2021 were collected and set as validation set.The clinical and pathological characteristics were compared between the modeling set and the validation set.In the modeling set,the independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy were screened by LASSO regression model analysis,and the nomogram model was constructed.Internal validation of the model was conducted using Bootstrap method,and the discrimination of the model was assessed by receiver operating characteristic(ROC)curve.The accuracy of the model was evaluated by the calibration curve and the clinical benefits and application value of the model were evaluated by clinical decision curve analysis(DCA).Results There were significant differences in surgical method and T stage between the patients in modeling set and validation set(P<0.05).The results of analysis of LASSO regression model showed that T stage,N stage,the use of platinum drugs and clinical efficacy evaluation were independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy(P<0.05).Based on the above variables,the nomogram models were constructed.In modeling set,area under curve(AUC)was 0.811(95%CI 0.763-0.859);in validation set,AUC was 0.801(95%CI 0.727-0.928).The Bootstrap method showed the C-index for internal validation was 0.79,indicating the model has good discrimination in both the modeling and validation sets.The calibration curve analysis showed that model predicted pCR rates had a good consistency with the actual observed values,and the DCA showed that model can bring clinical benefit.Conclusion The nomogram can accurately predict the pCR rates of TNBC patients after neoadjuvant chemotherapy and provide scientific basis for clinical diagnosis and treatment.
5.Targeted Metabonomics Combined with 16SrRNA Gene Sequencing to Analyze the Effect of Rehmanniae Radix on Intestinal Flora in Rats with Kidney Yin Deficiency Syndrome Before and After Processing
Xueke YE ; Guoshun SHAN ; Yu FU ; Ji SHI ; Yi YU ; Ming LIANG ; Wei YAO
Traditional Chinese Drug Research & Clinical Pharmacology 2023;34(12):1700-1712
Objective To investigate the effects of Rehmanniae Radix before and after processing on the intestinal flora of rats with kidney yin deficiency syndrome.Methods SD rats were randomly divided into blank group,model group,probiotic group(0.35 g·kg-1),high-/medium-/low-dose groups of Rehmanniae Radix Praeparata(3.5,1.75,0.875 g·kg-1),and high-/medium-/low-dose groups of Rehmanniae Radix(3.5,1.75,0.875 g·kg-1),with 9 rats in each group.Except for the blank group,rats in each group were injected intramuscularly with Dexamethasone Sodium Phosphate Injection(0.35 mg·kg-1)once a day for 21 days.The drug was administered by gavage once a day on the seventh day of modelling for 14 days.The adrenal histopathological changes were observed by using HE staining;the levels of serum cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),and corticosterone(CORT)were detected by ELISA;and the levels of short-chain fatty acids in the feces and changes in the diversity of intestinal flora were detected by a targeted metabolomic approach in conjunction with 16SrRNA sequencing in the rats in each group.Results(1)Compared with the blank group,the body mass of rats in the model group was significantly decreased on days 7,14 and 21(P<0.05,P<0.01);serum levels of cAMP,CRH,ACTH,CORT and the cAMP/cGMP ratio were all significantly increased(P<0.01),and the cGMP content was significantly decreased(P<0.01);and the adrenal cortex was thinned,with the boundaries of various layers of the cortex unclear.Compared with the model group,the body mass of rats in the Rehmanniae Radix Praeparata administration group on day 21 were all significantly increased(P<0.05,P<0.01),and the serum content of cAMP,CRH,ACTH,CORT and the cAMP/cGMP ratio were all significantly decreased(P<0.05,P<0.01),and the content of cGMP was significantly increased(P<0.05,P<0.01)in the rats;body mass of rats in the Rehmanniae Radix administration group did not change significantly(P>0.05),CRH and CORT contents in serum of rats in the high-dose group of Rehmanniae Radix were significantly reduced(P<0.01),and ACTH contents in serum of rats in the medium-dose group of Rehmanniae Radix were significantly reduced(P<0.05);the adrenal cortex of rats in all the administration groups were improved,in particular,the thickening of the adrenal cortex layers was obvious in the Rehmanniae Radix Praeparata group,and the improvement effect was superior to that in the Rehmanniae Radix group.(2)Compared with the blank group,the difference of Coverage index was not statistically significant(P>0.05),and the coverage of each group was good;the abundance index(Sobs,Ace,Chao)and diversity index(Shannon)of the model group were significantly increased(P<0.01),and the Simpson index was significantly decreased(P<0.01).Compared with the model group,Sobs index was significantly decreased in the medium-and high-dose groups of Rehmanniae Radix Praeparata(P<0.05),Chao index was significantly decreased in the administered groups of Rehmanniae Radix Praeparata and high-dose group of Rehmanniae Radix(P<0.05,P<0.01),and Simpson index was significantly increased in the high-dose group of Rehmanniae Radix Praeparata(P<0.05).The changes of Rehmanniae Radix on the richness and diversity of intestinal microbial community in kidney yin-deficient rats were small,while Rehmanniae Radix Praeparata could better maintain the stability of the richness and diversity of intestinal microbial community in kidney yin-deficient rats.(3)Compared with the blank group,the abundance of phylum firmicutes in the feces of the model group was significantly decreased,while the abundance of bacteroides and actinomycetes was significantly increased.The abundance of Lactobacillus was significantly decreased(P<0.01),while the abundance of norank_f__Muribaculaceae and Bifidobacterium was significantly increased(P<0.01).Compared with the model group,the trend of recovery of bacterial abundance in the probiotic group and the high-dose group of Rehmanniae Radix Praeparata was more similar to that of the blank group,which showed that it had the best regulating effect on the ratio of bacterial flora;the abundance of lactobacillus in all administered groups was increased,with that of the probiotic group was significantly increased(P<0.01);the abundance of norank__f__Muribaculaceae and Bifidobacterium were all decreased,among which the probiotic group and the medium-and high-dose groups of Rehmanniae Radix Praeparata were significantly decreased(P<0.01),and the effect was significantly superior to that of Rehmanniae Radix.The COG functions of the samples in each group were mainly focused on amino acid transport and metabolism,carbohydrate transport and metabolism,translation,ribosomal structure and biogenesis,replication,recombination and repair,but the abundance information of each function was different between groups,which may be due to the differences caused by dysbiosis of intestinal flora.(4)Compared with the blank group,the levels of acetic acid,butyric acid and propionic acid in the faeces of rats in the model group were significantly decreased(P<0.05,P<0.01),and the level of isobutyric acid was significantly increased(P<0.01).Compared with the model group,the levels of acetic acid,butyric acid and propionic acid in the faeces of rats in the probiotic group and the low-,medium-and high-dose groups of Rehmanniae Radix Praeparata were significantly increased(P<0.05,P<0.01)and the levels of isobutyric acid were significantly decreased(P<0.05,P<0.01);although the above indexes in the Rehmanniae Radix group were improved,the difference was not statistically significant(P>0.05).Conclusion The enhanced therapeutic effect of Rehmanniae Radix after processing on rats with kidney yin deficiency syndrome may be related to its adjusting effect on intestinal flora.
6.Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years.
Ya Wei LI ; Zheng LI ; Hao Can SONG ; Liang DING ; Sai Sai JI ; Miao ZHANG ; Ying Li QU ; Qi SUN ; Yuan Duo ZHU ; Hui FU ; Jia Yi CAI ; Chen Feng LI ; Ying Ying HAN ; Wen Li ZHANG ; Feng ZHAO ; Yue Bin LYU ; Xiao Ming SHI
Chinese Journal of Preventive Medicine 2023;57(5):686-692
Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.
Humans
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Male
;
Arsenic/urine*
;
Creatinine
;
East Asian People
;
Testosterone/blood*
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Urinalysis
;
Adolescent
;
Young Adult
;
Adult
;
Middle Aged
;
Aged
7.Study on the effect of personal radiological protective equipment used in diagnostic radiology
Qiang FU ; Lu WANG ; Yue XI ; Liang SUN ; Shengrong JI ; Zhonghao REN ; Jia WANG ; Bing LIU
Chinese Journal of Radiological Medicine and Protection 2023;43(6):462-468
Objective:To study the actual effect of the use of personal protective equipment of the examined individuals, and provide reference and basis for the correct use of personal protective equipment and the radiological health administrative law enforcement.Methods:From February to June 2022, the imaging department of Qingdao Municipal Hospital selected 170 patients who underwent X-ray imaging examination (oral panoramic, dental radiography, DR photography, CT scanning), including 25 with oral panoramic and dental radiography, 60 with CT scanning and 60 with DR imaging. The thermoluminescent dosimeter was used to detect the ambient dose equivalent at the point of concern for 170 examined individuals who have used personal protective equipment to cover their sensitive parts, and to analyze the data detected at the same point as above when routinely using the same equipment.Results:There was a statistically significant difference in the dose equivalent at the same points inside and outside the lead neckband ( t=-2.23, P<0.05). There was no statistically significant difference in the dose equivalent at the same point inside and outside the lead collar during dental radiography ( P>0.05). During DR photography (chest PA, lateral and lumbar AP), the examined individuals were wearing lead aprons. Among them, there was a statistically significant difference in the dose equivalent at the same points inside and outside the lead aprons of children′s chest PA and adults′ chest PA ( U=10.00, 19.00, P<0.05). There was no statistically significant difference in the dose equivalent at the same points inside and outside the lead aprons of adult′s chest PA and lumbar AP ( P>0.05). When performing CT scan (chest or upper abdomen), there was a statistically significant difference in the dose equivalent at the same points of wrapped lead aprons( U=878.50, 11.00, P<0.05). Conclusions:The correct use of personal protective equipment is a complex technical problem. It is very important to fully and accurately understand the optimization principle of radiation protection and correctly use personal protective equipment for the examined individuals. The administrative punishment of radiation health on the use of personal protective equipment of the examined individuals should be cautious.
8.Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial.
Lu-da YAN ; Zhong-Xian LI ; Yu ZHANG ; Xue-Song LIANG ; Jing-Jing LI ; Miao WU ; Guo-Ao SHI ; Rui-Ming CHEN ; Xiang JI ; Si-Yao ZUO ; Shi-Yun CHEN ; Peng ZHOU ; Wen-Bin FU
Chinese Acupuncture & Moxibustion 2023;43(3):255-260
OBJECTIVE:
To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.
METHODS:
Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.
RESULTS:
After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).
CONCLUSION
Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans
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Depression
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Quarantine
;
Serotonin
;
Sleep Initiation and Maintenance Disorders
;
COVID-19
;
Acupuncture Therapy
;
Comorbidity
9.Multimorbidity Pattern and Risk for Mortality Among Patients With Dementia: A Nationwide Cohort Study Using Latent Class Analysis
Che-Sheng CHU ; Shu-Li CHENG ; Ya-Mei BAI ; Tung-Ping SU ; Shih-Jen TSAI ; Tzeng-Ji CHEN ; Fu-Chi YANG ; Mu-Hong CHEN ; Chih-Sung LIANG
Psychiatry Investigation 2023;20(9):861-869
Objective:
Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk.
Methods:
This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate.
Results:
With adjustment for age, a three-class model was identified, with 42.7% of participants classified as “low comorbidity class (cluster 1)”, 44.2% as “cardiometabolic multimorbidity class (cluster 2)”, and 13.1% as “FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract).” The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708–14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281–1.953; p<0.001) in cluster 3.
Conclusion
Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.
10.Role of hyperglycemia-induced 5-hydroxytryptamine degradation of hepatic stellate cells in hepatic inflammation and fibrosis induced by type 2 diabetes mellitus.
Xiu Rui LIANG ; Xue Chun SHAN ; Jing GUAN ; Rui ZHANG ; Jing YANG ; Yi ZHANG ; Jia Qi JIN ; Yu Xin ZHANG ; Fan XU ; Ji Hua FU
Journal of Peking University(Health Sciences) 2022;54(6):1141-1150
OBJECTIVE:
To explore the role of 5-hydroxytryptamine (5-HT) in type 2 diabetes mellitus (T2DM)-related hepatic inflammation and fibrosis.
METHODS:
Male C57BL/6J mice were used to establish T2DM model by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. Then, the mice with hyperglycemia were still fed with high-fat diet for nine weeks, and treated with or without 5-HT2A receptor (5-HT2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (alone or in combination). To observe the role of 5-HT in the myofibroblastization of hepa-tic stellate cells (HSCs), human HSCs LX-2 were exposed to high glucose, and were treated with or without SH, CDP or monoamine oxidase A (MAO-A) inhibitor clorgiline (CGL). Hematoxylin & eosin and Masson staining were used to detect the pathological lesions of liver tissue section, immunohistochemistry and Western blot were used to analyze protein expression, biochemical indicators were measured by ELISA or enzyme kits, and levels of intracellular reactive oxygen species (ROS) were detected by fluorescent probe.
RESULTS:
There were up-regulated expressions of 5-HT2AR, 5-HT synthases and MAO-A, and elevated levels of 5-HT in the liver of the T2DM mice. In addition to reduction of the hepatic 5-HT levels and MAO-A expression, treatment with SH and CDP could effectively ameliorate liver lesions in the T2DM mice, both of which could ameliorate hepatic injury and steatosis, significantly inhibit the increase of hepatic ROS (H2O2) levels to alleviate oxidative stress, and markedly suppress the production of transforming growth factor β1 (TGF-β1) and the development of inflammation and fibrosis in liver. More importantly, there was a synergistic effect between SH and CDP. Studies on LX-2 cells showed that high glucose could induce up-regulation of 5-HT2AR, 5-HT synthases and MAO-A expression, increase intracellular 5-HT level, increase the production of ROS, and lead to myofibroblastization of LX-2, resulting in the increase of TGF-β1 synthesis and production of inflammatory and fibrosis factors. The effects of high glucose could be significantly inhibited by 5-HT2AR antagonist SH or be markedly abolished by mitochondrial 5-HT degradation inhibitor CGL. In addition, SH significantly suppressed the up-regulation of 5-HT synthases and MAO-A induced by high glucose in LX-2.
CONCLUSION
Hyperglycemia-induced myofibroblastization and TGF-β1 production of HSCs, which leads to hepatic inflammation and fibrosis in T2DM mice, is probably due to the up-regulation of 5-HT2AR expression and increase of 5-HT synthesis and degradation, resulting in the increase of ROS production in mitochondria. Among them, 5-HT2AR is involved in the regulation of 5-HT synthases and MAO-A expression.
Male
;
Mice
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Humans
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Animals
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Hepatic Stellate Cells/pathology*
;
Transforming Growth Factor beta1/pharmacology*
;
Serotonin/metabolism*
;
Reactive Oxygen Species/metabolism*
;
Diabetes Mellitus, Type 2/complications*
;
Hydrogen Peroxide/metabolism*
;
Mice, Inbred C57BL
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Liver Cirrhosis/etiology*
;
Hyperglycemia/pathology*
;
Monoamine Oxidase/metabolism*
;
Inflammation
;
Glucose/metabolism*
;
Cytidine Diphosphate/pharmacology*

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