Objective:To detect gene mutations in a pedigree with dominant dystrophic epidermolysis bullosa (DDEB) .Methods:A 20-year-old male proband presented with repeated blisters, ulceration, pigmentation, scars on the limbs, and deformation of the nails/toenails after birth. There were 5 patients in the 3-generation family, and they all presented with typical skin lesions. Peripheral blood samples were obtained from 14 members of the pedigree (including the 5 patients) and 100 unrelated healthy controls. Whole-exome sequencing was performed in the proband to identify relevant mutation sites, which were then confirmed in the family by Sanger sequencing.Results:Genetic testing indicated that the proband and the other 4 patients all carried a missense mutation (c.7885G>A) in exon 107 of the COL7A1 gene, resulting in the substitution of glycine by arginine at amino acid position 2629 (p.G2629R). The mutation was identified neither in the 9 healthy relatives nor in the 100 unrelated healthy controls. The mutation co-segregated with DDEB in the family, and was not included in databases such as Pubmed, HGMD or ClinVar, suggesting it was a novel missense mutation. The amino acid encoded by this mutation may alter the structure of type Ⅶ collagen, thereby affecting its function.Conclusion:A novel missense mutation was identified in exon 107 of the COL7A1 gene in the family with DDEB, expanding the spectrum of mutations in the COL7A1 gene.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

Objective To study the effects and mechanisms of molecular targeted drug combination on multi-driven proliferation hepatocellular carcinoma SK-Hep-1 cells. Methods Four molecular targeted drugs (HG6-64-1, Dasatinib, Crizotinib, and Sunitinib) were used to treat SK-Hep-1 cells, and the monophasic kinetic analysis curve and two-phase analysis curve were drawn. Western blot analysis was used to detect the effects of the above drugs on key signaling pathways in SK-Hep-1 cells. MTT assay was used to detect the effects of the above drugs and their combination on the proliferation of SK-Hep-1 cells. Results Compared with the monophasic kinetic analysis curve, the biphase analysis curve could better fit the effects of molecular targeted drugs on SK-Hep-1 cells, which predicted that the combination of HG6-64-1, Dasatinib, and MK-2206 could effectively inhibit the proliferation of SK-Hep-1 cells. Conclusion Two-phase kinetic analysis can quantitatively describe the response of multi-driven proliferation hepatocellular carcinoma SK-Hep-1 cells to molecular targeted therapy. The combination of HG6-64-1, Dasatinib, and MK-2206 is a potential drug combination for the treatment of hepatocellular carcinoma.

Objective: To investigate the cause of an incident of occupational contact dermatitis in a farm in Tianjin Prefecture, so as to provide insights into occupational safety. Methods: The disinfection process, use of disinfectants and individual protective measures in this farm were collected, and a field epidemiological investigation was conducted to collect the demographic characteristics, history of occupational contact, clinical symptoms, diagnosis and treatment data, and onset of disease among individuals with the same type of job. The cause of this incident was analyzed. Results: There were ten interns exposed to potassium hydrogen sulfate compounds simultaneously in this farm, and then, nine interns developed skin flushing across the body, and swelling and itching of the skin. Among these ten interns, five individuals were admitted to hospitals because of severe symptoms and were then clinically diagnosed as systemic contact dermatitis. All five individuals were cured following treatments. Epidemiological survey showed that all cases had a definite history of occupational contact with potassium hydrogen sulfate compounds but without use of any protective agents. In addition, there were thirty-five individuals with the same type of job in this farm that developed similar symptoms when they joined in the disinfection for the first time, and these individuals were self-cured following cessation to contact; however, recurrence of symptoms was found following contacts again. Conclusion This is a cluster of occupational contact dermatitis caused by exposure to potassium hydrogen sulfate compound.

Objective:To investigate the expression of circhipk3 in microglial cells in heat-induced neurological injury, and to preliminary analyze the effect of circhipk3 on microglial polarization in heat-induced neurological injury.Methods:Mice were randomly (random number) divided into a control group and a heat radiation disease 0.8 h group (HS 0.8), a heat radiation disease 8h group (HS 8), and a heat radiation disease 24 h group (HS 24). By establishing a mouse model of heat shock (HS), heat-damaged brain tissue was obtained, microglia were isolated and RNA was extracted. Quantitative PCR method was used to detect M1 and M2 marker molecules in microglia, and to evaluate the polarization direction and type of microglia. The expression level of circhipk3 was detected in microglial cells in heat-induced neurological injury, and the effect of circhipk3 on microglial polarization was further elucidated by intervening the expression of circhipk3 in microglial cells.Results:The expression of CD45 and CD11-b in the HS 8 group was significantly higher than that in the control group [(4.41±0.18) vs. (1±0.15), P=0.000], [(3.47±0.19) vs (1±0.15), P=0.000] , and the CD45 and CD11-b of the HS 24 group was significantly lower than that of the HS 8 group [(1.34±0.15) vs. (4.41±0.18), P=0.000], [(1.38±0.21) vs. (3.47±0.19), P= 0.001]. At the same time, the expression of CD206, FIZZ and Arg1 in the HS 8 group started to increase compared with the control group [(1.59±0.16) vs. (1±0.12), P=0.014], [(1.62±0.15) vs. (1±0.15), P=0.002 ], [(2.23±0.28) vs. (1±0.19), P=0.004], and CD206, FIZZ, and Arg1 in the HS 24 group were significantly higher than those in the control group [(2.67±0.20) vs. (1±0.12), P=0.002], [(2.19±0.15) vs. (1±0.15), P=0.000], [(3.04±0.18) vs. (1±0.19), P=0.001]; circhipk3 mimicis significantly increased the expression of Arg1 [(7.26± 0.06) vs. (3.86±0.06), P=0.000]; at the same time, circhipk3 inhibitor promoted the expression of CD45 and HO-1 [(2.96±0.03) vs. (1.63±0.09), P=0.000], [(2.52±0.10) vs. ( 1.30±0.02), P=0.000]. Conclusions:Microglial cells are predominantly M1-type in early neurological injury of heat radiation disease. HO-1 may be one of the microglial M1-type markers. The high expression of circhipk3 in microglial cells mainly promotes its transformation to M2 type.

Objective To study epidemic of schistosomiasis in the Qiandao Lake reservoir area,and to provide a reference for prevention and control of schistosomiasis in the construction of large water conservancy projects in the epidemic area of schistosomiasis.Methods The data over the years of snail condition and monitoring of schistosomiasis before and after building the dam,and water conservancy project reconstruction related information were collected.Based on the survey results of the river channel,the lake beach and the dissipation zone in the reservoir area,the influence of Xin'an River water conservancy project on epidemic of schistosomiasis in the Qiandao Lake reservoir area was analyzed,and the epidemic factors of the schistosomiasis in the Three Gorges reservoir were compared and analyzed.Results Before the dam was built,an area of 38 144 000 m2 was examined but Oncomelania was undetected.The Qiandao Lake reservoir area belonged to a non epidemic area of schistosomiasis.After the dam was built,557 cases of schistosomiasis were found in 6 232 immigrants during 1962-1965,resulting in an imported epidemic.In 1970-1980,an area of 379 654 m2 in which Oncomelania was found was examined and snails were mainly distributed in some rice fields and ditches in the end of the reservoir.949 cases of local schistosomiasis were found in the snails.The condition and condition of the snail are gradually controlled through several decades of comprehensive prevention and control.Compared with the epidemic factors of schistosomiasis in Qiandao Lake and the Three Gorges reservoir,the environment of elevation beach and ecologically fragile fluctuation zone coexist in the two reservoir areas.Conclusion From the long-term longitudinal monitoring data of the Qiandao Lake reservoir area and the epidemic regularity of schistosomiasis and the comparison with the ecology of the Three Gorges reservoir,it is concluded that the two reservoir areas will not cause a large range of schistosomiasis epidemic in general,but it does not exclude the possibility of the breeding of the inputting Oncomelania.

Objective To summarize the diagnosis and treatment of congenital pulmonary airway malformation in children.Methods The clinical data of 68 children with congenital pulmonary airway malformations from June 2014 to June 2017 were analyzed retrospectively,including 39 males and 29 females with mean age(1.1 ±:0.5) years old(from 2 months 12 days to 15 years),7 cases of pulmonary cyst resection in 68 cases,3 cases with lung segment resection,1 cases with lingulectomy,57 cases with lobectomy.Results 68 cases were cured and discharged without death.Postoperative short-term complications included subcutaneous emphysema in 5 cases,pleural effusion in 2 cases,pneumothorax in 2 cases.All cases were followed up well between 3 months and 1 year.Conclusion The diagnosis of congenital pulmonary airway malformation in children mainly depends on imaging examination.Because it is easy to repeat infection,and can not rule out malignant transformation,early diagnosis and early treatment should be done.Surgical resection is the only way to treat the disease.

Objective: To study the effects p-phenylenediamine (PPD) on lung function and health-related quality of life of occupational exposed workers. Methods: This study was based on data from a company that produce hair dye containing PPD in China. Workers who exposed to PPD were selected as the study group, and workers un-exposed to PPD were selected as the control group. Questionnaires on health-related quality of life of workers using the 36-item Short Form Health Survey (SF-36) . Occupational health examination assessment results were tested in Taizhou Cancer Hospital. The lung function test includes forced vital capacity (FVC) , forced expiratory volume in one second (FEV_1.0) , and ratio of FEV_1.0 to FVC (FEV_1.0/FVC) . Results: The difference in systolic blood pressure between the PPD exposed group and the control group was statistically significant (P<0.05) . FVC, FEV_1.0, and FEV_1.0/FVC of the lung function indexes in the exposed group were lower than those in the control group (P<0.05) . In the health-related quality of life, body pain (P=0.002) , general health (P=0.029) , vitality (P=0.038) , and mental health (P=0.003) were lower in the exposed group than in the control group. Conclusion Occupational exposed to PPD may induce hazard to the workers’lung function and may cause detrimental effect on workers’ health-related quality of life.

Objective: To study the effect of p-phenylenediamine (PPD) on liver and kidney function in occupational exposed workers. Methods: Workers in a hair dye production enterprise which used p-phenylenediamine as a raw material for production were selected as the main research population. Then we conducted a questionnaire survey on the basic conditions of workers and conducted occupational health checkups on general health status, liver and kidney function. Occupational health examination assessment results were tested in Taizhou Cancer Hospital. All data was built using EpiData 3.1 software, and statistical analysis was performed using software SPSS 20.0. Results: The liver function indicators including direct bilirubin, prealbumin, total protein, and white protein, globulin, aspartate aminotransferase, glutamyl transpeptidase, and total bilirubin in the workers exposed to high concentration of PPD were at high normal values, and these indicators were significantly different from low PPD concentration group (P<0.05) . The serum creatinine and serum uric acid in the renal function index were significantly higher in workers exposed to PPD than in workers exposed to low concentrations and in the control group (P<0.05) . Conclusion Occupational exposed to PPD may have a hazard to the workers’ liver and kidney function. Long-term occupational exposure to PPD may lead to increased cumulative exposure of workers, which may cause potential chronic liver and kidney damage in occupationally exposed populations.

The aim of this study was to identify antigens for a vaccine or drug target to control rabbit coccidiosis. A combination of 2-dimensional electrophoresis, immunoblotting, and mass spectrometric analysis were used to identify novel antigens from the sporozoites of Eimeria stiedae. Protein spots were recognized by the sera of New Zealand rabbits infected artificially with E. stiedae. The proteins were characterized by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) analysis in combination with bioinformatics. Approximately 868 protein spots were detected by silver-staining, and a total of 41 immunoreactive protein spots were recognized by anti-E. stiedae sera. Finally, 23 protein spots were successfully identified. The proteins such as heat shock protein 70 and aspartyl protease may have potential as immunodiagnostic or vaccine antigens. The immunoreactive proteins were found to possess a wide range of biological functions. This study is the first to report the proteins recognized by sera of infected rabbits with E. stiedae, which might be helpful in identifying potential targets for vaccine development to control rabbit coccidiosis.
Coccidiosis* ; Computational Biology ; Eimeria ; Electrophoresis ; HSP70 Heat-Shock Proteins ; Immunoblotting ; Mass Spectrometry ; Rabbits ; Sporozoites