Objective: To design and synthesize a series of 2-aryl-4-(trans-4-hydroxycyclohexanolamine)-7H-pyrrolo[2, 3-d] pyrimidine derivatives and test their inhibitory activity against Mer tyrosine kinase(MerTK)and tumor cell proliferation. Methods: 2, 4-Dichloro-7H-pyrrolo[2, 3-d]pyrimidine(1)was used as starting material to synthesize the target compounds via iodination, protection with p- Tosyl(Ts), nucleophilic substitution, Stille coupling, vinyl reduction, Suzuki coupling and deprotection of Ts. The MerTK inhibitory activity was tested by the Kinase-Glo Plus luminescence method. The antiproliferation activity was assayed using MV- 4-11, A549, MDA-MB-231, KB, and KB-vin tumor cell lines by the CCK8 and SRB methods. Molecular docking of MerTK and 6h was conducted using the DS3.0 software. Results: Nine compounds were synthesized, and their structures were confirmed by 1H NMR and MS. Compound 6h exhibited certain inhibitory effect on MerTK, with the(6.7±0.3)μmol/L of IC50 value, and could selectively inhibit the growth of MV-4-11 tumor cells, with the(6.6±1.1)μmol/L of GI50 value that was approximately 3-fold to 6-fold more potent than the GI50 value of 6h on the other tested tumor cells. Molecular docking showed that 6h could interact with MerTK on the binding site of UNC569 and overlapped well with the original ligand UNC569, but its binding energy was higher than the binding energy of UNC569. Conclusion: Compound 6h showed a selective inhibitory effect on the MV-4-11 cell growth, which might be further investigated via more biological experiments to explore whether the inhibitory effect is related to the inhibition of MerTK by 6h. The molecular docking results in the present study have suggested that further structural modification on the 2 and 5 position of 7H-pyrrolo[2, 3-d] pyrimidine skeleton could likely improve the MerTK inhibitory activity.

Objective Thermal injury causes pulmonary edema, which may lead to acute respiratory distress syndrome, sepsis, multiorgan failure and even death. The article aimed to study the mechanism of curcumin pretreatment on inflammatory factors in lung tissues and serum endotoxin of rats with dry-heat environment.Methods A total of 50 SD rats were randomly divided into 5 groups (n=10): normal control group, dry heat control group, low concentraion group (50mg/kg curcumin pretreatment group), middle concentraion group (100mg/kg curcumin pretreatment group), and high concentration group (200mg/kg curcumin pretreatment group). Rats in normal control group and dry heat control group were given normal saline by gavage, while rats in 3 curcumin pretreatment groups were given curcumin of different concentrations (50 mg/kg, 100 mg/kg, 200 mg/kg) by gavage once a day for 7 consecutive days. At 8d, all the other 4 groups except normal control group were transferred to the climate cabin (The Simulated Climate Cabin for Special Environment of Northwest of China) with the condition of (41±0.5)℃, (10±1)% relative humidity.The rats were put in the dry-heat environment for 150min, then they were anaesthetized and sacrificed at 150min to collect the blood, lung tissues for further analysis. Observation was made on the pathological changes of lung tissues of rats in each group and the changes of inflammatory factors such as IL-1β, IL-6, TNF-α and LPS.Results Compared with dry heat control group, the concentrations of IL-1β, IL-6, TNF-α and LPS in normal control group, curcumin pretreatment groups with low concentration, middle concentration and high concentration were significantly higher(P<0.01). The concentrations of IL-1β, IL-6, TNF-α and LPS in curcumin pretreatment group with low concentration were significantly lower than those curcumin pretreatment groups with middle concentration and high concentration(P<0.05). Compared with curcumin pretreatment group with middle concentration, LPS concentration of curcumin pretreatment group with high concentration decreased significantly (P<0.01). Pearson correlation analysis showed that there was a positive correlation between the plasma of LPS and inflammatory cytokines of IL-1β, IL-6, and TNF-α in lung tissues (correlation coefficient r=0.866, r=0.900, r=0.885, P=0.000).Conclusion Curcumin inhibits bacterial endotoxin in blood, reduces the expression of inflammatory factors, and plays an important role in alleviating secondary multiple organ damage, which means curcumin pretreatment can relieve lung damage caused by heatstroke and reduce the mortality of heatstroke.

OBJECTIVE To study the expressions of heat shock protein 70 and human papillomavirus16E7 protein in human laryngeal squamous cell carcinoma, and their relationship in the genesis of human laryngeal squamous cell carcinoma. METHODS The expressions of HSP70 and HPV16E7 protein were detected by the immunohistochemical method in 78 specimens with laryngeal squamous cell carcinoma, 24 specimens with vocal cord polyps and 10 specimens of normal laryngeal tissues. RESULTS In human laryngeal squamous cell carcinoma, vocal cord polyps and normal laryngeal tissues, the positive expression rates of HSP70 were 69.2 % , 8.3 % and 0 % respectively, with those of HPV16E7 protein being 43.6 % 4.2% and 0 % respectively. There was a significant difference of the expression rate of HSP70 or HPV16E7 protein between the laryngeal squamous cell carcinoma and the vocal cord polyps(P

OBJECTIVE To construct a prokaryotic expression plasmid encoding HPV16E7-HSP70 fusion gene for further study on the immunity of HPV16E7- HSP70 fusion protein against laryngeal carcinoma. METHODS HPV16E7 was PCR-amplified,digested by NheI and SacI,and ligated into pET28a. HSP70 was cloned into pGEMTeasy,then recut from the vector by SalI and NotI and ligated into pET28a-HPV16E7. PCR amplification, restrict enzyme digestion, DNA sequencing, IPTG induction and Western Blot were used to identify the recombinant plasmid. RESULTS Double digestion and PCR amplification of the recombinant plas- mid have shown that the size of the inserted fragment is as expected. Sequence analysis has demonstrated that the inserted fragment encodes for the HPV16E7- HSP70 fusion gene. IPTG induction and Western Blot have shown that the fusion protein is expressed suc- cessfully in the prokaryotic expression plasmid. CONCLUSION The recombinant prokaryotic expression plasmid pET28a-HPV16E7-HSP70 has been con- structed successfully.

OBJECTIVE: To identify the difference of CA IX and P-gp expression level between laryngeal squamous cell carcinoma (LSCC) and benign tissues, evaluate the relationship of these two proteins in LSCC, and their correlation with clinical and pathological features. METHOD: Immunohistochemical detection of CA IX and P-gp were performed in 47 cases of LSCC and 20 cases of vocal cord polyps. RESULT: Overexpression of CA IX and P-gp both in LSCC and in vocal cord polyp (P < 0.05) were confirmed, with a correlation between the two proteins in LSCC (r = 0.324, P < 0.05). The expression of CA IX was related to clinical staging and lymph node metastasis in LSCC (P < 0.05). While P-gp was related to clinical staging and histological grading in LSCC (P < 0.05). CONCLUSION The overexpression of CA IX and P-gp may play a role in LSCC progression.
ATP Binding Cassette Transporter, Subfamily B ; metabolism ; Antigens, Neoplasm ; metabolism ; Carbonic Anhydrase IX ; Carbonic Anhydrases ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Staging ; Polyps ; metabolism ; Vocal Cords ; metabolism ; pathology

BACKGROUND: Breast cancer is one of the most common cancer in women and a proportion of patients experiences brain metastases with poor prognosis. The study aimed to construct a novel predictive clinical model to evaluate the overall survival (OS) of patients with postoperative brain metastasis of breast cancer (BCBM) and validate its effectiveness. METHODS: From 2010 to 2020, a total of 310 female patients with BCBM were diagnosed in The Affiliated Cancer Hospital of Xinjiang Medical University, and they were randomly assigned to the training cohort and the validation cohort. Data of another 173 BCBM patients were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database as an external validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) Cox regression model was used to determine the fundamental clinical predictive indicators and the nomogram was constructed to predict OS. The model capability was assessed using receiver operating characteristic, C-index, and calibration curves. Kaplan-Meier survival analysis was performed to evaluate clinical effectiveness of the risk stratification system in the model. The accuracy and prediction capability of the model were verified using the validation and SEER cohorts. RESULTS: LASSO Cox regression analysis revealed that lymph node metastasis, molecular subtype, tumor size, chemotherapy, radiotherapy, and lung metastasis were statistically significantly correlated with BCBM. The C-indexes of the survival nomogram in the training, validation, and SEER cohorts were 0.714, 0.710, and 0.670, respectively, which showed good prediction capability. The calibration curves demonstrated that the nomogram had great forecast precision, and a dynamic diagram was drawn to increase the maneuverability of the results. The Risk Stratification System showed that the OS of low-risk patients was considerably better than that of high-risk patients ( P < 0.001). CONCLUSION The nomogram prediction model constructed in this study has a good predictive value, which can effectively evaluate the survival rate of patients with postoperative BCBM.
Female ; Humans ; Breast Neoplasms/surgery* ; Retrospective Studies ; Prognosis ; Brain Neoplasms/surgery* ; Nomograms

Corneal alkali burns are a common form of corneal trauma, and their treatment has been a challenge in ophthalmology. Traditional treatments include anti-inflammatory, immunosuppressive, and corneal transplantation, with limited results. This review focuses on the research progress of mesenchymal stem cells(MSCs)and their derived extracellular vesicles(MSCs-EVs)in the treatment of corneal alkali burns. MSCs have the ability of self-renewal, multidirectional differentiation, and immunomodulation, and the MSCs-EVs inherit its function from MSCs. MSCs-EVs inherit the functions of MSCs and has lower immunogenicity and better biocompatibility, which provides a new avenue for ophthalmic treatment. In addition, bioscaffolds are used as scaffolds or drug delivery systems in tissue engineering to promote tissue regeneration due to their excellent biocompatibility and degradability. This article reviews the mechanism of action and research progress of MSCs-EVs and combined bioscaffolds in the treatment of corneal alkali burns, and explores their potential in promoting the repair of corneal alkali burns and improving vision. These findings provide new strategies for the treatment of corneal alkali burns and are expected to improve the prognosis of patients.

Corneal alkali burns are a common form of corneal trauma, and their treatment has been a challenge in ophthalmology. Traditional treatments include anti-inflammatory, immunosuppressive, and corneal transplantation, with limited results. This review focuses on the research progress of mesenchymal stem cells(MSCs)and their derived extracellular vesicles(MSCs-EVs)in the treatment of corneal alkali burns. MSCs have the ability of self-renewal, multidirectional differentiation, and immunomodulation, and the MSCs-EVs inherit its function from MSCs. MSCs-EVs inherit the functions of MSCs and has lower immunogenicity and better biocompatibility, which provides a new avenue for ophthalmic treatment. In addition, bioscaffolds are used as scaffolds or drug delivery systems in tissue engineering to promote tissue regeneration due to their excellent biocompatibility and degradability. This article reviews the mechanism of action and research progress of MSCs-EVs and combined bioscaffolds in the treatment of corneal alkali burns, and explores their potential in promoting the repair of corneal alkali burns and improving vision. These findings provide new strategies for the treatment of corneal alkali burns and are expected to improve the prognosis of patients.

LSCs(limbal stem cells)are one of the adult unipotent stem cells located in the Vogt palisade area of the limbal cornea. It can supplement the repair of corneal epithelium by self renewal and play an important role in maintaining normal corneal epithelial integrity, corneal transparency and maintaining normal vision. The lack of corneal limbus stem cells caused by various reasons will lead to corneal turbid, ocular surface vascularization, and final blindness. The main methord to treat related diseases is to cultivate corneal limbal stem cells in vitro and retransplantation. How to effectively expand the limbal stem cells in vitro is the key to the success of the treatment. The location, acquisition methods and expansion methods of limbal stem cells were reviewed.

Background: The pathogenesis of obstructive sleep apnea (OSA) remains not fully understood. This study aimed to explore the mechanism of OSA by assessing the association between the human tandem of P domains in a weak inwardly rectifying K⁺ channel (TWIK)-related acid-sensitive K⁺ channel-1 (TASK-1) gene and OSA. Methods: A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Center for Hypertension of People’s Hospital of Xinjiang Uygur Autonomous Region (China) from April to December in 2016. Two single nucleotide polymorphisms (rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a kompetitive allele specific polymerase chain reaction genotyping system. Clinical-pathological characteristics and genotype data were compared between the severe and non-OSA groups to explore the association between TASK-1 gene polymorphism and severe OSA. Results: There were no significant differences in genotype distribution, allele frequency, and the recessive and dominant model of the two selected single nucleotide polymorphisms (rs1275988 and rs2586886) between the severe and non-OSA groups in the total population (P < 0.05). However, for patients with a body mass index (BMI) ≥28 kg/m², the distribution of genotypes and alleles, and the recessive model (GG + GA vs. AA) exhibited significant differences between the severe and non-OSA group (for genotypes: P = 0.014 and P = 0.026; for alleles: P = 0.006 and P = 0.011; for the recessive model: P = 0.005 and P = 0.009, respectively). The simple logistic regression analysis revealed that the GG genotype was a risk factor for OSA. The odds ratio (OR) and 95% confidence intervals (CI) were 4.902 (1.582–15.186, P = 0.006) for rs1275988 and 4.420 (1.422–13.734, P = 0.010) for rs2586886, respectively. In multivariate logistic regression analysis, the combination of GG genotypes of rs1275988 with BMI ≥28 kg/m² increased the risk of severe OSA (OR = 8.916, 95% CI 4.506–17.645, P < 0.001). Conclusion Both the GG genotype of rs1275988 and GG genotype of rs2586886 in the TASK-1 gene may play as potential risk factors in obese patients with OSA.