The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.
Humans ; Morphine/pharmacology* ; Hyperalgesia/metabolism* ; Analgesics, Opioid/pharmacology* ; Neurons/metabolism* ; Signal Transduction

Mechanical allodynia (MA), including punctate and dynamic forms, is a common and debilitating symptom suffered by millions of chronic pain patients. Some peripheral injuries result in the development of bilateral MA, while most injuries usually led to unilateral MA. To date, the control of such laterality remains poorly understood. Here, to study the role of microglia in the control of MA laterality, we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice. Surprisingly, the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA. Moreover, in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons. Consistent with behavioral results, microglial depletion did not prevent the opening of bilateral gates for Aβ pathways in the superficial dorsal horn. This study challenges the role of microglia in the control of MA laterality in mice. Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.
Mice ; Animals ; Hyperalgesia/metabolism* ; Microglia/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Spinal Cord Dorsal Horn/metabolism* ; Ganglia, Spinal/metabolism*

ObjectiveTo explore the improvement effect of Flos Puerariae， Hoveniae Semen， and their compatibility on acute alcoholic gastric mucosal injury， and lay a foundation for further development of Flos Puerariae， Hoveniae Semen， and their compatibility in the prevention and treatment of alcohol-induced multiple organ injury. MethodThe acute alcohol-induced gastric mucosal injury model of mice was established by multiple intragastric administration of 56% Hongxing Erguotou liquor （15 mL·kg^-1）. A total of 120 male ICR mice were randomly divided into 8 groups， namely， the blank group， model group， omeprazole group （0.026 g·kg^-1）， Flos Puerariae-Hoveniae Semen （compatibility） high， medium， and low-dose groups （29.2，14.6， 7.3 g·kg^-1）， Flos Puerariae group （19.5 g·kg^-1）， and Hoveniae Semen group （19.5 g·kg^-1）， with 15 mice in each group. After one week of adaptive feeding， the animals were pre-administrated with the corresponding drug at the rate of 10 mL·kg^-1 for 3 d. From the 4^th day， after 1 h of administration， Erguotou liquid was administrated at the rate of 15 mL·kg^-1 and the blank group was administrated with the same volume of deionized water to record the drunkenness and sober up time. The administration was lasted for 3 d. One hour after the last administration， the eyeballs were removed and the mice were sacrificed. The concentration of ethanol in serum was determined by gas chromatograph， and the activity of ethanol dehydrogenase （ADH） in gastric mucosa was determined by ultraviolet-vis spectrophotometer. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in gastric mucosa. Serum inflammatory factors were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of nuclear transcription factor-κB （NF-κB） p65 and NF-κB inhibitory protein α （IκBα） were detected by real-time polymerase chain reaction （Real-time PCR）. ResultAs compared with the normal group， the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in serum of mice in the model group was increased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues was increased （P<0.01）， and the mRNA expression of IκBα was decreased （P<0.01）. As compared with the model group， the drunkenness time of the omeprazole group， high and medium-dose compatibility groups， and Flos Puerariae group was prolonged （P<0.05）， the sober up time of the high and medium-dose compatibility groups was shortened （P<0.05）， the ethanol concentration in the serum of the high-dose compatibility group was decreased （P<0.05）， the ADH activity in the gastric mucosa of the omeprazole group and high and medium-dose compatibility groups was increased （P<0.05）， the macroscopic injury score of the high， medium， and low-dose compatibility groups and Flos Puerariae group was decreased （P<0.05）， the score of pathological injury in the omeprazole group， high， medium， and low-dose compatibility groups， and Flos Puerariae group was decreased （P<0.01）， the expression of IL-6 in serum of all drug groups was decreased （P<0.05）， the expression of IL-1β in serum of the omeprazole group， high， medium， and low-dose Flos Puerariae groups， and Hoveniae Semen group was decreased （P<0.05）， the expression of TNF-α in serum of high and medium-dose groups was decreased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues of all drug groups was decreased （P<0.05）， and the mRNA expression of IκBα in gastric mucosa tissues of the omeprazole group and high， medium， and low-dose compatibility groups was increased （P<0.05）. As compared with the high-dose compatibility group， the drunkenness time in the low-dose compatibility group and Hoveniae Semen group was shortened （P<0.01）， the sober up time in the Flos Puerariae and Hoveniae Semen groups was prolonged （P<0.01）， the concentration of ethanol in the serum of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group increased （P<0.05）， the macroscopic injury score of the medium and low-dose compatibility groups and Hoveniae Semen group was increased （P<0.05）， the pathological injury score of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， the content of IL-1β in serum of low-dose compatibility group， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， and the mRNA expression of IκBα in gastric mucosa of the Flos Puerariae group and Hoveniae Semen group was decreased （P<0.05）. As compared with the medium-dose compatibility group， the drunkenness time in the Hoveniae Semen group was shortened （P<0.05）， the sober up time in the Flos Puerariae group was prolonged （P<0.05）， the pathological injury score in the Flos Puerariae group and Hoveniae Semen group was increased （P<0.01）， and the content of IL-1β in serum of the low-dose compatibility group， the Flos Puerariae group， and Hoveniae Semen group was increased （P<0.05）. As compared with the low-dose compatibility group， the pathological injury score of the Hoveniae Semen group was increased （P<0.05）. ConclusionFlos Puerariae， Hoveniae Semen， and their compatibility play a role in preventing and treating acute alcoholic gastric mucosal injury in mice， which may be related to the inhibition of the expression of NF-κB signal pathway in gastric mucosa， and the high-dose compatibility group has the optimal effect.

OBJECTIVE: To compare the clinical efficacy of initial periodontal therapy in periodontitis patients with or without type 2 diabetes mellitus and its correlation with white blood cell counts. METHODS: In this study, 32 chronic periodontitis patients without systemic disease (CP group) and 27 chronic periodontitis patients with type 2 diabetes mellitus (CP+DM group) were enrolled. At admission, all the patients went through periodontal examination and fasting blood examination(baseline). Probing depth (PD), attachment loss (AL), bleeding index (BI), plaque index (PLI), white blood cells (WBC) counts and fasting blood glucose (FBG) were recorded respectively, while hemoglobin A1c (HbA1c) was recorded only in CP+DM group. After that, initial periodontal therapy was performed. All the tests were repeated 3 and 6 months after treatment. The changes of periodontal clinical indexes and WBC levels were compared between the two groups before and after treatment, and the correlation between WBC and periodontal clinical indexes and glucose metabolism indexes were analyzed by generalized linear mixed model. RESULTS: At baseline, the periodontal inflammation and destruction were similar in CP and CP+DM group, but the WBC level was significantly higher in CP+DM groups [(6.01±1.26)×10⁹/L vs. (7.14±1.99)×10⁹/L, P=0.01]. After 3 and 6 months of initial periodontal therapy, the mean PD, AL, BI, and PLI in CP+DM and CP groups were significantly lower than the baseline, and the PD in CP+DM group was further decreased by 6 months compared with 3 months [(3.33±0.62) mm vs. (3.61±0.60) mm, P < 0.05]. However, none of these periodontal indexes showed significant difference between the two groups by 3 or 6 months. In CP+DM group, HbA1c at 3 months and 6 months were significantly lower than the baseline [(7.09±0.79)% vs. (7.64±1.16)%, P < 0.05; (7.06±0.78)% vs. (7.64±1.16)%, P < 0.05], and FBG was significantly lower than the baseline by 6 months [(7.35±1.14) mmol/L vs. (8.40±1.43) mmol/L, P < 0.05]. The WBC level in CP group was significantly lower than the baseline level by 3 months [(5.35±1.37)×10⁹/L vs. (6.01±1.26)×10⁹/L, P < 0.05], while that in CP+DM group was significantly lower than the baseline level by 6 months [(6.00±1.37)×10⁹/L vs. (7.14±1.99)×10⁹/L, P < 0.05]. The analysis of genera-lized linear mixed model showed that WBC level was significantly positively correlated with PD and FBG (P < 0.05). CONCLUSION Initial periodontal therapy can effectively improve the periodontal clinical status of patients with or without type 2 diabetes mellitus, and have benefits on glycemic control in diabetic patients. However, the response of periodontal indexes and WBC level to initial therapy were relatively delayed in diabetic patients. WBC plays an important role in the correlation between diabetes mellitus and periodontitis.
Chronic Periodontitis/therapy* ; Diabetes Mellitus, Type 2/complications* ; Glycated Hemoglobin A/analysis* ; Humans ; Leukocytes/chemistry* ; Periodontal Index

Objective To establish bovine corneal opacity and permeability （BCOP） test， and determine its predictive ability for the eye irritation evaluation of cosmetics. Methods A total of ten reference chemicals were selected to establish the BCOP test. Then eye irritation of 16 routinely collected cosmetics in our laboratory was predicted. In vitro scores were calculated by the change in the opacity and sodium fluorescein permeability after exposure to the testing cosmetics， and subsequently compared with the historical data by Draize test. Results Reference chemicals with known irritation classification were correctly classified by the BCOP test， which was consistent with the classification of UN globally harmonized system of classification and labeling of chemicals. Moreover， the specificity of the BCOP test for the classification of non-irritating cosmetics samples was 80.0% （8/10）， and the sensitivity for weak to mild irritating cosmetics samples was 83.3% （5/6）. The BCOP test demonstrated an overall classification consistency of 81.3% （13/16） with in vivo test. Conclusion BCOP test may be independently used to identify chemicals with potential eye irritation and serious eye damage， suggesting it is significant for in vitro integrated test strategy for predicting eye irritation due to cosmetics.

As the increasing population aging,the incidence of age-related macular degeneration is increasing,blinding rate also increasing,so it is very important for the early diagnosis and treatment of age-related macular degeneration.There are many methods to check the aging macular degeneration,such as fundus angiography,optical coherence tomography (OCT),visual field and multifocal electroretinogram (mfERG).In recent years,many emerging ophthalmic methods have emerged and are gradually applied to clinical diagnosis,including optic coherence tomography angiography (OCTA).The function of these methods has its unique advantages,but there are also limitations.This paper will review these existing methods.

BACKGROUND:Jumonji domain-containing histone demethylase (JMJD) can promote osteoblast differentiation, and estrogen-related receptor alpha (ERRα) can promote osteoblast differentiation and increase bone formation. However, little is reported on the association between postmenopausal osteoporosis andJMJD and ERRα. OBJECTIVE: To study the changes in the JMJD2 family expression in patients with postmenopausal osteoporosis. METHODS: Postmenopausal patients with osteoarthritis of the hip scheduled for total hip arthroplasty, aged 50-70 years, were enroled, including 10 postmenopausal osteoporosis patients (experimental group) and 10 patients with no postmenopausal osteoporosis (control group). During the arthroplasty, the cancelous bone specimens from the femoral head were colected. Then, immunohistochemistry and western blot assay were used to detect expression of histone demethylase (JMJD2A, JMJD2B), histone methylation (H3K9me3, H3K36me3) and ERRα. RESULTS AND CONCLUSION:In the experimental group, the expressions of JMJD2A, JMJD2B and ERRαwere from weakly positive to positive; these expressions were significantly lower in the experimental group than the control group (P < 0.05). The expressions of H3K9me3 and H3K36me3 were significantly higher in the experimental group than the control group (P < 0.05). These findings indicate that the expression of JMJD2A and JMJD2B is consistent with the expression of ERRα in the patients with postmenopausal osteoporosis, and JMJD is likely to serve as an antagonistic enzyme of osteoporosis.

Objective To compare the MRI manifestations and characteristics of ≤ 3 cm nonepithelial hepatic angiomyolipomas (HAML)and small hepatocellular carcinoma (SHCC),then improve the preoperative diagnostic accuracy.Methods A retrospective analysis of 20 patients ≤3 cm nonepithelial HAML and 26 cases of SHCC,confirmed by clinical pathology,with both in clinical data and MRI characteristics.Results ≤3 cm nonepithelial HAML commonly occurs in women;The enhancement patterns“wash in and wash out”in 1 1 cases,6 cases “wash in but slow out”,3 cases with delayed enhancement;Mature adipose tissue found in 5 cases, 3 cases has pseudocapsule enhancemen in delayed phase,13 cases can see central vessels;While SHCC often occurs in men,with“wash in and wash out”enhancement pattern in 23 cases,1 7 cases with pseudocapsule enhancemen in delayed phase,12 cases can see central vessels in lesions.ADC values for SHCC was significantly lower than that for ≤3 cm nonepithelial HAML,the ADC values of SHCC significantly lower than the surrounding liver parenchyma;The ADC values between ≤3 cm nonepithelial and liver parenchyma around has no significant differences.ADC values of liver parenchyma with liver cirrhosis was lower than that without cirrhosis.Conclusion The existence of mature adipose tissue,the MRI enhancement pattern and the value of ADC can help to distinguish between ≤3 cm nonepithelial HAML and SHCC,then improve the preoperative diagnostic accuracy.

Objective To evaluate the diagnostic value of brain SPECT imaging with a novel Aβ plaque probe,131 I-2-(4'-dimethylaminophenyl) -6-iodoimidazo[ 1,2-α ] pyridine ( 131 I-IMPY) in early AD.Methods Thirteen patients with AD (3 males,10 females,age ranged 52 - 79 y),11 with mild cognitive impairment (MCI,4 males,7 females,age ranged 48 - 67 y) and 14 normal controls (6 males,8 females,age ranged 42 - 67 y) were enrolled in this study.131I-IMPY SPECT imaging was acquired in 2 -3 h after the agent injection.ROIs were drawn on cerebral lobes and cerebellum.The ratios of mean radioactivity of cerebral lobes over cerebellum (Rcl/cb) were calculated.The t-test was used for data analysis.Results In patients with MCI,Rcl/cb ratios were increased in parietal gyrus,temporal gyrus and frontal gyrus (right:1.15±0.18,1.18±0.12,1.14±0.14; left:1.16±0.11,1.19±0.18,1.15±0.09)compared with those in normal control group ( right:1.02 ± 0.12,1.05 ± 0.14,1.01 ± 0.12 ; left:1.03 ±0.13,1.05 ±0.13,1.01 ±0.14; t:2.1642 to 2.8757,all P ＜0.05).Rcl/cb ratios of basel ganglia and occipital gyms in MCI group (right:0.92 ±0.18,1.12 ±0.15; left:0.94 ±0.15,1.13 ±0.17) showed no statistical difference compared with those in normal control group (right:0.82 ±0.15,1.06 ±0.18;left:0.85 ±0.16,1.08 ±0.15; t:0.7805 to 1.4344,all P＞0.05).In patients with AD,Rcl/cb ratios were increased in parietal,temporal,basal ganglia and occipital lobes (right:1.16 ±0.19,1.24 ±0.17,1.16 ±0.13,1.14±0.11,1.23±0.10; left:1.17±0.21,1.25±0.15,1.18±0.08,1.17±0.16,1.25±0.11)compared with those in normal control group( t:2.1001 to 6.2789,all P ＜0.05).Rcl/cb ratios of parietal,temporal and frontal lobes in AD group showed no statistical difference compared with those in MCI group (t:0.1316 to 0.9806,all P ＞ 0.05 ),while Rcl/cb ratios of basal ganglia and occipital lobes in AD group were increased compared with those in MCI group ( t:2.0850 to 3.6772,all P ＜ 0.05 ).Conclusion 131 I-IMPY as a β- amyloid plaque probe for brain SPECT imaging may be potentially helpful for early diagnosis of AD.