[Pituitary Crooke cell neuroendocrine tumor of adrenocorticotropic hormone differentiation-specific transcription factor lineage: a clinicopathological analysis of six cases].

Objective: To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor (TPIT, also known as transcription factor 19, TBX19) lineage neuroendocrine tumors. Methods: Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China from October 2019 to October 2023 were collected. The clinical and pathological features of these cases were analyzed. Results: Among the six cases, one was male and five were female, with ages ranging from 26 to 75 years, and an average age of 44 years. All tumors occurred within the sella turcica. Clinical presentations included visual impairment in two cases, menstrual disorders in one case, Cushing's syndrome in one case, headache in one case, and one asymptomatic case discovered during a physical examination. Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases, elevated cortisol in two cases, elevated adrenocorticotropic hormone in one case, and one case with a mild increase in prolactin due to the pituitary stalk effect. Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm, all identified as macroadenomas. Microscopically, tumor cells exhibited irregular polygonal shapes, solid sheets, or pseudo-papillary arrangements around blood vessels. The cell nuclei were eccentric or centrally located, varying in size, with abundant cytoplasm. Some tumor cells showed perinuclear halo. Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases, focal weak positivity for TPIT in one case, diffuse strong positivity for adrenocorticotropic hormone in all cases, and faint staining around the nuclei in a few cells. CK8/18 showed a strong positive ring pattern in more than 50% of tumor cells, focal weak positive expression of p53, and the Ki-67 positive index ranged 1%-5%. Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas. Conclusions: Crooke cell tumor is a rare type of pituitary neuroendocrine tumors. Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers, such as CK8/18 exhibiting a ring or halo pattern. This entity represents a high-risk subtype among pituitary neuroendocrine tumors, displaying a high risk of invasion and a propensity for recurrence. Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.

[Effects of tibial second toe free flap bridged with blood flow and nerve in the treatment of severe flexion contracture of the proximal interphalangeal joint].

Objective: To investigate the effects of tibial second toe free flap bridged with blood flow and nerve in the treatment of severe flexion contracture of the proximal interphalangeal joint. Methods: A retrospective observational study was conducted. From March 2013 to October 2019, 9 patients with severe flexion contracture (type Ⅲ) of the proximal interphalangeal joint after trauma operation, conforming to the inclusion criteria, were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 5 males and 4 females, aged from 17 to 62 years. After the contracture tissue affecting the extension of the proximal interphalangeal joint was cut off, and the scar tissue was resected, the size of the volar wound near the proximal interphalangeal joint in extended position was 2.0 cm×1.0 cm-2.5 cm×1.5 cm, with the length of proper digital artery and nerve defect being 1.0-1.5 cm. A free flap of the same size as the wound was cut from the tibial side of the second toe and transplanted to repair the wound, and the defective proper digital artery and nerve was repaired by bridging with the tibial proper plantar digital artery and nerve of about 1.5 cm in length. The full-thickness skin graft was taken from the proximal tibial side of the lower leg to repair the wound at flap donor site. The wound at skin graft donor site was sutured directly. The survival of flap and skin graft was observed after operation. The patients were followed up, and at the last follow-up, the recovery of the affected finger and the second toe, including the donor and recipient areas were observed, the two-point discrimination distances of the flap repaired site and the pulp of the affected finger were observed and measured at the same time, the blood flow patency of bridged vessel of the affected finger was examined by Allen test, and the function of the proximal interphalangeal joint of the affected finger was evaluated according to Chinese Medical Association's standard for the range of motion of proximal interphalangeal joint. Results: The flaps and skin grafts survived smoothly after operation. The follow-up after operation lasted for 5 to 22 months, with a mean of 10 months. At the last follow-up, the flap repaired site had good shape, good color and texture, with the two-point discrimination distance being 9-12 mm, and the two-point discrimination distance of the pulp of the affected finger was 6-10 mm; the Allen test results of the affected fingers were all negative (i.e., the bridged vessels had good blood flow patency), with no recurrence of flexion contracture, and the function of the proximal interphalangeal joint was evaluated as excellent; the skin graft area of the second toe was not ruptured but was a little pigmented, and the flexion and extension activities of toe were good. Conclusions: The tibial second toe free flap bridged with blood flow and nerve has reliable therapeutic effect in the treatment of severe flexion contracture of the proximal interphalangeal joint, and the color and texture of the flap repaired area are good. Bridging to repair the severely contracted proper digital artery and nerve is beneficial to improve the blood supply of the finger body and rebuild the sensation.

Association between hepatitis C infection during pregnancy with maternal and neonatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: Studies of possible implications of the maternal hepatitis C virus (HCV) infection in terms of intrauterine fetal growth restriction (IUGR), preterm birth (PTB), low birth weight (LBW) infants, premature rupture of membranes (PROM), maternal and neonatal mortality are limited and inconclusive. Our study aims to assess the impact of HCV on maternal and neonatal outcomes. MATERIALS AND METHODS: Systematic literature search was done in PubMed, Scopus, and Google Scholar, Cochrane Library, and TRIP databases for all observational studies published from 1st January 1950 to 15th October 2022. The pooled odds ratio (OR) or risk ratio (RR) with a 95% confidence interval (CI) was estimated. STATA version 12.0 software was used for analysis. Heterogeneity among the included articles was evaluated by sensitivity, meta-regression, and publication bias analyses. RESULTS: A total of 14 studies involving 12,451 HCV (+) and 56,42,910 HCV (-) pregnant women were included in our meta-analysis. Maternal HCV during pregnancy was significantly associated with the increased risk of PTB (OR=1.66, 95% CI: 1.59-1.74), IUGR (OR=2.09, 95% CI: 2.04-2.14) and LBW (OR=1.96, 95% CI: 1.63-2.36) as compared to healthy pregnant women. Subgroup analysis based on ethnicity also suggested a strong association between maternal HCV infection and a higher risk of PTB in Asian and Caucasian populations. Maternal (RR=3.44, 95% CI: 1.85-6.41), as well as neonatal (RR=1.54, 95% CI: 1.18-2.02) mortality was significantly higher in HCV (+) cases. CONCLUSIONS: Mothers with HCV infection had a markedly increased probability of PTB and/or IUGR and/or LBW. In clinical practice, standard care of treatment and proper monitoring are needed for the pregnant population with HCV infection. Our findings may provide useful information for selecting appropriate therapy methods for HCV-positive pregnant women.

[A prospective study of position selection combined with autologous blood intrathoracic infusion in the treatment of postoperative persistent air leakage with an unexpanded lung].

We prospectively studied 17 patients with spontaneous pneumothorax or giant emphysematous bulla at Rizhao Hospital of Traditional Chinese Medicine from October 2020 to March 2022. All patients underwent thoracoscopic interventional therapy, had experienced continued air leakage for 3 days with closed thoracic drainage postoperatively, had an unexpanded lung on CT, and/or failed to intervention with position selection combined with intra-pleural thrombin injection(referred to as "position plus1.0"). They were all treated with position selection combined with autologous blood (100 ml) and thrombin (5 000 U) intra-pleural injection(referred to as "position plus 2.0").The success rate of the "position plus 2.0" intervention was 16/17, and the recurrence rate was 3/17. There were four cases of fever, four cases of pleural effusion, one case of empyema, and no other adverse reactions. This study has shown that the "position plus 2.0" intervention is safe, effective, and simple for patient with persistent air leakage failed to intervention with"position plus 1.0" after thoracoscopic treatment of pulmonary and pleural diseases related to bulla.

[Effectiveness and safety of medical glue assisted argon plasma coagulation union giant emphysematous bulla volume reduction via thoracoscope on the treatment of spontaneous pneumothorax with subpleural bullae].

Objective: To evaluate the effectiveness and safety of a new treatment protocol that combined "medical glue assisted argon plasma coagulation"(hereinafter called "APC plus") and "giant emphysematous bulla volume reduction"(hereinafter called "one thoracoscope plus one needle") via medical thoracoscopy on the spontaneous pneumothorax patients whose chest high resolution CT (HRCT) showed multiple subpleural bullae (SPB) and at least one SPB≥4 cm in diameter. Methods: A retrospective analysis was performed on the clinical data of 46 cases of spontaneous pneumothorax with multiple SPB(at least one SPB≥4 cm in diameter), 42 males and 4 females, aged from 31 to 79 (68.5±10.3) years,from June 2018 to December 2021 in Rizhao Hospital of Traditional Chinese Medicine. The time of air leakage discontinuance, the disappearance rate and reduction degree of target subpleural blebs one week after operation, the degree of reduction and the incidence of postoperative complications were observed. Two-year follow-up after operation was carried out to assess the recurrence rate and its short- and long-term complications. Results: Among the 46 patients, SPB disappeared or nearly disappeared in 39 cases (84.78%), decreased in number or reduced in volume in 5 cases (10.87%), and remained unchanged in 2 cases (4.35%) after the intervention of "APC Plus"; 40 patients stopped leaking within 1 week and 6 cases stopped leaking over a week. Eleven patients finished the 3-year follow-up, 13 finished 2-year follow-up and 6 finished 1-year follow-up, with only 1 relapse. No serious complications occurred in all these 46 patients. Conclusion: "APC plus" combining with "one thoracoscope plus one needle" is safe and effective in the treatment of pneumothorax patients with multiple subpleural bullae of varying sizes.

Characterizing occupational radon exposure greater than 100 Bq/m3 in a highly exposed country.

Radon is an established lung carcinogen concentrating in indoor environments with importance for many workers worldwide. However, a systematic assessment of radon levels faced by all workers, not just those with direct uranium or radon exposure, has not previously been completed. The objective of this study was to estimate the prevalence of workers exposed to radon, and the level of exposure (> 100-200 Bq/m3, 200-400 Bq/m3, 400-800 Bq/m3, and > 800 Bq/m3) in a highly exposed country (Canada). Exposures among underground workers were assessed using the CAREX Canada approach. Radon concentrations in indoor workplaces, obtained from two Canadian surveys, were modelled using lognormal distributions. Distributions were then applied to the susceptible indoor worker population to yield the number of exposed workers, by occupation, industry, province, and sex. In total, an estimated 603,000 out of Canada's 18,268,120 workers are exposed to radon in Canada. An estimated52% of exposed workers are women, even though they comprise only 48% of the labour force. The majority (68%) are exposed at a level of > 100-200 Bq/m3. Workers are primarily exposed in educational services, professional, scientific and technical services, and health care and social assistance, but workers in mining, quarrying, and oil and gas extraction have the largest number of exposed workers at high levels (> 800 Bq/m3). Overall, a significant number of workers are exposed to radon, many of whom are not adequately protected by existing guidelines. Radon surveys across multiple industries and occupations are needed to better characterize occupational exposure. These results can be used to identify exposed workers, and to support lung cancer prevention programs within these groups.

[Clinicopathological features of spinal solitary fibrous tumor].

Objective: To investigate the clinicopathological, molecular genetic, immunohistochemical and prognostic features of spinal solitary fibrous tumor (SFT). Methods: The clinical data of 12 cases of spinal SFT in Beijing Tsinghua Changgung Hospital, Affiliated to Tsinghua University, diagnosed from January 2015 to December 2021 were collected and reclassified. The clinical data, histopathology, immunohistochemistry and molecular genetics were analyzed. Follow-up and related literature reviews were conducted. Results: Among the 12 patients, there were 5 males and 7 females; the age ranged from 31 to 73 years, with a median age of 50.5 years. All 12 cases were primary tumors, including 4 cases diagnosed at the first time and 8 recurrent cases. Among the 12 cases, 8 were WHO grade 1, 3 were WHO grade 2, and 1 was WHO grade 3. Microscopically, the spinal SFT appeared as a spindle cell tumor, the stroma was rich in many thin-walled blood vessels with various histological features such as cell morphology and necrosis according to the different tumor grade. All (12/12) of the cases expressed vimentin and STAT6 (diffuse and strong nuclear stain), 11 cases (11/12) expressed both CD34 and bcl-2, and 7 cases (7/12) expressed CD99. Next-generation sequencing showed that 12 (12/12) of the patients had NAB2-STAT6 gene fusion. The 12 patients were followed up for 6 to 80 months. There were no recurrences or metastases in the 4 first cases after operation. Among the 8 recurrent cases, 2 of the patients relapsed and 2 died. Conclusions: Spinal SFT is rare and has a high recurrence tendency. Many aspects need to be considered in the diagnosis process. STAT6 is a relatively specific marker for the diagnosis of this tumor. Complete surgical resection is the preferred treatment while postoperative radiotherapy is recommended to reduce tumor recurrence.

[Treatment effects of sandwich-shaped resection and cheiloplasty applied in macrocheilia secondary to arteriovenous malformations].

To summarize the clinical experience of sandwich-shaped resection and cheiloplasty in the treatment of macrocheilia secondary to arteriovenous malformation, and to observe its clinical efficacy and complications. The clinical data of 27 patients with macrocheilia secondary to arteriovenous malformation who received surgical treatment from January 2018 to October 2020 in Linyi Cancer Hospital were retrospectively analyzed. There were 14 males and 13 females. The median age was 4.5 years (ranged from 2 to 57 years). There were 18 cases of upper lip and 9 cases of lower lip. All patients had received interventional embolization sclerotherapy for 5 to 10 times before surgery with unsatisfied effect. There was no obvious improvement in the appearance,whereas 3 cases progressed presenting as abnormal enlargement. Sandwich-shaped resection and cheiloplasty was performed in all the patients. Histopathological examinations confirmed arteriovenous malformations in all 27 cases. Twenty-six patients received one course of operation and one received two courses. Partial mucosal necrosis occurred in 1 case and healed after dressing change, while the rest healed by first intention. Local recurrence occurred in 2 cases within 6 months after operation. A four-level standard was used for long-term evaluation, and 24 cases got grade Ⅲ (good), three cases got grade Ⅱ (moderate) after 1 to 3 years of follow-up. Sandwich-shaped resection and cheiloplasty can achieve good long-term efficacy with excellent appearance and function. Due to its advantages of hidden incision and three-dimensional resection and reservation, it is worthy of further clinical promotion.

[Induction of peripheral blood mononuclear cells to hepatocyte-like cells and preliminary study of cell response to injury under the effect of acetaminophen].

Objective: To establish a method for the induction of peripheral blood mononuclear cells to hepatocyte-like cells, and preliminarily investigate cell response to injury under the effect of acetaminophen (APAP). Methods: The surface marker CD45 of peripheral blood mononuclear cells wase detected cells by using flow cytometry and immunofluorescence methods. The cellular morphology of induced hepatocyte-like cells was observed under an inverted microscope. Real-time fluorescent quantitative PCR (RT-PCR) was used to detect the expression level of hepatocyte-specific genes, such as cytochrome (CY) P1A2, CYP3A4, CYP2C9, albumin (ALB), alpha-fetoprotein (AFP), and hepatocyte nuclear factor (HNF)4α mRNA. Immunofluorescence method was used to detect intracellular hepatocyte markers AFP, HNF4α, and ALB expression at the protein level. Biochemical analyzer was used to detect hepatocyte-specific secretory functions of AFP, ALB, and urea. Luciferase chemiluminescence method was used to detect the activity of key drug metabolizing enzyme CYP3A4. Colorimetric assay was used to detect the effect of the drug acetaminophen on hepatocyte-like cells, and alanine aminotransferase (ALT) was used as an indicator of liver cell injury. The statistical differences between the data were compared with t-test and rank-sum test. Results: The positive expression rate of CD45 cell surface markers isolated from peripheral blood mononuclear cells was about 98%, and hepatocyte-like cell morphology changes appeared on 15th day of induction. Compared with isolated mononuclear cells, CYP1A2, CYP3A4, CYP2C9, ALB, AFP and HNF4α mRNA was markedly elevated. The expression level of AFP, ALB and HNF4α protein were equally increased, and the secretory function of AFP, ALB and urea were enhanced. Compared with primary hepatocytes, CYP1A2, CYP2C9, AFP, HNF4α mRNA, and CYP3A4 mRNA did not decrease. The expression levels of AFP, ALB, and HNF4α proteins in the cells did not decrease, and the secretory function of AFP, ALB, and urea did not decrease. In addition, the CYP3A4 enzyme activity produced by hepatocyte-like cells was similar to that of primary hepatocytes. Compared with hepatocyte-like cells incubated without APAP, hepatocyte-like cells incubated with APAP had higher ALT level. Under the effect of APAP, the ALT level of hepatocyte-like cells was higher than isolated mononuclear cells. Conclusion: Peripheral blood mononuclear cells can be induced into hepatocyte-like cells with partial characteristics of hepatocytes, including the activity of CYP3A4, a key enzyme of hepatocyte drug metabolism. Additionally, preliminarily ALT secretory features reflect the hepatocytes injury under the effect of acetaminophen.

[Early efficacy of three dimensional printed anatomical biomimetic cervical artificial disc replacement in the treatment of cervical degenerative diseases].

Objective: To investigate the efficacy and safety of a new cervical artificial disc prosthesis in the treatment of cervical degenerative diseases. Methods: The clinical data of 18 patients with single-level cervical degenerative diseases who underwent three dimensional printed anatomical bionic cervical disc replacement at Department of Spinal Surgery,Honghui Hospital,Xi'an Jiaotong University from May 2019 to July 2020 were analyzed retrospectively. There were 7 males and 11 females,aged (45±8) years old(range:28 to 58 years).The surgical segment was located at C3－4 level in 2 cases, C4－5 level in 5 cases, C5－6 level in 9 cases, and C6－7 level in 2 cases.The clinical and radiographic outcomes were recorded and compared at preoperative,postoperative times of one month and twelve months.The clinical assessments contained Japanese orthopedic association (JOA) score,neck disability index (NDI) and visual analogue scale (VAS).Imaging assessments included range of motion (ROM) of cervical spine, prosthesis subsidence and prosthesis anteroposterior migration.Repeated measurement variance analysis was used for comparison between groups,and paired t test was used for pairwise comparison. Results: All patients underwent the operation successfully and were followed up for more than 12 months.Compared with preoperative score,the JOA score,NDI and VAS were significantly improved after surgery (all P<0.01).There was no significant difference in postoperative ROM compared with 1-and 12-month preoperative ROM (t=1.570,P=0.135;t=1.744,P=0.099). The prosthesis subsidence was (0.29±0.13) mm (range: 0.18 to 0.50 mm) at 12-month postoperatively.The migration of prosthesis at 12-months postoperatively were (0.71±0.20) mm (range: 0.44 to 1.08 mm).There was no prosthesis subsidence or migration>2 mm at 12-month postoperatively. Conclusion: Three dimensional printed anatomical biomimetic cervical artificial disc replacement has a good early clinical effect in the treatment of cervical degenerative diseases, good mobility can be obtained while maintaining stability.

[Efficacy and safety of giant emphysematous bulla volume reduction via medical thoracoscope].

Objective: To evaluate the efficacy and safety of giant emphysematous bulla (GEB) volume reduction via medical thoracoscope. Methods: This was a prospective, single-arm study conducted between July 2018 and September 2020 in Ri Zhao Hospital of Traditional Chinese Medicine. Patients who met the inclusion criteria were treated with GEB volume reduction via medical thoracoscope and were followed up to evaluate the efficacy and safety of the technique. According to comparison of preoperative and postoperative chest CT results, the self-designed evaluation criteria of imaging efficacy were as follows: complete or nearly complete disappearance of GEB (GEB volume reduction ≥90%), significant reduction of GEB (75%≤GEB volume reduction<90%), reduction of GEB (50%≤GEB volume reduction<75%) and no change (GEB volume reduction<50%). Results: A total of 47 patients were included, among whom 43 were males, with an age M (Q1, Q3) of 63.0 (55.0, 67.0). The CT results showed complete or nearly complete disappearance of GEB in 43 patients, significant reduction of GEB in 3 patients and reduction of GEB in 1 patient before discharge. The degree of dyspnea improved significantly (P<0.05). Arterial partial pressure of carbon dioxide (PaCO2) decreased from (48.2±8.4)mmHg (1 mmHg=0.133 kPa) to (45.4±7.3)mmHg (P<0.05). The 6-minute walk test (6MWT) increased from (245.6±162.4)m to (283.5±152.2)m (P<0.05). Six-month postoperative follow-up was completed in 24 patients, and CT results showed that the efficacy of volume reduction was continuous compared with that before discharge. GEB was further reduced or even disappeared in 3 of the cases. Besides, the degree of dyspnea, 6MWT (384.4±148.2)m and PaCO2 (42.7±6.6)mmHg were improved significantly (P<0.05). The oxygenation index (356.86±61.21)mmHg was significantly higher than that before surgery (295.20±67.16)mmHg and before discharge (294.50±76.69)mmHg (P<0.05). No perioperative deaths occurred. Conclusions: GEB volume can be completely eliminated or significantly reduced by this innovative technique, while PaCO2, the degree of dyspnea and exercise endurance can be significantly improved after operation. The 6-month follow-up after surgery showed that the above benefits continued, and that the oxygenation index improved significantly.

[Efficacy and safety of position selection combined with intra-pleural thrombin injection in the treatment of postoperative persistent air leakage in bullous pulmonary-pleural diseases].

Objective: To explore the efficacy and safety of position selection in combination with intra-pleural thrombin injection in the treatment of persistent air leakage (PAL) after medical thoracoscopic treatment of bullous pulmonary-pleural diseases (e.g. spontaneous pneumothorax or giant emphysematous bulla). Methods: This was a prospective study conducted in Rizhao Hospital of Traditional Chinese Medicine from August 2018 to November 2020. Twenty patients(19 males,1 female) with a mean age of (62.3±8.1) years met the diagnostic criteria for PAL which was defined as the air leak persisted more than 3 days despite of the closed thoracic drainage after medical thoracoscopic treatment of bullous pulmonary-pleural diseases.They received the following treatment procedures (referred to as "position plus"):①Pleural cavity injection (50% glucose 20 ml+thrombin 5 000 U).②Changing the patient's position under continuous negative pressure suction to find the position causing the complete stop or significant reduction of air leakage, and keeping in the position for 24-48 hours.③If the PAL wasn't stopped 48 hours later, the procedures above would be repeated.The duration of air leakage after "position plus", times of pleural cavity injection, condition of lung re-expansion, recurrence of air leakage and complications during hospitalization were recorded. Descriptive statistics were used to summarize the results:¯x±s or M(P25, P75) for continuous variables; frequency and percentages for categoric variables. Results: A total of 20 patients were included. The average duration of air leakage after"position plus" was (1.32±0.97) days. The times of pleural cavity injection required were 1.0(1.0, 1.0).All the patients showed good lung re-expansion in review of imaging after PAL was stopped. One patient had recurrent air leakage during hospitalization. No serious complications occurred. Conclusion: The comprehensive "position plus" intervention method is effective, safe and easily operating for the treatment of PAL after medical thoracoscopic treatment of bullous pulmonary-pleural diseases.

Role of Discoidin Domain Receptor 2 in Craniofacial Bone Regeneration.

Bone loss caused by trauma, neoplasia, congenital defects, or periodontal disease is a major cause of disability and human suffering. Skeletal progenitor cell-extracellular matrix interactions are critical for bone regeneration. Discoidin domain receptor 2 (DDR2), an understudied collagen receptor, plays an important role in skeletal development. Ddr2 loss-of-function mutations in humans and mice cause severe craniofacial and skeletal defects, including altered cranial shape, dwarfing, reduced trabecular and cortical bone, alveolar bone/periodontal defects, and altered dentition. However, the role of this collagen receptor in craniofacial regeneration has not been examined. To address this, calvarial subcritical-size defects were generated in wild-type (WT) and Ddr2-deficient mice. The complete bridging seen in WT controls at 4 wk postsurgery was not observed in Ddr2-deficient mice even after 12 wk. Quantitation of defect bone area by micro-computed tomography also revealed a 50% reduction in new bone volume in Ddr2-deficient mice. Ddr2 expression during calvarial bone regeneration was measured using Ddr2-LacZ knock-in mice. Expression was restricted to periosteal surfaces of uninjured calvarial bone and, after injury, was detected in select regions of the defect site by 3 d postsurgery and expanded during the healing process. The impaired bone healing associated with Ddr2 deficiency may be related to reduced osteoprogenitor or osteoblast cell proliferation and differentiation since knockdown/knockout of Ddr2 in a mesenchymal cell line and primary calvarial osteoblast cultures reduced osteoblast differentiation while Ddr2 overexpression was stimulatory. In conclusion, Ddr2 is required for cranial bone regeneration and may be a novel target for therapy.

Oxycodone inhibits myocardial cell apoptosis after myocardial ischemia-reperfusion injury in rats via RhoA/ROCK1 signaling pathway.

OBJECTIVE: The purpose of this study was to investigate the effect of oxycodone on myocardial ischemia-reperfusion injury in rats through the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) signaling pathway. MATERIALS AND METHODS: A total of 48 Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group, oxycodone group, and inhibitor group, with 12 rats in each group. The rats in the sham operation group only underwent thoracotomy without ischemia-reperfusion injury, those in the model group were used to prepare the myocardial ischemia-reperfusion model with normal saline intervention, those in the oxycodone group were used to prepare the myocardial ischemia-reperfusion model with oxycodone intervention, and those in the inhibitor group were utilized to prepare the myocardial ischemia-reperfusion model with AG490 intervention. Then, the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) were detected by immunohistochemistry, the relative protein expressions of RhoA and ROCK1 were examined via Western blotting, and the messenger ribonucleic acid (mRNA) expressions of Bcl-2 and BAX were measured by quantitative Polymerase Chain Reaction (qPCR). Thereafter, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was adopted for apoptosis detection, and the levels of creatine kinase-muscle/brain (CK-MB), and cardiac Troponin I (cTnI) in serum were detected using an automatic biochemical analyzer. RESULTS: Immunohistochemistry results showed that compared with those in the sham operation group, the positive expression of BAX was remarkably increased (p<0.05), while that of Bcl-2 was significantly decreased (p<0.05) in the model group, oxycodone group, and inhibitor group. Compared with the model group, oxycodone group and inhibitor group had an evidently reduced positive expression of BAX (p<0.05) and an evidently raised positive expression of Bcl-2 (p<0.05). No differences were found in the positive expressions of BAX and Bcl-2 between oxycodone group and inhibitor group (p>0.05). According to Western blotting results, the relative protein expressions of RhoA and ROCK1 in the model group, oxycodone group, and inhibitor group were notably increased compared with those in the sham operation group (p<0.05). In comparison with those in the model group, the relative protein expressions of RhoA and ROCK1 in the oxycodone group and inhibitor group were predominantly reduced (p<0.05). There were no differences in the relative protein expressions of RhoA and ROCK1 between oxycodone group and inhibitor group (p>0.05). Moreover, it was discovered from qRT-PCR results that compared with those in the sham operation group, the mRNA expression of BAX was markedly raised (p<0.05), whereas that of Bcl-2 was decreased predominantly (p<0.05) in the model group, oxycodone group, and inhibitor group. Compared with the model group, oxycodone group, and inhibitor group had an evidently reduced mRNA expression of BAX (p<0.05) and a significantly raised mRNA expression of Bcl-2 (p<0.05). No differences were found in the mRNA expressions of BAX and Bcl-2 between oxycodone group and inhibitor group (p>0.05). In addition, TUNEL assay results manifested that compared with sham operation group, model group, oxycodone group, and inhibitor group had a markedly elevated apoptosis rate (p<0.05). In comparison with the model group, the apoptosis rate in oxycodone group and inhibitor group was remarkably reduced (p<0.05). There was no difference in the apoptosis rate between oxycodone group and inhibitor group (p>0.05). According to biochemical analysis results, the serum levels of CK-MB and cTnI in model group, oxycodone group, and inhibitor group were significantly increased compared with those in the sham operation group, with statistically significant differences (p<0.05). The levels of serum CK-MB and cTnI in the oxycodone group and inhibitor group were substantially lowered in comparison with those in the model group, displaying statistically significant differences (p<0.05). Besides, the levels of serum CK-MB and cTnI in the oxycodone group were not different from those in the inhibitor group (p>0.05). CONCLUSIONS: Oxycodone inhibits myocardial cell apoptosis after myocardial ischemia-reperfusion injury by suppressing the RhoA/ROCK1 signaling pathway.

Endocrine and genetic factors affecting egg laying performance in chickens: a review.

1. Egg-laying performance reflects the overall reproductive performance of breeding hens. The genetic traits for egg-laying performance have low or medium heritability, and, depending on the period involved, usually ranges from 0.16 to 0.64. Egg-laying in chickens is regulated by a combination of environmental, endocrine and genetic factors. 2. The main endocrine factors that regulate egg-laying are gonadotropin-releasing hormone (GnRH), prolactin (PRL), follicle-stimulating hormone (FSH) and luteinising hormone (LH). 3. In the last three decades, many studies have explored this aspect at a molecular genetic level. Recent studies identified 31 reproductive hormone-based candidate genes that were significantly associated with egg-laying performance. With the development of genome-sequencing technology, 64 new candidate genes and 108 single nucleotide polymorphisms (SNPs) related to egg-laying performance have been found using genome-wide association studies (GWAS), providing novel insights into the molecular genetic mechanisms governing egg production. At the same time, microRNAs that regulate genes responsible for egg-laying in chickens were reviewed. 4. Research on endocrinological and genetic factors affecting egg-laying performance will greatly improve the reproductive performance of chickens and promote the protection, development, and utilisation of poultry. This review summarises studies on the endocrine and genetic factors of egg-laying performance in chickens from 1972 to 2019.

Estimating the burden of lung cancer in Canada attributed to occupational radon exposure using a novel exposure assessment method.

OBJECTIVE: Exposure to radon causes lung cancer. The scope and impact of exposure among Canadian workers have not been assessed. Our study estimated occupational radon exposure in Canada and its associated lung cancer burden. METHODS: Exposed workers were identified among the working population during the risk exposure period (1961-2001) using data from the Canadian Census and Labour Force Survey. Exposure levels were assigned based on 12,865 workplace radon measurements for indoor workers and assumed to be 1800 mg/m3 for underground workers. Lung cancer risks were calculated using the Biological Effects of Ionizing Radiation (BEIR) VI exposure-age-concentration model. Population attributable fractions were calculated with Levin's equation and applied to 2011 Canadian lung cancer statistics. RESULTS: Approximately 15.5 million Canadian workers were exposed to radon during the risk exposure period. 79% of exposed workers were exposed to radon levels < 50 Bq/m3 and 4.8% were exposed to levels > 150 Bq/m3. We estimated that 0.8% of lung cancers in Canada were attributable to occupational radon exposure, corresponding to approximately 188 incident lung cancers in 2011. CONCLUSIONS: The lung cancer burden associated with occupational radon exposure in Canada is small, with the greatest burden occurring among those exposed to low levels of radon.

The Role of Discoidin Domain Receptor 2 in Tooth Development.

Collagen signaling is critical for proper bone and tooth formation. Discoidin domain receptor 2 (DDR2) is a collagen-activated tyrosine kinase receptor shown to be essential for skeletal development. Patients with loss of function mutations in DDR2 develop spondylo-meta-epiphyseal dysplasia (SMED), a rare, autosomal recessive disorder characterized by short stature, short limbs, and craniofacial anomalies. A similar phenotype was observed in Ddr2-deficient mice, which exhibit dwarfism and defective bone formation in the axial, appendicular, and cranial skeletons. However, it is not known if Ddr2 has a role in tooth formation. We first defined the expression pattern of Ddr2 during tooth formation using Ddr2-LacZ knock-in mice. Ddr2 expression was detected in the dental follicle/sac and dental papilla mesenchyme of developing teeth and in odontoblasts and the periodontal ligament (PDL) of adults. No LacZ staining was detected in wild-type littermates. This Ddr2 expression pattern suggests a potential role in the tooth and surrounding periodontium. To uncover the function of Ddr2, we used Ddr2slie/slie mice, which contain a spontaneous 150-kb deletion in the Ddr2 locus to produce an effective null. In comparison with wild-type littermates, Ddr2slie/slie mice displayed disproportional tooth size (decreased root/crown ratio), delayed tooth root development, widened PDL space, and interradicular alveolar bone defects. Ddr2slie/slie mice also had abnormal collagen content associated with upregulation of periostin levels within the PDL. The delayed root formation and periodontal abnormalities may be related to defects in RUNX2-dependent differentiation of odontoblasts and osteoblasts; RUNX2-S319-P was reduced in PDLs from Ddr2slie/slie mice, and deletion of Ddr2 in primary cell cultures from dental pulp and PDL inhibited differentiation of cells to odontoblasts or osteoblasts, respectively. Together, our studies demonstrate odontoblast- and PDL-specific expression of Ddr2 in mature and immature teeth, as well as indicate that DDR2 signaling is important for normal tooth formation and maintenance of the surrounding periodontium.

MiR-145 changes sensitivity of non-small cell lung cancer to gefitinib through targeting ADAM19.

OBJECTIVE: The aim of this study was to investigate the role of micro-ribonucleic acid (miR)-145 in acquired resistance of non-small cell lung cancer (NSCLC) to gefitinib, and to explore its potential mechanism. MATERIALS AND METHODS: PC-9 cells were continuously stimulated with low-concentration of gefitinib to induce the formation of acquired gefitinib-resistant PC-9/G cells. The sensitivity of PC-9 and PC-9/G cells to gefitinib was detected via Cell Counting Kit-8 (CCK-8) assay. The expressions of miR-145 and adamalysin-19 (ADAM19) in PC-9 and PC-9/G cells were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting. Subsequently, PC-9 and PC-9/G cells were transfected with miR-145 mimics and miR-145 NC, respectively. The changes in ADAM19 expression were detected via qRT-PCR and Western blotting. The changes in the sensitivity of cells to gefitinib after transfection were explored via CCK-8 assay. Moreover, the influences of miR-145 transfection on cell apoptosis, invasion and migration were detected via flow cytometry, wound healing assay and transwell assay, respectively. Target gene and acting site of miR-145 were verified via Dual-Luciferase reporter gene assay. Furthermore, targeted regulation of miR-145 on ADAM19 was verified by in vitro cellular experiments. RESULTS: The sensitivity of PC-9/G cells to gefitinib was significantly lower than that of PC-9 cells, with nearly 15-fold difference in half maximal inhibitory concentration (IC-50) (p<0.05). QRT-PCR results indicated that miR-145 expression in PC-9/G cells was significantly decreased (p<0.01). The results of Western blotting showed that the expression level of ADAM19 in PC-9/G cells was markedly higher than that of PC-9 cells. The overexpression of miR-145 could remarkably reduce the expression level of ADAM19 in PC-9/G cells, increase the sensitivity of PC-9/G cells to gefitinib, and inhibit cell invasion and metastasis. The detection of Luciferase activity revealed that miR-145 could bind to the 3'-untranslated region (UTR) of ADAM19 gene and negatively regulate the protein expression. CONCLUSIONS: MiR-145 improves the sensitivity of acquired gefitinib-resistant cells to gefitinib. Meanwhile, it inhibits cell invasion and metastasis through negative regulation on ADAM19. Furthermore, the low-expression of miR-145 may become a biomarker and therapeutic target for acquired resistance to gefitinib.

Burden of non-melanoma skin cancer attributable to occupational sun exposure in Canada.

PURPOSE: Outdoor workers are exposed daily to solar ultraviolet radiation, an important contributor in the development of non-melanoma skin cancer. This study aimed to quantify the health burden of non-melanoma skin cancers among outdoor workers in Canada. METHODS: Solar ultraviolet radiation exposure and estimates of exposure levels were applied to employment information from Canada census data to determine the exposed population in the risk exposure period (1961-2001). Risk estimates were drawn from meta-analyses selected based on quality and relevance to the current study. Population-attributable fractions were calculated using Levin's equation and attributable cases were estimated based on incidence data reported by the Canadian Cancer Society. RESULTS: In 2011, 6.31% (4556 cases) of non-melanoma skin cancer cases were estimated to be attributable to occupational exposure to solar ultraviolet radiation. The majority of these cases occurred in men in the agriculture or construction industries. CONCLUSIONS: These estimates of the burden of non-melanoma skin cancer in Canada identify the need for further prevention efforts, particularly in agriculture and construction. Introducing workplace sun safety measures could be an important area for policy development.

[Retrospective analysis of classification and treatment of microcystic lymphatic malformations of tongue].

Objective: To explore the clinical classification of microcystic lymphatic malformations of tongue and observe the treatment of microcystic lymphatic malformations of tongue by retrospective analysis, in order to provide reference for clinical practice. Methods: From October 2005 to October 2015, the complete data of 220 cases of microcystic lymphatic malformations of tongue (115 males and 105 females) received and treated in Provincial Special Department of Vascular Anomalies, Linyi Tumor Hospital was analyzed retrospectively. The age ranged from 8 months to 52 years old, with a median age of 16 years old. All patients were followed up for 3 years, and according to their clinical manifestations, they were divided into three types: localized type of 23 cases, diffuse type of 161 cases, and megaloglossia type of 36 cases. Injection with pingyangmycin merely was performed on 58 cases, whereas merely surgery on 20 cases, injection with pingyangmycin combined with high frequency electrocoagulation on 55 cases, and surgery combined with injection with pingyangmycin on 87 cases. The therapeutic effect was evaluated according to the grade 4 standard. The χ(2) test was used for statistical analysis of count data. Rank sum test was used for statistical analysis of ranked data. Results: The percentage of surgery merely of localized type was 87.0% (20/23), significantly higher than that of other types of lesions [0% (0/197)] (χ(2)=178.060, P<0.001). The percentage of injection with pingyangmycin of diffuse type was 100% (161/161), significantly higher than that of other types of lesions [66.1% (39/59)] (χ(2)=60.034, P<0.001). The percentage of surgery combined with injection with pingyangmycin of megaloglossia type was 100% (36/36), significantly higher than that of other types of lesions [27.7% (51/184)] (χ(2)=65.800, P<0.001). After follow-ups for 3 to13 years, there were 0 cases of gradeⅠ, 11 cases of grade Ⅱ, 50 cases of grade Ⅲ, and 159 cases of grade Ⅳ. There were statistically significant differences in clinical efficacy among different clinical types (H=158.668, P<0.001). The percentage of level Ⅳ efficacy of localized type, diffuse type and megaloglossia type were 100% (23/23), 82.6% (133/161) and 8.3% (3/36) respectively. Local mucosa ulcer appeared in 45 cases and was cured through oral care and expectant treatment. Fever occurred in 28 cases and returned to normal within 24 h after expectant treatment. The lingual frenum was shortened in 16 cases. There were 12 cases with mild tongue swelling, 6 cases with influence on eating but without influence on breathing, and recovered spontaneously one week later. Conclusions: The choice of different treatment methods of microcystic lymphatic malformations of tongue should be made according their clinical classification. The only surgical resection is recommended for localized protrude lesions. Injection with pingyangmycin in high tension combined with surgical resection or high frequency electrocoagulation is effective for diffuse lesions. Surgical resection combined with injection with pingyangmycin is suitable for the patients with megaloglossia type.