α2-Adrenoceptor agonists attenuate hypersensitivity under neuropathic conditions. However, the mechanisms underlying this attenuation remain largely unknown. In the present study, we explored the potential roles of purinergic receptor 7 (P2X7R)/extracellular signal-regulated kinase (ERK) signaling in the anti-nociceptive effect of dexmedetomidine in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. An animal model of CCI was adopted to mimic the clinical neuropathic pain state. Behavioral hypersensitivity to mechanical and thermal stimuli was determined by von Frey filament and Hargreaves' tests, and the spinal P2X7R expression level and ERK phosphorylation were analyzed using western blot analysis and immunohistochemistry. In parallel with the development of mechanical and thermal hyperalgesia, a significant increase in P2X7R expression was noted in the ipsilateral spinal cord on day 7 after CCI. Intrathecal administration of dexmedetomidine (2.5 µg) for 3 days not only attenuated neuropathic pain but also inhibited the CCI-induced P2X7R upregulation and ERK phosphorylation. Intrathecal dexmedetomidine administration did not produce obvious effects on locomotor function. The present study demonstrated that dexmedetomidine attenuates the neuropathic pain induced by CCI of the sciatic nerve in rats by inhibiting spinal P2X7R expression and ERK phosphorylation, indicating the potential therapeutic implications of dexmedetomidine administration for the treatment of neuropathic pain.
Animals ; Blotting, Western ; Constriction ; Dexmedetomidine* ; Hyperalgesia ; Hypersensitivity ; Immunohistochemistry ; Models, Animal ; Neuralgia* ; Phosphorylation* ; Phosphotransferases ; Rats* ; Sciatic Nerve ; Spinal Cord ; Up-Regulation

OBJECTIVETo investigate the association between vitamin D receptor (VDR) gene Apa I polymorphism and the susceptibility to bone and joint tuberculosis in Chinese Han population.

METHODSBetween May, 2015 and June, 2016, 100 patients with bone and joint tuberculosis and 100 healthy volunteers were recruited concomitantly in Heyuan Hospital of Traditional Chinese Medicine. Vitamin D receptor gene Apa I polymorphisms in these subjects were analyzed using SNaPshot.

RESULTThe genotype frequencies of Apa I-AA, Apa I-Aa and Apa I-aa were 51%, 41%, and 8% in the case group and 33%, 55%, and 12% in the control group, respectively, showing significant differences between the two groups (P<0.05). The genotype of Apa I-AA was significantly higher in the case group with an odds ratio (OR) of 2.073 (95% CI: 1.142-3.763).

CONCLUSIONThe Apa I polymorphisms of the VDR gene are associated with the susceptibility to bone and joint tuberculosis in Chinese Han population, and individuals with a Apa I-AA genotype are at greater risks to develop bone and joint tuberculosis.

Objective:To evaluate the test-retest reliability of MRI criteria in the 2019 Bosniak classification of cystic renal masses (CRMs) and to analyze the impact of lesions′ property, size and readers′ experience on the test-retest reliability.Methods:From January 2009 to June 2019, 207 patients with 207 CRMs were included in this retrospective study. All of them underwent renal MRI and surgical-pathologic examination. According to Bosniak classification, version 2019, all CRMs were independently classified twice by eight radiologists with different levels of experience. All radiologists were blinded to the pathology of the lesions. By using intraclass correlation coefficient (ICC), test-retest reliability was evaluated for all CRMs and for subgroups with different pathological properties (benign and malignant) and different sizes (≤40 mm and>40 mm). The test-retest reliability of 4 senior readers (≥10 years of experience) and 4 junior readers (<10 years of experience) were evaluated respectively. The comparison of ICC was performed using Z test. Results:The 207 CRMs included 111 benign lesions (83 benign cysts, 28 benign tumors) and 96 malignant tumors. There were 87 lesions with maximum diameter ≤40 mm and 120 with maximum diameter>40 mm. The test-retest reliability (ICC) of each reader for all lesions was 0.776-0.888, the overall ICC was 0.848 (95%CI 0.821-0.872). The ICCs of senior and junior readers were 0.853 (95%CI 0.824-0.880) and 0.843 (95%CI 0.811-0.871) respectively, without significant difference between the two groups ( Z=0.85, P=0.374). The ICC of all readers was 0.827 for benign lesions and 0.654 for malignant lesions, showing significant difference ( Z=2.80, P=0.005). The ICC was 0.770 for lesions ≤40 mm and 0.876 for lesions>40 mm, which was significantly different ( Z=-2.36, P=0.018). For CRM subgroups with different pathological properties and different sizes, there was no significant difference in test-retest reliability between senior and junior readers (all P>0.05). Conclusion:The test-retest reliability of MRI criteria in the 2019 Bosniak classification of CRMs is excellent and unaffected by readers′ experience. The reliabilities are not consistent among CRMs of different pathological properties and different sizes, but all reached the level of good and above.

Pregnancy ; Female ; Humans ; Milk, Human ; Overweight/genetics* ; Fatty Acids, Unsaturated ; Fatty Acids ; Adiponectin/genetics*

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.