Objective : To investigate the mechanisms of bromodomain-containing protein 4(BRD4) in TGF-β1-induced epithelial-mesenchymal transition in alveolar type II epithelial cells. Methods : MLE-12 cells were stimulated with different concentrations(5 ng/ml, 10 ng/ml) of TGF-β1 for 48 h to establish an EMT cell model. The cells were pretreated with 50 nmol/L BRD4 inhibitor JQ-1, 100 μmol/L high mobility group box 1 protein(HMGB1)inhibitor glycyrrhizin acid(GA), and 3 μg/ml rHMGB1. The experimental groups were divided as follows: control group, TGF-β1 group, JQ-1 group, JQ-1+TGF-β1 group, GA group, GA+TGF-β1 group, and JQ-1+TGF-β1+rHMGB1 group. The effect of JQ-1 on cell viability was examined using cell counting kit-8(CCK-8). The protein expression levels of CDH1, ZO-1, Vimentin, α-SMA, BRD4, HMGB1, TGF-β1, Smad2/3 and p-Smad2/3 were detected by Western blot. The cell migration ability was detected by a scratch test. Results : Compared with the control group, the levels of Vimentin and α-SMA in the TGF-β1 group increased, and the levels of CDH1 and ZO-1 protein decreased, suggesting that the EMT model was successfully established. In this model, the expression of BRD4 and HMGB1 significantly increased. Different concentrations of JQ-1 could inhibit the cell viability of MLE-12 in a concentration-dependent manner. Both JQ-1 and GA could effectively alleviate TGF-β1-induced EMT, and reduce the increase in HMGB1 expression and the activation of TGF-β1/Smad2/3 pathway caused by TGF-β1. Moreover, rHMGB1 treatment could reduce the effects of JQ-1 on EMT and the TGF-β1/Smad2/3 pathway. Additionally, both JQ-1 and glycyrrhizin could effectively decrease TGF-β1-induced cell migration, whereas rHMGB1 could alleviate the inhibitory effect of JQ-1 on the rate of cell migration. Conclusion BRD4 can regulate epithelial-mesenchymal transition in alveolar type II epithelial cells via HMGB1/TGF-β1/Smad2/3 signaling cascade, and BRD4 may be a potential target for inhibition of pulmonary fibrosis.

Objective:To evaluate the clinical efficacy of liquid phase concentrated growth factors (LPCGF) combined with a stabilization splint in treating temporomandibular joint osteoarthritis (TMJOA) compared to a stabilization splint alone.Methods:A retrospective analysis of 60 TMJOA patients from December 2020 to June 2022 at Department of Maxillofacial Surgery, Yinchuan Stomatology Hospital was conducted. Patients were divided into experimental group (LPCGF+stabilization splint) and control group (stabilization splint only). The experimental group received an initial LPCGF injection, followed by biweekly injections for two sessions. Clinical assessments, including visual analogue scale (VAS) scores, maximum mouth opening (MMO), and Friction index, were conducted at baseline and at 3, 6, and 12 months post-treatment.Results:At 3 months post-treatment, the VAS scores of both the control group and the experimental group [6.00 (5.00, 7.00), 6.00 (5.00, 7.00)] were significantly lower than those before treatment [2.00 (2.00, 3.00), 2.00 (2.00, 3.00)] (all P<0.001), and there was no statistically significant difference between the groups ( P>0.05). The MMO [36.00 (34.75, 39.00), 37.50 (35.00, 40.00) mm] were significantly larger than those before treatment [(29.32±4.83), (27.63±6.43) mm] (all P<0.001), and there was no statistically significant difference between the groups ( P>0.05). The craniiomandibular index (CMI), dysfunction index (DI), and palpation (PI) of both groups were significantly lower than those before treatment (all P<0.001), and there were no statistically significant differences between the groups ( P>0.05). At 6 months post-treatment, the VAS scores of both the control group and the experimental group were significantly higher than those before treatment (all P<0.001), the MMO were significantly larger than those before treatment ( P<0.001), and the Fricton index was significantly lower than that before treatment ( P<0.05). Among them, the VAS score, DI, and CMI of the experimental group were significantly lower than those of the control group (all P<0.05), and there was no statistically significant difference in MMO and PI between the two groups ( P>0.05). At 12 months post-treatment, the VAS score of the experimental group was significantly lower than that before treatment ( P<0.001), while there was no statistically significant difference between the control group and before treatment ( P>0.05). The VAS score of the experimental group was significantly lower than that of the control group ( P<0.001). The MMO of both the control group and the experimental group were significantly larger than those before treatment ( P<0.001), and the DI and CMI were significantly lower than those before treatment (all P<0.001). There were no statistically significant differences between the two groups ( P>0.05). There were no statistically significant differences in PI between the two groups compared with before treatment (all P>0.05), and there was no statistically significant difference between the two groups ( P>0.05). Conclusions:LPCGF combined with a stabilization splint offers a more effective long-term pain relief for TMJOA.

Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

Diabetic neurogenic bladder(DNB)is an autonomic neuropathy,which is a common complication of diabetes mellitus(DM)with a high disability rate.Emphysematous cystitis(EC)is a rare and life-threatening urological disease.A patient with DNB and EC was admitted to our hospital,who was complicated with bilateral hydronephrosis and double ureters.After comprehensive treatment with indwelling catheterization,intravenous application of broad-spectrum antibiotics,and Ins hypoglycemic therapy,the re-examination of urinary CT showed that bilateral hydronephrosis,double ureters,and bladder gas disappeared,and the indicators were improved compared with before.Due to the severe condition of the patient with DNB,the residual urine volume of the bladder increased day by day after the catheter was removed,which led to long-term indwelling catheter after discharge.

Objective:To evaluate the clinical efficacy of liquid phase concentrated growth factors (LPCGF) combined with a stabilization splint in treating temporomandibular joint osteoarthritis (TMJOA) compared to a stabilization splint alone.Methods:A retrospective analysis of 60 TMJOA patients from December 2020 to June 2022 at Department of Maxillofacial Surgery, Yinchuan Stomatology Hospital was conducted. Patients were divided into experimental group (LPCGF+stabilization splint) and control group (stabilization splint only). The experimental group received an initial LPCGF injection, followed by biweekly injections for two sessions. Clinical assessments, including visual analogue scale (VAS) scores, maximum mouth opening (MMO), and Friction index, were conducted at baseline and at 3, 6, and 12 months post-treatment.Results:At 3 months post-treatment, the VAS scores of both the control group and the experimental group [6.00 (5.00, 7.00), 6.00 (5.00, 7.00)] were significantly lower than those before treatment [2.00 (2.00, 3.00), 2.00 (2.00, 3.00)] (all P<0.001), and there was no statistically significant difference between the groups ( P>0.05). The MMO [36.00 (34.75, 39.00), 37.50 (35.00, 40.00) mm] were significantly larger than those before treatment [(29.32±4.83), (27.63±6.43) mm] (all P<0.001), and there was no statistically significant difference between the groups ( P>0.05). The craniiomandibular index (CMI), dysfunction index (DI), and palpation (PI) of both groups were significantly lower than those before treatment (all P<0.001), and there were no statistically significant differences between the groups ( P>0.05). At 6 months post-treatment, the VAS scores of both the control group and the experimental group were significantly higher than those before treatment (all P<0.001), the MMO were significantly larger than those before treatment ( P<0.001), and the Fricton index was significantly lower than that before treatment ( P<0.05). Among them, the VAS score, DI, and CMI of the experimental group were significantly lower than those of the control group (all P<0.05), and there was no statistically significant difference in MMO and PI between the two groups ( P>0.05). At 12 months post-treatment, the VAS score of the experimental group was significantly lower than that before treatment ( P<0.001), while there was no statistically significant difference between the control group and before treatment ( P>0.05). The VAS score of the experimental group was significantly lower than that of the control group ( P<0.001). The MMO of both the control group and the experimental group were significantly larger than those before treatment ( P<0.001), and the DI and CMI were significantly lower than those before treatment (all P<0.001). There were no statistically significant differences between the two groups ( P>0.05). There were no statistically significant differences in PI between the two groups compared with before treatment (all P>0.05), and there was no statistically significant difference between the two groups ( P>0.05). Conclusions:LPCGF combined with a stabilization splint offers a more effective long-term pain relief for TMJOA.

Diabetic neurogenic bladder(DNB)is an autonomic neuropathy,which is a common complication of diabetes mellitus(DM)with a high disability rate.Emphysematous cystitis(EC)is a rare and life-threatening urological disease.A patient with DNB and EC was admitted to our hospital,who was complicated with bilateral hydronephrosis and double ureters.After comprehensive treatment with indwelling catheterization,intravenous application of broad-spectrum antibiotics,and Ins hypoglycemic therapy,the re-examination of urinary CT showed that bilateral hydronephrosis,double ureters,and bladder gas disappeared,and the indicators were improved compared with before.Due to the severe condition of the patient with DNB,the residual urine volume of the bladder increased day by day after the catheter was removed,which led to long-term indwelling catheter after discharge.

Background Silicosis is an occupational disease mainly characterized by pulmonary progressive fibrosis induced by the accumulation of free silica (SiO₂) in the lungs due to long-term exposure to SiO₂ dust. It has been shown that neutrophil extracellular traps (NETs) are increased in the lung tissues of silicotic mice after 28 d SiO₂ exposure, but it is unclear how the levels of NETs change throughout entire progression of silicosis in mice. Objective To observe the levels of NETs and pathological changes in the lungs of silicotic mice after different duration of SiO₂ exposure, and to confirm the possible role and significance of NETsin the development of SiO₂-induced pulmonary fibrosis. Methods A total of 28 SPF male C57BL/6J mice were randomly divided into a control group, and a model group, and the model group was subdivided into, a 2 d model group, a 7 d model group, and a 28 d model group, with 7 mice in each group. The mice in the model groups were given intratracheal instillation with 10 mg SiO₂ suspension (50 μL), and the mice in the control group were received same volume of saline. Mice were sacrificed and samples were collected at designed time points. The pathological changes of lung tissues of mice were observed after hematoxylin-eosin (HE) and Van Gieson (VG) staining. Immunofluorescence was used to observe the NETs markers citrullination histone H3 (CitH3) and myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF), and the percentage of NETs-positive cells was calculated. PicoGreen fluorescent dye kit was used to detect the content of extracelluar DNA (ex-DNA) in mouse BALF, and the expression levels of fibrosis-related proteins α-smooth muscle actin (α-SMA) and fibronectin (FN) and NETs marker CitH3 in lung tissues of mice were detected by Western blot (WB). Results Compared with the control group, inflammatory cells accumulation, alveolar wall thickening, and collagen deposition were obviously observed in the lungs of the silicosis model groups, and a large number of silicone nodules were recorded in the lung tissues in the 28 d group. Compared with the control group, the expressions of α-SMA and FN in the lung tissue of the 28 d group were significantly increased (P<0.05). The percentages of NETs in BALF increased significantly in the 2 d and the 7 d model group, then decreased in the 28 d model group (P<0.05). Compared with the control group (7.434±0.258) ng·mL⁻¹, the ex-DNA levels in BALF of mice in the 2 d [(35.110±6.331) ng·mL⁻¹], the 7 d [(39.491±6.948) ng·mL⁻¹], and the 28 d [(23.360±4.809) ng·mL⁻¹] model groups were increased (P<0.05), and the increase of ex-DNA in the 2 d and the 7 d model groups were statistically significant (P<0.05). In comparison with the control group, the protein level of CitH3 was significantly increased in the lung tissues of mice in the 7 d model group (P<0.05). Conclusion The content of NETs increases significantly and reaches a peak in the early inflammatory stage of silicosis, and decreases as the disease progresses to the fibrotic stage, suggesting that NETs may play a role in early stage of silicosis.

Objective To investigate the effects of long-term exposure to three new types of light emitting diode (LED) sources on the behavior, learning, and memory of rats. Methods A total of 160 specific pathogen-free SD rats were divided into eight groups as followed, trichromatic fluorescent lamps color temperature control group, violet-chip full-spectrum white LED group, blue-chip white LED group, and blue-chip full-spectrum white LED group based on the light sources types, with color temperature of 4 000 K and 6 500 K groups in each group using the 4×2 factorial design. There were 20 rats in each group, with half of the rats were males and half females. Rats were exposed to artificial lighting, and the illumination was set at 750 lx. The rats in each group were exposed to different lighting environments for 12 hours per day for 24 weeks. The open-field and step-down tests were conducted in rats after 24 weeks exposure, followed by sacrifice of rats and measurement of organ coefficients. Differences in body weight, organ coefficients, and neurobehavioral indexes of rats in different groups were compared. Results The spleen coefficient of female rats decreased in blue-chip white LED of 6 500 K color temperature group, and the liver coefficient of male rats decreased in the violet-chip full-spectrum white LED of 4 000 K color temperature, blue-chip full-spectrum white LED of 4 000 K color temperature, and blue-chip full-spectrum white LED of 6 500 K color temperature groups, compared with the same-sex rats in trichromatic fluorescent lamps with same-color temperature control group (all P<0.05). The result of different types of light sources compared in the open-field test showed that the index of total distance and movement speed of female rats in the blue-chip full-spectrum white LED group were lower than those in the other three groups, and the time cost to the central area was longer than that in the blue-chip white LED group and the violet-chip full-spectrum white LED group (all P<0.05). The total distance and movement speed of male rats in the blue-chip full-spectrum white LED group were longer or higher than those in the violet-chip full-spectrum white LED group (all P<0.05). Based on the comparison of color temperature, the time and total distance of male rats in 6 500 K color temperature group were lower than that in the 4 000 K color temperature group (both P<0.05). In the step-down test, both male and female rats in the blue-chip full-spectrum white LED group made more errors compared with other three groups with the same gender (all P<0.05). Conclusion Based on the experimental conditions of this study, the blue-chip full-spectrum white light LED affects behavior, learning and memory of the rats, and trichromatic fluorescent lamp has the lowest effect on neurobehavior. The color temperature also affects behavior of the rats, and high color temperature has higher risk.

Objective:To study the clinical characteristics, diagnostic methods and genotypes of neonatal chronic granulomatous disease(CGD).Methods:From April 2013 to August 2020, neonates admitted to our hospital, diagnosed with neonatal CGD and confirmed using neutrophil respiratory burst test and genetic testing were retrospectively studied. Their clinical characteristics and diagnostic methods were summarized.Results:A total of eleven neonates with CGD were enrolled, including ten males and one female. The age of onset was 3-23 d and the age of admission was 11-28 d. 3 cases had family history. The initial symptoms were fever (10 cases) and coughing (1 case). The accompanying symptoms included coughing (6 cases), dyspnea (4 cases), skin pustules (3 cases), fever (1 case) and diarrhea (1 case). Lung CT showed patchy shadows (6 cases), pulmonary nodules (3 cases), round and irregular high-density shadow (1 case), pulmonary consolidation (1 case), pleural effusion (1 case) and pleural thickening (2 cases). CGD was pathologically diagnosed in one patient. Sputum culture showed Candida albicans (3 cases), Aspergillus fumigatum (2 cases), Aspergillus fumigatum combined with Klebsiella pneumoniae and Escherichia coli (1 case), Aspergillus fumigatum combined with Staphylococcus aureus (1 case). GM tests were positive in two cases and negative in other two cases. Blood and cerebrospinal fluid cultures were negative. White blood cell counts were (10.0-44.0)×10 9/L and C-reactive proteins were (14-165) mg/L. 11 cases had positive neutrophil respiratory burst test. Genetic tests showed CYBB gene mutations (9 cases) , NCF1 gene mutation(1 case) and NCF2 gene mutation (1 case). All cases received antibacterial and antifungal treatments for 2-5 weeks and were discharged with improvement. 8 patients survived, 5 received hematopoietic stem cell transplantation, 4 succeeded and one failed and continued to survive on oral medication. 3 cases took sulfamethoxazole, voriconazole or itraconazole orally for long periods. 3 cases died of severe infections after withdrawal of medication. Conclusions:Neonatal CGD is characterized by lung infections. Pulmonary CT shows mostly nodular or patchy shadows with occasional pulmonary consolidation or pleural effusion. It can be diagnosed by neutrophil respiratory burst test and genetic testing. X-linked CYBB gene mutations are common and autosomal recessive NCF1/NCF2 gene mutations less common.

Gastric carcinoma is extremely rare in pregnancy and the prognosis for this malignancy tends to be dismal. We herein describe a case of gastric cancer in pregnancy to alert clinicians to this rare possibility. A 29-year-old woman developed abdominal spastic pain and diarrhea during the 26 weeks of gestation and her condition was confusing and hard to recognize. The patient was initially misdiagnosed as enterogastritis and inflammatory intestinal obstruction and was finally confirmed by exploratory laparotomy with intestinal and peritoneum metastases. Because the disease was not detected early enough and progressed rapidly, the pregnancy was terminated by cesarean section at 30 weeks of gestation, and then followed by systemic chemotherapy, but eventually succumbed to the lethal pneumonia. Therefore, it is of great significance to alert clinicians to note this rare possibility and to consider the differential diagnosis of this disease in pregnant women with a long course of gastrointestinal symptoms that cannot be explained by pregnancy alone, and cancer should be suspected and tested with sophisticated diagnostic procedures.