Characteristics of Ground-Glass Nodules Detected by Low-Dose Computed Tomography as a Regular Health Examination Among Chinese Hospital Employees and Their Parents.

INTRODUCTION: Annual LDCT has been offered as a regular examination among many unit staff in China. Along with the wide application of LDCT, more and more ground-glass nodules were found. We focused on characteristics and relationship of ground-glass nodules detected by LDCT as a regular health examination among Chinese hospital employees and their parents. METHODS: We recorded LDCT-detected ground-glass nodules (GGNs) in the hospital employees and parents between 2019 and 2020. Clinical information, including age, gender, smoking status was collected and analyzed. RESULTS: A total of 5,574 employees and 2,686 employs' parents ≥60 years in Xiangya hospital performed annual physical examination. In total, LDCT incidentally detected ground-glass nodules 392 (24.78%, 392/1,582) in hospital employees and 254 in parents (10.80%, 254/2,352). The GGN-detection rate was significantly greater in employee group than parent group and more non-smokers in former (P <0.001). The detection rate was significantly greater in female than male both in employees group and parents group, and the proportion of female was bigger in employees group (P <0.001). There were more pure-GGNs both in employees group and parents group. There were less participants with solitary GGN in employee group than parent group (P = 0.033). Besides, there were more large GGNs (≥10 mm) (P <0.001), LU-RADS 4 GGNs (P <0.001) and LU-RADS 4B GGNs (P = 0.003), LU-RADS 4C-5 GGNs (P = 0.001) in parent group than employee group. There were 36 employee-parent pairs (27.07%) both had GGNs among 133 pairs who both performed LDCT. GGNs in employees were smaller and lower-grade than their parents (P < 0.001, P = 0.001). CONCLUSIONS: Among the employees and parents who had ground glass nodules, 1/4 of them both detected GGNs. Although the detection rate of GGNs in the parent group was lower than that in the employee group, the grade of nodules was significantly higher. All these suggest that the occurrence and development of ground glass nodules may be related to genetic factors.

Normalizing HDAC2 Levels in the Spinal Cord Alleviates Thermal and Mechanical Hyperalgesia After Peripheral Nerve Injury and Promotes GAD65 and KCC2 Expression.

Neuropathic pain is a worldwide health concern with poor treatment outcomes. Accumulating evidence suggests that histone hypoacetylation is involved in development and maintenance of neuropathic pain. Thus, many natural and synthetic histone deacetylase (HDACs) inhibitors were tested and exhibited a remarkable analgesic effect against neuropathic pain in animals. However, studies evaluating specific subtypes of HDACs contributing to neuropathic pain are limited. In this study, using the chronic constriction injury (CCI) rat model, we found that mRNA and protein levels of HDAC2 were increased in the lumbar spinal cord of rats after sciatic nerve injury. Intrathecal injection of TSA, a pan-HDAC inhibitor, suppressed the increase in HDAC2 protein but not mRNA, and showed a dose-dependent pain-relieving effect. By introducing HDAC2-specific shRNA into the spinal cord via a lentivirus vector, we confirmed that HDAC2 mediates mechanical and thermal hyperalgesia after nerve injury. Further examination found two essential participants in neuropathic pain in the inhibitory circuit of the central nervous system: GAD65 and KCC2 were increased in the spinal cord of CCI rats after HDAC2 knockdown. Thus, our research confirmed that HDAC2 was involved in mechanical and thermal hyperalgesia induced by peripheral nerve injury. Furthermore, GAD65 and KCC2 were the possible downstream targets of HDAC2 in pain modulation pathways.

[Trichostatin A suppresses up-regulation of histone deacetylase 4 and reverses differential expressions of miRNAs in the spinal cord of rats with chronic constrictive injury].

OBJECTIVE: To explore the analgesic mechanism of intrathecal trichostatin A (TSA) injection in a rat model of neuropathic pain induced by chronic constrictive injury (CCI). METHODS: Male SD rats were randomized into sham operation+ DMSO group (group S), CCI +DMSO group (group C), CCI +10 µg TSA group (group T), and in the latter two groups, rat models of neuropathic pain were established induced by CCI. The rats were given intrathecal injections of 10 µL 5% DMSO or 10 µg TSA (in 5% DMSO) once a day on days 7 to 9 after CCI or sham operation. The rats were euthanized after behavioral tests on day 10, and the lumbar segment of the spinal cord was sampled to determine the expression of histone deacetylase 4 (HDAC4) protein and mRNA and detect the differentially expressed miRNAs using a miRNA chip. MiR-190b-5p and miR-142-3p were selected for validation of the results using RT-qPCR. RESULTS: Compared with those in group S, the rats in group C showed significantly decreased paw withdrawal mechanical threshold (PWMT) from day 3 to day 10 after CCI (P < 0.05); intrathecal injection of TSA significantly reversed the reduction of PWMT following CCI (P < 0.05). Positive HDAC4 expression was detected mainly in the cytoplasm of the neurons in the gray matter of the spinal cord, and was obviously up-regulated after CCI (Ρ < 0.05). Intrathecal injection of TSA significantly suppressed CCI-induced up-regulation of HDAC4 at 10 days after the operation (P < 0.05). Compared with the miRNA profile in group S, miRNA profiling identified 83 differentially expressed miRNAs in group C (fold change ≥2 or ≤0.5, P < 0.05); TSA treatment reversed the expressions of 58 of the differentially expressed miRNAs following CCI, including 41 miRNAs that were decreased after CCI but up-regulated following TSA treatment. The results of real-time PCR validated the changes in the expressions of miR-190b-5p and miR-142-3p. CONCLUSIONS: TSA suppresses CCI-induced up-regulation of HDAC4 and reverses differential expressions of miRNAs in the spinal cord of rats, which may contribute to the analgesic effect of TSA on neuropathic pain.

[Lung cancer screening with low-dose spiral CT in a unit staff: Results of the baseline screening].

OBJECTIVE: To analyze the incidence and imaging characteristics of pulmonary nodules in a unit staff.
 Methods: Low-dose spiral CT (LDCT) scan were performed in 1 372 staffs ≥45 years old in a certain unit during the physical examination. The clinical and imaging data were collected to analyze the detection rate, imaging characteristics, and postoperative pathological conditions of pulmonary nodules.
 Results: The total detection rate for pulmonary nodules was 30.39% (417/1 372). The detected nodules were mainly single (227 cases), solid (343 cases), <5 mm in diameter (261 cases), and Lung-Reporting and Data System (Lung-RADS) category 2 nodules (340 cases). The single nodules were mostly found in the right upper lung (74 cases, 32.60%). The detection rate of pulmonary nodules tended to decrease but the detection rate of category 4 nodules increased with the increasing age (P<0.05), while the gender had no significant influence on the detection rate (P>0.05). Compared with the Lung-RADS category 3 nodules, the proportions of nodules in subsolid state, with irregular shape, lobulation sign, and vascular penetration in the Lung-RADS category 4 were increased (all P<0.05). Among them, 11 patients received surgical therapy, including 10 women. Postoperative pathology confirmed lung adenocarcinoma in 9 patients (2.16%), including 8 women, all non-smokers.
 Conclusion: The nodules in subsolid state with vascular penetration, irregular shape and lobulation sign tend to be malignant. Lung cancer screening with low-dose spiral CT in female non-smokers should be emphasized.

Suppression of HDAC2 in Spinal Cord Alleviates Mechanical Hyperalgesia and Restores KCC2 Expression in a Rat Model of Bone Cancer Pain.

Epigenetic modulation participates in the mechanism of multiple types of pathological pain, so targeting the involved regulators may be a promising strategy for pain treatment. Our previous research identified the analgesic effect of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) on mechanical hyperalgesia in a rat model of bone cancer pain (BCP) via restoration of µ-opioid receptor (MOR) expression. However, the specific types of HDACs contributing to BCP have not been explored. The present study investigated the expression pattern of some common HDACs and found that HDAC2 was up-regulated in a time-dependent manner in the lumbar spinal cord of BCP rats. TSA application suppressed HDAC2 expression in cultured PC12 cells and reversed the augmented HDAC2 in BCP rats. An RNA-interfering strategy confirmed the essential role of HDAC2 in the modulation of mechanical hyperalgesia following tumor cell inoculation, and we further examined its possible downstream targets. Notably, HDAC2 knock-down did not restore MOR expression, but it robustly reversed the down-regulation of potassium-chloride cotransporter 2 (KCC2). The impaired KCC2 expression is a vital mechanism of many types of pathological pain. Therefore, our results demonstrated that HDAC2 in spinal cord contributed to the mechanical hyperalgesia in BCP rats, and this effect may be associated with KCC2 modulation.

HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in a rat model of bone cancer pain by restoring µ-opioid receptor in spinal cord.

Bone cancer pain (BCP) is a common complication with inadequate management in patients suffering from advanced cancer. Histone deacetylase inhibitors showed significant analgesic effect in multiple inflammatory and neuropathic pain models, but their effect in bone cancer pain has never been explored. In this study, we utilized a BCP rat model with intra-tibial inoculation of Walker 256 mammary gland carcinoma cells, which developed progressive mechanical hypersensitivity but not thermal hypersensitivity. Intrathecal application of trichostatin A (TSA), a classic pan-HDAC inhibitor, ameliorated tactile hypersensitivity and enhanced the analgesic effect of morphine in BCP rats. The analgesic effect of TSA was blocked by co-administration of CTAP, a specific MOR antagonist, confirming the involvement of mu-opioid receptor (MOR). A reduction of MOR expression was observed in the lumbar spinal cord of BCP rats and TSA treatment was able to partially reverse it. In vitro study in PC12 cells also demonstrated the dose-dependent enhancement of MOR expression by TSA treatment. Taking all into consideration, we could draw the conclusion that HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in BCP rats, probably by restoring MOR expression in spinal cord.